Most people don't want to live forever. "It would be too boring. I would have explored everything," said Shekhar Biswas, a data scientist from Berlin. He speaks for most people I quizzed one afternoon in Berlin's Alexanderplatz no one said they'd be interested in eternal life. (Also read: Loss of neurons makes Alzheimer's patients drowsy: Study)

But what Biswas and many others would be interested in, I learned, is a long life maybe to the age of 100. Biswas said when he must die, he wants it to happen without the burden of any painful disease and sickness in his final years.

Nothing's going to stop death, most researchers conclude. But there could be ways to make life last longer, and the process of death shorter.

The gerontologists vs. the quacks

There are two horizons in the world of aging science, according to Dr. Nir Barzilai, who heads the Institute for Aging Research at the Albert Einstein College of Medicine in New York.

"One is people who are anti-aging," he said, like the people who sell multivitamins promising life extension through cellular renewal. "They're usually charlatans. They tell you to take this drug and you'll live forever. If you die, nobody sues them. Then there's geroscience. Those are scientists who are working on the biology of aging, who know which things to target, and they are very legitimate."

Barzilai, of course, is a geroscientist. He's been following a cohort of 750 centenarians (people who have lived to the age of 100) for years. He recently announced plans to expand his study to 10,000 people.

The new study isn't being backed by government grants but rather by a 26-year-old Bitcoin millionaire named James Fickel. This non-traditional funding stream may sound unusual. But when you start making sense of the logic behind aging research, the puzzle starts to fit together.

Healthspan, not lifespan

First things first: Geroscientists will tell you they aren't interested in prolonging lifespan the number of years you live but rather "healthspan," the number of years you are healthy and capable of living a normal life without complications or setbacks due to illness or disease.

Scientists estimate that more than 50% of deaths worldwide are due to diseases caused by aging like Alzheimer's, cardiovascular disease, cancer, type 2 diabetes and hypertension. That number increases in industrialized countries where access to modern medicine and healthcare means that people live long enough to contract age-related diseases and not die of diseases like malaria and dengue at a younger age.

If scientists like Barzailai can find a medication to help prolong people's healthspans, death will be quicker and less painful, they say.

James Kirkland, a professor of medicine at the Mayo Clinic and president of the American Federation for Aging Research, said they're looking to find a way to prevent something called "multimortality at the end of life.

If you've watched an elderly family member pass away, you probably know what that is. It starts with a cancer or dementia diagnosis and is then followed by a range of other issues. Problems like arthritis, cataracts, forgetfulness and osteoporosis all come together during the person's final years, making life feel like a daily fight.

Kirkland says it doesn't have to be like this. Instead, he said, death could look more like "going out and having a five-mile run and then just not waking up the next morning."

This concept is called compressed mortality decreasing the number of years or months in which a person goes through the process of dying.

Nature vs. nurture

Barzilai has been following centenarians for over 20 years now, looking to see if they can provide some clues on how to live to reach our 100s. Along with living long healthy lives, these people, he observed, often experienced "compressed mortality," dying over the course of a few weeks rather than years.

Is it something they eat, somewhere they live? Are they non-smokers or vegetarians? Are there certain things these elderly people are doing or have done during their lives that have allowed them to live so long?

The answer is no, Barzilai found.

"60% of the men are smokers, 30% of the women. More than 50% of them are overweight or obese and do not exercise. Only 2% were vegetarian. They're not special," he said.

A healthy lifestyle plays a role in longevity, so don't stop eating your vegetables. But Barzailai's research means that the elixir to youth will likely come in the form of a drug capable of targeting specific "longevity genes."

"It's 80% genetics and 20% the environment," he said. The question, then, is what do they have that people who die at 80 don't?

Centenarians don't have perfect genes or even obvious gene mutations protecting them from diseases like Alzheimer's, Barzailai said they just develop those diseases much later than non-centenarians.

Some of them had genes that prevented the functioning of growth hormones, Barzilai said. Through his research on centenarians, he's looking to identify genes or gene mutations that appear to influence aging. Once those pathways are identified, medications can be developed and tested to target them.

Drugs to halt aging processes

Barzilai is already in the process of testing how the medication Metformin, a diabetes drug, works to halt some effects of aging in the body. That's just one of many drugs that are being tested to see whether they're able to counteract aging; Matt Kaeberline, a University of Washington biologist, is running a trial to see if the drug Rapamycin impacts aging in dogs, with the hope to later test it in humans.

Aging can't be attributed to a single process that happens in the body. It's a combination of many different processes, and each of the medications is looking to address different variations of them.

One thing that causes the body to age is something called cell senescence. The cells in our body are constantly going through a process called cell division. But scientists have found that this process gets disrupted over time, causing some cells to stop dividing. Although these cells are dead, they don't leave the body and instead accumulate, causing health problems like inflammation.

Kirkland's work centers around developing drugs that would kill the unnecessary senescent cells in our bodies. Barzilai and Kaeberline's drugs try blocking the senescent cells from causing problems like inflammation, but don't extinguish the cells altogether.

Kirkland said it will probably be at least a decade before we know whether these drugs work to halt negative aging processes. But once they find the right solution, he's convinced it will be transformative.

"If some of these things actually work, it would be like the discovery of antibiotics," said Kirkland. "It would be that big, because these fundamental aging processes are root-cause contributors to everything."

The billionaires want in

Fickel, the backer of Barzailai's study, isn't the only uberwealthy interested in aging research. Russian-Israeli billionaire Yuri Milner-backed Altos Labs, a California-based biotechnology startup interested in aging research that's paying its scientists million-dollar salaries, launched early this year on a mission to "reverse disease to transform medicine."

It's not the first billionaire-backed attempt to unlock the secret to eternal youth. Google parent Alphabet's unit Calico Labs launched in 2013, but the company has so far been tight-lipped about its research and development.

Altos Labs is looking into many different solutions to a long life, some of which involve the processes being trialed by teams like Barzilai's, Kirkland's and Kaeberlein's. But they're also looking into more experimental science the kind that may not be able to receive support through traditional academic grants because it's so new.

Barzilai said that although Altos is a corporation, they aren't the textbook anti-aging charlatans. They've recruited some of the best scientists in the field of anti-aging research including Nobel Prize winners to look into another potential solution to increasing healthspan, called cell reprogramming.

The idea behind cell reprogramming, which is also sometimes called cell rejuvenation, is relatively simple to understand. Old cells would be transformed into the fresh, unblemished cells you were born with, cells that haven't been impacted by things like smoking or beer consumption, for example.

The science behind this is based on discoveries made through the cloning of Dolly the sheep. One of the biggest scientific developments to come based on that research was Shinya Yamanaka's discovery that four proteins can bring cells back to their original state. He won a Nobel Prize in 2012 for the research, which has been applied to several disciplines.

The scientists at Altos are looking to see if they can apply it to aging processes.

Scientists cautious but optimistic

There are a lot of obstacles to this research, one of the main ones being the cell's loss of identity once it's replicated. And we likely won't see any results for a long time even once researchers find a method that works, it will take years to test it on animals and people, and even longer for any potential medication to pass clinical trials to make it to the market for general use.

The medications being investigated by Barzilai, Kirkland, Kaeberlein and others will also need some time, but could hit the market in the coming decades if they pass clinical trials, Kirkland says.

That's a big if. The scientists are cautious about stoking any kind of excitement about the medications. Lots can fall apart in clinical trials; Kirkland said that of the dozens currently underway, most will fail. But they're optimistic that when the right treatment comes, it could have a great impact.

"I think most of us do believe that this is coming," said Kaeberlein. "I don't know if it's going to be 10 years, 20 years, 30 years, but it is happening and it is going to change things."

Edited by: Ashutosh Pandey

Read the rest here:
So you want to live forever? - Hindustan Times

Recommendation and review posted by Bethany Smith

Festival of Fresh 2022 is promising a rich mix of fantastic speakers across two tents as it throws the spotlight on the present and future of the UK fresh produce industry.

Hosted outdoors at Berry Gardens new packing and distribution site near Maidstone on 8 June, the event features a packed programme of interactive content focused on both Inspiration and Innovation.

Inspirational thinking

In the Inspiration Tent, following an introduction by Berry Gardens CEO Nick Allen, the day begins with an industry leaders panel discussion, where attendees will have the chance to put their questions to new NFU Horticulture Board chair Martin Emmett, British Growers CEO Jack Ward, British Apples & Pears executive chair Ali Capper and British Summer Fruits chief Nick Marston.

Talks and interviews follow on the subject of Production & Trade, with speakers including co-MDs of fast-growing fresh produce giant Jupiter Group, Mark and Yvonne Tweddle, as well as NCGM tenants association chair Gary Marshall and Tropical Directs Nigel West.

Looking at the major issues facing modern business, APS Groups Phil Pearson will address the topic of producing and innovating at a time of intense cost pressure, while MDS operations director Sapphira Waterson will explain how the graduate scheme is both expanding, and helping recruit ex-army personnel into industry jobs.

After a delicious lunch and opportunity to see displays of sumptuous fresh produce in the FOF22 Market Street, the focus of the Inspiration Tent switches to Retail & Marketing, with expert analysis of the sector from grocery commentator Steve Dresser, and inspirational branding with Barfoots Kim Barfoot-Brace and Berry Gardens Rob Harrison. Retailer participation is expected to be confirmed shortly.

Innovating for the future

Over in the Innovation Tent, meanwhile, the morning programme focuses on the road to net-zero production. NFU Energy director Jon Swain will discuss some of the new technologies helping the horticultural sector, while former AHDB Horticulture Board chair and sustainability consultant Hayley Campbell-Gibbons will look at how producers can navigate the tricky world of carbon-neutral products. Oli Kaberry, head of business operations at The Jones Food Company, will also outline some of the companys industry-leading work in vertical farming.

In the afternoon, science is under the microscope with the University of Lincolns Simon Pearson outlining the work of the Agricultural Universities Council, ItsFreshs Rob Ward talking shelf-life extension, robotics demonstrations and a series of quickfire presentations revealing groundbreaking PhD research that could solve a raft of industry problems.

Lively and interactive

The programme follows Fruitnet events trademark quick-fire format, with short and punchy presentations combined with a mixture of panel discussions, one-to-one interviews and lighthearted elements. There will be opportunity to ask questions and make comments, as well as relax and network throughout at the various social stations and stands across the festival. Further speakers will also be announced in the coming weeks.

Tours of Berry Gardens brand new packhouse will also give delegates a chance to see an industry-leading, environmentally friendly production facility up close.

Tickets will go on sale shortly atwww.fpjlive.com.

Read more:
Inspiration and innovation at Festival of Fresh 2022 - Fruitnet

Recommendation and review posted by Bethany Smith

Total measured and indicated mineral resources, which are inclusive of mineral reserves, now total1.3 million gold ounces, of which928,000gold ounces are open pit, a 65% increase sincethe 2020 resource estimate.

We have successfully replaced 2021 mining depletion and added another 1.5 years to the open-pit mine life at Tucano, Great Panther chairman and interim CEOAlan Hairsaid in a news release.

The Tucano tenement portfolio covers over 197,000 hectares over land along the Vila Nova greenstone belt, centred around the Tucano mining licence. The mine operation currently comprises eight open pits, the Urucum North underground project, a processing plant and tailings dam. Production to date has been sourced from all pits except Urucum East.

The company noted that it hascompleted a 19,000-metre drilling campaign on the Urucum North underground project, with engineering studies currently underway.

Going forward, a major objective is to progress the Urucum North underground project, with development scheduled for Q4 2022, while aggressively advancing opportunities for additional resource growth and mine life extension on multiple fronts, Hair added.

In the second half of the year, Great Panther is expected to actively pursue drilling to increase resources within the mine sequence and on near mine (20-kilometre radius) priority targets in the regional land package.

Read the rest here:
Great Panther increases Tucano open-pit resources by 65%, reserves by 24% - MINING.COM - MINING.com

Recommendation and review posted by Bethany Smith

Pronovias Atelier Unveils 2023 Bridal Collection In First Runway Show In 2 Years

After a long pause of 2 years, Pronovias makes its return to physical runway on April 22, marking the official start of a booming season for the bridal giant.

The new 2023 Versailles Collection by Pronovias Atelier, the high end couture brand of Pronovias Group, showcased a series of stunning bridal gowns in front of 1,800 guests on the final day of Barcelona Bridal Fashion Week. The event was broadcasted on a number of social media channels including Instagram, Facebook, YouTube and Twitch. Each and every dress that carries the Pronovias Atelier label is handmade by expert seamstresses in Barcelona using the finest fabrics and laces imported from France and Italy.

Alessandra Rinaudo, Artistic Director of Pronovias, says: Versailles has come to define luxury and beauty, which to me fits perfectly with Haute Couture bridal. This collection stands out for attention to detail and head-to-to exquisiteness. Its a modern, innovative interpretation of one of the most lavish periods in fashion history.

Rosa Crespo (left) and Sarah Mikaela (right), attending as UK VIPs wearing Vera Wang Bride ... [+] collection for Pronovias

Comprising 44 exquisite and opulent designs, the new Versailles Collection emanates a sense of royal luxury whilst staying true to the feminine beauty the brand is known for. Inspired by the glittering character of Versailles, the collections intricate embellishments and plush fabrics are complimented by extravagant veils, elegant elbow-length gloves, bustle-up capes and detachable, oversized sleeves. The casting is decidedly inclusive, with models of all age, body shape, ethnicity and gender diversity walking the runway and iconic supermodel Esther Canadas closing the show.

Marking Pronovias Groups commitment to cutting edge digital innovation in product design and technology and the first of its kind in the bridal industry Rinaudo has also helped create three NFTs, each reproducing the patterns, textures, beading of three dresses from the Versailles Collection. The three NFTs are uploaded to the OpenSea platform and can be viewed on the Pronovias website.

Pronovias Atelier debuts "Versailles Collection" at Barcelona Bridal Fashion Week

Speaking to Amandine Ohayon, the CEO of Pronovias Group, it is clear that the international bridal maison is looking into the future with Metaverse, sustainability as well as social responsibility on its mind.

My aim hasnt changed, says Ohayon in Barcelona a few days ahead of the show, referring to her goal of significantly accelerating the Groups international development when she first joined in 2018. And with the opening of the our Shanghai and New York flagship stores, we will continue with the expansion. The focus for the next 2-3 years will also be servicing the rising demand due to cancelled weddings over the pandemic.

Pronovias Atelier debuts "Versailles Collection" at Barcelona Bridal Fashion Week

Despite the difficulties posed by the closed shop floors and restrictions in personal contact during the past two years, Ohayon made sure each clients wishes were catered to, even if it meant shipping a gown across from Malaga to Houston for final alteration before sending it to the happy bride.

People want to party like they never partied before, Ohayon says with a smile as we discuss the trends for weddings. I see two major trends one being people wanting to have two or more dresses, as an increasing number of weddings consist of not just the big day itself, but also an event for the day before and another for the day after.

Pronovias Atelier debuts "Versailles Collection" at Barcelona Bridal Fashion Week

The second trend is the increasing appetite for more couture dresses. Ohayon tells me, Brides want things that are more dramatic and special, and we are seeing double digit growth in sales of the bridal accessories veil, cape, gloves, with lots of styling.

Coming from a background of beauty where the focus on sustainability is a lot more advanced than other areas of fashion and retail, especially the bridal industry, Ohayon was keen to identify and incorporate eco-friendly fabrics in the brands designs, as well as establish a sustainable practice within the Group. She and Rinaudo has since launched the EDEN collection, featuring a selection of sustainable #WeDoEco gowns.

Pronovias after party guests

In January this year, Ohayon furthered her sustainability initiative by launching Second Life at Pronovias, the wardrobe life extension initiative, releasing dresses designed specifically to be altered after the wedding and thus encouraging more wears and the longevity of wardrobe items. Rinaudo has designed a collection which can be transformed free of charge into a new style after the wedding, with the first launch consists of over 50 carefully selected bridal gowns that can be converted by altering the length, eliminating sleeves, or by adding belts, straps, sashes and other details to create a totally new look. The number of dresses that can be given a Second Life will increase with each new bridal collection launched by the brand.

The pandemic was the reason we did all these, Ohayon says, stating that the uncertain and at times dark experience in fact brought some great things and taught her, and the brand, to be agile and adaptive. We signed the deal with Vera Wang in 2020 over Zoom calls we now do business and develop relationships in a whole new way.

The Pronovias Atelier Versailles Collection will be available in store in September 2022.

Read more here:
Pronovias Unveils 2023 Bridal Collection With First Runway Show In 2 Years - Forbes

Recommendation and review posted by Bethany Smith

MANAGEMENT'S DISCUSSION AND ANALYSIS OF OPERATIONS AND FINANCIAL CONDITION

This Management's Discussion and Analysis of Operations and Financial Condition ("MD&A") should be read in conjunction with Yamana Gold Inc.'s (the "Company" or "Yamana") condensed consolidated interim financial statements for the three months ended March 31, 2022, and the most recently issued annual Consolidated Financial Statements for the year ended December 31, 2021 ("Consolidated Financial Statements"). All figures are in United States Dollars ("US Dollars") unless otherwise specified and are in accordance with International Financial Reporting Standards as issued by the International Accounting Standards Board ("IFRS").

The Company has included certain non-GAAP financial performance measures, which the Company believes, that together with measures determined in accordance with IFRS, provide investors with an improved ability to evaluate the underlying performance of the Company. Non-GAAP financial performance measures do not have any standardized meaning prescribed under IFRS, and therefore they may not be comparable to similar non-GAAP financial performance measures employed by other companies. The data is intended to provide additional information and should not be considered in isolation or as a substitute for measures of performance prepared in accordance with IFRS. The non-GAAP financial performance measures included in this MD&A include:

Cash costs per gold equivalent ounce ("GEO") sold;

All-in sustaining costs ("AISC") per GEO sold;

Net free cash flow;

Free cash flow before dividends and debt repayment; and

Average realized price per ounce of gold/silver sold

Reconciliations and descriptions associated with the above financial performance measures can be found in Section 11: Non-GAAP Financial Performance Measures in this MD&A. In addition, each non-GAAP financial performance measure in this MD&A has been annotated with a reference to endnote (1).

Cautionary statements regarding forward-looking information and mineral reserves and mineral resources can be found in Section 12: Disclosure Controls and Procedures in this MD&A.

Endnotes can be found on the final page of this MD&A.

1. HIGHLIGHTS AND RELEVANT UPDATES

For the three months ended March 31, 2022 unless otherwise noted

Operational, Earnings and Cash Flow Highlights:

Gold production of 210,533 ounces exceeded plan, following standout performances from Jacobina with 47,124 ounces, El Pen with 41,330 ounces and Cerro Moro with 25,254 ounces, and with gold production at other mines in line with plan, including at Minera Florida, where production was modestly impacted early in the quarter as a result of a previously disclosed labour action which has been resolved and resulted in a new long term collective bargaining agreement. Within the quarter, March was a standout month for Jacobina, with the mine achieving record monthly production and throughput. Quarterly gold production also exceeded the prior year comparative quarter.

Silver production of 2,198,669 ounces exceeded plan, following an exceptional performance from Cerro Moro. Quarterly silver production also exceeded the prior year comparative quarter.

GEO(2) production from Yamana mines(4) of 238,617 GEO(2) was in line with plan, despite a lower gold to silver ratio than anticipated in the plan and guidance. With the budget gold equivalent ratio, GEO(2) production would have exceeded plan as well. Quarterly GEO(2) production also exceeded the prior year comparative quarter production of 231,988 GEO(2), on the back of strong gold production. Cerro Moro in particular exceeded the prior year comparative period GEO production by 27%.

Quarterly total cost of sales, cash costs(1) and AISC(1) on a per GEO(2) basis of $1,212, $734, and $1,084 respectively. Costs were lower than plan, despite the first quarter being the lowest planned production quarter of the year, and the lower than plan and guidance gold to silver ratio which also impacted GEO(2) production. The Company continues to monitor the impact of inflationary pressures on its cost structure and notes that in the first quarter, the price of certain consumables, primarily diesel and mill balls, increased while certain others have remained relatively constant. Furthermore, higher base metal prices have had a positive impact on by-product credits allocated to GEO(2) costs. The impact of inflation on costs remains uncertain mostly because it is unclear if the geopolitical events that have occurred since the Company provided its guidance earlier in the year, which have driven price increases on certain items, will continue, or whether the events will continue to impact the price of those items. Equally, in the first quarter, the Company successfully mitigated inflationary trends through productivity improvements and overall, as aforementioned, costs in the first quarter were lower than plan and in line with guidance. While the Company plans to increase capital

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spending in each of the following quarters, as compared to the first quarter, this will coincide with increases in production and generation of cash flows and free cash flows. Further, the Company notes that cash flows in the second half of the year will also increase as higher income tax installments will have been paid, as normal, in the first half of the year.

Cash flows from operating activities before net change in working capital for the three months ended March 31, 2022 were $197.3 million, an increase of 7.6% compared to $183.4 million in the comparative period in 2021.

As at March 31, 2022, the Company had cash and cash equivalents of $516.4 million, including $218.3 million available for utilization by the MARA Project. Further, the Company has available credit of $750.0 million from its undrawn revolving credit facility. The Company notes that while production for the year is expected to be consistent quarter-over-quarter, except for a modestly lower first quarter as compared to other quarters, free cash flow is expected to steadily increase quarter-over-quarter, with the strongest free cash flow generation expected in the second half of the year, and in particular during the fourth quarter. The Company expects cash balances to increase steadily throughout the year with the strongest contribution in the latter half of the year.

Net earnings(3) for the three months ended March 31, 2022 were $57.8 million or $0.06 per share basic and diluted, compared to net earnings(3) of $54.7 million or $0.06 per share basic and diluted for the three months ended March 31, 2021. Adjusting items of $25.8 million(3), that management believes may not be reflective of current and ongoing operations, and which may be used to adjust or reconcile input models in consensus estimates, decreased net earnings(3) for the current period. For a complete list of adjustments attributable to Yamana Gold Inc. equity holders, refer to the Financial highlights section below.

The Company employs a balanced approach to capital allocation, which is expected to generate significant and growing cash balances during the guidance period. The cash balances are expected to be more than sufficient to finance and support the Company's planned growth campaign, while maintaining financial strength, and strengthening and increasing returns of capital to shareholders through dividends and share buybacks. To achieve this, the Company employs a disciplined capital spend framework during the guidance period with a target of $150 per GEO(2) of sustaining capital and net expansionary capital to not exceed $175.0 million per year on average. The Company expects to be in a position to further consider its cash return level later this year.

Please refer to Section 2: Core Business, Strategy and Outlook of this MD&A for further details on the capital allocation strategy of the Company, the ten-year production outlook and Yamana's investment and exploration strategy.

Strategic Developments, Construction Developments and Advanced Stage Projects:

Positive Development Decision on the Wasamac Project, Quebec

During 2021, the Company made a positive development decision on its wholly owned Wasamac project in the Abitibi-Tmiscamingue region of Quebec, Canada. Wasamac, a top-tier gold project in a region where Yamana has deep operational and technical expertise and experience, solidifies the Company's long-term growth profile with Yamana's average annual gold production in Quebec, including production from Wasamac and the Odyssey underground at Canadian Malartic, has the potential to increase to approximately 500,000 ounces by 2028, and continue at this level through 2041.

Yamana expects to receive all permits and certificates of authorization required for project construction by the third quarter of 2024. Construction time to processing plant commissioning is estimated at two and a half years, with the underground crusher and conveyor system scheduled for commissioning six months later and first gold production scheduled for 2026. Initial capital cost is expected to be relatively modest for a 7,000 tpd underground operation, at approximately $416 million.

During the first quarter, the Company continued to advance the bulk sample permitting process for Wasamac and expects to obtain the required approvals in the first quarter of 2023. The bulk sample permit would allow construction to commence on the ramps, enabling earlier access to the deposit to increase the level of confidence in metallurgical and geotechnical assumptions and optimize the processing flow sheet and mining sequence. Construction on surface facilities to support the ramp development activity and associated environmental requirements would also advance. The Company anticipates that a detailed update will be provided mid-year.

Exploration activities progressed as planned during the first quarter, with a focus on infill drilling on the Wasamac resource. Work on the Francoeur property during the quarter included ongoing modelling and compilation of drilling and other historic data. Field work is planned to start at Francoeur in the second quarter, including mapping and surface sampling and target definition in preparation for exploration drilling. For additional information on the planned Wasamac exploration initiatives, please refer to Section 6: Exploration.

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Canadian Malartic Underground Construction

The Company and its partner made a positive construction decision for the Odyssey project at Canadian Malartic in 2021. A National Instrument ("NI") 43-101 technical report completed in March 2021 included a full summary of the Odyssey underground project and demonstrated robust economics, a significant increase in mineral resources, first production from the Odyssey South deposit expected in 2023, and a mine life extension to at least 2039. As Canadian Malartic transitions from open pit to underground mining, underground production will offset a significant portion of the corresponding decline in open pit production. On a 100% basis, production from open pit mining from 2021 through 2028 is expected to be approximately 3.9 million ounces; the Odyssey underground mine plan supports annual gold production of 500,000 to 600,000 ounces when fully ramped up on a 100% basis. Furthermore, the Odyssey underground mine plan currently only includes about half of the project's 2.4 million ounces of Indicated Mineral Resources and 13.2 million ounces of Inferred Mineral Resources (on a 100% basis). Further upside from grade improvements and underground mine life extensions are expected to be realized through infill drilling to improve geological confidence, exploration drilling to extend known deposits and make new discoveries and engineering efforts, especially close to historical underground excavations and at depth at East Malartic.

Following significant advancement of the project in 2021, the Odyssey team is focusing on two key milestones:

Initiation of shaft sinking by the fourth quarter of 2022

First gold production from Odyssey South in the first quarter of 2023

The project continues to be on budget, and on schedule, and the Company shares the following updates:

The concrete pour to construct the 93-metre-tall headframe was completed on schedule in the fourth quarter of 2021, in preparation for shaft sinking slated to begin in the fourth quarter of 2022. Structural steel installation inside the headframe is ongoing. The production shaft will be 6.5 metres in diameter and 1,800 metres deep, with the first of two loading stations at 1,135 metres below surface. Construction of the temporary hoist building and waste silo is on schedule.

Ventilation is now provided directly through a fresh air raise to surface and two bays in the maintenance garage are now available.

As an employer of choice in the Abitibi, the Odyssey project is successfully building a highly skilled team and development rates are planned to continue increasing throughout the year.

Priority continues to be placed on the main ramp and also the level 16 exploration drift for infill drilling of the Odyssey South and Internal zones. The compressor building is expected to be completed in the second quarter and construction of the paste fill plant and 120 KV power distribution line are on schedule to support the Odyssey South stoping sequence.

Decree amendment and the mining lease process continue to be on target and all required permits to commence production from Odyssey South are expected by the end of 2022.

With a significant production platform, material cash flow generation and a prominent position within Quebec's Abitibi District, Canadian Malartic will remain one of the Company's cornerstone assets and one of the more prolific and generational mines in the world, particularly as the Odyssey mine is developed and comes into production. The Company is taking a disciplined approach to the development of Odyssey with a conservative outlook for initial throughput and production. While the Odyssey mine is expected to initially process 20,000 tonnes per day and produce 500,000 to 600,000 ounces per year, based on the current mine plan, the Company recognizes that there is a large inventory of ounces that is not currently in the mine plan.Odyssey ores will be processed through a plant with an original design capacity of over 55,000 tonnes per day, processing closer to 60,000 tonnes per day, which far exceeds the initial expected throughput of Odyssey. The plant was designed for the larger open pit operations that will end later this decade, and while the Company will scale the plant to the level required for the underground operation, that plant capacity will always be there. The Company's approach at its other mines has been to conduct extensive exploration which provides flexibility to maximize and increase throughput, and a similar approach will be taken with Odyssey, where delineation of extensions of underground mineralized zones and new zones of mineralization is already occurring. The extension of East Gouldie and discovery of Titan are examples of these underground exploration successes and opportunities. The Company's efforts at Camflo, East Amphi and Rand provide potential to add tonnage and production. The Company firmly believes that in its 10-year outlook period, these efforts will lead to more mining areas that will allow the Company to take advantage of available plant capacity, resulting in ore processing that will exceed 20,000 tonnes per day, and sustainable production will then significantly exceed the initial production plan of 500,000 to 600,000 ounces per year.

Jacobina Expansion Strategy

The Company's expansion strategy at Jacobina is well advanced and the Company anticipates that the low-cost operation will have a mine life that exceeds several decades, taking reserves and high conviction mineral resources into consideration. Production is expected to materially increase with phased expansions providing a

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pathway to sustainable production of 350,000 ounces per annum. This will increase the already excellent cash flow generation of the mine and deliver meaningful value. With well-below average costs at Jacobina, cash flows exceed those from mines that produce significantly, and as much as fifty per cent, more ounces. The mine currently has a reserve life of over 15 years plus a pipeline of resources and exploration targets that we believe will further extend mine life. Work performed since 2019 has allowed for the systematic exploration of the Company's large land package in the Jacobina district, which covers 155 kilometres of exploration potential, allowing for the definition of a fourteen-kilometre long belt of gold-bearing conglomerate located north of the mine complex and also extending the known mineralized reefs south of Joo Belo in a continuous area extending 2,200 metres. Further areas have been identified during reconnaissance exploration programs. Work will continue to define mineralized reefs exposed on surface and follow up with drill testing targeting both extensions of the mine complex and new standalone mine targets. Consequently, the Company sees significant opportunities to grow its regional presence and continue to build the world-class Jacobina Complex.

The Phase 2 expansion is progressing ahead of schedule and the mine is now expected to achieve the Phase 2 throughput objective approximately one year ahead of schedule, by the middle of 2022. Throughput in the first quarter averaged 7,850 tpd, a 3% increase over the previous quarter. During the fourth quarter of 2021, Jacobina received the expansion permit, allowing throughput to increase to 10,000 tpd, as announced in the December 6, 2021 press release "Yamana Gold Receives Permit at Jacobina, Initiating Ramp Up of Phase 2 Expansion, Expects Fourth Quarter Company Wide Production to Exceed 270,000 GEO With Costs Tracking to Be the Lowest of the Year". Receipt of the permit not only marks a significant milestone in the Phase 2 ramp up to 230,000 ounces of gold per year, but also facilitates the future Phase 3 expansion to increase production up to 270,000 ounces per year.

With the Phase 2 expansion advancing ahead of schedule, the Company is now pursuing the Phase 3 expansion to 10,000 tpd through continued incremental debottlenecking. With the permit to 10,000 tpd already in hand, Phase 3 is expected to increase gold production to approximately 270,000 ounces per year by 2025 with a modest capital expenditure of $20 million to $30 million.

The Phase 4 expansion, of up to 15,000 tpd, would increase gold production in excess of 350,000 ounces per year. To achieve the target throughput rates, a third grinding line would be added as well as an expansion of the leaching and CIP circuits. As the third ball mill was originally planned as part of the Phase 2 Feasibility Study, engineering for Phase 4 is well advanced. A comprehensive plan, aligning the processing plant, underground mine, and tailings management strategy, while managing capital expenditures and cash flow, is underway.

The Company is further evaluating the strategic options and direction related to Jacobina and the significant exploration that is available along the greenstone belt which hosts the mine. Jacobina is being envisioned as a complex of multiple mines, and more emphasis is being placed on regional and generative exploration.

Cerro Moro Scalable Plant and Heap Leaching Upside Opportunities

The objective at Cerro Moro is to create a sustainable ten-years of production of at least 160,000 GEO(2) per year, and up to 200,000 GEO(2) per year. If the Company successfully develops both the plant expansion and heap leach projects, which represent significant upside opportunities, along with conversion of the exploration targets to mineral resources, Cerro Moro could produce at least 200,000 GEO(2) per year.

During the first quarter, Yamana advanced the plant expansion, envisaged as a low-risk, phased expansion for Cerro Moro with quick payback from the initial phase used to fund subsequent phases. The Company is considering using fine screens instead of cyclones for classification to improve the efficiency of the existing ball mill which, combined with a slightly coarser grind size, is expected to increase throughput to at least 1,500 tpd, a 40% to 50% increase in capacity, without impacting gold and silver recoveries. The incremental capacity could be used for processing of lower grade mineralization, which is expected to increase annual gold and silver production, and in turn reduce fixed costs per unit at the mine, as those costs would be distributed over additional ounces. Preliminary analysis based on current operating data indicates that the existing crushing and flotation circuits are adequate for the higher throughput rate and reconfiguration of the leaching circuit could achieve the target throughput without requiring additional leach tanks. Upgrades to the concentrate thickener, clarifying filters, flocculant make-up system, and pumping would likely be required. The capital cost of this initial phase is estimated at a modest $15 million to $20 million. Many of the upgrades in phase 1 expansion would be sufficient for a second expansion phase to increase plant throughput to approximately 2,200 tpd, double the existing capacity, further increasing production and reducing operating unit costs. Capital estimates for the Phase 2 expansion are also $15 million to $20 million, for a total capital investment over the two expansion phases estimated at $30 million to $40 million. The Company is currently evaluating two options for phase 2 expansion,

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the addition of a high pressure grinding rolls ("HPGR") unit before the existing ball mill or the addition of a regrind unit. An expansion of the flotation circuit would also be required.

In parallel, a technical study on the potential heap leach project is underway following promising results from metallurgical testing conducted in 2021. Conceptual capital and operating cost estimation is expected to be completed in the second quarter, and an initial mineral inventory estimate, based on results from 2021 drilling, is planned for mid-2022. The results of testing indicate good potential for leaching of both oxidized near-surface vein material, zones with hypogene oxides (hematite) and some low sulphide gold-bearing veins, with extractions from column leaching averaging 68.6%. Gold recoveries at the Domos La Union and Michelle zones were particularly impressive, averaging 85.6% and as a result, exploration is focusing on these zones, with an objective of defining a heap leachable inventory of 5 to 8 million tonnes. Conceptual engineering for a 5,000 tpd heap leach operation commenced in the fourth quarter. A conventional heap leach configuration is envisaged with three stages of crushing. The leach pad, solution storage ponds, and Merrill-Crowe plant are conceptually planned to be located approximately 2 kilometres east of the current tailings storage facility. Average feed grade is estimated at approximately 1.0 to 1.4 g/t of gold, adding 45,000 to 65,000 ounces of gold production per year in addition to gold and silver production from the existing processing plant.

As Cerro Moro's mineral inventory increases, the Company will evaluate its options for alternative sources of power, which include a connection to the grid and wind power. Both options are expected to improve costs and further reduce greenhouse gas emissions, thereby accelerating the achievement of the Company's 1.5C science-based carbon emissions reduction target. The transition of Cerro Moro from high-cost diesel-generated electricity to wind power is the most attractive and compelling of several viable greenhouse gas reduction options. The conversion of approximately 50% of Cerro Moro's electricity requirements from diesel to wind power would meet the greenhouse gas emission reductions required between now and 2030 to achieve the Company's 1.5C science-based target. Further, it is expected that the transition to wind power would reduce operating costs, expand mineral reserves and mine life. A detailed evaluation, including a third-party feasibility study of this opportunity is underway. The third-party study to finalize the Company's evaluation of wind power indicates there should be a sufficient and sustainable supply of power as the Cerro Moro area of southern Argentina is considered one of the best on-shore locations in the world for wind energy. The results of the alternative power analysis will be considered in the plant expansion pre-feasibility and heap leach studies to explore synergies between the projects.

MARA Project Advances

The MARA Project represents a significant strategic value opportunity and a solid development and growth project. The Company intends to pursue all available avenues to continue to advance and unlock its value through its controlling interest while also considering strategic alternatives that could unlock significant value along the way. During the last year, several proposals were presented to the Company for its interest in MARA and, after consideration, the board determined that any strategic initiatives will be considered closer to the completion of the feasibility study and application for permitting as the certainty of the project from these events is expected to create more value for the project. The MARA Joint Venture is held by the Company (56.25%), Glencore International AG (25%) and Newmont Corporation (18.75%). The pending feasibility study, which is being overseen by the Technical Committee comprised of members of the three Companies, will provide updated mineral reserves, production and project capital cost estimates. The engineering effort for the feasibility study is expected to be completed by the end of 2022 and the finalized report in early 2023, however a considerable amount of information in the pre-feasibility study is already at feasibility study level as a result of the Integration. MARA is conducting field campaigns to complement the Environmental and Social Impact Assessment ("ESIA") baseline data. Preliminary results and advancement of the project are being shared with the Intergovernmental Commission of Catamarca, prior to filing the full ESIA. The Company plans to complete the ESIA definition for MARA by the end of 2022.

Work during the first quarter of 2022 focused on continuing the progress in 2021: advancing the feasibility study engineering, mine design and planning, metallurgical and geotechnical drilling campaigns, field work at site, baseline social and environmental studies, as well as permitting and working with local stakeholders. The field work plan continues, with the drilling campaign now covering the Agua Rica infrastructure and is expected to be completed by the third quarter of 2022.

MARA is the combined project comprised of the Agua Rica site, Alumbrera site as well as the Alumbrera plant and ancillary buildings and facilities, and will rely on processing ore from the Agua Rica mine at the Alumbrera plant. The project design minimizes the environmental footprint of the project incorporating the input of local stakeholders. MARA will be a multi-decade, low cost copper-gold operation with annual production of 556 million pounds of copper equivalent during the first ten years of production, and life-of-mine annual production of 469 million pounds of copper equivalent on a 100% basis. MARA will be among the top 25 copper producers in the world when in production, and is one of the lowest capital intensity copper projects globally.

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For full details on the aforementioned updates, please refer to Section 5: Construction, Development and Other Initiatives.

OPERATING

First quarter GEO(2) production of 238,617 ounces was in line with plan and exceeded prior year first quarter production of 231,988 GEO. Standout GEO production performances were delivered by Jacobina and Cerro Moro. First quarter total cost of sales, cash costs(1), and AISC(1) on a per GEO(2) basis were $1,212, $734, and $1,084 respectively. Costs were lower than plan, despite the first quarter being the lowest planned production quarter of the year, and the lower than plan and guidance gold to silver ratio which also impacted GEO(2) production. The Company continues to monitor the impact of inflationary pressures on its cost structure and notes that in the first quarter, the price of certain consumables, primarily diesel and mill balls, increased while certain others have remained relatively constant. Furthermore, higher base metal prices have had a positive impact on by-product credits allocated to GEO(2) costs. The impact of inflation on costs remains uncertain mostly because it is unclear if the geopolitical events that have occurred since the Company provided its guidance earlier in the year, which have driven price increases on certain items, will continue, or whether the events will continue to impact the price of those items. Equally, in the first quarter, the Company successfully mitigated inflationary trends through productivity improvements and overall, as aforementioned, costs in the first quarter were lower than plan and in line with guidance. While the Company plans to increase capital spending in each of the following quarters, as compared to the first quarter, this will coincide with increases in production and generation of cash flows and free cash flows. Further, the Company notes that cash flows in the second half of the year will also increase as higher income tax installments will have been paid, as normal, in the first half of the year.

GEO is calculated as the sum of gold ounces and the gold equivalent of silver ounces using a ratio of 78.29 for the three months ended March 31, 2022, and 68.84 for the three months ended March 31, 2021. GEO calculations are based on an average market gold to silver price ratio for the relevant period.

GEO(2)

Production

Sales

Per GEO sold data

Total cost of sales(6)

Cash costs(1)

AISC(1)

Production (ounces)

Sales (ounces)

Average realized price per ounce(1)

Average market price per ounce*

Production (ounces)

Sales (ounces)**

Average realized price per ounce(1)

Average market price per ounce*

* Source of information: Bloomberg.

** Included in three months ended March 31, 2022 silver sales ounces are 378,088 ounces, delivered under the silver streaming arrangement (2021: 335,699 ounces).

HEALTH, SAFETY, AND SUSTAINABLE DEVELOPMENT

Yamana's health, safety and sustainable development ("HSSD") approach is guided by the Company's corporate-level standards and programs; these are integrated into all operations, development projects, and exploration activities. Yamana recognizes the importance of striving to meet and exceed its HSSD responsibilities and objectives, and the role these efforts have in delivering on the overall objective of creating value for all stakeholders. Since early 2020, one of the most important considerations, in addition to the on-going priorities of safeguarding worker health and safety, protecting the environment and building privilege to operate with host communities has been the Company's response to the global COVID-19 pandemic.

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Through the Company's active responses to COVID-19, the Company has demonstrated its commitment to environmental, social and governance ("ESG") excellence in action and resilience. Consistent with the mission to mine precious metals profitably and responsibly, the Company is prepared to forego production to safeguard its efforts to promote health, safety and well-being of its workforce and host communities.

High vaccination rates amongst the Company's employees and contractors at all locations continue to protect people, host communities and our business. In the first quarter of 2022 host countries began to experience increases in the number of reported COVID-19 cases, although the rapid rise in caseloads that occurred in North American and Europe has yet to appear in our operating jurisdictions. The Company continues to actively monitor Omicron-related caseloads and healthcare system capacity in South America, government responses, and vaccination availability. Yamana also works closely with local and regional governments to ensure prevention procedures are followed.

As the pandemic transitions to an endemic situation, we continue to have low numbers of worker COVID-19 cases at sites. The Company's continued implementation of its highly successful prevention, monitoring, testing, quarantine and contact tracing protocols has limited their spread. Infected people are being isolated successfully with no operational impact. The number of active cases at the end of the first quarter 2022 was in the single digits, rates of third booster vaccine doses are climbing and fourth doses are currently being administered in Chile.

The Company continues to manage its business in a way that respects, and is mindful of, the impact that COVID-19 has had and could have on host communities.

As part of the continuing implementation of its Climate Action Strategy, the Company completed its inaugural Climate Action Report disclosing information on the recommendations of the Task Force on Climate-related Financial Disclosures ("TCFD"), which was published on the Company's website at http://www.yamana.com on April 11, 2022. The report builds on the Company's 2021 climate action work and includes information on the Company's approaches to climate governance, strategy, risk management, and targets, metrics and performance. The report also describes how the Company will achieve its 1.5C science-based target compared to pre-industrial levels by 2030. The Company is well positioned to achieve its 2030 climate action target with only modest expenditures. The transition of Cerro Moro from high-cost diesel-generated electricity to wind power is the most attractive and compelling of several viable greenhouse gas reduction options. The conversion of approximately 50% of Cerro Moro's electricity requirements from diesel to wind power would meet the greenhouse gas emission reductions required between now and 2030 to achieve the Company's 1.5C science-based target. Further, it is expected that the transition to wind power would reduce operating costs, expand mineral reserves and mine life. A detailed evaluation, including a third-party feasibility study of this opportunity is underway. The third-party study to finalize the Company's evaluation of wind power indicates there should be a sufficient and sustainable supply of power as the Cerro Moro area of southern Argentina is considered one of the best on-shore locations in the world for wind energy. The results of the alternative power analysis will be considered in the plant expansion pre-feasibility and heap leach studies to explore synergies between the projects. Work will continue during 2022 to progress other climate action objectives, including advancing the evaluation of other operational projects to reduce greenhouse gas emissions and estimation of our Scope 3 emissions.

Other recent highlights relating to HSSD are as follows:

The Company's Total Recordable Injury Rate ("TRIR") for the first quarter 2022 was 0.75*. We have modified our TRIR reporting to align with our financial reporting standards which include our wholly-owned operations, exploration projects, development projects (Wasamac and MARA), proportional consolidation of Canadian Malartic (50%), and closed projects. For comparison, the corresponding full-year 2021 result was 1.07*.

As of April 5, 2022 more than 99%** of the Company's employees and contractors at its wholly-owned operations and exploration projects have received at least one dose of a COVID-19 vaccine and more than 96%** have received two doses. Approximately 76%** of workers have received a third dose booster shot.

The Wasamac project opened a dedicated community relations office in Evain, QC to further enhance and bring focus to its commitment to open and transparent dialogue with host communities and the broader group of stakeholders.

* Calculated on a 200,000 exposure hours basis including employees and contractors.

** Vaccination rates are exclusive of Canadian Malartic, in which we hold a 50% interest. Vaccination rates at Canadian Malartic are in line with the high Abitibi-Tmiscamingue regional rates.

FINANCIAL

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Yamana Gold : MANAGEMENT'S DISCUSSION AND ANALYSIS OF OPERATIONS AND FINANCIAL CONDITION - Form 6-K - Marketscreener.com

Recommendation and review posted by Bethany Smith

PERTH (miningweekly.com) Diversified miner South32 has maintained its production guidance for 2022 following a strong March quarter, while operating cost expectations for its Australian and South African operations have increasedon the back of stronger producer currencies, higher raw material costs and an increase in commodity priceswhich has resulted in higher price-lined royalties.

We achieved a number of significant milestones in the quarter, making further progress to reshape our portfolio for a low carbon future, said CEO Graham Kerr on Tuesday.

We reported copper production for the first time, having completed our acquisition of a 45% interest in the Sierra Gorda copper mine. We moved a step closer to doubling our share of green aluminium production, delivering first metal from our Brazil Aluminium smelter following the end of the period. We also reported the prefeasibility results for our Taylor deposit, underlining its potential to add further growth in the metals critical to a low carbon future.

We achieved another excellent operating result, delivering to plan, capitalising on historically strong end markets for many of our commodities. Our strong financial position allowed us to close the acquisition of Sierra Gorda and return our balance sheet to a net cash position by the end of the March quarter, said Kerr.

Alumina production for the March quarter was down 1% on the previous quarter, to 1.3-million tonnes, while aluminium production in the same period also declined by 1%, to 243000 t.

During its first quarter of copper production, South32 delivered 8400 t of copper, following the completion of the 45% interest in the Sierra Gorda project.

Manganese ore production for the March quarter was down 4% on the previous quarter, to 1.2-million tonnes, while metallurgical coal production was up by 31% in the same period, to 1.5-million tonnes. South32 in December completed an extended longwall move at the Dendrobium mine, in New South Wales, with the December quarter also impacted by Covid-19 workforce restrictions impacted by labour availability.

Meanwhile, nickel production for the March quarter was up 1%, to 10600 t, payable zinc production was down by 5% on the previous quarter, to 16400 t, and payable lead production was up by 22%, to 34600 t.

In the nine months to date, both alumina and aluminium production remained stable at 3.9-million tonnes and 737000 t respectively, while manganese ore production declined by 5% on the previous corresponding period, to 3.9-million tonnes.

Metallurgical coal production in the nine months to March declined by 10% on the previous corresponding period, to 4.3-million tonnes, while nickel production was up by 33% in the same period, to 30900 t. Zinc production for the year-to-date was up 2%, to 49100 t, while lead production was up 5%, to 94800 t and silver production was up by 9%, to 10.3-million ounces.

South32 told shareholders that the Worsley Alumina operation, in Australia, remains on track to creep production beyond nameplate capacity in 2022, with the refinery benefitting from historical investment and ongoing improvement initiatives.

South32s Brazil Aluminium operation delivered first metal from the restart of the renewable-powered Alumar smelter following the end of the period, while the Hillside Aluminium and Mozal Aluminium continued to test their maximum technical capacity, taking advantage of record aluminium prices.

The Cannington operation delivered a 6% increase in year-to-date zinc equivalent production, benefitting from higher planned silver grades and a drawdown in run-of-mine inventory.

South32 also reported that the Cerro Matoso operation achieved a 33% increase in year-to-date nickel production, owing to higher grades from the Q&P pit and the prior periods successful furnace refurbishment.

Meanwhile, South32 on Tuesday also told shareholders that the company had been awarded a A$15-million grant from the New South Wales government in April to construct a commercial pilot ventilation air methane abatement facility at its Illawarra Metallurgical Coal operations.

The new facility, featuring cutting-edge technology to tackle fugitive methane emissions will be established with the support of the Commonwealth Scientific and Industrial Research Organisation and its own co-funding of A$4.5-million.

The project will make up part of South32s use of innovative technologies to reduce emissions, in line with its goal to halve operational carbon emissions by 2035 as part of its pathway to achieve net-zero operational carbon emissions by 2050.

The miner has, meanwhile, also downwardly revised its capital expenditure guidance for 2022, by $36-million, to $702-million, reflecting a deferral of capital spend at Worsley Alumina until 2023, reducing the 2022 improvement and life extension capital expenditure estimate by$11-million to $91-million, while also accounting for slower-than-expected contractor mobilisation at the Hermosa project, which has reduced the growth capital expenditure estimate for 2022 by $25-million to $90-million.

The company has also revised its operating cost guidance for the full-year, at the majority of its operations, to reflect the impact of stronger producer currencies, higher prices for raw materials and an increase in price-linked royalties.

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South32 sticks to its production outlook - Creamer Media's Mining Weekly

Recommendation and review posted by Bethany Smith

(CNN) After age and genetics, being a woman is the single most important risk factor for developing Alzheimers disease, experts say.

Two out of every three brains affected by Alzheimers disease are womens brains, said Dr. Richard Isaacson, director of the Alzheimers Prevention Clinic in the Center for Brain Health at Florida Atlantic Universitys Schmidt College of Medicine.

Now, a new study has good news when it comes to giving women a chance to reduce their increased risk. Personalized lifestyle interventions such as diet, exercise, stress reduction and sleep hygiene were able to reduce Alzheimers risk factors in both sexes, but they worked even better in women.

Our individually tailored interventions led to greater improvements in women compared to men across risk scales for Alzheimers and cardiovascular disease, said Isaacson, who coauthored the paper.

Women also showed greater improvements than men in biomarkers such as lower blood sugar and lower LDL, or low-density lipoprotein, which is the bad cholesterol.

This study clearly reinforces the need for additional larger studies to be able to better predict the baseline cognitive trajectory in aging females versus males, said Rudy Tanzi, a professor of neurology at Harvard Medical School. He is director of the genetics and aging research unit at Massachusetts General Hospital in Boston.

As we aim to find ways to nip this disease in the bud stage, we will need to know if prevention and treatment strategies will work equivalently on both men and women. This new study clearly brings us a big step closer to that goal, said Tanzi, who was not involved in the study.

Impact of personalized interventionsThe new study followed a subset of people participating in a 10-year study designed to test the impact of personalized recommendations on cognitive function and risk factors for dementia. The Comparative Effectiveness Dementia and Alzheimers Registry trial, which began in 2018, is being conducted at NewYork-Presbyterian/Weill Cornell Medical Center in New York City.

After full blood, physical, cognitive and genetic workups, patients were provided with individualized genetic counseling and education. Medications, vitamins and supplements were tailored to each persons unique results as well. In addition, all participants received personalized lifestyle interventions, such as counseling on exercise, diet, blood pressure control, sleep hygiene and stress reduction.

Everyone in the CEDAR trial has a family history of Alzheimers, but the majority had no signs of cognitive decline when the study began, Isaacson said. Of the 154 men and women participating in the research, 35 were diagnosed with mild cognitive impairment, or MCI, due to Alzheimers, but it was not severe enough to impact their daily lives, he said.

The original studys main findings were published in 2019. People with MCI saw their performance on cognitive tests for memory and thinking skills improve by nearly 5 points when they followed at least 60% of their lifestyle recommendations (on average, at least 12 of the 21 different recommendations) for 18 months.

However, the 2019 study found that people with mild cognitive impairment who followed less than 60% of the suggestions showed no cognitive improvement in fact, they continued to decline by 6 points on average.

The cognitively normal patients with a family history of Alzheimers disease, called the prevention group, were able to get an equally impressive cognitive boost of an average of 4.5 points by following at least some of the lifestyle recommendations. It didnt seem to matter if they followed less than 60% of them, Isaacson said.

The good news from our study is that there were actually cognitive improvements at 18 months in both women and men when compared to the control populations, Isaacson said. A lot of the drugs that have been studied aim to delay cognitive decline, but it is harder to show improved cognition over time.

Approximately half of the participants in CEDAR carry at least one APOE gene, which may increase the risk of developing Alzheimers disease. However, the study found no difference in the interventions cognitive benefits for those with one or two copies of APOE compared with those without the gene, so that was also reassuring, Isaacson said.

Impact on women versus menThe new study, published Tuesday in the journal of the Prevention of Alzheimers Disease, took the original 2019 study a step further by analyzing a subset of participants to see whether there was any difference between men and women when it came to how well the lifestyle interventions work.

Women have very different and unique risk factors than men for dementia, Isaacson said. Women have a 39% higher risk of dementia if they have fat accumulating around their midsection.

And the rapid decline in estrogen during the perimenopause transition can actually be one of the most impactful risk factors for developing Alzheimers pathology in the brain, he said.

In the new analysis, women in the prevention group, who started the trial with no cognitive issues, demonstrated greater improvements than men in two areas: one of two cardiovascular risk scales and in levels of the good cholesterol, HDL, or high-density lipoprotein, which is protective against heart disease.

Women with mild cognitive decline, called the early treatment group, showed greater improvements than men when it came to average blood sugar levels and two cardiovascular risk scales. This female cohort also had more significant improvements in several important cholesterol (or lipid) biomarkers than men in the early treatment group.

For all participants, complying with an additional 10% of the personalized recommendations resulted in an additional 0.9 point improvement for women and 0.41 points of improvement for men on tests of cognition.

How does reducing cardiovascular risk impact future cognition? Because whats good for the heart is good for the brain, experts say.

Vascular risk factors such as high blood pressure, high cholesterol, high blood sugar or diabetes may not be the cause of Alzheimers disease, but it can fast-forward Alzheimers pathology, Isaacson said. I would prefer to slam on the brakes rather than rev the engine on the path to cognitive decline.

Finding that women were able to reduce their risk even more than men is welcome news, Isaacson said, as it provides a promising area for future study and gives hope that women can tip the battle against Alzheimers in their favor.

By treating people in an evidence-based yet safe way, using multiple lifestyle and medical interventions, weve shown that you can really make an impact on brain health, he said.

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Recommendation and review posted by Bethany Smith

Peter and Sandra Krause and daughter Robyn, Sunnyside Wagyu, Inverell, right, with Troy Stephens and the Yulong Investments team and Peter Brazier from GDL after the $400,000 heifer sale.

AN incredible new benchmark has been set for the Australian seedstock industry, when last nights Elite Wagyu Sale held as part of the industrys 2022 Wagyu Edge Conference in Melbourne lit up with a series of blistering new records.

Heifers sold to an incredible $400,000, setting a new all-breeds record for any seedstock animal. The figure easily eclipsed the previous bull record held by a Brahman of $325,000, and the registered female record of $280,000 set by a Wagyu heifer (see Beef Centrals comprehensive list of record prices for bulls and females).

The depth of relentless bidding support last night from across Australia, plus North America, Europe and Asia saw 16 registered females average an incredible $67,406. Ten bulls offered and sold averaged $72,950 another all-breeds record hitting a new breed record high of $240,000. Eighty four individual embryos averaged $2632, while semen straws averaged $3178 each.

The sale can easily lay claim to being the strongest result ever seen in the beef seedstock industry, worldwide. Morew than 100 bidders were logged-on from across the globe, together with 300 live in the conference room last night.

Opening the sale and setting the new $400,000 all-breeds record was a 13-month-old unjoined female from Peter and Sandra Krause and familys Sunnyside Wagyu, Inverell. With all four $Indexes in the top one percent for the breed, and the highest marbling EBV in the catalogue at +3, the heifer drew bidding interest from all over the globe. The eventual buyer was Yulong Investments from Nagambie VIC, which was also a prominent buyer at the recent Mayura Wagyu genetics sale.

The top price bull, Sahara Park Yasufuku R153, a 16 month old son of high marbling performer World K Yasufuku Jr, offered by Dean and Sam Pollard of Sahara Park, Rockhampton QLD, was purchased by Que Hornery from Bar H Grazing, Moranbah. Mr Hornery said the bull, with a marbling EBV of +2.1 and an F1 Index of $175, would be the star in taking his business to another level.

Next best among the bulls at $220,000 was an unusual pick one of three offering from prominent Victorian Wagyu breeder David Blackmore all carrying rare combinations of elite Wagyu genetics.

The buyer was Hewitt Pastoral Enterprises, which has been an active participant in securing elite Wagyu genetics this year.

Post-auction approaches could see deals done in coming days on the remaining two bulls from the offering, Mr Blackmore told Beef Central.

Australian Wagyu Association president Charlie Perry said it was incredible to see the optimism being expressed by bidders and buyers throughout last nights sale.

It was a coming-of-age for this particular sale, which features only animals within the top five percent of Wagyu EBVs. Every single lot offered was of extremely high quality, and buyers clearly recognised that.

Mr Perry said the result was a testament to the confidence evident across the entire Australian beef industry at present, and the Wagyu sector in particular.

Buyers are recognising the contribution of the genetic tools that are now contributing to increasing the accuracy of animal performance figures. All entries were very proven animals, at least one generation back in their pedigrees.

GDL selling team fielding bids at last nights Elite Wagyu auction

Mr Perry agreed that the sale also flagged the value that the industry now placed in high performing females. For the first time in history, a female stands as the highest priced animal ever in the Australian seedstock industry.

Whats changing that is the contribution not only of embryo transfer work, but IVF, he said.

Suddenly, these elite females contain a whole lot more value than what they once did.

A similar trend was seen in the sales semen offering, selling to $37,500 for three straws of Macquarie Wagyus Coates Itoshigenami G113, and grossing almost $500,000 for 156 straws.

With IVF technology, one straw of semen can now yield 40 calves, instead of one or two in the past. Each straw has greater inherent value.

Underpinning all this is the current state of the cattle market, and the continued strong seasonal prospects in many parts of Australia. Its a great time to be in beef, Mr Perry said.

The current mood for securing elite quality Wagyu genetics was clearly set earlier this month at the annual Mayura Wagyu genetics sale, where principal Scott de Bruin sold a collection of 45 lots covering 22 heifers, 13 bulls, nine semen straw lots and a single offering of four embryos averaged $55,011/lot an all-time record for any single-vendor seedstock sale of any breed in Australia, and potentially, the world.

To have the best genetics on offer from 39 leading Wagyu breeders from around the world, in one place at one time last night, created an astounding event and spectacle, AWA chief executive Matt McDonagh said.

The AWA Elite Wagyu Sale has become the hallmark Wagyu genetics event for the global Wagyu sector. The result consolidates Wagyus position in the global beef industry at the cutting edge of progress.

Agents for the simultaneous live and online sale were Grant Daniel & Long and Elders.

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Elite Wagyu sale lights-up, with all-breeds record prices and averages - Beef Central

Recommendation and review posted by Bethany Smith

A recent portrait of Rosalind Morris. (Photo: Courtesy)

Rosalind Morris, a celebrated wheat cytogeneticist and professor, peacefully passed away on March 26, 2022, just a few weeks shy of her 102nd birthday. Morris fought a long battle with cancer in her 90s and, most recently, an infection of COVID-19, which proved fatal to her health.

According to her wishes, there was no funeral or memorial service. Morriss body was cremated, and her ashes deposited in her familys plot in Ontario, Canada.

Born in Ruthin, United Kingdom, in 1920 to schoolteacher parents, Morris pursued studies in agricultural sciences at the University of Guelph and earned a bachelors degree in horticulture. Morris would later earn a Ph.D. from Cornell Universitys department of plant breeding, becoming one of the first two women to accomplish this feat, along with Leona Schnell.

A pioneer in agricultural science and one of the first women scientists of her time, Morris dedicated her life and career to understanding and developing wheat genes. Her contributions include the development of wheat genetic stocks, or wheat populations generated for genetic studies, with far-reaching impact globally in explaining wheat genetics. The work of Morris provided a premier resource base for the emerging field of functional genomics, which explores how DNA is translated into complex information in a cell.

During World War II, Morriss deep concern over the effects of atomic bombs dropped on Hiroshima and Nagasaki led her to study and experiment with the effects of X-rays and thermal neutrons on crop plants. In 1979, Morris became the first woman honored as a fellow of the American Society of Agronomy.

While being an acclaimed scientist internationally, Morris was also known for her passion for teaching. In the same year Morris earned her doctoral degree from Cornell University, she was hired as the first female faculty member in the agronomy department at the University of Nebraska-Lincoln (UNL) in 1947. This career would last 43 years: first as an assistant professor in 1947, becoming a professor in 1958 and remaining in that role until 1990, when she gained the title of emeritus professor of plant cytogenetics.

Morris was a trailblazer for women in agronomy during a point in history when few women were given the opportunity to pursue a career in the sciences. Morris is remembered by her peers not only for her lifelong contribution to agricultural sciences but also her immense kindness and patience.

See the article here:
Celebrating the life of Rosalind Morris, trailblazer for women in agriculture - CIMMYT

Recommendation and review posted by Bethany Smith

By Brendan Foster

The pandemic makes daily life a struggle for many Pennslyvanians. Rather than help their constituents, opportunists in the legislature aim to make life even harder for some of the most vulnerable citizens of the Commonwealth.

Last year, Representative Barbara Gleim of Cumberland county introduced HB 972, which successfully passed committee last month. The bill bans public schools and colleges from allowing transgender women and girls to compete in sports designated for women.

As the name implies, the ostensible purpose of the bill is to protect cisgender women from competing against trans athletes, whom Gleim claims have an unfair advantage against their cis peers. However, like similar bills introduced nationwide, it actually uses trans women as pawns to ride a wave of backlash against advances in trans rights.

This bill is only one of a record-shattering 238 anti-LGBTQ bills proposed in state assemblies nationwide. While many restrict or ban vital treatment for transgender youth against the recommendations of medical and psychiatric experts, 25, including HB 972 restrict or ban trans women from womens sports.

Supporters of these bans often claim they are only recognizing the reality of biology, and Rep. Gleim is no different. At the same Education Committee meeting, she gave several examples of advantages trans women have over their cis peers, such as muscle mass and lung size. While this might make it seem like the science is settled, actual scientific studies show that things are not so clear.

A 2021 paper from the International Federation of Sports Medicine (FIMS) and the European Federation of Sports Medicine Associations (EFSMA) states that, while testosterone levels do give athletes an advantage, regulations for trans women must be written on a sport-by-sport basis. Nowhere do the authors recommend a total ban on trans women in womens sports like HB 972 proposes.

Another 2021 statement from FIMS argues that, while there is consensus on regulations for testosterone levels, there is a distinct lack of sports performance data to inform and update sports policy for transgender athletes. In other words, there is currently no scientific consensus supporting HB 972 or any regulations on trans women athletes beyond testosterone levels.

Clearly, the existence of trans athletes in Pennsylvania must be an urgent crisis for lawmakers to so blatantly ignore the scientific consensus. Which begs the question: where are the trans women dominating womens sports?

Gleim could not answer that at last months committee meeting, likely because trans people represent a tiny section of the population: A 2016 survey found 1.4 million American adults are trans, while more recent experimental data found around 2 million, a little more than 1% of the adult population. That means there are approximately 96,000 trans adults in the commonwealth.

In addition, intersexed people, people born with sex characteristics or genetics that do not fit into the male-female sex binary Gleim assumes, make up 1.7% of the population about the same number of red-haired people. The bill does not say where they go, despite being just as big a population as the trans people Gleim finds so threatening.

If this is purely an issue of preserving fairness in sports, which it is not, this might be the most inefficient way of going about it possible.

There is also the question of how Gleim wants to enforce the ban in the first place. Her ignorance of the available scientific data is once again demonstrated by the fact that the bill offers no guidelines regarding testosterone levels for trans women, as experts recommend; it simply states that sex is determined by the reproductive anatomy and genes. This language potentially subjects trans as well as cis students, including minors, to invasive sex tests to prove they fit a pre-determined definition of feminity.

As Lancaster high school student Olivia Heim stated in a speech for the Pennsylvania Youth Congress, the femininity of girls that are simply naturally taller and stronger might be challenged, subjecting them to sex tests to prove their bodies fit a narrow definition of what a female body should look like. Ironically, instead of protecting women and girls, HB 972 reinforces a system that takes a purely fictional idea of what a woman is, and uses it to crush and suppress any woman, cis or trans, that does not fit into it.

There is serious doubt that, even if passed by the General Assembly, the bill would last very long. Not only did Gove. Wolf state that he would veto it, similar bills have been struck down or blocked in federal courts. If attempting to pass the bill is so pointless, it is unclear why Gleim would propose it.

The simple answer is that Gleim, like other Republicans and conservative politicians nationwide, is attempting to ride a trend in the culture war by attacking one of the most vulnerable and maligned groups in Pennsylvania.

Trans people attempt suicide at a rate of 40%, and sports can create a sense of camaraderie and belonging for people who feel like outsiders. Defeating this bill is not just a fight for the right to belong, it is a fight for life itself.

Brendan Foster is a journalist based in Harrisburg, Pa.

See the article here:
Where are the trans women dominating womens sports? | Opinion - PennLive

Recommendation and review posted by Bethany Smith

SEATTLE If it werent for squirrels, Bagel probably wouldnt be here today at Washington State Universitys College of Veterinary Medicine. The yellow Labrador was destined to be a guide dog for the blind but flunked out because she was distracted by small animals. Now, this otherwise very good girl has a second chance to be of service by participating in the most comprehensive study ever conducted of health and aging in dogs.

Bagels owner, Brenda Voght, volunteered her to join a research pack that already includes more than 37,000 pet dogs across the country and is expected to swell to 100,000. Called the Dog Aging Project, the ambitious undertaking seeks to answer many of the questions dog owners ask and often anguish over: Why do some breeds live longer than others? How do genetics, environment and lifestyle affect longevity and the risk of disease? And, above all: How can we ensure our beloved companions stay healthy, happy and active for as long as possible?

I would like to know if there is something we can do as humans, as their partners, to extend their lives a little longer, says Voght. After her last dog died, it was a year before she was able to open her heart to another puppy.

She fostered Bagel for about a year, then adopted her after the canines career change the gentle euphemism used when guide dogs dont make the cut.

On average, yellow Labs live 10 to 12 years.

Bagel is 9.

The project welcomes dogs of all types and ages and plans to track them for at least 10 years, says Daniel Promislow, an evolutionary geneticist at UW Medicine who co-founded the initiative and helped assemble a national team of more than 80 researchers, veterinarians and data scientists to coordinate the massive undertaking.

No one has ever investigated such a large number of dogs over such a long period of time, especially at the level of detail Promislow and his colleagues envision. One branch of the study is sequencing the genomes of at least 10,000 dogs. Another zeros in on the oldest dogs in the pack the supercentenarians to look for keys to their longevity.

All of us are really excited about what will come out of it, says Elaine Ostrander, who pioneered genetic analysis of dogs more than two decades ago in Seattle at the Fred Hutchinson Cancer Research Center. She now works at the National Human Genome Research Institute.

Its long been clear that big dogs have shorter lifespans than small dogs, and that different breeds are predisposed to different ailments, says Ostrander, who is not involved in the project. Golden retrievers are prone to cancers. German shepherds often develop hip dysplasia. Doberman pinschers have a high prevalence of heart disease. The Dog Aging Project will help reveal more about the mechanisms behind those links, she says.

Theyre going to be able to make those connections pretty tightly because their data set is the biggest one out there.

The researchers also hope to gain insights into normal aging, along with the entire spectrum of ailments that plague older dogs, from arthritis and hearing loss to cataracts and cognitive decline. Discovering ways to help dogs live longer would be wonderful, says Promislow. But the primary goal is to prolong health span that golden period of well-being when dogs can leap and dive and fetch and snuggle free from pain or disability.

We want to help each dog live the longest, healthiest lifespan that it can, he says.

The findings could be relevant to human health as well.

Dogs suffer from many of the same diseases we do. And unlike mice and other animals used in laboratory studies, dogs are genetically diverse. They live in our homes, breathe the same air and experience the same conditions.

The sad fact that dogs lives are shorter than ours means its possible to gain that knowledge more quickly by focusing on humanitys best friends.

Most of the animals enrolled in the Dog Aging Project never have to leave their home turf. Owners fill out an annual, 116-page questionnaire that covers everything from diet and mobility to temperament, favorite types of toys, bowel habits, pesticide exposure, health status and sleeping arrangements. Environmental data, like air and water quality, is correlated to each dogs geographic location. Participants also can upload their dogs veterinary records, and more than 15,000 already have done so.

Dog owners are integral to the project, which keeps them in the loop with blog posts and a dedicated social media platform called the Dog Park. Its the kind of science that cuts across politics, demographics and geography because so many Americans are crazy about dogs, Promislow says.

Im really excited about the ability to bring science to the lives of people in a way thats fun and informative and educational.

A small subset of canines are candidates for more intensive study, which is why Voght made the drive from her home in Bothell to the other side of the state. Bagel is being evaluated for the most high-profile arm of the project: a clinical trial of a potential anti-aging drug.

Called rapamycin, the medication is used in human transplant patients to prevent organ rejection. But studies in yeast, worms and mice show that low doses can extend lifespan by up to 25%. Rapamycin also delays age-related maladies such as cognitive decline and cancer, and boosts heart health in mice.

Dr. Kate Creevy, chief veterinary officer for the project, is optimistic it might do the same for dogs. In one small trial, dogs who got the drug showed improved heart function. In another, owners said their dogs seemed more active.

Now, the team is recruiting 500 senior dogs for a year of treatment and two years of follow-up. Half the dogs will get rapamycin, and half will get a placebo. Neither owners nor scientists will know which until the end.

Even if we dont actually change lifespan, if we improve the experience of aging, that will be really, really valuable to dogs and the people who love them, says Creevy, of Texas A&M University.

The dogs in the study need to be healthy, so Bagel is getting the type of checkup available only in a veterinary teaching hospital such as WSUs. Staff leads her into an exam room, where she obligingly hops on the table and rolls onto her side.

Technicians shave a small patch of fur for analysis, draw blood, measure blood pressure and attach electrodes to monitor her heartbeat. Dr. Ryan Baumwart, a veterinary cardiologist, checks Bagels eyes and probes her heart with ultrasound, displaying the image of the beating organ on a wall-mounted computer screen.

The study is just getting started, and, so far, only about half of dogs examined have qualified. Bagels scans look promising, Baumwart says. Now, its a matter of waiting on the blood tests.

The dog aging project reflects a new approach to the most common causes of death in canines and people, says co-director and UW Medicine pathologist Matt Kaeberlein, who studies the basic biology of aging. Most research focuses on specific diseases, such as cancer or Alzheimers. But nearly all of the major killers are strongly linked with age, so Kaeberlein argues that it makes sense to focus on the aging process itself.

If we can understand aging biology and what it is at a cellular, molecular, mechanistic level, then maybe it will be feasible to target that biology with interventions, he says. Those might be nutritional strategies, drugs or gene therapy, with the goal of lowering the risk of all age-related diseases.

For example, rapamycin seems to work at least in part by reducing inflammation, which increases with age and impairs immune function. Older animals also accumulate more cellular debris, and rapamycin revs up the process of clearing it away.

Another arm of the project, called the Precision Cohort, will delve in unprecedented detail into biochemical changes and shifts in gene expression over time in 1,000 dogs.

We will know more about the biology and physiology of those dogs than probably anybody has ever known about dogs before, Kaeberlein says. We will be collecting very high-resolution data to try to understand the relationship between their unique genetic makeup and their unique environment thats influencing the aging process.

One of those dogs is Hana, a 3-year-old Cavalier King Charles spaniel with long, silky ears who lives on Bainbridge Island. Her owner, Masami Shimizu-Albergine, is a researcher herself and was eager to help.

Once a year, Hanas vet collects blood, urine, feces and hair samples for analysis at specialized labs. Its a level of medical monitoring few humans receive, and it will help pin down the role of gut microbes, metabolic function, toxin exposure and a host of other factors.

Theres really no end to what we can discover, Promislow says.

Analyzing the genomes of 10,000 dogs will uncover the genetic basis for a large swath of canine diseases, says Joshua Akey, a geneticist who started working on the dog project at the University of Washington and is now at Princeton Universitys Lewis-Sigler Institute for Integrative Genomics.

As in humans, though, its not likely to be simple. Most diseases result from multiple genes and environmental factors. But Akey says it should be possible to develop risk scores to alert owners to their dogs genetic predispositions. One UW researcher is focused on dogs with lymphoma, looking for a genetic biomarker for early diagnosis.

The link between a dogs size and lifespan appears to have a strong genetic basis. Big breeds have higher levels of a protein called IGF-1 (insulin-like growth factor), which is involved in regulating growth. In mouse studies, dialing down that protein can extend life and improve health.

So even though it might be possible to improve health for all dogs, a 150-pound Great Dane likely will never match the longevity of a 15-pound Chihuahua, Creevy says.

Distinct breeds were developed only in the past few centuries, and the trove of genetic information compiled for the project will help retrace that process. It could even settle the debate over when wolves were first domesticated and morphed from Canis lupus to Canis familiaris.

Some people say it was 10,000 years ago, and others have argued it was much longer, Akey says. I think well have a data set that can definitively answer some of these evolutionary questions.

Promislow, Creevy and Kaeberlein started kicking around the idea of a major dog study more than a decade ago. It took years to lay the groundwork and convince federal funders of its worth. Their first major grant $25 million from the National Institutes of Aging was awarded in 2018. The team also has funding from foundations, tech entrepreneurs and small donors such as the Irish wolfhound Association of New England.

All of the data will be freely shared online. The first batch, from about 25,000 dogs, was recently posted and already is showing some intriguing correlations. For example, dogs fed once a day appear to have higher cognitive scores and fewer health problems than dogs who eat multiple times a day.

That doesnt prove cause and effect, Kaeberlein cautions, but its a place to start digging deeper.

The project also has the potential to provide some of the best comparisons of dog diets, which now come in a dizzying array, from dry kibble to small-batch artisan concoctions. Promislow, who never imagined he would be cooking for a dog, started preparing a mix of sweet potatoes, oats, ground chicken and kibble for Frisbee, his 16-year-old mixed-breed female, after she was stricken with severe diarrhea.

We can do the careful science to evaluate the effects of raw-food diets, home-cooked diets, et cetera, he says. We will soon have more data than any other study on the consequences of a grain-free diet.

The project is nonprofit, but entrepreneurs are keen to apply the information it generates. Americans spent almost $104 billion on pet care in 2020, and the trendline points up, according to the American Pet Products Association.

Startups already are chasing more sophisticated genetic testing and anti-aging drugs for dogs. But they cant generate the massive amounts of data or conduct large-scale clinical trials like the Dog Aging Project does, says Celine Halioua, founder and CEO of Loyal. Kaeberlein is a scientific adviser to the Bay Area biotech, which is testing two drugs to increase health span in dogs.

The dog-aging database will be an invaluable resource, Halioua says.

Its a gift to the aging field for them to be doing this.

A week after the visit to WSU, Voght got the news: Bagel qualified for the rapamycin trial. Shell get a once-a-week dose, either real or placebo, for the next year, and physical exams every six months through 2025. Voght wont know until then whether Bagels pills are real. Either way, shes willing to keep making the trip to Pullman in hopes that the project will benefit Bagel, other dogs or even people.

Shes not expecting miracles, though.

Bagel is already slowing down a bit, and her face is frosted with white. If Labs can make it into the double digits, youre lucky, Voght says.

So she recently adopted what she calls her transition dog a 2-year-old black Lab named Delray.

Its nice to have another dog in the house to help you a little bit, she says. For when that time comes.

Go here to see the original:
The Dog Aging Project digs deeper than ever to help our best friends live better longer and the findings could help us, too - The Spokesman Review

Recommendation and review posted by Bethany Smith

Echoes from the Loafers Club Meeting

Do you have a toothpick?

What do you want with a toothpick? We havent eaten anything.

I feel lucky.

Driving by Bruces drive

I have a wonderful neighbor named Bruce. Whenever I pass his drive, thoughts occur to me. It was so windy I wanted to hide behind the toaster. A hood ornament blew past. It was a Dodge Ram blown from the hood of a truck. I wonder why a Dodge doesnt win every demolition derby?

The weather report had been: wind, snow, wind, cold, wind, rain, wind, repeat. The weather hadnt been all sunshine and rainbows. It never has been. We are overly optimistic about spring and spring things. We try to tease out bits of spring before they want to provide us company. The pessimists among us maintain Minnesota has only two seasonswinter and road construction. I want the National Weather Service to issue a nice weather warning. Perhaps they will offer a calm advisory on days that arent windy?

Life is good. An oncologist hugged me, which meant it was terrible news or marvelous news. It was marvelous. According to a poll conducted on behalf of Ancestry, only 47% of respondents could name all their grandparents. Only 4% could name all eight of their great-grandparents. I thanked all eight or nine (there is disagreement on one great-grandparent) for providing the genetics to make it possible for me to continue to exist.

A plentitude of photos

Do you ever get the feeling youre the only one who has too many photos? Cheer up, there are at least two of us. You and I are in this together and Im happy to have your company. I have thousands of bird, mammal, insect and wildflower photos for use in magazines and newspapers, but Im fixing to delete most of them. Im like your brother who replies to every emaileventually. Fixing to means Ill get around to it sometimemaybe, but first, I need to take a few more photos of those bald eagles on those two nests that look like upside-down Volkswagen Beetles in king trees.

Ive learned

If the police were here to protect us, wed all be under arrest.

Playing Scrabble is fun until someone loses an I.

If they want to speed up baseball games, MLB umpires should call a batter out anytime a fan in the stands catches a ball.

If youre being chased by an angry mob of taxidermists, dont play dead.

If I were a spy, tying me up in front of a TV showing any of the 24-hour news channels would quickly cause me to spill the beans.

Bad joke department

I dont trust stairs. Theyre always up to something.

A sock puppet is wanted in connection with a robbery. Police suspect someone else had a hand in it.

Exercise and extra fries sound too much alike.

How many conspiracy theorists does it take to change a light bulb? Do your own research.

What has four legs and if it fell out of a tree, it could break your leg? A pool table.

Does anyone else forget the abbreviation for Maine or is it just ME?

Nature notes

Whats all the yellowing about? Its about American goldfinches. They are turning a brilliant yellow. Dandelions are spring to some folks. The yellowing of spring. Is a group of dandelions called a pride? Mark Twain said, In the spring, I have counted 136 different kinds of weather inside of 24 hours.

Turkey vultures are checking the expiration dates of roadkill. Ive seen bald eagles in a few nests. The similar-sized golden eagle doesnt nest in Minnesota.

Im in awe of the birds in the April snow. I make it a cardinal rule to look at every cardinal. A red-tailed hawk soaring high caused me to think of the line from Oklahoma, We sit alone and talk and watch a hawk making lazy circles in the sky.

European starlings were introduced into this country by Shakespeare enthusiasts in 1890. Starling population is declining in the UK and North America. The Harriss sparrow is named after Edward Harris, Audubons pal and a horse breeder. The breeding range of this sparrow is all in Canada.

The crow-sized peregrine falcons returned in February to nest on the roof of the Mayo Building in Rochester. In early April, the female lays 3-4 eggs that hatch 35 days later in early to mid-May. Patients, staff and visitors name the nestlings.

My nature blog is at http://www.albatt.com/blogs

Meeting adjourned

Be the author of a great day written in kind words.

Read more from the original source:
Al Batt: A demonstration of dodging - Austin Daily Herald - Austin Herald

Recommendation and review posted by Bethany Smith

Whether youre working out or temperatures are heating up outside, theres nothing wrong with working up a little bit of perspirationsweating, after all, is perfectly natural. But if you notice youre dripping wet rather than just vaguely damp after even the slightest exertions, or after doing nothing at all, you may be somewhat concerned. And if you find yourself asking why do I sweat so much? on a regular basis, it might be a sign that something is amiss.

The overarching medical term for extreme sweating is hyperhidrosis. As John Whyte, M.D., M.P.H., the chief medical officer of WebMD explains, Hyperhidrosis is abnormally excessive sweating due to the fact that your sweat glands arent functioning properly and dont turn off. And its not necessarily uncommonsome 15 million people in the U.S. report having the condition.

Depending on the type (focal sweating in one or a few areas vs. sweating all over the body) and the severity of hyperhidrosis, it can sometimes be a sign of internal medical problemssuch as an overactive thyroid or low blood sugarand thus it is important to be examined by a doctor, Shadi Kourosh M.D., M.P.H., director of community health for the department of dermatology in the Mass General Brigham health system, adds.

Ahead, experts explain why you might be excessively perspiring, and offer some solutions to scale back the sweat.

Those with various types of diabetes may suffer from low blood sugar from time to time, which increased sweating can be an indication of dropping blood sugar. Moreover, Dr. Whyte says, Diabetes causes nerve damage, and some of that damage can be to nerves that control sweat glands, in turn causing excessive sweating. Finally, those who take certain medications for diabetes management may find increased perspiration a side effect of their prescription.

Thyroid disease may experience heightened sweating, as the conditions cause disruption to hormones and temperature regulation, notes Dr. Whyte. The thyroid gland affects many of our bodys processes such as our energy level, metabolism and body heat and temperature, Dr. Kourosh explains. Change in thyroid hormone levels will confuse the body into producing either too much heat or energy or not enough. For example, when a persons thyroid is not making enough thyroid hormone (hypothyroidism), they may experience fatigue or low energy, weight gain, and feel cold when others in the same room feel fine. Meanwhile if the thyroid is overproducing thyroid hormone (hyperthyroidism), the body may overheat leading to increased sweating.

In menopause, estrogen and progesterone levels change, which impacts your internal thermostat, Dr. Whyte says. As your body adapts to its new sense of temperature regulation, you may experience periods of excessive sweating. As a whole, Dr. Kourosh notes, Changing hormone levels can affect body temperature and sweating. When female hormones change during menopause, they can lead to hot flashes.

During pregnancy, there is a pronounced increase in the production of estrogen, as well as other hormone changes, Dr. Kourosh says. This, in turn, can actually raise your body temperature, and is enough to set off more pronounced sweating, especially during the early days of a pregnancy.

When youre feeling anxious, your bodys stress response is triggered, which drives activity in your nervous system. This can trigger your sweat glands to overreact, Dr. Whyte explains, which causes you to sweat.

Generally speaking, says Dr. Cederquist, if youre noticing a significant and abnormal increase in your sweat production, youll want to consult a doctor. For the slightly less pronounced over-sweating condition, over-the-counter and prescription-strength antiperspirants may help, as can medicated wipes. Opting for antiperspirants with aluminum can be particularly helpful, says Dr. Whyte.

If a health condition or medication is the culprit, addressing the core issue often alleviates the excessive sweating, Dr. Cederquist continues. These core issues would include the aforementioned thyroid conditions, diabetes, or hormonal changes.

If, however, your sweating is more extreme, oral medications, neuromodulator injections (like Botox, Dsyport, or Xeomin), treatment devices using ionized water and electricity or microwave energy on the sweat glands, and in severe cases even surgery, can be an option, says Dr. Kourosh. In each case, it is first important to see a doctor with expertise in the condition to understand the cause or combination of causes that might be affecting a person and create a treatment regimen that would be best suited, she adds.

Is it healthy to sweat a lot?

The short answer? It depends. Thats largely because the definition of a lot varies from body to body, and can be based on genetics. Even eating spicy foods can cause perspiration, says Dr. Whyte. Some people will naturally perspire more than others from any one of these stimulants, but that doesnt mean that theyre over-sweating.

No two people will sweat the same amount as a result of the same activity or environment, experts say. The amount that people sweat can vary greatly between individuals, and can be affected by several factors such as age, body size, muscle mass, health status, hormonal changes, fitness level, diet, as well as outside temperature, and humidity, explains Dr. Kourosh. Consequently, comparing how sweaty you are to the person next to you may not be the most effective measure of whether or not your perspiration levels are normal.

If you are noticing a significant and abnormal increase in your sweat production, first consult your physician, says Dr. Cederquist. Your doctor will help determine if an underlying medical condition and/or medication is causing you to sweat more. If a health condition or medication is the culprit, addressing the core issue often alleviates the excessive sweating. From there, your doctor could recommend one of many treatments for excessive sweating.

So if you find yourself going through deodorant tubes with a little bit more alacrity than youd like, dont panic. Not only are you far from alone, but a solution is likely well in reach.

This content is created and maintained by a third party, and imported onto this page to help users provide their email addresses. You may be able to find more information about this and similar content at piano.io

Read more:
Is It Normal to Sweat a Lot? 5 Reasons Why You Might Be Perspiring So Much - Prevention Magazine

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NFT horse racing is currently trending as one of the most popular NFT projects in the crypto industry

Horse racing is an unparalleled thrill for many. Like all mainstream sports, it has made its way to the digital world too. The GameFi movement powered by cryptocurrencies and NFTs further revives horse racing, blurring the line that separates entertainment and income.

There are many NFT projects that bet big on the booming gaming and horse-racing industries. They are characterized by transparency, fairness, and real ownership of assets. In this article, we take a look at the best of them.

These are the top three horse racing crypto games of this year.

1. Silks First Derivative Thoroughbred Horse Racing Game

2. Zed Run Pioneering Horse Racing Crypto Project

3. DeRace Horse Racing NFT Game with RNG technology

Youd be surprised to learn how each of these horse racing NFT projects marks themselves off with unique themes, gaming mechanisms, and play-to-earn features. Here is a detailed analysis of all three to help you find one that best suits your style.

Our pick as the best horse racing NFT game of this year is Silks.

Silks are the worlds first derivative thoroughbred horse racing game in the metaverse. It reimagines and democratizes thoroughbred racehorse ownership for the masses using mixed-reality technology, Web 3.0 gamification, and an immersive metaverse experience.

Every year, Silks will offer a new crop of Silks Horse NFTs, each of which represents a top one-year-old thoroughbred racehorse registered in the U.S. Decentralized data sets will then be used to ensure that the derivative NFT tracks the bloodlines, training progress, and racing performance of its real-world counterpart, and earns rewards for holders based on its racing and breeding success. Silk miners will verify the data on the blockchain in exchange for $SLK, the governance token of the ecosystem.

But this is only one of the many income-generating opportunities on the Silks platform. Lets take a detailed look at the dynamic play-to-earn mechanics.

The Silks ecosystem consists of a variety of in-game NFTs including Silks Avatars, Silks Horses, Land, and Stables. Silks Avatars will represent the unique identity of each player and the ownership of their affiliated digital assets within the Silks metaverse. The Silks Genesis Avatar Mint, the first NFT offering of Silks, will take place this Wednesday, April 27th. Silks Avatars are a crucial component of the platform as theyre required to obtain a Silks Horse in the inaugural Silks Horse Mint in mid-2022. If you cant afford to buy one dont fret, Silks allows for fractional horse ownership through syndication and even lets you join horse ownership pools to diversify your ownership and help mitigate risk.

Silks offer a vast infrastructure to help you take care of your Silks Horse just like a real thoroughbred. Users can purchase plots of Land (structured as NFTs) in the Silks metaverse which can be developed into horse farms. Users can also stake their Silks Horses to private community horse farms, where they will be housed and maintained in exchange for a small fee and a share of rewards.

You are rewarded in $STT, the in-game transaction token, every time the real-world counterpart of your Silks Horse wins a race or breeds offspring that is sold in the real world. As noted in the Silks whitepaper, the platform intends to launch new structures, businesses, roles, and sub-economies over time to support the play-to-earn system.

As previously mentioned, Silks first NFT offering will be its Silks Avatars which are set to go live on April 27th. For Early Access to the Silks Genesis Avatar Mint, visit the Silks website, silks.io.

Zed Run is an NFT metaverse dedicated to digital horse racing. Launched in early 2019, it is one of the earliest projects that allowed users to buy, breed, and race digital racehorses.

To get started on the platform, you need a racehorse NFT. You can buy them from OpenSea. The current floor price is 0.004 ETH. You can also get them for free by participating in community giveaways on social media platforms. Zed Run records and tracks racehorse ownership using the Ethereum blockchain, including comprehensive data like bloodline, genotype, gender, color, number of offspring, and race statistics. It uses the Polygon network to offer faster, cheaper transactions.

Zed Run has a carefully laid out horse breeding mechanism. A colt or stallion (a male racehorse) has to be bred with a filly or mare (a female racehorse) to create offspring. However, there are limits on how many times the male and female racehorses can breed every month and year. The offspring, once generated, will be sent to your wallet. If you dont own the male horse, you have to pay a stud fee to the colt or stallion owner. The charge is not predetermined. As a male horse owner, you can charge a breeding price you find apt. However, the game guides you in setting it up with minimum price suggestions.

Each Zed Run racehorse is suitable for a particular distance. However, you cant purchase a horse based on this criterion. Being a game of discovery, Zed Run requires you to test your horse and figure out the distance that best suits it over time. The platform hosts races of different distances and prize pools throughout the day. The prize pool will be divided between players who come first, second, and third.

Zed Run hosts tournaments with bigger prize pools to feature a better gaming experience for more stable owners. The team keeps the buzz around the game alive through live event streaming, Twitter talks, AMAs, and partnerships.

DeRace is a play-to-earn NFT horse racing metaverse that offers a personalized gaming experience to users. Leveraging the principles of blockchain technology, it guarantees transparent and fair gaming to all participants. One of the key features that helped DeRace make our list of top Horse Racing NFT Games is its unique gaming mechanics combining genetic algorithms and RNG technology.

DeRace horses are tokenized to feature unique sets of traits. They widely vary in rarity, performance, cool-down time, and value. You must own a DeRace Horse before you can sign up for races on the platform. While traits like sex, color, shape, breed, and racing cool-down are visible, speed and stamina are invisible. However, the invisible traits play a crucial role in determining the performance of the horse. You can gain an understanding of these invisible traits from its appearance, parent genetics, and historical statistics.

DeRace NFTs are available for purchase from primary and secondary marketplaces. Or, you can breed one from an existing pair. Apart from traits, you can judge a horse by its level. It is determined by the number of races participated, victories, and activities. As the level goes up, so does the value of the NFT.

DeRace has an interesting breeding system in place where any two (one male and the other female) NFTs create the third NFT. The offspring will feature a unique set of traits passed down by its parents. For this, both NFT horses are sent to GA (Genetic Algorithm) on the Ethereum smart contract. The genes from the parent horses are combined to create a third one, with a +- 5% deviation. After this, all three horses are sent back to the wallet.

DERC (DeRace Coin) fuels the gaming ecosystem by facilitating payments for races, winnings, horses, and trades. It is an ERC20-compliant cryptographic token. You can earn DERC by breeding two DeRace Horses, trading them, participating in races, hosting races in hippodromes, selling your analysis and predictions, reporting bugs, and even watching advertisements. You can also participate in the DeRace referral programs for wallet users, influencers, social media accounts, blogs, or news outlets among other reward programs to generate passive income from the platform.

The play-to-earn economies put forward by these NFT projects unlock the multi-billion-dollar video gaming and horse racing markets to the masses. They have great potential for growth in the coming years as the GameFi revolution picks up steam.

While most horse racing crypto games launch digital horses, Silks takes the idea a notch up by using derivatives or real-world racehorses. Here, the income opportunities are not limited to racing or breeding. You can also join horse ownership pools, develop Land, run a horse farm, or mine $SLK tokens to increase your earning potential. Besides, you are rewarded for the performance of the underlying real-world thoroughbred horse. The P2E mechanisms will expand as the project grows, nurturing a sustainable metaverse economy.

For the latest news and updates from Silks, join the community on Twitter and Discord.

VISIT SILKS

Disclaimer: The information posted in the article is for educational purpose only. By using this, you agree that the information does not constitute any investment or financial advice. Do conduct your own research and reach out to financial advisors before making any investment decisions.

Continued here:
NFT Horse Racing - The Best 3 NFT Projects for 2022 - Analytics Insight

Recommendation and review posted by Bethany Smith

On the 9th of August, Kenyans will once again queue to vote in the seventh general election since the introduction of multi-party politics in 1992. The elections will also mark the third time in Kenyas multi-party history that power will be transferred from one ruler to another through the ballot. In recent months, the question for many observers has been whether the elections and the transition process will be peaceful or violent.

Given Kenyas recent history of political violence, this is, actually, a genuine and legitimate concern, although a casual analysis of the previous elections shows a higher propensity for the elites to use violence when the incumbent is fighting for re-election than when not. Since the incumbent, Uhuru Kenyatta, is not fighting for re-election, we should, at least, be optimistic that the 2022 elections will not result in large-scale violence.

In this article, we go further and suggest that not only will the August 2022 elections be relatively peaceful (relative to the 2007 elections) but also that Kenyas history of large-scale political violence, may be a thing of the past. We base our prediction on the shift in the institutional and political landscape, facilitated by the political settlement that emerged out of the 2007/2008 post-election violence (PEV).

The key imperatives include the intervention by the International Criminal Court (ICC), the demobilisation of the highly charged political competition through devolution and the implicit peace commitment and political contract between Kenyas political elites and the citizens that has considerably diffused political tensions and the febrile atmosphere that previously nurtured large-scale violence. We argue that the three factors have, to an extent, fostered a tacit agreement among Kenyans that large-scale violence is too high a price to pay for any short-term political gains.

As in other sub-Saharan African countries, Kenyas transition to democracy has had confusing implicationsfacilitating multi-party competition and regime change through the ballot, but also fomenting political instability through violent politics. Although the root cause of political violence in Kenya has been primarily linked to the land question and the instrumentalization of grievances around land and resettlement, other accounts have focused on the elite fragmentation and state informalisation that began under Daniel Moi and continued under Mwai Kibaki with the inevitable diffusion of violence from the state to local gangs.

With the first two multi-party electionsin 1992 and 1997being violent, many observers had come to expect political violence to be a natural outcome of Kenyas elections until this conjecture was disrupted by the scale and intensity of the 2007/2008 PEV. With Kenya tottering towards anarchy, and fearing complete state collapse, the international community was forced to intervene in 2008, to not only halt the bloodletting but also engineer a major institutional reset through the 2010 constitutional change, and chaperone retributive justice via the ICC mechanism.

With Kenya approaching another election, and ten and five years respectively after the constitutional changes and the collapse of the ICC cases, we take stock of the implications of these major events on Kenyas political landscape.

First, the ICCs intervention in Kenya was remarkable as it was the first time that attempts were made to hold the countrys political elites accountable under an institutional mechanism that they could neither intimidate nor corruptly influence.

While observers have either lamented or celebrated (depending on ones ideological leaning) the failure of the ICC to successfully prosecute the so-called Ocampo Six (those the Court interdicted for their alleged planning of the 2007/2008 PEV), we argue that evaluating the performance of the ICC in the Kenyan crisis should be against its unprecedented attempt to confront the intractable impunity among the countrys political elites.

Since its post-independence birthing, Kenyan politicians had perfected the art of self-preservation through the construction of the perception that they were untouchable and above the law. The ICC, by hauling to its dock some of the big names in Kenyas political landscape, including the current president, Uhuru Kenyatta, and his deputy William Ruto, and in so far as it has fractured the elites pejorative attitude towards the rule of law, the courts intervention should be viewed as a partial success. Consider the narration of utter shame, frustration, humiliation and stigma among the Ocampo Six following their interdiction by the ICC, which clearly manifested their shock at being made to account under a neutral institution.

It was, therefore, not surprising that the accused and their enablers engaged in Machiavellian tactics, including counter-shaming strategies performed through neo-colonialism narratives, in order to delegitimise and undermine the ICCs prosecutorial authority in Kenya and elsewhere in Africa. Whereas these strategies contributed to the inevitable collapse of the Ocampo Six cases, if the Court action has been successful in institutionalising fear of future intervention in Kenya as a credible threat against political mischievousness among the elites, and if it has blunted their assumed political invincibility, then the intervention should be viewed as partially successful.

The ICCs intervention in Kenya was remarkable as it was the first time that attempts were made to hold the countrys political elites accountable.

Anecdotal evidence shows that the ICC intervention has brought Kenyas politics to an inflection point by gravitating the countrys political discourse towards greater forbearance. This is clearly manifested by the assimilation of the ICC vocabulary into Kenyan public discourse, frequently invoked by ordinary Kenyans and politiciansincluding those who joined Uhuruto (as Kenyatta and Ruto have been popularly known) in the public vituperation of the Courtto credibly threaten those perceived to be engaging in inflammatory narratives.

Also, an empirical outcome from the ICCs intervention has been the realisation among the Kenyan elites that accountability for inciting violence is no longer with the imagined political community of the tribe but, rather, on the individual politician. Consider the remarkable disposition by the elites to apologise and withdraw any inflammatory remarks attributed to themselves or to their lieutenants, something that was previously unthinkable.

A contributing factor to this transparency and the politics of extenuation has been the integration of social media in the way politics is chronicled and experienced in Kenya. The ubiquity of the smartphone, has ensured that the previous private sphere of reckless political talk and public deniability has been dissolved, as the private has become public via social media, forcing public apologies. Anybody, anywhere can now easily capture and post on social media negative political rhetoric that may yet, in the future, be used as evidence in court.

It is, therefore, not coincidental that the theatre of political violence in Kenya has recently shifted from the rural to the urban areaswith the state mostly implicated thus blunting its association with specific ethnic groups and leaders. The ICCs intervention in Kenya has to some extent fostered restraint against the large-scale political opportunism that was previously a feature in Kenyas politics and responsible for the violence, ushering in a period of negative peace but with the potential of transitioning to positive peace in the future, if these imperatives can be harnessed and institutionalised.

Constitutional reset and institutional dividends

Secondly, the 2010 institutional reset through constitutional changes has yielded significant political dividends for Kenyan political elites in the form of devolution of power and resources to counties and provided access to resources through the political party funds allocated by the exchequer.

While these outcomes have not completely eliminated the fierce electoral competition synonymous with Kenyas elections, we think that it has to an extent toned down the competition as losers now have alternative access to power and a platform from which to articulate and implement their policies. This has recently been manifested in the political tussling over local electoral seatsin the form of zoningas the two major coalitions, Azimio and Kenya Kwanza, attempt to craft a strategy that will ensure their dominance in the local seats in the August polls.

Previous analysis has shown that the institutional context under which elections are organised can either moderate or escalate adverse outcomes, including violence. Institutional designs that afford greater opportunities for losers through certain sweet points, including fair treatment of losers, may reduce tensions and appetite for political violence.

For Kenya, while the desired sweet points has not been fully achieved because decentralisation has widened patronage networks, it may yet provide vast eating opportunities for losers of presidential elections and their followers even as they wait to compete in the next polls. Likewise, losers in presidential elections may also be co-opted into the decentralised graft network through elected proxies, as some anecdotal evidence shows.

The ICCs intervention in Kenya has to some extent fostered restraint against the large-scale political opportunism that was previously responsible for the violence.

Meanwhile, the provision of political parties funds by the exchequer on the basis of the parties performance in local elections has also created opportunities for parties that compete in elections to access alternative resources. While there is yet no evidence of the extent to which this may have impacted political competition in Kenya, we think that it has shifted the former singular attention given to national political competition to local elections. This is because political leaders have had to strategize in order to win significant seats in local elections in order to access the funds. Consider the revelation that the ODM party is owed KSh7.5billion by the Office of the Registrar of Political Parties (ORPP) and the protracted infighting among the former NASA coalition partners over these funds.

On a different note, the creation of various political positions by the 2010 constitution, be they governor, senate or running mate positions, has rendered coalition building in Kenya a delicate affair as major political leaders have been forced to expend their political energy, previously fundamental to the orchestration of violence, on party politics at the expense of national political organisation. The creation of these positions and the dawn of ex-ante coalition building in Kenya has unexpectedly rewired political scheming from the national to internal, as manifested by the ongoing contestation over various seats in the forthcoming elections.

Cumulatively, we think that these institutional dividends including devolution, the provision of political party funds and the creation of diverse political positionshave generated diverse opportunities to be competed over by Kenyan politicians and this may yet deter the need for large-scale mobilisation of groups for political violence.

Thirdly, findings from recent fieldwork in Burnt Forest by one of us show that there is acute fatigue among Kenyans from the recursive violence and this is fostering some degree of tolerance for, and openness to, hitherto political nemeses. The fatigue has been especially reinforced by the realisation among Kenyans that the elites concerns are for their own interests and self-preservation.

Consider the dissatisfaction and grumbling that accompanied the political rapprochement between Uhuru Kenyatta and his long-term rival Raila Odinga in 2018. The reconciliation, popularly known as the handshake, wrong-footed the support base of both leaders, who were of the opinion that the political settlement was motivated more by Kenyatta and Odingas narrow interest of perpetuating conditions favourable to the durability of the dynastic political order, and less by genuine national interest.

Because the rapprochement did not yield retributive justice and compensation for the victims of political violence, it gave way to despondency among ordinary Kenyans. Most have since opted for suboptimal political outcomes, especially stability, whatever the electoral outcome, aptly conceptualised by the phrase accept and move on to capture the inherent need to sidestep the negative externalities associated with Kenyan elections.

Recent evidence from Burnt Forest shows that violence fatigue may have fostered tolerance among local groups and made them less supportive of large-scale collective violent action, precisely because previous violence yielded asymmetric outcomeseconomic and personal losses for the citizens and political gains for the political class. However, the full extent to which violence fatigue and citizen despondency may result in wholesome political stability in Kenya is something that needs further investigation.

Because the rapprochement did not yield some form of retributive justice and compensation for the victims of political violence, it gave way to despondency among ordinary Kenyans.

In conclusion, while it may be too soon to form concrete opinions on the feasibility of large-scale political violence occurring in Kenya in the upcoming elections and in the future, we have argued in this article that the ecology of events including the ICCs intervention, institutional dividends and violence fatigue among ordinary Kenyans may yet immunize the country against large-scale political violence.

We are aware that peace spoilers may emerge and threaten violence as a way of gaining power or accessing political office through some form of political settlement, but for now it seems that Kenya is at the point of a halfway house, occupying the institutional space between negative peace and the possibility of positive peace in the long-term, if these factors are institutionalised.

As long as the threat of the ICC endures, devolution and the political party funds are maintained and the Faustian bargain between Kenyan citizens and the political elites remains stablethat is, selecting peace whatever the political outcomesit is just possible that large-scale political violence akin to that witnessed in 2007/2008 may never again happen in Kenya.

But again, as Putins illegal invasion of Ukraine has shown, Never Again moments have the tendency to yield the very same conditions that were responsible for eliciting the Never Again statement. We, therefore, must remain hopeful but realistic that a major peace spoiler may yet emerge and usher in political disorder in Kenya.

Continued here:
MOHAMMED ALI - Patriarchy and the Biopolitics of FGM - The Elephant

Recommendation and review posted by Bethany Smith

When my husband and I found out we were pregnant with twins, we were shocked. They didnt run in my family and we werent doing any fertility treatments that might have increased our chances of twins, but there they were, two little blobs on the ultrasound printout. A few scans later and we found out they shared a placenta, which about 70 per cent of identical twins do, known as monochorionic twins. We also learned they were identical twins, which dont typically run in families the same way fraternal twins do.

As my belly grew, and grew, and grew, the more I talked to friends, neighbours and complete strangers about my pregnancy and how Id got two-for-one baking in the oven. And thats when I heard it, the bit of local hearsay that inspired this article. What I heard went something like this: Youre having twins? Did you know that the Sea to Sky corridor has one of the highest rates of twins in North America along with a small potato-farming town in the States? If only one person had mentioned it to me, I would have likely forgotten about it, but I heard it over and over from different people. Then, last summer, I got into my friends truck with three other women to go for a bike ride and one of them commented how crazy it was that not only were all four of us mothers of twins, but we all live in the same neighbourhoodthree of us even on the same street! What were the odds?

When I started researching this article, I reached out to the Sea to Sky Multiples group on Facebook (yes, its a thing) and a lot of them had heard almost exactly the same hearsay I had. I was not alone (or crazy).

I have 20-month-old identical twins and I have been told this many times by random people at Strong Start (Sea to Sky Community Services program) and at the park. Sarah Ewing, identical twin girls, Squamish.

I have heard that. I actually blamed the carrots after hearing this because I was eating a lot of Pemby carrots when I got pregnantsame soil! Jasmine Robinson, fraternal twin boys, Whistler.

When I was pregnant with my twins, nearly 10 years ago, my OBGYN in North Van said something about a study, but I never asked for specifics. Anon, Squamish.

I actually have heard that, but I dont know where. Someone also once said there were studies done in the area or they were going to do studies on the high number of twins in the area. Im not sure how true it is though! Jen Bang, fraternal twin girls, Whistler.

So, does this hearsay have any truth to it? Do we have a high number of twins in the Sea to Sky? If so, why? Can potatoes actually play any role in it? As it turns out, these questions dont have simple answers.

Youre going to need to ask some detailed questions to really understand this, explained Dr. Marina Tourlakis, life sciences tutor in molecular genetics at Squamishs Quest University, in an email. Fraternal, or non-identical twins, can result from fertility treatment, which often induces the release of more than one egg during a womans menstrual cycle (super-ovulation). Fertility issues are prevalent in our society and hence increased twinning rates, if non-identical, might be explained by increased awareness of, and accessibility to, fertility treatments. Hence, Id wonder if the proposed high rates of twinning in Whistler are of identical or fraternal twins as these are two very different questions to ask.

If the average age of the mothers in Whistler is high, and we are talking about fraternal twins, then Id wonder if this is indeed linked to an increase in fertility treatment (since fertility drops precipitously with age). Given that fertility treatments are expensive and Whistler is typically associated with an affluent demographic, this too would make me wonder if this is the main factor at play.

Statistics Canada helped me compare the number of twins born in the Sea to Sky to the rest of Canada between 2000 and 2020. For 12 out of those 20 years, Squamish, Whistler and Pembertons combined twin percentage rate was higher than the Canadian average. For six straight years spanning 2012 to 2017, the corridor remained above the national average. Its worth noting, however, that the mean average of those years puts the twinning rate at 3.1 per cent, in line with the rest of Canada, while a median average puts us at 3.3 per cent, just over.

Statistics Canada does not collect information on whether twins are identical or fraternal, or if they were conceived using fertility treatments, but for 60 per cent of that 20-year period, weve had more twins than the national average, so the hearsay about the Sea to Sky having an above-average amount of twins could be somewhat true, although the reasons why are an educated guess without more robust data.

What Tourlakis was saying about fertility treatment being the major driver in increased fraternal twin rates is echoed in a comprehensive, global study led by Christiaan Monden, a professor of sociology and demography at Oxford University. The research shows that over 40 years, the twinning rate worldwide has increased by a third, which means that one in every 42 babies is now born a twin.

Our results show that twinning rates were recently peaking at a historical high, with rates of over 15 twin deliveries per 1,000 deliveries in many countries, including the USA, Canada, the European Union, Israel, South Korea, Taiwan, and almost all African countries, the study says.

The report goes on to say the reasons for the increase are driven by fertility treatments (responsible for two-thirds of the increase) in combination with households delaying childbearing, in other words, older mothers (responsible for one-third of the increase).

An international collaboration (2020) involving researchers at The University of Western Australia (UWA), DePauw University in Indiana and the London School of Hygiene and Tropical Medicine found that women are more likely to conceive fraternal twins once they reach their 30s as a result of an evolutionary response to combat declining embryo viability.

This research offers important insights into how our evolutionary past still influences our modern lives, with fraternal twinning rates increasing as women increasingly delay childbearing, said Associate Professor Joseph Tomkins, UWA School of Biological Sciences.

Note that this research refers to fraternal twins specifically, as the reason an egg randomly splits to create identical twins is still a mystery. However, new research into epigenetics might be the start of unravelling this biological enigma.

Epigenetics refers to the turning on and turning off of genes, explains Dr. Nancy L. Segal, a professor of psychology, director of the Twin Studies Center at California State University, Fullerton and author of seven books on twins, speaking on the podcast, Speaking of Psychology: What Studying Twins Can Teach Us About Ourselves. What environmental triggers are there before birth and sometime after birth, that will activate a gene or perhaps silence it. And this is where identical twins, who differ in fundamental ways, may be of greatest use to us in the medical sciences because we know that the similarity rate of identical twins with diabetes or multiple sclerosis is only 50 per cent, schizophrenia maybe 40 per cent, so, if they come out into the world with the same genes, why is it that one twin expresses it and the other one does not? This is information we can all use to assist individuals in the non-twin population.

A 2019 CBC article stated that B.C. has the highest number of older mothers in Canada, with the average age of first-time mothers being 31.6 compared to the national average of 29.2. It went on to say that in B.C., between 2000 and 2017, the number of mothers aged 35 to 39 increased by 60 per cent, and the number of mothers aged 40 to 44 doubled.

Statistics Canada helped me dig into the Sea to Sky numbers and in 2020, the average age of a mother in the corridor was 33.5, so above both the national average (31.3) and the B.C. average (32.1). Of the children born to mothers in the corridor, 78 per cent were born to mothers aged 30 to 39. In 2000, that figure was just 54 per cent. UBC professor Paul Kershaw, founder of research and advocacy group Generation Squeeze, is quoted in the CBC article saying the numbers didnt come as a surprise. This is the province where hard work pays off the least for younger people in their prime childbearing years, Kershaw said.

Kershaws research compared todays young adults to those of a generation ago and found that the full-time incomes of British Columbians have dropped the most in Canada during that time while housing prices have increased the most.

The nature of work, housing, and the propensity towards play in the Sea to Sky could be a factor in people deciding to wait longer to start a family. The result? More issues conceiving, possibly fewer kids, but also a slightly higher chance, biologically speaking, of these women producing twins. Interestingly, while older mothers might have issues getting pregnant, they are statistically more likely to have a successful multiple pregnancy if one does occur, said researchers at Columbia University Irving Medical Center in a 2017 study.

A U.S. study by the National Center for Health Statistics spanning from 1980 to 2009 showed that the national twin birth rate rose an incredible 76 per cent over that period, from 18.9 to 33.3 per 1,000 births. Increases were seen across all 50 states and by more than 100 per cent in five statesConnecticut, Hawaii, Massachusetts, New Jersey, and Rhode Island.

The report notes that Connecticut had the highest number of twin births at five per cent in 2009. More recent figures published by Statista in May 2021 also show Connecticut as the state with the highest twin birth rate from 2017-19.

While it is known for its stunning fall foliage, Yale University and being the home of ESPN, Connecticut is not exactly known for potatoes. So, the Sea to Skys connection to a small, potato farming town in the U.S.? Still possible, but again, without more data, its difficult to say for sure. (The U.S. CDC was unable to narrow down where this mythical potato town with the high twinning rate is located.) Seed potatoes have been farmed in Pemberton for more than a century, so wouldnt the numbers of twins stay consistently high or spike when we had bumper crops? What a woman eats and drinks have not been scientifically linked to the subsequent production of twins, although some people think it could be.

Anna Capria, a human genetics and genomic data analytics masters student, led me to an article on a small Nigerian town called Igbo-Ora. Nigeria has one of the largest populations of twins in the world and the highest dizygotic/fraternal twinning rate (45 per 1,000). A recent 2020 study delved into the local peoples beliefs as to why this might be, and mentioned a soup produced with okra leaves and a local delicacy made from cassava, a root vegetable.

Since the same foods are consumed in neighbouring communities that have lower rates of twinning, we conjecture that nutritional and other environmental factors may produce epigenetic modifications that influence high DZ twinning rates in Igbo-Ora community. We conclude that more directed scientific studies based on these findings are required to further elucidate the etiology of the high rate of DZ twinning in Igbo-Ora, the study says.

My post on the Sea to Sky Multiples group helped to unearth other twin-heavy places in Brazil and India. In an article about Kodinh, a small village in India that counts more than 400 sets of twins, it was interesting to read that some of the pervasive reasoning for multiple births, like more mature mothers and access to fertility treatments, are not a factor there. The doctor interviewed mentioned that he thinks its something in the food or water in the area, but again, theres no concrete evidence.

One long-held twin myth that has recently been busted is the notion that identical twins dont run in families. We thought that for a very long time, says Segal. And yet, some recent research from Sweden and Singapore looking at inbred populations has found that there are these pockets of people around the world in India and Iran, where there are multi-generations of identical twins. And so, we think that within some families that theres a tendency towards zygotic splitting.

In the podcast, Segal goes on to explain that the offspring of two pairs of identical twins would be first-cousins and full siblings, because each parent is genetically interchangeable, which is rarebut a trend thats not so rare is identical twins marrying unrelated people, and that their children would be genetic half-siblings. Mind-blowing.

Whats become clear over the course of digging into this hearsay is that there is a serious lack of comprehensive research on twins, part of a longer trend in academia that tends to skew towards a male perspective.

Female reproduction has a long tradition of being studied primarily from a male lens (because researchers and medical doctors were primarily male) and poorly at that (perhaps because the funding bodies deciding what research to fund were also primarily male), says Tourlakis. Recently there has been a surge in attention (perhaps due to an aging mother population, and perhaps also due to increased numbers of women in research positions) to reproductive studies, which is leading to all kinds of interesting new findings about fertility, so I imagine we will continue to have exciting new findings hitting our science news feeds in the coming years.

So, one day we might be able to debunk or uphold this strange bit of Sea to Sky hearsay, but for now, its still a bit of a mystery.

Being the mother of twins in the Sea to Sky area these days may seem commonplace, but it doesnt take away from how incredibly special it is to have them. Sarah Lindsay, identical twin boys, Squamish.

Writers Note: Thank you to Dr. Marina Tourlakis and Anna Capria for explaining genetics basics and to David Raffo for patiently helping me draw some answers from the data.

Read more:
What's behind the abundance of twins born in the Sea to Sky? - Pique Newsmagazine

Recommendation and review posted by Bethany Smith

Every week, we update this list with new meetings, awards, scholarships and events to help you advance your career.If youd like us to feature something that youre offering to the bioscience community, email us with the subject line For calendar. ASBMB members offerings take priority, and we do not promote products/services. Learn how to advertise in ASBMB Today.

The International Union of Biochemistry and Molecular Biology is offering $500 to graduate students and postdocs displaced from their labs as a result of natural disaster, war or "other events beyond their control that interrupt their training." The money is for travel and settling in. Learn more and spread the word to those who could use assistance.

This conference, to be held in person in Athens, Ga., will address the multitude of roles that the O-GlcNAc protein modification has in regulating nuclear and cytosolic proteins. It will bring together researchers from diverse fields to share their research, tools and experience in O-GlcNAc biology. The abstract deadline is April 26, and the early registration deadline is May 9. Submit an abstract.Learn more in this Q&A with organizers Gerald Hart and Lance Wells.

The ASBMB Lipid Research Division features the work of young investigators at noon Eastern on Wednesdays. If you are interested in presenting, please contactJohn Burke. Registeronce to access the whole series.

The next seminar on April 27 will be aboutregulation of plasma membrane dynamics by PIP kinases. It will feature Nirmalya Bag of the Indian Institute of Technology and Federico Gulluni of the University of Turin in Italy.

The Sphingolipid Biology webinar seriescontinuesApril 27 with two talks on lysosomal storage diseases. Elsa Rodrigues ofUniversidade de Lisboa will give atalk titled "CYP46A1 as a therapeutic target in Niemann-Pick type C disorder," and Janet Deane of the Cambridge Institute for Medical Research will give a talktitled "Identifying new players in Krabbe disease: How galactosphingolipids alter membrane protein abundance." Register.

The National Institutes of Health will host speaker Joanna Fares of Emergence Therapeutics and Jenn Symonds of Spherix Consulting Group on April 27 for an 11 a.m. Eastern webinar on careers in scientific project management. Register.

Endpoints News is hosting a webinar titled "The R&D challenge: What are the best practices in drug development today?" Speakers/panelists include: Alise Reicin, president and chief executive officer of Tectonic Therapeutic; Arie Belldegrun, is executive chairman and co-founder of Allogene; Norbert Bischofberger, president and CEO of Kronos Bio; David Schenkein, a general partner at GV; and Abhay Kini, director of life sciences at Egnyte. Learn more.

DDN is hosing a seminar about interventions that target the bloodbrain barrier to facilitate drug delivery. It will feature Zhenpeng Qin of the Center for Advanced Pain Studies at the University of Texas at Dallas, Olaf van Tellingen of the Netherlands Cancer Institute, Costas Arvanitis, of the Georgia Institute of Technology and Emory University, and Graeme F. Woodworth of the Greenebaum Comprehensive Cancer Center at the University of Maryland. Learn more.

The ASBMB Annual Awards are given to outstanding professionals who have been recognized by their peers for contributions to their fields, education and diversity. In addition to a monetary award, recipients will give talks about their work at the 2023 annual meeting in Seattle.Know someone who deserves to be recognized for their work? Check out the available awards and submit your nomination today.

The American Neurological Association and the National Research Mentoring Network have teamed up for this lunchtime webinar about distance mentorship. Here's how they characterize it: "Distance mentorship allows mentormentee partners to continue to work together despite geography and continue to flourish virtually. Whether the mentorship is a long-distance one from the start or evolves to one over time, several best practices exist to succeed. This webinar is a roundtable discussion with mentors and mentees who will discuss the successes, challengesand tips that allowed their relationships to thrive." Register.

We were contacted by Caroline Mueller, assistant professor at Ohio University, about a survey for early-career medical educators. She wrote: "We hope that through this survey, we will identify the needs of early-career medical educators and develop appropriate resources for new faculty." Learn more and complete the survey by April 30.

The Genetics Society of America's DeLill Nasser Award for for Professional Development in Genetics "supports geneticists in their graduate or postdoctoral career stages by subsidizing participation in conferences and laboratory courses." The prize (up to $1,000) can be used for attending virtual or in-person events. Applicants must be members of GSA. Learn more.

The U.S. Department of Energy's Office of Science Graduate Student Research program is accepting applications until May 4. The program supports U.S. graduate students seeking to conduct part of their thesis research at a DOE national lab or host site with a DOE scientist. The program is open to Ph.D. students who are conducting their thesis research in targeted areas of importance to the DOE Office of Science. Learn more.

The 2020 documentary Coded Bias explores biases embedded into technology. These biases affect the behaviors, outputs and consequences of countless devices, tools and digital spaces and often lead to or perpetuate inequity. Self-driving cars, facial recognition software, motion-activated appliances, job applicant screens and algorithms used for medical decision making theyre only as good as the code that defines their functions. The film describes in chilling fashion numerous prejudicial and even dangerous outcomes caused by biases hard-wired into data-centric technologies, and it makes the case for systemic changes needed to safeguard users and hold the tech industry accountable. Interested? The ASBMB Women in Biochemistry and Molecular Biology Committee is hosting a screening and virtual panel discussion at 4 p.m. EDT on May 4. Committee member Meghna Gupta will moderate, and Jeff Kapler and Marina Holz will be panelists. The link to access the film will be sent to all registered attendees two weeks prior to the event. (The film also can be streamed on Netflix.) Register.

This in-person meetingin Kansas City, Mo., will showcasethe most recent insights into the cis-regulatory code, how cis-regulatory information is read out by transcription factors, signaling pathways and other proteins, how cellular diversity is created during development and how we can study this problem using cutting-edge genomics technology and computational methods.The meeting will simultaneously examine the problem from an evolutionary perspective: how cis-regulatory elements evolve, how regulatory variation affects gene expression and phenotypes, how these changes have shaped development and parallel evolution, and how noise affects regulatory circuits and their evolution. The abstract deadline for those who'd like to be considered for talks is May 6. The abstract deadline for poster presenters and the registration deadline is May 25.Submit an abstract.Learn more in this Q&A with two of the organizers.

The National Institutes of Health Office of Research on Womens Healthhas issued a request for information "on research gaps, clinical practice needs, and research opportunities to inform research priority setting at the intersection of the COVID-19 pandemic and/or long COVID and the health of women." Read the RFI.

The National Institutes of Health Office of Research on Womens Health is hosting its annual Vivian W. Pinn Symposium on May 12 to markNational Women's Health Week. The event will focus on the impacts of the COVID-19 pandemic on the careers of women in science. Learn more.

This five-day conference will be held Aug. 1418 in person in Cambridge, Massachusetts, and online. It will be an international forum for discussion of the remarkable advances in cell and human protein biology revealed by ever-more-innovative and powerful mass spectrometric technologies. The conference will juxtapose sessions about methodological advances with sessions about the roles those advances play in solving problems and seizing opportunities to understand the composition, dynamics and function of cellular machinery in numerous biological contexts. In addition to celebrating these successes, we also intend to articulate urgent, unmet needs and unsolved problems that will drive the field in the future. Registration and abstract submission begins Nov. 1. Abstracts are due May 16. Learn more.

The Protein Society is hosting a virtual workshop on emerging approaches in membrane protein design. It'll include presentations by Joanna Slusky of the University of Kansas, Anastassia Andreevna Vorobieva of the VIB-VUB Center for Structural Biology, Sarel Fleishman of the Weizmann Institute of Science, and Patrick Barth of EPFL, who is also the event organizer. Register.

For the Versatile PhD's webinar series, career coach Tina Li will provide advice on launching and building your brand online and offline. Learn about the series.

The Marion B. Sewer Distinguished Scholarship for Undergraduates offers financial support to students who demonstrate an interest in the fields of biochemistry and molecular biology and enhance the diversity of science. Students whose social, educational or economic background adds to the diversity of the biomedical workforce or who show commitment to enhancing academic success of underrepresented students are eligible. The scholarship provides up to $2,000 toward undergraduate tuition costs for one academic year and can be applied to fall or spring tuition of the year following scholarship award notification. Up to ten scholarships will be awarded each academic year. Applications by individuals from underrepresented groups are encouraged, although all qualified applicants will be considered without regard to race, gender, color, ethnicity or national origin. Apply.

The Oklahoma Cobre in Structural Biology at the University of Oklahoma is hosting its 10th annual structural biology symposium on June 16. Confirmed speakers include Hao Wu of Harvard University, Breann Brown of Vanderbilt University School of Medicine, Lorena Saelices of University of Texas Southwestern Medical Center, Satish Nair of the University of Illinois Urbana-Champaign and Erica Ollman Saphire of the La Jolla Institute for Immunology. Check here for details and to register.

The Journal of Science Policy & Governance, the United Nations Educational, Scientific and Cultural Organization and the Major Group for Children and Youth announced in February a call for papers for a special issue on "open science policies as an accelerator for achieving the sustainable development goals." The deadline for submissions is July 10. To help authors prepare their submissions, the group will be hosting a series of webinars (April 8 & 29, May 20, and June 10) and a science policy paper-writing workshop (March 2627). Read the call for submissions and learn more about the events.

Head to beautiful Denver, Colorado, for a summer experience as a PRIDE (Programs to Increase Diversity Among Individuals Engaged in Health-Related Research) scholar. PRIDE is an initiative of the National Heart, Lung and Blood Institute that trains junior faculty from underrepresented backgrounds and/or with disabilities to advance their scientific careers and make them more competitive for external research funding. The University of Colorado PRIDE (led by Sonia C. Flores, who also leads the ASBMB Minority Affairs Committee) is one of nine national PRIDE sites. Its focus is on the "impact of ancestry and gender on omics of lung and cardiovascular diseases" (which is why it's called PRIDEAGOLD). The program consists of two consecutive summer institutes (two and one week, respectively) that offer comprehensive formal instruction on multi-omics, data sciences and bioinformatics, with an emphasis on interpretations based on ancestry and/or gender; career development and grant-writing tools; pairing with expert mentors; and pilot funds to develop a small research project. Learn more.

This in-person meeting will be held Sept. 29 through Oct. 2 in Snowbird, Utah. Sessionswill cover recent advances and new technologies in RNA polymerase II regulation, including the contributions of non-coding RNAs, enhancers and promoters, chromatin structure and post-translational modifications, molecular condensates, and other factors that regulate gene expression. Patrick Cramer of the Max Planck Institute will present the keynote address on the structure and function of transcription regulatory complexes. The deadline for oral presentation abstracts is July 14. The deadline for poster presentation abstracts is Aug. 18.Learn more.

Most meetings on epigenetics and chromatin focus on transcription, while most meetings on genome integrity include little attention to epigenetics and chromatin. This conference in Seattle will bridge this gap to link researchers who are interested in epigenetic regulations and chromatin with those who are interested in genome integrity. The oral and poster abstract deadline and early registration deadline is Aug. 2. The regular registration deadline is Aug. 29.Learn more..

The ASBMB provides members with a virtual platform to share scientific research and accomplishments and to discuss emerging topics and technologies with the BMB community.

The ASBMB will manage the technical aspects, market the event to tens of thousands of contacts and present the digital event live to a remote audience. Additional tools such as polling, Q&A, breakout rooms and post event Twitter chats may be used to facilitate maximum engagement.

Seminars are typically one to two hours long. A workshop or conference might be longer and even span several days.

Prospective organizers may submit proposals at any time. Decisions are usually made within four to sixweeks.

Propose an event.

If you are a graduate student, postdoc or early-career investigator interested in hosting a #LipidTakeover, fill out this application. You can spend a day tweeting from the Journal of Lipid Research's account (@JLipidRes) about your favorite lipids and your work.

Originally posted here:
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Introduction

In recent years, break through progress has been made in immunotherapy of malignant tumors, and it has become a new treatment method for refractory or recurrent tumors. Immune checkpoint inhibitors (ICIs) can target programmed death-1 (PD-1), Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death ligand-1 (PD-L1) to reactivate the killing function of effector T cells in tumor cells, thus exerting an antitumor effect.1 Currently, ICIs are divided into three main types: PD-1 inhibitors, PD-L1 inhibitors and CTLA-4 inhibitors. Due to their unique mechanism of action, their adverse reactions are different from those of traditional chemoradiotherapy and targeted therapy, and immune dysfunction is the most common therefore, adverse reactions to ICIs are called immune-related adverse events (irAEs).2 Endocrine adverse reactions are one of the most common adverse reactions and mainly involve the pituitary gland, thyroid gland, pancreas, adrenal gland and other endocrine glands, resulting in corresponding endocrine dysfunction. The mechanism of irAEs is not clear, but it has been determined that it is related to the excessive immune response caused by ICIs. This article reports a case of irAEs related to type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA) after the occurrence of hypophysitis during immunotherapy and includes a review of the related literature to analyze the clinical characteristics of the disease and provide a basis for the diagnosis and treatment of endocrine system irAEs caused by such drugs.

1.The patient was a 45-year-old man with a body mass index of 25.51 kg/m2. In January 2018, a chest CT examination was performed due to cough and sputum, and it showed a mass in the right lower lung. An additional chest enhanced CT scan and bronchoscopy biopsy led to a diagnosis of right middle and lower lobe adenocarcinoma. In view of the rapid growth of the lesion and the difficulty of surgery, no surgical treatment was performed. The patient received pemetrexed, gemcitabine and platinum chemotherapy successively, routine blood tests were performed, and liver and kidney function and blood glucose were monitored regularly during chemotherapy; no abnormalities were found. Later, due to obvious adverse reactions to chemotherapy drugs, the patient was enrolled in the Phase II clinical trial to evaluate the efficacy, safety and drug resistance of KN046 in subjects with advanced non-small-cell lung cancer in July 2019 using KN046 (recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody Fc fusion protein injection), the clinical trial identifier number:KN046-201. The patient received KN046 223.5 mg intravenous drip treatment successively from July 2019 to July 2021 every 14 days as a cycle. After 11 months of starting treatment (June 2020), the patient went to the doctor due to fatigue, and hypopituitarism was found. At that time, the levels of cortisol and adrenocorticotropic hormone and thyroid hormone levels were lower than normal. An MRI of the pituitary gland was normal. After that, prednisone tablets (7.5 mg) and levothyroxine tablets (75 g) were taken daily as replacement therapy, and the symptoms improved.

2. On July 26, 2021, the patient developed nausea, vomiting and poor appetite without obvious causes and did not improve after receiving fluid reinfusion and gastric protection at the local hospital for acute gastroenteritis. On August 2, 2021, the patient was admitted to our hospital due to a fasting blood glucose (FBG) result of 360 mg/dl and HbA1c of 9.25%. The patient had no history of diabetes or hypertension. The patient regularly underwent routine biochemical review during immunotherapy, and his FBG was 7290 mg/dl. The last routine biochemical review suggested that the FBG was 100.8 mg/dl on July 20, 2021. On admission, the body temperature was 36.6 C, heart rate was 120 beats/min, breathing was 21 breaths/min, blood pressure was 136/105 mmHg, and blood oxygen saturation (SpO2) was 99%. At that time, he was conscious, poor in spirit, short of breath, and had dry skin.

3. Auxiliary examination: The blood glucose level of the fingertip was 291.6 mg/dl, and the blood ketone level of the fingertip was 6.4 mmol/L upon admission. The results of arterial blood gas analysis were as follows: pH: 7.14, partial pressure of carbon dioxide (PaCO2): 21 mmHg, partial pressure of oxygen (PaO2): 102 mmHg, bicarbonate: 7.1 mmol/L, residual alkali: 21.9 mmol/L; routine urinalysis: 3+ of ketone and + of glucose; HbA1c was 9.25% (normal range 4.06.5%) in the outpatient department. These data indicated the onset of diabetic ketoacidosis. Further examination results showed that there were no obvious abnormalities in the contrast-enhanced MRI scan of the pituitary gland (Figure 1) and the high-resolution CT of the pancreas, and the other laboratory examinations are shown in Table 1.

Table 1 Laboratory Results for the Patient

Figure 1 Sagittal and coronal slices of the pituitary MRI (A) Precontrast T1-weighted coronal slices MRI image. (B) Postcontrast T1-weighted coronal slices MR image. (C) Precontrast T1-weighted sagitta slices MRI image. (D) Postcontrast T1-weighted sagitta slices MR image. (E) Precontrast T2-weighted coronal slices MRI image. (F) Postcontrast T2-weighted sagitta slices MR image.

4. Diagnosis and treatment: The patient had no history of diabetes, and his FBG was within normal range according to regular tests; however, his HbA1c was high, so postprandial blood glucose could not be ruled out during KN046 immunotherapy. Insulin and C-peptide levels could hardly be detected after admission, suggesting that islet cell function had been lost. The patient was diagnosed with hypopituitarism for more than a year. Considering that immunotherapy involved the pituitary and caused hypophysis, HbA1c and postprandial blood glucose levels had not been monitored in the past. Therefore, based on the patients medical history and auxiliary examination, and referring to the domestic expert consensus (expert consensus on immune-related adverse reactions of the endocrine system caused by immune checkpoint inhibitors (2020)) for the recommended diagnostic criteria and disease classification of endocrine irAEs caused by ICIs, the following diagnoses were considered: 1. Immune checkpoint inhibitor-associated diabetes mellitus complicated by ketoacidosis, CTCAE grade 3; 2. Hypopituitarism hypofunction pituitary gland inflammation disease immune-checkpoint inhibitors correlation, CTCAE grade 2.3 The patient received intravenous fluid and insulin therapy in addition to oral rehydration and potassium. Intravenous insulin therapy was then followed by multiple injections of insulin aspart. For patients to stop taking prednisone and prior to administration of levothyroxine sodium replacement therapy, the hospital laboratory tests suggest that ACTH and cortisol levels are low, furthermore, Thyroxine was reduced, and thyroid stimulating hormone (TSH) was at the lower limit. To avoid pituitary induced crisis, the patients was temporarily placed on a 100 mg hydrocortisone intravenous drip. Nausea and vomiting ceased, and appetite improved markedly. After that, the prednisone tablets were substituted with low-dose therapy, and a physiological dose of levothyroxine sodium was supplemented. The patient has been treated with multiple daily subcutaneous insulin injections since August 5, 2021, and blood glucose gradually decreased and stabilized.

The main cause of irAEs induced by ICIs is excessive activation of T lymphocytes, while endocrine-related irAEs mainly include hypophysitis, thyroiditis, diabetes, and adrenal cortical hypofunction, and so on. Among them, hypophysitis and thyroiditis are the most common, while diabetes is relatively rare. Previous studies have focused on the incidence of a single endocrine irAEs; however, people with one autoimmune disease are at higher risk of developing a second autoimmune disease.4,5

A meta-analysis of ICI treatment found that 85 of 6472 patients had hypophysitis,6 but the clinical symptoms of hypophysitis were mostly atypical.7,8 The most common symptoms were headache and fatigue, and multiple hormone deficiencies were also common,9,10 including TSH, ACTH, follicle stimulating hormone and luteinizing hormone. Early pituitary MRI examination was helpful for differential diagnosis.11 There is currently no consensus on the pathogenesis of ICI-associated hypophysitis, and studies have found that the presence of antipituitary gland autoantibodies and human leukocyte antigens (HLAs) in the serum of patients may increase the susceptibility of ICIs-induced hypophysitis.12 The occurrence time of hypophysitis was related to ICI type,10 among which the incidence of PD-L1/PD-1 plus CTLA-4 inhibitor was the highest (6.4%), followed by CTLA-4 inhibitor (3.2%), PD-1 inhibitor (0.4%) and PD-L1 inhibitor (less than 0.1%).7,13 Some studies have shown that the incidence of hypophysitis induced by CTLA-4 inhibitor therapy is much higher in men than in women.6,9 The higher incidence in males may be explained by the positive effect of androgens on the expression of CTLA-4.12 Therefore, it is suggested that male patients treated with ICIs need to pay attention to the occurrence of hypophysitis, especially in those treated with CTLA-4 inhibitor or combination therapy, and the onset time is mostly within the first half-year after treatment.3 In this case, the patient was male, and hypopituitarism was found due to fatigue after KN046 immunotherapy, which was consistent with the sex characteristics of hypophysitis-related cases reported in the past, but the onset time was later than in most related cases. This patient was admitted to the hospital due to ICI involving pancreatic injury and causing DKA, and the patients previous hypopituitarism was considered to be due to hypophysitis caused by ICI treatment. After admission, pituitary-related target gland hormone levels were tested, and the levels of TT3, TT4, cortex alcohol and ACTH were still low, which may be related to the patients decision to stop taking levothyroxine tablets and prednisone tablets after the onset of this disease. At the same time, a pituitary MRI showed no abnormalities, which may be related to the patients longer onset and long-term hormone replacement therapy.

Diabetes is a relatively rare adverse reaction to ICIs, mainly seen in PD-1 inhibitor treatment, with a few cases occurring in PD-L1 inhibitor treatment and only a few cases reported in CTLA-4 inhibitor treatment.14 PD-L1 is widely expressed not only in lymphoid tissues, but also in target organs including pancreatic b cells. Blocking the interaction of PD-1 and PD-L1 might stimulate T cell proliferation and activation then leading to the destruction of b cells, providing a possible mechanism for anti-PD-1 induced T1DM.15 A meta-analysis of 7551 patients from 38 randomized clinical trials showed that ICI induced diabetes in 0.2% (13 cases).6 The combination of anti-CTLA-4 with anti-PD-1 or PD-L1 increased the frequency of irAEs by 60% compared with ICI monotherapy.16 Among these cases, the median time of onset was 20 weeks, with most cases associated with monotherapy against PD-1/PD-L1 occurring after 10 weeks.14 Similarly, a small number of patients developed T1DM later. Stamatouli et al described a case of T1DM at 228 weeks (54 months) after initial treatment.14 The onset time of T1DM in this case was 25 months after receiving KN046 immunotherapy, and the onset was sudden and reached the diagnostic criteria of ICI-related diabetes recommended by Chinese experts.3 This reminds clinicians to regularly monitor the indicators related to islet function during immunotherapy, and they still need to pay more attention even after a long period of treatment.

ICI-related diabetes has a more acute onset and rapid progression, and the symptoms may be present in a short time, with high blood glucose or DKA symptoms. During immune therapy, patients have no obvious thirst or polyuria, such as with nonspecific symptoms of diabetes, and periodically tested fasting glucose levels are within normal range. Therefore, in patients with clinical symptoms that are not obvious or with no specific symptoms, dynamic monitoring of other indicators is also required. According to European and American guidelines,2,1720 regular monitoring of blood glucose levels is recommended to detect type 1 or type 2 diabetes; however, even routine monitoring of blood glucose levels may not detect or predict its occurrence. After the onset of ICI-related diabetes, insulin and C-peptide often rapidly decreased to less than one-third of the normal value and may not return to normal for a long time. Therefore, we believe that dynamic monitoring of C-peptide levels is an effective means to predict ICI-related diabetes. In this case, the C-peptide level was too low to be detected after onset. This suggests that islet cell function was severely impaired after KN046 therapy, and some cases have reported that partial recovery of islet function can be achieved in individual patients due to the release of glycotoxicity or the onset of the honeymoon phase.21,22 Diabetes autoantibody positivity is not necessarily related to the occurrence of ICI-related diabetes but may be related to the occurrence time of diabetes. The onset time of ICI-associated T1DM with antibody positivity was shorter, and DKA occurred more frequently than in patients with insulin autoantibody negativity.14 The patients diabetes autoantibodies were negative, and the onset time was long, which was consistent with the onset characteristics of most cases at present.

In contrast to previous related cases, hypopituitarism was found in this patient for 14 months before the occurrence of DKA, suggesting that patients after ICI treatment may have multiple endocrine gland injuries. And such events have also been reported. For example, Giulia Lanzolla reported a case of hyperglycemia after 2 cycles of the PD-L1 inhibitor atezolizumab and DKA, primary adrenal hypofunction, and hypophysitis with pituitary insufficiency after 4 cycles of treatment.23 Malik Asif Humayun also reported a case of T1DM secondary to hypophysitis during treatment with nivolumab, a PD-1 inhibitor, in combination with ipilimumab, a CTLA-4 inhibitor.24 Laura Boswell reported a case of hypophysitis in the course of immunotherapy with ipilimumab, a CTLA-4 inhibitor, and then explosive T1DM after the cessation of combined immunotherapy.25 Therefore, patients undergoing immunotherapy need to pay close attention to changes in endocrine and glandular functions during treatment, and even after the treatment ends.26 We should not let our guard down, and especially in the course of combined immunotherapy, we should pay close attention to the function of other glands after the injury of one endocrine gland. More importantly, the new drug KN046 used in this patient was a PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu Corning & Jerrys Co. LTD. Its innovative design includes the fusion of CTLA-4 and PD-L1 single-domain antibodies with different mechanisms, which can simultaneously recognize PD-L1 and CTLA-4 and effectively enhance the killing of tumor cells.27 It is different from the combined immunotherapy used in previous cases, which may have caused injury to multiple endocrine glands in this patient, and the onset of the disease is late because of its unique therapeutic mechanism. In this case, a patient with polyendocrinopathy damage occurred during immunotherapy with KN046, and a trial on KN046 proposed a smart reagent that binds a nanoprobe and a double-blocking immunotherapy antibody, which improves the anti-tumor efficacy while having a high safety profile, which may reduce the incidence of irAEs.27 At present, we have not inquired about the endocrine-related irAEs caused by KN046 immunotherapy.

Due to lack of thyroid hormone function in this example patient, we were unable to determine whether the hypothyroidism is due to autoimmune thyroiditis or pituitary gland inflammation. However, the thyroid hormone function test results show that the TPOAb and TGAb levels were higher, and TRAb was negative, which may have been caused by autoimmune thyroiditis. It is also impossible to rule out whether thyroid dysfunction is caused by ICI-related thyroid damage. To determine the etiology, thyroid puncture can be performed to determine the pathological type. The causes of ICI-related thyroid dysfunction are related to the patients underlying thyroid disease, TSH levels, autoantibody titers, fluorodeoxyglucose uptake, and tumor immune microenvironment status.3

Unfortunately, the vast majority of patients described in these articles received no baseline assessment of endocrine gland function; thus, we cannot know how many had a silent metabolic/endocrine disorder before ICI therapy, and how many developed these conditions at a later date. Therefore, the strong need to have clear indications to assess patients before ICI therapy, along with a well-defined follow-up, plainly emerges.28

ICIs are widely used and can significantly prolong the survival period of tumor patients. However, we need to pay attention to various adverse reactions while focusing on their therapeutic effect. Among them, endocrine-related irAEs have unknown pathogenesis and complex clinical manifestations, which may endanger life in severe cases. In the course of ICI combination therapy, especially with immunosuppressive drugs such as KN046 that block both PD-L1 and CTLA-4 targets at the same time, patients may suffer damage to multiple endocrine glands, and it is necessary to pay close attention to the patients endocrine system irAEs for a long time, even after treatment.

Written informed consent for publication of their details was obtained from the patient. Based on the hospital there is no need for ethical clearance for the case report.

The authors declare that they have no competing interests in this work.

1. Dougan M, Pietropaolo M. Time to dissect the autoimmune etiology of cancer antibody immunotherapy. J Clin Invest. 2020;130(1):5161. doi:10.1172/JCI131194

2. Haanen J, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv119iv142. doi:10.1093/annonc/mdx225

3. Immune-endocrinology Group, Chinese society of Endocrinology, Chinese Medical Association. Chinese expert consensus on immune checkpoint inhibitors-induced endocrine immune-related adverse events (2020). Chin J Endocrinol Metab. 2021;37(01):116.

4. De Block C, De Leeuw I, Decochez K, et al. The presence of thyrogastric antibodies in first degree relatives of type 1 diabetic patients is associated with age and proband antibody status. J Clin Endocrinol Metab. 2001;86(9):43584363. doi:10.1210/jcem.86.9.7833

5. De Block C, De Leeuw I, Vertommen J, et al. Beta-cell, thyroid, gastric, adrenal and coeliac autoimmunity and HLA-DQ types in type 1 diabetes. Clin Exp Immunol. 2001;126(2):236241. doi:10.1046/j.1365-2249.2001.01668.x

6. Barroso-Sousa R, Barry W, Garrido-Castro A, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol. 2018;4(2):173182. doi:10.1001/jamaoncol.2017.3064

7. Faje A, Sullivan R, Lawrence D, et al. Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma. J Clin Endocrinol Metab. 2014;99(11):40784085. doi:10.1210/jc.2014-2306

8. Albarel F, Gaudy C, Castinetti F, et al. Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma. Eur J Endocrinol. 2015;172(2):195204. doi:10.1530/EJE-14-0845

9. Scott E, Long G, Guminski A, Clifton-Bligh R, Menzies A, Tsang V. The spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors for metastatic melanoma. Eur J Endocrinol. 2018;178(2):173180. doi:10.1530/EJE-17-0810

10. Chang L, Barroso-Sousa R, Tolaney S, Hodi F, Kaiser U, Min L. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr Rev. 2019;40(1):1765. doi:10.1210/er.2018-00006

11. Joshi M, Whitelaw B, Palomar M, Wu Y, Carroll P. Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review. Clin Endocrinol (Oxf). 2016;85(3):331339. doi:10.1111/cen.13063

12. Frasca F, Piticchio T, Le Moli R, et al. Recent insights into the pathogenesis of autoimmune hypophysitis. Expert Rev Clin Immunol. 2021;17(11):11751185. doi:10.1080/1744666X.2021.1974297

13. Sznol M, Postow M, Davies M, et al. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management. Cancer Treat Rev. 2017;58:7076. doi:10.1016/j.ctrv.2017.06.002

14. Stamatouli A, Quandt Z, Perdigoto A, et al. Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors. Diabetes. 2018;67(8):14711480. doi:10.2337/dbi18-0002

15. Yadav D, Sarvetnick N. Costimulation and pancreatic autoimmunity: the PD-1/PD-L conundrum. Rev Diabet Stud. 2006;3(1):610. doi:10.1900/RDS.2006.3.6

16. Wolchok J, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):13451356. doi:10.1056/NEJMoa1709684

17. Higham C, Olsson-Brown A, Carroll P, et al. Society for endocrinology endocrine emergency guidance: acute management of the endocrine complications of checkpoint inhibitor therapy. Endocr Connect. 2018;7(7):G1G7. doi:10.1530/EC-18-0068

18. Thompson J, Schneider B, Brahmer J, et al. NCCN guidelines insights: management of immunotherapy-related toxicities, Version 1.2020. J Natl Compr Cancer Netw. 2020;18(3):230241. doi:10.6004/jnccn.2020.0012

19. Brahmer J, Lacchetti C, Schneider B, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J Clin Oncol. 2018;36(17):17141768. doi:10.1200/JCO.2017.77.6385

20. Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):95. doi:10.1186/s40425-017-0300-z

21. Kumagai R, Muramatsu A, Nakajima R, et al. Acute-onset type 1 diabetes mellitus caused by nivolumab in a patient with advanced pulmonary adenocarcinoma. J Diabetes Investig. 2017;8(6):798799. doi:10.1111/jdi.12627

22. Matsumura K, Nagasawa K, Oshima Y, et al. Aggravation of diabetes, and incompletely deficient insulin secretion in a case with type 1 diabetes-resistant human leukocyte antigen DRB1*15:02 treated with nivolumab. J Diabetes Investig. 2018;9(2):438441. doi:10.1111/jdi.12679

23. Lanzolla G, Coppelli A, Cosottini M, Del Prato S, Marcocci C, Lupi I. Immune checkpoint blockade anti-PD-L1 as a trigger for autoimmune polyendocrine syndrome. J Endocr Soc. 2019;3(2):496503. doi:10.1210/js.2018-00366

24. Kikuchi F, Saheki T, Imachi H, et al. Nivolumab-induced hypophysitis followed by acute-onset type 1 diabetes with renal cell carcinoma: a case report. J Med Case Rep. 2021;15(1):214. doi:10.1186/s13256-020-02656-7

25. Humayun M, Poole R. A case of multiple immune toxicities from Ipilimumab and pembrolizumab treatment. Hormones. 2016;15(2):303306. doi:10.14310/horm.2002.1656

26. Boswell L, Casals G, Blanco J, et al. Onset of fulminant type 1 diabetes mellitus following hypophysitis after discontinuation of combined immunotherapy. A case report. J Diabetes Investig. 2021;12(12):22632266. doi:10.1111/jdi.13604

27. Jiang C, Zhang L, Xu X, et al. Engineering a smart agent for enhanced immunotherapy effect by simultaneously blocking PD-L1 and CTLA-4. Adv Sci. 2021;8(20):e2102500. doi:10.1002/advs.202102500

28. Ruggeri R, Campenn A, Giuffrida G, et al. Endocrine and metabolic adverse effects of immune checkpoint inhibitors: an overview (what endocrinologists should know). J Endocrinol Invest. 2019;42(7):745756. doi:10.1007/s40618-018-0984-z

Read more:
Polyendocrine gland injury induced by an immunosuppressant | DMSO - Dove Medical Press

Recommendation and review posted by Bethany Smith

The CHMP's recommendation was based on results from the pivotal KEYNOTE-522 trial, which was the first Phase 3 study with an immunotherapy to show positive event-free survival (EFS) results in high-risk early-stage TNBC. As previously reported, after a median follow-up of 39 months, the KEYTRUDA regimen (neoadjuvant KEYTRUDA plus chemotherapy followed by adjuvant KEYTRUDA monotherapy) reduced the risk of events or death by 37% (HR=0.63 [95% CI, 0.48-0.82]; p

Triple-negative breast cancer is an aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer.

"This positive CHMP opinion reinforces our efforts to advance the treatment of breast cancer in Europe and expand the use of KEYTRUDA in TNBC to potentially help even more patients with this aggressive disease who are in need of new treatment options," said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. "We look forward to the European Commission's decision and are excited about the prospect of bringing the first immunotherapy regimen for high-risk, early-stage TNBC to appropriate patients in Europe."

The CHMP's recommendation will now be reviewed by the European Commission for marketing authorization in the European Union, and a final decision is expected in the second quarter of 2022. If approved, this will be the second indication for KEYTRUDA in TNBC in Europe. In October 2021, KEYTRUDA plus chemotherapy was approved for the first-line treatment of certain patients with locally recurrent unresectable or metastatic TNBC.

Merck is rapidly advancing a broad portfolio in gynecologic and breast cancers with an extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across these areas.

About Triple-Negative Breast Cancer (TNBC)

Approximately 10-15% of patients with breast cancer are diagnosed with TNBC. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Triple-negative breast cancer tends to be more common in people who are younger than 40 years of age, who are Black or who have a BRCA 1 mutation.

About Merck's Early-Stage Cancer Clinical Program

Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry's largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.

KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):

Non-muscle Invasive Bladder Cancer

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Cancer

KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Endometrial Carcinoma

KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (

KEYTRUDA With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatments. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

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Pfizer and Biohaven's VYDURA Granted First Ever Marketing Authorization by European Commission for Both Acute Treatment of Migraine and Prophylaxis of...

Recommendation and review posted by Bethany Smith

Stem cells are key building blocks for the human body. At the start of life, they divide over and over again to create a fully developed baby from an embryo. Many individuals now even turn to services that store and preserve umbilical cords should a person ever be in need.

Stem cells have the potential to develop into different types of cells in the body, serving as a repair system of sorts for damaged or lost cells. In recent decades, scientists have shown the miraculous ways of medicine through stem cell treatments.

So just how are doctors using stem cells to treat and help heal people battling various ailments? Heres a look at five studies published on StudyFinds that demonstrate the wondrous ways of stem cell treatments.

A heart condition called dilated cardiomyopathy, or DCM, weakens muscles of the ventricles, which causes heart failure and often death in children. Currently, the only cure is a heart transplant, which can take long periods of time to find an acceptable donor and increases the risk of rejection of the donor tissue. One study finds that stem cell therapy could help DCM patients survive longer while awaiting a transplant or potentially eliminate the need for a new heart entirely.

Cardiac stem cells called cardiosphere-derived cells (CDCs) have proven to be effective at treating certain heart conditions. The CDCs grow into tissue cells of the heart and can counter the effects of DCM. To test the safety of the CDC therapy, a team of scientists at Okayama University in Japan demonstrated the efficacy of CDCs in tissue damaged from DCM. For the study, DCM symptoms were induced in pigs, after which CDCs were administered in various doses for treatment. In a control group, some pigs were given a placebo.

Results showed thickening of the heart muscle in pigs who were given the stem cell treatment. This allows increased blood flowto the rest of the body, thereby effectively repairing the damaged tissue. Due to the dosage used in animal trials, researchers could estimate the proper dosage for human trials.

The first of these included 5 younger patients who were diagnosed with DCM. Injections of CDCs resulted inbetter heart function without any serious side effects. Thus, scientists believe this type of treatment could minimize the need for heart transplants and allow DCM patients to have normal lives.

READ MORE: Stem cell treatment shows promise as treatment for rare heart condition in children

Although their use is sometimes controversial, scientists often look at stem cells as a potential miracle cure for many conditions. One study finds stem cells from a babys umbilical cord may save the most at risk of dying from COVID-19. A treatment derived from non-altered versions of these stem cells significantly improves the survival rate among coronavirus patients already on a ventilator.

In a double-blind, controlled, randomized study, 40 adultpatients in intensive careand on a ventilator received the treatment intravenously. The infusions contained stem cells coming from the connective tissue of a human umbilical cord. Half of the patients received infusions not containing stem cells to serve as a control group.

Results reveal survival rates climbed by 2.5 times among patients receiving stem cells. Those with a pre-existing health problem, making them high-risk for COVID, saw their changes of beating coronavirus jump by 4.5 times. Moreover, the study says the stem cell infusions did not cause any life-threatening complications or allergic reactions.

READ MORE: Stem cells from a babys umbilical cord doubles survival chances among COVID patients

In the fight against heart disease, a new super-weapon is now even closer to deployment, and its capabilities are turning out to be beyond expectations. A study aimed at combating heart disease finds that stem cells are not only showing promise in treating heart failure, but in rats are actually reversing problems associated with old age.

The specific type of stem cells used in the study are cardiosphere-derived cells, or CDCs. While the latest research involving CDCs indicates possibilities that have previously been in the realm of science fiction, the scientists leading the charge urge restraint in face of the excitement.

Nevertheless, the latest results of stem cell infusions in rats are startling. Not only did rats that received the CDCs experience improved heart function, they also had lengthened heart cell telomeres. Moreover, the rats that received the treatment also had their exercise capacity increase by about 20 percent. They also regrew hair faster than rats that didnt receive the cells.

Still, the doctors and scientists working to push the frontier of medicine forward are very optimistic about the real possibilities of the therapy. Researchers of the study said they are also studying the use of stem cells in treating patients with Duchenne muscular dystrophy and patients with heart failure with preserved ejection fraction, a condition that affects more than 50 percent of all heart failure patients.

READ MORE: Study: Cardiac stem cell injections reverse effects of aging

A new biomaterial can help regenerate tissue in people dealing with chronic lower back pain and spinal issues. A recent study finds the secret to this breakthrough therapy is all in the hiPS. Not thosehips, but human induced pluripotent stem cells.

The study explains that a common cause of lower back pain is the degeneration of intervertebral discs (IVDs). These discs sit between the vertebrae in the spine and help give the spinal column its flexibility. Severe IVD degeneration eventually leads to spinal deformity without treatment. In this study, scientists used cartilage tissue derived from stem cells to build back lost IVDs in lab rats.

Study authors used induced pluripotent stem cells (iPSCs) during their experiments. Importantly, scientists are capable of turning iPSCs into chondrocytes cells that produce and maintain cartilage. Previous studies have successfully used this same method to treat cartilage defects in animals. In the new study, researchers created human iPSC-derived cartilaginous tissue (hiPS-Cart) that they implanted into rats with no NP cells in their intervertebral discs.

Findings reveal that the hiPS-Cart implanted in the rats was able to survive and be maintained. IVD and vertebral bone degeneration were prevented. The researchers also assessed the mechanics and found that hiPS-Cart was able to revert these properties to similar levels observed in the control rats.

READ MORE: Stem cell cure for lower back pain is all in the hiPS

Stem cells taken from deceased patients may also help in creating a cure for blindness. Retina cells from a corpse continue to survive after being transplanted into the eyes of monkeys, scientists say.

RPE dysfunction is a leading cause of blindness, including causing disorders likemacular degeneration, which affects around 200 million people worldwide. Now, for the first time, scientists have successfully produced retina cells in monkeys using human stem cells. Human cadaver donor-derived cells can be safely transplanted underneath the retina and replace host function, and therefore may be a promising source for rescuing visionin patients with retina diseases.

For the study, researchers transplanted stem cells from the eyes of donated bodies under the monkeys macula, the central part of the retina. Following surgery, the transplanted patches remained stable for at least three months without any serious side-effects. The RPE created by the human stem cells partially took over from the old retina cells. In addition, this could successfully support the eyes light receptorswithout causing retinal scarring.

These unique cells could serve as an unlimited resource of human RPE, whichmay restore sightfor millions of people around the world. The scientists caution that they will need to conduct more research to see how the procedure works with human transplant patients. Human trials are still a long way off.

READ MORE: Eye stem cells transplanted from corpses to live patients could cure blindness

For more information on each of these stem cell treatments, you can refer to the READ MORE links in between each section.

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Stem Cell Magic: 5 Promising Treatments For Major Medical Conditions - Study Finds

Recommendation and review posted by Bethany Smith

The new report by Expert Market Research titled, Global Stem Cell Market Report and Forecast 2022-2027, gives an in-depth analysis of the globalstem cell market, assessing the market based on its segments like types, treatment types, applications and major regions. The report tracks the latest trends in the industry and studies their impact on the overall market. It also assesses the market dynamics, covering the key demand and price indicators, along with analysing the market based on the SWOT and Porters Five Forces models.

Request a free sample copy in PDF or view the report summary@https://www.expertmarketresearch.com/reports/stem-cell-market/requestsample

The key highlights of the report include:

Market Overview (2017-2027)

The stem cell business is growing due to an increase in activities to use stem cells in regenerative treatments due to their medicinal qualities. The increasing use of human-induced pluripotent stem cells (iPSCs) for the treatment of hereditary cardiac difficulties, neurological illnesses, and genetic diseases such as recessive dystrophic epidermolysis bullosa (RBED) is driving the market forward.

Furthermore, because human-induced pluripotent stem cells (iPSCs) may reverse immunosuppression, they serve as a major source of cells for auto logic stem cell therapy, boosting the industrys expansion. Furthermore, the rising incentives provided by major businesses to deliver breakthrough stem cell therapies, as well as the increased use of modern resources and techniques in research and development activities (R&D), are propelling the stem cell market forward.

Because of increased research and development (R&D) in the United States and Canada, North America accounts for a significant portion of the overall stem cell business. Furthermore, the increased frequency of non-communicable chronic diseases such as cancer and Parkinsons disease, among others, is boosting the use of stem cell therapy, boosting the industrys growth. Furthermore, the regions stronghealthcaresector is improving access to innovative cell therapy treatments, assisting the regional stem cell industrys expansion. Aside from that, due to the rising use of regenerative treatments, the Asia Pacific area is predicted to rise rapidly. Furthermore, rising clinical trials are assisting market expansion due to low labour costs and the availability of raw materials in the region, contributing considerably to overall industry growth.

Industry Definition and Major Segments

A stem cell is a type of cell that has the ability to develop into a variety of cells, including brain cells and muscle cells. It can also help to repairtissuesthat have been injured. Because stem cells have the potential to treat a variety of non-communicable and chronic diseases, including Alzheimers and diabetes, theyre being used in medical and biotechnological research to repair tissue damage caused by diseases.

Explore the full report with the table of contents@https://www.expertmarketresearch.com/reports/stem-cell-market

The major product types of stem cell are:

The market can be broadly categorised on the basis of its treatment types into:

Based on applications, the market is divided into:

The EMR report looks into the regional markets of stem cell-like:

Market Trends

The market is expected to rise due to increased research activity in regenerative medicine and biotechnology to personalise stem cell therapy. The usage of stem cells is predicted to increase as the need for treatment of common disorders, such as age-related macular degeneration (AMD), grows among the growing geriatric population. Due to multiple error bars during research operations, it becomes extremely difficult to characterise cell products because each cell has unique properties. As a result, the integration of cutting-edge technologies such as artificial intelligence (AI), blockchain, and machine learning is accelerating. Artificial intelligence (AI) is being used to analyse images quickly, forecast cell functions, and classify tissues in order to identify cell products, which is expected to boost the market growth.

With the rising frequency of cancer and cancer-related research initiatives, blockchain technology is increasingly being used to collect and assimilate data in order to improve access to clinical outcomes and the latest advances. Blockchain can also help with data storage for patients while improving the cost-effectiveness of cord-blood banking for advanced research and development (R&D) purposes. In addition, the use of machine learning techniques to analyse photos and infer the relationship between cellular features is boosting the market growth. The increased interest in understanding cellular processes and identifying critical processes using deep learning is expected to move the stem cell business forward.

Latest News on Global Stem Cell Market@https://www.expertmarketresearch.com/pressrelease/global-stem-cell-market

Key Market Players

The major players in the market are Pluristem Therapeutics Inc., Thermo Fisher Scientific Inc., Cellular Engineering Technologies, Merck KGaA, Becton, Dickinson and Company, and STEMCELL Technologies Inc The report covers the market shares, capacities, plant turnarounds, expansions, investments and mergers and acquisitions, among other latest developments of these market players.

About Us:

Expert Market Research is a leading business intelligence firm, providing custom and syndicated market reports along with consultancy services for our clients. We serve a wide client base ranging from Fortune 1000 companies to small and medium enterprises. Our reports cover over 100 industries across established and emerging markets researched by our skilled analysts who track the latest economic, demographic, trade and market data globally.

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Global Stem Cell Market To Be Driven By Increasing Activities To Use Stem Cells In Regenerative Medicines In The Forecast Period Of 2022-2027 ...

Recommendation and review posted by Bethany Smith

By Steve Gorman

(Reuters) The first all-private astronaut crew to fly aboard the International Space Station (ISS) headed for splashdown Monday off the coast of Florida, wrapping up a two-week mission that NASA has touted as a landmark in commercial spaceflight.

A SpaceX Crew Dragon capsule carrying the four-man team of Houston-based startup Axiom Space Inc began its return flight about 9 p.m. EDT Sunday (0100 Monday GMT) as it undocked from the space station orbiting about 250 miles (420 km) above Earth.

The Crew Dragon was expected to parachute into the Atlantic around 1 p.m. EDT on Monday (1700 GMT), capping a 16-hour ride home from orbit that had been postponed for several days because of unfavorable weather.

The multinational Axiom team was led by Spanish-born retired NASA astronaut Michael Lopez-Alegria, 63, the companys vice president for business development. His second-in-command was Larry Connor, 72, a technology entrepreneur and aerobatics aviator from Ohio designated the mission pilot.

Joining them as mission specialists were investor-philanthropist and former Israeli fighter pilot Eytan Stibbe, 64, and Canadian businessman and philanthropist Mark Pathy, 52.

Launched from NASAs Kennedy Space Center on April 8, they spent 15 days aboard the space station with the seven regular, government-paid ISS crew members: three American astronauts, a German astronaut and three Russian cosmonauts.

The ISS has hosted several wealthy space tourists from time to time over the years.

But the Axiom quartet was the first all-commercial team ever welcomed to the space station as working astronauts, bringing with them 25 science and biomedical experiments to conduct in orbit. The package included research on brain health, cardiac stem cells, cancer and aging, as well as a technology demonstration to produce optics using the surface tension of fluids in microgravity.

Axiom, NASA and SpaceX have hailed the mission as a milestone in the expansion of privately funded space-based commerce, constituting what industry insiders call the low-Earth orbit economy, or LEO economy for short.

It was the sixth human spaceflight for SpaceX in nearly two years, following four NASA astronaut missions to the ISS and the Inspiration 4 flight in September that sent an all-private crew into Earth orbit for the first time, though not to the space station.

SpaceX, the private rocket company founded by Tesla Inc electric carmaker CEO Elon Musk, has been hired to fly three more Axiom astronaut missions to ISS over the next two years. The price tag for such outings is high.

Axiom charges customers $50 million to $60 million per seat, according to Mo Islam, head of research for the investment firm Republic Capital, which holds stakes in both Axiom and SpaceX.

Axiom also was selected by NASA in 2020 to build a new commercial addition to the space station, which a U.S.-Russian-led consortium of 15 countries has operated for more than two decades. Plans call for the Axiom segment to eventually replace the ISS when the rest of the station is retired around 2030.

(Reporting by Steve Gorman in Los Angeles. Editing by Gerry Doyle)

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First all-private astronaut team aboard space station heads for splashdown - KFGO

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The change in the prevalence of HHD

At the global level, the prevalence of HHD increased by 137.91% from 7.82 million in 1990 to 19.60 million in 2019 (Fig.1A, Table S1). The prevalence rate went up year by year, while the ASPR was relatively stable (Fig. 1C). The ASPR was 233.77 (95% UI=170.52312.9) per 100,000 population in 2019, which increased slightly compared with that in 1990 with an EAPC of 0.17 (95% UI=0.150.18) (Fig. 1C, Tables S2 and S3). Compared with the ASPR trend of the female subjects (EAPC, 0.28, 95% UI=0.260.30), the trend of the male subjects was more stable during the study period (EAPC, 0.02, 95% UI=0.000.04, Table S3).

The global trend of hypertensive heart disease from 1990 to 2019. The number of prevalence (A), death (D), and DALY (G). The rate of prevalence (B), death (E), and DALY (H). Age-standardized rate of prevalence (C), death (F), and DALY (I). Dashed lines represent 95% uncertainty interval; DALY, disability adjusted life-year

HHD occurred mostly in people aged over 65 (Fig. S1A). We also found that the ASPR increased with age growth for both men and women in 1990 and 2019. The female prevalence rate was much higher than male in people aged over 80 during 2019, yet there was a similar prevalence rate for aged men and women in 1990 (Fig.2).

The gender-specific global prevalence, death, and DALY rate of hypertensive heart disease in 1990 and 2019. The vertical axis represents DALY, death, and prevalence rate (per 100,000 population). DALY, disability adjusted life-year

Among 25 GBD regions, top three regions with the highest prevalence cases were Asia, East Asia, and America. In addition, the three regions with the highest ASPR were East Asia (426.15, 95% UI=306.64574.76), Oceania (344.91, 95% UI=248.54477.87), and Southeast Asia (334.77, 95% UI=244.81451.58) (Table S4). At the national level, China carried the highest HHD prevalence, followed by the United States of America and India (Fig. S2A). The highest ASPR of HHD occurred in Cook Islands, Jordan, Kuwait and Seychelles (Fig. S2C).

A total of 1.16 (95% UI=0.861.28) million people were estimated to experience HHD associated deaths worldwide in 2019, which increased from 0.65 (95% UI=0.530.73) million death cases in 1990 (Table S1). The ASDR in females was 15.05 (95% UI=11.5117.09) per 100,000 population in 2019, which was moderately higher than that in males (14.95, 95% UI=10.3216.75) (Table S2). Although the number of HHD deaths grew up dramatically during 19902019, the trend of death rate was relatively stable and the global ASDR declined with a negative value of EAPC (0.74, 95% UI=-0.92--0.58) (Fig. 1D, E, and F, Table S3). Meanwhile, the male and female ASDR shared a similar trend (EAPC for men, 0.72, 95% UI=-0.95--0.50; EAPC for women, 0.79, 95% UI=-0.93--0.65).

For both men and women, age-specific distribution of death rate remained stable in 1990 and 2019 (Fig. 2). Like HHD prevalence, people aged over 65 were more likely to suffer HHD deaths (Fig. S1B).

At the regional level, Central Sub-Saharan Africa, Eastern Sub-Saharan Africa, North Africa and Middle East had the highest ASDR; Australasia, high-income Asia Pacific and Eastern Europe were the three regions with the lowest ASDR (Table S5). At the national level, China carried the highest HHD death burden, followed by India and the Untied States of America (Fig. S2D). Bulgaria, Afghanistan, and Central African Republic were the three countries with highest ASDR (Fig. S2F).

A total of 21.50 (95% UI=16.4023.90) million DALYs were estimated on a global scale in 2019, and 13.94 (95% UI=11.3115.65) DALYs in 1990 (Table S1). There was a consistent rise in DALY number (Fig. 1G). However, DALY rate declined between 1990 and 2005, then ascended during 20062019 (Fig. 1H). In addition, it shown a persistent decline for the age-standardized DALY rate over the 30years (Fig. 1I).

The age-standardized DALY rate in men was 277.86 (95% UI=199.58311.14) per 100,000 population in 2019, which was higher than that in women (256.81, 95% UI=205.22291.98) (Table S2). The DALY rate distribution for males and females in 2019 was similar to that in 1990 (Fig. 2). In 2019, the age-specific trends of DALY rate attributed to HHD were similar for both sexes.

On the observation of the regions scale, Central Sub-Saharan Africa, Eastern Sub-Saharan Africa, and Oceania were the three regions with the highest age-standardized DALY rates (Table S5). It revealed a considerable national disparity in the burden of HHD. DALY numbers varied more than 10-fold between countries (Fig.3A). China had the highest HHD DALY number, followed by India and Indonesia (Fig. 3D). After adjusting population, Bulgaria, Estonia, and Cook Islands were the three countries with the highest rate of DALYs (Fig. 3B and E). After adjusting for age and population, Afghanistan, Cook Islands, and Central African Republic had the highest age-standardized DALY rates (Fig. 3C and F).

Global map of the disease burden of hypertensive heart disease (A, DALY number; B, DALY rates; C, Age-standardized DALY rates) and the top 20 countries with disease burden (D, DALY number; E, DALY rates; F, Age-standardized DALY rates)

The drift of HHD-related ASPR, ASDR, and age-standardized DALYs rate among five SDI quintiles were presented in Fig.4. The ASPR of HHD was highest in the middle SDI region, and the lowest in the high SDI region between 1990 and 2019 (Fig. 4A). It was interesting to note that, as opposed to the regions with other SDI, the middle SDI region presented a descending trend of ASPR (EAPC, 0.24, 95% UI=-0.2--0.20) (Table S3). ASDR and age-standardized DALY rate decreased the fastest in the middle SDI region (EAPC, 1.58, 95% UI=-1.98--1.20 for ASDR; EAPC, 1.74, 95% UI=-2.11--1.41 for age-standardized DALY rate) (Table S3, Fig. 4B and C). In the middle SDI region, the trend of ASDR and age-standardized DALY rate presented undulating curves (Fig. 4B and C). Compared with a downward trend for females (EAPC, 0.28, 95% UI=-0.4--0.11), male age-standardized DALY rate showed an upward tendency in the high SDI region (EAPC, 0.34, 95% UI=0.110.57).

The age-standardized prevalence, death, and DALY rate for hypertensive heart disease by different SDI regions, 19902019. ASPR, age-standardized prevalence rate; ASDR, age-standardized death rate; DALY, disability adjusted life-year; SDI, socio-demographic index

ASPR, ASDR, and age-standardized DALY rate of HHD stratified by SDI were shown in Fig.5. ASPR of HHD rose before SDI value of 0.4 and then start to decrease (Fig. 5A). There was a negative and significant Pearsons correlation between HHD disease burden and SDI (r=0.74, 95% CI=-0.77--0.70, p<0.001, for age-standardized DALY rate; r=0.70, 95% CI=-0.74--0.66, p<0.001, for ASDR) (Fig. 5C). The univariate linear regression indicated that many socioeconomic variables (HDI, IHDI, SDI, HAQ, population with at least some secondary education, life expectancy, and physicians per 10,000 people) had a significantly negative correlation with age-standardized DALY rate (all p<0.001, Table1).

The trend in ASPR (A), ASDR (B), age-standardized DALY rate (C) of hypertensive heart disease in 21 regions based on SDI. Expected values are shown as the dark blue line. ASPR, age-standardized prevalence rate; ASDR, age-standardized death rate; DALY, disability adjusted life-year; SDI, socio-demographic index

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Global, regional, and national burden of hypertensive heart disease during 19902019: an analysis of the global burden of disease study 2019 - BMC...

Recommendation and review posted by Bethany Smith

- Collaboration combines Quell's pioneering autologous multi-modular Treg cell therapy platform and Cellistic's expertise in iPSC cell therapy platform development and scale-up

- Aims to accelerate the development of a next-generation allogeneic Treg platform that could open significant opportunities for Quell's creation of off-the-shelf Treg cell therapies targeting a wide range of diseases driven by immune dysregulation

- First announced collaboration for Cellistic, Ncardia's recently formed cell therapy process development and manufacturing services business

LONDON and GOSSELIES, Belgium, April 27, 2022 /PRNewswire/ --Quell Therapeutics Ltd ("Quell"), a leader in developing engineered T-regulatory (Treg) cell therapies for serious medical conditions driven by the immune system, and Cellistic,the iPSC-focused cell therapy process development & manufacturing partner recently launched by Ncardia to make large-scale allogeneic cell therapy production a reality,announce they have entered into a strategic collaboration for the co-development of an iPSC-derived Treg cell therapy platform. The goal of the partnership is to facilitate the future expansion of Quell's autologous Treg cell therapy pipeline by adding off-the-shelf, allogeneic Treg cell therapy products, leveraging Cellistic's expertise in differentiation and scale-up of iPSC processes for allogeneic cell therapy applications.

Iain McGill, Chief Executive Officer, Quell Therapeutics,said: "Quell has made significant progress advancing the first candidate from our autologous multi-modular Treg cell therapy platform into the clinic, with the initiation of our LIBERATE study of QEL-001 to prevent liver transplant rejection. We believe there is significant opportunity to transform outcomes for patients with QEL-001 and other autologous Treg cell therapy products in our pipeline. Our collaboration with Cellistic is a key building block in our investment towards a future, next-generation allogeneic Treg cell platform, which could significantly expand our opportunities to develop novel off-the-shelf treatments across a wide range of diseases driven by immune dysregulation. We highly respect the expertise and experience of Ncardia and the Cellistic team, and its track record in developing rapidly scalable iPSC cell therapy processes."

Stefan Braam, Chief Executive Officer, Cellistic,said: "Our partnership with Quell is emblematic of why we started Cellistic to bring together our focus and expertise in the development and implementation of iPSC cell therapy platforms with companies like Quell that have an equal depth of expertise in therapeutic development and share our vision for the future of cell therapy. We are excited to collaborate with the Quell team, both to develop the platforms, and to support Quell's long-term supply needs as they deliver impactful therapeutics to patients."

Under the terms of the agreement, Quell and Cellistic will collaborate in joint research to develop a process for differentiating iPSCs into highly functional Treg cell therapy products. Quell will contribute its Treg expertise and engineering technologies, as well as characterizing resulting Treg cells, while Cellistic will be responsible for the iPSC process science and development activities.

Based on a successful research phase, the collaboration will enter a product development phase with Quell having exclusive rights under the co-developed iPSC-Treg process for the development of multiple allogeneic iPSC-Treg cell therapeutics, and Cellistic as the exclusive CDMO partner for Quell's iPSC-Treg product pipeline, leveraging Cellistic's ongoing investment in downstream GMP capabilities.

Tracey Lodie, Chief Scientific Officer, Quell Therapeutics,added: "We have learnt in cell therapy development that the continuity from the R&D phase into the manufacturing phase is a critical success factor in achieving robust, scalable cell product processes. Cellistic emerged as a best-in-class and complementary partner to enable our path to an iPSC Treg cell therapy platform, and its ongoing investment in GMP capabilities provides the potential for a long-term partnership to accelerate the future development of allogeneic Treg cell therapies for patients."

About Quell Therapeutics

Quell Therapeutics is the world leader in developing engineered T-regulatory (Treg) cell therapies that aim to harness, direct and optimize their immune suppressive properties to address serious medical conditions driven by the immune system.

The Company is leveraging its pioneering phenotype lock technology, unique multi-modular platform and integrated manufacturing capabilities to design and develop a pipeline of highly engineered Treg cell therapies with greater potential for persistence, potency and stability than earlier generations of Treg cell therapy approaches.

Quell's lead candidate QEL-001 is being developed to induce operational tolerance following liver transplantation, with the potential to protect the post-transplant liver without the need for chronic immunosuppressive medications. Quell is also advancing additional programs in neuroinflammatory and autoimmune diseases. http://www.quell-tx.com.

About Cellistic

Launched in April 2022, Cellistic specializes in process development and manufacture of cell therapies based on human induced pluripotent stem cell (iPSC) technology. Its focus and expertise in iPSC reprogramming, differentiation, and expansion protocol development positions the business to be the partner of choice for innovative cell therapy developers to commercialize novel advanced therapies. Leveraging more than a decade of Ncardia's scientific and technical knowledge and experience, Cellistic possesses unique capabilities for the design and optimization of proprietary manufacturing platforms for iPSC-based cells that deliver quality products at scale. For more information, visit http://www.cellistic.com.

About Ncardia

Ncardia is a leader in contract research, development and manufacture of iPSC-based solutions for early and preclinical drug discovery. Its goal is to enable pharmaceutical and therapeutics companies to make more confident decisions in discovery and development by integrating iPSC technologies into their screening processes. Ncardia's capabilities include disease modeling, manufacturing, assay development and high-throughput screening especially for cardiac and neurodegenerative diseases. Ncardia was founded in 2011 and is majority-owned by KINICITI a private equity-backed advanced therapies platform. For more information, visit http://www.ncardia.com

Contacts for Quell TherapeuticsLuke Henry, Chief Business OfficerQuell Therapeutics[emailprotected]

Media: Mark Swallow, Sandi Greenwood, Eleanor PerkinMEDiSTRAVA Consulting+44 203 928 6900[emailprotected]

Investors: Christina TartagliaStern Investor Relations, Inc.+1 212 362 1200[emailprotected]

Contacts for Ncardia/CellisticAndy Holt, Chief Commercial OfficerCellistic[emailprotected]

SOURCE Quell Therapeutics and Cellistic

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Quell Therapeutics and Cellistic enter a strategic collaboration to develop an iPSC-derived allogeneic T-regulatory (Treg) cell therapy platform - PR...

Recommendation and review posted by Bethany Smith

TORONTO--(BUSINESS WIRE)-- Highland Therapeutics Inc., a privately held pharmaceutical company that through its wholly owned subsidiary, Ironshore Pharmaceuticals Inc., is focused on the commercialization of JORNAY PM (methylphenidate HCl) extended-release capsules (CII) for patients with ADHD, today announced the appointment of Stephanie C. Read as President/Chief Executive Officer, the appointment of Scott Myers as Chair of the Board and the additions of Kevin Bain and Ildiko Mehes as independent members of the Board of Directors. Stefan Antonsson, who has been serving as interim CEO will return to his role as an independent director.

It is my pleasure to congratulate Ms. Read in her transition from the Board of Directors to President/CEO, said Scott Myers, recently appointed Chair of the Board. Ms. Reads leadership in product development, corporate strategy, business development and specialty care commercialization will be key to driving sustainable growth with JORNAY PM, while enabling diversification into new therapeutic areas. I look forward to working closely with her to create value for patients, our employees and stakeholders."

The Board is grateful to interim CEO Stefan Antonsson for providing strategic direction and leadership continuity as we completed the financial restructuring of the company. After a brief transition, Stefan will return to his role as an independent member of the Board of Directors.

Commenting on her appointment, Ms. Read said, Highland and its subsidiaries are a rare instance of a privately held company with an exciting commercial product and experiencing rapid growth. I am pleased to join this seasoned executive team who have been successful in developing and launching JORNAY PM. With new capital from our shareholders and fresh perspectives from the new Board, we have the opportunity to continue to develop our products, people, processes and culture as we explore additional populations who may benefit from JORNAY PM."

Board of Directors:

Scott Myers, Chair of Board

Mr. Myers is a proven executive who brings nearly three decades of global pharmaceutical and medical technology most recently as CEO of AMAG, sold to Covis Pharmaceuticals, SA in November of 2020. Mr. Myers is a serial CEO, serving as Chairman and Chief Executive Officer of Rainier Therapeutics, a clinical-stage biotechnology company focused on metastatic bladder cancer that was purchased by Fusion Pharmaceuticals in March of 2020. Prior to joining Rainier, Mr. Myers served as Chief Executive Officer, President and as a director of Cascadian Therapeutics Inc. prior to its acquisition by SeaGen in March of 2018. Mr. Myers also served as Chief Executive Officer of Aerocrine AB, a medical device company from 2011 to 2015 prior to its acquisition by Circassia. Mr. Myers is currently an independent director of Selecta Biosciences where he serves as the Chair of the Compensation and Benefits Committee, as well as a member of the Nominating and Governance Committee. Mr. Myers also serves as the Chairman of the Board and Chairman of the Nomination and Governance committees and is a member of the Audit Committee for Harpoon Therapeutics, a clinical stage oncology company. Mr. Myers is also Chairman of the Board for Sensorion, SA, a gene therapy company focused on inner ear diseases. Mr. Myers is also Chairman of the Board of Dynavax Technologies, a Hepatitis B vaccine and COVID Adjuvant commercial stage company.

Stefan Antonsson, Independent Director

Mr. Antonsson has over 30 years of commercial experience in the pharmaceutical industry, primarily as a senior marketing executive, and he has established a proven track record of contributing to the success of rapidly growing pharmaceutical companies. Stefan was a key member of the Richwood/Shire senior management team and played a leadership role in launching Adderall and developing Adderall XR, acquiring and launching Carbatrol, and initiating the development of Intuniv. Stefan has also held senior marketing positions with Pharmacia and Forest Laboratories and executive positions with Vela Pharmaceuticals and Xanodyne Pharmaceuticals. Stefan has also been involved in several entrepreneurial ventures which successfully developed, licensed, and commercialized CNS products. Stefan also completed a long-term consulting assignment as Senior Vice-President of Marketing for Supernus Pharmaceuticals where he was part of the senior management team that established the commercial function for the company and successfully launched two anti-epilepsy drugs. Stefan earned his BA from Columbia College and MBA from The Stern School of Business, NYU.

Kevin Bain, Independent Director and Chair of Audit Committee

Mr. Bain is currently Chief Corporate Development Officer of Cell Research Corporation, a Singapore-based biologics company. This is a clinical-stage company developing a platform of products using stem cells from the umbilical cord lining membrane. From early 2006 through mid-2020, Kevin worked in the generic pharmaceutical and biosimilar business in companies founded and led by Robert Wessman. Kevin joined Alvogen in August 2009 as Chief Financial Officer, with responsibility for all Finance and Information Technology functions for the global Alvogen business. In November 2015, Kevin moved to a sister company named Alvotech as Chief Financial Officer. He has led several financing rounds, raising more than $1.5 billion in total value. Prior to joining Alvogen and Alvotech he spent almost four years with Actavis as Vice President of Finance for the US business of Actavis. From mid-2001 to early 2006, Mr. Bain was VP of Finance with a division of Danaher Corporation. From 1979 to 2001, Mr. Bain held positions of increasing responsibility within the finance organization of the Johnson & Johnson Family of Companies in both Canada and the US, including Vice President of Finance for J&J Medical Products. Mr. Bain graduated from the Accounting program at Fanshawe College in London, Ontario, Canada, and later earned his Certified Management Accountant (CMA) designation. Kevin is currently a Board member and Chair of the Audit Committee of Akorn Pharmaceuticals, a leading US-based specialty pharmaceuticals company.

Ildiko Mehes, Independent Director

Ms. Mehes is an advisor to investment management firms, consulting firms and pharmaceutical companies about a wide range of risks and opportunities in the pharmaceutical industry. She previously spent 12 years at Teva Pharmaceuticals in a variety of business and legal roles including, most recently, Senior Vice President & General Counsel. Her areas of responsibility in the U.S. and Canada spanned New Product & Portfolio, R&D, Regulatory Affairs, and Legal Affairs. She has extensive expertise in intellectual property, including related to ADHD drugs, and also has significant pharmaceutical M&A experience. Prior to Teva, Ildiko was a pharmaceutical patent and commercial litigator. Ildiko is admitted to the Bars of Massachusetts and Ontario, Canada. She is also the recipient of several awards, including the National Post/ ZSA Canadian General Counsel Award for Litigation Management and the Association of Corporate Counsels Global Award for Litigation Management. Ildiko holds a B.A. (Honors) in Economics from Queens University, a J.D. from Osgoode Hall Law School, both in Canada, and completed the Advanced Management Program at the Wharton Business School.

Stephanie C. Read, Chief Executive Officer

In addition to serving as the newly appointed President/CEO, Stephanie will continue to have a seat on the Board of Directors. Ms. Read also serves as a Non-Executive Director on the Board of ALSP Orchid Acquisition Corporation I. Ms. Read's 24-year biopharmaceutical career spans Global Research and Development, Medical Affairs, Alliance Management, Commercial and Business Development and Equity Investing. All leadership roles have included driving transformational change within organizations to accelerate top- and bottom-line growth, and diversification of company portfolios. Ms. Read's therapy area expertise includes Psychiatry (inventorship of MYDAYIS), Gastroenterology, Oncology & Pain, Infectious Disease, Immunology and Rare Diseases. Ms. Read's industry appointments include the last 6.5 years with CSL as global VP, Corporate Strategy and Business Development, 7.5 years with AstraZeneca/MedImmune in a variety of Medical Affairs, Commercial and Business Development roles, and over six years with Shire PLC in R&D and Global Medical Affairs (including inventing, developing and launching new treatments for ADHD). Stephanie holds a M.Sc. in Biotechnology from The Johns Hopkins University and a B.Sc. in Biology from Virginia Tech.

WARNING: ABUSE AND DEPENDENCE

See full prescribing information for complete boxed warning.

See additional important safety information below.

IMPORTANT SAFETY INFORMATION

WARNING: ABUSE AND DEPENDENCE

CNS stimulants, including JORNAY PM, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy.

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

PREGNANCY AND LACTATION

Please visit http://ironshorepharma.com/labeling.pdf for additional important safety information and the Full Prescribing Information, including Boxed Warning, for JORNAY PM.

About Highland Therapeutics Inc.

Highland Therapeutics Inc. is a pharmaceutical company whose mission is to develop and commercialize innovative, patient-centric treatment options. Based in North Carolina, subsidiary Ironshore Pharmaceuticals Inc. is responsible for the sales, marketing and distribution of pharmaceutical products within the US. Based in Grand Cayman, subsidiary Ironshore Pharmaceuticals & Development, Inc. develops novel therapeutics by leveraging its proprietary drug-delivery technology.

Forward-Looking Statements

This press release contains forward-looking information, which reflects the companys current expectations regarding future events. Forward-looking information is based on a number of assumptions and is subject to a number of risks and uncertainties, many of which are beyond the companys control that could cause actual results and events to differ materially from those that are disclosed in or implied by such forward-looking information. These forward-looking statements are made as of the date of this press release and, except as expressly required by applicable law, the company assumes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220426006027/en/

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Highland Therapeutics Announces Appointment of Stephanie C. Read as President/CEO, Changes to Board of Directors - BioSpace

Recommendation and review posted by Bethany Smith