Archive for the ‘Male Genetics’ Category

If one good thing has come out of 2020, its been the call to action to identifyand actively work to changethe many areas in our society where systemic inequality is impacting peoples ability to live a truly well life. One such area? Inequality in medical research.

Medical research might make you think of petri dishes and mice in a laboratory, but its actually a lot more relevant to your daily life than thatand the numbers are staggering. Nearly 40 percent of Americans belong to a racial or ethnic minority group, yet clinical trials skew heavily white (up to 90 percent), says Vincent Nelson, MD, vice president of medical affairs and interim chief medical officer at the Blue Cross Blue Shield Association.

To be specific, these trials have predominantly focused on white people who are straight and male, which has left out huge chunks of the population such as women, LGBTQ+ people, racial and ethnic minority groups, and people from low-income and/or rural communities, Dr. Nelson says.

Nearly 40 percent of Americans belong to a racial or ethnic minority group, yet clinical trials skew heavily white (up to 90 percent).

This lack of diversity is important because medical treatments may affect people of different groups differently, he explains, so in order to prescribe treatments and medications that will actually help, medical professionals need to have the right information.

Diversifying medical research can help reduce health inequities by answering questions such as why Black women are suffering from higher maternal mortality rates or why stroke is more common among rural communities, Dr. Nelson says. In order to answer these questions, researchers and the medical community need to have access to data that is truly representative of our diverse country.

So how do we fix this data diversity issue? The All of Us Research Program (which is managed by the National Institutes of Health) has been working on it since 2018, when All of Us set out to become the largest and most diverse research program ever. By partnering with volunteers who share their health info, All of Us is creating a massive data hub that gives researchers access to information thats actually reflective of the U.S. population.

By the numbers, the program already has over 360,000 participants (more than 50 percent of whom are people of color, and more than 80 percent are from underrepresented groups) with a goal of reaching at least one million people and tracking health changes over a decade. And, more than 300 studies have already begun using this data to study cancer, heart disease, Alzheimers, mental health, and more.

The All of Us Research Program already has over 360,000 participants, 80 percent of whom are from underrepresented groups.

Heres the catch: The program cant make the monumental impact its hoping to without volunteers, but a historically justified lack of trust between traditionally underserved communities of color and the medical field is a barrier for turning things around.

There is a lack of diversity with African Americans participating in medical research because there is significant mistrust in medical research based on the history of mistreatment, abuse, and deception with clinical programs within the African American community, says Shana Davis, senior program director at Black Womens Health Imperative. In addition, based on various negative and historical experiences, black and brown communities tend to be more skeptical about sharing personal information for fear that it will be exploited in some way.

To mend these bridges, All of Us is taking precautions to keeping all shared data safe and secure, and joining forces with groups like the Black Womens Health Imperative, the National Alliance for Hispanic Health, the Asian Health Coalition, and more to spread the word on the importance of this movementas well as to listen and learn how to be more culturally inclusive.

If we [Black women] are not part of the study, our specific needs will not be assessed nor addressed, Davis says. Black women are disproportionately underrepresented in clinical research. Therefore, so are our needs. Black women must be educated on why participating in clinical research is critical to our long-term health. [] One day, this work will allow clinicians to tailor their day-to-day treatment plans precisely for me based on my genetics.

If you or someone you know signs up, All of Us will ask for info (via surveys, electronic health records) on the factors that influence your health, like your lifestyle, activity levels, family health history, etc. You can also connect your fitness tracker (which you might qualify to receive for free if you dont already have one!) and provide a DNA sample for further study, which could help you learn more about your genetic ancestry. The key is, you only have to share what you personally are comfortable divulging.

If you decide to participate, youll be contributing to research that will help generations to come, Davis says. You could help ensure that people who share the same background, community, or orientation as you are represented and benefit from research. And thats a move toward equality you can definitely feel good about.

Sound like something youd be into? Click here to learn more and sign up to participate. Plus, you might qualify to receive one of 10,000 Fitbit devices participants will be given this year.

Top photo: The All Of Us Research Program

Blue Cross Blue Shield Association is an association of of independent Blue Cross and Blue Shield companies and owner of the Blue Cross and Blue Shield service marks.

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If Youre Not a Straight, White Man, Medical Research Might Be Overlooking YouBut Heres How To Change That - Well+Good

Fiona the hippo is still too young to think about boys.Cincinnati's hippo darling is turning 4 years old this month, now weighing more than 1,500 pounds.The sassy heartthrob has reached a certain level of maturity. But according to Wendy Rice, the head keeper at Cincinnati Zoo's Africa Department, Fiona needs to be at least 5 before she starts thinking about boys. And although she has hippo admirers across the country, Rice said Fiona is still a few years away from picking up a boyfriend.Of those hippo admirers, one such hippo is still laying it on thick. Timothy, a 3-year-old hippo from San Antonio, still pens Fiona weekly love notes on Facebook.But what ultimately will decide Fiona's potential future romance? It may not be cute love notes."The genetics are basically what's going to matter most," Rice said. "If and when Fiona were to get a breeding recommendation someday, it would be based entirely on who was genetically the best match for her that may or may not be Timothy."Fiona's genes are valuable in the world of Nile hippopotamuses. And eventually, Rice said the goal is to have Fiona breed if she can. But we're talking way down the road when Fiona is at least 5 years old.What happens then?"We obviously don't want her going anywhere," Rice said. "We love her. She's our baby and this hometown loves her. We're fairly certain people would riot if we said Fiona was leaving. We're hopeful that if she gets a breeding recommendation, that a male would be brought here for her so she wouldn't have to leave Cincinnati."Fiona the hippo was thrust into the spotlight due to her remarkable survival story.Born six weeks premature at the Cincinnati Zoo on Jan. 24, 2017, Fiona weighed only 29 pounds at birth 25 pounds less than the lowest recorded birth weight for her species. She survived because of her animal care team's tireless efforts to save her and has inspired many to care about her species and wildlife.Now weighing a healthy weight for a hippo her age (more than 1,500 pounds), Fiona is remarkable for being unremarkable, just a 3-year-old hippo who almost didn't make it.

Fiona the hippo is still too young to think about boys.

Cincinnati's hippo darling is turning 4 years old this month, now weighing more than 1,500 pounds.

The sassy heartthrob has reached a certain level of maturity. But according to Wendy Rice, the head keeper at Cincinnati Zoo's Africa Department, Fiona needs to be at least 5 before she starts thinking about boys. And although she has hippo admirers across the country, Rice said Fiona is still a few years away from picking up a boyfriend.

Of those hippo admirers, one such hippo is still laying it on thick. Timothy, a 3-year-old hippo from San Antonio, still pens Fiona weekly love notes on Facebook.

But what ultimately will decide Fiona's potential future romance? It may not be cute love notes.

"The genetics are basically what's going to matter most," Rice said. "If and when Fiona were to get a breeding recommendation someday, it would be based entirely on who was genetically the best match for her that may or may not be Timothy."

Fiona's genes are valuable in the world of Nile hippopotamuses. And eventually, Rice said the goal is to have Fiona breed if she can. But we're talking way down the road when Fiona is at least 5 years old.

What happens then?

"We obviously don't want her going anywhere," Rice said. "We love her. She's our baby and this hometown loves her. We're fairly certain people would riot if we said Fiona was leaving. We're hopeful that if she gets a breeding recommendation, that a male would be brought here for her so she wouldn't have to leave Cincinnati."

Fiona the hippo was thrust into the spotlight due to her remarkable survival story.

Born six weeks premature at the Cincinnati Zoo on Jan. 24, 2017, Fiona weighed only 29 pounds at birth 25 pounds less than the lowest recorded birth weight for her species. She survived because of her animal care team's tireless efforts to save her and has inspired many to care about her species and wildlife.

Now weighing a healthy weight for a hippo her age (more than 1,500 pounds), Fiona is remarkable for being unremarkable, just a 3-year-old hippo who almost didn't make it.

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From preemie to heartthrob: 4 minutes of hippo footage to celebrate Fionas 4th birthday - WLWT Cincinnati

How has the pandemic affected cancer research?

The outbreak of the SARS-CoV2 coronavirus that began slowly in Wuhan, China a year ago, before quickly enveloping the world has had widespread, devastating effects on lives, livelihoods and entire economies. Although much focus has rightly centered on the impressive scientific research directly tackling the pandemic, including work tracking the virus, trialing treatments for Covid-19 and developing vaccines, the impact on many other areas of medical research have been less documented and may take several years to fully come to terms with.

Cancer, for example, is the second leading cause of death in the U.S., with the American Cancer Society projecting over 600,000 cancer deaths in 2020. Despite a raging Covid-19 pandemic, this is roughly a quarter of a million people more than died of Covid-19 last year in the U.S.

A survey of 239 cancer research scientists in the U.K. in November of last year found that the researchers estimated that their work would be set back by an average of 6 months. The same researchers also estimated that major advances would be delayed almost 18 months due to numerous effects of the pandemic including lab shutdowns, reductions in funding and barriers to enrolling patients on clinical trials.

In the U.S., restrictions and setbacks to research vary widely depending on location and nature of the work. Cancer research is also a highly diverse topic with research not only developing new treatments and testing them in clinical trials, but also studies looking at the health of people who have survived cancer and racial and social disparities which affect care and outcomes of people with cancer.

Forbes Health interviewed several cancer researchers in the U.S. about their experiences during the pandemic so far, asking how the pandemic has affected them and their work.

Dr. Wayne Lawrence,DrPH, MPH, Cancer Prevention Fellow, Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD.

Dr. Wayne Lawrence (left), DrPH, MPH, Cancer Prevention Fellow, Division of Cancer Epidemiology and [+] Genetics, National Cancer Institute

My research is in the field of cancer epidemiology with an emphasis on minority and economically disadvantaged populations. My work lies at the intersection of biological susceptibility and inequities in health care delivery, said Lawrence. I am fortunate that I can work from home, as my research consists of analyzing large population-based data at a computer rather than working in a lab. However, the constant worry of family members becoming infected with Covid-19 pulls my focus away from my research often. This is intensified as I have family members that are essential workers in New York City, Lawrence added.

Lawrences research aims to develop new approaches to cancer prevention and improvement of long-term cancer survival in minority and economically disadvantaged people, an issue brought into sharper focus during the pandemic as it is now well-known that these people also have the highest risk of contracting, and dying from, Covid-19.

What is further challenging during this period is societys grapple with structural racism in the U.S. The ongoing Covid-19 pandemic has made focusing on my work difficult with the constant concerns of infection among family and friends. Watching the country struggle to grasp how deeply rooted racism is in society has compounded this difficulty, said Lawrence.

Academic researchers already experience high levels of burnout, stress and mental health difficulties compared to the general population and many are finding that the additional strain of the pandemic is compounding their abilities to run their research programs.

I am still grappling with the extent to which the ongoing pandemic is impacting my daily life. At this point, I will be more productive when my family and friends have received the Covid-19 vaccine. The constant worry of loved ones becoming infected and dying from Covid-19, especially those living in areas with alarming increases in cases, makes it difficult to concentrate on projects, said Lawrence.

OliviaGeneus, Ph.D. Candidate in Nanotechnologyat State University of New York, Buffalo, NY.

Olivia Geneus, Ph.D. Candidate at State University of New York, Buffalo.

Geneus is working on a nanotechnology solution to deliver targeted therapies directly to a type of brain tumor called a glioblastoma multiforme (GBM), which has a very poor survival rate currently. Her campus at State University of New York in Buffalo was temporarily shut down during the first wave of the pandemic.

With the abrupt campus lockdown including our laboratories, experiments that were conducted prior had to be immediately terminated without any plan as to how to proceed forward. Accessing our instrument centers to test our samples also became difficult due to the campus-wide social distancing guidelines. And on the front end, laboratory materials and chemicals now take much longer to ship when ordered, said Geneus.

Geneus like many graduate students, helps to mentor and train other students earlier on in their careers, yet another aspect of research which was been disrupted.

During the pandemic, it is quite apparent that virtual learning has decreased feedback and engagement from my students. I never want my students to feel isolated from their learning environment and experience. Additionally, as a graduate research mentor, my undergraduate mentees are unable to receive the laboratory and research experience that they would have normally been provided, said Geneus.

However, an unexpected positive for Geneus was that the enforced time away from her lab gave her a chance to finish off some previous work.

It is quite difficult to accurately estimate how much the Covid-19 pandemic has delayed my research progress. Obtaining accurate data from laboratory experiments that are conducted are the biggest factor driving such setbacks. However, what is in my control is the time spent on completing my first-author research paper for publication, said Geneus.

Dr. ChristopherSweeney, MBBS, medical oncologist at Dana-Farber Cancer Institute in Boston, MA.

Dr. Christopher Sweeney, medical oncologist at Dana-Farber Cancer Institute:

Dr. Sweeney is a practicing oncologist and professor at Harvard Medical school. His research mainly focuses on international phase III trials for men with prostate cancer. In April 2020, the international team had just launched a new clinical trial to test out a new therapy for a particular type of prostate cancer and had to move quickly to modify the trial so that patients could still participate.

The global team convened and modified the trial in accordance with the relevant government regulations to allow tele-health visits and delivery of drugs to patients homes and so minimize in-person visits to a health care facility while maintaining the ability to safely monitor patients and deliver the care needed. We also adjudicated that some visits were still essential and ensured isolation protocols were in place so patients could still get the treatments designed to manage their advanced prostate cancer. It took some quick yet judicious thinking and adjustments and in the end has proven to be a successful model and allowed the safe continuation of research that has the potential to decrease the chancemen will die of prostate cancer, said Sweeney.

Dr. Erica T.Warner, ScD MPH, Assistant Professor of Medicine, Massachusetts General Hospital and Harvard Medical School in Boston, MA.

Erica T. Warner, ScD MPH, Assistant Professor of Medicine, Massachusetts General Hospital and [+] Harvard Medical School

Dr. Warners research focuses on breast cancer risk factors and racial disparities in breast cancer treatment, diagnosis and survivorship, as well as ways to improve patient care in these areas.

I had several projects, including a American Cancer Society and Pfizer funded study on breast cancer survivorship in Black women, that were ready to launch right when all observational research was halted in March. Those projects have been significantly delayed by the pandemic because of the stoppage, and then the time it took the redesign them to recruit and enroll participants and conduct the study remotely, said Warner.

Warner estimates that her groups projects have been delayed approximately a year, so far, by the pandemic. However, like many researchers, Warner has also created projects to address problems caused by, or exacerbated by the pandemic.

We conducted a national survey in partnership with several breast cancer advocacy organizations to understand from the patient perspective how the pandemic has affected breast cancer diagnosis and treatment. Im also working with several collaborators to use large institutional databases to see how screening rates have declined as a result of the pandemic, and to better understand how to bring women back to care, said Warner.

Dr. Elizabeth Wayne, PhD, biomedical engineer at Carnegie Mellon University in Pittsburgh, PA.

Dr Elizabeth Wayne, biomedical engineer at Carnegie Mellon University.

Dr. Wayne recently started her own research group and focuses on studying immune cell interactions with biomaterials for the purpose of drug delivery, diagnostics, and drug discovery.

My work is heavily experimental and as such the reductions in density [of people] requirements have made it challenging to schedule and conduct laboratory experiments. Moreover, I am an early career professorI started my position in August 2019my lab is so young we are still in a training phase. Being in close proximity to someone outside of your household for prolonged periods of time is the one thing you arent supposed to do and yet it is exactly the thing that I need, said Wayne.

Wayne, like many other researchers also has academic teaching and mentoring duties, which have been severely affected by the ongoing pandemic. The need to pivot largely to virtual learning solutions has created many challenges, especially for students studying sciences as many programs require hands-on laboratory-based experience.

Postdocs, graduate students have felt like they were in a holding pattern and this has uncovered or exacerbatedphysical, social and mental health challenges.I also enjoy mentoring undergraduates, but it has been very challenging providing meaningful research experience. Myself along with other colleagues have pivoted to creating virtual lab experiences and I believe this is something that could have great utility even after the pandemic. Nonetheless, I absolutely worry about how this will affect students abilityto demonstrate their capacity for research, something that is valued if not required for admission into STEM PhD programs, said Wayne.

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How Has The Covid-19 Pandemic Impacted Cancer Research? - TechnoCodex

Newswise LEXINGTON, Ky. (Jan. 5, 2021)Understanding the mechanisms behind successful plant reproduction can lead to more reliable crop production and higher yields. In a recent study, an international group of scientists led by researchers from the University of KentuckyCollege of Agriculture, Food and Environmentidentified signaling and motor proteins that help guide the male nuclei toward its female counterparts to allow reproduction to occur in flowering plants.

Flowering plants use a unique method called double fertilization in which two male nuclei and two female nuclei containing the plants genetic material must meet to produce a seed. This study sheds new light on how the connection between nuclei occurs.

We knew plants controlled the migration of the male nucleus differently than animals, but how this dynamic movement occurred in plants remained unclear until now, said Tomokazu Kawashima, assistant professor in the UKDepartment of Plant and Soil Scienceswho led the project.

In the recent study, which was published in the Proceedings of the National Academies of Sciences, the scientists also found plant reproductive cells use a unique signaling pathway which differs from signaling systems in other parts of the plant.

This means that the knowledge we have accumulated from studies in leaves and stems do not apply to plant sexual reproduction, including seed development, Kawashima said. Further detailed investigation directly into these sexual cells are critical to helping scientists understand how the reproductive process has evolved.

Kawashima specializes in land plant evolution and says this finding will not only help him better understand how flowering plants control double fertilization to produce seeds but may help scientists determine how to efficiently produce crops, particularly in unstable climate conditions.

Higher or lower temperatures can negatively affect plant fertilization, including the migration of the male nucleus, Kawashima said. This finding will give scientists new ideas and strategies to maintain or improve crop production.

Kawashima was joined on the project by UK doctoral students Mohammad Foteh Ali and Fatema Umma. Samuel Hacker, a recent graduate of the colleges agricultural and medical biotechnology program, also contributed to the project.

We were really excited about our achievement, and even during this pandemic, we kept going to get results for this publication, Kawashima said. Mohammad and Fatema were really impressive and completed the work without any delay! Moreover, I am grateful to have had a talented ABT undergraduate student, Sam Hacker, in my lab for this project. He understands how to process microscopy images to extract quantitative data for comparative analyses.

Additional contributors to the paper include scientists from Wuhan University in China and Yokohama City University in Japan.

Research reported in this publication was supported by theNational Science FoundationDivision of Integrative Organismal Systemsunder Award Number1928836.The opinions, findings, and conclusions or recommendations expressed are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

The paper is available online athttps://www.pnas.org/content/early/2020/12/01/2015550117.

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Plant Reproduction Finding by University of Kentucky Scientists Could Lead to More Reliable Crop Production - Newswise

The center has led the Mexican wolf cross-fostering program that began in 2014. Founded in 1971, it sits on 63 isolated, wooded acres, designed to match the cold, silent and humanless habitat where Mexican wolves live.

Through cross-fostering, 8- to 14-day-old pups born in captivity are placed in a den of similar-aged wild pups in remote areas of the Southwest.

Being able to take puppies from facilities like the Endangered Wolf Center and sneaking them into wild litters is a great way for us to be able to get new genetics out into the wild to help keep that wild population healthier, said Regina Mossotti, director of animal care and conservation at the Endangered Wolf Center.

Mexican wolves breed in April and May, leaving a narrow window for cross-fostering.

To successfully cross-foster a wolf pup, officials must identify a wild wolf that has given birth about the same time that a female wolf in captivity at the center gives birth.

When that does happen, the clock starts ticking.

We have to be able to find a flight, the weather has to work and we have to have enough people to do it, Mossotti said. So all these things, these logistics have to come together to make it happen.

Once the team from the Endangered Wolf Center arrives in Arizona, Game & Fish employees join them on a hike to a specific wolf den, often hidden in the rugged terrain along the Arizona-New Mexico state line.

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Diversifying the pack: Cross fostering helps Mexican wolf population boost genetic mix - Arizona Daily Star

A well attended online Campus course staged by the SIG Reproductive Genetics heard that the expansion of sequencing analysis is poised to push forward the development of cost-effective preconception tests able to identify several underlying genetic causes of infertility

The everyday implications of preconceptional medicine have so far been largely evident in lifestyle advice conducive to successful pregnancy, but a well attended online Campus meeting staged in December suggests that genomic medicine has an increasingly important role to play. Sessions at the meeting not only covered the much debated subject of genetic risk assessment by expanded carrier screening, but explored the application of genome-wide sequencing in recurrent miscarriage, in predicting ART outcomes from parental genome analysis, and even in explaining the different responses to ovarian stimulation with gonadotrophins. Such subjects, especially expanded carrier screening, are not without their ethical problems, notably in the disclosure (or not) of secondary findings, so it was also appropriate at this meeting to hear a preview of ESHREs forthcoming recommendations on expanded carrier screening in ART.

In his opening lecture Stphane Viville, a former coordinator of ESHREs SIG Reproductive Genetics, said that known genetic and chromosomal factors account for around 20% of all infertility cases, with three additional (and relatively unknown) phenotypes now moving into active research: POI, oocyte maturation defect, and preimplantation embryonic lethality, all of which were covered at this meeting. Viville added that so far at least 21 genes have been implicated in POI and advised that genetics is now getting more and more into IVF labs and no longer confined to chromosomal aberrations or microdeletions on the Y chromosome.

Much of the content of this Campus course has been explored in detail in a recent Human Reproduction Update review, whose first author, Antonio Capalbo, is deputy of ESHREs SIG Reproductive Genetics and an organiser of this course.(1) In the review, as was repeatedly implied at this meeting, Capalbo et al note that the expansion of sequencing analysis may enable the development of cost-effective preconception tests capable of identifying underlying genetic causes of infertility, which until now have largely been defined as idiopathic.

One such step in this move towards a more positive and personalised approach to preconceptional medicine is in genetic risk assessment by expanded carrier screening, which occupied a large section of this meeting. James Goldberg, prominent in the development of ECS, said its availability now steps beyond the disparities and restrictions of ethnicity-specific screening and aims to inform couples about their risk of having children with autosomal recessive and X-linked recessive disorders and thereby to support informed decision making. Nevertheless, two of the current guidance statements on ECS cited by Goldberg both from the USA are largely based on ethnicity screening with an emphasis on cystic fibrosis and spinal muscular dystrophy. ECS, said Goldberg, represents a more equitable approach to identifying risk. Such risk assessment in both the general population and IVF couples - will allow identification of those who carry recessive mutations, and thereby provide increased reproductive autonomy to couples deemed at risk and where PGT is available for embryo selection.

However, when a publicly provided ECS programme was set up in Amsterdam offering a test panel of 50 genes (at a cost of 650 euro per test) and following the guidance of the European Society of Human Genetics, there was a relatively quiet response (20%) from the general risk population, and higher (80%) from the high risk population.(2) Nevertheless, assessment of the programme, began in 2016, appeared to raise more questions than answers, and no clear resolution of how such a programme might be best provided. Capalbo and his fellow Update reviewers concluded that ECS represents one of the most effective and advanced applications of preconception genomic medicine worldwide today and is expected to grow in application in coming years.

The preview of recommendations from ESHREs Ethics Committee was specifically about ECS ahead of ART (and not just involving gamete donors). Thus, asked Dutch bioethicist Guido de Wert, would the offer of ECS to all such applicants be proportionate, and if so, for what kinds of disorders and under what conditions? Applying the three ethicists principles of proportionality, respect for autonomy and justice, De Wert firstly noted that any possible benefits should clearly outweigh any possible harms, that ECS should still be embedded in a research framework, and that a couples access to ECS should only be on condition that they take preventive measures and apply for PGT, donor gametes, or, maybe, prenatal diagnosis.

Even the outcome of fertility treatments may well be affected by genetic mutations, and such extreme outcomes as oocyte maturation failure and embryonic developmental arrest are now investigated as a genetic cause of infertility. Indeed, Semra Kahraman from theIstanbul Memorial Hospital reported that variants in more than 2000 genes are now predicted to be involved in various infertility pathways. She described her own study in which 22 IVF patients whose repeated failure was attributed to oocyte maturation failure and embryo development arrest and who were investigated using whole exome sequencing panels. Family history analysis had also identified infertility and early menopause in the family of nine of the subjects. The analysis identified genomic variants in eight of the 22 subjects, including four genes known to be lethal at the embryonic stage.

With ovarian ageing identified as one of todays most frequent causes of infertility, John Berry, an MRC investigator from Cambridge, reported in a keynote lecture that ten years ago population studies had identified four common genetic variants associated with menopause. Today, he added, there are now more than 300 loci identified, which explain around 10% of the heritable component. Too few to be clinically useful? he asked. Again, there appeared more questions than answers, notably if POI can be explained solely by monogenic alleles and if menopausal age can indeed be predicted by genetics.

The conclusions from this meeting, as well as the increasing number of genes and variants identified, suggest that genomic assessment ahead of conception may have real clinical benefits at both the individual (in identifying genetic risks in the male and female partner) and the couple level (in allowing a specific reproductive prognosis). Information at this early stage may thus lay the basis for personalised interventions, and certainly make at-risk couples better informed of their reproductive choices.

1. Capalbo A, Poli M, Riera-Escamilla A, et al. Preconception genome medicine: current state and future perspectives to improve infertility diagnosis and reproductive and health outcomes based on individual genomic data, Hum Reprod Update 2020; doi:10.1093/humupd/dmaa044

2. Henneman L, Borry P, Chokoshvili D, et al. Responsible implementation of expanded carrier screening. Eur J Hum Genet 2016; 24: e1-e12. doi:10.1038/ejhg.2015.27

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The expanding role of genomics in preconceptional 'personalised' medicine - ESHRE

21 December 2020

Session three of the Progress Educational Trust (PET) annual conference explored the genetic and genomic links to susceptibility to severe COVID-19. Sarah Norcross, director at PET, opened the session with the unfortunate news that one of the speakers Dr Kri Stefnsson was unable to participate in the session due to illness.

The session was chaired by Dr Roger Highfield, science director at the Science Museum Group mild-mannered and a clear speaker, he chaired the session with ease. Dr Highfield introduced the first speaker Dr Sharon Moalem a scientist and physician who specialises in genetics. Dr Moalem is a bestselling author, with titles including: 'How Sex Works', 'Inheritance: How Our Genes Change Our Lives and Our Lives Change Our Genes', and 'The Better Half: On the Genetic Superiority of Women' (see BioNews 1050).

Dr Moalem focused his talk on the law of homogameity, and whether COVID-19 illustrates the genetic/genomic resiliency of women. He began by briefing the audience on the basics of mammalian genetics, how we have 46 chromosomes, one pair of which is sex chromosomes, containing either XX for a female, termed homogametic, or XY for a male, termed heterogametic. A system has arisen in females, where in each cell one X chromosomes is 'turned off', called X-inactivation or silencing. However, it has now been discovered that X-inactivation is not complete, and that about 25 percent of the second X chromosome is still active. Dr Moalem explained that this allows females to have more 'genetic horse power' within each of her cells.

X-linked conditions, such as fragile X, red-green colour blindness and Duchene muscular dystrophy, are more common in males, as men do not have another X chromosome. Females do not simply have a 'back up X', but in some cases their non-faulty gene produces and shares the required protein, essentially rescuing the cells containing the faulty gene, which would have died. In other cases, cells with such a mutation do not survive, but cell lines with the healthy X proliferate to compensate. This leads to tissues with an uneven distribution of active Xs, called X-skewing.

Moving onto COVID-19, why is the mortality rate for males higher than that for females? Dr Moalem proposed the law of homogameity, which predicts that the homogametic sex has a survival advantage across the life course. Females have a greater genetic diversity due to having an extra X-chromosome, which equates to 1000 more genes. The X chromosome contains many immune-related genes eg, TLR7 which is used by certain cells in the body to detect for single-stranded RNA viruses, like SARS-CoV-2, the virus which leads to COVID-19. As females have two variations of TLR7 they have two different immune cell populations to help detect the virus. However, there is a cost to homogameity increased autoimmunity, with 'long COVID' proving to be four times more common in women.

In the USA there is currently no requirement for drug approval from the FDA to use both male and female cells. Scientists can use just one sex, yet females' cells work in a corporative way. Dr Moalem believes there should be a completely separate drug approval process as many drugs behave differently in men and women.

Dr Highfield returned to introduce the second speaker Dr Qian Zhang a research associate at the St Giles Laboratory of Human Genetics of Infectious Diseases, at Rockefeller University in New York City. Dr Zhang's research specialises in inborn errors of immunity (IEIs) inherited disorders that impair normal immune development and function.

Dr Zhang focused her talk on type I interferon immunity in patients with life-threatening COVID-19 and began by explaining how early on in the pandemic it became clear that people infected with SARS-CoV-2 responded differently. Most were asymptomatic and developed either no or very mild clinical symptoms. A small proportion of patients developed life-threatening disease. This phenomenon is seen in all infectious diseases from bacteria, fungi and viruses.

Dr Zhang and her research team studied whether the same genetic mutations already known to be associated with life-threatening influenza infections also increase the risk of life-threatening COVID-19 pneumonia. There are three genes, TLR3, IRF7 and IRF9, in the type I interferon pathway that are mutated in people who develop life-threatening influenza. In addition, ten further genes, IFNAR1, IFNAR2, STAT1, STAT2, IRF3, UNC93B, TRIF, NEMO, TRAF3 and TBK1, are reported to affect severity of other viral infections.

Type I interferon is a cytokine and has 17 different subtypes, which lead to the stimulation of several hundred interferon-stimulated genes that have an antiviral function. Hence, if this pathway is disrupted by a genetic mutation, viruses are able to gain a foothold more easily.

Dr Zhang's team sequenced the whole of the genome of over 600 severe COVID-19 patients to determine whether they had mutations in any of these 13 genes and discovered over 118 variants, of which, 24 resulted in loss of function.

Four patients with autosomal recessive mutations causing a complete loss of function in IRF7 and IFNAR1had never been hospitalised before contracting COVID-19, much to Dr Zhang's surprise. IRF7 is a transcription factor that amplifies the antiviral signal of type I interferon, and IFNAR1 is one of two proteins that make the receptor for type I interferons. Patients with these mutations are unable to mount an interferon response to COVID-19 infection.

Dr Zhang reassuringly explained that these mutations are rare, less than one in 1000 in the population, as such they cannot explain why there are so many people dying of COVID-19. This led Dr Zhang to the second part of her research: studying whether auto-antibodies against type I interferons lead to the same phenotype as these rare mutations.

Over ten percent of patients with life-threatening COVID-19 make auto-antibodies against two of the type I interferons. These neutralising auto-antibodies can entirely block the protective effect of type I interferons, which may be the cause of severe COVID-19.

Surprisingly, 95 percent of patients with these auto-antibodies were male and only six were female. One of these female patients had incontinentia pigmenti (IP), which is caused by a NEMO mutation on the X chromosome, leading to skewed X-inactivation a perfect example of the genetic diseases Dr Moalem was discussing earlier in the session. Even though such patients have two X chromosomes, most of the tissues in their bodies express just one X chromosome, and so these females are more similar to males in terms of susceptibility.

Combining both parts of her research, Dr Zhang's team discovered that selected patients with TLR3 and IRF7 mutations could simply be treated with type I interferon. However, this treatment did not work for patients with IFNAR1 mutations because the receptor is absent, but treatment with wildtype IFNAR1 was successful. Unfortunately, neither treatment worked for patients with auto-antibodies.

In her opinion COVID-19 could be considered an X-linked disease, even though the candidate on the X-chromosome has yet to be discovered and furthermore, type I interferon immunity is essential to control COVID-19 infection.

Dr Highfield returned to update the audience on Dr Stefnsson's research, investigating the genetic code of each COVID-19 infection in Iceland, giving an insight into the origins, and how the infection was caught, spread and mutated. Surprisingly, a large number of cases came from the UK. Similar research in the UK has detected 1356 independent introductions of the virus, mostly due to inbound international travel a third came from Spain, over a quarter from France and 14 percent from Italy.

The session provoked interesting discussions within the Q&As, with the first asking Dr Moalem whether females are less severely affected by other viruses, which he concluded as true, particularly for influenza. But even for HIV-1, women are much better at clearing the virus and have a much lower viral load.

With a personal interest, I took the opportunity to ask Dr Zhang whether patients with type I interferon IEIs were more susceptible to severe COVID-19, as such a disease affects members of my own family. Dr Zhang confirmed that such patients are more likely to suffer with severe COVID-19 and had now tested 20 IP patients discovering at least a quarter had high levels of autoantibodies to type I interferons. She warned that these females should be very cautious and shield as much as possible, as any patient with auto-antibodies is very difficult to treat. Reassuringly, patients with certain genetic mutations that do not have high levels of autoantibodies to type I interferon can simply be treated early with interferon injections.

I will leave with a final comment from Dr Moalem: 'Men are more biologically fragile when compared to women.' Whoever said that women were the weaker sex?

PET would like to thank the sponsor of this session, the Anne McLaren Memorial Trust Fund, and the other sponsors of its conference - the Edwards and Steptoe Research Trust Fund, ESHRE, Wellcome, the European Sperm Bank, Ferring Pharmaceuticals, the London Women's Clinic, Merck, Theramex, Vitrolife and the Institute of Medical Ethics.

Originally posted here:
Correlation and Causation: What Can Genetics and Genomics Tell Us about COVID-19? - BioNews

We all have 46 chromosomes: 23 of them are inherited from our father and 23 are from our mother. The genetic information for our entire body is stored within these chromosomes. Two of the 46 are sex chromosomes and determine whether we are male (XY) or female (XX). Therefore, the Y chromosome contains all the necessary information for differentiating males from females as well as for sperm production.

The study of Y chromosome microdeletions consists of checking if chromosome Y is complete and, as such, has all the necessary information for satisfactory sperm production or if, on the contrary, small fragments are missing. The loss of such fragments leads to altered spermiogramme which can mean poor sperm production (oligozoospermia) or even no production at all (azoospermia).

For all those patients with an altered seminogram sperm count, this test is of utmost importance since it will provide information on if the low sperm count is down to genetics and, therefore, may be passed on to male children.

The techniques used in laboratories the world over involve molecular biology techniques which only check a small number of Y chromosome regions.

As a part of our commitment to provide our patients with the very latest in innovative technology and deliver top results, we have recently introduced a new technique (MLPA, multiplex ligation-dependent probe amplification) which enables a greater number of Y chromosome regions to be studied. This means that we are able to diagnose more cases since we can detect the presence or absence of a greater number of Y chromosome regions. As such, more patients will get information on the cause of their sperm production issue. It will also enable the specific region of the Y chromosome which has been lost to be identified and, therefore, depending on which region it is, disclose whether a total loss of sperm production may occur in the future. If the patient is currently producing sperm, this will open up the possibility of freezing before production comes to a complete standstill, thus allowing for biological descendants in the future.

We must not forget that Y chromosome microdeletions mean a loss of genetic material. And that in such cases the fertility issue will be passed on to future male generations. Appropriate reproduction and genetics counselling is, therefore, a must. Instituto Bernabeu has a unit which is specialised in genetics and reproduction counselling where each case is evaluated on an individual basis and the patient is given appropriate advice.

Dr. Beln Lled, IBBIOTECH scientific Director of Instituto Bernabeu.

Here is the original post:
Y chromosome microdeletion: Male sterility and genetic ...

Type of genetic haplogroup

In human genetics, a human Y-chromosome DNA haplogroup is a haplogroup defined by mutations in the non-recombining portions of DNA from the male-specific Y chromosome (called Y-DNA). Many people within a haplogroup share similar numbers of short tandem repeats (STRs) and types of mutations called single-nucleotide polymorphisms (SNPs).[1]

The human Y-chromosome accumulates roughly two mutations per generation.[2] Y-DNA haplogroups represent major branches of the Y-chromosome phylogenetic tree that share hundreds or even thousands of mutations unique to each haplogroup.

The Y-chromosomal most recent common ancestor (Y-MRCA, informally known as Y-chromosomal Adam) is the most recent common ancestor (MRCA) from whom all currently living humans are descended patrilineally. Y-chromosomal Adam is estimated to have lived roughly 236,000 years ago in Africa. By examining other bottlenecks most Eurasian men (men from populations outside of Africa) are descended from a man who lived 69,000 years ago. Other major bottlenecks occurred about 50,000 and 5,000 years ago and subsequently the ancestry of most Eurasian/non-African men can be traced back to four ancestors who lived 50,000 years ago.[3][4][5][clarification needed]

Y-DNA haplogroups are defined by the presence of a series of Y-DNA SNP markers. Subclades are defined by a terminal SNP, the SNP furthest down in the Y-chromosome phylogenetic tree.[6][7] The Y Chromosome Consortium (YCC) developed a system of naming major Y-DNA haplogroups with the capital letters A through T, with further subclades named using numbers and lower case letters (YCC longhand nomenclature). YCC shorthand nomenclature names Y-DNA haplogroups and their subclades with the first letter of the major Y-DNA haplogroup followed by a dash and the name of the defining terminal SNP.[8]

Y-DNA haplogroup nomenclature is changing over time to accommodate the increasing number of SNPs being discovered and tested, and the resulting expansion of the Y-chromosome phylogenetic tree. This change in nomenclature has resulted in inconsistent nomenclature being used in different sources.[1] This inconsistency, and increasingly cumbersome longhand nomenclature, has prompted a move towards using the simpler shorthand nomenclature. In September 2012, Family Tree DNA provided the following explanation of its changing Y-DNA haplogroup nomenclature to individual customers on their Y-DNA results pages (note that the haplogroup mentioned below relates to a specific individual):[9]

Long time customers of Family Tree DNA have seen the YCC-tree of Homo Sapiens evolve over the past several years as new SNPs have been discovered. Sometimes these new SNPs cause a substantial change in the "longhand" explanation of your terminal Haplogroup. Because of this confusion, we introduced a shorthand version a few years ago that lists the branch of the tree and your terminal SNP, i.e. J-L147, in lieu of J1c3d. Therefore, in the very near term, Family Tree DNA will discontinue showing the current "longhand" on the tree and we will focus all of our discussions around your terminal defining SNP.This changes no science it just provides an easier and less confusing way for us all to communicate.

Haplogroup A is the NRY (non-recombining Y) macrohaplogroup from which all modern paternal haplogroups descend. It is sparsely distributed in Africa, being concentrated among Khoisan populations in the southwest and Nilotic populations toward the northeast in the Nile Valley. BT is a subclade of haplogroup A, more precisely of the A1b clade (A2-T in Cruciani et al. 2011), as follows:

The defining mutations separating CT (all haplogroups except for A and B) are M168 and M294. The site of origin is likely in Africa. Its age has been estimated at approximately 88,000 years old,[11][12] and more recently at around 100,000[13] or 101,000 years old.[14]

The groups descending from haplogroup F are found in some 90% of the world's population, but almost exclusively outside of sub-Saharan Africa.

FxG,H,I,J,K is rare in modern populations and peaks in South Asia, especially Sri Lanka.[10] It also appears to have long been present in South East Asia; it has been reported at rates of 45% in Sulawesi and Lembata. One study, which did not comprehensively screen for other subclades of F-M89 (including some subclades of GHIJK), found that Indonesian men with the SNP P14/PF2704 (which is equivalent to M89), comprise 1.8% of men in West Timor, 1.5% of Flores 5.4% of Lembata 2.3% of Sulawesi and 0.2% in Sumatra.[15][16] F* (FxF1,F2,F3) has been reported among 10% of males in Sri Lanka and South India, 5% in Pakistan, as well as lower levels among the Tamang people (Nepal), and in Iran. F1 (P91), F2 (M427) and F3 (M481; previously F5) are all highly rare and virtually exclusive to regions/ethnic minorities in Sri Lanka, India, Nepal, South China, Thailand, Burma, and Vietnam. In such cases, however, the possibility of misidentification is considered to be relatively high and some may belong to misidentified subclades of Haplogroup GHIJK.[17]

Haplogroup G (M201) originated some 48,000 years ago and its most recent common ancestor likely lived 26,000 years ago in the Middle East. It spread to Europe with the Neolithic Revolution.

It is found in many ethnic groups in Eurasia; most common in the Caucasus, Iran, Anatolia and the Levant. Found in almost all European countries, but most common in Gagauzia, southeastern Romania, Greece, Italy, Spain, Portugal, Tyrol, and Bohemia with highest concentrations on some Mediterranean islands; uncommon in Northern Europe.[18][19]

G-M201 is also found in small numbers in northwestern China and India, Bangladesh, Pakistan, Sri Lanka, Malaysia, and North Africa.

Haplogroup H (M69) probably emerged in South Central Asia or South Asia, about 48,000 years BP, and remains largely prevalent there in the forms of H1 (M69) and H3 (Z5857). Its sub-clades are also found in lower frequencies in Iran, Central Asia, across the middle-east, and the Arabian peninsula.

However, H2 (P96) is present in Europe since the Neolithic and H1a1 (M82) spread westward in the Medieval era with the migration of the Roma people.

Haplogroup I (M170, M258) is found mainly in Europe and the Caucasus.

Haplogroup J (M304, S6, S34, S35) is found mainly in the Middle East and South-East Europe.

Haplogroup K (M9) is spread all over Eurasia, Oceania and among Native Americans.

K(xLT,K2a,K2b) that is, K*, K2c, K2d or K2e is found mainly in Melanesia, Aboriginal Australians, India, Polynesia and Island South East Asia.

Haplogroup L (M20) is found in South Asia, Central Asia, South-West Asia, and the Mediterranean.

Haplogroup T (M184, M70, M193, M272) is found at high levels in the Horn of Africa (mainly Cushitic-speaking peoples), parts of South Asia, the Middle East, and the Mediterranean. T-M184 is also found in significant minorities of Sciaccensi, Stilfser, Egyptians, Omanis, Sephardi Jews,[20] Ibizans (Eivissencs), and Toubou. It is also found at low frequencies in other parts of the Mediterranean and South Asia.

The only living males reported to carry the basal paragroup K2* are indigenous Australians. Major studies published in 2014 and 2015 suggest that up to 27% of Aboriginal Australian males carry K2*, while others carry a subclade of K2.

Haplogroup N (M231) is found through northern Eurasia, especially among speakers of the Uralic languages.

Haplogroup N possibly originated in eastern Asia and spread both northward and westward into Siberia, being the most common group found in some Uralic-speaking peoples.

Haplogroup O (M175) is found with its highest frequency in East Asia and Southeast Asia, with lower frequencies in the South Pacific, Central Asia, South Asia, and islands in the Indian Ocean (e.g. Madagascar, the Comoros).

No examples of the basal paragroup K2b1* have been identified. Males carrying subclades of K2b1 are found primarily among Papuan peoples, Micronesian peoples, indigenous Australians, and Polynesians.

Its primary subclades are two major haplogroups:

Haplogroup P (P295) has two primary branches: P1 (P-M45) and the extremely rare P2 (P-B253).[21]

P*, P1* and P2 are found together only on the island of Luzon, in The Philippines.[21] In particular, P* and P1* are found at significant rates among members of the Aeta (or Agta) people of Luzon.[22] While, P1* is now more common among living individuals in Eastern Siberia and Central Asia, it is also found at low levels in mainland South East Asia and South Asia. Considered together, these distributions tend to suggest that P* emerged from K2b in South East Asia.[22][23]

P1 is also the parent node of two primary clades:

Haplogroup Q (MEH2, M242, P36) found in Siberia and the AmericasHaplogroup R (M207, M306): found in Europe, West Asia, Central Asia, and South Asia

Q is defined by the SNP M242. It is believed to have arisen in Central Asia approximately 32,000 years ago.[24][25] The subclades of Haplogroup Q with their defining mutation(s), according to the 2008 ISOGG tree[26] are provided below. ss4 bp, rs41352448, is not represented in the ISOGG 2008 tree because it is a value for an STR. This low frequency value has been found as a novel Q lineage (Q5) in Indian populations[27]

The 2008 ISOGG tree

Haplogroup R is defined by the SNP M207. The bulk of Haplogroup R is represented in descendant subclade R1 (M173), which likely originated on the Eurasian Steppes. R1 has two descendant subclades: R1a and R1b.

R1a is associated with the proto-Indo-Iranian and Balto-Slavic peoples, and is now found primarily in Central Asia, South Asia, and Eastern Europe.

Haplogroup R1b is the dominant haplogroup of Western Europe and also found sparsely distributed among various peoples of Asia and Africa. Its subclade R1b1a2 (M269) is the haplogroup that is most commonly found among modern Western European populations, and has been associated with the Italo-Celtic and Germanic peoples.

More:
Human Y-chromosome DNA haplogroup - Wikipedia

Uncommon congenital variations of sex-associated characteristics

Intersex people are individuals born with any of several variations in sex characteristics including chromosomes, gonads, sex hormones or genitals that, according to the UN Office of the High Commissioner for Human Rights, "do not fit the typical definitions for male or female bodies".[1][2] This range of atypical variation may be physically obvious from birth babies may have ambiguous reproductive organs, or at the other extreme range it is not obvious and may remain unknown to people all their lives.[3]

Intersex people were previously referred to as hermaphrodites or "congenital eunuchs".[4][5] In the 19th and 20th centuries, some medical experts devised new nomenclature in an attempt to classify the characteristics that they had observed. It was the first attempt at creating a taxonomic classification system of intersex conditions. Intersex people were categorized as either having true hermaphroditism, female pseudohermaphroditism, or male pseudohermaphroditism.[6] These terms are no longer used: terms including the word "hermaphrodite" are considered to be misleading, stigmatizing, and scientifically specious in reference to humans.[7] A hermaphrodite is now defined as "an animal or plant having both male and female reproductive organs".[6] In 1917, Richard Goldschmidt created the term intersexuality to refer to a variety of physical sex ambiguities.[6] In clinical settings, the term "disorders of sex development" (DSD) has been used since 2006.[8] This shift has been controversial since the label was introduced.[9][10][11]

Intersex people face stigmatization and discrimination from birth, or from discovery of an intersex trait, such as from puberty. This may include infanticide, abandonment, and the stigmatization of families.[12][13][14] Globally, some intersex infants and children, such as those with ambiguous outer genitalia, are surgically or hormonally altered to create more socially acceptable sex characteristics. However, this is considered controversial, with no firm evidence of favorable outcomes.[15] Such treatments may involve sterilization. Adults, including elite female athletes, have also been subjects of such treatment.[16][17] Increasingly, these issues are considered human rights abuses, with statements from international[18][19] and national human rights and ethics institutions (see intersex human rights).[20][21] Intersex organizations have also issued statements about human rights violations, including the 2013 Malta declaration of the third International Intersex Forum.[22]

Sex assignment at birth usually aligns with a child's anatomical sex and phenotype. The number of births where the baby is intersex has been reported to be roughly 1.7%, depending on which conditions are counted as intersex.[23][24] The number of births with ambiguous genitals is in the range of 0.02% to 0.05%.[25] Other intersex conditions involve atypical chromosomes, gonads, or hormones.[26] Some intersex persons may be assigned and raised as a girl or boy but then identify with another gender later in life, while most continue to identify with their assigned sex.[27][28] In 2011, Christiane Vlling became the first intersex person known to have successfully sued for damages in a case brought for non-consensual surgical intervention.[29] In April 2015, Malta became the first country to outlaw non-consensual medical interventions to modify sex anatomy, including that of intersex people.[30][31]

According to the UN Office of the High Commissioner for Human Rights:

Intersex people are born with sex characteristics (including genitals, gonads and chromosome patterns) that do not fit typical binary notions of male or female bodies.Intersex is an umbrella term used to describe a wide range of natural bodily variations. In some cases, intersex traits are visible at birth while in others, they are not apparent until puberty. Some chromosomal intersex variations may not be physically apparent at all.[2]

According to World Health Organization:Intersex is defined as a congenital anomaly of the reproductive and sexual system. An estimate about the birth prevalence of intersex is difficult to make because there are no concrete parameters to the definition of intersex.

In biological terms, sex may be determined by a number of factors present at birth, including:[32]

People whose characteristics are not either all typically male or all typically female at birth are intersex.[33]

Some intersex traits are not always visible at birth; some babies may be born with ambiguous genitals, while others may have ambiguous internal organs (testes and ovaries). Others will not become aware that they are intersex unless they receive genetic testing, because it does not manifest in their phenotype.

From early history, societies have been aware of intersex people. Some of the earliest evidence is found in mythology: the Greek historian Diodorus Siculus wrote of the mythological Hermaphroditus in the first century BCE, who was "born with a physical body which is a combination of that of a man and that of a woman", and reputedly possessed supernatural properties.[34] Ardhanarishvara, an androgynous composite form of male deity Shiva and female deity Parvati, originated in Kushan culture as far back as the first century CE.[35] A statue depicting Ardhanarishvara is included in India's Meenkashi Temple; this statue clearly shows both male and female bodily elements.[36]

Hippocrates (c.460 c.370 BC Greek physician) and Galen (129 c.200/216 AD Roman physician, surgeon and philosopher) both viewed sex as a spectrum between men and women, with "many shades in between, including hermaphrodites, a perfect balance of male and female".[37] Pliny the Elder (AD 23/2479) the Roman naturalist described "those who are born of both sexes, whom we call hermaphrodites, at one time androgyni" (andr-, "man," and gyn-, "woman," from the Greek).[38] Augustine (354 28 August 430 AD) the influential catholic theologian wrote in The Literal Meaning of Genesis that humans were created in two sexes, despite "as happens in some births, in the case of what we call androgynes".[37]

In medieval and early modern European societies, Roman law, post-classical canon law, and later common law, referred to a person's sex as male, female or hermaphrodite, with legal rights as male or female depending on the characteristics that appeared most dominant.[39] The 12th-century Decretum Gratiani states that "Whether an hermaphrodite may witness a testament, depends on which sex prevails".[40][41][42] The foundation of common law, the 17th Century Institutes of the Lawes of England described how a hermaphrodite could inherit "either as male or female, according to that kind of sexe which doth prevaile."[43][44] Legal cases have been described in canon law and elsewhere over the centuries.

Some non-European societies have sex or gender systems that recognize more than the two categories of male/man and female/woman. Some of these cultures, for instance the South-Asian Hijra communities, may include intersex people in a third gender category.[45][46] Hawaiian culture in the past and today see intersex individuals as having more power "mana", both mentally and spiritually, than a single sex person. Althoughaccording to Morgan Holmesearly Western anthropologists categorized such cultures "primitive," Holmes has argued that analyses of these cultures have been simplistic or romanticized and fail to take account of the ways that subjects of all categories are treated.[47]

During the Victorian era, medical authors introduced the terms "true hermaphrodite" for an individual who has both ovarian and testicular tissue, "male pseudo-hermaphrodite" for a person with testicular tissue, but either female or ambiguous sexual anatomy, and "female pseudo-hermaphrodite" for a person with ovarian tissue, but either male or ambiguous sexual anatomy. Some later shifts in terminology have reflected advances in genetics, while other shifts are suggested to be due to pejorative associations.[48]

The term intersexuality was coined by Richard Goldschmidt in 1917.[49] The first suggestion to replace the term 'hermaphrodite' with 'intersex' was made by Cawadias in the 1940s.[50]

Since the rise of modern medical science, some intersex people with ambiguous external genitalia have had their genitalia surgically modified to resemble either female or male genitals. Surgeons pinpointed intersex babies as a "social emergency" when born.[51] An 'optimal gender policy', initially developed by John Money, stated that early intervention helped avoid gender identity confusion, but this lacks evidence.[52] Early interventions have adverse consequences for psychological and physical health.[21] Since advances in surgery have made it possible for intersex conditions to be concealed, many people are not aware of how frequently intersex conditions arise in human beings or that they occur at all.[53]

Dialogue between what were once antagonistic groups of activists and clinicians has led to only slight changes in medical policies and how intersex patients and their families are treated in some locations.[54] In 2011, Christiane Vlling became the first intersex person known to have successfully sued for damages in a case brought for non-consensual surgical intervention.[29] In April 2015, Malta became the first country to outlaw non-consensual medical interventions to modify sex anatomy, including that of intersex people.[30] Many civil society organizations and human rights institutions now call for an end to unnecessary "normalizing" interventions, including in the Malta declaration.[55][1]

Human rights institutions are placing increasing scrutiny on harmful practices and issues of discrimination against intersex people. These issues have been addressed by a rapidly increasing number of international institutions including, in 2015, the Council of Europe, the United Nations Office of the United Nations High Commissioner for Human Rights and the World Health Organization. These developments have been accompanied by International Intersex Forums and increased cooperation amongst civil society organizations. However, the implementation, codification, and enforcement of intersex human rights in national legal systems remains slow.

Regulatory suspension of non-consensual medical interventions

Stigmatization and discrimination from birth may include infanticide, abandonment, and the stigmatization of families. As noted in the "Intersex human rights" page, the birth of an intersex child was often viewed as a curse or a sign of a witch mother, especially in parts of Africa.[12][13] Abandonments and infanticides have been reported in Uganda,[12] Kenya,[56] South Asia,[57] and China.[14]

Infants, children and adolescents also experience "normalising" interventions on intersex persons that are medically unnecessary and the pathologisation of variations in sex characteristics. In countries where the human rights of intersex people have been studied, medical interventions to modify the sex characteristics of intersex people have still taken place without the consent of the intersex person.[58][59] Interventions have been described by human rights defenders as a violation of many rights, including (but not limited to) bodily integrity, non-discrimination, privacy, and experimentation.[60] These interventions have frequently been performed with the consent of the intersex person's parents, when the person is legally too young to consent. Such interventions have been criticized by the World Health Organization, other UN bodies such as the Office of the High Commissioner for Human Rights, and an increasing number of regional and national institutions due to their adverse consequences, including trauma, impact on sexual function and sensation, and violation of rights to physical and mental integrity.[1] The UN organizations decided that infant intervention should not be allowed, in favor of waiting for the child to mature enough to be a part of the decision-making this allows for a decision to be made with total consent.[61] In April 2015, Malta became the first country to outlaw surgical intervention without consent.[30][31] In the same year, the Council of Europe became the first institution to state that intersex people have the right not to undergo sex affirmation interventions.[30][31][62][63][64]

Explicit protection on grounds of intersex status

Explicit protection on grounds of intersex within attribute of sex

People born with intersex bodies are seen as different. Intersex infants, children, adolescents and adults "are often stigmatized and subjected to multiple human rights violations", including discrimination in education, healthcare, employment, sport, and public services.[2][1][65] Several countries have so far explicitly protected intersex people from discrimination, with landmarks including South Africa,[31][66] Australia,[67][68] and, most comprehensively, Malta.[69][70][71][72][73]

Standing to file in law and compensation claims was an issue in the 2011 case of Christiane Vlling in Germany.[29][74] A second case was adjudicated in Chile in 2012, involving a child and his parents.[75][76] A further successful case in Germany, taken by Michaela Raab, was reported in 2015.[77] In the United States, the Minor Child (M.C. v Aaronson) lawsuit was "a medical malpractice case related to the informed consent for a surgery performed on the Crawford's adopted child (known as M.C.) at [Medical University of South Carolina] in April 2006".[78] The case was one of the first lawsuit of its kind to challenge "legal, ethical, and medical issues regarding genital-normalizing surgery" in minors, and was eventually settled out of court by the Medical University of South Carolina for $440,000 in 2017.[79]

Access to information, medical records, peer and other counselling and support. With the rise of modern medical science in Western societies, a secrecy-based model was also adopted, in the belief that this was necessary to ensure "normal" physical and psychosocial development.[20][21][80][81][82][83]

The Asia Pacific Forum of National Human Rights Institutions states that legal recognition is firstly "about intersex people who have been issued a male or a female birth certificate being able to enjoy the same legal rights as other men and women."[22] In some regions, obtaining any form of birth certification may be an issue. A Kenyan court case in 2014 established the right of an intersex boy, "Baby A", to a birth certificate.[84]

Like all individuals, some intersex individuals may be raised as a certain sex (male or female) but then identify with another later in life, while most do not.[85][27][pageneeded][86][87] Recognition of third sex or gender classifications occurs in several countries,[88][89][90][91] However, it is controversial when it becomes assumed or coercive, as is the case with some German infants.[92][93] Sociological research in Australia, a country with a third 'X' sex classification, shows that 19% of people born with atypical sex characteristics selected an "X" or "other" option, while 52% are women, 23% men, and 6% unsure.[28][94]

Research in the late 20th century led to a growing medical consensus that diverse intersex bodies are normal, but relatively rare, forms of human biology.[27][pageneeded][95][96][97] Clinician and researcher Milton Diamond stresses the importance of care in the selection of language related to intersex people:

Foremost, we advocate use of the terms "typical", "usual", or "most frequent" where it is more common to use the term "normal." When possible avoid expressions like maldeveloped or undeveloped, errors of development, defective genitals, abnormal, or mistakes of nature. Emphasize that all of these conditions are biologically understandable while they are statistically uncommon.[98]

Some people with intersex traits self-identify as intersex, and some do not.[99][100] Australian sociological research published in 2016, found that 60% of respondents used the term "intersex" to self-describe their sex characteristics, including people identifying themselves as intersex, describing themselves as having an intersex variation or, in smaller numbers, having an intersex condition. A majority of 75% of survey respondents also self-described as male or female.[28] Respondents also commonly used diagnostic labels and referred to their sex chromosomes, with word choices depending on audience.[28][94] Research by the Lurie Children's Hospital, Chicago, and the AIS-DSD Support Group published in 2017 found that 80% of affected Support Group respondents "strongly liked, liked or felt neutral about intersex" as a term, while caregivers were less supportive.[101] The hospital reported that "disorders of sex development" may negatively affect care.[102]

Some intersex organizations reference "intersex people" and "intersex variations or traits"[103] while others use more medicalized language such as "people with intersex conditions",[104] or people "with intersex conditions or DSDs (differences of sex development)" and "children born with variations of sex anatomy".[105] In May 2016, Interact Advocates for Intersex Youth published a statement recognizing "increasing general understanding and acceptance of the term "intersex"".[106]

However, a study by the American Urological Association found that 53% of participants didnt like the term intersex.[107] Another study in 2020 found that 43% didnt like the term intersex.[108] Another study in 2020 found that around 43% of 179 participants thought the term intersex was bad, while 20% felt neutral about the term.[109]

A hermaphrodite is an organism that has both male and female reproductive organs. Until the mid-20th century, "hermaphrodite" was used synonymously with "intersex".[50] The distinctions "male pseudohermaphrodite", "female pseudohermaphrodite" and especially "true hermaphrodite"[110] are terms no longer used, which reflected histology (microscopic appearance) of the gonads.[111][112][113] Medical terminology has shifted not only due to concerns about language, but also a shift to understandings based on genetics.

Currently, hermaphroditism is not to be confused with intersex, as the former refers only to a specific phenotypical presentation of sex organs and the latter to a more complex combination of phenotypical and genotypical presentation. Using hermaphrodite to refer to intersex individuals is considered to be stigmatizing and misleading.[114] Hermaphrodite is used for animal and plant species in which the possession of both ovaries and testes is either serial or concurrent, and for living organisms without such gonads but present binary form of reproduction, which is part of the typical life history of those species; intersex has come to be used when this is not the case.

"Disorders of sex development" (DSD) is a contested term,[9][10] defined to include congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. Members of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology adopted this term in their "Consensus statement on management of intersex disorders".[8][52] While it adopted the term, to open "many more doors", the now defunct Intersex Society of North America itself remarked that intersex is not a disorder.[115] Other intersex people, activists, supporters, and academics have contested the adoption of the terminology and its implied status as a "disorder", seeing this as offensive to intersex individuals who do not feel that there is something wrong with them, regard the DSD consensus paper as reinforcing the normativity of early surgical interventions, and criticize the treatment protocols associated with the new taxonomy.[116]

Sociological research in Australia, published in 2016, found that 3% of respondents used the term "disorders of sex development" or "DSD" to define their sex characteristics, while 21% use the term when accessing medical services. In contrast, 60% used the term "intersex" in some form to self-describe their sex characteristics.[94] U.S. research by the Lurie Children's Hospital, Chicago, and the AIS-DSD Support Group published in 2017 found that "disorders of sex development" terminology may negatively affect care, give offense, and result in lower attendance at medical clinics.[102][101]

Alternatives to categorizing intersex conditions as "disorders" have been suggested, including "variations of sex development".[11] Organisation Intersex International (OII) questions a disease/disability approach, argues for deferral of intervention unless medically necessary, when fully informed consent of the individual involved is possible, and self-determination of sex/gender orientation and identity.[117] The UK Intersex Association is also highly critical of the label 'disorders' and points to the fact that there was minimal involvement of intersex representatives in the debate which led to the change in terminology.[118] In May 2016, Interact Advocates for Intersex Youth also published a statement opposing pathologizing language to describe people born with intersex traits, recognizing "increasing general understanding and acceptance of the term "intersex"".[106]

However, another study found that around 69% agree the term disorders of sex development applied to their condition or were neutral, 31% thought the term didnt apply to their condition.[119]

Intersex can be contrasted with transgender,[120] which is the condition in which one's gender identity does not match one's assigned sex.[120][121][122] Some people are both intersex and transgender.[123] A 2012 clinical review paper found that between 8.5% and 20% of people with intersex variations experienced gender dysphoria.[86] In an analysis of the use of preimplantation genetic diagnosis to eliminate intersex traits, Behrmann and Ravitsky state: "Parental choice against intersex may ... conceal biases against same-sex attractedness and gender nonconformity."[124]

The relationship of intersex to lesbian, gay, bisexual and trans, and queer communities is complex,[125] but intersex people are often added to LGBT to create an LGBTI community. Emi Koyama describes how inclusion of intersex in LGBTI can fail to address intersex-specific human rights issues, including creating false impressions "that intersex people's rights are protected" by laws protecting LGBT people, and failing to acknowledge that many intersex people are not LGBT.[126] Organisation Intersex International Australia states that some intersex individuals are same sex attracted, and some are heterosexual, but "LGBTI activism has fought for the rights of people who fall outside of expected binary sex and gender norms."[127][128] Julius Kaggwa of SIPD Uganda has written that, while the gay community "offers us a place of relative safety, it is also oblivious to our specific needs".[129] Mauro Cabral has written that transgender people and organizations "need to stop approaching intersex issues as if they were trans issues" including use of intersex as a means of explaining being transgender; "we can collaborate a lot with the intersex movement by making it clear how wrong that approach is".[130]

An intersex character is the narrator in Jeffrey Eugenides' Pulitzer Prize-winning novel Middlesex.

The memoir, Born Both: An Intersex Life (Hachette Books, 2017), by intersex author and activist Hida Viloria, received strong praise from The New York Times Book Review, The Washington Post, Rolling Stone, People Magazine, and Psychology Today, was one of School Library Journal's 2017 Top Ten Adult Books for Teens, and was a 2018 Lambda Literary Award nominee.

Television works about intersex and films about intersex are scarce. The Spanish-language film XXY won the Critics' Week grand prize at the 2007 Cannes Film Festival and the ACID/CCAS Support Award.[131] Faking It is notable for providing both the first intersex main character in a television show,[132] and television's first intersex character played by an intersex actor.[133]

Intersex peer support and advocacy organizations have existed since at least 1985, with the establishment of the Androgen Insensitivity Syndrome Support Group Australia in 1985.[134] The Androgen Insensitivity Syndrome Support Group (UK) established in 1988.[135] The Intersex Society of North America (ISNA) may have been one of the first intersex civil society organizations to have been open to people regardless of diagnosis; it was active from 1993 to 2008.[136]

Intersex Awareness Day is an internationally observed civil awareness day designed to highlight the challenges faced by intersex people, occurring annually on 26 October. It marks the first public demonstration by intersex people, which took place in Boston on 26 October 1996, outside a venue where the American Academy of Pediatrics was holding its annual conference.[137]

Intersex Day of Remembrance, also known as Intersex Solidarity Day, is an internationally observed civil awareness day designed to highlight issues faced by intersex people, occurring annually on 8 November. It marks the birthday of Herculine Barbin, a French intersex person whose memoirs were later published by Michel Foucault in Herculine Barbin: Being the Recently Discovered Memoirs of a Nineteenth-century French Hermaphrodite.

In Hinduism, Sangam literature uses the word pedi to refer to people born with an intersex condition; it also refers to antharlinga hijras and various other hijras.[138] Warne and Raza argue that an association between intersex and hijra people is mostly unfounded but provokes parental fear.[57]

In Judaism, the Talmud contains extensive discussion concerning the status of two intersex types in Jewish law; namely the androgynous, which exhibits both male and female external sexual organs, and the tumtum which exhibits neither. In the 1970s and 1980s, the treatment of intersex babies started to be discussed in Orthodox Jewish medical halacha by prominent rabbinic leaders, for example Eliezer Waldenberg and Moshe Feinstein.[139]

Erik Schinegger, Foekje Dillema, Maria Jos Martnez-Patio and Santhi Soundarajan were subject to adverse sex verification testing resulting in ineligibility to compete in organised competitive competition. Stanisawa Walasiewicz was posthumously ruled ineligible to have competed.[140]

The South African middle-distance runner Caster Semenya won gold at the World Championships in the women's 800 metres and won silver in the 2012 Summer Olympics. When Semenya won gold in the World Championships, the International Association of Athletics Federations (IAAF) requested sex verification tests. The results were not released. Semenya was ruled eligible to compete.[141]

Katrina Karkazis, Rebecca Jordan-Young, Georgiann Davis and Silvia Camporesi have claimed that IAAF policies on "hyperandrogenism" in female athletes, are "significantly flawed", arguing that the policy will not protect against breaches of privacy, will require athletes to undergo unnecessary treatment in order to compete, and will intensify "gender policing". They recommend that athletes be able to compete in accordance with their legally recognised gender.[142]

In April 2014, the BMJ reported that four elite women athletes with 5-ARD (an intersex medical condition) were subjected to sterilization and "partial clitoridectomies" in order to compete in sport. The authors noted that partial clitoridectomy was "not medically indicated" and "does not relate to real or perceived athletic 'advantage'."[16] Intersex advocates regard this intervention as "a clearly coercive process".[143] In 2016, the United Nations Special Rapporteur on health, Dainius Pras, criticized "current and historic" sex verification policies, describing how "a number of athletes have undergone gonadectomy (removal of reproductive organs) and partial clitoridectomy (a form of female genital mutilation) in the absence of symptoms or health issues warranting those procedures."[144]

Estimates of the number of people who are intersex vary, depending on which conditions are counted as intersex.[145]

Leonard Sax estimated that the prevalence of intersex was about 0.018% of the world's population.[145] A 2018 review reported that the number of births with ambiguous genitals is in the range of 0.02% to 0.05%.[25]

The now-defunct Intersex Society of North America stated that:

If you ask experts at medical centers how often a child is born so noticeably atypical in terms of genitalia that a specialist in sex differentiation is called in, the number comes out to about 1 in 1500 to 1 in 2000 births [0.070.05%]. But a lot more people than that are born with subtler forms of sex anatomy variations, some of which won't show up until later in life.[146]

Anne Fausto-Sterling and her co-authors said in two articles in 2000 that 1.7 percent of human births (1 in 60) might be intersex, including variations that may not become apparent until, for example, puberty, or until attempting to conceive.[147][148] Their publications have been widely quoted,[62][149][150] though aspects are now considered outdated, such as use of the now scientifically incorrect term hermaphrodite.[151]Eric Vilain et al. highlighted in 2007 that the term disorders of sex development (DSD) had replaced "hermaphrodite" and improper medical terms based on it.[152]

Of the 1.7%, 1.5 percentage points (88% of those considered intersex in this figure) consist of individuals with late onset congenital adrenal hyperplasia (LOCAH). Leonard Sax stated that "[f]rom a clinicians perspective, however, LOCAH is not an intersex condition."[145]

The figure of 1.7% is still maintained by Intersex Human Rights Australia "despite its flaws".[153] "This estimate relates to any 'individual who deviates from the Platonic ideal of physical dimorphism at the chromosomal, genital, gonadal, or hormonal levels' and thus it encapsulates the entire population of people who are stigmatized or risk stigmatization due to innate sex characteristics."

Individuals with diagnoses of disorders of sex development (DSD) may or may not experience stigma and discrimination due to their sex characteristics, including sex "normalizing" interventions. Human rights institutions have called for the de-medicalization of intersex traits, as far as possible.[20][62][154][155]

The following summarizes some prevalence figures of intersex traits (a fuller 'List of conditions' is provided below, at the end of 'Medical classifications'):

Population figures can vary due to genetic causes. In the Dominican Republic, 5-alpha-reductase deficiency is not uncommon in the town of Las Salinas, resulting in social acceptance of the intersex trait.[175] Men with the trait are called "gevedoces" (Spanish for "eggs at twelve"). 12 out of 13 families had one or more male family members that carried the gene. The overall incidence for the town was 1 in every 90 males were carriers, with other males either non-carriers or non-affected carriers.[176]

The common pathway of sexual differentiation, where a productive human female has an XX chromosome pair, and a productive male has an XY pair, is relevant to the development of intersex conditions.

During fertilization, the sperm adds either an X (female) or a Y (male) chromosome to the X in the ovum. This determines the genetic sex of the embryo.[177] During the first weeks of development, genetic male and female fetuses are "anatomically indistinguishable", with primitive gonads beginning to develop during approximately the sixth week of gestation. The gonads, in a "bipotential state", may develop into either testes (the male gonads) or ovaries (the female gonads), depending on the consequent events.[177] Through the seventh week, genetically female and genetically male fetuses appear identical.

At around eight weeks of gestation, the gonads of an XY embryo differentiate into functional testes, secreting testosterone. Ovarian differentiation, for XX embryos, does not occur until approximately week 12 of gestation. In typical female differentiation, the Mllerian duct system develops into the uterus, Fallopian tubes, and inner third of the vagina.In males, the Mllerian duct-inhibiting hormone MIH causes this duct system to regress. Next, androgens cause the development of the Wolffian duct system, which develops into the vas deferens, seminal vesicles, and ejaculatory ducts.[177]By birth, the typical fetus has been completely "sexed" male or female, meaning that the genetic sex (XY-male or XX-female) corresponds with the phenotypical sex; that is to say, genetic sex corresponds with internal and external gonads, and external appearance of the genitals.

There are a variety of symptoms that can occur. Ambiguous genitalia being the most common sign, there can be micropenis, clitoromegaly, partial labial fusion, electrolyte abnormalities, delayed or absent puberty, unexpected changes at puberty, hypospadias, labial or inguinal (groin) masses (which may turn out to be testes) in girls and undescended testes (which may turn out to be ovaries) in boys.[178]

Ambiguous genitalia may appear as a large clitoris or as a small penis.

Because there is variation in all of the processes of the development of the sex organs, a child can be born with a sexual anatomy that is typically female or feminine in appearance with a larger-than-average clitoris (clitoral hypertrophy) or typically male or masculine in appearance with a smaller-than-average penis that is open along the underside. The appearance may be quite ambiguous, describable as female genitals with a very large clitoris and partially fused labia, or as male genitals with a very small penis, completely open along the midline ("hypospadic"), and empty scrotum. Fertility is variable.

The orchidometer is a medical instrument to measure the volume of the testicles. It was developed by Swiss pediatric endocrinologist Andrea Prader. The Prader scale[179] and Quigley scale are visual rating systems that measure genital appearance. These measurement systems were satirized in the Phall-O-Meter, created by the (now defunct) Intersex Society of North America.[180][181][182]

In order to help in classification, methods other than a genitalia inspection can be performed. For instance, a karyotype display of a tissue sample may determine which of the causes of intersex is prevalent in the case. Additionally, electrolyte tests, endoscopic exam, ultrasound and hormone stimulation tests can be done.[183]

Intersex can be divided into four categories which are: 46, XX intersex; 46, XY intersex; true gonadal intersex; and complex or undetermined intersex.[citation needed]

This condition used to be called "female pseudohermaphroditism". Persons with this condition have female internal genitalia and karyotype (XX) and various degree of external genitalia virilization.[184] External genitalia is masculinized congenitally when female fetus is exposed to excess androgenic environment.[178] Hence, the chromosome of the person is of a woman, the ovaries of a woman, but external genitals that appear like a male. The labia fuse, and the clitoris enlarges to appear like a penis. The causes of this can be male hormones taken during pregnancy, congenital adrenal hyperplasia, male-hormone-producing tumors in the mother and aromatase deficiency.[178]

This condition used to be called "male pseudohermaphroditism". This is defined as incomplete masculinization of the external genitalia.[185] Thus, the person has the chromosomes of a man, but the external genitals are incompletely formed, ambiguous, or clearly female.[178][186] This condition is also called 46, XY with undervirilization.[178] 46, XY intersex has many possible causes, which can be problems with the testes and testosterone formation.[178] Also, there can be problems with using testosterone. Some people lack the enzyme needed to convert testosterone to dihydrotestosterone, which is a cause of 5-alpha-reductase deficiency.[178] Androgen Insensitivity Syndrome is the most common cause of 46, XY intersex.[178]

This condition used to be called "true hermaphroditism". This is defined as having asymmetrical gonads with ovarian and testicular differentiation on either sides separately or combined as ovotestis.[187] In most cases, the cause of this condition is unknown; however, some research has linked it to exposure to common agricultural pesticides.[187]

This is the condition of having any chromosome configurations rather than 46, XX or 46, XY intersex.[178] This condition does not result in any imbalance between internal and external genitalia.[178] However, there may be problems with sex hormone levels, overall sexual development, and altered numbers of sex chromosomes.[178]

There are a variety of opinions on what conditions or traits are and are not intersex, dependent on the definition of intersex that is used. Current human rights based definitions stress a broad diversity of sex characteristics that differ from expectations for male or female bodies.[2] During 2015, the Council of Europe,[62] the European Union Agency for Fundamental Rights[154] and Inter-American Commission on Human Rights[155] have called for a review of medical classifications on the basis that they presently impede enjoyment of the right to health; the Council of Europe expressed concern that "the gap between the expectations of human rights organisations of intersex people and the development of medical classifications has possibly widened over the past decade".[62][154][155]

Medical interventions take place to address physical health concerns and psychosocial risks. Both types of rationale are the subject of debate, particularly as the consequences of surgical (and many hormonal) interventions are lifelong and irreversible. Questions regarding physical health include accurately assessing risk levels, necessity, and timing. Psychosocial rationales are particularly susceptible to questions of necessity as they reflect social and cultural concerns.

There remains no clinical consensus about an evidence base, surgical timing, necessity, type of surgical intervention, and degree of difference warranting intervention.[188][189][190] Such surgeries are the subject of significant contention due to consequences that include trauma, impact on sexual function and sensation, and violation of rights to physical and mental integrity.[1] This includes community activism,[48] and multiple reports by international human rights[18][62][22][191] and health[83] institutions and national ethics bodies.[21][192]

In the cases where gonads may pose a cancer risk, as in some cases of androgen insensitivity syndrome,[193] concern has been expressed that treatment rationales and decision-making regarding cancer risk may encapsulate decisions around a desire for surgical "normalization".[20]

Notes

Bibliography

Media related to Intersex at Wikimedia Commons

Read more:
Intersex - Wikipedia

The human geneticist Bryan Sykes, who has died aged 73, pushed forward the analysis of inherited conditions such as brittle bone disease and double-jointedness, and was one of the first to extract DNA from ancient bone.

The same Bryan Sykes, holder of a personal chair at Oxford University, analysed hair supposedly taken from mythical hominids such as the Bigfoot and Yeti, and announced the results in a three-part television series. His delight in science and enthusiasm for communicating it to popular audiences were both aspects of an expansive personality that alternately inspired and exasperated his colleagues.

Sykes was not the only one to realise that the ability to read sequences of DNA code opened up the possibility of tracing human ancestry to our early origins. He was exceptional, however, in seeing that the wider public would connect emotionally to these stories if the dry details of the science could be presented accessibly. His book The Seven Daughters of Eve (2001) proposed that every living European could trace his or her ancestry to one of seven women living between 8,500 and 45,000 years ago. They, in turn, would share descent from a single Eve, who lived in Africa even earlier. He gave the seven women names and, anticipating peoples desire to know which tribe they belonged to, the same year set up the first direct-to-consumer genetic testing company, Oxford Ancestors, as an Oxford University spinout.

Sykes began this work long before modern methods of whole-genome DNA sequencing were available. When, in the late 1980s, he, Erica Hagelberg and Robert Hedges of Oxfords Research Laboratory for Archaeology first extracted DNA from bones up to 12,000 years old, they opted to focus on mitochondrial DNA (mtDNA). There are more than 1,000 mitochondria in each cell but only one nucleus (where most of our DNA resides), increasing the chances of retrieving mtDNA. But Sykes soon appreciated that it has another property. It is inherited largely unchanged in the maternal line over thousands of years, while nuclear DNA is mixed with every generation. To test whether it would be possible to use mtDNA to trace distant ancestors, Sykes first confirmed that domesticated golden hamsters from numerous locations, which he had heard were all descended from a single wild-caught female, had the same signature in their mtDNA.

Sykes went on to use this method to solve the mystery of the origins of islanders scattered throughout the Pacific Ocean: whether they had arrived from the Americas, as Thor Heyerdahl had suggested on the basis of the 1947 voyage of the Kon-Tiki raft, or from Asia. Receiving hospital treatment on Raratonga in the Cook Islands after a motorcycle accident while on holiday in the mid-90s, Sykes realised he could resolve this uncertainty using mtDNA. He went on to collect samples from Pacific islands and Pacific Rim countries, and established that Polynesia was in fact entirely settled from Asia.

In 1987 he won a British Association for the Advancement of Science media fellowship that enabled him to spend seven weeks working with Channel 4 News. The lessons he learned about what makes a good story came to the fore in Seven Daughters and his subsequent books.

Adams Curse (2003) drew some controversial conclusions about the influence of the Y chromosome on male behaviour, but also covered studies that traced descent via Y chromosomes. These pass from father to son, like British surnames, though without the uncertainty introduced by nonpaternity events. When the chairman of the pharmaceutical company GlaxoSmithKline, Sir Richard Sykes, wondered if the two of them might be related, Bryan collected DNA from dozens of Sykeses in Britain. He discovered that more than half of them shared the same unusual Y chromosome variant, suggesting a single founding father in Yorkshire in the 13th or 14th century.

His collaboration with enthusiasts searching for the Bigfoot and Yeti raised eyebrows even higher. Hairs from bits of mystery creatures that had long lain in museums and temples made their way to his lab. The three-part Channel 4 series Bigfoot Files (2015) maintained the suspense to the end, but all the samples proved to come from known animal species. A hasty claim that a Yeti specimen was a match to a prehistoric polar bear proved to be a case of mistaken identity. For Sykes it was all education as entertainment he never seriously believed that such creatures existed, but sought to encourage curiosity rather than squashing it.

Born in London, Bryan was the son of Frank Sykes, an accountant, and his wife, Irene. He attended the independent boys school Eltham college, near his home in south-east London, and developed passions for the natural world, experiments and inventions. He also excelled at cross-country running, rugby and swimming.

He studied biochemistry at the University of Liverpool, and did a PhD at the University of Bristol on the connective tissue protein elastin. He arrived at Oxford in 1973 as a research fellow in the Nuffield department of orthopaedic surgery, continuing to work on elastin and collagen. By the time he was appointed lecturer in molecular pathology in 1987, he was deploying new genetic techniques to explore inherited disorders of bone and connective tissue. His collagen genetics group moved from orthopaedic surgery to Oxfords newly established Institute of Molecular Medicine, founded by the geneticist Sir David Weatherall, who was an important mentor. He was appointed to a personal chair in human genetics in 1997, and formally retired in 2016.

Sykess expertise in bone led to his involvement in the effort to extract DNA from ancient specimens. As his interest in studies of human populations developed, he recruited lab members who worked in that area alongside those who continued his pathological studies. Colleagues remember the lab as being unusually collaborative, though occasionally disrupted by TV cameras, and Sykes himself as encouraging and supportive. He took them all to Scotland in 1998 to assist with the collection of samples for his work on prehistoric migration into Britain (published as Blood of the Isles, 2006). A keen fisherman, he got out his rods in the bar of their hotel to teach them how to cast a fly.

Sykes was extremely smart and a brilliant communicator, with a streak of mischief: he didnt turn a hair when Italian colleagues casually invited him to access the bone store at Pompeii by climbing over a fence (they had arrived before opening time), and there was always champagne in the lab when anyone published a paper.

Sykes met Sue Foden when she was a student in Oxford, and they were married in 1978. Though the marriage was annulled in 1984, he and Sue remained close and had a son, Richard, born in 1991. His later marriage to Janis Wilson ended in divorce. In 2007 he collaborated with the Danish artist Ulla Plougmand on an exhibition featuring the seven daughters of Eve, and their subsequent relationship lasted until the end of his life. In later years, as his health deteriorated, Bryan was increasingly supported and cared for by Sue. She, Ulla and Richard survive him.

Bryan Clifford Sykes, geneticist, born 9 September 1947; died 10 December 2020

See original here:
Bryan Sykes obituary - The Guardian

Smoking is consistently seen as a risk for various cancers, and in recent years it has been connected to colorectal cancer in particular. In 2014, the US Surgeon General issued a report on tobacco claiming smoking as a direct cause of colorectal and liver cancer, and a factor that increases the failure rate of cancer treatment.

Several studies have been conducted that assess the link between smoking and colorectal cancer, including one in 2020 in the American Journal of Epidemiology examining how anatomic subsite and sex affect risk. What are some of the specific colorectal cancer risks clinicians can discuss with patients who smoke?

This study evaluated more than 215,000 men and women from 45 to 75 years old. These participants were enrolled from 1993 to 1996 and answered a questionnaire that included information on their smoking habits and ascertained information on colorectal cancer history through either their death or through December 31, 2013.

The researchers found that while female smokers had less pack-years of smoking than male smokers, both sexes had similar smoking-related risk for colorectal cancer. Clinicians should make their female patients aware that they may be putting themselves at significant risk for colorectal cancer regardless of how long they have been smoking.

The researchers also found that postmenopausal women in particular had high smoking-related risk of right colon cancer. This finding held true regardless of whether participants had undergone hormone therapy during menopause. When discussing smoking-related risks for women, physicians should let these patients know that they may face even greater risk once they go through menopause.

An October 2020 study published in Cancer Research and Management investigated colorectal cancer risk factors and found tobacco use to be a significant contributing factor. In addition to estimating that 12% of colorectal cancer deaths can be attributed to tobacco use, the researchers claim that smokers showed an earlier average age of onset of colorectal cancer.

Frequent alcohol consumption has also been associated with colorectal cancer risk. Patients who smoke should be advised of this, as there can be a social relationship between alcohol and tobacco use that can potentially increase add risk.

Smoking in tandem with certain diseases may present individuals with unique risks. A 2020 study published in Medicine (Baltimore) looked at risk factors associated with colorectal cancer in patients with ulcerative colitis. The researchers found that while only 5.5% of the 254 subjects were smokers at their last recorded appointment, active smoking was a significant risk factor for colorectal cancer. In this study, former smokers were categorized as nonsmokers.

Although any smoking history may be a risk for colorectal cancer, medical professionals may want to warn patients that active and prolonged smoking habits may present an added risk for them.

References

Read more here:
Smoking Risks for Colorectal Cancer to Discuss With Patients - Cancer Therapy Advisor

In 1932, when there was no known treatment for syphilis, the US Public Health Service (PHS) began a study into the disease at the Tuskegee Institute. The agency recruited 600 Black men into the project, primarily impoverished sharecroppers who had never visited a doctor before. Of this group, 399 had latent syphilis, while 201 others were disease-free. The participants were informed that they were being treated for bad blood, a colloquialism that was used at the time to describe numerous conditions.

The men were treated with placebos, such as aspirin and supplements, even after penicillin began to be recommended to treat syphilis in 1947, so that researchers could use them to follow the full progression of the disease. The men were not helped even as the disease progressed to late-stage infection, in which people experience a wide range of neurological symptoms including erratic behaviour, paralysis, sensory loss and eventually death. It can take up to 20 years from initial infection for these symptoms to manifest.

Details of the study were leaked to the press by a social worker and epidemiologist named Peter Buxtun in 1972. Buxtun had learned of the existence of the study in 1965 when he began working for the PHS and had unsuccessfully attempted to get it shut down twice over the following years. The story prompted public outrage and forced the study to finally be cancelled, four decades after it initially began.

By this stage, 28 of the participants had died from syphilis and 100 more had died of related complications. At least 40 of their spouses had been diagnosed with the disease and it had been passed down to 19 of the participants children.

Historical atrocities such as the Tuskegee experiment have left many people from communities of colour distrustful of the medical sector. Its a major problem, one that has become even more serious in the age of Covid-19.

People of colour have been shown to face higher mortality rates from the disease in both the US and UK. This is due to a multitude of intersecting demographic, geographical and socioeconomic factors, such as place of residence and occupational exposures. Extensive evidence also indicates that people of colour still do not receive the same levels of care as white people in community healthcare settings, which only exacerbates the matter.

Now, surveys in the US have shown that Covid-19 vaccine hesitancy is significantly higher among Black people than white people, with half of Black adults saying they wont take a Covid-19 vaccine. Likewise, a UK study has found that Black, Asian and minority ethnic (BAME) people were almost three times more likely to reject a Covid-19 vaccine for themselves and their children than the white population.

This mistrust is unsurprising given that US surveys have found medical staff to be less communicative with non-white patients than with white patients. A 2016 study even found that white medical students in the US were shockingly likely to believe Black patients experienced less pain than white patients.

Across the pond, BAME patients in the UK have reported lower satisfaction with the NHS and an overall less positive experience with doctors and nurses than white patients. Black women in the UK are five times more likely than white women to die during childbirth, and over 60% of Black people do not believe their health is as protected by the NHS as white peoples is.

Black people have generationally been hesitant to engage on initiatives like clinical trials and vaccines, says African Caribbean Leukaemia Trust (ACLT) co-founder and CEO Orin Lewis OBE. Thats historical, based on what has been done to the Black race for a long, long time throughout our history. People start to feel that if the medical establishment is going to trial something, theyll try it first on Black people, because were expendable. Whether thats true or not, it very much becomes folklore and trust becomes a problem.

People of colour are also less likely than white people to volunteer to take part in medical research. In the UK, 93% of people who signed up for the trials registry for the development of the Covid-19 vaccine were white.

People of colour have disproportionately suffered throughout the pandemic, in both the UK and US, but the legacy of institutional racism in medicine still leaves many mistrustful of the Covid-19 vaccine.

The medical establishment doesnt want to acknowledge this, they just kind of want to forget about it, says TruGenomix co-founder and chief scientific officer Dr Tshaka Cunningham. Thats not what certain communities are dealing with, particularly the African American community. That type of stuff leaves a psychological scar, but it can be overcome with rebuilding.

One way to heal these historic wounds, Cunningham says, is through the work of medical industry honest brokers. Honest brokers refer here to people of colour who are knowledgeable about medical matters, who can then share this insight with other members of their community.

Cunningham says: Lets say I were to bring a white male scientist in to talk to a group of African American church members. Theyre going to listen and be polite, but theyre not really going to trust it. When I deliver the same message, but Im just from the community, it gives a certain level of authenticity to it that helps them get over their distrust.

As a member of the Faith-based Genetic Research Institute, Cunningham goes into communities of colour predominantly African American churches to talk about genetics and genomics research and how and why people of colour can and should get involved. This year, these conversations have expanded to Covid-19 too.

Cunningham says: What I do almost daily is interface with different groups of people of colour, even in my local networks, about Covid-19 and how to stay safe. Ive done podcasts, Ive been on internet shows, Ive been on Instagram feeds with prominent hosts, talking specifically to minority communities about what we need to do to stay safe and debunking any myths that they have.

The burden here cannot fall on the honest broker alone its important work, but theres a limit to what can be expected of individual people facing up to an issue that requires institutional change. The medical industry at large, from pharmaceutical companies to public health organisations, needs to do far, far more.

Cunningham says: Once you have more Black and Brown people participating, it cant just be all on them to build the trust. Trust is a two-way street. People need to be really authentic and engaged and not view themselves as other or their patients as other.

I give some very simple solutions. Firstly, diversify the medical workforce, diversify the scientific research workforce and be very intentional about it. If you havent created opportunities or blocked certain groups from having opportunities to get training and to rise up in careers in these areas, then stop that process, because thats institutional racism.

Secondly, be authentic, engage with the community and allow the community to share in the profits that come out of their participation. Dont come to the Black and Brown community and say give us your health information and not give anything back.

I think a final piece is that just as the government has contributed to making it bad, they need to contribute to making it better. That will require some specific funding on things like cultural competency training.

The best thing to do would be some public health campaigns with scientists like myself alongside prominent sporting figures and celebrities. Lets say you took LeBron James and teamed him with me and some of my scientific colleagues that are people of colour and did a PSA about the vaccine that would send the right message to people.

The historical suffering of people of colour at the hands of the medical establishment isnt something that can be overcome overnight. The industry urgently needs to pay more credence to the concerns and fears of people of colour, in order to build the level of trust needed to ensure that vaccine uptake among ethnic minorities.

Theres no silver bullet, and things like grassroots community advocacy and engagement, diversifying the face of the industry and public health campaigns targeted at people of colour will all be necessary in ensuring the uptake of the vaccine and developing a medical industry that serves the needs of all patients.

Passive Thermal Protection and Cargo Security Solutions for the Global Supply Chain

28 Aug 2020

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Racism in the medical industry could harm the Covid-19 vaccine rollout - pharmaceutical-technology.com

Supporting stockmen in the region is a crucial part of the clubs activities and a fantastic display of young animals were brought forward to the selected venues Ballymena, Hilltown, Swatragh, Enniskillen, Keady, Camlough, Armoy, Dungannon, Markethill and Clogher. Given the restrictions we found ourselves in this year it was up to the market how they saw fit to distribute out the prize money.

Attracting good local support, the sales are always an excellent window of opportunity for commercial buyers to obtain Limousin cross cattle that are suitable for the current beef market. This year was no exception.

1st Prize 400kg 2100 (5.25p) sold by OKane Farm Ltd, Dunloy , Ballymena.

2nd Prize 350kg 1700 (4.85p) sold by Ian Lynn, Glenshesk Armoy.

3rd Prize 380kg 1820 (4.79p) - sold by Ian Lynn, Glenshesk Armoy.

1st Prize 270kg 900 (3.33p) sold by J Campbell, Ballyvaddy Road, Carnlough.

2nd Prize 210kg 700 (3.33p) sold by ST MACNISSIS College, Garron Tower.

3rd Prize 270kg 890 (3.29p) sold by J Campbell, Ballyvaddy Road, Carnlough

1st Prize 320kg 880 (2.75p) Sold by D Litter, Derrall Road, Portadown.

2nd Prize 260kg 700 (2.69p) Sold by D Litter, Derrall Road, Portadown.

1st Prize - 300kg 930 (3.10p) sold by N Hammond, Ballymaguire, Stewartstown.

2nd Prize 270kg 805 (2.98p) sold by N Hammond, Ballymaguire, Stewartstown.

1st Prize 318kg 1370 (4.30p) sold by Nigel Deens, Markethill

2nd Prize 340kg 1260 (3.71p) sold by J Rice , Armagh

1st Prize 244kg 770 (3.15p) sold by E McKeown, Crossmaglen

2nd Prize 284kg 880 (3.10p) sold by A Nugent , Keady

1st Prize 285kg 790 (2.77p) sold by Gabriel Emerson, Cushendall

2nd Prize 254kg 650 (2.56p) sold by Danny McBride, Ballycastle

1st Prize 230kg 720 (3.13p) sold by Gabriel Emerson, Cushendall

2nd Prize 210kg 650kg (3.10p) sold by Gabriel Emerson, Cushendall

1st Prize 308kg 1260 (4.09p) sold by Paul Faulkner

2nd Prize 356kg 1400 (3.93p) sold by Martin Diamond

1st Prize 282kg 930 (3.30p) sold by Paul Faulkner

2nd Prize - 452kg 1410 (3.12p) sold by Paul Faulkner

1st Prize 440kg 2250 (5.11p) sold by Darren McSorley, Omagh

2nd Prize 440kg 1900 (4.32p) Sold by Darren McSorley, Omagh

1st Prize 550kg 1250 (2.50p) sold by Ian Elliott, Enniskillen

2nd Prize 535kg 1100 (2.05p) sold by Jason Sawyers , Sixmilecross

1st Prize - 293.90 per 100 kilos sold by Alan Falloon, Armagh

2nd Prize - 282.60 per 100 kilos sold by P J McNally

1st Prize - 361.10 per 100 kilos sold by P J McNally

2nd Prize - 316.00 per 100 kilos sold by Joe Smith

1st Prize - 391.30 per 100 kilos sold by Kevin and Gerard McKee

2nd Prize - 314.80 per 100 kilos sold by Kevin and Gerard McKee

1st Prize -367.70 per 100 kilos sold by Thomas Nugent

2nd Prize 316.70 per 100 kilos sold by Kevin and Gerard McKee

1st Prize 326kg 1180 (3.62p) sold by Emmett Kelly, Augher, Co Tyrone

2nd Prize 392kg 1400 (3.57p) sold by Gordon Cutler, Florencecourt, Enniskillen

1st Prize 250kg 730 (2.92p) sold by Raymond McGovern, Derrylin

2nd Prize 270kg 740 (2.74p) sold by Raymond McGovern, Derrylin

Successful exhibitors were:

1st Prize Leo and Aaron Fearon

3rd Prize Leo and Aaron Fearon

The strength in the market for Limousin calves demonstrates how the breeds genetics continue to stand out within the sector.

The market demands fast finishing, efficient, low-cost cattle that produce carcases consistent in weight and quality.

It is a blueprint for the breed, one which it delivers extremely well and is the principle reason that buyers seek Limousin stock of all ages.

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Local Limousin calves are on the money at recent suckled calf sales - Farming Life

Recent reports suggest that both clinical and genetic risk factors may contribute to COVID-19 susceptibility and severity. Catherine Ball, Chief Scientific Officer of Ancestry, discusses results of the companys COVID-19 Research Study, designed to explore non-genetic and genetic associations with disease outcomes.

ONE OF THE more puzzling aspects of SARS-CoV-2, the causative agent of COVID-19, is that infection can produce a remarkably diverse spectrum of outcomes, ranging from asymptomatic to fatal. In the US, most infections result in mild illness that can be managed at home, yet about 14 percent of cases are hospitalised and approximately five percent are fatal.

Known risk factors for severe COVID-19, as identified by epidemiological studies, include common health conditions such as hypertension, diabetes and obesity as well as older age and male sex. For example, reports of higher susceptibility to and severity of SARS-CoV-2 infections in men could suggest important differences in immune response to the virus in men relative to women.

The growing toll of the COVID-19 pandemic has heightened the urgency of identifying those who are most at risk of infection and severe outcomes

Emerging evidence suggests that genetic variation may contribute to COVID-19 susceptibility and severity. An early genome-wide association study (GWAS) of COVID-19 cases with respiratory failure identified two genetic loci that achieved genome-wide significance: one signal on chromosome 9 near the ABO gene, which determines blood type, and one signal on chromosome 3 near a cluster of genes with known immune function.1 Both genetic signals were later replicated by meta-analyses conducted by the COVID-19 Host Genetics Initiative (HGI), which combines more than 30 individual GWAS. The HGI additionally identified novel associations on chromosome 6, near FOXP4; on chromosome 12, near a gene cluster encoding antiviral restriction enzyme activators; on chromosome 19 near TYK2; and on chromosome 21, near IFNAR2. Multiple studies have also reported evidence of rare-variant associations, though such discoveries have not yet successfully been replicated in independent cohorts.

The growing toll of the COVID-19 pandemic has heightened the urgency of identifying those who are most at risk of infection and severe outcomes; hence, the need for further investigation to assess patterns of susceptibility and severity in large datasets. The Ancestry COVID-19 Research Study, one of the largest studies of infection susceptibility and severity to date, was designed to:

To replicate and discover non-genetic and genetic associations with COVID-19 outcomes, we engaged AncestryDNA adult members in the US a majority of the 18 million individuals in our global network. On 22 April 2020, we issued a 54-question COVID-19 survey intended to assess exposure, risk factors, symptomatology and demographic information that had previously been identified as associated with COVID-19 susceptibility and severity. Within four weeks, more than 500,000 AncestryDNA customers from all 50 states who consented to participate in research responded, including more than 4,700 individuals with COVID-19, as measured by a selfreported positive nasal swab test. All data were de-identified prior to subsequent analyses.

Rates of hospitalisation calculated from the self-reported positive cases in the Ancestry data are consistent with characteristics seen in a CDC data analysis (10 percent of individuals reported hospitalisation in the Ancestry data compared to 14 percent in the CDC dataset). In addition, these data represent a unique view of the US population, including the range of symptoms experienced by those who tested positive for COVID-19 as well as those who have been exposed to SARSCoV-2 but have not experienced any symptoms. From these self-reported outcomes, we assessed susceptibility by comparing those who reported a positive COVID-19 nasal swab test result to those who reported a negative swab test result. We also looked at severity by comparing COVID-19 positive individuals who were hospitalised to COVID-19 positive individuals who were not hospitalised.

We observed significant associations between several risk factors and COVID-19 susceptibility and severity outcomes.2 Given the scale of our database, we were able to account for known exposures to COVID-19 to try to understand potential risk factors not explained by differences in exposures, which has not been accounted for in most other work. We found males were more likely than females to test positive for COVID-19 (odds ratio [OR]=1.36), even among people with the same known exposures to COVID-19 and age. This exposureadjusted result is novel and distinct from previous reports of elevated severity risk in males. Among those who tested positive for COVID-19, males (6.6 percent) were more likely than females (3.9 percent) to report progression to a critical case of the virus, consistent with CDC findings.

People aged 18-29 reported higher exposure to COVID-19 than all other age groups and were at a slightly elevated risk (OR=1.28) for positive diagnosis compared to those aged 50-64, even among people with the same exposure and sex. People aged 65 and older were significantly more likely to be hospitalised (OR=1.60) compared to those aged 50-64, even when accounting for differences in health conditions, obesity and biological sex.

We identified three novel loci indicating genetic associations with COVID-19 outcomes

AfricanAmericans were more likely to develop COVID-19 (OR=1.23) and were also significantly more likely to report progression to a critical case compared to those with European ancestry (OR=2.34), after accounting for health conditions, obesity, age and biological sex. We developed risk models to robustly predict individualised COVID-19 outcomes and were able to accurately predict an individuals susceptibility risk based on self-reported demographics, exposures and symptoms. We trained a peer-reviewed susceptibility model3 on our training cohort and found that our models perform slightly better (Ancestry area under a curve [AUC]=0.94, Litmodel AUC=0.90). We were also able to accurately predict an individuals severity risk based on selfreported demographics, preexisting conditions and symptoms. The severity risk models performed slightly better than previously reported clinical models despite not relying on clinical risk factors (eg, bloodwork), suggesting that selfreported data can be used to accurately assess risk of both susceptibility and severity in lieu of clinical data. We assessed the risk models across different age, sex and genetic ancestry cohorts and we can report reasonably high performance in all cohorts; highlighting the potential utility and generalisability of these models to the broader population. To our knowledge, the assessment by genetic ancestry is the first of its kind in the COVID-19 risk modelling literature.

To explore possible differences in biological response to COVID-19 infection, we analysed both susceptibility and severity outcomes using sex-stratified GWAS and sex-combined meta-analyses to identify genetic determinants associated with COVID-19 susceptibility and severity from more than 500,000 respondents reporting COVID-19 symptoms, outcomes, risk factors and exposures. These analyses included over 2,400 individuals with COVID-19 and 250 hospitalised cases in a cohort of European ancestry individuals.

Importantly, we identified three novel loci indicating genetic associations with COVID-19 outcomes.4 The strongest association was near IVNS1ABP, a gene involved in influenza virus replication, and it was only associated in males. It is unclear why this association is present only in males, though it may provide a clue as to why males appear to be at higher risk of COVID-19 infection, hospitalisation and mortality. We speculate that sex hormones or behavioural differences might trigger different cellular responses to COVID-19 infection in men and in women, and one such difference may involve differential expression of IVNS1ABP. The other two novel loci harbour genes with established roles in viral replication or immunity.

Our results add to a growing body of evidence that individual genetic variation contributes to both susceptibility to COVID-19 and severity of illness. These results also suggest that identification of these genetic risk factors could provide profound insight into why COVID-19 manifests differently in individuals, particularly in men.

This research highlights the value of selfreported epidemiological data at scale to provide public health insights into the evolving COVID-19 pandemic. Further, these survey responses, coupled with genomic data for over 500,000 individuals who have consented to research, provides Ancestry with the unique ability to quickly contribute to the global effort to better understand this disease. We are working to gain a deeper understanding of COVID-19 by investigating genomic and clinical components that influence how people contract and respond to the virus. We know that this information may be useful in the effort to develop treatments, preventatives or vaccines for the disease. In that spirit, we are making a subset of data from this study available to other qualified scientists through the European Genome-phenome Archive (EGA) to help inform their research.

Cathy Ball, PhD has served as Chief Scientific Officer for AncestryDNA, LLC since September 2016. She joined as Vice President of Genomics and Bioinformatics in 2011, helping to establish the companys approach to genetic genealogy leading to the launch of AncestryDNA. Cathy is a genomic scientist who has annotated and mined the genomes of various organisms and created resources to help clinicians, citizens and other scientists exploit and explore genome data. Cathy also led the Stanford Microarray Database, the largest academic database of its kind. She has presented seminars at leading universities and contributes to National Institutes of Health committees. She received a BS in Biology and a PhD in Molecular Biology from the University of California, Los Angeles. Cathy was a post-doctoral fellow at the University of California, Berkeley prior to her research in the Departments of Genetics and Biochemistry at Stanford University School of Medicine.

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Predicting COVID-19 susceptibility and severity - Drug Target Review

We know from history that traumatic experiences in childhood can have long-lasting effects, impacting both the physical body and our mental health. Research has shown that these stressful experiences in life can also impact the offspring of individuals whom have endured trauma.This contradicts some of the basic underpinnings of genetic hereditary. How can experiences in life affect our gametes the sperm and egg cells which pass on hereditary information through DNA to our offspring? Scientists are focusing on the role that the epigenome plays here.

The epigenome, which regulates gene activity by mechanisms which, put simply, involve "switching on" and "switching off" of genes, can be influenced by biological molecules.

A new study led by Professor Isabelle Mansuy at the University of Zurich's Brain Research Institute explored how circulating factors in the blood communicate with the embryonic precursors of gametes (germ cells) in both animal models and human participants.1Mansuy and colleagues focused their efforts on studying the biological impact of trauma. They found that traumatic experiences in early life cause changes in the blood composition namely metabolites that are passed on to the next generation.

Technology Networks spoke with Mansuy to learn more about the field of epigenetic inheritance, the specifics of the study and the possible impact these data may have on matters of public health.

Molly Campbell (MC): Your new study contributes to a research field known as epigenetic inheritance. For our readers that may be unfamiliar, can you please tell us more about this field of research, and its applications?Isabelle Mansuy (IM): This field of research studies a form of heredity that has hardly been studied before and that involves epigenetic factors. Heredity is classically known as depending on genetics, and our genetic code (or genome), which is transferred from parent to offspring through gametes (reproductive cells: oocyte and sperm cell). This is innate heredity, which is the inheritance of natural or intrinsic traits. But there is also acquired heredity, which is the inheritance of traits acquired during life upon exposure to the environment and life experiences. This form of inheritance depends on the epigenome, which are factors around the DNA sequence that regulate its activity. The applications are broad, and include a better understanding of diseases linked to the environment/experiences such as psychiatric disorders, autoimmune diseases, cardiovascular diseases, cancer, etc whose causes and mechanisms remain poorly known and which have no treatment.

MC: Epigenetic inheritance is a field that has been deemed "controversial" in the past. In your opinion, are attitudes towards the research area changing? IM: Yes, because people realize how fundamental it is, and how it can answer questions that have remained unsolved for a long time, like the complex diseases, the transmission of the effects of life experiences (diet, stress or endocrine disruptors). Also, there is now a lot more evidence for its existence. Many studies and reports now document epigenetic inheritance in various species.

MC: Why did you decide to focus on the effects of trauma specifically in your study?IM: We are neurobiologists interested in brain functions and in the mechanisms of brain diseases, in particular psychiatric disorders. The possibility that adverse experiences in childhood can alter mental and physical health later in life and affect future generations is an extremely important public health issue. It needs to be understood mechanistically to help patients, doctors and the society.

MC: Why did you hypothesize that blood metabolites (an example of circulating factors) carry signals induced by exposure to germ cells? What previous research supported this hypothesis?IM: The hypothesis stems from our observation that many cells and tissues are affected by trauma exposure in early life and that some of the changes are comparable across tissues, suggesting that there is a common inducing factor. It was logical to think of blood since it provides nutrient to all tissues and cells across the body. The fact that blood factors can communicate with germ cells was not known before, it was even deemed impossible mid-19th century by August Weissmann, purely based on a theory he put forward that the soma cannot communicate with the germline (the Weismann barrier). It relied, for instance, on the observation that if you cut the tail of a mouse at each generation, the offspring will never be born with a cut tail. This theory was erroneous from the start but somewhat blocked proper thinking for a long time.

MC: In mice, you found that exposure to trauma upregulated certain metabolic pathways, and that this upregulation was also detected in the male progeny of these mice in adulthood. Can you expand on the metabolic pathways that you analyzed and why, and what the key results were?IM: Some metabolites are up-regulated but others are down-regulated. We analysed all metabolites by mass spectrometry (unbiased method) and observed that lipid metabolism is perturbed with polyinsaturated fatty acids metabolites being increased. We also saw that glucose and insulin are dysregulated.

MC: You also assessed the relevance of these findings in a cohort of children, specifically children from an SOS Children's Village in Lahore, Pakistan. Can you discuss the choice of human sample used in this study? Why is it representative? Are there any potential limitations?IM: The Pakistani cohort was selected to resemble as much as possible our mouse model. The children were separated from their mother after their lost their husband (father). Our mouse model uses unpredictable maternal separation combined with unpredictable maternal stress. It is representative of a severe family trauma. The limitations are that it is a small cohort (25 SOS and 14 controls) however we have now expanded this sample and that we have blood samples from only one time point. Ideally, we would like to follow the children across time. A positive point though is that we have a small group of adult men who were in the SOS village when younger and who do show changes in blood (this data is not published).

MC: How did the results of the human analyses compare to the results you obtained in mice?IM: There are lots of similarities in symptoms of trauma e.g. depression, and in physiological parameters e.g. altered glycemia, dyslipidemia, decreased HDL, etc

MC: What can the data tell us about how trauma is altering metabolic pathways, and why this might be passed on to the next generation?IM: We do not know exactly how trauma alters metabolic pathways, but it is likely by perturbing liver, pancreas, the endocrine system, etc. The effects are systemic, and every tissue is affected. The effects of trauma are passed to the next generation (demonstrated in mice) because germ cells (here sperm) carry molecular alterations e.g. altered RNA populations, that are passed to the embryo upon fertilization with the oocyte.

MC: What clinical applications might this research have?IM: Perhaps the identification of a signature of trauma in blood, saliva and/or sperm which could help diagnostics and treatment monitoring.

MC: Finally, what are your next steps in this research space?IM: Identify the mechanisms responsible for changes in germ cells (male and female) and how these changes are perpetuated/maintained in the offspring.

Professor Isabelle Mansuy was speaking to Molly Campbell, Science Writer for Technology Networks.

Reference:

1. van Steenwyk G, Gapp K, Jawaid A, et al. Involvement of circulating factors in the transmission of paternal experiences through the germline. EMBO J.. 2020;39(23):e104579. doi:10.15252/embj.2020104579.

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Exploring the Biological Inheritance of Childhood Trauma - Technology Networks

The Conversation

The world is eagerly awaiting the release of several COVID-19 vaccines, but Brazilian President Jair Bolsonaro is not. Im not going to take it. Its my right, he said in a Nov. 26 social media broadcast. Bolsonaro, who came down with COVID-19 in July, has also criticized face masks. He and his more faithful supporters oppose any suggestion of mandatory coronavirus vaccinations. Vaccine resistance has a long history in Brazil. In November 1904, thousands of people in the city of Rio de Janeiro protested government-mandated smallpox vaccinations in a famous revolt that nearly ended with a coup. Making modern BrazilThe smallpox vaccine had arrived in Brazil almost a century earlier. But the syringes were long, left skin pockmarked and could transmit other diseases such as syphilis. Between 1898 and 1904, only 2% to 10% of Rios population was vaccinated yearly, according to historian Sidney Chalhoub. In 1904, smallpox killed 0.4% of Rio residents a higher percentage of the population than COVID-19s victims in New York City this year.But these were not the only reasons Brazil made vaccinations mandatory in 1904. As part of a modernization plan to attract European immigration and foreign investment, President Rodrigues Alves was committed to eradicating epidemics not just smallpox, but also yellow fever and the bubonic plague.To rid Rio de Janeiro, then the nations capital, of sanitary hazards while opening space for Parisian-style avenues and buildings, hundreds of tenements were demolished between 1903 and 1909. Almost 40,000 people mostly Afro-Brazilians but also poor Italian, Portuguese and Spanish immigrants were evicted and removed from downtown Rio. Many were left homeless, forced to resettle on nearby hillsides or in distant rural areas. Meanwhile, public health agents accompanied by armed police systematically disinfected homes with sulfur that destroyed furniture and other belongings whether residents welcomed them or not. Conspiracy and barricadesPoliticians and military officers who opposed President Alves saw opportunity in the outrage these health initiatives caused. They stoked discontent.With the help of labor organizers and news editors, Alves opponents led a campaign against Brazils public health mandates throughout 1904. Newspapers reported on violent home disinfections and forced vaccinations. Senators and other public figures declared that mandatory vaccinations encroached on peoples homes and bodies.In mid-November of that year, thousands of protesters gathered in public squares to rally against public health efforts. Rio police reacted with disproportionate force, triggering six days of unrest in the city. A racially diverse crowd of students, construction workers, port workers and other residents fought back, armed with rocks, housewares or the tools of their trade, flipping over streetcars to barricade the streets. Meanwhile, behind the scenes, conspirators were mobilizing young military cadets. Their plan: to overthrow Alves government. Their scheme was foiled when the president called upon both the Army and the Navy to contain protesters and detain alleged insurgents. Brazils great vaccine revolt was soon suppressed. The language of rightsAfterward, newspapers portrayed protesters as an ignorant mass, manipulated by cunning politicians. They deemed one of the uprisings popular leaders, Horcio Jos da Silva known as Black Silver a disorderly thug.But Brazils vaccine revolt was more than a cynical political manipulation. Digging into archives, historians like me are learning what really motivated the uprising.The violent and segregationist features of Alves urban plan are one obvious answer. In early 20th-century Brazil, most people women, those who couldnt read, the unemployed couldnt vote. For these Brazilians, the streets were the only place to have their voices heard.But why would they so virulently oppose methods that controlled the spread of disease?Delving into newspapers and legal records, I have found that critics of Brazils 1904 public health drive often expressed their opposition in terms of inviolability of the home, both on the streets and in courts.For elite Brazilians, invoking this constitutional right was about protecting the privacy of their households, where men ruled over wives, children and servants. Public health agents threatened this patriarchal authority by demanding access to homes and womens bodies.Poor men and women in Rio also held patriarchal values. But for them there was more than privacy at stake in 1904. Throughout the 19th century, enslaved Afro-Brazilians had formed families and built homes, even on plantations, carving out spaces of relative freedom from their masters. After slavery was abolished in 1888, many freed Afro-Brazilians shared crowded tenements with immigrants. By the time of Alvess vaccination drive, the poor of Rio had been fighting eviction and police violence for decades. For Black Brazilians, then, defending their rights to choose what to do or not to do with their homes and bodies was part of a much longer struggle for social, economic and political inclusion. Deadly learning experienceFour years after the 1904 revolt, Rio was struck by another smallpox epidemic. With so many people unvaccinated, deaths doubled; almost 1% of the city perished.[Deep knowledge, daily. Sign up for The Conversations newsletter.]It was a deadly learning experience. From then on, Brazilian leaders framed mandatory smallpox, measles and other vaccines as a means to protect the common good, and invested in educational campaigns to explain why. Throughout the 20th century, vaccinations were extremely successful in Brazil. Since the 1990s, 95% of children have been vaccinated, though the numbers are dropping.Today, Brazil is one of the countries hardest hit by the coronavirus pandemic. As in the past, Afro-Brazilians are hurting more than others.By invoking Brazilians individual right not to get vaccinated against COVID-19, President Bolsonaro is ignoring the lessons of 1904 undermining a century of hard work fighting disease in Brazil.This article is republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Pedro Cantisano, University of Nebraska Omaha.Read more: * COVID-19 is deadlier for black Brazilians, a legacy of structural racism that dates back toslavery * In Brazils raging pandemic, domestic workers fear for their lives and theirjobsPedro Cantisano does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Man caught breaking into Tom Brady and Gisele Bndchen's Massachusetts mansion - Yahoo News

Following a frustrating year plagued by transport restrictions caused by Covid-19 and tilapia lake virus, Til-Aquarecently decided to branch out from selling live tilapia fry a move that has netted them the first of a new breed of deal this week.

Like many other companies, we are currently confronted with transport issues limited available flights and closed borders due to the coronavirus. The import restrictions that some countries have imposed regarding the tilapia lake virus had already severely limited our current operations. As a result, we decided to change course drastically so as not to lose 25 years of genetic effort: we have put our genetics for sale to interested parties, explains Eric Bink, director of the Dutch firm.

Til-Aquas first deal in the new era has been signed with Gardsfisk, a fast-growing tilapia producer in Sweden. According to Bink, they will need about 3 million tilapia fingerlings for their own company and partners net year, which would make it a very significant deal by European standards.

They will start producing NMT soon and in a few months also YY production. There are several other YY genetic centres to be set up soon (Saudi Arabia, Algeria, Morocco, US, Tanzania) and we are now in advanced negotiations for transferring the YY technology to various parties worldwide, adds Bink.

Despite the radical shift, Bink's plans appear to have been validated.

We believe that transferring our YY technology to countries for local YY production is the best option. These parties would own YY-males and YY-females and would receive the information on how to maintain these lines. With these fish, they can produce their own YY-males; the broodstock that produces NMT [natural male tilapia] offspring. These YY-males can be both used for your own NMT production and distributed to interested parties. [our own] NMT production has since stopped. We will be able to supply our YY-males until the end of December 2020, he adds.

Excerpt from:
The pivot that's helping a tilapia producer cope with covid restrictions - The Fish Site

The Conversation

The world is eagerly awaiting the release of several COVID-19 vaccines, but Brazilian President Jair Bolsonaro is not. Im not going to take it. Its my right, he said in a Nov. 26 social media broadcast. Bolsonaro, who came down with COVID-19 in July, has also criticized face masks. He and his more faithful supporters oppose any suggestion of mandatory coronavirus vaccinations. Vaccine resistance has a long history in Brazil. In November 1904, thousands of people in the city of Rio de Janeiro protested government-mandated smallpox vaccinations in a famous revolt that nearly ended with a coup. Making modern BrazilThe smallpox vaccine had arrived in Brazil almost a century earlier. But the syringes were long, left skin pockmarked and could transmit other diseases such as syphilis. Between 1898 and 1904, only 2% to 10% of Rios population was vaccinated yearly, according to historian Sidney Chalhoub. In 1904, smallpox killed 0.4% of Rio residents a higher percentage of the population than COVID-19s victims in New York City this year.But these were not the only reasons Brazil made vaccinations mandatory in 1904. As part of a modernization plan to attract European immigration and foreign investment, President Rodrigues Alves was committed to eradicating epidemics not just smallpox, but also yellow fever and the bubonic plague.To rid Rio de Janeiro, then the nations capital, of sanitary hazards while opening space for Parisian-style avenues and buildings, hundreds of tenements were demolished between 1903 and 1909. Almost 40,000 people mostly Afro-Brazilians but also poor Italian, Portuguese and Spanish immigrants were evicted and removed from downtown Rio. Many were left homeless, forced to resettle on nearby hillsides or in distant rural areas. Meanwhile, public health agents accompanied by armed police systematically disinfected homes with sulfur that destroyed furniture and other belongings whether residents welcomed them or not. Conspiracy and barricadesPoliticians and military officers who opposed President Alves saw opportunity in the outrage these health initiatives caused. They stoked discontent.With the help of labor organizers and news editors, Alves opponents led a campaign against Brazils public health mandates throughout 1904. Newspapers reported on violent home disinfections and forced vaccinations. Senators and other public figures declared that mandatory vaccinations encroached on peoples homes and bodies.In mid-November of that year, thousands of protesters gathered in public squares to rally against public health efforts. Rio police reacted with disproportionate force, triggering six days of unrest in the city. A racially diverse crowd of students, construction workers, port workers and other residents fought back, armed with rocks, housewares or the tools of their trade, flipping over streetcars to barricade the streets. Meanwhile, behind the scenes, conspirators were mobilizing young military cadets. Their plan: to overthrow Alves government. Their scheme was foiled when the president called upon both the Army and the Navy to contain protesters and detain alleged insurgents. Brazils great vaccine revolt was soon suppressed. The language of rightsAfterward, newspapers portrayed protesters as an ignorant mass, manipulated by cunning politicians. They deemed one of the uprisings popular leaders, Horcio Jos da Silva known as Black Silver a disorderly thug.But Brazils vaccine revolt was more than a cynical political manipulation. Digging into archives, historians like me are learning what really motivated the uprising.The violent and segregationist features of Alves urban plan are one obvious answer. In early 20th-century Brazil, most people women, those who couldnt read, the unemployed couldnt vote. For these Brazilians, the streets were the only place to have their voices heard.But why would they so virulently oppose methods that controlled the spread of disease?Delving into newspapers and legal records, I have found that critics of Brazils 1904 public health drive often expressed their opposition in terms of inviolability of the home, both on the streets and in courts.For elite Brazilians, invoking this constitutional right was about protecting the privacy of their households, where men ruled over wives, children and servants. Public health agents threatened this patriarchal authority by demanding access to homes and womens bodies.Poor men and women in Rio also held patriarchal values. But for them there was more than privacy at stake in 1904. Throughout the 19th century, enslaved Afro-Brazilians had formed families and built homes, even on plantations, carving out spaces of relative freedom from their masters. After slavery was abolished in 1888, many freed Afro-Brazilians shared crowded tenements with immigrants. By the time of Alvess vaccination drive, the poor of Rio had been fighting eviction and police violence for decades. For Black Brazilians, then, defending their rights to choose what to do or not to do with their homes and bodies was part of a much longer struggle for social, economic and political inclusion. Deadly learning experienceFour years after the 1904 revolt, Rio was struck by another smallpox epidemic. With so many people unvaccinated, deaths doubled; almost 1% of the city perished.[Deep knowledge, daily. Sign up for The Conversations newsletter.]It was a deadly learning experience. From then on, Brazilian leaders framed mandatory smallpox, measles and other vaccines as a means to protect the common good, and invested in educational campaigns to explain why. Throughout the 20th century, vaccinations were extremely successful in Brazil. Since the 1990s, 95% of children have been vaccinated, though the numbers are dropping.Today, Brazil is one of the countries hardest hit by the coronavirus pandemic. As in the past, Afro-Brazilians are hurting more than others.By invoking Brazilians individual right not to get vaccinated against COVID-19, President Bolsonaro is ignoring the lessons of 1904 undermining a century of hard work fighting disease in Brazil.This article is republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Pedro Cantisano, University of Nebraska Omaha.Read more: * COVID-19 is deadlier for black Brazilians, a legacy of structural racism that dates back toslavery * In Brazils raging pandemic, domestic workers fear for their lives and theirjobsPedro Cantisano does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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The world is eagerly awaiting the release of several COVID-19 vaccines, but Brazilian President Jair Bolsonaro is not. Im not going to take it. Its my right, he said in a Nov. 26 social media broadcast. Bolsonaro, who came down with COVID-19 in July, has also criticized face masks. He and his more faithful supporters oppose any suggestion of mandatory coronavirus vaccinations. Vaccine resistance has a long history in Brazil. In November 1904, thousands of people in the city of Rio de Janeiro protested government-mandated smallpox vaccinations in a famous revolt that nearly ended with a coup. Making modern BrazilThe smallpox vaccine had arrived in Brazil almost a century earlier. But the syringes were long, left skin pockmarked and could transmit other diseases such as syphilis. Between 1898 and 1904, only 2% to 10% of Rios population was vaccinated yearly, according to historian Sidney Chalhoub. In 1904, smallpox killed 0.4% of Rio residents a higher percentage of the population than COVID-19s victims in New York City this year.But these were not the only reasons Brazil made vaccinations mandatory in 1904. As part of a modernization plan to attract European immigration and foreign investment, President Rodrigues Alves was committed to eradicating epidemics not just smallpox, but also yellow fever and the bubonic plague.To rid Rio de Janeiro, then the nations capital, of sanitary hazards while opening space for Parisian-style avenues and buildings, hundreds of tenements were demolished between 1903 and 1909. Almost 40,000 people mostly Afro-Brazilians but also poor Italian, Portuguese and Spanish immigrants were evicted and removed from downtown Rio. Many were left homeless, forced to resettle on nearby hillsides or in distant rural areas. Meanwhile, public health agents accompanied by armed police systematically disinfected homes with sulfur that destroyed furniture and other belongings whether residents welcomed them or not. Conspiracy and barricadesPoliticians and military officers who opposed President Alves saw opportunity in the outrage these health initiatives caused. They stoked discontent.With the help of labor organizers and news editors, Alves opponents led a campaign against Brazils public health mandates throughout 1904. Newspapers reported on violent home disinfections and forced vaccinations. Senators and other public figures declared that mandatory vaccinations encroached on peoples homes and bodies.In mid-November of that year, thousands of protesters gathered in public squares to rally against public health efforts. Rio police reacted with disproportionate force, triggering six days of unrest in the city. A racially diverse crowd of students, construction workers, port workers and other residents fought back, armed with rocks, housewares or the tools of their trade, flipping over streetcars to barricade the streets. Meanwhile, behind the scenes, conspirators were mobilizing young military cadets. Their plan: to overthrow Alves government. Their scheme was foiled when the president called upon both the Army and the Navy to contain protesters and detain alleged insurgents. Brazils great vaccine revolt was soon suppressed. The language of rightsAfterward, newspapers portrayed protesters as an ignorant mass, manipulated by cunning politicians. They deemed one of the uprisings popular leaders, Horcio Jos da Silva known as Black Silver a disorderly thug.But Brazils vaccine revolt was more than a cynical political manipulation. Digging into archives, historians like me are learning what really motivated the uprising.The violent and segregationist features of Alves urban plan are one obvious answer. In early 20th-century Brazil, most people women, those who couldnt read, the unemployed couldnt vote. For these Brazilians, the streets were the only place to have their voices heard.But why would they so virulently oppose methods that controlled the spread of disease?Delving into newspapers and legal records, I have found that critics of Brazils 1904 public health drive often expressed their opposition in terms of inviolability of the home, both on the streets and in courts.For elite Brazilians, invoking this constitutional right was about protecting the privacy of their households, where men ruled over wives, children and servants. Public health agents threatened this patriarchal authority by demanding access to homes and womens bodies.Poor men and women in Rio also held patriarchal values. But for them there was more than privacy at stake in 1904. Throughout the 19th century, enslaved Afro-Brazilians had formed families and built homes, even on plantations, carving out spaces of relative freedom from their masters. After slavery was abolished in 1888, many freed Afro-Brazilians shared crowded tenements with immigrants. By the time of Alvess vaccination drive, the poor of Rio had been fighting eviction and police violence for decades. For Black Brazilians, then, defending their rights to choose what to do or not to do with their homes and bodies was part of a much longer struggle for social, economic and political inclusion. Deadly learning experienceFour years after the 1904 revolt, Rio was struck by another smallpox epidemic. With so many people unvaccinated, deaths doubled; almost 1% of the city perished.[Deep knowledge, daily. Sign up for The Conversations newsletter.]It was a deadly learning experience. From then on, Brazilian leaders framed mandatory smallpox, measles and other vaccines as a means to protect the common good, and invested in educational campaigns to explain why. Throughout the 20th century, vaccinations were extremely successful in Brazil. Since the 1990s, 95% of children have been vaccinated, though the numbers are dropping.Today, Brazil is one of the countries hardest hit by the coronavirus pandemic. As in the past, Afro-Brazilians are hurting more than others.By invoking Brazilians individual right not to get vaccinated against COVID-19, President Bolsonaro is ignoring the lessons of 1904 undermining a century of hard work fighting disease in Brazil.This article is republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Pedro Cantisano, University of Nebraska Omaha.Read more: * COVID-19 is deadlier for black Brazilians, a legacy of structural racism that dates back toslavery * In Brazils raging pandemic, domestic workers fear for their lives and theirjobsPedro Cantisano does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Employing a strategy known as population modification, which involves using a CRISPR-Cas9 gene drive system to introduce genes preventing parasite transmission into mosquito chromosomes, University of California researchers have made a major advance in the use of genetic technologies to control the transmission of malaria parasites.

University of California, Irvine postdoctoral researcher Adriana Adolfi, in collaboration with colleagues at UC Irvine, UC Berkeley and UC San Diego, followed up on the groups pioneering effort to develop CRISPR-based gene drive systems for making mosquito vectors resistant to transmitting malaria parasites by increasing gene drive effectiveness in female mosquito progeny.

This work mitigates a big issue with the first gene drive systems, which is the accumulation of drive-resistant mosquitoes that could still transmit malaria parasites, said UC Irvine vector biologist Anthony James, the Donald Bren Professor of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, who was a co-primary investigator on the study.

The second-generation gene drive system described in this paper can be applied to any of the several thousand genes that are essential for insects tosurviveor reproduce, said UC San Diego Distinguished Professor Ethan Bier, a co-author of the study and science director at theTata Institute for Genetics and Society. While it was developed in fruit flies, this system is readily transportable to a broad selection of insect species that serve as vectors for devastating disorders such as Chagas disease, sleeping disease, leishmaniasis andarboviraldiseases.

Study resultsappear inNature Communications. Theydescribe a highly efficient second-generation version of the teams original gene drive, developed for the Indo-Pakistani malaria vector mosquitoAnopheles stephensi. The 2015 work, published inProceedings of the National Academy of Sciences,wasthe first demonstration of a CRISPR-based gene drive in mosquitoes.

In that first study, the gene drive was transmitted to about 99 percent of progeny when the parent in which the gene drive was inserted was a male but only 60 to 70 percent of offspring when the parent in which the gene drive was inserted was a female. A significant number of drive-resistant chromosomes are generated in females; this, in principle, could allow those females to continue to transmit parasites.

Adolfi, lead author of the new study, and collaborators solved the failure to drive efficiently through females by equipping the gene drive with a functional copy of the target gene into which the drive is inserted. Normal function of this target gene is required in this mosquito species for female survival and fertility after she feeds on blood, and its functionality is usually disrupted when the drive system is inserted into the gene.

The resulting female mosquitoes showed strong and consistent drive in a population cage study and negligible production of drive-resistant chromosomes. This strategy of inserting a gene drive into a gene essential for viability or fertility and at the same time including a functional gene that rescues the loss of viability or fertility provides a general solution to drive resistance through females. Also, as with a catalytic converter removing combustion pollution from automobiles, the new system efficiently eliminates genetic errors made in the drive process.

This gene drive system in combination with genes for blocking parasite transmission can now be used to design field-ready strains of mosquitoes. Thorough testing is required to demonstrate safety and efficacy before advancing to field testing.

Nijole Jasinskiene, Hsu-Feng Lee, Arunachalam Ramaiah, J.J. Emerson and Kristy Hwang of UC Irvine; Valentino Gantz, Gerard Terradas and Emily Bulger of UC San Diego; and Jared Bennett and John Marshall of UC Berkeley also participated in the study, which resulted from collaborations between the UC IrvineMalaria Initiative and the UC San Diego Tata Institute for Genetics and Society.

Research support was provided by the Tata Institute for Genetics and Society, the UC Irvine Malaria Initiative,the National Institutes of Health (AI29746,DP5OD023098 andGM123303)and the DARPA Safe Genes program (HR0011-17-2-0047).

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One researcher is in Texas. One is in Nebraska. Together, they are striving to launch the hybridized wheat industry.

Lush green plots of hybridized wheat are dotted with people walking through them

Hybridization is the cross breeding of two genetically different varieties or species. And much like what has been accomplished in cotton and corn, hybridizing wheat is expected to improve the crops strength and health and ability to feed a rapidly growing population.

Amir Ibrahim, Ph.D., Texas A&M AgriLife Research wheat breeder in Texas A&Ms Department of Soil and Crop Sciences, Bryan-College Station, has spent the past seven years studying the hybridization of wheat in a partnership with Stephen Baenziger, Ph.D., University of Nebraska-Lincoln small grains breeder.

Ibrahim and Baenziger jointly have tested more than 600 lines of hybrid wheat varieties in Nebraska and Texas, and are now developing the necessary knowledge base, germplasm and enhanced trait pools or patterns from these lines to support the development of hybridized wheat.

Plant breeding partnerships grant

The teams newest project, Plant breeding partnerships: Continuing to develop and validate the tools for hybrid wheat, is supported by a $650,000 U.S. Department of Agriculture National Institute of Food and Agriculture grant.

Together our project team has made great strides toward developing tools to foster hybrid wheat development to maximize wheat yield potential, Baenziger said. This project is expected to help create the scientific and germplasm foundations for successfully launching a U.S. hybrid wheat industry.

Using an integrated approach involving in-house germplasm, chemical hybridizing agents, breeding, phenotyping, genomic selection and quantitative trait loci mapping, the collaborations objectives are to:

Validate increased function from previously made and predicted wheat hybrids in replicated trials.

Continue male and female parent line evaluation for characteristics needed to develop experimental and commercial wheat hybrids in a cost-efficient manner.

Develop those groups showing enhanced traits or patterns and test multiple mating designs for wheat hybrids.

Continue cytoplasmic male sterility line development and identify and validate restorer genes for wheat hybrids.

Ibrahim explained hybrid crops have increased vigor over the two parents in yield and other traits. In hybrids, the female parent does not produce viable pollen, but is used as a seed plant. The male parent has the role of pollinator. Together they have the capacity to combine and express hybrid vigor.

For wheat, past conventional breeding efforts increased hybrid vigor about 10%, but Ibrahim said they want to raise that figure to 15%-20% to make it attractive to producers.

We believe hybrid wheat, which is more climate resilient than pure-line wheat, can contribute to achieving this goal, he said.

Also participating in this latest project are Vikas Belamkar, Ph.D., University of Nebraska geneticist and plant breeder; Bhoja Basnet, Ph.D., International Maize and Wheat Improvement Center, or CIMMYT, hybrid wheat breeder, El Batan, Mexico; and Jochen Reif, Ph.D., Leibniz Institute of Plant Genetics and Crop Plant Science department head, Gatersleben, Germany.

The science needed for cost-effective adoption

Anil Adhikari, Ph.D., a Texas A&M doctoral student who is now at the University of Wisconsin, said for commercial success of hybrid wheat, a cost-effective hybrid seed production method is required. Adhikari worked extensively with Ibrahim on the genetic side of hybridization.

Hybrid seed production based on cytoplasmic male sterility is only feasible if the male lines have fertility-restoring genes, Adhikari said. These genes override the cytoplasmic male sterility in the hybrid seed and make the seeds fertile.

In his study, fertility-restoring genes in a promising restoration source were mapped using linkage mapping approach in a population of 300 recombinant inbred lines. Three consistent major quantitative trait loci, or QTLs,were mapped explaining 18%-40% phenotypic variance. KASP markers were developed using flanking markers of these QTLs.

The KASP markers from this study can be used for characterizing fertility-restoring gene sources and transferring them to male parents in the hybrid breeding program. In addition, the identified candidate genes can serve as a guide to fine map and clone these fertility-restoring genes.

To meet population and food projections, the improvement in wheat productivity needs to be between 1.4% and 1.6% per year. Currently, the productivity increase is about 1% or less.

The researchers say we now have effective chemical hybridizing agents to make experimental hybrids, have identified lines with good traits to facilitate cross-pollination, genomic tools for predicting hybrid vigor, statistical approaches for better estimates of hybrid yield in large experiments, and genomic tools for better use of cytoplasmic male sterile systems.

Hybrid wheat appears to be more stable than conventional wheat under stresses, a trait that is growing in importance, Ibrahim said. Also, he knows the research spin-offs from these efforts may have far-reaching improvements for his and other wheat breeders conventional pure-line breeding.

We know hybrid wheat will still take time but based on these tools we have been working with and the results we are seeing, we believe its time has come, Ibrahim said.

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Archaeologists have discovered the rare burial of a young child who was laid to rest 8,000 years ago without arm and leg bones, a new study finds.

The child, who was no older than 8, was buried on what is now Alor Island, Indonesia. During the burial ceremony, the long bones in the child's arms and legs were removed and disposed elsewhere, and part of the child's face was painted with red ochre, a pigment often used in burials across the ancient world.

"Ochre pigment was applied to the cheeks and forehead and an ochre-colored cobblestone was placed under the child's head when they were buried," study lead researcher Sofia Samper Carro, a lecturer of archaeology at Australian National University in Canberra, said in a statement.

Related: 8,000-year-old heads on stakes found in mysterious underwater grave

This isn't the only burial from this region with missing arm and leg bones. "The lack of long bones is a practice that has been documented in several other burials from a similar time period in Java, Borneo and Flores, but this is the first time we have seen it in a child's burial," Samper Carro said. "We don't know why long bone removal was practiced, but it's likely some aspect of the belief system of the people who lived at this time."

Archaeologists don't know whether the child was male or female, but an analysis of their teeth and skeleton suggests the youngster likely died between the ages of 4 and 8. However, the dental analysis suggests that the child was slightly older (6 to 8 years old), while the skeleton was so small, it looked like it belonged to a 4 to 5 year old, indicating that the child's growth may have been stunted by genetic or environmental factors.

"We want to do some further paleo-health research to find out if this smaller skeleton is related to diet or the environment or possibly to being genetically isolated on an island," Samper Carro said, referring to the idea that some species shrink when they live on an isolated island, such as the extinct dwarf elephants that used to live in Flores.

Granted, ancient adult skulls found on Alor are also small. And if genetics don't explain their short stature, it's possible nutrition played some role, Samper Carro said. "These hunter-gatherers had a mainly marine diet and there is evidence to suggest protein saturation from a single food source can cause symptoms of malnourishment, which affects growth," she said. "However, they could have been eating other terrestrial resources, such as tubers."

Whatever the researchers learn will shed light on this region's cultural practices during the early mid-Holocene epoch, which began at the end of the last ice age about 11,500 years ago. "Child burials are very rare, and this complete burial is the only one from this time period," Carro said.

Child burials become more common in the archaeological record starting about 3,000 years ago, she said. "But, with nothing from the early Holocene period, we just don't know how people of this era treated their dead children. This find will change that."

The study was published online Oct. 28 in the journal Quaternary International.

Originally published on Live Science.

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A recent study published in the Journal of Hypertension indicates that there is a direct association between social ties and risk of hypertension in women. The longitudinal study including more than 28,000 people between the ages of 45 and 85 years found that women with a small social circle and limited social participation (less than two social activities in a month) are more likely to get hypertension than women who had better or more social interactions. Hypertension risk was also found to be higher in widowed women than married women.

Hypertension (high blood pressure) is assumed to be more prevalent in the male population. However, experts suggest that it affects both the genders equally. In fact, after a certain age, women are more prone to the condition than men and the former have several very unique risk factors for high blood pressure both in the pre and post-menopausal age.

Unique risk factors

According to the American Heart Association, high blood pressure is not directly related to gender. However, pregnancy, menopause and use of birth control pills are some unique factors that put women at a higher risk of hypertension.

Research suggests that women who smoke, have a genetic predisposition to hypertension or are overweight are highly likely to have high blood pressure on regular use of birth control pills.

Similarly, pregnant women often experience high blood pressure. If you have had a history of hypertension, you may have to consult your doctor before trying to conceive since high blood pressure can harm both the baby and the mother.

Gestational hypertension develops after 20 weeks of pregnancy; you may develop this type of hypertension even if you never had the condition before. And then there is pre-eclampsia, a pregnancy complication wherein the woman has high blood pressure and limb swelling and protein in urine. Pre-eclampsia can be life-threatening for the mother and preterm delivery is the only way to resolve it.

Finally, after menopause, when the estrogen levels drop, a womans chances of developing hypertension increases significantly. Studies suggest that a combination of various factors including individual genetics, body mass index (BMI) and increased sympathetic nervous system activity are responsible for this spike in risk. The sympathetic nervous system is responsible for the flight and fight response. It increases blood pressure, decreases intestinal motility and accelerates heart rate.

Difference in symptoms

As per the European Society of Cardiology, hypertensive women experience more arterial stiffness, atrial fibrillation and heart failure in older age than hypertensive men. Since they have a smaller diameter of arteries, aneurysms in women rupture at a much smaller size than in men.

Hypertension is said to be a silent killer. Usually, it does not show any symptoms unless there is organ damage. However, in some young and middle-aged women, the condition can also be symptomatic. Such women report some of the following symptoms:

A lot of these symptoms are associated with stress or menopause. Experts suggest that if you notice these symptoms, it is best to consult a doctor, especially if you have a family history of hypertension.

For more information, read our article on High blood pressure.

Health articles on News18 are written by myUpchar.com, Indias first and biggest resource for verified medical information. At myUpchar, researchers and journalists work with doctors to bring you information on all things health.

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