Archive for the ‘Female Genetics’ Category

There are certain milestones a woman never forgets. Her first kiss. The day she lost her virginity. Her first menstrual period. The day she became A Woman.

I remember my first period with a shudder becomes of one unhappy detail: I was wearing mens underwear when it happened. It was my mother who forced me to wear mens boxers against my furious protests. What should have been a beautiful feminine moment was warped because I was unhappily wearing ugly, blue, mens boxer shorts that I hated.

I reference that story because it perfectly illustrates the struggle the daughter of a narcissistic mother undergoes to achieve adulthood and womanhood with Mom fighting her, tooth-and-nail, every step of the way.

Your Narcissistic Mother is The Woman.

Youre justfemale.

No matter how experienced, how successful, how old, how wrinkled you become, she is The Woman. Mother Superior. She will never look you in the eye, grasp your hand and acknowledge you as an equal nor as an adult nor as an Equal Adult Woman.

My grandmother never acknowledged my mother as her equal. My mother never acknowledged me as her equal. They both demanded the role of superior female dominating the inferior female and succeeded.

Take motherhood out of the equation. View the quagmire in which youre mired as just two unrelated women. When you take the Cult of Motherhood out of scenario, woman-on-woman abuse will make your stomach churn.

Your mother set the agenda for you before you were born. Some of you ladies were pigeonholed as your mothers scapegoat. Other daughters were born to give their mothers the vicarious life she always dreamed of living.

Some of you were designated to be your mothers covert incest pseudo-spouse. Like me, you were forced to spoon with your mother, to submit to having her wash your genitals when you were old enough to do it for yourself and to have no privacy and no lock on your bedroom door. She waltzed in and out of the most private areas of your life, irregardless of your age. My mother was the first person to touch my breast. I was fifteen years old.

I was assigned the role of Mothers Friend. She wasnt much good at making or keeping friends, so she gave birth to her lifelong friend, just as her mother had done before her.

I was my mothers only friend and, for much of my life, she was my only friend. She made sure of that. It only took a hint or two and I would kick my girlfriends to the curb to please my mother and avoid shaming, censure and furious pouting. Love-bombing will make you do that.

But it was friendship with a twist: she called the shots. This friend could destroy me for the smallest infraction, real or imagined, of her rules.

A controlling mother can be understood. A controlling friendship can be terminated. But when Control, Friendship and Motherhood are combined it forms a toxic mixture from which a good daughter cannot escape.

Because of this cringeworthy experience, I can never have a female friend. The very thought makes me want to vomit. I am terrified of women, especially those older than me.

Your mother isnt just The Woman. Actually, she owns you: heart, soul, body, relationships, sexuality, financeseverything.

Oh! You think I meant that symbolically? Hyperbolically?

Honey, I mean it literally. Practically. Exactly as written.

You do not belong to yourself. You belong to your Narcissistic Mother.

If you have it, she owns it. It is herslock, stock and barrel. She may dole out a facet of yourself to youtemporarily. But she can snatch it back at any moment, for any reasonor none at all. Youre merely a marionette dancing while she pulls your strings.

This godlike status was instilled in me from babyhood. If I was naughty, I went flying to my mother to confess and be forgiven. She demanded I narc on myself which I faithfully did, regardless of how much she would yell at me before pronouncing unto me the Forgiveness of Mother. With her seeming ability to look into my soul and ferret out sin (real, projected or imagined), she owned my soul, my spirituality, my Eternal Fate.

Growing up changesbupkis. You may be an adult woman numerically but your mother still controls everything.She decides when and if you can have privacy when youre bathing or dressing (you cant.) She controls if you can shave and exactly which parts of yourself youre allowed to shave. She controls your hair, makeup, nail color. She dictates what style of shoes and clothes you may wear. (You cant have that. It looks too good on you.) She may confiscate your make-up, your nail clipper or forbid you from touching your own face, as my parents did.

She will hold up your mail to the light as my Mom laughed about doing. She will demand your passwords. She will read your emails. She controls where you go, when you go, if you go and with whom you go. A good rule of thumb is that if Mom doesnt do XY, then youre not allowed to do XY either. For me, that meant things like staying out past dusk or driving freeways or moving out of Mommys home into a home of my own.

She may tell you what jobs to keep and which jobs to quit. And if youre allowed to date at all, she decides who you may go out with and when you will dump himno cogent reason required.

If you take the mother part out of this dynamic, its freaking creepy. One adult woman so completely dominating another adult woman requires strong words like violation.

Its entirely possible you may have a lovely relationship with your (engulfing) narcissistic mother as a little girl.

But when puberty hits! All Hell will break loose. You dont merely become a woman with your first menstrual period. Oh no! You become The Other Woman. A threat. The competition.

I remember when it happened for me. One day I was struggling to adjust to that fakakta training bra and the next day Mom was taking me aside and telling me that I was no longer allowed to hug my father. Hes a man and youre a woman, she said, smiling smarmily. Duggar-style hugs only, please, and if he does accidentally bump your breastswhich began to happen at puberty and became an almost daily accidental attempt in my late twentiesshe told me to always tell her. Then the victim could be angrily lectured and blamed every time I failed to protect myself.

Thus the father/daughter relationship that should never have been sexualized was sexualized by the woman who shouldve been the last person on Earth to want it to be sexualized: my mother. From then on, every time my father came near me, I seized up with paranoia, with guilt. Helluva way to live.

The onset of menstruation made it all worse. Puberty put me squarely in the crosshairs for every insane accusation Mom could dream up while Dad withdrew his love and approval of me due to my dermatillomaniathe only stress relief I had to keep me sane. I was desperate to win back his smile which only further convinced my mother that I was being inappropriate to her husband, my biological father. It was a suspicion she never quite forgot, never stopped accusing me of.

As my god, if she implied I was incestuous, I owned that shame. If she said, you have bad sexual genetics, I humbled myself and repented. She boomeranged between brightly informing me that I was sexual whether you know it or not (as if I didnt know) to accusing me of planning to find ways to flaunt myself for my father. Later, she decided that pregnancy was so dangerous and informed me she was glad I didnt have a husband. It was a wild, crazy-making ride full of implied slut-shaming.

Despite everything, like the educated idiot that I am, I worshiped the ground that woman walked on. Because her personality was so cheerful (unless crossed), her affection was so warm (clingy!) and her smile was sickly-sweet-smarmy, I trusted her implicitly. Even when she was hugging all over my new husband.

She was The Experienced Wife. I was a newbie.

She was The Woman. I was merely female.

I didnt feel right unless I had her approval. It was more cult-like than mother/daughter like.

Ive said it before and Ill say it again: theres nothing children of narcissists need more than a good old fashioned bar/bat mitzvah. The Right of Passage is intrinsic in so many cultures so why have we jettisoned it? If you were raised by narcs that line-in-the-sand signalling the end of childhood and the beginning of adulthood just never happened. There was no Coming of Age. You are Never 21. You never know about the Age of Emancipation. Like me, you may have been forced to even give up attending Rites of Passage like your own graduation ceremonies.

There was never a moment when your parent looked you in the eye, grasped your hand and said, Youre my equal as an adult. Youve arrived. I respect you as an equal man/equal woman. My mother gave it lip service, Of course youre an adult but her actions screamed louder than her words.

But now Im forty. To quote Bette Davis in All About Eve:

Lloyd, Im not twentyish.I am not thirtyish. Three months ago,I was forty years old.Forty. Four oh.That slipped out, I hadnt quite made up my mindto admit it.

When my mother failed to acknowledge her only childs fortieth birthday, something went click!

I dont need my mommy anymore.

I dont believe in the godlike image of her anymore. She used your sweetness and cuteness to disguise a shitload of abuse. Frankly, when you look at it all en masse, my mother creeps the hell outta me.

I was one helluva good daughter.

She worked hard to drive me away.

Her loss. Not mine.

I dont need her.

Its time I look myself squarely in the eye, grasp my own hand (metaphorically) and say, You are an Adult Woman in your own right whether your Mommys fragile ego can stand it or not. And youre doing a helluva job running your own life. You dont need herand you havent needed her for twenty years.

There are millions of you ladies out there in the same boat. You email me. You post desperate comments. I read them all. The mother/daughter relationship is probably the most talked about relationship, the hardest to escape, the most painful to endure.

But take motherhood out of the equation. View the quagmire in which youre mired as just two unrelated women. When you take the Cult of Motherhood out of scenario, woman-on-woman abuse will make your stomach churn.

You wouldnt let a female friend treat you that way. You wouldnt tolerate it from a lesbian partner. So why are we letting our mothers violate us like this!?!

Its high time we let Mom attend to her own knittin while we attend to ours. Because thats what it was all about in reality. She positioned us to think we needed her when in reality, she believed she needed us. By sticking around were enabling her faux victimhood. The most loving thing we can do is let Mom sink or swim on her own.

As Mothers Day approaches, I challenge you to do the most bloody, horrifically painful thing Ive ever had to do: cut ties with your narcissistic mother. It flies in the face of nature, but it must be done.

Dont let another woman control you, even if she is your mother.

The rest is here:
How Daughters of Narcissistic Mothers Struggle to Become Adult Women In Their Own Right (Part 1 and 2) - PsychCentral.com

Artificial Intelligence (AI) is an umbrella term that refers to computer technology and software. Artificial Intelligence primarily appears to be intelligent and can do things that would typically require human intelligence. The technologies for Artificial Intelligence include Neural Networks, Machine Learning, Deep Learning, Computer Vision, Natural Language Processing, Big Data, Robotics, and more.

You might think of AI as personal digital assistants like Siri, google image recognition, or the future of self-driving cars. The reality is that artificial intelligence is much broader than that. It is used to help diagnose diseases, detect credit card fraud, assist you in making a reservation, and make recommendations on Netflix, Amazon, and Pandora.

As Andrew Ng put it in his 2017 talk, Artificial Intelligence is the New Electricity, Just as electricity transformed almost everything 100 years ago, today I actually have a hard time thinking of an industry that I dont think AI will transform in the next several years.

Here is a list of the top 20 Artificial Intelligence Speakers to have at your next event.

Noelle is the Vice President of Digital Technology at National Public Radio and a passionate technical evangelist. For more than 20 years, Noelle has been a trainer, architect, and transformer with some of the worlds largest tech companies and has worked on projects ranging from conversational Artificial Intelligence to cloud transformation. Prior to joining NPR, she worked at Microsoft and Amazon.

Max is a Professor at MIT doing physics & AI research and the best-selling author of Life 3.0: Being Human in The Age of Artificial Intelligence. Max speaks on subjects ranging from precision cosmology, the ultimate nature of reality, and what will happen once machines outsmart us at all tasks.

Yoshua is a Machine learning researcher and Full professor at Universit de Montral. Recognized as one of the worlds leading experts in artificial intelligence and a pioneer in deep learning, he speaks about the social impacts of AI and for the Responsible Development of Artificial Intelligence.

Neil is an IBM Master Inventor, United Nations Artificial Intelligence subject matter expert, and Faculty at UC Irvine. He speaks on The Hype and the Real Power of AI, Responsible AI, and AI for Social Good.

Cathy is a leading female futurist specializing in the impact emerging technology is having on communications and business. For 2 straight years in a row, LinkedIn has named her one of the Top 10 Technology Voices on the platform globally. Shes a sought after speaker and thought leader, and speaks on subjects ranging from Artificial Humans, Augmented Reality, Brain-Machine Interface, the Augmented Workforce, Virtual Humans, Artificial Intelligence in Business, and Strategic Foresight.

Suzanne is Founder and co-CEO of Sanctuary.ai, previously co-founder of Kindred AI. Suzannes dream is to create robots that are indistinguishable from humans and is an expert on topics ranging from AI, superconducting microprocessors and quantum machine learning.

Lauren is CEO at Pandorabots, Inc. the worlds leading platform for building and deploying artificially intelligent chatbots. She speaks about chatbots and AI at conferences like Mobile World Congress and South by Southwest and for publications like TechCrunch and Quartz.

Nick is a Professor at Oxford University, where he is the founding director of the Future of Humanity Institute and director of the Strategic Artificial Intelligence Research Center. His talks discuss how to structure our thinking about the really big picture and how the coming machine intelligence revolution will change society and the economy.

Hilary is the founder of Fast Forward Labs and Data Scientist in Residence at Accel Partners. She speaks about Machine learning and AI and its tremendous potential to transform enterprises.

Swami is VP, Machine Learning, Amazon Web Services and is considered a pioneer in cloud computing. He speaks on the adoption of artificial intelligence and data science by making it available for developers, corporations, and laymen alike.

Anita is CEO and Co-founder at Iris.ai: Artificial Intelligence for academics and chemists. She speaks on Artificial Intelligence in general, Scientific publishing, running a startup, disrupting entire industries, and all things future of technology with a focus on ethics.

Allie is the US Head of AI Business Development, Startups, and Venture Capital at Amazon. She was recently named Forbes AI Innovator of the Year and LinkedIn Top Voice for Technology. Allie serves as National Ambassador for AAAS and Advancing Women in Product.

Franziska is the Head of Data Science Platforms at Uber. She speaks on AI applications as varied as forecasting, anomaly detection, Natural Language Processing, conversational AI, experimentation, segmentation, and more.

Pranav is the CEO of NEON, which unveiled their artificial humans at this years CES. Before NEON, he was President and CEO, STAR Labs, and best known for his inventions of SixthSense and the Samsung Gear. Pranav speaks on subjects ranging from Artificial Intelligence, Robotics, Wearable Computing, Augmented Reality, and Gestural Computing.

Andrew is Founder and CEO of Landing AI and Founder of deeplearning.ai. Author or co-author of over 100 published papers in machine learning, robotics, and related fields, he speaks about Deep Learning and the Future of Robotics and Artificial Intelligence.

Taryn is an artist, writer, and producer with more than 700 million views across her online content. One of Taryns current projects is a music album titled I AM AI, composed entirely with artificial intelligence. She recently launched a documentary titled I AM HUMAN that explores the future of humanity + technology.

Gary is CEO and Founder at Robust.AI and Co-author Rebooting AI. He speaks on fields ranging from human and animal behavior to neuroscience, genetics, and artificial intelligence.

Danny is Vice President of Artificial Intelligence and Machine Learning at Unity Technologies and previously worked for Uber, Amazon, Microsoft, and IBM. He discusses the role of intelligence in biological evolution and learning and demonstrates why a game engine is the perfect virtual biodome for AIs evolution.

Ramses is an Electrical Engineer, neuroscientist, previous CEO of Pharo LLC, and current CEO of Neurable. Ramses speaks on brain-computer interfaces and the race in understanding the brain and how it connects to human-computer interaction.

Jrmeis Vice President of Artificial Intelligence at Facebook with a 20-year involvement in artificial intelligence, natural language processing, big data, and machine learning. As a speaker, he highlights the societal benefits of artificial intelligence, as well as some of the challenges and risks that AI researchers are facing.

Brad is the editor overseeing contributed content at ReadWrite.com. He previously worked as an editor at PayPal and Crunchbase. You can reach him at brad at readwrite.com.

See the original post:
Top AI Speakers to Have at Your Event - ReadWrite

More men are dying from COVID-19 worldwide than women, and the potential reasons run the gamut from biology to bad habits.

The World Health Organization (WHO) reports that 68 percent of deaths related to COVID-19 in Europe have been among men.

A study by the Higher Health Institute of Rome found that among Italians hospitalized for the novel coronavirus, 8 percent of men died compared to 5 percent of women.

In New York City, men have been dying of coronavirus at almost twice the rate of women. The citys health department reports 43 COVID-19 deaths for every 100,000 men, compared with 23 deaths for every 100,000 women.

The Centers for Disease Control and Prevention (CDC) currently isnt reporting COVID-19 deaths by gender, but experts see no reason the trend would differ elsewhere in the country.

Some of the underlying reasons why COVID-19 may be more deadly for men than women may include the fact that heart disease is more common in elderly men than in elderly women, Dr. Stephen Berger, an infectious disease expert and co-founder of the Global Infectious Diseases and Epidemiology Network (GIDEON), told Healthline. Studies also find that high blood pressure and liver disease are more prevalent in men and these all contribute to more negative outcomes with COVID-19.

Genetics may also play a big role, Berger said. Women, because of their extra X chromosome, have a stronger immune system and response to infections than men.

You cant get away from biology and genetics, agreed Salvatore J. Giorgianni, PharmD, a pharmacist and senior science advisor for the Mens Health Network, which advocates for the health of men and boys.

Males are culturally conditioned to think of themselves as strong, Giorgianni told Healthline, but women are not the weaker sex when it comes to immunity.

Moreover, he noted, men have higher rates in 9 out of 10 of the leading causes of death in the United States.

That means theyre more likely to have preexisting conditions that can make COVID-19 more dangerous.

Behaviors that impact lung health, such as smoking, also may play a role in the diseases deadly impact on men.

In China, for example, smoking is largely a male habit, resulting in many men suffering from chronic lung disease, Berger said. This puts men at a much greater disadvantage should they get COVID-19.

The WHO estimates that air pollution kills more than 4 million people annually by contributing to illnesses such as asthma, bronchitis, emphysema, lung and heart diseases, and respiratory allergies.

A recent study from the Harvard T.H. Chan School of Public Health in Massachusetts reported that people who live in areas with high levels of air pollution are also more likely to die of COVID-19 than those in less polluted areas.

Pollution could also be playing a role in elevated COVID-19 mortality rates among men.

In most cultures, men are more likely to be engaged in outdoor work, exposing them to conditions associated with extreme climate and pollution, Berger said. This could directly impact their response to an infection like COVID-19.

High-risk occupations deemed essential under pandemic emergency orders notably first responders also may be disproportionately jobs men traditionally do, Derek M. Griffith, PhD, director of the Institute for Research on Mens Health at Vanderbilt University in Tennessee, told Healthline.

Higher rates of death among men in pandemics is not new.

Research on the worldwide flu of 1918, for example, found that non-elderly adult males died at a much higher rate than women, possibly because more men had a history of lung-damaging tuberculosis.

Male behavior during the pandemic also could be increasing their exposure to the novel coronavirus.

A Gallup poll taken between March 2 and 13 found that women were more concerned about COVID-19 than men were (by a 62 to 58 percent margin).

Its possible that men are more at risk because they tend to expose themselves more to larger crowds and social exchanges, including things like handshaking and sporting events, Berger said.

There are men with invincibility syndrome that underpins a lot of behaviors, and they tend to be less compliant with pandemic-related restrictions such as physical distancing, Giorgianni said.

For other men, he said, the issue isnt so much a cavalier attitude as simply being conditioned to think of health as not their job.

COVID-19 prevention messages aimed at men should focus on these traditional male roles, not ignore millions of year of biology and natural selection, Giorgianni said.

Guys are very concerned for their families, so tell them dont do it for yourself, do it for those who love you, he said. Even if they feel like theyre in good shape and can fight it off, they can still be a carrier can cause the death of their spouse or daughter or their dad.

Griffith cautioned, however, that much remains unknown about COVID-19, including its different impact on men and women.

Its worth considering these factors, but its a little premature, he said. Most of these statements seem to assume we know more about this disease than we do.

One thing that is well-proven, however, is that men tend to delay seeking healthcare and ignore or dismiss symptoms of illness.

Many men see self-care as an admission of weakness, David Ezell, chief executive officer of Darien Wellness, a mental health group in Connecticut, told Healthline. We are taught to be self-sufficient and there for everyone but ourselves. That results in ignoring telltale symptoms of not only COVID but any life-threatening condition.

Dr. Deborah Birx, the COVID-19 response coordinator for the Trump administration, noted at an April 9 briefing that 56 percent of people who have been tested for the illness are male compared to 44 percent female.

Of the men who were tested, 23 percent were positive for COVID-19, compared to 16 percent of women.

It gives you an idea about how men often dont present in the healthcare delivery system until they have greater symptomatology, Birx said. This is to all of our men out there, no matter what age group: If you have symptoms, you should make sure that you are tested.

More here:
Why COVID-19 Is Hitting Men Harder Than Women - Healthline

INTRODUCTION

Interplanetary space is populated by densely ionizing particle radiation not naturally present on Earth (1). Life on Earth has evolved under the protection of a geomagnetic field, which deflects high-charge, high-energy (HZE) ions; however, the constant flux of HZE ions in deep space is essentially impossible to shield, making astronaut exposures inevitable (2).

In the absence of human epidemiological data for exposures to HZE radiation, uncertainties surround the cancer risk estimates for space flight crews that venture beyond low Earth orbit. The current NASA space radiation cancer risk model is built largely upon epidemiological data from the survivors of the Hiroshima and Nagasaki atomic bombings, a cohort of individuals exposed predominantly to -rays (35), a form of photon radiation. One key assumption in this NASA model is that the spectra of tumor types, and their biologic behaviors, will be similar for individuals exposed to ionizing radiation, whether particle or photon. However, notable physical differences exist between ionizing photon and particle radiation, and these physical differences translate to unique ionization and damage patterns at the molecular, cellular, and tissue levels. HZE ion exposures produce spatially clustered DNA double-strand breaks, along with other DNA lesions in close proximity to break sites (6). In contrast, -rays produce sparse ionization events that are random in spatial distribution and less likely to have additional DNA lesions immediately adjacent to the break sites. Other assumptions in the model are that radiogenic tumors are no more lethal than their sporadic counterparts and that females are at greater risk for radiogenic cancers than males (7).

In assessing cancer risks to astronauts, the premise that HZE ion exposures increase the risk for the same types of tumors that arise in human populations exposed to -rays is supported by the few animal studies of HZE ion carcinogenesis conducted to date (8). These studies, conducted on genetically homogeneous animals, have demonstrated that tumor types arising in HZE ionirradiated animals are the same as those that occur spontaneously in these animals or following exposure to photon radiation (8). However, all previous data are from either inbred mice (9, 10) or rats (11), F1 hybrid mice (12, 13), or rat stocks with limited genetic heterogeneity (11, 1416), and the tumor types that arise in inbred rodents are determined, in very large part, by their genetic background. Therefore, the spectrum of tumors that might arise in a genetically diverse population exposed to HZE ions is unknown.

With the emergence of multiparent outbreeding strategies that produce highly recombinant mouse populations with allelic variants from multiple founder strains (1719), it is possible to model the effects of population diversity in carcinogenesis studies by minimizing the overwhelming effects of genetic background and increasing the phenotypic repertoire available within a test population. These populations also allow for high-precision genetic mapping (18, 20). Quantitative trait locus (QTL) mapping is a powerful forward-genetics approach that allows for unbiased testing of genetic variants that may influence gene-environment interactions for radiation effects (21, 22). Highly recombinant populations were constructed for the purpose of mapping complex traits, and QTL can often be resolved to megabase resolution (1820). In addition, complete sequence information can be used on genotyped individuals by imputing the substantial genomic resources available for the founder strains.

Studying tumors that arise in irradiated, genetically diverse mouse populations presents a unique opportunity to test key assumptions of the NASA risk model, particularly whether HZE ions induce the same tumors by the same mechanisms as -rays. If so, the current practice of extrapolating human epidemiological data from individuals exposed to -rays to astronauts exposed to HZE ions would be a valid approach for risk calculation in the space radiation environment.

To study the effects of HZE ion irradiation in a genetically heterogeneous population, 1850 HS/Npt stock mice (23) of both sexes were genotyped for 77,808 single-nucleotide polymorphism (SNPs) and exposed to (i) 0.4 gray (Gy) of 28Si ions (240 MeV/n) [linear energy transfer (LET), 80 keV/m; = 0.031 particles/m2] or (ii) 56Fe ions (600 MeV/n) (LET, 181 keV/m; = 0.014 particles/m2), (iii) 3 Gy of 137Cs -rays, or (iv) sham irradiation. We chose 56Fe ions because of their high abundance in galactic cosmic radiation (GCR) and because their high charge (Z = +26) makes them particularly damaging (24). The 28Si ions were selected because their LET more closely approximates the dose average LET of secondary fragments generated by GCR penetrating an aluminum spacecraft hull (25). The mice were monitored daily until they reached 800 days of age or became moribund. Comprehensive necropsies were performed on each mouse and involved all organ systems. Each detected lesion was characterized histologically by a board-certified veterinary pathologist. Tumors were the predominant cause of morbidity and mortality for both HZE ionirradiated (n = 622) and -rayirradiated (n = 615) populations as well as for the population of unirradiated mice (n = 613). Overall life span was significantly reduced for irradiated populations (Fig. 1A), which can be attributed to the increased incidence and decreased median survival for radiation-induced tumors. For irradiated mice, populations exposed to 0.4-Gy HZE ions had increased survival times compared to mice exposed to 3.0 Gy of -rays (Fig. 1A). Although these doses seem disparate, their selection is based on preliminary dose-response studies (26), which reveal that 0.4 Gy of HZE ions and 3.0-Gy -rays are each maximally tumorigenic.

Overall survival for HS/Npt mice, plotted as Kaplan-Meier survival, is presented for each exposure group (A). The incidence of specific tumor histotypes (B) and median survival times for these tumors (C) are plotted for each exposure group, which demonstrates that certain tumor types occur at an increased frequency following exposures to radiation of specific qualities and survival times in irradiated mice are decreased for some tumor types. The incidence of specific tumor histotypes within HS/Npt families is plotted for unirradiated (D), -rayirradiated (E), and HZE ionirradiated families (F) and demonstrates that specific tumor types often occur at very high incidence within some families and not at all in others, indicating heritability of tumor susceptibility. Furthermore, adjacent families are more closely related, and tumor incidences, for example, family 23 and adjacent families, have a high incidence of B cell lymphoma. The 47 HS/Npt families are arranged along the x axis (D to F).

A wide variety of tumor diagnoses [82 distinct tumor histotypes (table S1)] were observed in HS/Npt mice. Although most of these tumor types were rare, 18 histotypes were observed at incidences greater than 1%. Overall, the spectra of tumor histotypes produced in genetically diverse populations exposed to HZE ions and -rays were similar (Fig. 1B). Furthermore, tumor types induced by radiation were generally similar to those arising spontaneously in HS/Npt mice; however, radiation-exposed populations demonstrated decreased median survival times associated with tumor development (Fig. 1C and figs. S7 to S22) and increased incidences for specific tumor types, such as leukemias and Harderian gland adenocarcinomas, following radiation (Fig. 1B). The structure of the HS/Npt population can be divided into families that consist of mice more closely related to one another. Many tumor histotypes show high incidences within some families but are absent or rare in others (Fig. 1, D to F), which is consistent with genetic susceptibility to certain tumor types. Furthermore, certain tumorsparticularly lymphomas, pulmonary adenocarcinomas, hepatocellular carcinomas, Harderian gland tumors, and myeloid leukemiasdemonstrate a periodicity in tumor incidence (Fig. 1, D to F) where adjacent families often display similar incidences, which could be predicted on the basis of the circular breeding design used to generate HS/Npt, in which adjacent families are more related to one another than families further removed.

Although the tumor spectra are similar for each irradiated population, the different radiation qualities demonstrate varied efficiencies for producing specific tumor histotypes. -rayirradiated mice were at greater risk for myeloid leukemia, T cell lymphoma, pituitary tumors, and ovarian granulosa cell tumors than unirradiated mice; HZE ionirradiated mice demonstrated an intermediate susceptibility to these histotypes (Fig. 1B). For Harderian gland tumors, thyroid tumors, hepatocellular carcinomas, and sarcomas, HZE ion and -rayirradiated mice were at a similarly and significantly increased risk compared to unirradiated controls (fig. S7 to S22).

NASA permissible exposure limits for radiation limit the number of days an astronaut can spend in space based on modeled cancer risk. These limits are different for men and women (27) due primarily to epidemiological data that indicate that women are at greater risk for radiogenic cancers than men due to their longer life spans and susceptibility to specific cancer types, such as lung, ovarian, and breast carcinomas. Female HS/Npt mice have longer life spans than males (P = 2.7 106, log-rank test), with unirradiated females living 43 days longer (686.1 days), on average, than males (643.2 days) (fig. S1A). In contrast, no survival difference is observed between -rayirradiated females and males (P = 0.51) or HZE ionirradiated females and males (P = 0.06), indicating that female HS/Npt mice are more susceptible to radiation-induced morbidities and mortalities than males (fig. S1, B and C). Irradiated female mice had increased incidences of (i) ovarian tumors, (ii) mammary tumors, (iii) central nervous system tumors (pituitary adenomas, choroid plexus tumors, and ependymomas), (iv) diffuse large B cell and lymphoblastic B cell lymphomas, (v) osteosarcomas, and (vi) leiomyosarcomas (fig. S1D). Female mice were at lower risk for radiogenic lung cancer (fig. S1D and table S1), which is a major contributor to limiting flight time for female astronauts. Modeling risk by sex in humans has been confounded by different smoking rates between men and women in the atomic bomb survivor cohort (28).

To determine whether the genetic variants that increase tumor susceptibility following -ray irradiation also increase tumor susceptibility following HZE ion irradiation, genome-wide association mapping was performed for 18 tumor types in which there was an incidence of greater than 1%. Genomes were reconstructed for each mouse using a probabilistic model to predict founder haplotypes from high-density genotype data (18). Reconstructed genomes represent the unique accumulation of meiotic events for each individual and form a scaffold for the imputation of known sequencing information from the eight parental inbred strains. Polygenic covariance among related individuals is of significant concern in multiparent crosses and was corrected for during QTL mapping with a kinship term (18, 29). Mapping was performed for each phenotype using both a generalized linear mixed-effects model and proportional hazards regression model with the aforementioned kinship to adjust for polygenic covariance between related mice. To determine the significance thresholds for a model in which no QTL is present, the phenotypes were permuted, the regression model was run, and the maximum statistic was retained from each permutation (30). The 95% significance threshold was minimally variable between phenotypes with a mean threshold of log(P) > 5.8, and this value was used to identify significant associations. This is consistent with the estimated 0.05 Bonferroni genome-wide corrected threshold of log(P) > 6.0, which is considered overly conservative for QTL mapping (30).

At least one QTL was identified for 13 of the 18 tumor phenotypes examined. For tumor incidence, 35 QTL were identified with an average confidence interval of 3.4 Mb (table S2). For QTL at the 95% confidence threshold, effect sizes average 3.7% of the phenotypic variance with a range of 0.75 to 7.46%. For most of the tumors, the genetic architecture was complex with multiple QTL individually explaining a small proportion of the total variance. Although loci with moderate effects on the phenotype were most common, 11 large effect QTL were observed for seven tumor histotypes, with effect sizes greater than 5% (table S2).

To determine potential effects of genetic variants on tumor latency following irradiation, mapping was also performed using proportional hazards regression model (table S3) and 38 QTL were identified for 12 tumor types. QTL associated with tumor survival times mirrored those identified for tumor incidence, indicating that the genetic variants that control susceptibility to radiation-induced tumors also determine latencies.

Neoplasia is a binomially distributed trait, and therefore, the power to detect significant associations is primarily dependent on tumor incidence and QTL effect size. This leads to important considerations for the ultimate goal of this analysis, which is to determine similarities between QTL for specific neoplasms in populations exposed to different qualities of radiation. For some tumor types, a significant peak was observed in one exposure group with a suggestive peak present at the same locus in the alternative exposure group. We speculate that the reason certain radiation qualities produce only suggestive QTL for certain tumor phenotypes is likely due to decreased mapping power as a result of the variation in incidence between groups. In these cases, if the peak was more significant when combining radiation groups, the QTL was considered significant for all irradiated animals regardless of radiation quality.

Thyroid tumors are a well-known radiation-induced entity for both humans and mice; however, relatively little is known about genetic variants that increase susceptibility to this disease in mice. In HS/Npt mice, spontaneous thyroid adenomas occurred at relatively low frequencies and had a uniformly late onset, with tumors occurring between 700 and 800 days of age (Fig. 2A). In contrast, thyroid tumors arising in HZE ion or -rayexposed mice occur with significantly earlier onsets, with tumors arising as early as 250 days of age (Fig. 2A).

Thyroid follicular adenoma Kaplan-Meier survival estimate (A) along with genome-wide association plots for thyroid adenoma in HZE ionirradiated, -rayirradiated, HZE ion and -rayirradiated, and unirradiated mice (B) and an expanded plot for chromosome 2 (C), which contains the most significant association locus; gray lines indicate 95% (upper line) and 90% confidence (lower line) for log10(P values). Genome-wide association results reveal significant results in HZE ion and -rayirradiated mice that are further bolstered by combining the groups. The top panel of (D) shows strains that contribute the reference allele for the SNPs highlighted in red in the middle panel, indicated by vertical lines (D); the C57BL/6J strain contributes an allele that differs significantly from the other seven strains. The middle panel shows the log10(P value) of each SNP in the interval (D); the most significant SNPs are highlighted in red, and the bottom panel lists genes within the QTL interval. Genes that contain splice site, missense, or stop-related SNPs are colored red (D). Resample model averaging was performed within chromosome 2 to compare the distribution of peak log10(P values) for each exposure group (E); there is broad overlap for HZE- and -rayirradiated mice, and grouping all irradiated mice together further narrows the distribution of peak log10(P values). Mbp, megabase pair.

Association mapping reveals a significant 3.4-Mb interval on chromosome 2 for HZE ionexposed animals (Fig. 2, B and C). The same locus is identified in the -rayirradiated population if the significance threshold is decreased to a level at which 30% of identified QTL will be false positives. Combining both irradiated populations markedly increases the significance of the QTL identified on chromosome 2. The QTL interval (119 to 125 Mb) contains 39,179 SNPs (Sanger Mouse Genomes, REL-1505) and 142 genes (Ensembl version 85) (Fig. 2D). Within the QTL region, the C57BL/6J parental strain contains an introgression from the Mus musculus musculus genome (31); we found that HS/Npt mice carrying the C57BL/6J haplotype at the QTL have increased thyroid tumor incidence regardless of whether they are exposed to HZE ions or -rays.

To further explore the possibility that the QTL identified on chromosome 2 controls susceptibility following -ray and HZE ion exposures, we used a nonparametric resample model averaging procedure (32) across the entire chromosome to identify genomic loci that consistently reappear in resampled populations. Briefly, genome scans are repeated for each new dataset created, in which some individuals may be sampled more than once and some not at all (32). Resample model averaging consistently identifies the same locus for all groups of mice, regardless of radiation exposure (Fig. 2E). Furthermore, the resample model averaging procedure identifies the same locus for tumors arising spontaneously (Fig. 2E). Data from this tumor phenotype indicate that the same inheritable genetic variants contribute to an individuals risk of developing thyroid cancer, regardless of radiation exposure.

Acute myeloid leukemia (AML) is another common radiation-induced tumor in both mice and humans (33, 34). In concordance with previous studies conducted with inbred mice (26), -ray exposures in HS/Npt mice are more efficient at inducing AML than HZE ion exposures. In our -irradiated mice, 15.6% (96 of 615) developed AML compared to 2.9% (18 of 622) of those exposed to HZE ions and 1.6% (10 of 613) of unirradiated mice. AML median survival times were similar for all groups (Fig. 3A). Association mapping revealed a significant QTL for the -irradiated population on chromosome 2 that reached the 95% confidence threshold (Fig. 3, B and C), but no QTL was observed for the HZE ionexposed population, in which the incidence of AML was much lower. However, when grouping HZE ion and -rayirradiated mice together, the same QTL was significantly bolstered (Fig. 3B). If the susceptibility alleles identified at this locus were only contributing to disease following -ray irradiation and were, therefore, randomly distributed among the affected mice in the HZE ionexposed group, then we would expect the log10(P values) to decrease when combining -irradiated mice; however, the log10(P value) for this locus significantly increases when repeating the mapping procedure included all irradiated mice.

(A) Kaplan-Meier plots for myeloid leukemia demonstrate similar median survival estimates for myeloid leukemia between groups. (B) Genome-wide association procedures identify a narrow QTL on chromosome 2; two gray lines indicate 95% (upper line) and 90% confidence (lower line) for log10(P values). Expanded mapping results are depicted in (C) along with contributing strains for the reference allele. The A/J, AKR/J, C57BL/6J, DBA/2J, and LP/J strains contribute alleles that differ from the other strains, indicated by vertical lines in the top panel (C). The middle panel shows the log10(P value) of each SNP in the interval. The most significant SNPs are highlighted in red. The bottom panel shows the genes in the QTL interval. Genes that contain splice site, missense, or stop-related SNPs are indicated in red. Copy number results for Spi1 and Asxl1 in splenic samples from mice diagnosed with myeloid leukemia are plotted by exposure group (D).

Radiation-induced AML is a well-characterized disease in mice (10, 35, 36) and is most commonly the result of a radiation-induced minimally deleted region on chromosome 2 containing the PU.1 gene (current murine nomenclature, Spi1) and a recurrent point mutation that inactivates the remaining Spi1 allele (37). Figure 3C depicts mouse chromosome 2 with the positions of the QTL identified in our irradiated mice and the Spi1 gene. To test the hypothesis that AMLs occurring in HZE ionexposed animals will contain the same molecular aberrations know to occur in AML arising in -rayexposed mice, the copy number for Spi1 was investigated in leukemia samples to assess for deletions. As expected, most of the leukemias occurring in -rayexposed mice had a deletion in one copy of Spi1. In contrast, Spi1 deletions in spontaneously occurring AML were less common (Fig. 3D). Similar to -rayirradiated mice, leukemias that developed in mice exposed to HZE ions, although fewer in number, also have an increased incidence of Spi1 deletion. This finding indicates that AML arises by similar molecular mechanisms following exposures to HZE ions or -rays.

Because the QTL identified on chromosome 2 is approximately 60 Mb from the commonly deleted region containing Spi1 and because radiation-induced deletions can be notoriously large, we considered the possibility that the identified QTL was also deleted in these leukemias, resulting in loss of one copy of the QTL region. To test this hypothesis, we determined the copy number for a gene located at distal to the QTL support interval, Asxl1. As expected, we found that Asxl1 was not deleted in any sample in which Spi1 was not deleted; however, in 69% of cases with a Spi1 deletion, Asxl1and presumably the entire QTL regionwas also deleted (Fig. 3D). This demonstrates that most of the radiation-induced AML cases arose from progenitor cells haploinsufficient for the entire QTL region.

HZE ion and, to a lesser extent, -ray irradiation were particularly effective in inducing Harderian gland tumors at the doses used in this study, which was expected on the basis of extensive published radiation quality data on these tumors (8, 38). In the HZE ionirradiated group, Harderian gland tumors were observed in 22.7% (221 of 622) of mice and 3.2% (20 of 622) were malignant. In the -irradiated group, 15.3% (94 of 615) of mice developed Harderian gland tumors and 2.7% (17 of 615) were malignant. In contrast, spontaneous Harderian gland tumors occurred in only 4.1% (25 of 613) of unirradiated mice and 0.7% (4 of 613) were malignant. Despite the differences in tumor incidences following irradiation, median survival times for Harderian gland adenocarcinoma were similar for all groups (HZE ion, 582 days; -ray, 571 days; and unirradiated mice, 571 days).

Two QTL were observed for Harderian gland adenocarcinomas in HZE ionirradiated mice, one on chromosome 4 and another on chromosome 9 (Fig. 4A). The 1.7-Mb interval identified on chromosome 4 (Fig. 4B) is similar to previously discussed QTL regions in that combining both irradiated populations markedly increases the significance of this locus, which suggests that this QTL is associated with Harderian gland adenocarcinoma susceptibility in both HZE ion and -rayirradiated mice. In contrast, a 2.3-Mb QTL interval on chromosome 9 is observed only in HZE ionirradiated mice, and the locus is absent when combining all irradiated mice and repeating the mapping procedure (Fig. 4C). To further evaluate these QTL, resample model averaging was performed within chromosomes 4 and 9 to determine the distribution of peak log10(P values) along each chromosome. For chromosome 4, there is substantial spatial overlap identified in peak log10(P value) associations in the HZE ionexposed population and the -rayirradiated population, and the HZE ion and -rayirradiated population yields the most consistent identification of the QTL region (Fig. 4D). In contrast, although nearly all identified peak log10(P values) were identified in the 2.3-Mb QTL interval on chromosome 9 for HZE ionirradiated mice, the distributions of peak log10(P values) for other exposure groups do not substantially overlap and are widely distributed along the chromosome (Fig. 4E). The resample model averaging results indicate that while the chromosome 4 QTL contributes to susceptibility to Harderian gland adenocarcinomas in both HZE ion and -rayirradiated populations, the QTL identified on chromosome 9 appears to only be involved in Harderian adenocarcinoma susceptibility following HZE ion exposures.

Genome-wide association plots for Harderian gland adenocarcinoma (A) for HZE ionirradiated, -rayirradiated, HZE ion and -rayirradiated, and unirradiated mice; two gray lines indicate 95% (upper line) and 90% confidence (lower line) for log10(P values). Chromosome 4, which is expanded in (B), reveals a significant QTL associated with HZE ion irradiation, which is further increased significantly when grouping all irradiated mice (HZE ion and -ray irradiated) together, which indicated that the genetic variants in this location are important for Harderian gland adenocarcinoma following exposures to either HZE ion or -ray irradiation. In contrast, chromosome 9, which is expanded in (C), reveals a significant QTL associated only with HZE ion irradiation; this locus is absent when grouping all irradiated mice (HZE ion and -ray irradiated) together, which suggests that the allele(s) present in this region may only play a role for HZE ioninduced tumors. Resample model averaging was performed within chromosomes containing significant QTL. There is significant spatial overlap identified on chromosome 4 for peak log10(P value) associations in the HZE ionexposed population, the -rayirradiated population, and the HZE ion and -rayirradiated population that demonstrates the most consistent identification of the QTL region (D). In contrast, although nearly all identified peak log10(P values) were identified in the chromosome 9 QTL interval for HZE ion irradiated mice, the peak log10(P values) for other exposure groups are widely distributed along the chromosome (E).

In addition to looking for similarities between individual, selected QTL for HZE ion and -rayexposed populations, we also sought a more holistic method in which entire genome-wide association results could be compared between groups in an unsupervised process. We used hierarchical clustering to create cluster dendrograms using entire genome-wide scans for a given phenotype. By considering results from genome-wide associations, rather than individualized peaks observed within genome-wide associations, we submit for comparison not only highly significant QTL regions but also the numerous loci detected with lower confidence.

Unsupervised hierarchical clustering of genome scans creates significant clustering events that often occur for the same histotype regardless of radiation exposure (Fig. 5A). Multiple tumor histotypesincluding mammary adenocarcinoma, thyroid adenoma, and hepatocellular carcinomacluster by histotype, regardless of radiation exposure. To demonstrate and validate the methodology of QTL clustering, genome-wide scans for coat colors in each treatment group are evaluated and coat color genome-wide scans cluster together, as expected (Fig. 5B). These results further support the hypothesis that host genetic factors are highly important in determining risk of radiation carcinogenesis, whether following HZE ion or -ray exposures.

(A) Unsupervised hierarchical clustering of genome-wide association scans for tumor phenotypes reveals that the most significant clustering events often occur for the same histotype regardless of radiation exposure; these include mammary adenocarcinoma, thyroid adenoma, and hepatocellular carcinoma. (B) As expected, clustering genome scans for coat color demonstrates the expected results: that genome scans cluster together despite exposure group. The green line represents the 99% confidence level of the most significant dendrogram heights by permutations (log10 values permuted with genetic markers) to determine a distribution of dendrogram heights under the null hypothesis that no associations exist (C), demonstrating that the observed clusters are highly unlikely to occur randomly.

Permissible exposure limits for astronauts are based on the risk of death from cancer rather than cancer development, and the incidence to mortality conversion used in the risk calculation uses spontaneously occurring cancers in the U.S. population. Thus, there is an assumption that radiogenic tumors are no more lethal than spontaneous tumors. To determine whether tumors that arise following HZE ion exposure are more malignant than their counterparts arising in unirradiated or -rayirradiated mice, metastatic disease was characterized for each group. Pulmonary metastases were consistently observed in cases of hepatocellular carcinoma, Harderian gland adenocarcinoma, osteosarcoma, and ovarian granulosa cell tumor. Metastases were no more frequent in irradiated animals than in controls, and there was no significant difference in metastatic incidence between HZE ionirradiated mice and -rayirradiated mice (fig. S5A), and pulmonary metastatic density is similar between groups (fig. S5, B to D).

Tumor latency following irradiation was compared between exposure groups using survival statistics. Differences in tumor latency in this context indicate a decrease in time for tumor initiation or promotion. Since radiation is efficient at both initiation and promotion, decreased latencies are expected for irradiated population. Tumor progression is not evaluated, and our results therefore do not demonstrate whether tumors arising in irradiated individuals are more likely to progress rapidly than those arising spontaneously. As expected, tumors arising in both HZE ion and -rayirradiated mice show significantly decreased latencies in comparison to the unirradiated population (fig. S7 to S22). However, HZE ions did not further decrease latencies when compared to -rayirradiated mice.

Carcinogenesis as a result of space radiation exposure is considered the primary impediment to human space exploration (2). Compared to forms of radiation found naturally on Earth, including x-rays, -rays, and particles, HZE ions in space are much more difficult to shield (2) and have a distinct ionization pattern that aligns along dense track structures, resulting in clustered damage to chromatin (6). Because HZE ions, a highly penetrating component of GCRs, are not amenable to shielding (28, 29), exposure risks are inherent to manned missions in interplanetary space, but estimating the risk associated with this unique form of particle radiation is complicated by the essential lack of data for human exposures (28). As a substitute, human exposure data from other forms of ionizing radiation, primarily -ray (35) photon radiation, are used in cancer risk models with the assumption that photon and particle radiation have qualitatively comparable biological effects.

Animal models are a vital component in determining the validity of the extrapolation of human terrestrial radiation exposure data to exposures that will occur in astronauts in the space radiation environment. To date, carcinogenesis studies designed to evaluate the effects of HZE ions have used rodents with limited genetic heterogeneity (916). The advantage of removing genetic variability in animal models is the consequent decrease in phenotypic variability, which allows for fewer individuals to detect potential environmental effects on phenotype; the disadvantage is that strain-specific responses in genetically identical populations are significant and can obscure the variability that one might expect in a diverse population, such as humans. By using a genetically diverse population with a wide range of tumor susceptibilities, the spectra of tumors that occur following exposures to particle and photon radiation can be compared. The results of this study indicate that the spectrum of tumor histotypes observed in a genetically diverse population exposed to particle radiation is not unique to that observed in a population exposed to photon radiation or to the tumor spectrum observed in an unirradiated population. Despite the similarities observed in tumor spectra following radiation exposures, the radiation qualities and doses used for this study have unique efficiencies at producing specific tumor types, and while this work demonstrates that the underlying genetics of susceptibility can be similar for tumorigenesis following both high- and low-LET radiation, further work is necessary to define risks for specific tumor histotypes based on exposures.

This study uses a highly recombinant mouse population (HS/Npt stock) that is genetically diverse and designed for genome mapping (1921, 23), a forward-genetics approach that allows for an unbiased search of the entire genome for genetic associations. In contrast, genetically engineered mouse models rely on a reverse-genetics approach in which a given gene is first altered and the resulting phenotypes are then characterized. Studies using forward-genetics are most informative in populations that contain abundant genetic and phenotypic diversity. HS/Npt mice are a multiparent cross derived from eight inbred strains (A/J, AKR/J, BALBc/J, CBA/J, C3H/HeJ, C57BL/6J, DBA/2J, and LP/J); each individual contains a unique mosaic of founder haplotypes and a high degree of heterozygosity, and recombination events become increasingly dense with each generation. Our population of HS/Npt mice was obtained from generation 71 of circular outbreeding. Creating these populations is not trivial and has been a central goal of communities involved in genetics research over the past few decades, resulting in the creation of rodent populations ideal for genome mapping (1820, 3942).

Genome mapping allows the discovery of QTL associated with susceptibility to complex traits, such as radiogenic cancers; this approach is uniquely suited to comparing inheritable risk factors for cancers following exposures to unique carcinogens, such as particle and photon radiation. In broader terms, this work demonstrates the utility of highly recombinant mouse models created for genetic mapping in carcinogenesis studies, an application that has not been previously attempted. Mapping QTL in carcinogenesis studies provides inherent challenges due to the structure of binomial data, potential confounding causes of death following irradiation and aging, the fundamental stochastic nature of radiation tumorigenesis, and incomplete penetrance of potential allelic variants. Despite these challenges, we were able to map QTL for 13 neoplastic subtypes and many of these identified loci are previously unidentified.

At the doses used in this study, HZE ions appear to be less effective than -rays in inducing precursor T cell lymphoblastic lymphoma (pre-T LL) and ovarian tubulostromal adenomas and granulosa cell tumors. This may be due to a combination of dose inhomogeneity in HZE ionirradiated tissues and the major role cell killing plays in the etiology of these specific tumors. pre-T LL can be prevented by transplanting irradiated mice with unirradiated syngeneic bone marrow cells or by shielding some of their bone marrow during irradiation (43, 44). The underlying mechanism by which unirradiated bone marrow cells suppress lymphomagenesis may involve a cell competition process by which older T cell progenitors resident in the thymus are normally replaced by fresh progenitors that immigrate from the bone marrow. Radiation kills these fresh bone marrow cells or reduces their fitness, which, in turn, prolongs the time that older T cell progenitors already in the thymus survive and self-renew. This, along with the increased proliferative cycles of the older T cell progenitors needed to maintain production of mature T cells, results in a corresponding increase in the oncogenic mutations that they accumulate and a concomitant increase in lymphomagenesis (45). Replenishing dead or damaged bone marrow cells by transplantation or preventing their damage through shielding suppresses lymphomagenesis.

At the 3-Gy dose of -rays used in this study, all of the bone marrow cells are uniformly irradiated. This is not the case for HZE particle radiation. The average diameter of a murine bone marrow cell nucleus is around 6 m (46). At the fluence of HZE ions used in this study, the probability that a 6-m-diameter nucleus will be traversed by a 28Si ion and a 56Fe particle is 0.88 and 0.40, respectively. On the basis of a Poisson distribution, the probabilities of a nucleus not being traversed at all are 0.41 and 0.67 for 28Si and 56Fe irradiation, respectively. Thus, many of the T cell progenitors in the bone marrow are not irradiated (although they receive a small dose from -rays). These cells should exert a protective effect similar to transplanting unirradiated bone marrow cells or shielding some of the bone marrow during irradiation, rendering HZE ions less efficient for lymphomagenesis. Given that most of the pre-T LL in the HZE ionirradiated group are likely spontaneous, it is expected that they cluster more closely to spontaneous pre-T LL than to -rayinduced pre-T LL.

The mechanism leading to murine tumors of ovarian surface epithelium origin is well understood. Loss of primordial follicle oocytes by radiation-induced apoptosis results in a decrease in estrogen production, which, in turn, leads to elevated levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the circulation. FSH and LH drive proliferation of ovarian surface epithelium cells (47). Ovarian tumors can be induced in some animal models by artificially manipulating levels of these hormones (4749). Irradiated mice can be protected from tubulostromal adenomas and granulosa cell tumors by shielding one ovary during irradiation or by transplanting the mice with an unirradiated ovary (50, 51); these interventions protect some oocytes and thereby maintain proper regulation of FSH and LH levels.

Assuming that the target cells are primordial follicle oocytes with a diameter of 12 m, the probabilities of no traversals are 0.2 for 56Fe and 0.03 for 28Si at the 0.4-Gy dose used here. The probabilities for one or fewer traversals are 0.52 for 56Fe and 0.14 for 28Si. Whether a sufficient number of follicles survive at 0.4 Gy to account for the observed ovarian tumor sparing is unknown. Mishra and colleagues (52) observed a dose-dependent decrease in primordial stage follicles in C57BL/6 mice 8 weeks after irradiation with 56Fe ions (600 MeV/n). Sixteen percent of the follicles survived at the 0.3-Gy dose, and normal levels of serum FSH and LH were present; at 0.5 Gy, only 1% of the follicles survived and an increase in serum FSH was observed. Caution is needed in using Mishras results in interpreting our own since we used mice with different genetic backgrounds and the FSH and LH levels in the 0.3 Gyirradiated mice may increase relative to unirradiated controls if time points beyond 8 weeks are assayed. In any event, microdosimetric effects should be incorporated into any risk model for tumors in which cell killing plays a prominent role.

The location of the chromosome 2 QTL in a region frequently deleted in radiogenic AMLs may be happenstance, but there are scenarios in which its chromosomal location would be crucial to its function. One possibility is that the polymorphism increases the frequency of AML-associated chromosome 2 deletions in irradiated hematopoietic cells by controlling the spatial confirmation of the chromosome such that the proximal and distal deletion breakpoints are in close proximity to one another (46). This type of proximity mechanism has been evoked to explain recurrent chromosomal rearrangements seen in radiation-induced papillary thyroid carcinoma and some spontaneous cancers (53, 54). In this scenario, the QTL could be a structural polymorphism (e.g., segmental duplication or interstitial telomeric sequence), which would affect chromosomal conformation, yielding a different conformation in susceptible mouse strains than resistant strains. Structural polymorphisms are easily missed in the assembly of the strain-specific genomic sequences used for mapping studies, so we would be unaware of its existence. A second possibility is that the polymorphism is in a gene needed for myeloid progenitor cell survival. Mouse strains resistant to myeloid leukemia would have a hypomorphic allele of this gene. If one copy is lost (i.e., through radiation-induced deletion), then the remaining copy would be insufficient for cell survival. Thus, in mouse strains resistant to radiogenic AML, a chromosome 2 deletion, which is the first step in radiation leukemogenesis, is a lethal event and leukemogenesis is thereby halted. Susceptible strains would have a fully functional allele of the gene, so that if one copy is deleted, the remaining copy maintains cell viability, allowing further leukemogenic events to occur (46). A caveat to both the chromosome conformation and haploinsufficiency scenarios is that the chromosome 2 deletions mapped in radiogenic AMLs from the F1 progeny of AML-susceptible CBA/H mice and AML-resistant C57BL/6 mice do not occur preferentially in the CBA/H origin chromosome (55). However, in that study, only 10 tumors were informative. In addition, susceptibility to radiogenic AML is multigenic, so it is possible that the difference in susceptibility between the CBA/H and C57BL/6 strains is not due to the chromosome 2 QTL.

HZE ions seem particularly effective in inducing Harderian gland tumors at the doses used in this study. This result was expected on the basis of extensive published radiation quality data on these tumors (8, 38). The mechanism responsible for higher tumorigenic efficacy of HZE ions relative to -rays is unknown; however, we have identified a QTL associated with Harderian gland adenocarcinoma following HZE ion exposures that does not appear to lend susceptibility to the same tumor following -ray exposures (Fig. 4C). Furthermore, HZE ioninduced Harderian gland adenomas and adenocarcinomas cluster away from spontaneous and -rayinduced Harderian gland tumors (Fig. 5), indicating non-overlap of some of the susceptibility loci. There are data that suggest that HZE ion irradiation has an effect on tumor promotion that -ray irradiation lacks. The observation is that pituitary isografts, which result in elevated levels of pituitary hormones, enhance the induction of Harderian gland tumors and decrease their latency in mice irradiated with -rays or fission neutrons but do not increase tumor prevalence in mice irradiated with 56Fe ions (600 MeV/n) (12). This would explain the high relative biological effectiveness (RBE) for 56Fe ions. It would also render QTLs that act in the promotion of -ray and spontaneous tumors irrelevant to HZE ioninduced tumors.

The use of unsupervised clustering on genome-wide association results is a novel approach to search for shared tumorigenic mechanisms between radiogenic and spontaneous tumors or between tumors induced by different radiation qualities. Potentially, the results could be used to inform risk modeling. For example, using the 99% confidence interval as a cutoff, thyroid adenomas, pituitary tumors, osteosarcomas, B cell lymphoblastic leukemia, mammary tumors, and hepatocellular carcinomas cluster by histotypes regardless of whether they arose in HZE ionirradiated or -rayirradiated mice. Of these, the incidences of thyroid tumors, pituitary tumors, and osteosarcomas are significantly increased following exposures to either HZE ions or -rays. Taking pituitary adenoma as an example, these findings suggest that it would be reasonable to extrapolate the risk of HZE ioninduced pituitary adenoma as a multiple of -rayinduced pituitary adenoma risk (i.e., using a relative risk model). Because there were too few spontaneous pituitary adenomas to position them on the dendrogram, we cannot determine whether the risk of HZE ioninduced pituitary adenoma could reasonably be modeled on the basis of the incidence of the spontaneous tumor. Another pattern of association is observed for Harderian gland adenoma and follicular B cell lymphoma in which, at the 99% confidence interval, spontaneous tumors cluster with -rayinduced tumors but not with HZE ioninduced tumors. There are a number of ways that this could occur. Three possibilities are as follows: (i) HZE ions act through a tumorigenic mechanism different from that of spontaneous and -rayinduced tumors. (2) HZE ions bypass the need for one or more of the genetically controlled steps required for spontaneous and -rayinduced tumors, and (iii) there are multiple pathways to tumor formation, and HZE ion irradiation forces tumorigenesis through only one (or a subset) of them. Harderian gland tumors may fall into the second possibility. As described earlier, observations on mice receiving pituitary isografts before irradiation suggest that HZE ions may have Harderian gland tumor promotion effects that -rays lack. If so, the QTL controlling those effects would be inconsequential in the tumorigenesis of HZE ioninduced Harderian gland tumors, and those tumors would cluster away from their spontaneous and -rayinduced counterparts. Whether a relative risk model, an absolute risk model, or a combination of the two would be most appropriate in Harderian gland tumor risk calculations would depend on which of the above possibilities is most accurate.

NASA seeks to limit the risk of exposure-induced death (REID) from radiogenic cancer to below 3% (56). For multiple missions aboard the International Space Station (flown in solar minimum conditions), the model projects that males will exceed permissible exposure limits at 24 months and females, at 18 months; women are considered at greater risk for radiogenic cancers than men because of longer life spans and increased susceptibility to specific cancer types, including lung, ovarian, and breast carcinomas. Because the 3% REID is derived from the upper 95% confidence interval for the risk estimate (57), decreasing the uncertainty for space radiationinduced cancers can significantly increase the flight time allowed for astronauts. The 95% confidence interval surrounding the risk estimates not only primarily reflects uncertainties in our understanding of HZE ions but also includes uncertainties surrounding dose-rate effects, transfer of risk between human populations, space dosimetry, and errors in the existing human epidemiology data. Concerning sex predilections, our results also demonstrate a sex difference in carcinogenesis risk, where female mice are at greater risk for radiogenic cancers than males, following either HZE ion or -ray exposures. These results are consistent with the current NASA model to calculate cancer risk from space radiation exposures (5).

Whether genotypic assays of radiosensitivity can improve the precision of risk assessment in humans will depend on a number of factors. One is the extent to which heritable sequence variants determine cancer risk from HZE ion exposures. HZE ion radiation exposures result in more complex molecular lesions that are less amenable to repair (58). Thus, it could be argued that sequence variants that result in subtle differences in DNA repair and damage response pathways would have a lesser impact on HZE ion radiation carcinogenesis. However, this work demonstrates that genetic susceptibility does indeed have a significant role in tumorigenesis following HZE ion exposures. Personalized approaches to cancer risk assessments may eventually allow for greater reductions in uncertainties when generating space radiation cancer risk estimates (28).

There are limitations to a mouse carcinogenesis study comparing acute -ray and HZE ion exposures. First, for cost efficiency and logistics reasons, a single dose was used for each radiation quality: 3.0 Gy for -ray exposures and 0.4 Gy for HZE ion exposures. Preliminary studies have demonstrated that these doses produce the maximum tumor incidence in inbred strains (24). Because tumor susceptibility and association mapping were the primary goals of this study, doses were chosen with the goal of generating the greatest tumor incidences and, therefore, the greatest power to detect significant QTL. However, caution must be taken when comparing the two single-dose groups, as it is impossible to untangle dose responses in such a study. An additional benefit of the selected doses is that 0.4 Gy of HZE ions represents a realistic dose, received over 20 to 30 months, for a flight crew traveling to Mars. Second, the applicability of these findings to human populations is limited, as rodents serve only as models of carcinogenesis.

The results presented here indicate that host genetic factors dictate risk for tumor development following radiation exposures, regardless of radiation quality. Therefore, at a population level, risks can be extrapolated from terrestrial exposures to the space radiation environment and at an individual level, and humans harboring susceptibility alleles for radiation-induced tumors developed on Earth are also likely at increased risk in space.

Male and female HS/Npt mice (n = 1850) were generated from breeding pairs obtained from Oregon Health and Sciences University (Portland, OR). The mice were group-housed (five mice of the same sex per cage) in a climate-controlled facility at 70F (21.1C) with free access to food (Teklad global rodent diet 2918) and sterile water and a 12-hour light cycle. Mice were shipped to Brookhaven National Laboratories (Upton, NY) where they were exposed to accelerator-produced HZE ions at the NASA Space Radiation Laboratory at 7 to 12 weeks of age. HS/Npt stock mice of both sexes were exposed to 0.4 Gy of 28Si ions (240 MeV/n) (n = 308) or 56Fe ions (600 MeV/n) (n = 314), 3 Gy of 137Cs -rays (n = 615), or sham irradiated (n = 622). Following irradiation exposure or sham irradiations, mice were returned to Colorado State University (Fort Collins, CO) and monitored twice daily for the duration of the study. The mice were evaluated for cancer development until they reached 800 days of age or became moribund. All animal procedures were approved by the Colorado State University Institutional Animal Use and Care Committee.

This study uses a highly recombinant mouse population (HS/Npt stock) that is genetically diverse and designed for genome mapping (1921, 23). HS/Npt mice are a multiparent cross derived from eight inbred strains (A/J, AKR/J, BALBc/J, CBA/J, C3H/HeJ, C57BL/6J, DBA/2J, and LP/J); each individual contains a unique mosaic of founder haplotypes and a high degree of heterozygosity, and recombination events become increasingly dense with each generation. Our population of HS/Npt mice was obtained from generation 71 of circular outbreeding.

DNA was isolated from tail biopsies taken from each mouse at 9 to 10 weeks of age. DNA was extracted and purified (QIAGEN, catalog no. 69506) according to the manufacturers instructions. GeneSeek (Lincoln, NE) performed genotyping assays using the Mega Mouse Universal Genotyping Array (MegaMUGA) (59) for a total of 1878 mice (including 28 inbred mice representing the founder strains). The MegaMUGA is built on the Illumina Infinium platform and consists of 77,808 single-nucleotide polymorphic markers that are distributed throughout the genome with an average spacing of 33 kb.

The heterogeneous stock mice are descendants of eight inbred founder strains. For each mouse, allele calls from the MegaMUGA array were used to calculate descent probabilities using a hidden Markov model (HMM), in which the hidden states were the founder strains and the observed data were the genotypes. The HMM generates probabilistic estimates of the diplotype state(s) for each marker locus and produces a unique founder haplotype mosaic for each mouse (18).

For this lifetime carcinogenesis study, all disease states were interpreted within the context of a systematic pathologic evaluation directed by board-certified veterinary pathologists (E.F.E. and D.A.K.). Structured necropsy and tissue collection protocols were followed for each mouse and involved photodocumentation of all gross lesions, collection of frozen tumor material, and preservation of tumor material in RNAlater. All tissues were grossly evaluated for all mice. To evaluate brain tissues and Harderian glands, craniums were decalcified for 48 hours in Formical-4 (StatLab, McKinney, TX 75069, product 1214) and five coronal sections of the skull were reviewed for each mouse. All gross lesions were evaluated microscopically and fixed in 10% neutral-buffered formalin and paraffin-embedded, and 5-m sections were stained with hematoxylin and eosin (H&E) and evaluated by a veterinary pathologist. For mice with solid tumors, all lung fields were examined histologically to detect the presence or absence of micrometastases. Tumor nomenclature was based on consensus statements produced by the Society of Toxicologic Pathology for mouse tumors (www.toxpath.org/inhand.asp). Representative histologic images routinely stained with H&E are presented in figs. S2 (A to E) and S3 (A and B).

Tissue microarrays were constructed to immunophenotype and subcategorize lymphoid neoplasms, which were the most commonly diagnosed tumors in irradiated and unirradiated HS/Npt mice. Identification of tissue sampling regions was performed by a veterinary pathologist. For each case, duplicate cores were taken from multiple anatomic locations (lymph nodes, spleen, thymus, etc.). Thirteen tissue microarrays were created, each of which contained six cores of control tissue at one corner of the array (haired skin, spleen, thymus, or liver); these control tissues were present in a unique combination and allowed for (i) orientation of the resulting sections, (ii) verification that the slide matched the block, and (iii) positive controls for immunohistochemistry. Figure S3D illustrates one tissue microarray as well as the resulting immunohistochemistry results for one thymic lymphoma (fig. S3E) and a core containing normal spleen (fig. S3F). Immunohistochemistry for T cell identification was performed using a rabbit monoclonal, anti-CD3 (SP7) antibody obtained from Abcam (ab16669; 1:300). Immunohistochemistry for B cell identification was performed using two rabbit monoclonal antibodies: an anti-CD45 antibody (ab10558; 1:1000) and an anti-PAX5 antibody (ab140341; 1:50). All immunohistochemistry was performed on a Leica BOND-MAX autostainer with the Leica BOND Polymer Refine Red Detection system (Leica DS9390, Newcastle Upon Tyne, UK). In addition to defining the immunophenotype, lymphomas were characterized according to the Mouse Model of Human Cancer Consortiums Bethesda protocols (60). For these protocols, anatomic location is important for the final diagnosis, and therefore, lymph node involvement was used from necropsy reports when necessary. Additional features included cell size, nuclear size, chromatic organization, and mitotic figure frequency, and the presence or absence of a leukemic phase was defined by bone marrow involvement within the sternum or femur. The most common lymphoma subtypes (fig. S4A) were evaluated for survival (fig. S4B), and pre-T LL typically presented with early-onset and large thymic masses.

Droplet digital polymerase chain reaction (ddPCR) was performed on cases of AML to assess deletion status via copy number variation for two genes: Spi1 and Asxl1. These genes are both located on chromosome 2 at base pair locations 91,082,390 to 91,115,756 for Spi1 and 153,345,845 to 153,404,007 for Asxl1. To establish a reference for normal diploid copy number in each AML sample, the copy number of H2afx was also determined. H2afx is located on chromosome 9, and deletions in this region have not been reported in murine AML. Bio-Rad PrimePCR probes were used for all assays as follows: Asxl1 ddPCR probe (dMmuCPE5100268), Spi1 ddPCR probe (dMmuCPE5094900), and H2afx ddPCR probe (dMmuCPE5104287). Ratios were created between the test gene and the reference gene (Spi1:H2afx and Asxl1:H2afx) to determine copy number with the assumption that the reference gene would not be deleted or amplified. Ideally, ratios of 1:1 represent equal copy numbers for both the test gene and the reference gene, and ratios of 1:2 represent a deletion in one copy of the test gene. However, since the tumor samples contained neoplastic cells as well as stromal cells and other cells, the ideal 1:2 ratio was not commonly observed. This is because stromal cells, which occur at unknown proportions in each tumor and which should not have chromosomal deletions, artificially increase ratios for tumor samples in which a deletion is indeed present. To account for stromal cell contamination, a cutoff ratio of 3:4 was established. Tumor samples with ratios below 3:4 were considered to have a deletion in one copy of the test gene.

For cases in which a solid tumor was identified, a standard section containing all lung lobes was processed and evaluated histologically. In cases where pulmonary metastases were observed, whole-slide scanning was performed at 200 magnification using an Olympus VS120-S5 and the OlyVIA software suite (www.olympusamerica.com/) to generate images for quantification of metastatic density (fig. S5). An analysis software, ImageJ (https://imagej.nih.gov/ij/), was used to quantify the total area of normal lung and the total area of metastatic foci (fig. S5). Metastatic density is reported as a percentage of the total metastasis area divided by the total lung area.

Association mapping was performed using a mixed-effects regression model with sex and cohort as fixed effects and a random-effects term to adjust for relatedness between mice by computing a matrix of expected allele sharing of founder haplotypes for each pair of mice (22). Three statistical models were fit to account for the wide range of trait distributions in this study. A generalized linear regression model was fit for binomial distributions, such as neoplasia. Cox regression analysis was incorporated to model time-to-event distributions to evaluate genetic contributions to tumor latency. Following genome-wide association analyses, resample model averaging methods were used to identify QTL that are consistently reproduced within subsamples of the mapping population.

Thresholds were determined using a permutation procedure in which the genotypes were fixed and the phenotype values were rearranged randomly within each sex. The distribution of the maximum negative log(P value) of association under the null hypothesis that no associations exist (null model) was determined for each genome scan with permuted data. One thousand permutations were performed for each phenotype in each radiation exposure group, simulating effects arising from covariates, the linkage disequilibrium structure of the genome, and effects due to phenotype distribution. A threshold was defined as an estimate of the genome-wide significance for which a type I statistical error will occur at a given frequency (29). Confidence intervals for each QTL were determined by nonparametric resample model averaging procedures using bootstrap aggregation with replacement. In this procedure, the mapping population is sampled to create a new dataset in which some individuals may be omitted and some may appear multiple times (30), and the locus with peak significance is recorded. Resampling is repeated 200 times for each phenotype to determine a 95% confidence interval for a given QTL. Effect sizes were calculated using the Tjur method for association mapping with logistic regression and pseudo-R2 for mapping with Cox proportional hazard regression. Statistical significance for each model was assessed using a permutation strategy to randomize genotypes via resampling without replacement and maintaining covariates. Permutation analysis was performed (1000 tests) for each trait and exposure group to generate estimations of genome-wide significance thresholds. As genome scans with hundreds of thousands of imputed SNPs are computationally intensive, parallel computing was essential and accomplished using spot instances of resizable Elastic Compute Cloud hosting resources.

Comparisons were made between whole-genome scans using Pearson correlations as a similarity measure with clustering based on average linkage. Significance of clustering results was estimated with 10,000 random permutations of the dataset (log10 values permuted with genetic markers) to determine a distribution of dendrogram heights under the null hypothesis that no associations exist. Each permutated dataset simulates a null distribution of the maximally significant clustering based on a randomly assorted set of P values for each genomic locus.

Bootstrap aggregation is a resample model averaging procedure that has been demonstrated to produce highly accurate estimates of QTL in structured populations (32). The procedure is relatively simple: for a genome-wide association study (GWAS) of n individuals, a sampling of n draws is obtained, with replacement, from the observed individuals to form a new dataset in which some individuals are omitted and some appear multiple times. For each new dataset created this way, an estimate of the QTL location is calculated. This process is repeated many times and is the basis for determining a confidence interval for a given result. The use of bootstrap procedures is commonly used this way to estimate QTL support intervals in experimental crosses; however, this statistical method can potentially be applied to other areas of QTL research, including comparative QTL mapping.

When an identical QTL is observed for two distinct traits, one explanation is that a single gene is involved for two distinct biologic processes, also known as pleiotropy. This was sometimes assumed in early mouse QTL studies that resulted in coincident loci for distinct traits. Another possibility, however, is that two distinct genetic variants are present in close proximity, each independently contributing to the two phenotypes. Because the two hypothetical genetic variants happen to be in close proximity, they are difficult to distinguish in low-resolution mapping studies. Using resample model averaging in highly recombinant mice is proposed to best differentiate precise locations of the QTL; if the same markers were repeatedly identified, then the case for pleiotropy was strengthened. For comparative QTL mapping in tumorigenesis studies, nonparametric resample model averaging could similarly be leveraged to identify whether the same QTL renders an individual susceptible to distinct environmental carcinogens. One significant advantage to using bootstrap procedures to detect potential coincident loci is that comparisons can be made between groups based on the identification of a highly significant QTL identified in only one exposure group (e.g., at a false-positive rate of 1 per 20 scans). This QTL may be present in the alternative exposure group, but at lower confidence (e.g., at a false-positive rate of 1 per 10 scans), and therefore discarded in a typical GWAS. A diagrammatic representation of the comparative QTL bootstrap procedure is presented in fig. S6. Because the resultant genetic positions derived from bootstrapping are composed of the most significant locus for each resampling regardless of the significance level for the mapping procedure, comparisons can be drawn between QTL that might have been discarded on the basis of the stringent statistical demands of an assay involving hundreds of thousands of independent tests. Using this procedure on thyroid tumors demonstrates that the same loci are consistently identified whether exposed to particle or photon irradiation (Fig. 2E). Using the comparative QTL procedure described, it can be determined whether an individuals cancer risk from one carcinogen will be predictive of that individuals cancer risk to another carcinogen. The application of this procedure is well illustrated by the space radiation problem, where much is known about -ray exposures and little is known about space radiation exposures.

In addition to looking for similarities between individual selected QTL for HZE ion and -rayexposed populations, we also sought a more holistic method in which entire genome scans could be compared between groups in an unsupervised process. By using entire genome scans, we submit for comparison not only highly significant regions but also the numerous loci detected with lower confidence. To determine similarity of genetic association profiles for all phenotypes and to detect possible coincident QTL, clustering procedures were used to compare genome-wide association scans between different radiation exposure groups. To demonstrate and validate the methodology of QTL clustering, genome-wide scans for coat colors in each treatment group are evaluated (Fig. 5B). As expected, genome-wide scans for coat color are unaffected by radiation exposures, and therefore, clustering is based entirely on coat phenotype rather than radiation exposure group. Using the same procedure for neoplasia indicates that tumor types often clustered together as well, regardless of radiation exposure (Fig. 5A). Genome scans for thyroid tumors and mammary adenocarcinomas in radiation-exposed groups and all hepatocellular carcinoma genome scans cluster together. This finding supports the hypothesis that host genetic factors are more important in determining neoplasm incidence than radiation exposure type. Unlike other statistic procedures, such as regression models, clustering lacks a response variable and is not routinely performed as a formal hypothesis test. Therefore, determining the significance of a clustering result can be problematic, as no consensus method exists for cluster validation. Permutation analysis provides the distribution of clustering results that will randomly occur from a given dataset; this can then be used as a baseline from which to determine a significance level on a given dendrogram tree [green line in Fig. 5 (A to C)]. While the overall validity of a given cluster can be accomplished by cluster permutation analysis, no method is identified to estimate the number of clusters that should be present in a dataset. Furthermore, methods to determine the significance of specific subset of objects clustering together do not exist; in such cases, the permutation threshold is likely overly stringent.

Go here to read the rest:
Genomic mapping in outbred mice reveals overlap in genetic susceptibility for HZE ion and -rayinduced tumors - Science Advances

As the global death toll from the novel coronavirus mounts, evidence is growing that more men than women are becoming seriously ill and dying from the virus. In New York state as of April 9, for example, more than 60 percent of over 6,200 total deaths have been men.

From the early days of the first coronavirus outbreak in China, men were turning up severely ill at a higher rate than women. And this pattern seems to be largely repeating itself if in slightly different numbers in country after country.

Researchers are still not entirely sure why this is. But there are already some intriguing clues.

Could it be higher rates of smoking among men? A higher likelihood of delaying medical care? Or do the answers lie among the genes and sex hormones in our bodies that are setting men on a riskier course if they encounter the virus?

As Marcia Stefanick, a professor of medicine at Stanford University School of Medicine, told the Wall Street Journal, There are profound sex differences in immune systems, and this pandemic is revealing them. But, she noted, What is biology versus what are our social norms and gender behaviors confounds our ability to understand whats going on.

Finding answers could help develop more effective treatment protocols and prevention measures, as well as lead to a more successful vaccine.

One key piece of context for these questions is that there are, in general, a variety of key biological differences in the way men and women fight off infections. Women, for example, tend to mount a stronger immune response. Researchers think this is in part because most women have two X chromosomes, and the X chromosome happens to contain most of the genes related to the immune system (and those with two X chromosomes instead of one also have a wider diversity of immune responses). This extra immune functioning, however, also seems to put women more at risk for autoimmune diseases, such as rheumatoid arthritis and Crohns disease.

Hormones might also help provide women with a more effective defense. Some important immune cells have estrogen receptors, and an estrogen supplement has been shown to increase general immune responses in mice.

A 2017 study in the Journal of Immunology specifically looked into sex differences from the coronavirus that causes SARS (which seems to have killed more men than women during an outbreak in 2003). In that study, researchers found that male mice were more susceptible to the virus. But when they blocked estrogen from working normally in the female mice, the females fell ill at higher rates.

Women might also be more likely to launch an earlier attack on infections in general, saving the body from needing to use all of its virus-fighting might later an event that can skyrocket inflammation and often do more damage to key organs.

These sex patterns are not universal among infections. And data from other viruses, including influenza, sometimes even skews in the other direction, with more women dying than men. Theres still a lot to learn about the novel coronavirus, and so far there arent any studies on it looking specifically at these biological factors. We dont yet know how these biological differences play out for Covid-19, if they do at all. But theyre definitely possibilities.

There are also clues that differences in behavior could be putting men at higher risk for severe Covid-19. It can be a difficult (and time-consuming) endeavor for epidemiologists to untangle behavioral risk factors from one another, so its important to remember that at this point, what we have are correlations that suggest possible risks, not hard proof.

One factor could be smoking rates. A review of existing research as of March 17 concluded that smoking is most likely associated with the negative progression and adverse outcomes of Covid-19. There are a couple of reasons this could be the case, the World Health Organization notes. One is that smokers are more likely to have lung disease, which is an established risk factor for severe infection. The other is that when smoking, a person is more likely to touch their mouth or face, possibly allowing the virus an easy path in.

And smoking is often more common among men than women. According to a 2017 analysis in the Journal of Epidemiology & Community Health, 54 percent of Chinese adult men smoked tobacco, compared with just 2.6 percent of Chinese women. The World Bank reports that, as of 2016, about 41 percent of South Korean men smoked versus about 6 percent of women. (Spain also shows the same general trend, as does the US, but the sex difference isnt as large as it is for China and South Korea.)

Because the research on all of this is so new, it will still probably be some time before we have a clear understanding of what role smoking might play.

Other broad social and cultural variations among genders (that, to be sure, are not universal) might be further exacerbating this trend. For example, in the US, various studies show that men wash their hands less often and are less likely to seek care earlier in an illness. A March 24 poll from Reuters revealed that a smaller percentage of men than women were taking warnings about the coronavirus seriously including changing their behavior.

In this pandemic, the information being reported around the world varies widely. And due to continued lack of testing and increasing concern about deaths being underreported, we still do not have a complete picture of how sex is playing out as a risk factor for the disease and how that might be different in different countries. (Some governments, including the US, are not even reporting cases by sex.) Despite the fuzzy details, however, the pattern is holding steady.

Analysis of data from about 2,000 patients during Chinas main outbreak, from December through February, showed that about 60 percent of patients were men. And Chinas Center for Disease Control reported a fatality rate of 2.8 percent for men versus 1.7 percent for women.

In South Korea, men were actually far less likely to be confirmed to have Covid-19, according to a March 31 paper in Clinical Infectious Diseases. There, just 38 percent of patients were male. But, according to that analysis, men were about twice as likely to die from the disease (1.19 percent for men versus 0.52 percent for women).

In Spain, men and women comprise about an equal number of Covid-19 cases, as the countrys Health Ministry reported on April 3. But men were more than twice as likely to wind up in the ICU and more likely to die (making up almost two-thirds of deaths).

An April 6 study of the hard-hit region of Lombardy, Italy, found that 82 percent of patients admitted to the ICU were men. And in Italy overall, about 70 percent of people dying from coronavirus have been male.

The US CDC isnt releasing coronavirus case breakdowns by sex at this time (it also doesnt prominently feature this data for other infectious diseases, like influenza). This is an additional blow to those who are trying to understand this rapidly spreading illness because the US now has by far the largest number of cases.

Some US states have released sex breakdowns, however. A Washington Post report found that of 13 states that have substantial outbreaks and are reporting these details, men make up a larger number of deaths. As an emergency department nurse told the Post, In general, Ive seen more male patients. And when they do come in, they are at a sicker state. (Recent US data also shows concerning patterns of racial disparities.)

Learning more about how the virus impacts men and women could help determine the most effective treatment for individual patients. For example, it might point to different or earlier interventions in men, or more targeted public health messaging for people who might be more likely to delay seeking care.

Better understanding the nuances of mens and womens immune response to the virus could also be crucial to developing a good vaccine. There are well-documented differences in vaccine effectiveness among men and women, with women tending to be better protected after vaccination. So it will be especially important to ensure that sex is taken into account when designing and analyzing vaccine trials in both animal studies and human ones.

Although men seem to be dying at slightly higher rates than women, everyone is at risk even the young.

There are also some factors that might put some women more at risk. For example, in the US, 76 percent of health care workers are women, according to the US Census Bureau. That means they are at the forefront of this pandemic, coming into contact with potentially infected people on a daily basis.

Additionally, digging deeper into the data reveals other emerging trends in subpopulations. For example, according to an April 2 report from the Italian government, in those 90 and older, women were more likely to die from Covid-19 than men. And, although the overall numbers are small, it seems as though women with certain risk factors (including heart failure, hypertension, and dementia) were more likely to die from Covid-19 than the men who had those conditions.

What has become clear from all this data is that we still have a lot to learn about why some cases of Covid-19 end in respiratory failure or death, or severe illness, and some dont regardless of a persons sex. And we all still have the responsibility to reduce our own odds of getting the virus, and of it spreading to others. It remains crucial for everyone to do their part (washing hands, maintaining social distancing, etc.) to keep the virus from spreading.

Support Voxs explanatory journalism

Every day at Vox, we aim to answer your most important questions and provide you, and our audience around the world, with information that has the power to save lives. Our mission has never been more vital than it is in this moment: to empower you through understanding. Voxs work is reaching more people than ever, but our distinctive brand of explanatory journalism takes resources particularly during a pandemic and an economic downturn. Your financial contribution will not constitute a donation, but it will enable our staff to continue to offer free articles, videos, and podcasts at the quality and volume that this moment requires. Please consider making a contribution to Vox today.

Read more:
Coronavirus deaths: Why is the virus killing more men than women? - Vox.com

Scientists have created a mathematical model that can help explain why so many pregnancies and in vitro fertilization attempts fail.

The Rutgers-led study, which may help to improve fertility, is published in the journalProceedings of the National Academy of Sciences.

Mistakes in female meiosis, the cell division process that creates egg cells, result in eggs with an abnormal number of chromosomes (too many or too few). This phenomenon is strongly associated with the repeated loss of pregnancies and the failure of in vitro fertilization (IVF) procedures, as well as developmental disorders such as Down syndrome.

"Our study demonstrates that in the future, mathematical models can be powerful tools for predicting the outcomes of in vitro fertilization for infertility patients and/or provide the basis for considering alternative family planning options, such as adoption," said senior authorJinchuan Xing, an associate professor in theDepartment of Geneticsin theSchool of Arts and Sciencesand at theHuman Genetics Institute of New JerseyatRutgers University-New Brunswick.

"Modeling efforts such as ours can provide guidelines on, for instance, how many eggs must be collected during a single IVF cycle to ensure there will be at least one chromosomally normal conception," said co-authorKaren Schindler, an associate professor in the Department of Genetics and at the Human Genetics Institute of New Jersey.

Pregnancy loss is extremely common, with nearly 20 percent of clinically recognized pregnancies resulting in miscarriage, and many more unrecognized pregnancies end earlier, the study notes.

A leading cause of early miscarriage is called aneuploidy, when eggs have the wrong number of chromosomes, and it's also the main cause of IVF failure. The vast majority of eggs with chromosome problems are linked to errors in female cell division that increase as women age. Understanding how that happens is crucial because the average age at conception is rising in developed countries.

"Such basic knowledge is required to pave the way for future diagnostic and therapeutic innovations to improve human fertility," the study says.

The scientists developed a mathematical model describing all possible abnormal chromosome count issues in eggs due to cell division errors. Using data on 11,157 early stage human embryos (blastocysts), the model revealed previously unknown patterns of errors.

The model can be used to identify IVF patients who produce an extreme number of abnormal embryos. It's also a powerful tool for understanding why abnormal numbers of chromosomes arise when cells divide and for predicting the outcomes of IVF reproduction. The model potentially could provide guidance for clinicians on the expected number of IVF cycles needed to get a normal conception for each patient. The modeling framework can also be expanded and adapted to address other processes, such as predicting errors in sperm.

Original post:
Why do so many pregnancies and in vitro fertilization attempts fail? - Jill Lopez

THE number of people dying from coronavirus across the world is continuing to rise every day - with just under 130,000 deaths in 210 countries.

And in the UK alone,the total of deathspushed past the 12,000 barrier yesterday - with the grim total expected to be 15 per cent higher than reported due to people dying outside of hospital.

4

However, scientists have now revealed that there are some key factorsthat people who pass away from Covid-19have in common.

A team of researchers from eight institutions in China and the United States including the Chinese Peoples Liberation Army General Hospital in Beijing, and the University of California Davis recently looked at the data of 85 patients who died of multiple organ failure after having received care for severe Covid-19.

All individuals whose data the study used received care at either the Hanan Hospital or the Wuhan Union Hospital between January 9 and February 15, 2020.

And the researchers who conducted the study,that appears in the American Journal of Respiratory and Critical Care Medicine,uncovered a series of factors that the majority of these patients shared.

Here, we outline these key factors...

The killer new coronavirus appears to be posing a particular threat to men.

The researchers found that 72.9 per cent of those who died from the new coronavirus - Sars-Cov-2 - were male.

Experts believe there are a few reasons for more men dying than women, including some biological and other lifestyle choices.

Hand washing is one of the best ways to prevent infection - but multiple studies show that women are much more likely to wash their hands and use soap than men.

4

Akiko Iwasaki, a professor of immunology at Yale University, told the New York Times that men may have a "false sense of security" about coronavirus.

Meanwhile, Chinese men are much more likely to smoke than women, which can lead to a weaker immune system.

China has the largest population of smokers in the world - accounting for nearly a third of the world's smokers - but just two per cent of them are women.

Meanwhile, in the UK 16.5 per cent of men - around 3.9 million - and 13 per cent of women - around 3.2 million - reported being current smokers.

Chinese men also have higher rates of high blood pressure, type 2 diabetes and chronic obstructive pulmonary disease than women.

All of these conditions can increase the risk of complications following infection of coronavirus.

Meanwhile, some experts believe that oestrogen, the female sex hormone, may also play a role in protecting women.

The new strain of deadly coronavirus doesn't discriminate and can infect anyone of any age.

However, it's older adults - aged 60 and upwards - who are more likely to get seriously ill from it - with the scientists discoveringthat those who died from Covid-19 had amedian age of 65.8 years.

Medics say it's because our immune systems weaken with age, meaning an older person's body is less able to fight Covid-19.

Dr Sarah Jarvis, GP and Clinical Director of Patient Access, told The Sun: "We know that as you get older, your immune system becomes less efficient thats why older people are at higher risk of serious complications of coronavirus infection.

4

CORONAVIRUS CRISIS - STAY IN THE KNOW

Don't miss the latest news and figures - and essential advice for you and your family.

To receive The Sun's Coronavirus newsletter in your inbox every tea time, sign up here.To follow us on Facebook, simply 'Like' our Coronavirus page.Get Britain's best-selling newspaper delivered to your smartphone or tablet each day - find out more.

"If your immune system isnt strong, its more likely that the virus can multiply deep inside your lung, causing inflammation and scarring.

"Your immune system will try and fight it off, and will often destroy healthy lung tissue in the process.

"This makes you more prone to get secondary infections like pneumococcal pneumonia."

In fact, evidence from China, where the deadly virus originated, shows one in seven of those over 80 known to have contracted coronavirus have died.

Those who died from Covid-19 in the study mostly had underlying chronic conditions, such as heart problems or diabetes.

The greatest number of deaths in our cohort were in males over 50 with noncommunicable chronic diseases, the researchers said.

We hope that this study conveys the seriousness of Covid-19 and emphasises the risk groups of males over 50 with chronic comorbid conditions, including hypertension (high blood pressure), coronary heart disease, and diabetes," they added.

4

In fact, another study recently revealed that your risk of dying from coronavirus is 80 per cent higher if you have just one underlying health issue.

For those with two pre-existing conditions or more, the chances of being admitted to intensive care are even higher, experts warned.

Some of the chronic conditions said to heighten the risk among patients are asthma, cancer, cystic fibrosis, chronic obstructive pulmonary disease (COPD), diabetes and HIV and AIDS.

People who are obese or seriously overweightfall into the high risk category for coronavirus.

This is because being overweight or obese can weaken the bodys immune system which could make people more likely to catch coronavirus and makes it harder for the body to fight the bug.

The NHS has said people with a BMI of 40 or above have a greater risk of developing complications if they catch the virus.

More than 60 per cent of patients in intensive care with the virus were overweight or classed as morbidly obese, arecent NHS survey found.

Those who were overweight, with a BMI of 25 to 40, made up 64 per cent of the 194 coronavirus patients who were in ICU at the time, while seven per cent were classed as obese with a BMI over 40.

BMI is a measure of whether youre a healthy weight for your height, you can calculate yours on the NHS website.

In the past, studies have shown overweight and obese people are at greater risk of serious complications or death from infections, like flu.

The extra weight on obese people's diaphragms puts pressure on lungs and makes it harder to breathe, starving them of oxygen.

Clogged up arteries can also make it harder for blood carrying immune cells to circulate and travel to fight infection around the body.

In terms of other potentially relevant information, the research team found that 81.2 per cent of those who died from Covid-19 in the study had very low eosinophil counts on admission to the hospital."

This is a type of white blood cells, which are specialised immune cells that help fight infection.

The medics suggested that having abnormally low levels of eosinophils a condition known as eosinophilopenia may correlate with a greater risk of severe outcomes in people who have contracted Covid-19.

While the scientists hope that their current findings may help other doctors better understand and prepare for fighting coronavirus, the researchers nevertheless urge other experts to keep on recording all possible information about people receiving care for this new illness.

Our study, which investigated patients from Wuhan, China, who died in the early phases of this pandemic, identified certain characteristics, the researchers said.

Give now to The Sun's NHS appeal

BRITAINs four million NHS staff are on the frontline in the battle against coronavirus.

But while they are helping save lives, who is there to help them?

The Sun has launched an appeal to raise 1MILLION for NHS workers.

The Who Cares Wins Appeal aims to get vital support to staff in their hour of need.

We have teamed up with NHS Charities Together in their urgent Covid-19 Appeal to ensure the money gets to exactly who needs it.

The Sun is donating 50,000 and we would like YOU to help us raise a million pounds, to help THEM.

No matter how little you can spare, please donate today here

http://www.thesun.co.uk/whocareswinsappeal

Live Blog

VIRUS CRISISChief medic says UK is seeing 'flattening curve' with lockdown update tomorrow

Breaking

DEADLY COMPETITIONVirus 'WAS made in Wuhan lab as China tried to prove dominance over US'

THAT'S RICHAll megarich residents on $40m luxury Florida island can get virus tests

CRIME RATE DOWNCrime falls by 28% since lockdown - but anti-social behaviour soars by 59%

UK SHUNS TRUMP SNUBUK has 'no plans' to stop WHO funding after Trump freezes $500m payment

SPACE FORE ALLGolf clubs pressured to open to public so people can exercise in lockdown

DOUBLE TRAGEDYFitness instructor & mum both killed by Covid-19 within days of each other

CLASS ACTIONTeachers demand PPE as schools could reopen next month to kick-start economy

IN DEMANDLiam Gallagher and Lewis Capaldi crash NHS Fest raffle website

FULL STEAM AHEADMinisters shrug off economy fears to give final go-ahead to 106bn HS2

"Yet as the disease has spread to other regions, the observations from these areas may be the same, or different.

They added: Genetics may play a role in the response to the infection, and the course of the pandemic may change as the virus mutates, as well.

"Since this is a new pandemic that is constantly shifting, we think the medical community needs to keep an open mind as more and more studies are conducted.

Go here to see the original:
The 5 factors that increase your risk of dying from coronavirus - The Sun

Following is a transcript of the video.

Narrator: Depending on the stallion, horse semen is one of the most expensive liquids on the planet.

Matson: So, we collected about 80 mils, and this is gonna be worth in excess of $100,000.

Narrator: That means that a gallon of this horse's semen is worth $4.7 million. And that's nowhere near the most expensive. Once it's collected, horse semen can be separated and sold in small tubes called straws.

Matson: One of these straws is worth about $1,200. We're putting about 150 million to 200 million sperm cells in each individual straw. Big Star's produced about 60 or 70 of them here.

Narrator: Super-fertile stallions like Big Star can ejaculate once a day. Theoretically, this means he could produce over $20 million worth of semen during an eight-month stud season. And if a stallion's semen is high quality, it can be frozen in straws for future use.

Matson: So, in this room is the heart of really Stallion AI Services. This room's built like actually a nuclear bunker in here. This is where all the semen is now kept. We've got hundreds and hundreds of thousands of straws in here. We've got over 1,200 different stallions. So, in here, stored at minus 196 degrees, is hundreds of millions of dollars' worth of semen ready to be used to inseminate mares.

Narrator: In the horse-breeding world, genetics is king. Wealthy investors are willing to pay high prices for proven winners' semen, hoping that the resulting foal provides a large return on investment.

Matson: Big Star is one of the most prolific show jumpers of all time. He's a double-gold-medal-winning stallion, which, there's very few of them out there. He's got the perfect genetics, really, to go on to show jumping. So you mix that with another genetic line on the female side and cross those two together. You can pay $1,200 for a single straw, you can have a foal, and maybe three or four years later, you can sell that foal for sometimes $100,000. In Big Star's case, he's hit those bells. He had the highest-price foal in the UK, and that sold for in excess of $100,000.

Narrator: Even though most stud farms offer guarantees on producing a live foal, commercial and competitive success is still a gamble, even with strong genetics. In fact, the bloodline of all stallion horses is closer than you might think. According to an international team of scientists who studied the Y chromosomes of 52 horses from 21 breeds, practically all modern horses descended from just a few original stallions, from carriage horses hauling tourists in the streets right through to champion racehorses like Galileo, the world's most expensive sire. Even more surprisingly, 95% of all thoroughbred racehorses, like him, can be traced back to just a handful of ancestors, who are all linked to one single superstud: the Darley Arabian, born in 1700. But the value of thoroughbred semen is a little harder to quantify, since breeding must occur naturally for racehorses.

Matson: In the sport-horse world, we're very lucky. We can use artificial insemination to breed our mares with, as opposed to the thoroughbred world, everything's got to be done naturally. They've got to literally cover the mare naturally. Their concern with their gene pool, if they would allow AI into the thoroughbred world, it would mean the gene pool would shrink because one horse could then cover thousands of mares.

Narrator: And anyone wishing to naturally cover their mare with Galileo needs serious financial backing. Even though his price is listed as private, it's widely reported that his stud fee sits at around $650,000, comfortably the world's highest. But because thoroughbred horses must be bred naturally, and therefore a collection of sperm cannot be purchased, equating the cost of Galileo's semen requires some extrapolation. Assuming that during the course of a natural covering, Galileo ejaculates the average of 50 mil of semen, and assuming that the semen is high-enough quality to impregnate a mare successfully, and assuming that a breeder paid $650,000 for that service, then we can deduce that a gallon of Galileo's semen could be worth a whopping $49 million, making it the most expensive liquid on earth. But is it worth it?

Matson: Like anything, there's a lot of work, there's a lot of luck in it. But you've got to make your luck, and you've gotta start off with the right genetics. The chances, obviously, you need to breed a lot to get that particular horse, but with the right genetics, you've got a much better chance.

Narrator: Galileo's position as the top sire is cemented by the achievements of his offspring. He has sired no less than 84 winners, including Frankel, who himself has now been put to stud, commanding the second-highest stud fee in the UK of around $220,000. In turn, he has sired a further 10 winners. Like father, like son.

Despite generally being safer for both stallion and mare, artificial insemination is criticized for its ethics around science and nature. But the analysis of thoroughbred-racehorse genetics has added to the controversy surrounding horse breeding. Roughly 10% experience orthopedic problems, and the majority suffer exercise-induced bleeding in the lungs. PETA investigators captured video from inside the breeding barns at Darley in Kentucky, one of the world's most expensive thoroughbred-breeding facilities, where stallions were goaded to cover more than 100 mares each in a breeding season. Some thoroughbreds were even sold for slaughter at a horse meat market.

With so much money to be made in racing, show jumping, dressage, and more, the price of horse semen will remain stable.

Read the original here:
Why thoroughbred horse semen is the world's most expensive liquid - Business Insider - Business Insider

Bird keepers at the Smithsonian Conservation Biology Institute (SCBI) in Front Royal, Virginia, are celebrating the arrival of a female white-naped crane chick that hatched April 2. She is the fourth chick for parents Brenda and Eddie and is the 46th to hatch at SCBI. Animal care staff at SCBI have had great success producing chicks from cranes that have behavioral or physical impediments that prevent them from breeding. The chicks parents are one of the only white-naped crane pairs living at the research facility capable of breeding naturally. Prior to hatching, scientists confirmed the chicks sex using DNA samples takenfrom inside of the egg. Keepers are closely monitoring the chicks development while leaving the experienced parents to bond with their chick without interference. They report Brenda and Eddie are providing excellent care to their chick. There are an estimated 5,000 white-naped cranes living in the wild, and the species is listed as vulnerable by the International Union for Conservation of Nature (IUCN).

As a public health precaution due to COVID-19, the Smithsonians National Zoo and Conservation Biology Institute is temporarily closed to the public.Animal keepers and veterinary staff remain working on site at the Zoo and SCBI to provide the usual highest quality care for the animals.The Zoos legacy of conservation work extends beyond the public Zoo in Washington, D.C., to SCBI headquarters in Front Royal, Virginia. Scientists at this 3,200-acre campus study and breed more than 20 species. The sprawling environment allows for unique studies that contribute to the survival of threatened, difficult-to-breed species with distinct needs, especially those requiring large areas, natural group sizes and minimal public disturbance. SCBI scientists tackle some of todays most complex conservation challenges by applying and sharing what they learn about animal behavior and reproduction, ecology, genetics, migration and conservation sustainability.

View post:
White-Naped Crane Hatches at the Smithsonian Conservation Biology Institute - Smithsonian's National Zoo and Conservation Biology Institute

Hair removal is one of the most physically intimate worker-client relationship that (legally) exists. And as the coronavirus spreads throughout the country, governors in many states ordered nonessential businesses including salons and waxing/threading centers to temporarily shut their doors. If youve ever had your brows threaded or upper lip waxed, you know why: its impossible to maintain 6 feet of social distance while depilating a client's chin (or anything else).

Unsurprisingly, the approximately $5.7 billion appearance enhancement industry, made up primarily of small business owners, is going to take a massive hit, as are the primarily female service providers in it. Some of us customers are trying to keep our local salons afloat by purchasing gift certificates and thats absolutely something you should do if its within your budget and you value your local small businesses.

But when it comes to the services these trusted professionals have been providing us, were on our own until the end of state-enforced social distancing. So maybe, just maybe, as our natural hair colors grow in and our split ends assert themselves, the quarantine can also serve as a moment for women to reset our relationship with our body hair.

In other words: Lets all get a lot hairier ... and stay that way.

Transgressive acts arent always comfortable at first, especially when a lot of us are staring at our own faces more than ever in Zoom meetings. But a random hair growing out of your chin won't ruin your life, nor will a mild shadow on your upper lip. Maybe your face wont look so quite as angular with grown-out brows the look my friend dubbed the coronabrow but who cares? You only have to look to actresses such as Gaby Hoffman and Lily Collins, or models such as Natalia Castellar and Cara Delevingne for proof that bushy brows are beautiful.

Carpe diem et carpe pilus! Reject the norms that have long served as tools of social control over womens lives and bodies!

Get the think newsletter.

Even though the Western beauty ideal for the female body is smooth and nearly hairless, the truth is that womens facial and body hair is natural and normal. The amount of hair a woman might have is determined by hormones and genetics, dermatologist Hal Weitzbuch told the blog Fatherly, though certain medical conditions, like polycystic ovarian syndrome and Cushings syndrome, can lead to an actual excess of facial hair on women.

But, really, any sort of facial hair is broadly perceived as unfeminine and an embarrassing problem to be solved, not just an excess caused by an underlying medical condition. And despite the broad prevalence of some minor facial hair in women, we devote a lot of time, money and mental space getting rid of the shadows on our lips, the perceived bushiness in our brows and the peach fuzz on our jaws.

Girls learn from the mass media, peers and even their own families that this sort of hair needs to be groomed upon arrival (which usually happens in puberty, whether its on their upper lips, chins, filling in their eyebrows or at the edges of their hairlines). I was no different: as a 10-year-old, I thought my eyebrows looked like thick, black caterpillars, so I cut them off with scissors, which turned out not to be the look I was going for.

And once we start dyeing, trimming, waxing, threading and otherwise depilating that hair, we spend more or less the rest of our adult lives doing so.

This beauty standard has been causing us grief for more than a century, if not longer. In her 2015 book Plucked: A History of Facial Hair, Rebecca M. Herzig describes how, in the early 20th century, physician after physician described the severe depression, self-imposed seclusion and nausea common to women afflicted with heavy hair growth particularly hair on the face.

It causes emotional distress in modern times, as well: A 2006 study of 88 women with suspected polycystic ovary syndrome who had unwanted facial hair found that 40 percent reported they felt uncomfortable in social situations, and 75 percent reported clinical levels of anxiety. (It also said they spent an average of 104 minutes per week dealing with the hair.)

Not being able to engage in professional body hair removal during the coronavirus outbreak will be a big change for a lot of women. Herzig notes that more than 99 percent of American women are regularly depilating, and 85 percent do so regularly; a 2017 YouGov poll found that 43 percent of women personally remove hair from their faces; and a British study in 2017 suggested that about a third of women who regularly wax do so exclusively at salons.

Undoubtedly, some of us are going to try waxing, threading, bleaching, depilating or tweezing at home; salon professionals discourage women from shaving the hair on their face because it leaves stubble.

Some of us, though, won't want to bother with the time commitment or the expense, what with the sudden need to homeschool kids and cook for ourselves while (hopefully) also holding down our regular jobs on our home wireless connections while stressing about the pandemic itself. If there were ever a time for women to reassess the money and effort we put into removing our facial hair, its now.

After all, there has not been such a widespread reason for all women to put this aspect of personal care on pause; the great hair removal debates have largely been seen as a matter of personal choice. But, as with other personal decisions made by women, the viability of that choice is influenced by the larger cultural moment.

Already prior to the pandemic, celebrities, ad campaigns and influencers had promoted the idea that keeping one's leg, armpit and even pubic hair natural is a normal and even trendy choice; in a way, facial hair is the last frontier. If all of us are recalibrating our priorities and most of us are cutting back on unnecessary expenses, given burgeoning unemployment and the crashing economy perhaps we can also reassess the stringent standards of feminine upkeep to which weve hewn.

Put another way: Is a little chin hair really what you want to be focusing on during a global health and economic crisis?

I realize that, with so many scary things happening in the world, people may hold tight to what they can control, and some personal care can be embraced as self-care. But this is a great opportunity to collectively recalibrate our expectations of feminine beauty, freeing both women and girls from centuries of discomfort, insecurity and external control.

So embrace your coronabrow: if nothing else, it could end up being summers hottest trend.

Read the rest here:
Coronavirus closures mean no lip waxing or brow threading. Maybe that'll be good for us. - NBC News

Now that lambing is essentially finished at Lyons, we are focused on setting up the grazing rotations for the various groups of sheep we have on the farm.

his year we have five main grazing groups. These include the ewe lambs and their lambs, the 'main flock', Jonathan Higgins' two grazing groups for his research study and a small group of triplet-rearing ewes.

The triplet-rearing ewes are receiving 750g of concentrate per day at this stage. These lambs will be weaned onto a crop of Redstart in late May. The preparation for the sowing of this crop began last week, with an area towards the bottom of the hill sprayed off in advance of cultivation. This will also allow us an opportunity to reseed this section of the hill next near.

We run the ewe lambs as a separate group up to weaning to reduce competition from the mature ewes. We find this works well and gives this important group the best chance of hitting their mating targets in October.

The ewe lambs merit special attention because they are the future of the flock and should represent the best genetics within your breeding female population.

If you do not view them and treat them as such, then the question needs to be asked as to why they are being retained within the flock. Too often, ewe lambs are an after-thought; this should not be the case.

After a rather cool March, which had a negative impact on grass growth, growing conditions are improving across the farm.

In March our average temperature was 0.5C below average, and while this does not seem like much, it was enough to have a negative impact on grass growth.

Luckily April has been much warmer, with an average temperature to date of 9.1C, which is over one degree above the average for this time of year.

Tonic

Rainfall in April so far is scarce, as it was in March. In March we received approximately 65pc of our normal rainfall, though this did follow on from an exceptionally wet February, which delivered three times the normal monthly rainfall.

Conditions are good now for grass growth and last week's sunshine was a welcome tonic for the lambs. Dry weather is a real catalyst for lamb growth.

This year we encountered a small outbreak of contagious ovine digital dermatitis (CODD) in the flock just before lambing. This is a rather contagious type of lameness, which does not respond to the normal treatments that work for foot rot.

It is a separate disease, but as we discovered this year, foot rot and CODD can be present in the same foot, at the same time.

Traditionally one method for differentiating between the two was the strong smell associated with foot rot, which is absent with CODD.

However, in our most recent outbreak we had animals with the symptoms of CODD and the smell of foot rot, indicating both diseases are present at the same time. These animals responded well to antibiotic treatment and the issue is pretty much resolved now.

The next four weeks will be focused on research to a large part, with the start of faecal egg sampling on the experimental ewes and lambs, lamb weighing at six weeks of age to indicate ewe milk production, and ewe condition scoring.

The main flock will continue in their rotation and we will also be paying close attention to the parasite forecasts for control of Nematodirus in the lambs.

Indo Farming

Go here to read the rest:
Tommy Boland: Ewe lambs deserve special treatment - they are the future of your flock - Farm Ireland

Text Size:A- A+

New Delhi:As the world reels from the impact of the Covid-19 crisis, which has also induced an economic recession, there are many working tirelessly at the forefront to tackle the challenge. In India, several women are working round-the-clock, seven days a week, to ensure the smooth functioning of key departments administration, diagnosis, prevention, research and cure.

ThePrint takes a look at some of those leading these efforts.

Preeti Sudan, secretary at the Ministry of Health and Family Welfare, has been working on aligning all departments to execute the Narendra Modi governments policies to prevent the spread of the disease. Beela Rajesh, health secretary of Tamil Nadu, has been proactive in engaging with citizens through her department and Twitter. The state currently has more than 600 active cases, one of the highest in the country.

Dr Priya Abraham, director of National Institute of Virology, Pune, has made a significant medical breakthrough by isolating the deadly coronavirus. This helps in understanding the disease better and finding treatment regimens.

Dr Nivedita Gupta, senior scientist at Indian Council of Medical Research (ICMR), is busy designing the treatment and testing protocols for the country while Dr Renu Swarup, secretary, Department of Biotechnology, is spending her time trying to find a vaccine.

Also read: Coronavirus has challenged & changed how worlds top scientists work to find a cure

A 1983 batch IAS officer from the Andhra Pradesh cadre, Sudan is usually seen leaving her office at Nirman Bhawan late at night.

An M.Phil. in Economics and postgraduate in Social Policy and Planning from the London School of Economics, Sudan also served the World Bank in Washington as a consultant.

Her ministry is the nodal agency for fighting the present coronavirus challenge. Sudan, along with Union Health Minister Harsh Vardhan, coordinates with sister departments in the central and state government. The two conduct regular reviews of the evolving situation.

She is also involved in the regular review of preparedness with the states and union territories. Also, she is the first point of contact for any query arising from Prime Minister Narendra Modis office or from the office of Union Minister, said a senior official from her ministry who did not wish to be identified.

She played a major role in the evacuation of the 645 students from Wuhan, China, the official added.

Among her cadre, Sudan has a distinguished track record of serving in finance, disaster management, tourism and agriculture.

Also read: How experts are using maths to stay ahead of the coronavirus

Working in the Division of Epidemiology & Communicable Diseases, and in-charge of viral diseases at the countrys apex health research department, Dr Guptas primary responsibility is building testing and treatment protocols in India.

She was also the primary scientist involved in the investigations and containment of the Nipah virus outbreak in Kerala last year.

An MBBS from Lady Hardinge Medical College, Dr Gupta is the key person to augment the Covid-19 diagnostic capacity all across the country. In the short time span of two months, over 130 laboratories in the government sector and 52 laboratories in the private sector were roped in to diagnose coronavirus cases.

She worked day and night, including Sundays, to investigate the Nipah cases last year. It was not even a pandemic like coronavirus. Nowadays, for several days together, several scientists stay in the office to conclude the investigations, including her, said an official in her department, also on the condition of anonymity.

Gupta has a PhD in molecular medicine from Jawaharlal Nehru University and has been instrumental in setting up the virus research and diagnostic laboratory network of ICMR. This network was established subsequent to the 2009 pandemic influenza outbreak. The Virus Research and Diagnostic Laboratory (VRDL) network of 106 laboratories is largely considered as the backbone of the nation, and has ensured the capacity to detect the virus in almost all parts of the country.

Dr Gupta has aggressively investigated the viral outbreaks such as enteroviruses, arboviruses (dengue, chikungunya, Japanese encephalitis & Zika), influenza, measles and rubella among others. She was part of the team that worked extensively on deciphering the aetiology, and developed management guidelines, for the acute encephalitis syndrome in different parts of India.

Also read: Pancreatitis drug trials to a wastewater test for tracking virus top research on Covid-19

Swarup has been working at the Ministry of Science and Technologys Department of Biotechnology (DBT) for the past 30 years. She held the position of Scientist H which denotes an outstanding scientist until April 2018, when she was appointed as secretary.

A key person in the formulation of the Biotechnology Vision in 2001, the National Biotechnology Development Strategy in 2007 and Strategy II in 2015-20, Swarup is now involved in the crucial research to develop a coronavirus vaccine.

In an interview to ThePrint, Swarup had said that she is busy scaling up the manufacturing capacity of start-ups that have made low-cost testing kits and ventilators for Covid-19.

Her ministry has asked all IIT incubators to focus on research and development of portable ventilators, genome sequencing and isolation of the strain of the novel coronavirus from blood samples.

A PhD in Genetics and Plant Breeding, Swarup is known for promoting women in science, and was a member of the Task Force on Women in Science, which was constituted by the Scientific Advisory Committee to the Prime Minister.

Also read: 5 new projects India will pursue to find treatment for Covid-19 and similar diseases

Abraham leads the backbone of the country right now the National Institute of Virology (NIV), Pune, which is affiliated to the ICMR. The NIV was initially the only testing centre in the country for Covid-19.

As the number of cases spike on a daily basis, the NIV has succeeded in reducing the testing time of Covid-19 samples to just four hours a sample from 12-14 hours.

The NIV had confirmed the first three positive Covid-19 cases in India. The institute had initially done all the testing, but ICMR subsequently increased the number of laboratories, anticipating a jump in cases. Under Abrahams leadership, theNIV helped these labs with troubleshooting, and ensured reagent supplies to the network of labs.

The achievements which NIV has made at this crucial juncture were not possible without a hardworking and well-coordinated team, Abraham told ThePrint.

Abraham holds an MBBS, MD (Medical Microbiology) and PhD from Christian Medical College in Vellore, where she was also the former head of the department of Clinical Virology at CMC Vellore. She is also a fellow of the Royal College of Pathologists and Royal Society of Tropical Medicine and Hygiene. On invitation from the Medical Council of India, Abraham also drafted the syllabus for the Doctor of Medicine (DM) in Virology.

Her achievements also include being a key member of the WHOs Guidelines Development Working Group Meeting for Hepatitis and HIV in 2012, and for Hepatitis B in 2014. In 2017, she served as WHO consultant in Myanmar to formulate the National Hepatitis Testing.

Also read: India Covid-19 death rate lower than Italy, UK, but cant play down virus impact: NIV chief

As the health secretary of Tamil Nadu, Rajesh has been at the forefront of tackling the challenge in her state.

A 1997 batch IAS officer, she is known as a media-friendly bureaucrat and is very active on Twitter.

Virus can affect anyone, lets be gentle and sensitive towards each other and wage a coordinated battle against Covid19, she posted recently.

Apart from sharing her thoughts, she also responds to queries directed at her or her department.

An MBBS graduate from Madras Medical College, Beela earlier served as sub-collector of Chengalpattu, commissioner of Fisheries and commissioner of Town and Country Planning in Tamil Nadu. She was also the commissioner of Indian Medicine and Homeopathy before being transferred as the health secretary in 2019.

Tamil Nadu ranks third among all Indian states in the NITI Aayog Health Index given its vastly improved health outcomes.

Under Rajesh, the Tamil Nadu Health System Reform Program was set up with the state government, Centre and World Bank signing a $287 million loan agreement in June 2019. The program aims to improve the quality of health care, reduce the burden of non-communicable diseases (NCDs), and fill equity gaps in reproductive and child health services in Tamil Nadu.

Also read: These are the 11 Indian women scientists the new STEM chairs are named after

ThePrint is now on Telegram. For the best reports & opinion on politics, governance and more, subscribe to ThePrint on Telegram.

Subscribe to our YouTube channel.

Read more from the original source:
Doctors, IAS officers & a scientist the 5 women leading Indias fight against Covid-19 - ThePrint

United States, Wisconsin, Waukesha 04-13-2020 (PRDistribution.com) Dr. Victoria J. Mondloch, Medical Director of Wisconsin Stem Cell LLC and President/Founder of Victoria J. Mondloch, MD, SC., has recently been selected for the Empowered Woman of the Year Award for 2020 by the International Association of Top Professionals (IAOTP). Her exemplary role as a female business professional in a male dominated industry displays her influence, capability and determination.

While inclusion with the International Association of Top Professionals is an honor in itself, only a few women are chosen for this distinction based on their years of experience, professional accomplishments, academic achievements, leadership abilities and contributions to their communities. With innovation and compassion, these women empower others to reach their goals, while creating change for future generations.

Stephanie Cirami, President of IAOTP stated that Choosing Dr. Mondloch for this honor was an easy decision for our panel to make. She is a pro-active physician, who is insightful and empathetic in all aspects of her treatments. Dr. Mondloch displays empowerment through her ability to listen and understand her patients and staff. We are thrilled to be honoring her this year at IAOTPs Annual Awards Gala being held at the Plaza Hotel in New York City.

Dr. Mondloch is being recognized for having over three decades of professional experience as a Physician practicing Womens Health, Family Medicine, Preventive Health and Wellness for Women and Men. She is also a successful Author and Educator who empowers her patients to choose healthier options in order to lead a healthier lifestyle. She utilizes both traditional and integrative methods to enhance her patients course of treatment. Dr. Mondloch earned her MD from the Medical College of Wisconsin, did her internship in Internal Medicine and her residency in OB-GYN at St. Josephs Hospital in Milwaukee, WI.

Her practice and areas of expertise include but are not limited to: practicing traditional and non-traditional Family Medicine with an emphasis on Wellness and Preventive Health, Bio-identical hormone balancing including female/male sex hormones, Adrenals, thyroid and insulin with diabetes prevention as well as diabetes management, in-Office laboratory services, in-office supplements, vitamins and essential oils and in-Office sports medicine/Chiropractor services including Sarapin trigger point injections for muscular pain and paresthesia or numbness caused by nerve entrapment to upper and lower extremities. Dr. Mondloch practices a multi-faceted approach to common diagnoses such as abnormal periods, PMS, uterine fibroids, endometriosis and ovarian cysts, using hormone balancing to help prevent surgery. Other common diagnoses that are routinely addressed include: fibrocystic breast disease, polycystic ovarian disease, migraines, hot flashes/night sweats, insomnia, urinary incontinence, vaginal atrophy, low libido, abdominal bloating, fibromyalgia, Heart palpitations, Fatigue, Constipation, Headaches, Acne, excess facial hair, sciatica, low back pain and Hair loss with in-office all natural hair care products that help stimulate hair follicles to regenerate new hair growth. Dr. Mondloch practices a patient-centric style of medicine, dedicated to educating and empowering her patients to help them understand their health and help them get off of medication and remain out of the healthcare system.

Throughout her remarkable career, Dr. Mondloch remains active in her community, and has been recognized worldwide for her outstanding leadership and commitment to the profession. For 2020 she was featured on the famous Reuters Building in Times Square, NYC. In 2019 she graced the front cover of TIP (Top Industry Professionals) Magazine and she was selected as Top Medical Director of the Year by IAOTP where she was honored at their Annual Awards Gala at the Bellagio Hotel in Las Vegas.

Aside from her successful career, Dr. Mondloch is also a sought-after speaker and published author. She is the author of 2 books: Blossoming; Becoming a Woman and Full Bloom: Perimenopause, Menopause, Post-Menopause and Beyond. Blossoming is a mother-daughter guide to the pitfalls of hormone imbalance in the adolescent female and how to recognize the signs and symptoms as well as how to work with your healthcare provider to check hormone levels and correct imbalances. Blossoming is the 1st of a 3 book female book series that is planned to address hormone imbalances in women of multiple ages and stages. Full Bloom is the 3rd of a 3 book female book series that is planned which addresses hormone imbalances in women going through the rollercoaster of symptoms and hormone imbalances of perimenopause and then the safety profile and multiple health advantages of continuing to balance hormones into a womans postmenopausal years. Dr. Mondlochs 2nd book is for the multiple hormone pitfalls that accompany the menstruating female in her 20s, 30s and 40s and her 4th book is for hormone balancing in men. Dr. Mondloch was also featured in a 10-week radio series on CUTV News Internet Radio regarding adolescent health and a 10-week Radio series on CUTV News Internet Radio to help promote Full Bloom, Perimenopause, Menopause and Beyond. Dr. Mondlochs radio shows are archived on CUTV News Internet Radio by checking her website, victoriajmondlochmdsc.com and find her shows by date on the media page.

Moving forward, Dr. Mondloch has further expanded her practice to include the ability to more accurately target a patients specific organ systems and allow her patients own genetics to help guide their medical journey to wellness in a personalized and very individualized way.

Dr. Mondloch attributes her success to her perseverance, strength, her positive attitude and her passion for helping her patients. She has an in-office practice as well as a telemedicine preventive medical practice to offer medical advice to patients both in-office and remotely. When not working she enjoys traveling and spending time with her husband and 3 highly successful adult daughters. For the future, she will continue to grow as a professional and wants to continue to make a difference in peoples lives anyway that she can.

For more information on Dr. Mondloch please visit https://www.linkedin.com/in/victoria-mondloch-23b373/

To view her Video Biography please visit:

About IAOTP

The International Association of Top Professionals (IAOTP) is an international boutique networking organization who handpicks the worlds finest, most prestigious top professionals from different industries. These top professionals are given an opportunity to collaborate, share their ideas, be keynote speakers and to help influence others in their fields. This organization is not a membership that anyone can join. You have to be asked by the President or be nominated by a distinguished honorary member after a brief interview.

IAOTPs experts have given thousands of top prestigious professionals around the world, the recognition and credibility that they deserve and have helped in building their branding empires. IAOTP prides itself to be a one of a kind boutique networking organization that hand picks only the best of the best and creates a networking platform that connects and brings these top professionals to one place.

For more information on IAOTP please visit http://www.iaotp.com

Media Contacts:

Company Name: iaotpFull Name: Leah MontelloPhone: 2126344427Email Address: Send EmailWebsite: http://www.iaotp.com

For the original news story, please visit https://prdistribution.com/news/dr-victoria-mondloch-selected-as-empowered-woman-of-the-year-by-the-international-association-of-top-professionals-iaotp.html.

Powered by WPeMatico

More here:
Dr. Victoria Mondloch selected as Empowered Woman of the Year by the International Association of Top Professionals (IAOTP) - Life Pulse Health

Lets hear it for the female of the species and (more guardedly) for her second X-chromosome! Female superiority in colour vision, immune response, longevity, even basic survival from birth to death are illustrated in Sharon Moalems The Better Half. After decades, if not centuries, of bad press for women and their vulnerable biology, this book argues that in fact almost everything that is biologically difficult to do in life is done better by females.

Moalem, a Canadian-born physician, is a research geneticist who has identified two new rare genetic conditions. He has worked across the world in paediatric medicine, including clinics for HIV-infected infants and is also a biotechnology entrepreneur and bestselling author. The Better Half is his latest foray into the field of popular science, and presents a general argument for the superiority of womens biology to mens.

In most circumstances, a human female has two X-chromosomes, one from her father and one from her mother; a male has just one, inherited from his mother, which is paired with a Y-chromosome, inherited from his father. Moalem believes that the X-chromosome has always received a poor press, and that it is time this negative view is counteracted. He draws on swathes of medical and historical data to show that, in many instances, the superiority of womens biology is explicitly linked to their possession of the second X-chromosome. The greater complexity of womens biology, he claims, is the secret of their success it is more difficult to make a female but, once made, she trumps the male in her lifelong survival skills, for instance in her hyperefficient immune system shrugging off infection and maximising the benefits of vaccination which means that females can avoid the consequences of a wide range of life threatening events ranging from starvation and cancer to, Moalem has cautiously concluded, Covid-19.

In mainstream genetics it was long held that, despite having two X-chromosomes, female cells only made use of one: the second randomly switched off or deactivated early on in embryonic development, a process rather summarily described as an instance of genetic redundancy. There was some evidence that the deactivation reduced female chances of succumbing to X-linked problems, due to the availability of an undamaged back-up. It was acknowledged, for example (though rather grudgingly), that women generally escaped being colour blind. Moalem notes that when he was studying genetics there was much emphasis on the tiny Y-chromosome as what makes a man. He observes wryly that maybe this positivity was related to the fact that most of the people who were speaking breathlessly about the Y had one as well.

Now a new spin on the X-inactivation story is emerging in genetics. Via a process called escape from X-inactivation, it turns out that the silenced X-chromosome is not so silent after all there are escapees which may continue to offer back-up services, for instance providing extra cellular recovery options in the face of traumatic injury. It is to the benefits offered by this flexible availability within different cells that Moalem attributes the secrets of womens biological superiority.

Statistics going back as far as 1662 show women living longer than men, and todays figures show that 95% of people who have reached the age of 110 and over are female. In sport, womens success in races such as ultra-marathons offer a different perspective on what it means to be physically superior. In the spirit of Angela Sainis book Inferior, Moalem notes that this superiority has largely been ignored by medical science. And he discusses the medical trial data whose absence is observed by Caroline Criado-Perez in Invisible Women, her exploration of how the world is designed for men. Medicine needs to stop ignoring the secrets of womens biological successes, Moalem argues, and find ways of harnessing them to improve the survival chances of the whole of the human race.

Imagine you live in a world where most individuals can see 1m colours. But in one group of these people (lets call them males), about 8% cannot tell the difference between colours such as red and green, and a smaller number are totally colour blind. In a second group in this population (lets call them females), almost all can see the standard 1m colours, but some (perhaps as many as 15%) can see 100m colours. Would you excitedly rave about the amazing talent of this latter group? Or would you just describe them as not usually colour blind? This same group has an immune system that has a profound talent to fight off many forms of infection and reap major benefits from vaccinations with the down side that sometimes such hyperefficiency can lead to autoimmune disorders such as multiple sclerosis. Would you celebrate the former or emphasise the latter? For years, it is the drawbacks that have been underlined.

Research geneticists rarely get out in the field to notice the much greater survival rates of girls in paediatric ICUs

The Better Half is an eye-opening book. In explaining why the advantages that accompany females greater genetic options have to date been largely ignored, Moalem points to paradigm blindness, and to the fact that research geneticists rarely get out in the field to notice, for example, the much greater survival rates of girls in paediatric ICUs (rates which, he discovers, have been clearly obvious to the nurses doing the frontline caring).

I take issue with one part of his chapter on The Male Brain, for the moment setting aside the unproven assumption that the brains of men are different from the brains of women. Moalem chooses to consider autism, and it appears as a given in his book that autism is more common in boys than girls (itself an assumption that is increasingly being challenged). Yet at the more impaired end of the autism spectrum, it is possible that there are as many girls as boys, and his suggestion that females have a different kind of autism doesnt quite prove his wider argument. The X-linked disorders such as fragile-X or Rett syndrome receive only a passing mention not surprisingly perhaps as they run counter to his argument about the superiority of the X-chromosome.

What about hormones? Moalem has perhaps missed a good opportunity to counter oestrogens frequently negative press, and to laud its potentially neuroprotective effects. The greater susceptibility of women to Alzheimers disease is put down by Moalem to a form of anti-inflammatory process linked to an overefficient immune system; their lesser susceptibility to Parkinsons disease (surely a possible inclusion in the list of female genetic successes) is unexplained.

One section of the book focuses on why womens health is not mens health, and considers the failures of drug companies to test their products on females as well as males. For sure this has had detrimental consequences on, for example, the accuracy of dosage rates. But in at least one of the examples he gives, that of Ambien, body mass and blood volume are key factors in calculating dosage rates: because people vary enormously in size and shape, simply dividing test participants into males and females still risks inaccuracy. He is talking about averages, its true, but even so Moalem seems firmly wedded to the notion that genetic females and genetic males can be neatly categorised into two distinct types, and that the understanding of genetic sex will provide all the answers we need.

The impression given in The Better Half is that there is a lifelongfree-ranging choice between X-chromosomes available to the female, her cells dancing back and forth between the best options that will help her to heal quicker after a car crash or to overcome the bacterial infection that might lead to an ulcer. There are brief and tantalising hints about the escapees from X-inactivation in several chapters of Moalems book, but it is a shame that we are never given a full, head-on account.

Yet this book is full of wonderful titbits of information from the existence of a female prostate gland to the number of honey bee flying miles it takes to make 1lb of honey. The celebration of the genetic diversity offered by the females second X-chromosome is wholehearted and the examples Moalem gives are highly effective. He has written a powerful antidote to the myth of the weaker sex.

The Better Half: On the Genetic Superiority of Women by Sharon Moalem is published by Allen Lane (RRP 20).

Originally posted here:
The Better Half by Sharon Moalem review on the genetic superiority of women - The Guardian

By Jennifer Couzin-FrankelApr. 9, 2020 , 11:35 AM

In college in the 1990s, Alix Timko wondered why she and her friends didnt have eating disorders. We were all in our late teens, early 20s, all vaguely dissatisfied with how we looked, says Timko, now a psychologist at Childrens Hospital of Philadelphia. Her crowd of friends matched the profile she had seen in TV dramasoverachievers who exercised regularly and whose eating was erratic, hours of fasting followed by a huge pizza.

My friends and I should have had eating disorders, she says. And we didnt.

It was an early clue that her understanding of eating disorders was off the mark, especially for the direst diagnosis of all: anorexia nervosa. Anorexia is estimated to affect just under 1% of the U.S. population, with many more who may go undiagnosed. The illness manifests as self-starvation and weight loss so extreme that it can send the body into a state resembling hibernation. Although the disorder also affects boys and men, those who have it are most often female, and about 10% of those affected die. Thats the highest mortality rate of any psychiatric condition after substance abuse, on par with that of childhood leukemia. With current treatments, about half of adolescents recover, and another 20% to 30% are helped.

As a young adult, Timko shared the prevailing view of the disease: that it develops when girls, motivated by a culture that worships thinness, exert extreme willpower to stop themselves from eating. Often, the idea went, the behavior arises in reaction to parents who are unloving, controlling, or worse. But when Timko began to treat teens with anorexia and their families, that narrative crumbledand so did her certainties about who is at risk. Many of those young people dont have body dissatisfaction, they werent on a diet, its not about control, she found. Their mom and dad are fabulous and would move heaven and Earth to get them better.

Timko wasnt alone. Other researchers were also questioning psychological theories of anorexia that had reigned for generations. Hunger is a basic drive, says Cynthia Bulik, a clinical psychologist who runs eating disorder centers at the University of North Carolina, Chapel Hill, and at the Karolinska Institute. The idea that patients use willpower to override hunger never rang true, she says. My patients have said for years that when they starve, they feel better. She began to consider another possibility: What if their biology is driving them to eschew food?

Bulik and Timko are now part of a small band of researchers working to untangle the biology of anorexia. The more they look, the more they find to suggest the diseases biological roots run deep. For instance, genetic studies indicate its about as heritable as obesity or depression. The circuitry of the brains reward system behaves differently in unaffected volunteers than in people with anorexia and those who have recovered. And new treatments drawing on biology are being tested, including deep-brain stimulation and psychedelic drugs. Those experiments aim not only to improve the outlook for patients, but also to explore how closely the disease aligns with others across psychiatry, including obsessive-compulsive disorder (OCD) and addiction.

Scientists pursuing those new ideas face a challenge, in part because of money: For fiscal year 2019, anorexia got $11 million in funding from the National Institutes of Health (NIH), a figure that hasnt changed notably in many years and that researchers decry as shockingly low given the diseases burdens. By contrast, schizophreniawhich has a similar prevalence and also surges during adolescencegarnered $263 million. The dearth of funder interest, many say, springs from the view that anorexias roots are cultural, along with shame and stigma still clouding the disease. But evidence is mounting that biology is at its core.

Many researchers lament that eating disorders, including anorexia nervosa, are underfunded given their prevalence. These numbers are drawn from 2017 data for the United States; the number of individuals affected is an estimate.

(GRAPHIC) X. LIU/SCIENCE; (DATA) BRYN AUSTIN/BOSTON CHILDRENS HOSPITAL; NATIONAL INSTITUTES OF HEALTH

Lori Zeltser pivotedto anorexia from studying obesity. A developmental neuroscientist at Columbia University, she studied the brains of developing mice, trying to identify feeding circuits that increase susceptibility to obesity in adulthood. Then about 10 years ago, Zeltser saw a notice for funding from the Klarman Family Foundation, formed by hedge fund manager Seth Klarman and his wife, Beth, now the foundations president. The foundation wanted to stimulate basic research into eating disorders, and because of Zeltsers research on appetite, she submitted a proposal.

To get up to speed on anorexia, Zeltser turned to the literature. Researchers in Sweden and Minnesota had compared anorexia rates in identical and fraternal twins, a common approach to tease out heritability of complex traits and diseases. Those reports showed that 50% to 60% of the risk of developing anorexia was due to genes, implying DNA is a powerful driver. By contrast, family studies suggest the heritability of breast cancer is about 30%, and that of depression is roughly 40%. I was shocked, Zeltser says.

Layered on the genetics work was a data point that caught Zeltsers attention. An antipsychotic drug, olanzapine, which causes profound weight gain as a side effect, had little to no effect on weight when tested in people with anorexia. Something in peoples biology prevented olanzapine from causing weight gain, Zeltser believes. That is not just [mental] control.

But a deep schism remains, with many practitioners concerned that biology is getting more attention than it deserves. If I had to choose nature versus nurture in the development of anorexia and other eating disorders, I would choose nurture, says Margo Maine, a psychologist who has treated eating disorders for years. Eating disorders are primarily female, she says, in part because gender is a cultural experience.

Psychotherapist Carolyn Costin, who recovered from anorexia in the late 1970s and established a network of private treatment centers around the United States, says biology plays a role but that cultural messages and psychological stressors are also important factors. She worries especially that the way biology research is described could discourage patients about their prospects for recovery. About 8 years ago, she says, Clients started coming in, saying, Its genetic, why bother trying to get well?

Such comments agitate researchers like Bulik. The patients she treats, she says, are reassured, not distressed, to learn that the disorder is rooted in biology and that biology doesnt translate into destiny. Although she, Zeltser, and others agree that anorexia has environmental drivers, as most chronic conditions do, they object to the idea that environment leads the way. Exposure to this ideal [of thinness] is ubiquitous, but everybody doesnt get anorexia nervosa, Bulik says. None of the sociocultural literature has ever been able to explain why. She adds, A lot of patients will say, It was never about being thin for me, ever.

If you look at psychiatric syndromes over 200 years, anorexia hasnt changed at all, whereas our culture has, says James Lock, a child psychiatrist who heads the child and adolescent eating disorders program at Stanford University School of Medicine.

To begin digging into the biology of anorexia, Zeltser used a 2010 grant from the Klarman foundation to build a mouse model of the disease. Because feeding is easy to measure, she reasoned that anorexias restrained feeding behavior is well-suited for animal modeling. Her goal was to study the eating and starvation patterns of the mice and explore how genetics and the environment interact to trigger the disorder.

In a 2016 issue ofTranslational Psychiatry,Zeltser described micewith a variant in a gene that in people is linked to anorexia. On its own, the variant didnt noticeably affect mouse feeding behavior. To mimic the pullback from eating that often precedes a diagnosis, the researchers restricted the animals caloric intake by 20% to 30%. Then they induced stress, another factor linked to anorexia, by housing the normally social animals alone. The result: The mice stop eating, Zeltser says.

Lori Zeltser, a developmental neuroscientist at Columbia University, has developed a mouse model of anorexia nervosa.

Zeltser is talking with clinical colleagues about comparing her rodents behavior with videos of patients in a feeding lab, where researchers observe how much people eat, which nutrients they choose, and which they avoid. If the behaviors seem parallel, the mice could help point the way to new treatments or even different environments that could better support eating.

But publishing her animal work has proved difficult. Zeltser is often asked, How do you know if what youre finding is relevant to humans? Thats a common question of anyone doing mouse work, but Zeltser says the challenge here runs deeper. This is not taken seriously as a disease that has a biological basis, she says. Instead, its dismissed as extreme girl behavior and oh my God, theyre crazy, pushback she finds immensely frustrating.

Accumulating genetic data could change that by making anorexias biological roots harder to ignore. Some of the strongest evidence emerged last summer, when Bulik and others published inNature Geneticsthe largest genetics study on the disease, with roughly $9 million in funding from the Klarman foundation and additional funds from NIH. By analyzing the genomes of nearly 17,000 people with anorexia and more than 55,000 people without, the researchers identified eight statistically significant genomic regions, along with other patterns of genetic associations that yielded important clues. Some of those associations tracked with results of studies of other psychiatric illnesses, including OCD and depression, which didnt surprise Bulik. What did were overlapping associations with DNA controlling body mass index (BMI), lipids, and other metabolic traits.

We said, This doesnt look like any other psychiatric disorder, Bulik says. It might be the inverse of obesitythese people might be genetically predisposed to low BMI. In the February 2019 issue of theJournal of the American Academy of Child & Adolescent Psychiatry, she and her teamsifted through BMI recordsfor young people later diagnosed with anorexia and other eating disorders. The BMIs of 243 people diagnosed with anorexia began to diverge from those of a control group before they started kindergarten.

Bulik is now launchingthe Eating Disorders Genetics Initiative, with more than $7 million from NIH, additional funding from Sweden and the United Kingdom, and potential infusions from other countries and individual donors. The initiative aims to include 100,000 people with anorexia nervosa, bulimia nervosa, and binge eating disorder. Although genetics is unlikely to offer quick solutions, Bulik hopes it can shine the light in the direction you need to go for effective therapies, including medications.

The genetic findingsmight one day intersect with another line of research: studies of brain structures and signaling that are revealing tantalizing differences between people with and without anorexia. At Columbia, psychiatrist Joanna Steinglass wanted to understand how the brains of people with anorexia guide their food choices. In two studies, she and her colleagues recruited inpatients with eating disorders along with a control group. In people with anorexia, both during and after hospitalization, MRI scans showed the region of the brain associated with selecting foods was the dorsal striatum, which is key to forming habits. In people without an eating disorder, a different brain region guides choices. The work first appearedin 2015 inNature Neuroscience, and the team presented more findings at a conference last year.

Theyre using different circuits when they make decisions, Steinglass says. This jibes with her idea that as people repeatedly restrict eating, the behavior moves to a different brain region and becomes less amenable to change. That could help explain why many recovered patients relapse.

Another clue to how the brain might throw eating off trackwas reported last month inThe American Journal of Psychiatry. Walter Kaye, a psychiatrist who directs the eating disorders program at the University of California (UC), San Diego, led a study looking at how the brains of people with anorexia behave when their bodies are hungry. Kaye, whose program treats about 70 patients per day, ran a study that included 48 women, 26 of whom had anorexia. Each was studied twice with brain imaging, once immediately after a meal and, on a separate visit, after fasting for 16 hours.

Kaye knew hunger activates brain circuits that in turn motivate eating, making food desirable. That relationship was clear during brain imaging of the control group volunteers: When they were offered sugar water after 16 hours of fasting, their reward and motivation circuits lit up. But in people with anorexia, those circuits were much less active after fasting. They could identify being hungry, Kaye says, but their brains couldnt convert that into a desire to eat. The patients also experienced heightened anxiety and inhibition, along with diminished reward signaling in their brains. That effect may further impair their drive to eat. Kaye suggests people with anorexia miscode food as risky rather than rewarding.

A lot of patients will say, It was never about being thin for me, ever.

Psychiatrist Rebecca Park at the University of Oxford also suspects the disease hijacks the brains reward system. Some of her patients experience this sense of aberrant reward, almost a high from starvation, she says. Parks neuroscience research indicates aberrant brain responses to reward cues.

Are those brain differences a cause or a result of starvation? Studying people in remission eliminates the effects of malnutrition on the brain but cant definitively answer the question. Its likely that starvation in adolescence is going to damage your brain, Park says. One way to begin to disentangle whether the brain differences predate the disease is to study people very early in its course. Steinglass is in the third year of a brain scanning study of reward circuitry, which now includes 55 recently diagnosed teenagers and a control group of 25 others. The coronavirus pandemic has halted enrollment for now, but Steinglass hopes to have results in 2 to 3 years. Other researchers are working to understand how, and to what degree, the brain recovers once eating resumes.

Theres an overall sensethat were joining the rest of the world by finally applying scientific methods to anorexia nervosa, Steinglass says. The ultimate goal is new treatments, which are sorely needed.

The most studied and most effective strategy to date is called family-based treatment (FBT), which originated at the Maudsley Hospital in London. It was later refined by Lock and psychologist Daniel Le Grange, of UC San Francisco, who trained at Maudsley.

FBT asks parents to set aside many of their familys day-to-day activitiesscaling back school, work, hobbiesto sit with their children, requiring them to eat. Faced with food as a form of medicine, and with their world having contracted, many young people do start to eat again despite the fear and anxiety it causes them. Researchers are working to understand how FBT is intertwined with the biology of the illness, but for about half who try FBT in adolescenceand perhaps 70% who try it early in the diseasethe treatment is effective.

But many families arent told about that therapeutic strategy, even though decades have passed since it first showed success in a randomized trial, in 1987. Practitioners may not be familiar with FBT, Timko says, they may believe the family played a role in anorexias onset, or they may feel that adolescents must want to get better before starting FBTa view she disputes.

Laura Collins Lyster-Mensh experienced the regimen up close after her daughter Olympia, then 14, stopped eating one day in 2002. Lyster-Mensh says a succession of therapists urged her and her husband to stand back and let Olympia eat when she was ready. Meanwhile, her weight continued to spiral downward. We had been told she wouldnt recover, families were really at fault, to back off and let her do this on her own, Lyster-Mensh says. Then she learned about FBT from a newspaper article and raced to try it.

The first agonizing meals took hours, while Olympia mashed her food into a pulp or cried and raged at her parents. I know families whose kids have jumped out of moving cars to avoid a sandwich, says Lyster-Mensh, echoing comments of many clinicians who describe patients crushing fear of food. Olympia ultimately recovered, although not without challenges that included a relapse during college.

The young patients treated with FBT who do start to eat again do well on the one measure that predicts longer-term prognosis: early weight gain. In 2019, a study in theEuropean Eating Disorders Reviewled by Le Grange confirmed earlier research showing thatgaining about 2.3 kilograms in the first month of treatment is a predictor of health1 year later. Girls with anorexia who boosted their calorie intake and gained weight experienced increases in estrogen levels (which plummet in starvation), reduced stress, and improved ability to navigate different situations, a psychological trait called flexibility.

Researchers are exploring ways to build on and improve FBTor find new strategies to help patients in whom it has failed. Some clinical trials are testing whether certain talk therapies, such as cognitive behavioural therapy to help patients reframe their thinking, can helpfor example, by reducing anxiety or other impediments to eating.

New biological models of anorexia hint at other kinds of interventions. An 18-person study at Johns Hopkins University is offering the psychedelic drug psilocybin to patients. Early data suggest it holds promise in helping smokers quit and combating alcoholismand many researchers believe that in certain ways, anorexia shares some features with addiction. Park is leading a seven-person study of deep-brain stimulation in people with severe enduring anorexia, some of whom also have OCD.

Theres a certain neural network thats well characterized in OCD, she says, and disrupting the signaling in that network with deep-brain stimulation can help those patients. Because OCD and anorexia have shared features and some genetic links, shes interested in whether disrupting the same neural network might also help people with the eating disorder.

Still, studies remain sparse, Lock says. With limited funding, theres little chance of attracting new scientists to a small field. As researchers, you dont want to go to the pot thats empty, he says. Why arent we investing more? Its especially frustrating because, Lock points out, many patients with anorexia successfully heal and enjoy a bright future. What [other] illness in psychiatry can you say you cure? he asks.

For families, regardless of whether a patient recovers, the shame can persistand with it hesitation to speak up and lobby for funding. Lyster-Mensh is an exception. After her familys experience, she began to voice support for evidence-based treatmentfirst in a memoir,Eating with Your Anorexic, which she wrote under the name Laura Collins, and then throughFEAST, a message board turned advocacy group.

Its still a pretty small group, Lyster-Mensh says, of those willing to speak openly. Most families are so burned out, crushed, guilty, that they dont want to come forward, she says. There are still these myths out therethat these are chosen illnesses and parents somehow failed to prevent, or caused, or exacerbated the problem. Still, she hopes that as researchers doggedly track the diseases biological roots in genes and the brain, those enduring myths will fade.

Read the rest here:
Rethinking anorexia: Biology may be more important than culture, new studies reveal - Science Magazine

Men and women who undergo treatment for cancer react differently to radiotherapy (RT), according to evidence drawn from a literature review.

The study found a small but significant difference in response to RT.

Women generally derive a greater survival benefit and are more likely than men to be cured, but the side effects that they suffer are more severe, say the authors.

However, a radiation oncologist who was approached for comment cautioned that the literature review was selective and that more data from larger studies are needed before claims of a differences between sexes in their response to radiotherapy can be considered "definitive."

The new article, published in Critical Reviews in Oncology/Hematology, highlights the importance of including gender as a variable in clinical trials, say the authors.

"It is clear that gender plays a role in the occurrence and response to therapy of many diseases," coauthor Eva Bezak, PhD, professor of medical radiation and director of translational cancer research, University of South Australia, Adelaide, told Medscape Medical News.

"Gender should definitely be considered in this era of individualized medicine," Bezak said.

"We need to take into account the biological differences between males and females and how these differences can affect responses to treatment and even the propensity to develop certain cancers," she said.

"For example, it is already well established that men are more susceptible to head, neck, and blood cancers and women are more prone to autoimmune diseases as well as osteoporosis. In addition, scientists know that individual responses to radiotherapy are up to 80% determined by genetics," Bezak said.

The differences in responses to radiation are evident from two important historical events, Bezak noted: the Chernobyl nuclear reactordisaster in 1986, and the atomic bombing of Hiroshima and Nagasaki in 1945.

After Chernobyl, women were at increased risk for endocrine imbalance, thyroid cancer, and brain tumors, and the male-to-female birth ratio was slightly increased, probably because, as an effect of low-dose radiation, fewer girls were born to irradiated men, she said.

After Hiroshima and Nagasaki, the risk for solid cancers increased by 35% for men and by 58% for women. "This shows us that there is great cause to suspect a significant difference in the effect of radiation between genders," Bezak said.

For the current review, Bezak and her coauthors assessed eight articles on the in vitro and in vivo response to RT, and they categorized the results by gender.

In a preclinical study that involved a rodent model of pediatric RT, cognitive impairment, as measured by novel odor recognition after cranial irradiation, occurred in male mice, but female mice showed cognitive impairment only during certain stages of the estrous cycle.

In another preclinical study that focused on differences in acute lung toxicity between genders, 60% of irradiated male rats developed pneumonitis, compared with 50% of irradiated female rats. Similarly, 80% of irradiated male rats developed vasculitis, compared with 70% of female rats.

Studies conducted in patients with rectal and esophageal cancers also highlight differences in response between men and women, Bezak said.

An in vitro study that investigated gender differences of colonic motility after chemotherapy and RT for rectal cancer showed that colonic samples from males demonstrated a higher sensitivity and greater response to carbachol and histamine stimulation than did samples from females.

And a retrospective cohort study of cardiotoxicity during RT for esophageal cancer showed that women developed cardiac toxicity earlier and at much lower doses than did men.

Other studies show that women have an advantage when it comes to survival, Bezak said.

One study that assessed the impact of gender on progression-free survival (PFS) and overall survival (OS) after RT for esophageal squamous cell carcinoma found that for males, the median PFS was 10.6 months and OS was 15.9 months, whereas for females, the median PFS was 14 months and OS was 20.8 months (P = .0005).

"The increased survival here may be due to the heightened radiosensitivity in women, leading to a greater therapeutic effect," Bezak said.

Many factors could affect a person's response to radiotherapy, said Bezak.

"Obviously, there are differing anatomic and body shapes, lipid distribution, among men and women. There are lifestyle differences, because it is known that males are more likely to drink alcohol and smoke more than women. Then looking internally, we have different hormones and enzymes which dictate how we will respond to radiotherapy. We know that estrogen has some protective effect, especially when it comes to head and neck irradiation. Males can lose their sense of smell, but women don't. We speculate, because we don't have enough evidence as yet, that this could be a protective effect of estrogen," she said.

"Ideally, if we want to improve therapies, we should be developing more gender-specific treatment options," she said.

Gender is often not considered to be an independent prognostic factor, but it should be, Bezak said.

"Gender is often not isolated when people do various multivariate analyses, but researchers should start looking a bit more at gender as one of the factors. When we do preclinical research and are using cell lines, we should make sure we are using cell lines that are derived both from males and females. When we are doing animal studies, we should be using male and female animals," she said.

"I am researching head and neck cancer and also pancreatic cancer. In some of my past studies, I admit that we used female mice only, because they were less likely to bite you. At the moment, I am doing research on head and neck cancer, and unfortunately most of our cell lines are from males, so I need to record that as a potential bias. But in my pancreatic cancer research, I have made sure that 50% of the cell lines have been derived from males and 50% from females, so that will mitigate bias," Bezak said.

Approached for comment, Brian Marples, PhD, professor of radiation oncology at the University of Rochester Medical Center, New York, said this is "a nice review of selective literature."

This article "poses a question, but the answer to this question is unknown," he cautioned.

"This manuscript does not answer that question either but highlights that much more work in this area is needed," Marples told Medscape Medical News.

Marples, who is also vice chair of the American Society of Radiation Oncology'sScience Council, said the article is selective in nature.

"It does not describe negative studies, for example, and focuses instead on eight studies that show differences, and most of these are too small for firm or definitive conclusions. For example, the research on atomic bomb survivors showed more female than male cancers, but these were largely breast cancers, and data support induction of radiation-induced breast cancers, so this observation is somewhat expected," Marples said.

He agrees that gender plays a role in diseases generally and that the health of males is generally worse than females for a number of reasons, including weight, smoking history, inactivity, and different hormonal backgrounds.

However, in terms of radiosensitivity, this difference has yet to be definitively demonstrated.

"We know sex differences exist in mice in response to radiation and radiation response for some assays, with female mice less prone to cognitive defects of cranial irradiation and also potentially lung sensitivity, but we need more data from much larger studies for these claims to be definitive," Marples said.

Bezak and Marples report no relevant financial relationships.

Crit Rev Oncol Hematol. 2020 Mar;147:102881. Abstract

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc.

See the original post here:
Differences in How Men and Women Respond to Radiotherapy? - Medscape

We all have inherited family traits eye colour, height, stature and even mannerisms which set us apart from others and remind us that we belong to a certain family group.

But while many of these attributes are welcome, there are some genetic traits were not be so keen to have namely, a gene mutation which puts us at an increased risk of developing cancer.

Niki Warner knows only too well the reality of this as not only did she lose her mother, Judit, to cancer, but she discovered they are both carriers of the faulty BRCA1 gene mutation.

Originally from Hungary, Judit was first diagnosed with breast cancer in 2005, then again in 2010 and then, unfortunately, it returned for the third time in April 2016 and this is when Niki realised that her mother was going to die.

I went into autopilot, finished my exams and spent the summer at home working in a local cafe, says the 22-year-old, who is currently doing a PhD in Health Psychology at NUIG.

My mums family came from Hungary and she went there herself to avail of different treatments. Dad and I used to get out of the house sometimes when it got too much - we went for ice-cream in Carrick-on-Shannon, with embarrassing regularity. Dad was brilliant but its a very personal and long-winded thing, and I myself havent come to grips with how I coped. It wasnt a conscious decision, but its just something you do and get on with.

Judit sadly passed away in August 2016, having also been diagnosed with the genetic mutation, and since then her daughter has been trying to pick up the pieces.

Its not been easy and I threw myself into learning what a BRCA mutation is, what being a carrier implies, and have tried to digest any bit of information I can lay my hands on, says Niki, who has a younger brother called Zoli (16) and two older half-siblings, Zac and Jess.

I remember the exact moment I found out about the mutation. Mum knew she was terminal at the time, and we were walking on a beach. I dont know if I fully comprehended what it meant and whether I grasped that I had a 50/50 chance of inheriting the genetic mutation, but she told me that I would also have to be tested.

It got put to the backburner but, after she passed away, I decided to get tested. I had an amazing GP, Dr Marion Brogan, who sorted my referral, and with Dads support I went through the process in 2017, which ended up confirming that I too carried the BRCA1 mutation.

I dont know if I was shocked, and I dont think it affected me as strongly as I retrospectively think it should have. But I guess it wasnt necessarily a bad thing, as I now have the luxury that my Mum wasnt afforded, which is to have my preventative surgeries and get ahead of the mutation.

Armed with this information, Niki is extra vigilant about her health and also about her future plans.

Im not eligible for screening in Ireland as I am too young, but when I visit my family in Hungary, I get screened there, which is good for my own assurance, she says. Its more than likely premature but I had a scare last year when they thought theyd found something in my left breast, but thankfully it amounted to nothing.

Once I get to around 30, I suppose it will be time to consider kids as Id like to have a salpingo-oophorectomy [removal of ovaries and fallopian tubes] by 35. But Im hopeful that by then, we might see newer prophylactic techniques, such as initially only removing the fallopian tubes and delaying the removal of the ovaries so I dont have to go through premature menopause, and all the issues surrounding heart, bone and brain health which go hand-in-hand with it.

However, this is still not fully researched so Im obviously holding off on that decision for now. Ill aim to have my double mastectomy, with reconstruction, around 35 as well. But for now, Im keeping myself as up-to-date as I can be with the preventative options available, and Ill make those choices when the time comes.

Nikis circumstances have also influenced her career choice, as she is now putting all her academic efforts into research to develop an online intervention to help improve coping mechanisms and knowledge following a BRCA mutation diagnosis in Ireland.

My whole career path has been funnelled into an area of research within psychology I was previously blind to, she says. I decided that the psychological care, or extreme lack of, following a BRCA mutation diagnosis was really grim, to the point where when I contacted a helpline, I was told that they didnt know what a BRCA mutation was. And then, through a cancer support centre, I was put in touch with a woman carrying a mutation who was against her children being tested as she, falsely, thought if they had a positive result it would be hard for them to get health insurance.

And while the medical team I met with were beyond kind and compassionate, there wasnt a whisper of a counselling service to be found. Its near-criminal to inform someone of their genetic predisposition to developing cancer, explain that theyll probably need to undergo both a preventative double mastectomy and salpingo-oophorectomy, and not refer them for psychological care. The ongoing implications, in relation to childbearing prospects, body image and the cancer-related distress, can be severe.

Niki says her experience was the driving force to begin her PhD, in 2018, under the supervision of Dr AnnMarie Groarke in NUI Galway and has made her a more empathetic researcher.

I will learn [through interviews] about the experiences of people diagnosed with carrying a BRCA mutation when they get the news, and Im keen to learn about what resources they found useful and what they would have liked to happen following their diagnosis. Im hoping to hear from as many people as possible, to make sure I can accurately portray this experience, and so if anyone was diagnosed with a BRCA1 or BRCA2 mutation in Ireland, Id love to hear from them. My email is n.warner1@nuigalway.ie.

In addition to my PhD experience, I became part of a group which I met through the Marie Keating Foundation, all of whom carry a BRCA mutation. The social support I get from these ladies is outstanding. We are a mixed bunch, all with different experiences, but I think that becoming a part of this group has helped enormously with my coping. Its a true gift to have such a vast array of experiences to learn from, both for my own personal BRCA journey, but also within the context of my research.

Almost four years after the death of her mother, and the discovery of her own genetic mutation, Niki would advise others who have recently been diagnosed to learn as much about the mutation as possible and seek support from others in the same situation.

Take time to process what youve just learned as I think its so important to try to frame it as a positive you may carry a BRCA mutation, but being aware of it and having the knowledge means you are at such an advantage compared to the generations before you, she says. Im lucky in that I have the chance now to take the preventative measures, and hopefully stay cancer-free.

Also, there are a few Facebook groups which are nice to be a part of, but predominately Ive found conferences such as the Marie Keating Foundations annual BRCA mutation conference and the BRCALink NI conference to be excellent events for learning about the most recent research in the field. Its also a great place to meet other people in similar circumstances.

The Marie Keating Foundation had planned to host its third annual BRCA Conference for men, women and their families that have tested positive for a BRCA gene mutation on April 24th in the Red Cow Moran Hotel in Dublin. It will now take place via webinar. Full details and registration is available at mariekeating.ie/events.

BRCA1 and BRCA2 are human genes which produce tumour suppressor proteins. These proteins help repair damaged DNA and, therefore, play a role in ensuring the stability of each cells genetic material. When this gene is mutated, these proteins are not produced properly and, as a result, cells are more likely to develop additional genetic alterations which can lead to cancer.

Both BRCA 1 and BRCA 2 gene mutation increase the carriers likelihood of developing cancer during their lifetime.

Female BRCA1 carriers have a 70 to 85 per cent risk of developing breast cancer during their lifetime, and a 40 to 50 per cent lifetime risk of ovarian cancer.

Males with BRCA1 mutation also have a slightly increased risk of breast cancer.

Female BRCA2 carriers have a 50 to 80 per cent risk of developing breast cancer during their lifetime and a 10 to 40 per cent lifetime risk of ovarian cancer.

Specific inherited mutations in BRCA1 and BRCA2 most notably increase the risk of female breast and ovarian cancers. People who have inherited mutations in BRCA1 and BRCA2 tend to develop breast and ovarian cancers at younger ages than people who do not have these mutations.

Men with BRCA2 mutations, and to a lesser extent BRCA1 mutations, are at increased risk of breast cancer and prostate cancer.

Due to a lack of data on BRCA-mutation carriers in Ireland, there are no comprehensive numbers for precisely how many people are BRCA positive in Ireland.

All women known to carry a BRCA1 or BRCA2 mutation are offered annual breast screening from age 30. Women age 30 are screened with annual MRI and, after the age of 40, digital mammogram is also performed. When a woman reaches 50 years, the radiologist will decide whether it is necessary to continue with MRI in addition to annual mammograms.

Three public hospitals offer genetics services to people considering BRCA testing in Ireland. The majority of genetic screening is carried out in the department of clinical genetics in Crumlin and St Jamess hospital Dublin.

Link:
BRCA1: Im lucky that I have the chance to take preventative measures - The Irish Times

PROVIDENCE, R.I. [Brown University] As novel coronavirus continues its sweep across the globe, among the most confounding aspects of the disease, COVID-19, and the causal virus, SARS-CoV-2, has been why symptoms are so severe for some patients yet milder for many others. Undoubtedly, age and underlying health conditions play a role but they dont account for fatalities among younger, otherwise healthy patients.

Physicians and scientists continue to publish data on cases, and one trend evident is that COVID-19 severity and fatalities tend to be greater among men than women. In one recent analysis of 13 U.S. states that report numbers of deaths among men and women, men died more frequently in every case.

In a letter to the editor in the journal Dermatologic Therapy, Dr. Carlos Wambier an assistant professor of dermatology and clinician educator at Brown Universitys Warren Alpert Medical School and a team of researchers from New York University, Applied Biology, Inc., and universities in Spain, India and Italy lay the groundwork for a hypothesis: the same male hormones that cause hair loss are linked to the vulnerability of patients to SARS-CoV-2.

While more research is needed to test that hypothesis, Wambier says a link between androgen hormones and COVID-19 could help to explain the higher severity for men and have implications for how health care providers test and treat patients. In the following Q&A, he shares more about the journal letter titled What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy and what it might mean, if confirmed, for both patients and physicians.

The main insight is that excess activation of androgens essentially, hormones that regulate what we think of as male characteristics is intrinsically linked to the vulnerability of patients to SARS-CoV-2. This is because the first step to the viruss entry into a cell is a bite from a protease enzyme that is produced only by action of androgen hormones. The infection by SARS-CoV-2 seems to be mediated by androgens.

From a dermatological point of view, androgen receptors, which bind to DNA, have genetic variations that predispose individuals to hyperandrogenic features the receptor binds with more affinity to the male hormones. These hyperactive polymorphisms are very common and cause features such as scalp hair loss (androgenetic alopecia). Other clinical signs of excess male hormone activity include high density of facial or chest hair, acne and oily skin. It is intuitive to think that if the androgen receptor is hyperactive in an individual, that person will have more of a protease called TMPRSS2 in their cell surface, too and weve seen in early studies in the wake of novel coronavirus that TMPRSS2 is key to SARS-CoV-2 infection.

In other words, the scientific evidence gives us reason to believe that beardy, bald men may be more vulnerable to COVID-19 than other individuals.

Exactly. We currently know that men have more severe COVID-19 disease and a higher rate of fatality compared to women, and we also know that children under age 10 seem extremely resistant.

Before age 10, in normal conditions, neither girls or boys have increased androgens. The first androgens start to appear during a period called adrenarche, around age 8, but those androgens produced by the adrenal glands are not very potent. After age 10 comes puberty, and androgens rise, produced by the gonads increasing hair density in some areas, as well as oily scalp and acne. The peak of androgen production is in adult life, and they drop a little in the elderly. After menopause, women start to overexpress androgens, because of the huge drop of estrogen (female hormone), and there is an increase in facial hair and also a decrease in scalp hair density.

Taken together, this could help to explain why were seeing more severe and fatal COVID-19 cases in men, with a lower rate for women and very few for young children.

Q: What are the key pieces of evidence that point to the potential implication of androgens in the severity of COVID-19 cases?

In the journal article, we link two well-known scientific facts. First, that SARS-CoV-2 needs its spikes to be primed by the TMPRSS2 protease. Second, that the TMPRSS2 gene has only one known gene promoter, which is the androgen receptor. The gene requires androgen hormones to bind to the androgen receptor, so the cell can initiate the transcription of TMPRSS2 gene to produce the protease a cell-surface protein that eats other proteins. Without this protease, host cells are not infected with SARS-CoV-2 because the virus spikes cannot bind to ACE2, a receptor implicated in COVID-19 and severe acute respiratory syndrome. The protease eats the spikes so they can connect to the ACE2. So more androgen activity means more proteases, which we think leads to more severe infection.

Yes. Benign prostate enlargement is caused by a very potent androgen hormone, called DHT. This is the most potent natural androgen and it binds with great affinity to the androgen receptor making it express proteins like TMPRSS2, which has been studied for decades in prostate health and prostate cancer research and is now known to open the door to novel coronavirus.

Women also produce DHT and testosterone, though at much lower levels than men. However, due to ovary diseases such as PCOS or ovary adenomas, women can produce very high levels of male hormones. We know PCOS is related to obesity and diabetes, so women with these conditions and post-menopausal women are likely more susceptible to severe infections, following the androgen vulnerability rationale.

Im an expert in hair biology. I like to see hair growing in the scalp of my patients it is fun and gratifying. My colleague and co-author, Dr. Andy Goren, is a respected scholar in hair and Minoxidil research, and we often discuss insights and new therapy for hair growth and also diagnostic tools. In recent months, weve explored hair genetics and polymorphisms of androgen receptors and binding sites.

Then, the pandemic came, priorities changed and instead of doing cosmetic dermatology procedures, I felt the need to contribute however possible in protecting the lives of the health care professionals, soldiers, police officers and others who could be affected by COVID-19. Dr. Goren and I started to share ideas about targeting the coronavirus, and since we already knew a lot about TMPRSS2 expression, we began to research other mechanisms to explain male vulnerability, including changes in pulmonary surfactant proteins (which protect against influenza) and lung cells due to male hormones. We reviewed much of the early research on COVID-19 and our journal piece synthesizes our ideas with what we learned from SARS-CoV-2 studies into the hypothesis we present.

Im also part of a research team that will conduct a clinical trial for COVID-19 prophylaxis among volunteer health care workers in Rhode Island, where I am researching population vulnerability, with phenotype and genotype characteristics.

With a new target for therapy, clinical trials could be a next step several classes of anti-androgen drugs could hold promise for decreasing the severity of COVID-19. If confirmed, vulnerable subjects like men and women with androgenetic alopecia may be able to start prophylaxis or at least avoid risk environments for COVID-19, such as working in emergency departments or intensive care units for COVID-19 patients.

In the same way the U.S. Centers for Disease Control and Prevention recommended avoiding corticosteroids in COVID-19 patients, it might be important to avoid androgen hormones during the pandemic, particularly for police officers, health care workers and members of the military. Theres a link in that some corticosteroids also bind to androgen receptors. In addition, women who use progestogens for birth control that increase androgen activity (those that can cause acne or increased facial hair), might also consider contraceptive progestogens with anti-androgen activity.

To test this hypothesis, it would be informative to study the epidemiology of COVID-19 patients who are predisposed to either lower or higher androgen receptor expression, such as males with androgenetic alopecia or benign prostatic hyperplasia or women with PCOS. One of my hopes is that researchers publishing information about COVID-19 cases and cohorts can add precise data on male and female patients that had severe disease or fatal outcomes. For new research, it will also be important to evaluate signs of excess male hormones oily skin/hair, acne, facial hair and particularly scalp hair thinning or alopecia.

In addition, our research team is considering studying polymorphisms of androgen receptor in patients that presented mild vs. severe COVID-19 disease. As a plan for that research formalizes, well ultimately be looking for individuals diagnosed with COVID-19 who are willing to participate in clinical study.

Read more from the original source:
Conversations on COVID: Exploring genetic links to COVID-19 severity - Mirage News

B-roll for media use:

Carnivore keepers at the Smithsonian Conservation Biology Institute (SCBI) in Front Royal, Virginia, are about to welcome a litter of chirping cheetah cubs. Five-year-old female Echo is having contractions and birthed one cub already shortly after 11 a.m., which can be viewed via the Cheetah Cam. They were sired by 4-year-old Scott. Animal care staff will leave Echo to bond with and care for her cubs without interference, so it may be some time before they can determine the cubs sexes.

Staff are closely monitoring Echo and her cubs behaviors via webcam, which is now live on the Zoos website. Virtual visitors can observe Echo and her cubs on this temporary platform until the cubs leave the den. Keepers provided Echo with access to multiple dens, so it is possible she may move the cubs to an off-camera location. An Animal Cam Educational Packet is available to parents and educators looking for student and child home activities.

Its thrilling and humbling to witness something as special as an animal birth, said Steve Monfort, John and Adrienne Mars Director of the Smithsonians National Zoo and Conservation Biology Institute. Im eager to watch the newborn cubs in their early days. During this extremely tumultuous and isolating time, we want the new cheetah cam and all our live animal webcams to provide much needed moments of relief and inspiration from our natural world.

SCBI is part of the Cheetah Breeding Center Coalitiona group of 10 cheetah breeding centers across the United States that aim to create and maintain a sustainable North American cheetah population under human care. These cubs are a significant addition to the Association of Zoos and Aquariums Species Survival Plan (SSP) for Cheetahs, as each individual contributes to this program.

This was Echos first pregnancy, but were confident in her maternal instincts and abilities, said Adrienne Crosier, cheetah reproductive biologist at SCBI and head of the Cheetah SSP. She was raised by her own mother without human intervention, so theres a good chance Echo has learned cheetah parenting behaviors from the best teacherher mother.

The SSP scientists determine which animals to breed by considering their genetic makeup, health and temperament, among other factors. Echo and Scott were paired and bred Jan. 4 and 5. In February, keepers trained Echo to voluntarily participate in ultrasounds. SCBI veterinarians confirmed her pregnancy Feb. 26. Since 2007, 14 litters of cheetah cubs have been born at SCBI.

Cheetahs live in small, isolated populations mostly in sub-Saharan Africa. Many of their strongholds are in eastern and southern African parks. Due to human conflict, poaching and habitat and prey-base loss, there are only an estimated 7,500 to 10,000 cheetahs left in the wild. TheInternational Union for Conservation of Natureconsiders cheetahs vulnerable to extinction.

As a public health precaution due to COVID-19, the Smithsonians National Zoo and Conservation Biology Institute is temporarily closed to the public.Animal keepers and veterinary staff remain working on site at the Zoo and SCBI to provide the usual highest quality care for the animals.Additional information on the Zoos COVID-19 response is posted to the Zoos website. During the closure, the Zoo is sharing animal updates from behind the scenes using the hashtag #NatZooZen on Facebook, Instagram and Twitter.

The Zoos legacy of conservation work extends beyond the public Zoo in Washington, D.C., to SCBI in Front Royal, Virginia. Scientists at SCBI study and breed more than 20 species, including some that were once extinct in the wild, such as black-footed ferrets and scimitar-horned oryx. Animals thrive in specialized barns and building complexes spread over more than 3,200 acres. The sprawling environment allows for unique studies that contribute to the survival of threatened, difficult-to-breed species with distinct needs, especially those requiring large areas, natural group sizes and minimal public disturbance.

SCBI spearheads research programs at its headquarters in Virginia, the Zoo in Washington, D.C., and at field research stations and training sites worldwide. SCBI scientists tackle some of todays most complex conservation challenges by applying and sharing what they learn about animal behavior and reproduction, ecology, genetics, migration and conservation sustainability.

# # #

Photo Credit: Smithsonian Conservation Biology Institute

More here:
Cheetah Cubs Born at the Smithsonian Conservation Biology Institute - Smithsonian's National Zoo and Conservation Biology Institute

Data: More men die of COVID-19 than women

An infectious disease expert says factors like men having more underlying health conditions than women are reasons why there is a disparity between male and female fatality rates with COVID-19.

BERKELEY, Calif. - New questions are emerging as the coronavirus continues to take livesand data in multiple parts of the worldshow that men withCOVID-19 have a higher fatality rate than women.

Inthe San Francisco Bay Area, SantaClaraCountyreported 1,224 confirmed cases Monday with a gender breakdown of52% menand48% women.The gender of those who died from COVID-19, however, show67%of the deathsin the countyare men.

A preliminary study fromChinaalso shows more malethan femalepatients dying fromCOVID-19and aWorld Health Organization Chartfor Italyand Spainhas a higher rate of death for men fromCOVID-19.

"There are several factors that contribute to this gender difference," saidDr. Lee Riley, a University of California atBerkeley professorand head of the division of Infectious Disease and Vaccinology at the school of Public Health.

Behavior could be one big factor, with men tending to smoke and drink alcohol more than women.

"That can contribute to different type of cardiovascular diseases and cardiovascular diseases themselves are also associated with bad outcomes in coronavirus infection," Riley said.

Santa Clara County statistics for 2014 show the ratio of smoking rates for men and women in the county are similar to the coronavirus fatality ratio.

Riley saidstudies show men also tend to wait longer than women to visit doctors.

"So by the time they get to a doctor, they may have more severe disease," said Dr. Riley.

Riley said there is researchthat indicates genetics might give women's immune systems an advantage,with twoX chromosomes.

"In the X chromosome there are a couple genes that are involved in the immune response whereas the males there's only one," he said.

Researchers sayCOVID-19 is not the only respiratory disease that shows a gender difference.

"The SARS epidemic we saw 17 years ago, again, there was a male predominance in deaths," Riley said."Tuberculosis is another major respiratory infectious disease and we see a ratio of 70 to 30, the disease being much more common in males."

Riley said as researchers look for vaccines and cures, it is important to collect and analyze data for genderand alsoanalyzedifferences in race and ethnicity.

"This particular coronavirus infection is greater among African Americans and people of ethnic minority backgrounds so those type of data are very important," Riley said.

InIllinois, health officials sayAfricanAmericans account for 30%of all coronavirus casesand inChicago,nearly 70%of the deaths are amongAfricanAmericans.MayorLoriLightfoot says the numbers highlight a longstanding disparity in health care access that needs to be addressed.Many of the victims haveother underlying health conditions.

Lousiana Governor John Bel Edwards announced that about 70% of the deaths in his state are African Americans and mentioned that hypertension was one of the factors in the deaths.

On Monday, theLawyersCommittee forCivilRightsUnder Law sent a letter toHealth and Human Services SecretaryAlex Azar.The letter calls forthe government to releasemore datato the public on the race and ethnicityof people with COVID-19.

Jana Katsuyama is a reporter forKTVU. Email Jana atjana.katsuyama@foxtv.comand follow her on Twitter@JanaKTVU

View original post here:
Data: More men die of COVID-19 than women - KTVU San Francisco

Sam Williams Macaw Recovery Network in Costa Rica rewilds captivity-hatched fledgling scarlet and great green macaws. But introducing young birds into a complex forest world bereft of the cultural education normally provided by parents is slow and risky.

For 30 years or so scientists have referred to the diversity of life on Earth as biological diversity, or just biodiversity. They usually define biodiversity as operating at three levels: the diversity of genes within any particular species; the diversity of species in a given place; and the diversity of habitat types such as forests, coral reefs, and so on. But does that cover it? Not really. A fourth level has been almost entirely overlooked: cultural diversity.

Culture is knowledge and skills that flow socially from individual to individual and generation to generation. Its not in genes. Socially learned skills, traditions and dialects that answer the question of how we live here are crucial to helping many populations survive or recover. Crucially, culturally learned skills vary from place to place. In the human family many cultures, underappreciated, have been lost. Culture in the other-than-human world has been almost entirely missed.

We are just recognising that in many species, survival skills must be learned from elders who learned from their elders. Until now, culture has remained a largely hidden, unrecognised layer of wild lives. Yet for many species culture is both crucial and fragile. Long before a population declines to numbers low enough to seem threatened with extinction, their special cultural knowledge, earned and passed down over long generations, begins disappearing. Recovery of lost populations then becomes much more difficult than bringing in a few individuals and turning them loose.

Many young birds learn much by observing their parents, and parrots probably need to learn more than most. Survival of released individuals is severely undermined if there are no free-living elder role models. Trying to restore parrot populations by captive breeding is not as easy as training young or orphaned creatures to recognise what is food while theyre in the safety of a cage then simply opening the door. In a cage, Williams says, you cant train them to know where, when and how to find that food, or about trees with good nest sites. Parents would normally have done exactly that.

A generational break in cultural traditions hampered attempts to reintroduce thick-billed parrots to parts of south-west America, where theyd been wiped out. Conservation workers could not teach the captive-raised parrots to search for and find their traditional wild foods, skills they would have learned from parents.

Landscapes, always complex, are under accelerated change. Culture enables adaptation far faster than genes alone can navigate hairpin turns in time. In some places, pigeons and sparrows have learned to use motion-sensors to get inside enclosed shopping malls and forage for crumbs. Crows have in some locales learned to drop nuts on the road for cars to crack. In at least one area they do this at intersections, so they can safely walk out and collect their cracked prizes when the light turns red and the cars stop. Theyve developed answers to the new question: How can we survive here, in this never-before world?

Because the answers are local, and learned from elders, wild cultures can be lost faster than genetic diversity. When populations plummet, traditions that helped animals survive and adapt to a place begin to vanish.

In a scientific article on the vocabulary of larks living in north Africa and Spain titled, Erosion of animal cultures in fragmented landscapes, researchers reported that as human development shrinks habitats into patches, isolation is associated with impoverishment. They write: Song repertoires pass through a cultural bottleneck and significantly decline in variety.

Unfortunately, isolated larks are not an isolated case. Researchers studying South Americas orange-billed sparrow found that sparrow song complexity the number of syllables per song and song length deteriorated as humans continued whittling their forests into fragments. When a scientist replayed 24-year-old recordings of singing male white-crowned sparrows at the same location shed recorded them, they elicited half the responses they had when first recorded. The birds responses show that changes in the dialect lead to changes in listener preference, a bit analogous to pop music. And as with humans, preferences can affect whether a particular bird will be accepted as a mate. White-crowned sparrows singing a local dialect become fathers of more offspring than do singers of unfamiliar dialects, indicating females prefer a familiar tune.

Im not just talking about a few songs. Survival of numerous species depends on cultural adaptation. How many? Were just beginning to ask such questions. But the preliminary answers indicate surprising and widespread ways that animals survive by cultural learning. Regionally different vocalisations are sometimes called song traditions but the more commonly used word is dialects. More than a hundred studies have been published on dialects in birds. And its not just birds but a wide array of animals Including some fish.

Cod particularly, said Steve Simpson of the University of Exeter, have very elaborate calls compared with many fish. You can easily hear differences in recorded calls of American and European Atlantic cod. This species is highly vocal with traditional breeding grounds established over hundreds or even thousands of years. Many fish follow elders to feeding, resting and breeding areas. In experiments, introduced outsiders who learned such preferred locales by following elders continued to use these traditional routes after all the original fish from whom they learned were gone.

Cultural survival skills erode as habitats shrink. Maintaining genetic diversity is not enough. Weve become accustomed to a perilous satisfaction with precariously minimal populations that not only risk genetic viability of populations but almost guarantee losing local cultural knowledge by which populations have lived and survived.

In all free-living parrots that have been studied, nestlings develop individually unique calls, learned from their parents. Researchers have described this as an intriguing parallel with human parents naming infants. Indeed, these vocal identities help individuals distinguish neighbours, mates, sexes and individuals; the same functions that human names serve.

Williams tells me that when he studied Amazon parrots, he could hear differences between them saying, essentially, Lets go, Im here, where are you? and Darling, I just brought breakfast. Researchers who develop really good ears for parrot vocalisation and use technology to study recordings show that parrot noise is more organised and meaningful than it sounds to beginners like me. In a study of budgerigars, for instance, birds who were unfamiliar with each other were placed together. Groups of unfamiliar females took a few weeks for their calls to converge and sound similar. Males copied the calls of females. Black-capped chickadees flock members calls converge, so they can distinguish members of their own flock from those of other flocks. The fact that this happens, and that it takes weeks, suggests that free-living groups must normally be stable, that groups have their own identity, and that the members identify with their group.

Group identity, we see repeatedly, is not exclusively human. Sperm whales learn and announce their group identity. Young fruit bats learn the dialects of the crowds theyre in. Ravens know whos in, whos out. Too many animals to list know what group, troop, family or pack they belong with. In Brazil, some dolphins drive fish toward fishermens nets for a share of the catch. Other dolphins dont. The ones who do, sound different from the ones who dont. Various dolphin groups who specialise in a food-getting technique wont socialise with other groups who use different techniques. And orca whales, the most socially complex non-humans, have layered societies of pods, clans and communities, with community members all knowing the members of all their constituent pods, but each community scrupulously avoiding contact with members of another community. All this social organisation is learned from elders.

Elders appear important for social learning of migratory routes. Various storks, vultures, eagles and hawks all depend on following the cues of elders to locate strategic migration flyways or important stopover sites. These could be called their migration cultures. Famously, conservationists have raised young cranes, geese and swans to follow microlight aircraft as a surrogate parent on first migrations. Without such enculturation, they would not have known where to go. The young birds absorbed knowledge of routes, then used them in later seasons on their own self-guided migrations. Four thousand species of birds migrate, so Andrew Whiten of the University of St Andrews in Scotland speculates that following experienced birds may be an underappreciated but very significant realm of cultural transmission.

When you look at free-living animals, you dont usually see culture. Culture makes itself visible when it gets disrupted. Then we see that the road back to reestablishing cultures the answers to the questions of how we live in this place is difficult, often fatal.

Young mammals too moose, bison, deer, antelope, wild sheep, ibex and many others learn crucial migration routes and destinations from elder keepers of traditional knowledge. Conservationists have recently reintroduced large mammals in a few areas where theyve been wiped out, but because animals released into unfamiliar landscapes dont know where food is, where dangers lurk, or where to go in changing seasons, many translocations have failed.

Williams describes his procedure with the macaws as very much a slow release. First his team trains the birds to use a feeder. With that safety net, they can explore the forest, gain local knowledge, begin dispersing and using wild foods.

Some rescue programmes declare success if a released animal survives one year. A year is meaningless for a bird like a macaw that doesnt mature until its eight years old, says Williams.

I ask what theyre doing for those eight long years.

Social learning, Williams replies immediately. Working out whos who, how to interact, like kids in school.

To gain access to the future, to mate and to raise young, the birds Williams is releasing must enter into the culture of their kind. But from whom will they learn, if no one is out there? At the very least they must be socially oriented to one another. Ex-pets are the worst candidates for release; they dont interact appropriately with other macaws, and they want to hang around near humans.

To assess the social abilities of 13 scarlet macaws who were scheduled for release, Williams and his crew documented how much time they spent close to another bird, how often they initiated aggression, things like that. When the bird scoring lowest for social skills was released, he flew out the door and was never seen again. The next-to-lowest didnt adapt to the free-living life and had to be retrieved. The third-lowest social scorer remained at liberty but stayed alone a lot. The rest did well.

All of the above adds up to this: a species isnt just one big jar of jellybeans of the same colour. Its different smaller jars with differing hues in different places. From region to region, genetics can vary. And cultural traditions can differ. Different populations might use different tools, different migration routes, different ways of calling, courting and being understood. All populations have their answers to the question of how to live where they live.

Sometimes a group will be foraging in a tree, Williams says. A pair will fly overhead on a straight path. Someone will make a contact call, and the flying birds will loop around and land with the callers. They seem to have their friends. Bottom line, said Williams, there is much going on in the social and cultural lives of his macaws and other species, much that they understand but we dont. We have a lot of questions. The answers must lurk, somewhere, in their minds.

As land, weather and climate change, some aspects of cultural knowledge will be the tickets necessary for boarding the future. Others will die out. Across the range of chimpanzees, cultures vary greatly, as do habitats. All populations but one use stick tools. Some use simple probes, others fashion multi-stick toolsets. Only one population makes pointed daggers for hunting small nocturnal primates called bush-babies hiding in tree holes. Only the westernmost chimpanzees crack nuts with stones.

As researchers have noted, distinctive tool-using traditions at particular sites are defining features of unique chimpanzee cultures. Whiten wrote: Chimpanzee communities resemble human cultures in possessing suites of local traditions that uniquely identify them A complex social inheritance system that complements the genetic picture.

Some chimpanzee populations have learned to track the progress of dozens of specific trees ripening in their dense forests. Others live in open semi-savannah. Some are more aggressively male-dominated, some populations more egalitarian. Some almost never see people; some live in sight of human settlements and have learned to crop-raid at night. For a long, long time chimpanzees have been works in progress. Weve learned, writes Craig Stanford, not to speak of The Chimpanzee. Chimpanzees vary and chimpanzee culture is variable at every level.

Its not just the loss of populations of chimps that worries me, Cat Hobaiter emphasised when I spent several weeks with her studying chimpanzees in Uganda. I find terrifying the possibility of losing each populations unique culture. Thats permanent.

Diversity in cultural pools perhaps more crucially than in gene pools will make species survival more likely. If pressures cause regional populations to blink out, a species odds of persisting dim.

Williams goal is to re-establish macaws where they range no longer, in hopes that they, and their forests, will recover. (Most of the central American forests that macaws need have been felled and burned, largely so fast-food burger chains can sell cheap beef.) It often takes a couple of generations for human immigrant families to learn how to function effectively in their new culture; it may take two or three generations before an introduced population of macaws succeeds. In other words, macaws are born to be wild. But becoming wild requires an education.

So whats at stake is not just numbers. Whats at stake is: ways of knowing how to be in the world. Culture isnt just a boutique concern. Cultural knowledge is what allows many populations to survive. Keeping the knowledge of how to live in a habitat can be almost as important to the persistence of a species as keeping the habitat; both are needed. Cultural diversity itself is a source of resilience and adaptability to change. And change is accelerating.

This is an edited extract from Becoming Wild: How Animals Learn to be Animals by Carl Safina, which published in the UK by Oneworld on 9 April and in the US by Henry Holt and Co on 14 April

More here:
The secret call of the wild: how animals teach each other to survive - The Guardian

IRVINE, Calif., April 1, 2020 /PRNewswire/ -- In a joint research effort studying the genetics of the androgen receptor in androgenetic alopecia, scientists discover a possible genetic variation that pre-disposes COVID-19 patients to develop severe symptoms. The team led by Andy Goren, MD Chief Medical Officer at Applied Biology and Medical Advisor to the Department of Dermatology of the Alpert Medical School of Brown University, Carlos G. Wambier, MD, PhD Director of Cosmetic Research at the Department of Dermatology of the Alpert Medical School of Brown University and John McCoy, PhD Vice President of R&D at Applied Biology along with a team of collaborators from other institutions submitted their discovery to publication in the medical journal Dermatologic Therapy. The manuscript titled "WHAT DOES ANDROGENETIC ALOPECIA HAVE TO DO WITH COVID-19? AN INSIGHT INTO A POTENTIAL NEW THERAPY" (DOI: 10.1111/dth.13365) elucidates the possible role of androgens in controlling the infectiveness of SARS-CoV-2 in human lung cells. According to Dr. Wambier: "we believe that androgens are required for the expression of the serine protease TMPRSS2. This proteolytic priming of the spikes of the coronavirus is the first step required for binding to the ACE2 receptor in cells. Male hormones might also affect ACE2 receptor expression in lung cells. To the best of our knowledge these are required for the novel coronavirus to infect humans." According to Dr. Goren: "men and women are known to have different levels of androgens as well as androgen receptor expression patterns which may explain the differential mortality rate between the genders." The team is now exploring a diagnostic test to identify COVID-19 patients at high risk for developing severe symptoms or mortality. In addition, the group is embarking on a clinical study to explore the use of anti-androgen therapy in COVID-19 patients.

ABOUT APPLIED BIOLOGYFounded in 2002, Applied Biology, Inc. (www.appliedbiology.com), headquartered in Irvine, California, is a biotechnology company specializing in hair and skin science. Applied Biology develops breakthrough drugs and medical devices for the treatment of androgen mediated dermatological conditions. Applied Biology's R&D pipeline includes a topically applied prophylactic treatment for chemotherapy induced alopecia; a novel diagnostic device that can aid dermatologists in identifying non-responders to topical minoxidil; an adjuvant therapy for non-responders to topical minoxidil; and a novel therapy for female pattern hair loss.

Contact:Monica Naegle(949) 387-4526[emailprotected]www.appliedbiology.com

SOURCE Applied Biology, Inc.

http://www.appliedbiology.com

Read the original:
Applied Biology in Collaboration with Brown Researchers Announce the Discovery of a Possible Association Between the Genetic Cause of Hair Loss and...

1. Nettie Stevens (1861-1912, American) discovered that a fetuss sex is determined by chromosomes contributed by the parents during conception. Previously it was believed that the environmental factors during conception determined sex.

2. Charlotte Auerbach (1899-1994, German) has been called the mother of mutagenesis due to her discovery of genetic mutations caused by mustard gas. It only took her 2 months to discover these mutations in X chromosomes of males flies exposed to the gas. She received a Keith Prize in 1948.

3. Barbara McClintock (1902-1992, American) is known for her groundbreaking discovery of mobile genetic elements at the young age of 29, one of the greatest experiments of modern biology. For this work she was awarded the Nobel Prize in Physiology and Medicine in 1983.

4. Salome Gluecksohn-Waelsch (1907-2007, German) co-founded the field of developmental genetics. She used mouse embryo to study the effects of naturally occurring genetic mutations and the t-complex, a group of genes that direct the development of mouse tails. For all of her work in developmental genetics she was awarded the National Medal of Science in 1993 when she was 85 and still hard at work.

5. Rosalind Franklin (1920-1958, British) contribute to the major discovery of discovering the structure of DNA. She found that DNA takes two forms A and B. It was a photo of form B, photo 51, that provided Watson and Crick the the information that DNA was a double helix structure. Franklin also made major contributions on the filtration properties of types of coal during World War II. Franklin hypothesized that Tobacco Mosaic Virus was a hollow tube made of proteins that contained a single strand of RNA that spiraled inside the length of the tube like a thread spiraling inside a donut hole. After her early death at 38 from ovarian cancer, this hypothesis was found correct.

6. Esther Lederberg (1922-2006, American) provided foundation for future research in genetic inheritance in bacteria, gene regulation, and genetic recombination. She co-invented a simple method, replica plating, to reproduce bacterial colonies in masses while maintaining the original geometry of the colonies.

Photo credits top to bottom:The Marine Biological Laboratory,Jewish Studies,Encyclopdia Britannica,Albert Einstein College of Medicine,Nukas,Estherlederberg.com

Continue reading here:
6 Women Who Impacted Genetics | My Gene Counsel - Post ...

Two years after Ebola ravaged parts of West Africa, the deadly virus in 2018 was making a comeback in the Democratic Republic of the Congo.

Researchers at the University of Texas Medical Branch in Galveston sprang into action, reverse engineering the construction of a new vaccine and delivering 7,500 doses of it to the central African country for widespread use, all within 72 hours.

It was, in the words of Ben Raimer, interim president of UTMB, a proud moment for the university system, a collaborative effort that yielded life-saving results. Raimer cautioned, however, against the unrealistic expecations the Ebola success may have created for university researchers now grappling with the nuances of the far more complex novel coronavirus.

Were not a 72-hour virus maker here at UTMB, Raimer said. Weve done it one time for Ebola, but its not likely for this virus until we get a better understanding on how it functions in its various forms.

Coronavirus updates: Stay informed with accurate reporting you can trust

Public health experts generally predict that a coronavirus vaccine will take much longer and wont be ready for at least 12 to 18 months from the first known infection in late December. Whilemore than 20 vaccine candidates are in development, most are in the early stages, well before clinical trials. Uncertainty over the timeline has led to an unquenchable thirst for any morsel of good news regarding progress researchers have made in understanding how the virus attacks humans.

Scott Weaver understands this reality better than most. As the director of UTMBs infectious disease research programs, Weaver is tasked with helping manage nearly two-dozen projects related to the coronavirus, from macro initiatives like vaccine and antiviral treatment to more nuanced efforts such as why the virus affects people who smoke or vape more acutely.

For now, vaccine development is moving at a slower pace than Ebola, Weaver said, though he is hopeful that a previously developed SARS vaccine will prove effective. That vaccine, developed by researchers at Baylor College of Medicine and UTMB researchers, effectively protected mice against SARS, or severe acute respiratory syndrome, the pneumonia-causing virus from the same family a coronavirus that spread in the early 2000s. The vaccine never progressed to human testing because manufacturing of it wasnt completed until 2016, long after SARS had burned out.

Weaver noted two key challenges to completing work on the SARS vaccine: the genetically-altered laboratory mice used to test this vaccine had to be recreated from scratch; and funding sources, particularly from commercial interests, are hard to come by.

UTMB has cleared one hurdle. The transgenic mice embryos used for the original vaccine were recently implanted into female and male mice, and the first offspring were born several weeks ago. Of course, even after these mice are used to test vaccine candidates, those vaccines will have to be tested on non-human primates before the FDA will consider permission for clinical trials in people.

But even if UTMB does not win the vaccine arms race, the universitys coronavirus research has already made a significant difference in understanding the viruss complexities.

We have here three virologist faculty scientists who focus their work on coronavirus, so we were well prepared to gear up very quickly to do research on this virus, Weaver said.

Indeed, at the outset of the viral outbreak, UTMB developed a reverse genetic system to manipulate the virus genome. The Galveston National Laboratory at UTMB, a high-security biocontainment lab, was one of three labs in the country to get the coronavirus isolate in February after the Centers for Disease Control worked on the first virus sample in Washington state and cultured it in Atlanta.

Pei-Yong Shi, a professor of human genetics at UTMB, led this effort, which allows scientists to essentially recreate the virus from scratch.

We can understand the mutations and history of the virus. We will be able to manipulate the virus, to understand which regions are causing the disease so we can make vaccines and therapeutics, Shi said.

The UTMB genetic system played a vital role in helping develop badly needed diagnostic tests. The universitys World Reference Center for Emerging Viruses and Arboviruses stockpiled the viral RNA the genetic material needed to optimize tests for federal approval.

There was a time period in late February where we were literally the only laboratory in the world providing these RNA samples for diagnostic (test) development, Weaver said. A lot of the big companies that you see now are starting to scale up diagnostics - like LabCorps and Quest and many of the big hospitals including some in Houston and here in Galveston - we provided that critical RNA to them so they could get their tests up and running as quick as possible.

One of the primary projects capturing the attention of UTMB scientists is testing antiviral drugs to treat the symptoms of the coronavirus, Weaver said. The drugs currently being tested were developed for other viral infections or non-infectious diseases, such as remdesivir, which was used to combat Ebola infections.

Both President Trump and the World Health Organization have highlighted remdesivir as a promising coronavirus treatment, though clinical trials are still ongoing to determine how effective the drug can be. UTMB has a clinical trial set up in the coming weeks to test remdesivir in Galveston County coronavirus patients.

Coronavirus in Houston: All of the latest news, numbers and analysis to keep you up-to-date, only on HoustonChronicle.com

In the middle of an outbreak like this, there are going to be so many people who are hospitalized and eligible for these clinical trials that well learn very quickly whether (remdesivir) has efficacy or not, Weaver said. I think thats really the best prospect for an improvement in patient care in the near future.

Tapping into funding sources to continue vaccine research is a bigger problem. One of the major differences between Ebola in 2018 and coronavirus that contributed to how quickly UTMB was able to develop a vaccine was the sustained funding for Ebola research. Besides the SARS outbreak in the early aughts and MERS in 2012, coronaviruses typically dont attract the same interest.

Its much harder to get funding, especially commercial interest, in the coronavirus vaccine, Weaver said. Unfortunately, that means we dont have as much to start from. There were some vaccines that were developed. They never went very far down the pipeline towards clinical trials, but at least were not starting completely from scratch.

But for as much work is being done behind the scenes in the race to cure and treat the coronavirus, Weaver said the immediate outcome and toll of this pandemic will be determined by public health measures such as social distancing.

One person on average transmits the virus to 3 or 4 additional people and if one of those is a high-risk person, they may die, if one of those is a healthcare worker, they may spread it to many more people, Weaver said. I just hope that everyone takes this very seriously.

nick.powell@chron.com

Go here to read the rest:
UTMB once helped defeat Ebola. Can it replicate that success with coronavirus? - Houston Chronicle

The illegal killing of this rare species of giraffe and her calf leaves a lone surviving male in the entire world. The death of the white giraffe, whos alabaster color is caused by leucism, a condition that only produces dark pigments on soft tissues, has left the community of Ijara, Kenya saddened.

Not only is this a long-term loss of research industries, but tourism will also take a hit.

This is a very sad day for the community of Ijara and Kenya as a whole, Mohammand Ahmednoor, manager of the Ishaqbini Hirola Community Conservancy, said. We are the only community in the world who are custodians of the white giraffe.Its killing is a blow to tremendous steps taken by the community to conserve rare and unique species, and a wake-up call for continued support to conservation efforts.

The Ishaqbini Hirola Community Conservancy where the giraffes lived is located in a vast, non fenced-in area within two villages.

The Hirola Conservation Program was formed to support conservation efforts and continued research of the giraffes after the female white giraffe was first spotted in the conservancy in 2017. But the female giraffe was first discovered in Kenya in March 2016 in Tanzania at the Tarangire National Park. She recently gave birth to two calves in August 2019.

While the poachers have yet to be identified, the Kenya Wildlife Society is investigating the killings.

Today, the female giraffes surviving male calf is the only remaining white giraffe in the world and, according to the Giraffe Conservation Foundation, the total population of giraffes living in Africa has decreased by 30% since their count in 1980s with an even more dramatic drop on other areas of the world.

This is a long-term loss given that genetics studies and research which were significant investment into the area by researchers has now gone to the drain, Ahmednoor said. Further to this the white giraffe was a big boost to tourism in the area.

FALL FUNDRAISER

If you liked this article, please donate $5 to keep NationofChange online through November.

See the article here:
Unique female white giraffe and calf killed at hands of illegal poachers in Kenya - NationofChange