Abbott Nutrition has resumed formula production in its Michigan plant to address the nationwide formula shortage; 2 distinct strains of monkeypox may indicate rapid, undetected spread nationwide; the overturn of Roe v Wade could have an effect on in vitro fertilization and genetic testing.

Abbott Nutrition resumed production of baby formula on Saturday in order to address the nationwide shortage after getting the green light from the FDA. Production of EleCare and other specialty and metabolic formulas will be the first to restart production, with a product release of June 20 as the target date, according to CNBC. Abbott Nutrition was initially closed in February due to contamination. The FDA has said in a statement that it is working diligently to ensure safe resumption of infant formula production. The FDA also said that it hopes that this measure will put more baby formula on the shelves nationwide.

A recent genetic analysis of monkeypox cases indicated that there are 2 distinct strains in the United States, which could mean that the virus has been circulating in the country for some time, according to AP News. There are many monkeypox cases with the same strain as the recent cases in Europe; however, the recent analysis showed a different strain as well and both strains were in the United States last year. More analysis will need to be done to determine how long monkeypox has been in the United States. These findings could mean that the virus will be difficult to contain in the future.

The overturning of Roe v Wade could have effects on reproductive medicine at large as state policies could determine how birth control is provided or in vitro fertilization (IVF), according to STAT News. In the states that are expected to ban or limit abortion, lab-made embryos would also have legal protections, which could make IVF more complicated. Preimplantation genetic testing could also come under scrutiny as embryos that arent implanted may not be able to be frozen if they are considered people with legal rights. Alabamas anti-abortion law only applies to embryos in the womb, which would allow IVF; however, experts are still figuring out whether Oklahomas anti-abortion law will also extend to IVF.

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What We're Reading: Abbott to Resume Formula Production; 2 Strains of Monkeypox; Impact of SCOTUS Decision on IVF, Embryo Genetic Testing - AJMC.com...

Recommendation and review posted by Bethany Smith

From left, Farah Khan, Tracy Ismail, Sophia Ahmed, Amara Ismail and Durrah Khan

Three siblings have already had their stomachs removed after testing positive for a faulty cancer gene following the deaths of their mother and sister from the disease.

Now further members of the family have been found to carry the faulty gene, with several children, who are too young to be tested, under threat of inheriting it.

Walsall siblings Sophia Ahmed, 42, Tahir Khan, 48, and Omar Khan,31 underwent the surgery after a series of tests at Addenbrooke's Hospital in Cambridge.

The family joined Cancer Research UKs Familial Gastric Cancer study after losing their mum and sister to hereditary stomach cancer.

Determined to give back to the charity that has given them hope, Sophia, who has recently had her breasts removed as well as her stomach, is joining with four other female relatives to help launch Cancer Research UKs Race for Life Pretty Muddy events across the region.

Sophia and her two brothers took their radical decision to have their stomachs removed after genetic testing showed they had the CDH1 gene and were at high risk of the same cancer that killed their mother, Pearl Khan, in 2002 at the age of 49, and their sister, Yasmin Khan, in 2012 at the age of 32.

The family team named Little Hooligans Get Dirty for Cancer - is being led by Amara Ismail, 32, manager of the Little Hooligans soft play centre in Walsall, and her mum Tracy Ismail, 51, the only one of the five siblings unaffected by the gene. Joining Amara is her cousin, Farah Khan, 23, whose father Tahir had preventive surgery to remove his stomach.

Youngest of the team is 14-year-old Durrah Khan, whose mum, Yasmin Khan, passed away from stomach cancer in 2012. It was Yasmins death that spurred the rest of the family to find out about research being done in the area, and led to them joining the Familial Gastric Cancer study.

Farah has also tested positive for the faulty gene and is taking part in the same Cancer Research UK research study as her father. She is regularly monitored at Addenbrookes hospital in Cambridge and may also be offered the opportunity to have preventative surgery.

Sophia said: Having your stomach removed is a fairly drastic thing to do, but after I had the surgery they told me that the cancer had already started in my stomach and I would have been dead within a year if it hadnt been removed. I was at very high risk of breast cancer too, so a double mastectomy was the best way to prevent it.

Research is so important. Its thanks to research that Im alive, and that other members of my family are still here too. I truly believe that more research could lead to the complete eradication of this genetic form of cancer.

The team has signed up for Pretty Muddy Sandwell - a mud-splattered obstacle course that raises money for life-saving research - which takes place at Sandwell Valley Country Park on Saturday, June 25. There is also the chance for boys and girls aged five to 12 to take part in Pretty Muddy Kids - their own version of the fun event.

Amara said: Cancer research UK is a very close charity to me and my family. My aunt Yasmin was the same age as I am now when she passed away. My surviving auntie and two uncles have all had preventative surgery at Addenbrookes hospital with the help of Cancer Research UK. Their very high risk of cancer was discovered after they had genetic testing which showed they had the CDH1 gene.

I am very fortunate in that my mum was the only one of five siblings not to have the faulty gene, so it hasnt been passed onto me either. But the impact on my wider family has been huge and has affected every generation.

My cousin's genetic tested showed she also had the faulty gene and she is now waiting to find out how it is going to affect her life. We have a further six children, including Durrah who is part of the Pretty Muddy team, who are yet to reach the age where they can be tested.

Were so grateful for this research study that is helping all of us stay healthy and avoid cancer. But also, as a family we're invested in helping our future generations.

Farah, who inherited the genetic fault from her father, Tahir, is regularly screened for the disease. She said: Its good to know that screening will pick up early signs of any problems and that, like my dad, I can take steps to prevent cancer in the future.

Jane Redman,Cancer Research UKs spokesperson in the West Midlands, said: We are incredibly grateful to all the wonderful ladies from this special family their support. Their story speaks volumes about how important research is and why we need to keep funding it.

Our Race for Life eventsareopen to all. For some people, the Race for Life is literally a walk in the park. For others, its a jog. Some may opt to push themselves harder, taking up the challenge of Pretty Muddy or even pushing for a new personal best time.

Were looking forward to welcoming people of all ages and abilities. Race for LifePretty Muddy in Sandwellwill be a fun, emotional, colourful, uplifting and unforgettable event this year.

To enter, visitraceforlife.org. To sponsor the team, go to fundraise.cancerresearchuk.org/team/little-hooligans-gets-dirty

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Black County family affected by genetic cancer in action plea - Express & Star

Recommendation and review posted by Bethany Smith

Includes oral presentation onProspera test's two-threshold algorithm, showing the combination of donor quantity and donor fraction outperformsdonor fraction alone

AUSTIN, Texas, June 8, 2022 /PRNewswire/ -- Natera, Inc.(NASDAQ: NTRA), a global leader in cell-free DNA (cfDNA) testing, today announced that ithas presented data on the clinical utility of the company's Prospera and Renasight tests in 14 sessions at the American Transplant Congress (ATC) 2022 meeting. This expands on the thirteen peer-reviewed papers that have been published over the last twelve months, demonstrating the strong performance of both assays.

Phil Halloran, M.D., Ph.D., director of the Alberta Transplant Applied Genomics Centre, presented new data on the latest findings of the global, multisite, prospectiveTrifecta study, "Combining fraction and estimated amount of dd-cfDNA to assess kidney transplant rejection using molecular diagnoses and histology." The study demonstrates that the new two-threshold algorithm for the Prospera test - includingboth dd-cfDNA fraction and quantity -performed better than dd-cfDNA percentage alone in detecting active rejection, with an AUC of 0.88 when compared against molecular biopsy assessment and 0.82 when compared against histological biopsy assessment. This analysis in the Trifecta study features 367 fully-biopsy-matched samples from the 22 participating clinics in the U.S. and Europe.

"The data presented at ATC, combined with other important studies, highlight Natera's dedication to innovation and continued leadership in testing for transplant rejection and genetic risks for kidney disease," said Sangeeta Bhorade, M.D., chief medical officer for organ health at Natera. "The evidence continues to support the use of Natera technology for aiding clinicians in making major care decisions for transplant patients."

Data from theTrifecta study was also presented inthree other ATCsessions, and a full listing of Natera's scientific sessions and presence can be found at https://www.natera.com/events/prospera-conference/

About the Prospera test

The ProsperaTM test leverages Natera's core single-nucleotide (SNP)-based massively multiplexed PCR (mmPCR) technology to identify allograft rejection non-invasively and with high precision and accuracy, without the need for prior donor or recipient genotyping. The test works by measuring the fraction of donor-derived cell-free DNA (dd-cfDNA) in the recipient's blood. It may be used by physicians considering the diagnosis of active rejection, helping to rule in or out this condition when evaluating the need for diagnostic testing or the results of an invasive biopsy. The Prospera test has been clinically and analytically validated for performance regardless of donor relatedness, rejection type, and clinical presentation. It has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.

About the Renasight test

The RenasightTM test is a germline genetic test that screens for hereditary causes of kidney disease. It is indicated for patients with diagnosed kidney disease and is run from a patient's blood or saliva sample. Providers can use the Renasight test to identify a genetic predisposition, clarify a clinical diagnosis, or identify the etiology of an unknown kidney disease to help inform medical management. Additionally, genetic counseling and familial testing can be offered based on the test result. The test has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.

About Natera

NateraTM is a global leader in cell-free DNA testing, dedicated to oncology, women's health, and organ health. Our aim is to make personalized genetic testing and diagnostics part of the standard of care to protect health and enable earlier and more targeted interventions that help lead to longer, healthier lives. Natera's tests are validated by more than 100 peer-reviewed publications that demonstrate high accuracy. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas and San Carlos, California. For more information, visit http://www.natera.com.

Forward-Looking Statements

All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera's plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera's expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, our expectations of the reliability, accuracy and performance of our screening tests, or of the benefits of our screening tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera's recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at http://www.natera.com/investors and http://www.sec.gov.

Contacts

Investor Relations: Mike Brophy, CFO, Natera, Inc., 510-826-2350

Media: Kate Stabrawa, Communications, Natera, Inc., 720-318-4080 pr@natera.com

View original content to download multimedia:https://www.prnewswire.com/news-releases/natera-showcases-leadership-in-transplantation-at-atc-2022-with-new-data-on-its-prospera-and-renasight-tests-301563616.html

SOURCE Natera, Inc.

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Natera Showcases Leadership in Transplantation at ATC 2022 with New Data on its Prospera and Renasight Tests - BioSpace

Recommendation and review posted by Bethany Smith

Quenton Tompkins family tree is deeply rooted in rural McCormick County, South Carolina.

His grandfather was a sharecropper in McCormick. His mother, who turns 88 this month, grew up as the youngest of 24 children. Branches of aunts, uncles, and cousins now stretch from Florida to Chicago.

And although 48-year-old Tompkins has heard plenty of stories, his family holds its secrets, too.

He didnt know until he was an adult that his grandfather died of leukemia. And hes still unsure if his fathers bout with prostate cancer runs in the family. Tompkins mother and her siblings have dealt with a range of health issues, including diabetes, heart attacks, and strokes, but he still doesnt know what killed his grandmother more than 70 years ago.

Those are questions I go through personally, said Tompkins, a lobbyist for the Medical University of South Carolina. Theres another side to knowing where you come from.

Twenty-two years ago, President Bill Clinton announced the completion of a draft version of the Human Genome Project, a breakthrough he described as the language in which God created life. He predicted that scientists, armed with genetic discoveries, would find cures for Alzheimers disease, cancer, Parkinsons disease, and diabetes in the coming years.

Clintons prediction, of course, hasnt yet come to pass. But researchers in Charleston are hopeful that a large genetics research project underway across South Carolina may help scientists address some of the states persistent health disparities, which disproportionately impact its Black residents and regularly rank among the nations worst.

The university health system intends to enroll 100,000 of South Carolinas 5 million residents in genetic testing over the next four years in hopes of better understanding how DNA influences health. Researchers also want to recruit participants who reflect the diversity of the states population.

Its an ambitious goal. With nearly 27% of South Carolina residents identifying as Black or African American, the MUSC genetics research project, called In Our DNA SC, would if successful accomplish something most other genetics research projects have failed to do. Historically, diverse participation in this type of research has been very low.

Theres a trust factor. Its plain and simple, said Tompkins, who is developing an outreach program for the project.

He referenced Henrietta Lacks, a Black woman in Baltimore whose cells were used without her or her familys knowledge for research purposes by doctors at Johns Hopkins University in the 1950s, and the Tuskegee syphilis study, conducted over nearly 40 years starting in the 1930s. Researchers deceived hundreds of Black men enrolled in the study, telling them they were being treated for syphilis when, in fact, they were left untreated, even after penicillin became widely available.

Those are still fresh in many peoples minds, Tompkins said. Weve come a long way from those stories it doesnt dismiss what happened but there are a lot more controls and oversight in place to ward those things off from happening again.

But its not only history feeding this distrust. Bias and racism evident in medicine today contribute to the problem.

Diversity in genetics research is so low that approximately 90% of participants in projects launched since the first sequencing of the human genome have been individuals of European descent or those who identify as white, said Dr. Shoa Clarke, a pediatric cardiologist and geneticist at Stanford University.

These numbers affect real-life health care. Clarke and others published research last year showing that a DNA-based tool used to assess a patients risk of developing high cholesterol works reliably well only when administered to those of Northern European descent. Thats because the tool was developed using information from genetic bio-banks largely made up of DNA from white people. And aside from a large DNA bank compiled by the Department of Veterans Affairs, this is generally the norm.

Human beings, regardless of race, are more than 99% genetically identical, but small variations and mutations passed down through generations can influence health outcomes in huge ways, Clarke explained.

Genetics is not the cause of health disparities, he said. But as we move toward using genetics in clinical settings, its very possible they could create new disparities.

In South Carolina, health disparities between Black and white patients are already acute, said Marvella Ford, a researcher at MUSCs Hollings Cancer Center in Charleston.

South Carolina compared to the rest of the country were usually in the bottom tier, Ford said. The prostate cancer mortality rate in South Carolina, for example, is 2 times higher for Black men than white men, she said.

When you look at most other chronic conditions, she said, you see the same thing.

She called the genetics project at MUSC a great opportunity to open the doors. Even so, the topic of recruiting Black research participants for genetics studies is complex.

Theres debate on how we should be doing this work, said Shawneequa Callier, an attorney and an associate professor of bioethics at George Washington University. Theres just so much diversity in Africa. Its the cradle of humanity.

Men and women transported to Charleston and other American port cities during the transatlantic slave trade came from a wide region of Africa mostly from West Central Africa, but in large numbers from regions farther north, too. Once in America, they were often separated and forced hundreds of miles apart. This explains why someone whose ancestors lived on one of South Carolinas barrier islands may have inherited different genetic variants than someone from a multigenerational Black family inland in McCormick County, just north of Augusta, Georgia.

Thats also why categorizing genetics research participants simply as Black or African American, without more context, may not yield particularly useful research insights, Callier said.

If you dont study the data and study it well, thats a real dereliction of ethical duty, Callier said.

Those who choose to participate in the MUSC project stand to benefit from it directly, its organizers said. After submitting a saliva sample, each participant will receive a report indicating if they have one or more of three genetic conditions that may put them at a higher risk for heart disease and certain cancers such as one of the BRCA mutations linked to breast cancer. If they test positive for one of these conditions, they will be connected at no cost to a genetics counselor, who can assist with information and treatment options related to a patients inherited risks. Participants will also learn where their ancestors likely lived.

The de-identified DNA data will then be used by researchers at MUSC, as well as those at Helix, a private California-based genomics company, which will process the saliva samples and extract the genetic information from each participants sample. Researchers at MUSC and Helix have indicated they hope to use the results to better figure out how DNA affects population health. Heather Woolwine, an MUSC spokesperson, said the project will cost $15 million, some of which will be paid to Helix. Hospital revenue will fund the research, she said.

Tompkins expects to receive a lot of questions about how it all will work. But hes used to questions. He said he encountered much of the same hesitancy when he helped set up MUSC covid testing and vaccine sites across the state. Many people regardless of race worried microchips or tracking technology had been embedded into the covid vaccines, he said.

Tompkins found that the key to persuading residents in rural parts of the state to consider the covid vaccine was to seek out invitations from trusted, local leaders, then set up events with them. South Carolinas covid vaccination rate remains lower than the national average, but Tompkins said some skeptics have been more receptive to MUSCs message because the hospital system has focused on building relationships with organizers outside Charleston. He hopes to use those relationships to spread word about the new genetics research project.

You have to build those relationships and find community champions that can help you open doors and gather people, he said. Then, its about letting them choose.

Lauren Sausser: lsausser@kff.org,@laurenmsausser

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Addressing the Trust Factor: South Carolina Researchers Tackle Health Disparities Using Genetics - Kaiser Health News

Recommendation and review posted by Bethany Smith

CARMEL, Ind. The founder of the Safe Haven Baby Boxes claims the Department of Child Services is giving a surrendered infant back to his parent without doing a DNA test first.

We cannot be just pretty sure that this is the bio parent, their words, not mine, Monica Kelsey, founder of the Safe Haven Baby Boxes, said in a popular video posted to social media.

Kelsey said she has spoken with a relative of the woman claiming to be the mother of an infant surrendered in a Carmel Safe Haven Baby Box in mid-May. She said the family member says a DNA test has not been done yet the reunification process has started.

Kelsey said the anonymity of these boxes is crucial to this service, and in all cases makes it impossible to figure out who the biological mother is without DNA testing.

No cameras are around these boxes and so, mother or a father places this child inside this box, there is no way for us to know who that parent is, Kelsey said.

The baby boxes are located at fire stations and hospitals around the state. Kelsey said once a baby is placed in the box, they are given medical care and then taken to the states Department of Child Services.

If theyre not going to do a DNA test or a drug test, or vet this family, we know has not happened, Kelsey explained. We have contact with the family. We know this has not happened yet. I have a problem with that. I have to be this little guys voice.

We investigated these claims, and reached out to DCS. The agency said the safe haven law prevents them from discussing a particular case, but they gave us this statement:

A social media post has raised questions regarding the steps the Indiana Department of Child Services takes after a baby is surrendered under theIndiana Safe Havenlaw.

It is common for children to come into DCS care without the identity of one or both parents being immediately known. DCS would never, under any circumstance, send a child home with someone claiming to be their parent without first confirming with certainty that persons relationship to the child. This may include genetic testing, along with many other steps to ensure safe reunification if it is in the best interest of the child. If an individual comes forward claiming parentage, DCS works hand in hand with the juvenile court to determine whether the child was surrendered with the knowing consent of both parents.

Information regarding Safe Haven surrenders is sealed under Indiana law as part of confidential juvenile records, and, with few statutory exceptions, only parties to the case are privy to those details.

Indiana law does not address this specific situation. We know it has captured the attention of State Senator Travis Holdman is aware of this situation and is in communication with DCS.

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Baby Box founder claims infant will be given back to parent without DNA test - FOX 59 Indianapolis

Recommendation and review posted by Bethany Smith

NEW YORK Based on findings from a small pilot study in a relatively well-off patient population in London, a UK team has suggested that a combination of whole-genome sequencing, panel sequencing, and comprehensive medical testing and imaging is feasible in a family practice setting and may benefit patients and their families.

Ros Eeles, a researcher with the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust shared early findings from the study at the American Society of Clinical Oncology's annual meeting in Chicago on Friday. Together with Michael Sandberg, a general practitioner and medical director at the private healthcare center 90 Sloane Street, she co-led the 90S Study, named in a nod to that central London center.

"We had a group of specialists who wanted to look at what would happen if you brought whole-genome sequencing into primary care," Eeles said, noting that the 90 Sloane Street center has built in electrocardiogram, echocardiogram, abdominal and pelvic ultrasound, and routine blood test capabilities.

In the context of cancer, for example, germline and somatic mutations can impact everything from disease screening to treatment strategies, for example. Indeed, large-scale clinical and population sequencing studies looking at germline genetic variation and their ties to human traits or disease are increasingly common, as are efforts to characterize germline and somatic mutations in cancer patients.

But studies on the potential for sequencing individuals in a family medicine setting are much rarer, and it remains to be seen whether the approach is feasible, scalable, cost-effective, and/or beneficial for patients with or without an existing diagnosis.

"What we wanted to ask was, 'Should you use whole-genome screening in next-generation health screening in primary care?'" Eeles said.

For the pilot stage of the study, the team had thirtyfold average whole-genome germline sequencing done commercially on 104 seemingly healthy individuals ranging in age from 29 to 82 years old, who were recruited between 2020 and 2022. The participants tended to have high socioeconomic status and more than 94 percent had a family history of cancer or cardiac disease in a first- or second-degree relative.

All but one of the participants was symptom-free, and 13 had a history of cancer. European ancestry was reported for more than 95 percent of those enrolled.

Since researchers had their sights set on finding as many informative variants as possible, they rounded out short-read genome sequence data with targeted panel sequence data to try to avoid missing deletions. They profiled pharmacogenomics-related variants, polygenic risk contributors, and other genetic features using whole-genome sequence data, which provided insights on up to 566 genes, and used targeted sequence data to search for actionable changes in dozens of cancer- or cardiac-related genes.

The team also considered participants' personal and family health histories, as well as results from a full medical with the same general practitioner. For that medical, participants were profiled with a variety of clinical screens ranging from blood tests to organ imaging.

The team opted to report only variants that could prompt actionable changes to a patient's care, she added, but they established a system for returning to suspicious variants in the genomes as the definition of actionable mutations continues to expand or evolve in the future and new drug targets turn up.

All told, the newly generated genome sequences led investigators to relatively rare, clinically actionable germline mutations in 27 study participants. They flagged cancer-related genetic risk variants in genes in 10 of the participants, for example, while two more individuals carried actionable cardiac rhythm disorder-associated variants, and still other patients had variants in genes involved in clotting, lipid metabolism, or other processes.

Far more individuals around 80 percent of individuals in the study were identified as carriers of variants implicated in autosomal recessive conditions, the team reported, including conditions that are relevant to reproductive screening programs. A significant proportion of sequenced individuals had at least one variant linked to pharmacogenomic responses.

The kinds of risky germline variants detected sometimes tracked with the new diagnoses made or with an individual's personal or family health history, but not always.

The medicals alone led to new heart disease or prostate cancer diagnoses in several study participants. On the other hand, 70 percent of individuals who ended up having cancer susceptibility-linked variants in their germline would not have been found without the genetics program, Eeles said.

"Clearly we are picking up mutations in those without a family history, and that's where geneticists giving advice is going to be important," she explained.

"The majority of patients had a significant change in management for themselves or their families," Eeles and her co-authors wrote in an abstract accompanying the ASCO presentation. "Whole-genome sequencing as part of health screening in family practice is feasible and is likely to have significant beneficial health management implications."

The team tapped into the common variant data collected from participants for a research arm of the study, which looked at polygenic risk for conditions such as colorectal cancer or prostate cancer.

While the research was done within a private clinic setting, the investigators also looked at what aspects of the program might be retained, jettisoned, or tweaked if attempting to apply it through a public health system such as NHS.

Speaking remotely at the ASCO meeting, Fergus Couch, a laboratory medicine and pathology researcher at the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, noted that the 90S Study is "a really nice model for evaluating how exome sequencing, genome sequencing, or panel sequencing might actually be useful in the clinical setting."

For example, he noted that the program picked up risky variants that would have been missed by following current family- or personal medical history-based genetic testing guidelines in the UK.

Still, Couch questioned whether the patient population for the 90S Study was representative of the broader population, since family histories of disease and rates of clinically actionable changes in cancer-related genes such as BRCA1 were higher than that described in the past.

He also noted that care is needed in general when incorporating sequencing into clinical care for symptom-free individuals, not only when it comes to defining actionability or implementing information on specific variants or risk scores but also when selecting the sequencing strategy used and setting up appropriate referrals for patients with actionable variants or recessive disease carrier status.

"Could this type of sequencing and the data that comes from it actually be handled by general medicine, family medicine, or community practices around the country? Is this really just too much?" he wondered, noting that "in the absence of a very strong referral network, this could be really quite challenging for the vast majority of non-tertiary medical centers."

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UK Team Tests Whole-Genome, Targeted Sequencing in Family Practice Setting - GenomeWeb

Recommendation and review posted by Bethany Smith

Published

2022-06-08 14:56

2:56

June 8, 2022

pm

Almost 20 years ago, Italy tested what it would look like if embryos were given the same rights as a living person. The country put stringent limits on in vitro fertilization treatments (IVF), banning embryo preservation, limiting the number of embryos created a time to three and mandating that they all be transferred to the uterus.

In the years the law was in place, before it was ultimately repealed in full, more IVF treatments failed, more pregnancies resulted in no live births or more multiple births, and IVF became more difficult to access and more expensive. Italian patients who could afford it traveled to other countries across Europe to receive treatment. Success rates at IVF clinics dropped, high-risk pregnancies increased and doctors had to risk transferring embryos that could lead to medical complications for the pregnant person. Single parents and many LGBTQ+ parents couldnt access IVF at all because surrogacy and sperm donation were also banned.

To doctors in the United States, Italy was an extreme example of what could happen if embryos were treated as people, even though in most cases both in the lab and in nature a large portion of embryos never become babies. Now, theyre worried that the increased barriers and cost that doctors saw in Italy is a preview of what could happen in the United States.

Any day now, the Supreme Court is likely to overturn its 1973 Roe v. Wade decision, according to a draft of the decision leaked in May, leaving the choice of how to limit abortion access up to states. The impact is expected to trickle down to fertility treatments. States including Louisiana, Nebraska and Oklahoma have tried to pass abortion restrictions that revise the definition of life to begin at fertilization and that limit or ban discarding embryos, creating the standard that led Italy to impose its IVF restrictions in 2004. While those efforts have so far failed, states are expected to try again if Roe is overturned.

Not only could a decision like that impact patients health, but it could take a procedure that is already prohibitively expensive for many families and make it even less accessible, reproductive endocrinologists told The 19th.

Already, one cycle of IVF in the United States runs patients about $23,000 on average. Most patients will go through two or more cycles before they have a successful pregnancy, a cost of about $50,000, according to FertilityIQ, which collects IVF cost data.

In a typical cycle here, IVF involves extracting 10 to 15 eggs for fertilization and testing the embryos before choosing typically one for transfer to the uterus. The rest are often frozen, donated or discarded. That approach has led to high success rates for IVF, fewer transfers, and fewer high-risk pregnancies and losses.

Limiting the number of eggs that can be extracted in a cycle, limiting genetic testing or banning embryo preservation means the likelihood that IVF treatments are successful will decrease. That means patients will have to endure and pay for more IVF transfers, and doctors will have to assume potential risks if faced with decisions about eliminating embryos.

The issue is also one of racial justice.

The fertility industry is one where the typical patient is somebody who has money, typically White, a little bit older. [It] has already been catering to a narrow population, said Kimberly Mutcherson, the dean of Rutgers Law School and a reproductive justice scholar. The majority of low-income workers are women of color, and low-income women are also most likely to have Medicaid coverage, which is prohibited from covering abortion care and does not cover IVF. Mutcherson points out that while they wont pay for IVF, most state Medicaid programs do cover some form of sterilization.

According to a survey of nearly 1,500 fertility patients published in 2020, more than 75 percent of IVF patients are White and more than 80 percent have annual household incomes higher than $100,000. Black women are the most likely to report facing barriers to fertility treatment, and Black and Latina women traveled twice as far as White and Asian women for treatment.

Low-wage people of color, who already have the least access to fertility care, are the same people who have the least access to abortion care.

That limited access is now under siege on both ends, said reproductive endocrinologists and IVF experts, if treatments become more costly.

Patients with the means to do so may move to states with more expansive laws for IVF, and doctors in states that might restrict IVF will move to states where they can continue to practice, said Dr. Lora Shahine, a reproductive endocrinologist at Pacific NW Fertility in Seattle and host of the Baby or Bust Podcast. That will result in further limiting access to patients, particularly in states in the South where the majority of low-wage women of color are concentrated and where most of these personhood bills have been introduced.

Dr. Robert K. Hunter II, the practice director at Kentucky Fertility Institute in Louisville, said the fear of losing his job and having to potentially move to another state is very real for him. Kentucky has tried to pass a personhood bill in the past, and its one of 13 states with a trigger law that would ban abortion immediately if Roe is overturned.

If doctors are limited in the number of eggs they can fertilize, whether or not they can perform genetic testing or whether they can cryopreserve eggs the same limitations Italy imposed that could increase the number of IVF cycles patients have to undergo to have a successful pregnancy, and it can increase risk for doctors, he said.

The cost of continuing to do business will increase for providers, and that will absolutely get passed down to patients, Hunter said. And not to mention if we cant do genetic testing and cryopreservation thats a lot of added cost and disappointment and emotional cost with that, as well.

Hunter said that if that happened, he would become only one piece in a complex IVF process that could see patients seeking care in multiple states.

For me to become someone that is just making embryos to ship them to Illinois or wherever the closest women-friendly state is Is that a sustainable business for me? If I just become a monitoring center for a practice that can still perform IVF for another state? I dont know that thats a viable practice model for me, he said. I dont know what is coming down the pike. I will certainly do my best to fight for my patients, but at the same time, in all my years of medical school, residency training, fellowship training, I never thought Id be affected. That wasnt part of the gig.

IVF is still protected, doctors stressed, but they have also started to think about what could happen in a world where its not.

In Nebraska, Dr. Stephanie Gustin knows it could become a reality. In April, the state tried to pass an abortion bill that redefined life as beginning at fertilization. It lost by two votes. Republican Gov. Pete Ricketts has indicated that if Roe v. Wade is overturned, he will call a special session this summer to reintroduce the legislation. Gustin is part of a coalition of doctors working to inform legislators about the implications such a bill would have for fertility care.

Gustin, who is the medical director of the Heartland Center for Reproductive Medicine in Omaha, one of only two fertility clinics in the state, is conflicted about what to do if it passes.

I made this promise to do no harm. Why would I provide my patient with substandard care that, if they could drive to Colorado or Minnesota they could get the standard care of IVF, just to keep my business alive? I wouldnt be able to sleep at night, Gustin said. The problem is that by not having a fertility clinic here, there will be many people who cant seek IVF care, period. Those people may be like, We would rather have something than nothing. She hasnt yet figured out how she would navigate that.

Programs that provide grants and loans to families seeking IVF treatment are also teasing out how it could impact them and the people they serve. Many of those programs were born of former IVF patients who have faced the challenges of cost firsthand.

Teresa Barbosa, the CEO of Gift of Parenthood, a program that awards quarterly IVF grants to families in financial need, said she created the program in 2019 after spending more than $60,000 her life savings on ultimately unsuccessful IVF treatments.

Gift of Parenthood awards grants as high as $20,000 four times a year; more than 15 babies have been born as a result of the treatments they helped facilitate. Many of those who come seeking help are women of color, like her, who are running out of options, Barbosa said.

They dont have the access its really scary, she said. Gift of Parenthood this year added a fundraising feature on its site to help families raise funds for their procedures, as well as a response to the degree of need.

She feels in limbo, Barbosa said, facing the possibility that even more people will need help paying for IVF and she will be able to help an even smaller slice.

Fertility loan providers like EggFund, which helps streamline the application process for IVF patients, already makes accessing loans easier for patients through one application that ensures the money goes to them and not a clinic. That could help in the case that a clinic closes in a state with changing IVF laws, said founder Carmela Rea. EggFund also allows participants to apply with other people, including siblings and parents, to help reach the requirements for a loan. But higher IVF costs will likely mean higher loans and more debt.

Rea created EggFund in 2017 after spending $80,000 of her savings on her own IVF treatments.

I felt it was wrong that only the wealthy could procreate, and I think its a human right if you want to have a family to be able to have it and not to have money be the consideration that decides whether you can have a family if you want it or whether you can end a pregnancy if you dont want it, Rea said. It shouldnt come down to your wealth.

Already insurance coverage for IVF is limited at best and nonexistent at worst. Few employers cover it, and those that do are typically larger companies that employ higher-paid workers, like major tech companies.

At the Baby Quest Foundation, one of the most well-known IVF grant programs in the country, founder Pamela Hirsch said she is working to get more employers to cover IVF. Hirsch has helped give 200 grants since launching in 2012 after her own daughter underwent four unsuccessful IVF cycles before welcoming two babies via surrogates.

Abortion restrictions could make it less likely for employers to include IVF coverage in their insurance plans, experts said.

Its almost like a collision course: Which direction is fertility moving in? More access to care because people will be lucky to have insurance coverage from their work or the whole industry closing down? Hirsch said.

Currently, New York requires that large-group insurance policies cover three rounds of IVF. That law leaves out Medicaid patients and those who work for employers with fewer than 100 employees, an estimated 2 million New Yorkers, said Risa Levine, an infertility advocate and former member of the board of directors at RESOLVE: The National Infertility Association, who helped pass the legislation in New York.

She spent $270,000 on fertility treatments.

As a White Jewish woman whose parents wanted her to have a kid, I was able to borrow money from my parents, Levine said. But, it absolutely impacted my financial security. It put me in a precarious financial situation.

Low-income women wouldnt even have that choice, she said. And insurance providers are going to reflect the new risk brought on by changes that redefine how IVF can be performed.

What insurance company is going to cover a clinic and a doctor for malpractice or for criminal behavior if they define life as beginning at conception outside of the womb? Levine said.

For providers, the entire discussion puts into question all the advancements IVF has made scientifically and politically in recent years.

There are numerous questions and few answers. What will happen to the pace of scientific discovery if fertility clinics close and IVF becomes a niche service? What will happen to patients, if companies are less willing to cover IVF and conversations about insurance covering the procedure die out?

We are so far from one another, Shahine said, and I feel like any restrictions are going to make those gains weve already made fall backward.

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Many low-income people are already shut out of IVF. Could abortion bans make it even more expensive? - The 19th*

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With a history of breast cancer in her family, Andrea Cronin has been careful to get annual mammograms since she was in her early 30s.

Like a lot of women, though, she skipped the test in 2020 due to the pandemic. She was relieved when her 2021 test came back negative, but she wanted more reassurance. Cronins mother was diagnosed with breast cancer 28 years ago, and the cancer has since metastasized to her stomach and bones. Cronin also has dense breasts, which can make reading a mammogram more difficult.

With my mothers history, I just wanted to be proactive, recalled Cronin, 47, who is from Haddonfield. My doctor suggested alternating mammograms and MRIs every six months.

This past January, Cronins MRI showed a tumor, which was confirmed by an ultrasound. She was diagnosed with stage II invasive ductal carcinoma.

Cronins hunch that she needed further testing paid off. Not waiting another year to find the cancer means her prognosis is good, said Zonera Ali, Cronins oncologist at the Lankenau Institute for Medical Research.

But her situation is unusual, her doctor and experts stressed.

Most patients cancers are picked up on the mammogram, but about twice a year I see a patient whose cancer is found through the MRI, said Ali. When cancers are detected earlier, chances of cure are much higher.

For Cronin, getting additional testing made sense, given her mothers bouts with breast cancer. But that is not advised for women without a family history of cancer. The increased sensitivity that MRIs offer can show something that looks like a problem but may not actually be a problem, said Richard Bleicher, leader of the Breast Cancer Program and professor of surgical oncology at Fox Chase Cancer Center.

MRIs can result in three times more unnecessary biopsies than mammograms, he noted.

We end up doing a lot of biopsies, more testing and interval testing, and sometimes unnecessary surgeries that cause pain and discomfort for women, not to mention costs and anxiety, he said.

When Cronins cancer was detected, she was given the option of having a lumpectomy, in which just the lump and surrounding tissue would be removed, but opted to have both breasts removed in a double mastectomy, given her mothers history of recurrence.

This would require only one surgery and get me back into my life of dentistry quicker, Cronin said.

Her mother, Joyce Makarczyk, was first diagnosed with breast cancer through a routine mammogram in 1993, at the age of 46.

I was going to go for a second opinion but the doctor said it was an aggressive cancer so I shouldnt waste any time, recalled Makarczyk, who lives in Mays Landing. Cancer was also discovered in her lymph nodes, so she had one breast removed, followed by chemotherapy and radiation.

About 10 years later, the cancer returned in her right breast. She had a lumpectomy and radiation and was cancer-free for five years. But then she started having stomach problems. The cancer had metastasized into her stomach and bones.

READ MORE: Maria Quiones-Snchez went public after being diagnosed with breast cancer. Now she begins the next chapter of her story. | Helen Ubias

Makarczyk, now 75, has taken the targeted therapy Ibrance ever since and has PET scans every six months. A couple of times, the scan showed cancer cells in her stomach, which were surgically removed.

Im feeling OK, she said. The cancer doesnt cause me any trouble at all.

During Cronins double mastectomy in March, cancer was found in one of the 11 lymph nodes tested. In late April, she started eight sessions of chemotherapy over four months, which will be followed by one month of radiation.

Once cancer escapes into the lymph nodes, the chance of that cancer going somewhere else is higher, said Ali. Especially in women below the age of 50, we recommend chemotherapy and post-mastectomy radiation.

After Cronins cancer diagnosis, her older sister Erica Toffenetti also is seeking additional screening.

The fact that my sister showed no symptoms, it wouldnt hurt to have these tests done for a baseline, said Toffenetti, 51, from Buena, N.J. Im feeling a little nervous but also more relieved. With my mother Ive been dealing with breast cancer more than half my life.

Toffenetti, who has two children, had genetic testing done in 2012 and again in 2019 as the testing became more advanced. Like her sister, she doesnt have the BRCA gene associated with higher risks of cancer.

Both sisters have dense breasts, as do nearly half of all women age 40 and older who get mammograms, according to the NIH. Dense breasts have relatively high amounts of glandular tissue and fibrous connective tissue, which make it more difficult to see potential tumors.

The American Cancer Society recommends mammograms as a choice for women aged 40 to 44. Women aged 45 to 54 should get a mammogram every year; and women 55 and older should switch to a mammogram every two years, or can continue yearly screening.

At this time, experts do not agree what other tests, if any, should be conducted in addition to mammograms in women with dense breasts, according to the American Cancer Society website.

ACS recommends mammograms for dense breasts without any other high-risk factors, said Karen E. Knudsen, chief executive officer of the American Cancer Society and former enterprise director of the Sidney Kimmel Cancer Center at Jefferson Health.

When Renee Anderson, Cronins ob/gyn at Pennsylvania Hospital, sends mammogram results to patients with dense breasts, she includes an explanation of what it means.

In those cases, Anderson gives her patients the option for more testing, and about half, most often those with a family history of cancer, choose to have an MRI or ultrasound.

When you get a discrepancy like what you have with Andrea, it could have been missed because of dense breasts, she said. Or whats more worrisome is that you could have a very aggressive form of cancer that started quickly and is growing quickly.

READ MORE: The war on cancer at 50: How a socialite citizen-lobbyist started a movement

Cronin, whose cancer is slow growing, was fortunate that her insurance covered the MRI. Thats not the case for every woman. In 2020, Pennsylvania Gov. Tom Wolf signed into law legislation requiring insurers to cover breast MRIs or ultrasounds for women at increased risk of breast cancer. But the patient still may be responsible for co-pays and deductibles, which can be costly.

Anderson stressed that the most important form of self-care is seeing your gynecologist and having a mammogram annually, especially for older women. The ACS guidelines say screening should continue as long as a woman is in good health and is expected to live 10 more years or longer.

For some women as they get older, 50 and above, they dont think they need to come to a gynecologist, so nobody is doing an exam, she said.

Breast cancer is associated with the BRCA1 and BRCA2 genes, but just 0.25% of the general population who have breast cancer have the BRCA gene, said Ali, Cronins oncologist. That number jumps to 2.5% among Ashkenazi Jewish women.

With an 11-year-old daughter, Cronin was eager to have genetic testing. She was tested for 35 different genes related to an increased risk for certain cancers and was negative for all of them, including the BRCA genes.

Unfortunately, I feel that I still have to worry about her, because I dont have the gene but still got cancer, she said.

Cronin shared her experience in an email to her dental patients, alerting them to the fine print disclaimer at the bottom of some mammogram reports that says extreme breast density decreases the sensitivity of mammograms. Please discuss family history and any concerns with your provider.

So many patients have thanked me directly for being so transparent with them, Cronin said. Specifically, two patients told me that after sharing my emails, their mothers demanded more testing after first being told no. Its so important to be your own patient advocate.

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An MRI detected breast cancer in this Haddonfield woman. Should you consider having one? - The Philadelphia Inquirer

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Four years ago, Annik Greenhill discovered she had an inherited mutation of the BRCA1 gene, which predisposes her to breast cancer.

While discovering the gene potentially saved her life, it led to challenges with insurance that have left her in a difficult position.

Insurance companies were concerned the BRCA1 gene made her high risk, and she had to be on a premium health insurance plan to be covered, she said.

In New Zealand insurance companies are allowed to ask to see the results of genetic tests, which has led to accusations of discrimination.

READ MORE:* Beware of DNA health tests by ancestry companies* Preventative double mastectomy worth it for mum-of-two living with the BRCA gene mutation* I tried to ignore genetic warnings about cancer, and that could have been fatal

After returning to New Zealand, Greenhill struggled to find an insurance company willing to cover the gene. Her insurance broker told her most insurers would exclude any treatment relating to the gene, or only cover her after prophylactic surgeries were undertaken.

Abigail Dougherty/Stuff

Annik Greenhill is a BRCA1 carrier and has been affected by genetic discrimination as a result.

I thought the fact I know I am a carrier should in some ways reduce my overall risk to an insurance company because I am in an early detection programme, I was a carrier whether I knew it or not.

Breast Cancer Foundation NZ chief executive Ah-Leen Rayner said insurance discrimination around the BRCA gene was a serious problem, and a law change was needed.

So long as New Zealand insurers are able to ask about genetic test result, people with the BRCA gene will be discriminated against, even though they might not get breast cancer.

Greenhill eventually took out an UltraCare policy with Southern Cross, the only insurer who would offer coverage related to the gene, she said.

However, had to be on the second-highest plan, and only after a three-year stand down period would she be eligible for BRCA related covershe said.

Health insurance cost the family $580 a month, a significant expense, she said.

Southern Cross said that it would cover cancer treatment without a stand down period. But because she already knew she had BRCA1, she would not be covered for monitoring the gene or for prophylactic treatment for three years.

She also applied for additional chemotherapy cover of $300,000 a year, but was capped at $60,000.

Southern Cross said while Greenhill would not be excluded from taking out a Chemo 300 plan, she would need to meet the terms and conditions, which included possible exclusions for family history.

ROSA WOODS/STUFF

Ashleigh Stallard has the BRCA gene and was faced with a strong risk of developing breast cancer. She chose to have a preventive mastectomy at age 23. (Video first published in October 2019)

While grateful Southern Cross offered some cover, she said it still felt like she was being punished for gaining a better understanding of her health.

Greenhill did not regret her decision to get tested, but was concerned others in her position would be discouraged because of the genetic discrimination she encountered.

Its a conundrum that Georgia Eve, a 22-year-old social support worker, is grappling with.

She was planning to donate one of her eggs to a fertility organisation, until she heard it could lead to genetic discrimination from insurers.

Egg donors are required to take a genetic test as part of predonation health checks. But potential donors are told the results of that test can be legally asked for and used by insurers in underwriting decisions.

Despite having wanted to donate an egg for some time, the potential for genetic discrimination in later life was a dealbreaker, Eve said.

Its a bit of a risk to take. I am someone who wants to travel, so I am concerned about affording access to travel insurance later in life. I am thinking it might be better not to do it, she said.

Eve said insurers position on genetic testing was affecting broader public health.

If people are being dissuaded by insurance companies not to get genetic testing, they are losing an opportunity to live healthier lives. But as it stands many people are choosing not to know.

Abigail Dougherty/Stuff

Georgia Eve had been considering donating an egg to a fertility service. But to do so she would have had to undergo a genetic test, and in New Zealand an insurance company can ask to see the results.

A United States survey found 28% of participants declined genomic testing because of concerns about insurance discrimination, the New Zealand Medical Journal reported recently.

But Australia and Canada are legislating to protect individuals from genetic discrimination by insurance companies.

Canada, in 2017, introduced a complete ban on the use of genetic test results to discriminate, including for insurance and employment.

The Australian life insurance industry, in 2019, introduced a five-year ban on the use of genetic tests in underwriting.

New Zealand insurance companies have not followed suit.

Auckland University Centre for Cancer Research acting director Professor Andrew Shelling said New Zealand was a significant disparity from other first-world countries in the way it handled genetic information.

People should be very concerned about insurers using genomic information, and the patient advocacy group Against Genetic Discrimination Aotearoa, was calling for a complete ban, Shelling said.

Genetic testing allowed people to make informed health care decisions, and people were refusing to undergo testing because of the potential insurance consequences, he said.

For people who are at risk of genetic conditions, choosing not to be tested may have serious health impacts.

While there was no New Zealand data to draw from, he believed it would be similar to the rest of the world, where between 10% and 30% of people were declining testing.

Thats an extraordinary number of people and is likely to be having a significant impact on people at risk of serious genetic disease.

Southern Cross chief sales and marketing officer Kerry Boielle said it did not add a pre-existing condition exclusion as a result of a genetic abnormality, and typically would not increase premiums or refuse to issue a policy based on that information.

However, it may exclude any consultations, further tests, or treatment required in its policy as a result of an abnormality.

Southern Cross said that in the past five years, 51 members had disclosed a genetic abnormality or mutation, and 51 people had exclusions applied to their policy as a result of genetic abnormalities.

Three other insurance companies said they were members of the Financial Services Council (FSC) and complied with the councils code of conduct and guidelines around genetic tests.

FSC chief executive Richard Klipin said the issue of genetic testing was complex.

To ensure that insurance remains sustainable and fair for all customers, some insurers may ask customers to disclose known information about the results of their genetic tests, Kiplin said.

But, insurers were never asked to carry out genetic testing, he said.

CORRECTION: An earlier version of this article stated Southern Cross required a stand down period of three years before it would cover cancer related to the BRCA1 gene. However, the stand down period relates to prophylactic treatment. (Amended at 12.54pm on June 8, 2022)

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Kiwis should be 'very concerned' about genetic discrimination - Stuff

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The novel coronavirus SARS-CoV-2, which causes COVID-19, has caused millions of infections worldwide. As time has passed, it has become increasingly clear that COVID-19 is not a cookie-cutter disease.

People vary significantly in their susceptibility to infection, symptoms, and disease severity. Certain risk factors clearly play a role. Could genetics also play a part?

Researchers are examining the role of genetics in peoples reactions to the virus. While far from conclusive, data indicates that some of your genes may influence how SARS-CoV-2 affects your health.

Read on to learn what research has uncovered.

To look for genes that may influence the impact of COVID-19, geneticists scan the DNA of large study groups. This helps them find and identify connections between specific DNA sequences and disease characteristics.

Early genetic studies have uncovered compelling clues that certain genomic variants and blood types may play a role in how people react to the SARS-CoV-2 virus.

Angiotensin-converting enzyme 2 (ACE2) receptors are proteins found on the surface of certain cells. ACE2 receptors generate other proteins that regulate cell function. ACE2 receptors also allow the SARS-CoV-2 virus to enter your cells.

ACE2 receptors are located in the lungs, blood vessels, kidneys, and other parts of the body. They help regulate blood pressure, wound healing, and inflammation.

Everyone has ACE2 receptors, but their amount and locations vary. Multiple studies, including a 2021 study reported in the European Journal of Medical Research, found a link between ACE2 levels and vulnerability to COVID-19.

The same study also found that people with a specific type of genetic variation in ACE2 are at higher risk of SARS-CoV-2 infection. Another finding was a heightened susceptibility to SARS-CoV-2 infection in men compared to women.

Cytokines are proteins released by cells. Cytokines help cells communicate with each other. They also work to regulate inflammation and the bodys immune response to infection.

A cytokine storm is an overreaction of the immune system to infection from an invading host, such as SARS-CoV-2. During a cytokine storm, your cells release too many cytokines. This causes high levels of inflammation and the overactivation of certain immune cells.

The results of a cytokine storm can be severe and include tissue damage, organ failure, and sometimes death.

A review of multiple studies found that several genetic variants in cytokine genes may be related to cytokine storm and disease severity. Studies also found that these variants might be related to COVID-19 complications, including venous thrombosis.

A large study analyzed genes found along a stretch of chromosome 3. The study found compelling information about specific genes and their potential impact on respiratory failure caused by COVID-19.

Researchers identified a gene cluster on chromosome 3 linked to susceptibility to respiratory failure in COVID-19 patients. According to researchers, the gene cluster confirmed that ABO blood type played a role, indicating a higher risk for respiratory failure from COVID-19 for people with type A blood.

The HLA gene helps regulate your bodys immune response. Decades of research have found that people with certain HLA alleles (slight gene mutations, or variations) are prone to various autoimmune, inflammatory, and malignant diseases. Scientists call this phenomenon HLA disease association.

A 2021 review found that people with certain HLA alleles were more vulnerable to COVID-19 and severe illness than the general population.

If you were assigned male at birth, you might be at higher risk for serious illness from COVID-19. While some data points to lifestyle factors more common in men (such as smoking or drinking alcohol), genetic factors are also at play.

Men tend to express higher amounts of ACE2, making them more susceptible to COVID-19. A 2021 study suggests that this alone doesnt account for the difference in response.

The study also highlights genes present in men that might make them more prone to infection and genes present in women that may help them fight off infection.

There are also genes on the X-chromosome that influence your immune response. There are about 55 times as many of these genes on the X-chromosome as on the Y-chromosome.

As men only have one copy of the X-chromosome, variants in genes on this chromosome may have a greater effect on how COVID-19 progresses.

Its also important to remember that genetic traits are sometimes clustered among people with the same nationality, ethnicity, or culture. This can skew study results, especially in places where poor living conditions or poverty are factors.

Still, three 2021 studies (1, 2, 3) state that we cant ignore ethnic differences in COVID-19 susceptibility. Some genes that influence the course of COVID-19, such as HLA alleles, are more prevalent in certain ethnicities.

Another study noted that Black people tend to have more variations in the genes that affect ACE2.

Again, more research is needed before we fully understand the true impact.

COVID-19 is known to present with a wide variety of symptoms. While some symptoms are common, the virus tends to affect people in many different ways. Your genetics may play a role here too.

A 2021 study linked COVID-19 with altered gene expression in specific tissues or cells. This suggests that certain genetic variations may make you more likely to experience certain symptoms.

The study also noted that some of the genes they studied were also linked to ethnicity. This means that some symptoms may be more common in certain ethnic groups.

Researchers and geneticists are sharing their findings on genetics and COVID-19 through the COVID-19 Host Genetics Initiative.

As more studies take place, the biological pathways that affect your susceptibility or natural immunity to this disease may become more apparent.

This research may help generate new types of drugs that can treat COVID-19. It may also help determine why some people have a severe reaction to infection, and others experience mild to no symptoms.

While exciting and compelling, its important to remember that the research on genetics and COVID-19 is still new. We need more research before we can fully understand the impact of genes on this disease.

Knowing your risk factors can help you make decisions concerning exposure to the virus. Risk factors for COVID-19 and severe symptoms include:

No gene makes you fully immune to COVID-19. No matter what your own risk may be, these measures can help protect you from infection:

A growing body of evidence has linked certain genes and gene mutations to COVID-19 susceptibility. While compelling, this information is still new. We need more research to fully understand how our genes affect our response to the coronavirus.

As this body of science grows, it may better inform us on how to treat or even prevent COVID-19.

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Genetic Susceptibility to COVID-19: What We Know So Far - Healthline

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Height is typically a predestined characteristic in most people. According to Medical News Today, up to 80% of someone's height is based on their DNA. If you come from a tall or short family, you are more likely to be taller or shorter. Yet despite baseline genetics, there are a variety of actions to take during childhood and teen years to ensure that your reach your maximum potential height according to your DNA.

Basically, it's the health advice you've likely heard several times before but not everyone follows. Obey a nutritious dietby eating lots of fruits and veggies every day. Make sure you have enough calcium to grow healthy bones as well as plenty of protein. Get adequate exercise to strengthen bones and muscles.

One of the biggest things teens need to reach optimal height is sleep. A growth hormone is released while you're in certain sleep stages (via Verywell Health). If sleep is insufficient, a body won't likely reach maximum growth.

There are numerous ways to predict how tall a boy will be as he grows. The Mayo Clinic outlines two different techniques. In the first prediction, add the mother's height to the father's height and then add 5 inches for boys. (Subtract 5 inches for girls). Then just divide by two. The second way to estimate height is to find a boy's height at age 2 and then double it. (For girls, do the same at age of 18 months.)

As a general rule, men stop growing when they're 18. There is a slight possibility that if a teen boy began puberty late, he may grow a bit in his early 20s, but that is unusual. The reason is simple and it has to do with growth plates (via Healthline). That's the area of the bone made of cartilage that continues to grow. However, they meld together right after puberty, meaning there is no more potential to grow once they have fused.

Over the years the average height of men has grown and that's because men are now getting better nutrition, exercise, and sleep both as children and teens. In the early 1900s, men were averaging 5 feet, 8 inches tall (via A Hundred Years Ago). Currently, in the United States, the average height for men is approximately 5 feet, 9 inches tall, according to the Centers for Disease Control and Prevention (CDC)while the average weight for menrests at 197.9 pounds.

Oddly enough, there are certain states where heights differ. According to the World Population Review, the U.S. states with the tallest men, averaging 5 feet, 10.8 inches or more, are Alabama, Iowa, Kentucky, Montana, Nebraska, North Dakota, South Dakota, Tennessee, Utah, West Virginia, and Wyoming. The states with the shortest average male heights, averaging below 5 feet, 10 inches, are New York, New Jersey, California, Nevada, New Mexico, Hawaii, and Texas. All the remaining states lie somewhere in between.

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What Is The Average Height For Men In The US? - The List

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Participants

For factor analyses, we restricted our analyses to autistic individuals from the SSC and SPARK cohorts. Participants had to have completed the two phenotypic measures (details are below) to be included in the factor analyses. We also excluded autistic individuals with incomplete entries in either of the two measures (n=5,754 only in the SPARK cohort). This resulted in 1,803 participants (n=1,554 males) in the SSC, 14,346 participants (n=11,440 males) in SPARK version 3 and 8,271 participants (n=6,262 males) in extra entries from SPARK version 5 (SSC, mean age=108.75 months, s.d.=43.29 months; SPARK version 3, mean age=112.11 months, s.d.=46.43 months; SPARK version 5, mean age=111.22 months, s.d.=48.19 months). Only the SCQ was available for siblings in the SPARK study.

We conducted analyses using data from four cohorts of autistic individuals: the SSC (n=8,813)30, the Autism Genetic Resource Exchange (AGRE, CHOP sample) (nmax=1,200)64, the AIMS-2-TRIALS Longitudinal European Autism Project (LEAP) sample (nmax=262)65 and SPARK (n=29,782)31. For sibling comparisons, we included siblings from the SSC (n=1,829) and SPARK (n=12,260) cohorts. For trio-based analyses, we restricted to complete trios in the SSC (n=2,234) and SPARK (n=4,747) cohorts. For all analyses, we restricted the sample to autistic individuals who passed genetic quality control (QC) and who had phenotypic information.

We conducted factor analyses using the SCQ29 and the RBS28. The SCQ is a widely used caregiver report of autistic traits capturing primarily social communication difficulties and, to a lesser extent, repetitive and restricted behaviors29. There are 40 binary (yes-or-no) questions in total, with the first question focusing on the individuals ability to use phrases or sentences (total score, 039). We used the Lifetime version rather than the current version as this was available in both the SPARK and SSC studies. Of note, in the Lifetime version, questions 119 are about behavior over the lifetime, while questions 2040 refer to behavior between the ages of 4 to 5 years or in the last 12 months if the participant is younger. We excluded participants who could not communicate using phrases or sentences (n=217 in the SSC and n=17,092 in SPARK) as other questions in the SCQ were not applicable to this group of participants. The RBS is a caregiver-reported measure of presence and severity of repetitive behaviors over the last 12 months. It consists of 43 questions assessed on a four-point Likert scale (total score, 0129). Higher scores on both measures indicate greater autistic traits.

We conducted exploratory factor analysis on a random half of the SSC (n=901 individuals, of which 782 were males) using promax rotation to identify correlated factors as implemented by psych (ref. 66) in R. We conducted three sets of exploratory correlated factor analyses: for all items, for social items and for non-social items. Previous studies have provided support for a broad dissociation between social and non-social autism features12,23 and have conducted separate factor analyses of social (for example, refs. 67,68) and non-social autism features (for example, refs. 69,70). Thus, we reasoned that separating items into social and non-social categories might aid the identification of covariance structures that may not be apparent when analyzing all items together. We divided the data into social (all of the SCQ except item 1 and nine other items and item 28 from the RBS) and non-social (nine items from the SCQ (items 8, 11, 12 and 1418) and all items from RBS except item 28) items, which was carried out after discussion between V.W. and X.Z. The ideal number of factors to be extracted was identified from examining the scree plot (Supplementary Fig. 2), parallel analyses and theoretical interpretability of the extracted factors. However, we examined all potential models using confirmatory factor analyses as well to obtain fit indices, and the final model was identified using both exploratory and confirmatory factor analyses.

We then applied the model configurations from promax rotated exploratory factor analysis for bifactor models to explore the existence of general factor(s). In addition to a single general factor bifactor model, we divided the data into social and non-social items as mentioned earlier and applied bifactor models separately for the social and non-social items. Hierarchical values and explained common variances were then calculated for potential models as extra indicators of the feasibility of bifactor models, but hierarchical values were not greater than 0.8 for most of the models tested, and explained common variances were not greater than 0.7 (refs. 71,72,73) for any of the models tested (Supplementary Table 2).

Three rounds of confirmatory factor analyses were conducted: first for the second half of the SSC, followed by analysis of SPARK participants whose phenotypic data were available in version 3 of the data release and, finally, analysis of SPARK participants whose phenotypic data were available only in version 4 or version 5 of the data release and not in the earlier releases. To evaluate the models, multiple widely adopted fit indices were considered, including the comparative fit index (CFI), the TLI and the root mean square error of approximation. In CFA, items were assigned only to the factor with the highest loading to attain parsimony. We conducted three broad sets of confirmatory factor analyses: (1) confirmatory factor analyses of all correlated factor models, (2) confirmatory factor analyses of the autism bifactor model and (3) confirmatory factor analyses of social and non-social bifactor models. For each of these confirmatory factor models, we limited the number of factors tested based on the slope of the scree plots and based on the number of items loading onto the factor (five or more). For the confirmatory factor analyses of social and non-social bifactor models, we iteratively combined various numbers of social and non-social group factors. In bifactor models, items without loading onto the general factor in the correspondent EFA were excluded. Items were allocated to different group factors, which were identified based on the highest loading (items with loading <0.3 were excluded). Due to the ordinal nature of the data, all CFAs were conducted using the diagonally weighted least-squares estimator (to account for the ordinal nature of the data) in the R package lavaan 0.6-5 (ref. 74). We identified the model most appropriate for the data at hand with TLI and CFI>0.9 (TLI and CFI>0.95 for bifactor models), low root mean square error of approximation and good theoretical interpretability based on discussions between V.W. and X.Z. Additionally, as sensitivity analyses, the identified model (correlated six-factor model) was run again with two orthogonal method factors mapping onto SCQ and RBS-R to investigate if the fit indices remained high after accounting for covariance between items derived from the same measure, as these measures vary subtly during the period of time evaluated. We also reanalyzed the identified model after removing items that were loaded onto multiple factors (>0.3 on two or more factors) to provide clearer theoretical interpretation of the model. For genetic analyses, we used factor scores from the correlated six-factor model without including the orthogonal method factors and without dropping the multi-loaded items.

QC was conducted for each cohort separately by array. We excluded participants with genotyping rate <95%, excessive heterozygosity (3s.d. from the mean), non-European ancestry as detailed below, mismatched genetic and reported sex and, for families, those with Mendelian errors >10%. SNPs with genotyping rate <10% were excluded, or they were excluded if they deviated from HardyWeinberg equilibrium (P<1106). Given the ancestral diversity in the SPARK cohort, HardyWeinberg equilibrium and heterozygosity were calculated in each genetically homogeneous population separately. Genetically homogeneous populations (corresponding to five super-populations: African, East Asian, South Asian, admixed American and European) were identified using the five genetic principal components calculated using SPARK and 1000 Genomes Phase 3 populations75 and clustered using UMAP76. Principal components were calculated using linkage disequilibrium-pruned SNPs (r2=0.1, window size=1,000kb, step size=500 variants, after removing regions with complex linkage disequilibrium patterns) using GENESIS77, which accounts for relatedness between individuals, calculated using KING78.

Imputation was conducted using the Michigan Imputation Server79 with 1000 Genomes phase 3 version 5 as the reference panel49 (for AGRE and SSC), with the HRC r1.1 2016 reference panel80 (for AIMS-2-TRIALS) or using the TOPMed imputation panel81 (for both releases of SPARK). Details of imputation have been previously reported82. SNPs were excluded from polygenic risk scores if they had minor allele frequency <1%, had an imputation r2<0.4 or were multi-allelic.

We restricted our PGS associations to four GWAS. First, we included a GWAS of autism from the latest release from the iPSYCH cohort (iPSYCH-2015)83. This includes 19,870 autistic individuals (15,025 males and 4,845 females) and 39,078 individuals without an autism diagnosis (19,763 males and 19,315 females). All individuals included in this GWAS were born between May 1980 and December 2008 to mothers who were living in Denmark. GWAS was conducted on individuals of European ancestry, with the first ten genetic principal components included as covariates using logistic regression as provided in PLINK. Further details are provided elsewhere49. We additionally included GWAS for educational attainment (n=766,345, excluding the 23andMe dataset)35, intelligence (n=269,867)34, ADHD (n=20,183 individuals diagnosed with ADHD and 35,191 controls)36 and schizophrenia (69,369 individuals diagnosed with schizophrenia and 236,642 controls)37. These GWAS were selected given the relatively large sample size and modest genetic correlation with autism. Additionally, as a negative control, we included PGS generated from a GWAS of hair color (blonde versus other, n=43,319 blondes and n=342,284 others) from the UK Biobank, which was downloaded from https://atlas.ctglab.nl/traitDB/3495. This phenotype has SNP heritability comparable to that of the other GWAS used (h2=0.15, s.e.=0.014), is unlikely to be genetically or phenotypically correlated with autism and related traits, and has a sample size large enough to be a reasonably well-powered negative control.

PGS were generated for three phenotypes using polygenic risk scoring with continuous shrinkage (PRS-CS)84, which is among the best-performing polygenic scoring methods using summary statistics in terms of variance explained85. In addition, this method bypasses the step of identifying a P-value threshold. We set the global shrinkage prior () to 0.01, as is recommended for highly polygenic traits. Details of the SNPs included are provided in Supplementary Table 3.

De novo variants were obtained from Antaki et al.19. De novo variants (structural variants and SNVs) were called for all SSC samples and a subset of the SPARK samples (phase 1 genotype release, SNVs only). To identify high-impact de novo SNVs, we restricted data to variants with a known effect on protein. These are damaging variants: transcript_ablation, splice_acceptor_variant, splice_donor_variant, stop_gained, frameshift_variant, stop_loss, start_loss or missense variants with MPC86 scores >2. We further restricted data to variants in constrained genes with a LOEUF score <0.37 (ref. 87), which represent the topmost decile of constrained genes. For SVs, we restricted data to SVs affecting the most constrained genes, that is, those with LOEUF score <0.37, representing the first decile of most constrained genes. We did not make a distinction between deletions or duplications. To identify carriers, non-carriers and parents, we restricted our data to samples from the SPARK and SSC studies that had been exome sequenced and families in which both parents and the autistic proband(s) passed the genotyping QC.

For genes associated with severe developmental disorders, we obtained the list of constrained genes that are significant genes associated with severe developmental disorders from Kaplanis et al.27. To investigate the association of this set of genes with autism and developmental disorders, we first identified autistic carriers with a high-impact de novo variant and then divided this group into carriers who had at least one high-impact de novo variant in a DD gene and carriers with high-impact de novo variants in other constrained genes.

Only individuals with undiagnosed developmental disorders are recruited into the Deciphering Developmental Disorders study, and, as such, known genes associated with developmental disorders that are easy for clinicians to recognize and diagnose may be omitted from the genes identified by Kaplanis et al.27. To account for this bias, we ran sensitivity analyses using a larger but overlapping list of genes identified from the Developmental Disorder Gene-to-Phenotype database (DDG2P). From this database, we used constrained genes that are either confirmed or probable developmental disorder genes and genes for which heterozygous variants lead to developmental phenotypes (that is, mono-allelic or X-linked dominant).

We identified 19 autism core and associated features that (1) are widely used in studies related to autism; (2) are a combination of parent-, self- and other-reported and performance-based measures to investigate if reporter status affects the PGS association; (3) are collected in all three cohorts; and (4) cover a range of core and associated features in autism. The core features are

ADOS88: social affect

ADOS88: restricted and repetitive behavior domain total score

ADI89: communication (verbal) domain total score

ADI89: restricted and repetitive behavior domain total score

ADI89: social domain total score

RBS28

Parent-reported Social Responsiveness Scale-2 (ref. 90): total raw scores

SCQ29

Insistence of sameness factor (F1)

Social interaction factor (F2)

Sensorymotor behavior factor (F3)

Self-injurious behavior factor (F4)

Idiosyncratic repetitive speech and behavior (F5)

Communication skills factor (F6).

The associated features are

Vineland Adaptive Behavior Scales91: composite standard scores

Full-scale IQ

Verbal IQ

Nonverbal IQ

Developmental Coordination Disorders Questionnaire92.

Measures of IQ were quantified using multiple methods across the range of IQ scores in the AGRE, SSC and LEAP studies. In the SPARK study, IQ scores were available based on parent reports on ten IQ score bins (Fig. 1c). We used these as full-scale scores. For analyses involving the SPARK and SSC cohorts, we converted full-scale scores from the SSC into IQ bins to match what was available from the SPARK study and treated them as continuous variables based on examination of the frequency histogram (Supplementary Fig. 8). For the six factors, we excluded individuals who were minimally verbal (Factor analyses), but these individuals were not excluded for analyses with other autism features.

We identified seven questions relating to developmental delay in the SPARK medical screening questionnaire. These are all binary questions (yes or no). Summed scores ranged from 0 to 7. The developmental phenotypes include the presence of

ID, cognitive impairment, global developmental delay or borderline intellectual functioning

Language delay or language disorder

Learning disability (learning disorder, including reading, written expression or math; or nonverbal learning disability)

Motor delay (for example, delay in walking) or developmental coordination disorder

Mutism

Social (pragmatic) communication disorder (as included in DSM IV TR and earlier)

Speech articulation problems.

We included the age of first words and the age of walking independently for further analyses. This was recorded using parent-reported questionnaires in the SPARK study and in ADI-R89 in the SSC study. While other developmental phenotypes are available, we focused on these two, as they represent major milestones in motor and language development and are relatively well characterized.

Before any statistical analyses, we visually inspected the distributions of the variables. All continuous variables were approximately normally distributed with the exception of the age of first words, the age of walking independently and the count of co-occurring developmental disabilities. For these three variables, we used quasi-Poisson or negative binomial regression to account for overdispersion in the data and because the variance was much greater than the mean. These models produced the same estimate but modestly different standard errors. Both have two parameters. However, while quasi-Poisson regression models the variance as a linear function of the mean, the negative binomial models the variance as a quadratic function of the mean. The model that produced the lower residual deviance was chosen between the two. For all other continuous variables, we used linear regression and parametric tests. For binary data, we used logistic regression as there was not a large imbalance in the case:control ratio.

For each cohort, PGS and high-impact de novo variants were regressed against the autism features with sex and the first ten genetic principal components as covariates in all analyses, with all continuous independent variables standardized. In addition, array was included as a covariate in SSC and AGRE datasets. This was performed using linear regression for standardized quantitative phenotypes, logistic regression for binary phenotypes (for example, association between PGS and the presence of a high-impact de novo variant), Poisson regression for count data (number of developmental disorders or delays, not standardized) and negative binomial regression for the age of walking independently or the age of first words (not standardized; MASS93 package in R).

For the association between genetic variables and core and associated autism phenotypes, we first conducted linear regression analyses for the four PGS first using multivariate regression analyses with data from SPARK (waves 1 and 2), SSC, AGRE and AIMS-2-TRIALS LEAP. This is of the form:

$$yapprox {textrm{PGS}}_{textrm{autism}} + {textrm{PGS}}_{textrm{schizophrenia}} + {textrm{PGS}}_{textrm{EA}} + {textrm{PGS}}_{textrm{intelligence}} + {textrm{sex}} + {textrm{age}} + 10 {textrm{PCs}},$$

(1)

where EA is educational attainment and 10PCs are ten principal components. For the negative control, we added the negative control as an additional independent variable in equation (1):

$$begin{array}{lll}yapprox {textrm{PGS}}_{textrm{autism}} + {textrm{PGS}}_{textrm{schizophrenia}} + {textrm{PGS}}_{textrm{EA}} + {textrm{PGS}}_{textrm{intelligence}} \+ {textrm{PGS}}_{textrm{hair color}} + {textrm{sex}} + {textrm{age}} + 10{textrm{PCs}}.end{array}$$

(2)

For the AGRE and SPARK studies, we ran equivalent mixed-effects models with family ID modeled as random intercepts to account for relatedness between individuals. This was carried out using the lme4 (ref. 94) package in R.

For high-impact de novo variants, we included the count of high-impact de novo variants as an additional independent variable in equation (1) and ran regression analyses for SPARK (wave 1 only) and SSC. To ensure interpretability across analyses, we retained only individuals who passed the genotypic QC, which included only individuals of European ancestries. Family ID was included as a random intercept:

$$begin{array}{l}yapprox {textrm{PGS}}_{textrm{autism}} + {textrm{PGS}}_{textrm{schizophrenia}} + {textrm{PGS}}_{textrm{EA}} + {textrm{PGS}}_{{mathop{{{rm{intelligence}}}}} } \+ {textrm{high-impact de novo count}} + {textrm{sex}} + {textrm{age}} + 10{textrm{PCs}.}end{array}$$

(3)

Effect sizes were meta-analyzed across the three cohorts using inverse-variance-weighted meta-analyses with the following formula:

$$begin{array}{l} {w_{i}} = {{mathrm{SE}}_{i}^{-2}} \ {{mathrm{SE}}_{mathrm{meta}}} = {surd}left(left({Sigma}_{1} w_{i}right)^{-1}right)\ {{beta}_{mathrm{meta}} = {Sigma}_{i}{{beta}_{i}}{{w}_{i}}{left({{Sigma}_{i}}{{w}_{i}}right)}^{-1}},end{array}$$

(4)

where i is the standardized regression coefficient of the PGS, SEi is the associated standard error and wi is the weight. P values were calculated from Z scores. Given the high correlation between the autism features and phenotypes, we used BenjaminiYekutieli false discovery rates to correct for multiple testing (corrected P<0.05). We calculated heterogeneity statistics (Cochrans Q and I2 values) for the PGS meta-analyses but not for the associations with high-impact de novo variants, as the latter were calculated using only two datasets (SSC and SPARK).

For the SPARK and SSC studies, we investigated the association between PGS (equation (1)) and being a carrier of a high-impact de novo variant (equation (3)) and the age of first walking and first words using negative binomial regression and conducted inverse-variance meta-analyses (equation (4)). We ran the same analyses for the SPARK study to investigate the association between PGS (equation (1)) and high-impact de novo variants (equation (3)) and counts of co-occurring developmental disabilities (quasi-Poisson regression). Leave-one-out analyses were conducted by systematically excluding one of seven co-occurring developmental disabilities and reconducting the analyses.

To investigate additivity between common and high-impact de novo variants, we conducted logistic regression with carrier status as a dependent binary variable and all PGS included as independent variables and genetic principal components, sex and age included as covariates. This was carried out separately for SPARK (wave 1) and SSC and meta-analyzed as outlined earlier.

Statistical significance of differences in factor scores between sexes were computed using t-tests. Associations with age and IQ bins were conducted using linear regressions after including sex as a covariate.

Matrix equivalency tests were conducted using the Jennrich test in the psych66 package in R. Power calculations were conducted using simulations. Statistical differences between pairwise correlation coefficients (carriers versus non-carriers) in core and associated features were tested using the package cocor95 in R. Using scaled existing data on full-scale IQ, adaptive behavior and motor coordination, we generated correlated simulated variables at a range of correlation coefficients to reflect the correlation between the six core factors and the three associated features. We then ran regression analyses using the simulated variable and high-impact de novo variants as provided in equation (3). We repeated this 1,000 times and counted the fraction of outcomes for which the association between high-impact de novo variant count and the simulated variable had P<0.05 to obtain statistical power. Differences in the age of walking and the age of first words between groups of autistic individuals and siblings were calculated using Wilcoxon rank-sum tests.

Polygenic transmission deviation was conducted using polygenic transmission disequilibrium tests14. To allow comparisons with midparental scores, residuals of the autism PGS were obtained after regressing out the first ten genetic principal components. These residuals were standardized by using the parental mean and standard deviations. We obtained similar results using PGS that had not been residualized for the first ten genetic principal components. We defined individuals without co-occurring ID as individuals whose full-scale IQ is above 70 the SSC and SPARK studies. Additionally, in the SPARK cohort, we excluded any of these participants who had a co-occurring diagnosis of intellectual disability, cognitive impairment, global developmental delay or borderline intellectual functioning. Analyses were conducted separately in the SSC and SPARK cohorts and meta-analyzed using inverse-variance-weighted meta-analyses. We additionally conducted pTDT analyses on non-autistic siblings to investigate differences between males and females.

For sex differences in high-impact de novo variants, we calculated relative risk in autistic females versus males based on (1) all carriers, (2) carriers of DD genes and (3) carriers of non-DD genes (SPARK wave 1 and SSC). For sensitivity analyses, we conducted logistic regression with sex as the dependent variable and carrier status for DD genes and either full-scale IQ and motor coordination scores (in SPARK wave 1 and SSC) or number of developmental disorders (only in SPARK wave 1) as covariates. For each sensitivity analysis, we provide the estimates of the unconditional analysis as well (that is, without the covariates).

We opted to conduct heritability analyses using unscreened population controls rather than family controls (that is, pseudocontrols or unaffected family members), as this likely reduces SNP heritability96 owing to parents having higher genetic likelihood for autism compared to unselected population controls55 and due to assortative mating97. Casecontrol heritability analyses were conducted using the ABCD cohort as population controls; specifically, the ABCD child cohort in the USA, recruited at the age of 9 or 10 years. This cohort is reasonably representative of the US population in terms of demographics and ancestry. As such, it represents an excellent comparison cohort for the SPARK and SSC cohorts. The ABCD cohort was genotyped using the Smokescreen genotype array, a bespoke array designed for the study containing over 300,000 SNPs. Genetic QC was conducted identically as for SPARK. Genetically homogeneous groups were identified using the first five genetic principal components followed by UMAP clustering with the 1000 Genomes data. We restricted our analyses to 4,481 individuals of non-Finnish European ancestries in the ABCD cohort. Scripts for this are available at https://github.com/vwarrier/ABCD_geneticQC. Imputation was conducted, similar to the analysis of SPARK data, using the TOPMed imputation panel.

For casecontrol heritability analyses, we combined genotype data from the ABCD cohort and from autistic individuals from the SPARK and SSC cohorts. We restricted the analysis to 6,328,651 well-imputed SNPs (r2>0.9) with minor allele frequency >1% in all datasets. Furthermore, we excluded multi-allelic SNPs and SNPs with minor allele frequency difference of >5% between the three datasets and, in the combined dataset, were not in HardyWeinberg equilibrium (P>1106) or had genotyping rate <99%. We additionally excluded related individuals, identified using GCTA-GREML, and individuals with genotyping rate <95%. We calculated genetic principal components for the combined dataset using 52,007 SNPs with minimal linkage disequilibrium (r2=0.1, 1,000kb, step size of 500 variants, removing regions with complex long-range linkage disequilibrium). Visual inspection of the principal-component plots did not identify any outliers (Supplementary Fig. 9). While our QC procedure is stringent, we note that there will be unaccounted-for effects in SNP heritability due to fine-scale population stratification, differences in genotyping array and participation bias in the autism cohorts. However, our focus is on the differences in SNP heritability between subgroups of autistic individuals, and unaccounted-for casecontrol differences will not affect this.

We calculated SNP heritability for autism and additionally in subgroups stratified for the presence of ID, sex, sex and ID together, and the presence of high-impact de novo variants. We also conducted SNP heritability in subgroups of autistic individuals with scores >1s.d. from the mean for each of the six factors, autistic individuals with F1 scores>F2 scores and autistic individuals with F2 scores>F1 scores.

We calculated the observed-scale SNP heritability (baseline and subgroups) using GCTA-GREML52,53 and, additionally, using PCGC54. In all models except for the sex-stratified models, we included sex, age in months and the first ten genetic principal components as covariates. In the sex-stratified models, we included age in months and the first ten genetic principal components as covariates. For sex-stratified heritability analyses, both case and control data were from the same sex. For GCTA-GREML, the observed-scale SNP heritability was converted into liability-scale SNP heritability using equation (23) from Lee et al.98. PCGC estimates SNP heritability directly on the liability scale using the prevalence rates from Maenner et al.99. For all analyses, we ensured that the number of cases did not exceed the number of controls, with a maximum case:control ratio of 1.

We used prevalence rates from Maenner et al.99, which provides prevalence of autism among 8 year olds (1.8%). The study also provides prevalence rates by sex and by the presence of ID. However, there is wide variation in autism prevalence. We thus recalculated the SNP heritability across a range of state-specific prevalence estimates obtained from Maenner et al.99. For estimates of liability-scale heritability for subtypes defined by factor scores >1s.d. from the mean, we estimated a prevalence of 16% of the total prevalence. For F1>F2 and F2>F1, prevalence was estimated at 50% of the total autism prevalence. Estimating approximate population prevalence of autistic individuals with high-impact de novo variant carriers is difficult due to ascertainment bias in existing autism cohorts. However, a previous study has demonstrated that the mutation rate for rare protein-truncating variants is similar between autistic individuals and siblings from the SSC and autistic individuals and population controls from the iPSYCH sample in Denmark, which does not have a participation bias100, implying that the de novo mutation rate in autistic individuals from the SPARK and SSC cohorts may be generalizable. Using the sex-specific proportion of de novo variant carriers and autism prevalence, we calculated a prevalence of 0.2% for being an autistic carrier of a high-impact de novo variant.

For sex-stratified SNP heritability analyses, we additionally calculated SNP heritability for a range of state-specific prevalence estimates to better model state-specific factors that contribute to autism diagnosis. In addition, using a total prevalence of 1.8%, we estimated SNP heritability using a male:female ratio of 3.3:1 (ref. 51) to account for diagnostic bias that may inflate the ratio.

We used GCTA-GREML to also estimate SNP heritability for the six factors, full-scale IQ and the bivariate genetic correlation between them. We used the same set of SNPs used in the casecontrol analyses. We were unable to conduct bivariate genetic correlation for the casecontrol datasets due to limitations of sample size.

We received ethical approval to access and analyze de-identified genetic and phenotypic data from the three cohorts from the University of Cambridge Human Biology Research Ethics Committee.

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

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Genetic correlates of phenotypic heterogeneity in autism - Nature.com

Recommendation and review posted by Bethany Smith

Among neurologic complaints, migraines are the most common cause of productivity loss and emergency room visits. Migraines may be the most painful type of headache, increasing stroke, and heart attack risk in men.

While migraines tend to affect more women, migraines in men do happen. About 9% of men are regular sufferers (vs. 17% of women), and certain types of headaches like cluster headaches are more common in men. Genetics also play a role since approximately 70% of sufferers have a close relative with the problem.

Today, some consider chronic migraine (>15 migraine days per month) as an individual and societal burden as it is more disabling than episodic migraine. A hypothesis to this higher probability of progression could be that men are often not diagnosed or misdiagnosed. The theory may be that they are less likely to report or seek medical treatment for migraines.

It is a false notion that migraine is a women's disease- This stigmatizes the disorder and denies men access to proper care. It is important to be aware of these statistics and seek help if you suffer with migraines. Read on to find out moreand to ensure your health and the health of others, don't miss these Sure Signs You've Already Had COVID.

A few years ago, scientists started looking at the influence of female hormones in men with migraine. This study reports that men with migraine displayed an increased level of estradiol (type of estrogen hormone) and clinical evidence of androgen deficiency (less male hormones). If you are having more than 15 headaches a month that are debilitating and interfere with your daily functioninga visit is warranted to your physician. Once the initial workup is normal, they can refer you to a migraine specialist once conservative measures fail. Looking at medications, supplements and your daily triggers will help you reduce pain and frequency of attacks. There are daily medications and well as preventive prescription medications that can control the overactivity of migraine attacks.

Use a migraine app to track your symptoms so you can make a correlation to your triggers and symptoms as they occur. The first thing I start with my patients are lifestyle changes to ensure better overall health. Daily habits can go a long way to help you have fewer, less-severe migraines.6254a4d1642c605c54bf1cab17d50f1e

Sleep cycle regulation is very important, go to bed at the same time every day, including on weekends and holidays. The brain's pathways responsible for sleep if disrupted can contribute to migraines.

It is important to seek out complementary medicine that is proven effective in migraines:

Apply lavender oil or peppermint to the base of your neck or use aromatherapy. Inhaling lavender essential oil may ease migraine pain.

Acupuncture can help to mitigate pain and the severity of attacks in many patients.

Ginger prevents nausea that can occur in many migraine patients.

Yoga and biofeedback help many patients cope with pain along with complimentary as well as medication management.

There are many migraine-specific vitamins that your migraine neurologist can recommend along with treatment.

There are also devices for migraines that attempt to interrupt pain signals, more specifically an external trigeminal nerve stimulation (eTNS) unit. The premise of the Cefaly is similar to that of other neurostimulators being tested for migraine treatment. SpringTM may be another option. You hold this device at the back of your head at the first sign of a headache, and it gives off a magnetic pulse that stimulates part of the brain. In addition, there is a noninvasive vagus nerve stimulator called gammaCore. When placed over the vagus nerve in the neck, it releases a mild electrical stimulation to the nerve's fibers to relieve pain. Nerivio is a wireless remote electrical neuromodulator.

Avoid certain foods. Diet plays a vital role in preventing migraine attacks. Your diet plays a part, too. In about 10% of people with these headaches, food is a trigger. Choose better food. Eat as much wholesome, fresh food, like fruits and vegetables, as you can. Avoid processed and packaged foods.

Some common trigger foods include:

Tyramine is a natural compound that forms in protein-rich foods as they age. It's also a trigger for migraines. These cheeses are high in tyramine:

Chemicals added to food to enhance their flavor or help them stay fresh longer may bring on a headache:

Limit stress as tension's a common trigger. Using mediation, music, meditation, yoga, and massage to relieve tension can help. There are many evidence-based complementary techniques. Along with your prescribed treatment, you might want to try one of these to help prevent migraines, such as acupuncture, massage & cognitive behavioral therapy

It is wise to avoid a drop in blood sugar which can set off a migraine. My patients know to drink at least 4-5 glasses of water to avoid dehydration, which can trigger headaches.

Exercise regularly, many of my patients are afraid it might trigger a migraine. Overdoing a workout may trigger a headache for some people, but research suggests regular, moderate aerobic exercise may make migraines shorter, less severe, and happen less often for many people. Vigorous exercise might be a trigger in migraineurs, but overall the benefits of physical activity far outweigh the risk for people with migraine.

Regular exercise is associated with a reduction in the frequency and intensity of migraines, says. Avoid exercise if you're in the middle of a migraine attack, as it can make the pain worse. When you're exercising it can help keep future away attacks by relieving stress, a common migraine trigger.

Exercise also stimulates the release of feel-good hormones called endorphins and enkephalins which are our natural painkillers and natural antidepressants. Migraines share brain receptors with serotonin responsible for our mood.

Preventive or good habits can go a long way to prevent migraines. Yet, it is not a substitute for a proper evaluation by a migraine neurologist. Good sources of information are the American Headache Society (AHS) and the American Migraine Foundation (AMF). The most important thing I keep in mind when treating my patients is that everyone is unique and the approach is never a one size fits all solution. Be aware of overusing over-the-counter pain relievers as they can actually trigger medication overuse headaches and cause stomach upset and ulcers. There is hope for your pain and you do not have to suffer in silence. And to protect your life and the lives of others, don't visit any of these 35 Places You're Most Likely to Catch COVID.

Shae Datta, MD, co-director, NYU Langone's Concussion Center, and director of cognitive neurology at NYU Langone HospitalLong Island.

The rest is here:
Best Habits to Prevent a Migraine, Says Neurologist Eat This Not That - Eat This, Not That

Recommendation and review posted by Bethany Smith

Research News

The subfossil jawbone of a polar bear that lived 115,000 to 130,000 years ago in Norways Svalbard archipelago. A genomic study includes an analysis of DNA extracted from a tooth attached to this jawbone, which is now housed at the Natural History Museum at the University of Oslo. Photo: Karsten Sund, Natural History Museum, University of Oslo

By CHARLOTTE HSU

A new study is providing an enhanced look at the intertwined evolutionary histories of polar bears and brown bears.

Becoming separate species did not completely stop these animals from mating with each other. Scientists have known this for some time, but the new research draws on an expanded data set including DNA from an ancient polar bear tooth to tease out more detail.

The story that emerges reveals complexities similar to those that complicate human evolutionary history.

The formation and maintenance of species can be a messy process, says Charlotte Lindqvist, associate professor of biological sciences, College of Arts and Sciences, and an expert on bear genetics. Whats happened with polar bears and brown bears is a neat analog to what were learning about human evolution: that the splitting of species can be incomplete.

As more and more ancient genomes have been recovered from ancient human populations, including Neanderthals and Denisovans, were seeing that there was multidirectional genetic mixing going on as different groups of archaic humans mated with ancestors of modern humans. Polar bears and brown bears are another system where you see this happening.

We find evidence for interbreeding between polar bears and brown bears that predates an ancient polar bear we studied, she says. And, moreover, our results demonstrate a complicated, intertwined evolutionary history among brown and polar bears, with the main direction of gene flow going into polar bears from brown bears. This inverts a hypothesis suggested by other researchers that gene flow has been unidirectional and going into brown bears around the peak of the last ice age.

A mother polar bear and her 2-year-old cubs in northwestern Greenland. Photo: ystein Wiig

The study was published June 6 in the Proceedings of the National Academy of Sciences. It was led by Lindqvist; Luis Herrera-Estrella at the National Laboratory of Genomics for Biodiversity (LANGEBIO) in Mexico and Texas Tech University; and Kalle Leppl at the University of Oulu in Finland. Tianying Lan, a former UB postdoctoral researcher now at Daicel Arbor Biosciences, was co-first author with Leppl.

The concept of Arctic-adapted polar bears capturing genetic material from brown bears, which are adapted to life in lower latitudes, is one of several findings of possible interest for scientists concerned with climate change impacts on threatened species.

As the world warms and Arctic sea ice declines, polar bears and brown bears may run into each other more frequently in places where their ranges overlap. This makes their shared evolutionary history a particularly intriguing subject of study, Lindqvist says.

An adult male polar bear in northwestern Greenland. Photo: ystein Wiig

Splitting of species can be messy process

As Lindqvist explains, scientists once thought modern humans and Neanderthals simply split into separate species after evolving from a common ancestor. Then, researchers found Neanderthal DNA in modern Eurasian people, implying that modern human populations received an influx of genes from Neanderthals at some point in their shared evolutionary history, she says.

Only later did scientists realize that this genetic intermingling also supplemented Neanderthal populations with modern human genes, Lindqvist adds. In other words, interbreeding can be complex, not necessarily a one-way street, she says.

The new study on bears reveals a remarkably similar story: The analysis finds evidence of hybridization in both polar bear and brown bear genomes, with polar bears in particular carrying a strong signature of an influx of DNA from brown bears, researchers say. Earlier research proposed the inverse pattern only, Lindqvist says.

Its exciting how DNA can help reveal ancient life history. Gene flow direction is harder to determine than merely its presence, but these patterns are vital to understanding how past adaptations have transferred among species to give modern animals their current features, says Leppl, postdoctoral researcher in the research unit of mathematical sciences at the University of Oulu.

Population genomics is an increasingly powerful toolbox to study plant and animal evolution, and the effects of human activity and climate change on endangered species, says Herrera-Estrella, Presidents Distinguished Professor of Plant Genomics and director of the Institute of Genomics for Crop Abiotic Stress Tolerance in the Texas Tech Department of Plant and Soil Science. He is also a professor emeritus at LANGEBIO. Bears dont provide simple speciation stories any more than human evolution has. This new genomic research suggests that mammalian species groups can hide complicated evolutionary histories.

The subfossil jawbone of a polar bear that lived 115,000 to 130,000 years ago in Norways Svalbard archipelago. Photo: Karsten Sund, Natural History Museum, University of Oslo

Evidence from modern bear genomes and DNA from an ancient tooth

The study analyzed the genomes of 64 modern polar and brown bears, including several new genomes from Alaska, a state where both species are found.

The team also produced a new, more complete genome for a polar bear that lived 115,000 to 130,000 years ago in Norways Svalbard archipelago. DNA for the ancient polar bear was extracted from a tooth attached to a subfossil jawbone, which is now housed at the Natural History Museum at the University of Oslo.

Using this data set, researchers estimate that polar bears and brown bears started to become distinct species about 1.3 to 1.6 million years ago, updating prior assessments made by some of the same scientists. The age of the split has been and remains a topic of scientific debate, with past interbreeding and limited fossil evidence for ancient polar bears among factors that make the timing hard to pinpoint, Lindqvist says.

In any case, after becoming their own species, polar bears endured dramatic population decline and a prolonged genetic bottleneck, leaving these bears with much less genetic diversity than brown bears, the new study concludes. The findings confirm past research pointing to the same trends, and add evidence in support of this hypothesis.

Genomes analyzed in a new study on bears include that of this bear, pictured here in 1995 on Alaska's North Slope. Scientists had wondered if this bear might be a brown bear-polar bear hybrid, but the new research finds that, This bear is not a hybrid, but simply a light-colored brown bear, says UB biologist Charlotte Lindqvist. Photo: Richard Shideler, Division of Wildlife Conservation, Alaska Department of Fish and Game

Together with the analysis of gene flow, these findings are providing new insights into the messy, intertwined evolutionary history of polar bears and brown bears.

The international research team included scientists from UB, LANGEBIO, Texas Tech, the University of Oulu, the Far Northwestern Institute of Art and Science, the Alaska Department of Fish and Game, the Natural History Museum at the University of Oslo, Nanyang Technological University, University of Helsinki and Aarhus University.

The research was funded by the National Fish and Wildlife Foundation, U.S. National Science Foundation, Alaska Department of Fish and Game, and U.S. Geological Survey.

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Study offers better look at tangled evolutionary histories of polar bears, brown bears - UB Now: News and views for UB faculty and staff - University...

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TWH Extreme weather sometimes reveals unknown or unexplored archaeological sites. A prolonged drought in Iraq has threatened its harvest and resulted in authorities releasing water from the Mosul reservoir for crop irrigation.

As the waters receded, the ruins of a Bronze Age, Mitanni city emerged. Archaeologists excavated the site and found defensive walls, towers, a multi-story warehouse and more than 100 cuneiform boards.

Archaeologists have dated the ruins to around 1400 B.C.E. The ruins are those of Zakhiku, a city in the Mitanni Empire. That empire controlled parts of northern Syria and Mesopotamia from 1550 to 1350 B.C.E.

In 2018, when an earlier drought had lowered the water height in the reservoir, the palace of Zakhiku emerged. Archaeologists seized the opportunity to examine its ruins.

In 2019, The University of Tbingen reported that this palace had walls up to seven meters tall (22.9 feet). They partially excavated eight rooms of the palace. Its inner, plastered walls had heights and thicknesses of up to two meters (6.6 feet). Vivid reds and blue murals covered those walls. Archaeologists think that such murals would have been common. Few Mitanni buildings, however, have survived.

Only three other Mitanni palaces have ever been found, but they were all from the outskirts of the empire. In contrast, Zakhiku lies close to the Mitanni heartland.

They also found ten cuneiform tablets. One of these tablets identified the site as the ancient city of Zakhiku. Other Mitanni records from 1800 B.C.E. refer to Zahiku. As these ruins date to roughly 1400 B.C.E, Zakhiku lasted for, at least, four-hundred years.

The palace had stood on an elevated platform, 20 meters (65.6 feet) from the east bank of the Tigris. The city lay to the palaces north.

In 2021, the waters of the reservoir had receded enough to expose the ruins of Zakhiku. Archaeologists knew that the water levels in the reservoir would begin to rise soon. They decided to excavate the ruins while they were above water. Kurdish archaeologist, Dr. Hasan Ahmed Qasim, joined two German archaeologists, Professor Dr. Ivana Puljiz of the University of Freiburg, and Professor Dr. Peter Pflzner of the University of Tbingen. Oasim chairs the Kurdistan Archaeology Organization.

In their excavations, they found a massive fortification with walls and towers, as well as a multi-story warehouse, and a complex of workshops.

In 2022, the University of Tbingen reported on the significance of that warehouse. The size of the warehouse indicated that it stored a large number of goods. For Qasim, this capacity showed that the site was an important center in the Mitanni Empire.

Inside the warehouse, excavators found five ceramic jars containing more than 100 cuneiform tablets. These tablets do not date from the Mitanni period. They date from the latter Middle Assyrian period from 1350 to 1100 B.C.E.

The Mitanni Empire collapsed around 1350 B.C.E., and Zakhiku fell under Assyrian control. The cuneiform tablets may contain information about that transition.

A strong earthquake struck the region around 1350 B.C.E. which destroyed the city. The upper walls of buildings collapsed and buried the lower parts of the building which may have helped to preserve the structures.

Dried bricks formed the main building material in Zakhiku. The lack of water damage stunned the research team.

After excavation, archaeologists covered most of the site in tight-fitting plastic. Then they covered the buildings with gravel. The Mosul reservoir has returned to capacity. Now, water covers Zakhiku once more, at least until the next drought strikes.

The Mitanni Empire extended from the eastern Mediterranean to northern Iraq. Its center lay in northeastern Syria.

Egyptian texts record that Mitanni had a similar status to that of Babylon, Egypt, and the Hittites. Mitanni rulers intermarried with Egyptian pharaohs.

The Smithsonian Magazine reported that the Mitanni produced the worlds oldest horse training manual. Masters of horsemanship, the Mitanni developed improved wheel technology for their war chariots.

Of all the kingdoms of the Bronze Age in Anatolia, Mesopotamia, and the Levant, the Mitanni Empire remains one of the least known. Very few of their records have survived and their religion left few remains. Surviving mentions of the Mitanni Empire mainly occur in treaties with Egypt, the Hittite Empire, or Assyria. Their Empire combined elements of the indigenous Hurrian culture with migrating or invading Indo-Aryan culture.

Map of Eastern Mediterranean and Middle East in 14th century Image credit: Alexikoua, CC BY-SA 3.0

Indo-Aryan refers to a branch of the Indo-European languages. That branch spread from the steppe region of Eurasia into south and western Asia. Another branch of that language spread into Europe.

Humans being human, people mix genetics and cultures. Languages can spread from one population to another, without one genetic population replacing another. Indo-European is a linguistic, not a genetic concept.

In their paper, About the Mitanni-Aryan Gods, Arnaud Fournet argued that Indo-Aryan words appear in surviving Mitanni texts. Those tablets include what may be the worlds oldest horse training manuals. Two surviving Hittite-Mitanni treaties mention major gods of the RigVeda, and specifically name Mitra, Varuna, Indra, and the Nasatya.

Other words in other surviving texts appear to be Hurrian. That language has no relation to any Indo-European or Semitic languages.

In The Storm-Gods of the Ancient Near East: Summary, Synthesis, Recent Studies, Daniel Schwemer argues for the prominence of storm gods in Upper Mesopotamia. Among the Hurrians, the major storm god had the name, Teub. [Variations on spellings include: Teshub which is also written as Teshup,Teup, orTeup] Schwemer called Teub, the head of the Hurrian pantheon, a divine king.

Chamber A, main scene depicting (left to right) the God Kumarbi (chief god of the Hurrians), the weather and storm god Teshuba, the earth goddess Hepat, Sharumma (son of Teshuba & Hepat) and Alanzu (daughter of Teshup Hepat), Yazlkay in Hittite capital city of Hattusa, Image credit: Carole Raddato, FRANKFURT, Germany CC BY-SA 2.0

The main, barely-surviving Hurrian myth involves generational conflict. It only survives in fragments, mostly written in Hittite. The sky god, Anu, deposes his father, the primeval god, Alahu.

Kumarbi, of the same generation as Anu, then fights Anu and overthrows him. In that fight, Kumarbi bites off (and maybe eats) Anus genitals. That act of castration and absorption brings the divine line into the usurper, Kumarbi.

Anu, apparently still male, gives birth to a new generation of gods, including Tessub. His children, including Tessub, defeat Anu. Tessub becomes the new King of the Gods. Kumarbi returns and makes an alliance with the sea and underworld gods. Tessub eventually defeats that alliance.

This mythic complex has obvious parallels with the Uranus-Cronus-Zeus cycle. Modern Pagans may choose to view this myth cycle through a genderqueer lens. Scholars have studied its fragmentary sources, however, through a reconstructed language. A certain humility is in order. Some things are forever lost in the past, and we may never know.

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Mitanni City emerges from the Mosul Reservoir - Middle East, News, Paganism, Science, US, Uncovering the Past, World - The Wild Hunt

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Mice receiving a gene for a telomere-building enzyme have had their lifespan extended by 41%. Treatment with another gene, this time for follistatin (FST), extended their lives by 36%. Both treatments significantly boosted glucose tolerance, physical performance and stalled body mass decline and fur loss.

The life extension came as a surprise to the researchers. We wanted to see what the effects were [of the gene therapy], explains Hua Zhu at Rutgers New Jersey Medical School. In the meantime, we saw that the [24] control mice died, whereas all [36]experimental mice were still alive, so the treatment clearly was significantly increasing the lifespan of the mice.

Telomeres are repetitive DNA sequences that cap chromosomes and tend to shorten with ageing. Efforts to extend the healthy lifespan of people is an active area of research, and features a range of techniques such as caloric restriction and small molecules that target metabolic pathways linked to ageing.

The researchers delivered the gene for telomerase reverse transcriptase, which activates and encourages telomere lengthening, and FST, a secretory protein with an important role in muscle development and maintenance, using a herpes virus.

Monthly treatment began in mice aged 18 months. After two months, the treated mice looked stronger and had shinier, healthier fur than controls, which started to lose their fur and suffered declining body weight, notes Zhu. Injections were repeated monthly to sustain high levels of the protein. All mice in control groups died by 29 months, while the mice in the experimental groups died between 38 and 42 months.

Liz Parrish, chief executive of the biotech firm BioViva that provided funding for the research, notes that the next step will be to test the safety and efficacy of the gene therapy in monkeys using weakened strains of a rhesus virus. Based on the result of the monkey studies, we will submit our report to the [US Food and Drug Administration] to give us permission to start clinical trials in humans, she explains.

There are major hurdles for anyone wishing to treat ageing with a gene therapy approach, says Ilaria Bellantuono, a professor of muscular ageing at the University of Sheffield, UK. We find difficulties proposing a drug approach, which is far less expensive and risky, so a gene therapy approach would encounter [a] higher level of resistance.

Bellantuono says that it is still hard for any treatment for ageing to compete with diet and exercise. Therefore, the best approach would be to target an age-related condition such as muscle loss or dementia, she says. This would require a clinical trial to test whether the intervention prevents such conditions.

A preventive trial is very complex. You need to give the treatment. Then wait for the disease to manifest, says Bellantuono. You would need biomarkers, which would tell us within three to six months whether an intervention gene therapy or drug is working.

Peter Lansdorp, a molecular biologist at the University of British Columbia in Canada, notes that ageing is multi-factorial and it seems unlikely that a single protein could have such a large impact on lifespan. He notes also that side effects from repeated activation of the immune system by viral vector infection are of concern in humans, but not so much in mice. First, possible effects of the transgene on viral virulence need to be excluded, Lansdorp says. Next this study needs to be reproduced in mice by other, independent groups.

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Gene therapy showcases technique to extend life in mice - Chemistry World

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Space junk sounds like a cyberpunk problem but is very much a real-world issue today. A couple of months ago, the European Space Agency had to take emergency debris collision avoidance action for its Sentinel-1A satellite, part of the Copernicus radar observatory program.

Japanese space technology company Astroscale is working to solve the problem of orbital space objects in conjunction with Ansys Government Initiatives (AGI). We spoke with Cody Short, AGIs principal astrodynamicist, to learn more about this space safety project.

According to NASA, there are more than 27,000 pieces of space debris being tracked, but that is only a small amount of what is really out there. Space debris orbits around the Earth at about 15,700 mph in low Earth orbit. It could cause significant damage to a satellite or a spacecraft in case of a collision.

Some measures have been taken to attempt to resolve the issue, including coating for satellites, but a coordinated approach is needed and fast.

According to Short,

Space is big, but particular orbital slots, especially those of high value, are crowded and becoming increasingly so. As a result, satellite operators must burn expensive fuel meant to sustain the delivery of services and profits to instead move their satellites to safer or more advantageous orbits. Up until now, the way we have operated in space has been bad for the space environment, and bad for space business. But its on this unsustainable foundation that we are trying to build a trillion-dollar space economy.

Astroscale and Ansys are working together to increase space safety and solve the problem of space debris. Their collaboration includes improving situational awareness, enabling life extension and other on-orbit servicing, and offering end-of-life options with active debris removal. The project is called ELSA (The End-of-Life Services by Astroscale).

Short explains:

By focusing on developing the technologies, informing the international policies, and building the economics for orbital sustainability, Astroscale is reorienting governments and businesses long-term decisions. In the end, it is building a sustainable space infrastructure in the process.

Astroscale is taking two key approaches to the space debris problem.

The first approach is about mitigation and preparation. The idea is to stack a common docking plate so that servicer satellites can remove them at the end of their useful life or in the event of a launch failure.

The second approach is to coordinate removals, in partnership with national governments and space agencies. The idea is to find and target larger pieces of debris that pose some of the highest risks. This might include upper-stage rocket bodies, for example.

A great part of this work depends on a digital mission engineering application, Ansys Systems Tool Kit, or STK, by engineering company Ansys. According to Short, this digital tool is

an indispensable digital mission engineering application for the aerospace, defense, telecommunications, and other industries. It features an accurate, physics-based modeling environment to analyze platforms and payloads in a realistic mission context.

Short adds that Ansys Systems Tool Kit enables the simulation of

multidomain scenarios that extend simulation beyond systems to an interactive model of the operational environment.

Fundamentally, this means that four-dimensional three-dimensional, plus time models can be built up to include terrain, imagery, RF environments, and other elements of the environment.

Short told us more about this digital mission:

STK extends digital engineering to the mission the operational environment in which your systems and systems of systems must succeed. While it feels like something that comes at the end of your projects life cycle once your system is designed its more than that. Digital mission engineering should be applied early and often, from design through development, test, operations, and sustainment. Uncover problems sooner rather than later and youll have a design that excels against your adversaries, ready to deploy far quicker than your competition.

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Space Safety: How to Solve the Problem of Orbital Debris? - DirectIndustry News - DirectIndustry e-Magazine

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MSM IS FOCUSED ON TURNAROUND PLAN AMIDST THE

RISING MAIN PRODUCTION COST

KUALA LUMPUR, JUNE 8, 2022 - MSM Malaysia Holdings Berhad (MSM) remains focused on sustaining its turnaround plan amidst the rising main production cost elements namely raw sugar, freight, natural gas and foreign exchange. The producer of the national refined sugar brand "Gula Prai" has turnaround with improved financial performance since 2020 despite market challenges.

Relatively, MSM recorded an improved profit before tax (PBT) of RM81 million for FY2021, against RM36 million in FY2020. The Group also recorded 3% increase in revenue of RM2.26 billion for 12 months FY2021 compared to RM2.18 billion in the last financial year. During FY2021, gain from disposal of MSM Perlis Sdn Bhd amounting to RM91.8 million has contributed to the Group recording a total consolidated PBT of RM170 million.

Within a continually challenging environment, MSM key focus for 2021 was on the execution of the turnaround plan through reorganisation and asset optimisation, staying resilient with strengthened income streams and building integration for sustainable performance.

"For financial year 2021 (FY2021), MSM recorded a revenue of RM2.3 billion with a profit before tax (PBT) of RM81 million on the back of total assets of RM2.87 billion. This is an encouraging improvement from 2020 despite challenges faced throughout the year. MSM also has returned to a dividend-paying stock where we declared a dividend of 3 sen per share for FY2021," said MSM Group Chief Executive Officer, Syed Feizal Syed Mohammad during the 11th Annual General Meeting that was held virtually today attended by 1,057 shareholders online.

MSM produced close to 900,000 tonnes of refined sugar that is sold under "Gula Prai" brand amidst slower domestic and competitive international markets in 2021 due to the COVID-19 pandemic and the movement control order. MSM was challenged by many different factors in 2021 but appropriate mitigation measures were taken to address them.

MSM has a dynamic 3-year strategic blueprint with 2021 being Turnaround, 2022 Resilient and 2023 Integration. MSM Johor remains a key focus of MSM Group on the ramp-up programme and achieving profitability while MSM Prai will be undergoing a rejuvenation process with a 30-year life extension in sweating the assets.

"We will work to increase our domestic market share while opening up new market channels through Last Mile general trades, HORECA and small SKU packaging suited for convenient chains. MSM shall continue to gain greater market share within Asia Pacific and penetrate Singapore retail segment viewed from a domestic lens and logistics strategy. We shall also increase more volumes of value-added products such as liquid sugar and premix which has higher margins and great demand in markets like China. As part of strengthening Johor, MSM remains open to have a right fit partner with strong export market and operational experience," Syed Feizal said.

As for financial year 2022 (FY2022), MSM foresees greater challenges with rising main production cost. For first quarter (1Q) FY2022, MSM posted an expected loss after tax (LAT) of RM28 million as compared to profit after tax (PAT) of RM31 million for 1Q2021. This was largely due to higher production cost largely 29% higher NY11, 57% increase in freight cost and weaker Ringgit. The Group's refining cost also recorded an increase of 28%, largely driven by 86% increase in gas cost. In response to cost pressures, MSM as a joint industry has engaged the government on the need to revise the controlled ceiling prices for the retail segment. The sugar refining price has had a net increase of only 1 sen/kg since 2011.

"We strived to reinforce our brand positioning, stayed on track for current and long-term targets maximising our capabilities through market expansion and greater outreach. Critically, we continued to strengthen our balance sheet and enhanced liquidity. MSM has a healthy gearing ratio of 26% in FY2021 versus 33% in FY2020. In initiatives, we stepped-up with acceleration our ESG journey and kicked-off digitalisation towards IR 4.0 during the year," Syed Feizal added.

Moving forward, MSM will further exploring strategic partnership to strengthen export segment and to further unlock synergistic value in 2022 in ensuring consistent returns and greater shareholder value as the nation's leading premium sugar refiner.

-ENDS-

2

About MSM Malaysia Holdings Berhad (MSM)

MSM Malaysia Holdings Berhad (MSM) is Malaysia's leading refined sugar producer and one of the biggest sugar refiners in Asia. MSM is involved in producing, marketing and selling refined sugar products under the "Gula Prai" brand. The company conducts its business principally through two operating subsidiaries, MSM Prai Berhad and MSM Sugar Refinery (Johor) Sdn Bhd. In addition, MSM also operates a logistics company - MSM Logistics Sdn Bhd.

At present, MSM's annual production capacity is up to 2.05 million tonnes of refined sugar. In 2021, MSM produced 895,222 tonnes of refined sugar, of which 246,101 tonnes are catered for the export market. Currently, MSM corroborates up to 60% of the domestic market share. MSM has been listed on the Main Market of Bursa Malaysia since 2011 and has a market capitalisation of RM900 million as at 31 December 2021. MSM combines economic success with environmental protection and social responsibility for a sustainable future.

MSM offers a variety of products ranging from white refined sugar of various grain sizes to soft brown sugar. These are marketed and sold in a variety of packaging options under its flagship brand - Gula Prai. MSM also sells molasses, a by-product of the refining process, to distilleries and producers of ethanol, animal feed and yeast, among other products. Aside from household consumers, MSM sells to a wide range of customers in Malaysia and in other countries directly and indirectly through traders, wholesalers and distributors. Its customers include major companies in the beverage and confectionery industries, hotels, restaurants and food outlets.

For more information, please visit http://www.msmsugar.com

Forward Looking Statements

Certain statements in this media release regarding MSM's operations may constitute forward-looking statements. These statements can be identified by key words such as "believes", "estimates", "anticipates", "expects", "intends", "may", "will", "plans", "outlook" and other words of similar meaning in connection with a discussion of future operating or financial performance. These statements relate to the plans, objectives, goals, strategies, future operations and performance of MSM. Actual results and outcomes may differ materially from those projected in any forward-looking statements due to various events, risks, uncertainties and other factors. We neither intend to nor assume any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

For media enquiries, please contact:

Siti Noorbaya Mohd Yunus

Syahidah Ismail

+603 2181 5018 ext. 158

+603 2181 5018 ext. 154

+6016 677 6118

+6019 225 9705

noorbaya.my@msmsugar.com

syahidah.i@msmsugar.com

3

Disclaimer

MSM Malaysia Holdings Bhd published this content on 08 June 2022 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 08 June 2022 08:31:07 UTC.

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MSM Malaysia Berhad : IS FOCUSED ON TURNAROUND PLAN AMIDST THE RISING MAIN PRODUCTION COST - Marketscreener.com

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Anti-submarine warfare capability, or ASW, is one of the U.S. Navys top priorities. After all, adversary submarines such as the Russian Typhoon class and Red Chinas Type-093A Shang-II Class pose arguably the deadliest threat to American carriers. To counter the threat of silent submersible stalkers, the Navy continues to use an aerial platform that has served faithfully for over 50 years: the Lockheed Martin P-3 Orion.

Still Going Strong

Though the P-3 Orion is slowly but surely being replaced by the Boeing P-8 Poseidon for ASW work, the transition is far from complete. The older Orion unlike other famous Cold War-era Navy warplanes such as the F-14 Tomcat, A-6 Intruder, and A-7 Corsair IIhas definitely not been retired yet. The P-3 is currently being used by two Navy Reserve patrol squadrons, VP-62 and VP-69. It also lives on as a land-based multi-intelligence reconnaissance variant, the EP-3E Aries II.

And thats without even counting the 16 foreign countries that still fly the Orion.

The P-3 was based on a commercial airliner, the Lockheed L-188 Electra, that was first flown in 1957. This is somewhat akin to how the E-3 Sentry AWACS plane was based on the commercial Boeing 707. The militarized Orion variant made her maiden flight in November 1959 and officially entered service in August 1962a mere two months before the Cuban Missile Crisis. Thus, in 2012, the P-3 joined the pantheon of military aircraft that the U.S. has used for 50-plus years, joining the B-52, the KC-135, the C-130, and the U-2.

The keydistinguishing feature of the P-3 that you wont see on the civilian L-188 is the Magnetic Anomaly Detection boom at the tail end of the fuselage. This feature makes the P-3s submarine-hunting mission feasible in the first place. Needless to say, the Cold War never went hot, so the Orion never got to put its sub-killing potential to the test in the real world. But that doesnt mean the Orion didnt get battle-tested.

P-3 Orions over Afghanistan, Iraq, and the Balkans

Indeed, it was during 2002s Operation Anaconda in Afghanistan that the P-3 pulled off what is arguably its most remarkable wartime feat. As noted by the official Lockheed Martin website, During a key battle in the Shah-e-Kot Valley, P-3 crews scouted the rugged valleys below and radioed in movement of enemy vehicles, allowing Special Operations Forces soldiers on the ground to set up strategic ambushes and save countless lives. Not bad for a fifty-year-old sea-searching aircraft design on duty in the middle of the desert.

Rewind 11 years to 1991s Operation Desert Storm: It was here that the P-3 first showed its potential as a land surveillance aircraft, monitoring Iraqi troop activities and providing battle-damage assessments on the ground. The introduction of new long-range video cameras for use over the skies of Bosnia allowed these planes to provide real-time combat intelligence for NATO commanders, a tactical advantage that proved equally useful during Operation Deliberate Force in 1995.

The P-3 Orion: A Versatile Plane

One characteristic shared by all the planes that have reached a half-century of service is versatility, and the P-3 Orion is no exception in this regard. Beside the military applications weve already covered, this old warbird has also proven adaptable for civilian law enforcement, namely anti-narcotics smuggling and anti-illegal immigration missions. It is flown by the intrepid aircrews of the Air and Marine Operations component of one of my former employers, the U.S. Customs & Border Protection. The CBP dubs its P-3 variant the Long Range Tracker.

Like its fellow 50-somethings, the P-3 hasnt failed to keep up with technological advances. To quote the Lockheed Martin folks one more time, The P-3 MLU [Mid-Liffe Upgrade] Program is the answer to maintaining effectiveness and reliability in a critical global economy. It consists of a life extension kit replacing the aircraft outer wings, center wing lower section and horizontal stabilizer with new production components.

MLU removes all current P-3 airframe flight restrictions and provides 15,000 additional flight hours, greatly enhancing capability leveraged with cost-effectiveness. The design replaces all fatigue-life-limiting structures on the aircraft with enhanced-design components and new improved corrosion-resistant materials that will greatly reduce the cost of ownership over the aircrafts remaining service life. This is an affordable solution that Lockheed Martin has proven can be installed in 11 months.

Specifications/General Characteristics

Primary Function:Anti-Submarine warfare and Anti-Surface Warfare

Contractor:Lockheed Martin Aeronautical Systems Company

Propulsion:Four Allison T-56-A-14 turboprop engines (4,600 hp each)

Length:116.7 feet (35.57 meters)

Height:33.7 feet (10.27 meters)

Wingspan:99.6 feet (30.38 meters)

Weight:Maximum takeoff, 139,760 pounds (63,394 kilograms)

Airspeed:411 knots; Cruise, 328 knots

Ceiling:28,300 feet (8,626 meters)

Range:2,380 nautical mile radius; for three hours on station at 1,500 feet, 1,346 nautical miles

Crew:Three pilots, two naval flight officers (NFOs), two flight engineers, three sensor operators and one in-flight technician

Armament:AGM-84 Harpoon, AGM-84K SLAM-ER, AGM-65F Maverick missiles, Mk46/50/54 torpedoes, rockets, mines and depth bombs

Christian D. Orr is a former Air Force officer, Federal law enforcement officer, and private military contractor (with assignments worked in Iraq, the United Arab Emirates, Kosovo, Japan, Germany, and the Pentagon). Chris holds a B.A. in International Relations from the University of Southern California (USC) and an M.A. in Intelligence Studies (concentration in Terrorism Studies) from American Military University (AMU). He has also been published in The Daily Torch and The Journal of Intelligence and Cyber Security.

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P-3 Orion: The Plane Built to Hunt and Kill Russia's Submarines - 19FortyFive

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USS Vicksburg, a Ticonderoga-class guided-missile cruiser, passes through the Strait of Gibraltar on March 31, 2015. The House Armed Services Committees subpanel on seapower and projection forces plans to prohibit the Navy from cutting the Vicksburg as well as four landing dock ships from its fleet, according to committee aides. (Anthony Hilkowski/U.S. Navy)

WASHINGTON House lawmakers will push to save five ships that the Navy is slating for retirement, rejecting the service branchs proposal to decommission 24 ships in its fiscal 2023 budget.

The House Armed Services Committees subpanel on seapower and projection forces plans to prohibit the Navy from cutting the cruiser USS Vicksburg as well as four landing dock ships from its fleet, according to committee aides. Lawmakers will recommend the changes to the full House committee this week as it drafts the National Defense Authorization Act, an annual sweeping military policy and funding bill.

Theres consensus that USS Vicksburg should be retained, an aide said, speaking on condition of anonymity. With respect to [landing dock ships], theres strong support for the commandant of the Marine Corps assessment that he needs no fewer than 31 amphibious ships so prohibiting the retirement of the [landing dock ships] certainly gets after that.

The USS Vicksburg, a Ticonderoga-class guided missile cruiser that launched in 1991, is nearing the end of a nearly $500 million modernization overhaul in Virginia that began in 2020. Rep. Kay Granger, the ranking Republican of the House Appropriations Committee, admonished Navy officials at a hearing last month for seeking to decommission the cruiser.

At a time when the ship is still in its maintenance period, the Navy is proposing to scrap it, the Texas congresswoman said. If the Navy experts expect Congress to support its vision for this fleet, it must do a much better job of managing the inventory it has. We will not stand idly by as valuable taxpayer funds are wasted.

Other cruisers on the Navys chopping block include USS Bunker Hill, USS Mobile Bay, USS San Jacinto and USS Lake Champlain.

Retirements are also planned for two Los Angeles-class submarines, two oilers, two expeditionary transfer docks and all nine of the Navys Freedom-class littoral combat ships, some of which have been in service less than five years. One of the four landing dock ships that lawmakers are hoping to keep the Whidbey Island-class USS Tortuga is undergoing the same service-life extension repairs as the USS Vicksburg.

Navy officials said decommissioning will save about $3.6 billion in the next five years, allowing the Navy to get rid of aging ships and systems that are expensive to maintain and instead invest in unmanned platforms and other technology. The divest to invest strategy has repeatedly frustrated lawmakers who are warily eyeing Chinas rapidly growing fleet.

Congress last year reversed the Navys plan to retire seven cruisers, forcing the service to hang on to two, and ordered the Navy to build 13 ships instead of a requested eight. Next years proposed $180 billion Navy budget also calls for building eight ships a plan that Rep. Elaine Luria, a retired Navy commander, described as anemic.

The Navy has no strategy, Luria, D-Va., tweeted in March. Stop saying you do, because if you did you would be able to explain how this fleet size will allow us to defend Taiwan.

Rep. Rob Wittman, the ranking Republican on the seapower subcommittee, noted last month that the Navy is congressionally mandated to have 355 ships. The Navys proposed cuts would immediately shrink the current 298-ship fleet to 285 ships, he said.

We dont expand our naval capacity and capabilities by subtracting more than we add, the Virginia congressman said. The budget request definitely does not support [Defense] Secretary [Lloyd] Austins stated intent of pacing the Chinese naval capabilities whose force is expected to exceed 460 ships by the turn of this decade, at which point our fleet will be only two-thirds the size of the Peoples Liberation Army Navy.

Despite the criticism, the subcommittee will recommend sticking to the Navys shipbuilding plan, committee aides said. The Navy is aiming to acquire two Virginia-class attack submarines, two Arleigh Burke-class destroyers, one frigate, one amphibious transport dock, one oiler and one towing, salvage and rescue ship.

House lawmakers will also seek to set a statutory floor of 31 amphibious ships and require the Navy secretary to consult with the Marine Corps commandant on all major decisions concerning amphibious force structure and capability, committee aides said.

Other recommendations by the subcommittee include allowing the Air Force to retire eight of its C-130 transport aircraft and 13 of its air-refueling tanker aircraft and authorizing the Navy secretary to enter into procurement contracts for up to 15 guided-missile destroyers and up to 25 Ship-to-Shore connector crafts, according to aides.

The House Armed Services Committee will announce parts of its legislative agenda for the 2023 NDAA during six subcommittee markups this week, with a full committee markup scheduled for June 22. The Senate Armed Services Committee will begin unveiling its version of the bill next week.

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House panel aims to save five ships from retirement, rejecting Navy's plan to decommission them - Stars and Stripes

Recommendation and review posted by Bethany Smith

When the MiG-25 Foxbat entered service with the Soviet Union in 1970, it gave NATO airpower planners plenty to worry about. The Foxbat was the fastest interceptor in the world at the time, and the ever-pervasive fear of the unknown flew alongside it. However, much of that fear dissipated after the defection of MiG-25 pilot Lt. Viktor Belenko in 1976. Belenko helped to eliminate the aura of mystery that had surrounded this high-speed aircraft.

But the Soviet war machine didnt let Belenkos defection deter them from improving on the concept. Thus the MiG-31 Foxhound was born.

From Foxbat to Foxhound

The Foxhound made her maiden flight in September 1975 and officially entered into service with the Soviet PVO (voyska protivovozdushnoy oborony, or Anti-Air Defense Troops) in 1981.

The MiG-31 bears a striking cosmetic resemblance to the MiG-25, which probably explains at least in part why NATO retained the Fox portion when assigning its codename to the successor aircraft. However, look beneath the surface and you will find the Foxhound equipped with state-of-the-art digital avionics that its older foxy sibling lacked.

For one thing, the MiG-31 was the first Soviet fighter aircraft to have true look-down/shoot-down capability, thanks to its phased array radar. Earlier USSR fighter radars had a tendency to run afoul of ground clutter. In addition, the Foxhound can work efficiently in all weather conditions while fulfilling visual flight rules and instrument flight rules, day and night.

Yet another improvement was the newer planes extended range, which increased to 1,900 miles (3,000 kilometers) upon initial takeoff, and further bolstered to 3,400 miles (5,400 kilometers) with one aerial refueling. By contrast, the gas-guzzling Foxbat bore the curse of a relatively short range: 1,160 miles (1,860 kilometers) at Mach 0.9 and 1,013 miles (1,630 kilometers) when zipping along at Mach 2.35. This underscored how lucky the aforementioned Belenko was to make his initial escape from Vladivostok to Hokkaido, Japan. (In retrospect, perhaps NATO shouldve codenamed the MiG-25 the Cheetah. It can pursue its prey at tremendous speeds, but only for short distances.)

The Foxhounds pilots also enjoyed a reduced likelihood of failure to communicate. As my 1945 colleague Caleb Larson explains,MiG-31s can network with other airplanes in their sortie, relaying information on enemy aircraft locations and thus covering a much wider area than unnetworked groups of airplanes.

Foxhound Flies On

Five hundred and nineteen Foxhounds have been produced so far, out of which 370 were delivered to the Russian Air Force and 30 are in service with Kazakh air force. In July 2020, Russias Defense Ministry announced its intention to invest in modernization and life extension programs for its MiG-31 fleet.

MiG-31 customers outside of the former Soviet republics have been few and far between. In 1992, right on the heels of the collapse of the Soviet Union, the cash-starved post-Soviet Russian arms industry offered the Mig-31 to Finland, but the Finns turned it down. Meanwhile, Syria ordered eight MiG-31E airframes for its own air force in 2007, but the order was suspended in May 2007. Six of these MiGs may or not have been delivered to Syria as of August 2015, depending on whether you choose to believe the Turkish or the Russian media.

What is not in dispute is that the Russians themselves have deployed the MiG-31 in missions over Syria. In addition, the Foxhound has been blooded in Vladimir Putins so-called special military operation in Ukraine. On March 18, a MiG-31K variant launched a strike on a Ukrainian arms depot near the Polish border, evidently using a Kh-47M2 Kinzhal hypersonic missile. In turn, on April 26, the Ukrainians managed to shoot down a Foxhound with a British-made Starstreak missile.

Specifications

General Characteristics

Crew: Two (pilot and weapons system officer)

Length: 22.69 m (74 ft 5 in)

Wingspan: 13.46 m (44 ft 2 in)

Height: 6.15 m (20 ft 2 in)

Wing area: 61.6 m (663 ft)

Empty weight: 21,820 kg (48,100 lb)

Armament

1 GSh-6-23 23 mm cannon with 260 rounds.

Fuselage recesses for 4 R-33 (AA-9 Amos) (or for MiG-31M/BM only 6 R-37 (AA-X-13 Arrow) long-range air-to-air missiles)

4 underwing pylons for a combination of:

Christian D. Orr is a former Air Force officer, Federal law enforcement officer, and private military contractor (with assignments worked in Iraq, the United Arab Emirates, Kosovo, Japan, Germany, and the Pentagon). Chris holds a B.A. in International Relations from the University of Southern California (USC) and an M.A. in Intelligence Studies (concentration in Terrorism Studies) from American Military University (AMU). He has also been published in The Daily Torch and The Journal of Intelligence and Cyber Security.

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MiG-31 Foxhound Is One Really Fast Russian Jet - 19FortyFive

Recommendation and review posted by Bethany Smith

The National Aerospace Laboratories (NAL) in Bengaluru on Sunday marked 55 years of the 1.2mm trisonic wind tunnel, the only industrial wind tunnel providing the high-speed aerodynamic data for national aerospace programmes, both in the civil and military sectors.

Wind tunnels are used for simulating flight conditions in the laboratory. The NAL stated that the facility will continue to meet the experimental aerodynamic data requirement of future programmes.

Council of Scientific and Industrial Research (CSIR)-NAL is currently working towards setting up a continuous wind tunnel facility to meet the increased demand for high speed experimental aerodynamic data. Practically each and every indigenously developed aerospace vehicle in the country has graduated out of this facility. To cater to the emerging requirements of the country, continual upgrades of the facility have been implemented in CSIR-NAL, leading to many state-of-the-art techniques related to high-speed wind tunnel testing mainly to improve the data quality, productivity and life extension of various components of the wind tunnel, a statement from CSIR-NAL read.

The 1.2m trisonic wind tunnel was built by the CSIR between 1963 and 1967. The first blow-down (test) was conducted on May 29, 1967. The vision of the late Dr P Neelakantan, the first Director of CSIR-NAL, enabled the realisation of this facility, which is the major workhorse for all the national aerospace programmes. The highest speed of this tunnel is Mach 4.0 which is four times the speed of sound, the release said.

The mission of this facility is to provide advanced technology solutions to national aerospace programs, fighter aircraft, defence systems, launch vehicles and satellites and space systems.

This wind tunnel was primarily conceived for research and development in experimental aerodynamics. Subsequently, as the Indian Space Research Organization (ISRO) and Defence Research and Development Organization (DRDO) started the development of launch vehicles, missiles and aircraft, the need for high-speed wind tunnel tests in the 1.2m wind tunnel increased. To name a few, DRDOs missiles such as Agni, Akaash, Prithvi, Pralay, SRSAM, LRSAM, ASTRA, NAG, LRAShM, BrahMos, Nirbhay, Unmanned Aerial Vehicles, etc. were characterized in this facility.

Similarly, aerodynamic characterisation of the ISROs launch vehicles such as ASLV, PSLV, SLV, SSLV, GSLV, RLV and GAGANYAAN programmes were carried out extensively. The nations first Light Combat Aircraft (LCA-TEJAS) was conceived at this facility and now it is flying in the sky. Many weapon integration programmes on LCA, Mirage-2000, Sukhoi-30, Jaguar, MiG aircraft etc., were successfully carried out in this facility.

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Bengaluru: NAL marks 55 years of 1.2m trisonic wind tunnel - The Indian Express

Recommendation and review posted by Bethany Smith

Dive Brief:

Though small in scope, Immatics and Editas deal adds to a flurry of recent activity involving treatments that harness gamma delta T cells, rare white blood cells with unique tumor-fighting capabilities.

Unlike the T cells used in Novartis, Gilead and Bristol Myers Squibbs treatments, gamma delta cells have elements of both innate and adaptive immunity, which could enable them to generate a broader response against cancers. These cells also have key differences that make them less likely to trigger graft-versus-host disease, give them the potential to persist in the body for years, and to recognize a range of targets.

Those traits have already prompted drugmakers including Takeda, Johnson & Johnson, Bristol Myers and Regeneron to make investments. Clinical data presented at the American Society of Clinical Oncology has further elevated the profile of gamma delta cell therapy, as a treatment from Adicet Bio has shown early promise against non-Hodgkins lymphoma.

Immatics has already capitalized on the momentum, turning its alliance with Bristol Myers into a new, lucrative deal. Now Immatics is bringing gene editing tools in as well.

Genetic engineering is already part of many cell therapies, as CAR-T treatments involve modifications that help T cells recognize cancer. But CRISPR and other gene editing approaches could help do more. Allogene Therapeutics, for example, uses gene editing to make changes aimed at reducing the risk of graft-versus-host disease. Nkarta and CRISPR Therapeutics plan to give treatments involving natural killer cells, which share some similarities with gamma delta T cells, more tumor-killing punch.

Immatics and Editas appear to share a similar goal, saying in a statement that they want to make gamma delta cells with enhanced tumor recognition and destruction. Those potential benefits do come with added risk, however. U.S. regulators halted testing of Allogenes programs last year to investigate whether the gene editing involved in its treatment led to a chromosomal abnormality in a treated patient. Follow-up investigation exonerated Allogenes treatment, but the setback led to a lengthy delay.

For Editas, the deal adds to multiple other partnerships involving cell therapy. The company is already working with Bayer's Bluerock Therapeutics subsidiary on natural killer cell therapies for solid tumors, and with Bristol Myers on so-called alpha-beta T cell treatments.

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Immatics and Editas join up to bring CRISPR to 'gamma delta' cell therapy - BioPharma Dive

Recommendation and review posted by Bethany Smith

CRISPR Therapeutics (NASDAQ:CRSP Get Rating) and Inhibrx (NASDAQ:INBX Get Rating) are both medical companies, but which is the superior business? We will compare the two companies based on the strength of their valuation, earnings, dividends, institutional ownership, profitability, analyst recommendations and risk.

Earnings and Valuation

This table compares CRISPR Therapeutics and Inhibrxs revenue, earnings per share and valuation.

Profitability

This table compares CRISPR Therapeutics and Inhibrxs net margins, return on equity and return on assets.

Analyst Recommendations

This is a summary of recent ratings and recommmendations for CRISPR Therapeutics and Inhibrx, as reported by MarketBeat.

CRISPR Therapeutics presently has a consensus price target of $114.71, indicating a potential upside of 70.25%. Inhibrx has a consensus price target of $44.33, indicating a potential upside of 291.64%. Given Inhibrxs stronger consensus rating and higher possible upside, analysts plainly believe Inhibrx is more favorable than CRISPR Therapeutics.

Insider & Institutional Ownership

56.1% of CRISPR Therapeutics shares are owned by institutional investors. Comparatively, 59.6% of Inhibrx shares are owned by institutional investors. 10.7% of CRISPR Therapeutics shares are owned by company insiders. Comparatively, 25.8% of Inhibrx shares are owned by company insiders. Strong institutional ownership is an indication that large money managers, endowments and hedge funds believe a stock will outperform the market over the long term.

Volatility & Risk

CRISPR Therapeutics has a beta of 2.04, suggesting that its stock price is 104% more volatile than the S&P 500. Comparatively, Inhibrx has a beta of 3.1, suggesting that its stock price is 210% more volatile than the S&P 500.

Summary

CRISPR Therapeutics beats Inhibrx on 8 of the 14 factors compared between the two stocks.

About CRISPR Therapeutics (Get Rating)

CRISPR Therapeutics is a gene-editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene-editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

About Inhibrx (Get Rating)

Inhibrx, Inc., a clinical-stage biotechnology company, focuses on developing a pipeline of novel biologic therapeutic candidates. The company's therapeutic candidates include INBRX-109, a tetravalent agonist of death receptor 5, which is in Phase 2 clinical trials to treat cancers, such as chondrosarcoma, mesothelioma, and pancreatic adenocarcinoma; INBRX-105, a tetravalent conditional agonist of programmed death-ligand 1 and a conditional agonist of 4-1BB that is in Phase 1 clinical trials to treat patients with locally advanced or metastatic solid tumors; and INBRX-101, an alpha-1 antitrypsin (AAT)-Fc fusion protein therapeutic candidate, which is in Phase 1 clinical trials for use in the treatment of patients with AAT deficiency. It also provides INBRX-106, a hexavalent agonist of OX40 for a range of oncology indications. The company was founded in 2010 and is headquartered in La Jolla, California.

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Analyzing CRISPR Therapeutics (NASDAQ:CRSP) and Inhibrx (NASDAQ:INBX) - Defense World

Recommendation and review posted by Bethany Smith

- Vertex announces three additional abstracts on the burden of beta thalassemia and sickle cell disease accepted for poster presentation

BOSTON & ZUG, Switzerland & CAMBRIDGE, Mass., June 02, 2022--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and CRISPR Therapeutics (NASDAQ: CRSP) today announced new late-breaking clinical data accepted for oral presentation at the 2022 European Hematology Association (EHA) Congress. Vertex also announced three abstracts accepted for poster presentation at EHA.

Late-breaking abstract #LB2367 entitled "Efficacy and Safety of A Single Dose of CTX001 For Transfusion-Dependent eta-Thalassemia and Severe Sickle Cell Disease," will be an oral presentation on Sunday, June 12 at 09:4511:15 CEST. The abstract from Vertex and CRISPR Therapeutics includes data on patients treated in CLIMB111 and CLIMB121 and followed in CLIMB131 with CTX001, now known as exagamglogene autotemcel (exa-cel). This abstract has been selected for the media briefing program and is therefore embargoed until Saturday, June 11 at 09:00 am CEST.

In addition, three real-world evidence and health economics abstracts from Vertex have been accepted for poster presentation.

Abstract #P1704 entitled "Projected Lifetime Economic Burden of Severe Sickle Cell Disease in the United States," will be a poster presentation on Friday, June 10 at 16:3017:45 CEST. The abstract posted online projects the per-patient lifetime direct health care cost of severe sickle cell disease (SCD) from a U.S. health care payer perspective using an economic model developed based on published model frameworks.

Abstract #P1703 entitled "Economic Burden of TransfusionDependent BetaThalassemia in the United States," will be a poster presentation on Friday, June 10 at 16:3017:45 CEST. The abstract posted online estimates the economic burden of transfusion-dependent beta thalassemia (TDT) using administrative claims data to estimate the costs and health care utilization associated with disease management in the U.S.

Abstract #P1482 entitled "Patients With Severe Sickle Cell Disease on Standard-of-Care Treatment Are Very Unlikely to Become VOCFree for One Year: A Cohort Study of Medicaid Enrollees," will be a poster presentation on Friday, June 10 at 16:3017:45 CEST. The abstract posted online contextualizes the efficacy of exacel in eliminating vasoocclusive crises (VOCs) in patients with SCD using nationwide U.S. Medicaid claims data from 2000 to 2014 to assess the proportion of patients with recurrent VOCs who became VOCfree during a 1year follow up on standard of care.

Story continues

The accepted abstracts are now available online on the EHA website.

Exacel is being investigated in multiple ongoing clinical trials as a potential one-time therapy for patients with either TDT or SCD.

About exagamglogene autotemcel (exa-cel)

Exacel, formerly known as CTX001, is an investigational, autologous, ex vivo CRISPR/Cas9 geneedited therapy that is being evaluated for patients with TDT or SCD characterized by recurrent VOCs, in which a patients own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygencarrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. The elevation of HbF by exacel has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, exacel has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. Exa-cel has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.

Among geneediting approaches being evaluated for TDT and SCD, exacel is the furthest advanced in clinical development.

About CLIMB111 and CLIMB121

The ongoing Phase 1/2/3 openlabel trials, CLIMB111 and CLIMB121, are designed to assess the safety and efficacy of a single dose of exacel in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after exacel infusion. Each patient will be asked to participate in CLIMB131, a longterm followup trial.

About CLIMB-131

This is a longterm, openlabel trial to evaluate the safety and efficacy of exacel in patients who received exacel in CLIMB111, CLIMB121, CLIMB141 or CLIMB151. The trial is designed to follow participants for up to 15 years after exacel infusion.

About CLIMB141 and CLIMB151

The ongoing Phase 3 open-label trials, CLIMB141 and CLIMB151, are designed to assess the safety and efficacy of a single dose of exacel in patients ages 2 to 11 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now open for enrollment and currently enrolling patients ages 5 to 11 years of age and will plan to extend to ages 2 to less than 5 years of age at a later date. Each trial will enroll up to 12 patients. Patients will be followed for approximately two years after infusion. Each patient will be asked to participate in CLIMB-131, a longterm followup trial.

About the GeneEditing Process in These Trials

Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patients cells will be edited using the CRISPR/Cas9 technology. The edited cells, exacel, will then be infused back into the patient as part of an autologous hematopoietic stem cell transplant (HSCT), a process which involves a patient being treated with myeloablative busulfan conditioning. Patients undergoing HSCT may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of exacel. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of exacel on multiple measures of disease and for safety.

About the VertexCRISPR Collaboration

Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. Exacel represents the first potential treatment to emerge from the joint research program. Under an amended collaboration agreement, Vertex now leads global development, manufacturing and commercialization of exacel and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule, cell and genetic therapies in other serious diseases where it has deep insight into causal human biology, including sickle cell disease, beta thalassemia, APOL1mediated kidney disease, pain, type 1 diabetes, alpha1 antitrypsin deficiency and Duchenne muscular dystrophy.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 12 consecutive years on Science magazine's Top Employers list and one of the 2021 Seramount (formerly Working Mother Media) 100 Best Companies. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

(VRTX-GEN)

Vertex Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, our plans and expectations to present clinical data from the ongoing exa-cel clinical trials during the EHA Congress, expectations regarding the abstracts that will be made available on the virtual platform and the clinical data that will be presented during the EHA Congress, including anticipated projections and estimates related to the various economic impacts of SCD and TDT, the potential benefits, efficacy, and safety of exa-cel, including the potentially transformative nature of the therapy and the potential of the treatment for patients, our plans and expectations for our clinical trials and pipeline products, the status of our clinical trials of our product candidates under development by us and our collaborators, including activities at the clinical trial sites, patient enrollment and expectations regarding clinical trial follow-up. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from a limited number of patients may not be indicative of final clinical trial results, that data from the company's development programs, including its programs with its collaborators, may not support registration or further development of its compounds due to safety and/or efficacy, or other reasons, that internal or external factors that could delay, divert, or change our plans and objectives with respect to our research and development programs, that future competitive or other market factors may adversely affect the commercial potential for exa-cel, and other risks listed under the heading "Risk Factors" in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission (SEC) and available through the company's website at http://www.vrtx.com and on the SECs website at http://www.sec.gov. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(CRSP-GEN)

About CRISPR Therapeutics

CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR Therapeutics Forward-Looking Statement

This press release may contain a number of "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, as well as statements regarding CRISPR Therapeutics expectations about any or all of the following: i) the safety, efficacy and clinical progress of the ongoing exa-cel clinical trials, including expectations regarding the abstract that will be made available on the virtual platform and our plans to present and the clinical data that are being presented during the EHA Congress; and (ii) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects" and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, existing and prospective investors are cautioned that forward-looking statements are inherently uncertain, are neither promises nor guarantees and not to place undue reliance on such statements, which speak only as of the date they are made. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: the potential for initial and preliminary data from any clinical trial and initial data from a limited number of patients (as is the case with exa-cel at this time) not to be indicative of final or future trial results; the potential that the exa-cel clinical trial results may not be favorable or may not support registration or further development; that future competitive or other market factors may adversely affect the commercial potential for exa-cel; CRISPR Therapeutics may not realize the potential benefits of its collaboration with Vertex; potential impacts due to the coronavirus pandemic, such as to the timing and progress of clinical trials; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology and intellectual property belonging to third parties; and those risks and uncertainties described under the heading "Risk Factors" in CRISPR Therapeutics most recent annual report on Form 10-K, quarterly report on Form 10-Q, and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at http://www.sec.gov. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220601006221/en/

Contacts

Vertex Pharmaceuticals Incorporated Investors: Michael Partridge, +1 617-341-6108OrManisha Pai, +1 617-961-1899OrMiroslava Minkova, +1 617-341-6135

Media: mediainfo@vrtx.com orU.S.: +1 617-341-6992orHeather Nichols: +1 617-839-3607orInternational: +44 20 3204 5275

CRISPR Therapeutics Investors: Susan Kim, +1 617-307-7503susan.kim@crisprtx.com

Media: Rachel Eides, +1-617-315-4493.rachel.eides@crisprtx.com

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Vertex and CRISPR Therapeutics Announce Acceptance of Late-Breaking Abstract for CTX001 at the 2022 Annual European Hematology Association (EHA)...

Recommendation and review posted by Bethany Smith