More and more threatened species are relying on captive breeding to avoid extinction. Some species on the brink only exist in captivity, and others depend on captive breeding for their recovery before theyre released to the wild.

Captive breeding programs face major challenges to achieve the best conservation outcomes, particularly high economic costs, and loss of vital genetic diversity from wild populations after even a few generations in captivity.

Our economic and genetic modelling published today shows how freezing genetic material and using assisted reproduction could provide a much-needed support-tool for captive breeding programs, solving genetic and economic issues and allowing zoos to breed more species and expand their valuable work.

These are the same tools and technologies commonly used in animal agriculture, research, medicine and disease and human fertility to boost production, lower costs, and produce healthy and strong humans and animals.

No-one should doubt the value of captive breeding to conservation. The European bison, California condor and Australias Southern Corrobboree Frog are three iconic species which would be extinct without captive breeding. Iconic Australian species the Orange-bellied Parrot and greater bilby have been captive bred for over 30 years.

Captive breeding is expensive in resources, labour and capital. Programs have high start-up costs, in the hundreds of thousands or even millions of dollars. High annual on-going costs, on average, are over $200,000 per year for a single species. Many programs are open-ended and will be required for many years or even decades if they are to achieve their objectives.

The high costs of current programs prevent conservationists from assisting many species that desperately need captive breeding. Amphibians are a case in point. Disease and habitat loss is decimating wild amphibian populations globally. There are now over 900 amphibian species which need captive populations. Over 200 of these species need it urgently to avoid extinction. Despite hundreds of species in need, the estimated global capacity and available resources can provide captive populations for no more than 50 amphibian species.

Read more: Swingers' hookup program can find the right match for endangered species

The costs are one thing, the genetics are something else. Captive breeding programs face significant challenges with genetic diversity. These are common even in some of the longest running and well-resourced captive breeding programs, such as giant pandas and Tasmanian devils.

Genes are lost after even one generation of captive breeding, and in just a few generations, animals most likely to thrive and breed in captivity show traits of domestication and adaptation to captivity. Inbreeding depression is unavoidable in small captive colonies typical of some captive programs. The loss of wild genes affects the overall fitness of captive bred animals for release back to the wild.

To counter the loss of genes in captive populations, the common global target for captive programs is to maintain 90% of the original captive populations genetic diversity for one hundred years. This is considered gold standard practice and aims to ensure reintroductions of animals into the wild long in the future will occur using animals with minimal genetic issues.

This target is unachievable in most programs because it is not feasible to keep colonies large enough to reduce inbreeding rates to the level required. But using biobanking and existing or developing assisted reproductive technologies could solve genetic and cost issues and finally make this target achievable.

Biobanking is the frozen storage of various living cells from threatened species, particularly sex cells, including sperm, eggs and embryos. Frozen samples can be kept long-term as insurance against extinction or thawed for use in conservation genetic management.

Read more: Tasmanian devils reared in captivity show they can thrive in the wild

Biobanking is not uncommon. Large commercial biomedical biobanks routinely store cell lines for cancer and other medical research. Biobanking is used extensively to store seeds of crops and threatened plants and in animal agriculture to store rare or valuable breeds of livestock animals.

Biobanks exist for conservation also, for example the Frozen Zoo in San Diego, the UKs Frozen Ark and the Australian Frozen Zoo store frozen samples of some of the worlds most threatened species. Biobanking is helping save the black-footed ferret from extinction after the last remaining ferrets (less than twenty) were brought into a captive breeding program in the 1980s and supplemented with frozen sperm after many years to add back lost genes.

Using real data on the economic costs of captive breeding, we generated models for the threatened Oregon spotted frog (Rana pretiosa), a native of Canada and North America, which predict program costs and rates of genetic diversity loss for captive populations of any size. We then calculated how these costs change, and inbreeding rates reduce, when genes are added back into captive populations each generation using cryopreserved sperm. These models will work on any species where costs of captive breeding are available.

Read more: Personality matters: when saving animals, fortune favours the bold

The results for the Oregon spotted frog model were startling. Biobanking dramatically slowed the rate of inbreeding and required far fewer live frogs to be held. Under normal captive breeding conditions, over 1,800 live frogs were required to meet the genetic target. By using biobanking, this number was reduced to 58 live frogs.

The estimated cost savings and the improved genetic fitness for the Oregon spotted frog were profound. The conventional captive population required to meet the genetic target of 90% genetic diversity would cost over $2.8 million to set up, followed by $537 million in a total 100-year program. The biobanked population would cost $121,000 to set up, followed by total costs of only around $20 million over the same period. This represents a 26-fold reduction in overall costs from normal captive breeding to the biobanking approach.

Investment in the biobanking approach could allow captive breeding institutions to maintain animals that are fitter and more like those from wild populations. Captive breeding programs could meet genetic targets which have never been achieved and produce animals more suited for release to the wild.

The drastically reduced costs would allow institutions to hold many more species. With investment in research on the underlying technologies, the approach would not be limited to amphibians and could work in any species. Building in biobanking could usher in a new era of captive breeding for a much greater number of species in desperate need.

Read more: Zoos aren't Victorian-era throwbacks: they're important in saving species

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Human reproductive technologies like sperm freezing and IVF could be used to save threatened species - The Conversation AU

CLAIMVaccine hesitancy and anti-vaccine claims are surging across the world, even as we get closer to having a COVID-19 vaccine ready. This has also affected one of the prime vaccine candidates we have right now, Pfizer, which has also applied for emergency authorization in India. Pfizer-BionTechs novel COVID-19 vaccine, BNT-162, which is one of the most promising vaccines approved for selective use right now has, too, been subjected to criticism and false claims, despite its strong safety and efficacy reports.

According to reports surfacing on social media pages, some users suggest that Pfizers vaccine could be bad for women of reproductive age.

The growing claims are raising concerns on the public level, as authorities draw up lists to inoculate the first doses amongst healthcare workers, senior citizens and hospital staff in the coming week.

A viral report, which cites Pfizers head of research suggests people to not take the vaccine jab, as it can cause female sterilization.

The social media post, which has been widely shared and circulated also offers a sort of explainer, adding that the vaccine works to deliver a robust immune response against a spike protein, 'synctin-1', which is vital for placental formation and once the vaccine is administered, it could cause sterilization and problems related to infertility.

The post reads:

"The vaccine contains a spike protein (see image) called syncytin-1, vital for the formation of human placenta in women. If the vaccine works so that we form an immune response AGAINST the spike protein, we are also training the female body to attack syncytin-1, which could lead to infertility in women of an unspecified duration."

The claim is similar to the one which suggested that the Oxford-Astrazeneca shot may be bad for males, and contains parts of human aborted fetus.

Related posts also suggests that some of the leading scientists and ex-heads of Pfizer have urged the medical community to draw COVID vaccination studies to an end because of significant safety concerns and threats to reproduction

TRUTHEven though the vaccine studies being conducted right now are happening in an accelerated, unprecedented manner, Pfizers vaccine jab is one of the earliest shots in the offering right now which carries a strong 94% efficacy rate.

Pfizer's vaccine, which is wrapping up phase III trials makes use of a novel mRNA approach, which trains the immune system to 'recognize' an illness-causing strain or germ.

The vaccine, which has been widely tested on 30,000 + volunteers (both healthy and young) hasnt been observed to carry adverse reactions or side-effects which could impact its functioning.

Also, most trials are being regulated under the purview of the World Health Organisation (WHO) and subject to stringent norms. None of the trials differentiate between male and female volunteers. Hence, the odds of any vaccine being bad for just one sex would be a tall claim to make.

Secondly, as of right now, none of the volunteers who have spoken up about the vaccine trials have reported suffering from mysterious side-effects such as the one being reported on social media.

VERDICT

Original post:
Coronavirus fact-check: Can the Pfizer vaccine affect a woman's reproductive health? Myth debunked! - Times of India

A long-term study of macaques given mitochondrial replacement therapy (MRT) found that both treated individuals and their offspring were healthy and developed normally.

Researchers report, after a decade of careful monitoring, that the first primates born after treatment with a gene therapy designed to prevent inherited mitochondrial disease developed normally and that the treatment had no adverse health effects in either the treated individuals or their offspring.

The scientists say their results support the scientific basis for testing mitochondrial replacement therapy (MRT) in human clinical trials, with one important caveat; in the study the team found varying levels of carry-over maternal mitochondrial DNA (mtDNA) that had preferentially replicated and accumulated within some internal organs, although not enough to cause health effects.

Our data show that MRT is compatible with normal development, fertility and aging in nonhuman primates without any detected adverse effects, write the authors. However, carry-over maternal or paternal mtDNA contributions increased substantially in selected internal tissues/organs of some MRT animals, implying the possibility of mtDNA mutation recurrence.

The study was led by Dr Shoukhrat Mitalipov, director of the Oregon Health & Science University (OHSU) Center for Embryonic Cell and Gene Therapy, US.

Mitochondria control respiration and energy production within every cell of the body, so mitochondrial gene mutations contribute to a range of incurable and potentially fatal disorders affecting organs with high-energy demands such as the heart, muscle and brain. To prevent the transmission of pathogenic mtDNA from mother to offspring, scientists developed MRT a gene therapy in which mtDNA from a healthy donor is transferred in oocytes prior to fertilisation.

In the five rhesus macaques used in the study, the mtDNA was transferred in such a way that the donor mtDNA accounted for >97 percent of the total, maternal mtDNA was less than three percent and paternal mtDNA was <0.1 percent after birth.

According to the study, all five MRT macaques developed normally to adulthood and were unremarkable from control animals in both their general health and fertility. Additionally, their offspring also developed normally.

It is reassuring that the monkeys appear to be healthy and fertile through generations, said co-author Dr Paula Amato, professor of obstetrics and gynecology in the OHSU School of Medicine. It adds to a growing body of evidence that would support moving forward with clinical trials to prevent the transmission of mitochondrial disease.

This will not occur in the US, because of Congress using a budgetary rider to prevent the Food and Drug Administration (FDA) from providing oversight for such clinical trials. However, gene therapies are currently being evaluated in trials in the UK and Greece.

The question was always there about the long-term safety of this technique, Mitalipov said. We wanted to find out whether this procedure will somehow show negative effects later in life. We saw no adverse health effects across two generations.

The only concern highlighted in the study was that despite maternal mtDNA accounting for less than three percent of the total in blood, urine and skin cells samples after birth, when the internal tissues and organs of the animals were analysed after death, one individual had substantially increased levels of maternal mtDNA up to 16.6 percent in the small intestine. While this falls well below the level Mitalipov says would be considered disease-causing (60 percent), there is a possibility that such increases could result in disease recurrence.

Another curious finding of the study was that, although mtDNA is normally passed from mother to child, in two macaques up to 33 percent of the mtDNA in selected tissues was contributed by the paternal line. This is unusual, although not unprecedented, and Mitalipov said he is interested in learning more about why the minute level of mtDNA in sperm cells replicated exponentially as the cells divided and the embryos grew.

The study was published in the journalHuman Reproduction.

See more here:
Mitochondrial replacement therapy (MRT) shown to be safe in monkeys - Drug Target Review

Since the birth of the first test tube baby in the United Kingdom in 1978, more than eight million babies conceived through in vitro fertilizationfertilizing human eggs in a laboratory and then implanting them into a womans uterushave been born, the vast majority of them in Europe and North America. Between 1 and 2 percent of all children born in the United States each year are conceived through in vitro fertilization. For many couples who struggle to conceive naturally, IVF allows them to become parents in a way unimaginable only two generations ago.

Who could find fault with that?

In reality,the methods by which children are conceived through IVF can be problematic for anyone who believes that human life begins at conception and should occur through natural means. That is the teaching of the Catholic Church,which also teaches that the removal of the conception of a child from the sexual relationship between spouses is a problematic notion.Many other many religious traditions worldwide accept IVF technology, with varying definitions of what processes should be allowed.

Over the last four decades, bioethicists and church leaders have tried to reconcile church teaching on these issues with the fact that, for many couples, technological assistance is necessary to conceive. We are not anti-science, the church has argued, but we are against treatments and procedures that violate the dignity of human life and discard a central reason for marriage.

The church objects to IVF on two separate grounds, the first being that fertilizing an egg in a laboratory removes the conception of the child from the marriage act. In a 1998 article for the U.S. Conference of Catholic Bishops, Begotten Not Made: A Catholic View of Reproductive Technology, John Haas, then the president of the National Catholic Bioethics Center and a consultant to the N.C.C.B. Committee for Pro-Life Activities, stated the rationale behind this objection:

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The Vatican made a similar argument in a 1987 clarification issued by the Congregation for the Doctrine of the Faith and signed by Cardinal Joseph Ratzinger, then the prefect of the C.D.F., titled Donum Vitae (The Gift of Life). Implanting a fertilized egg into the uterus in the hopes of a pregnancy, the document stated, objectively effects an analogous separation between the goods and the meanings of marriage because it is seeking a procreation which is not the fruit of a specific act of conjugal union. In other words, sex between married persons is meant not just to be unitive, bonding the couple in love, but also procreative, meant for the conception of children. A parallel understanding of sexunderpins the churchs teaching in Humanae Vitae (On Human Life), the 1968 papal encyclical affirming the churchs ban on artificial birth control.

Donum Vitae further stated, citing Canon 1061 of the Catholic Churchs code of canon law, that fertilization is licitly sought when it is the result of a conjugal act which is per se suitable for the generation of children to which marriage is ordered by its nature and by which the spouses become one flesh. But from the moral point of view procreation is deprived of its proper perfection when it is not desired as the fruit of the conjugal act, that is to say of the specific act of the spouses union.

Similarly, a 2008 document from the C.D.F., Instruction Dignitas Personae on Certain Bioethical Questions, signed by its prefect at the time, Cardinal William Levada, argued that any medical techniques used for the treatment of infertility must respect three fundamental goods: a) the right to life and to physical integrity of every human being from conception to natural death; b) the unity of marriage, which means reciprocal respect for the right within marriage to become a father or mother only together with the other spouse; c) the specifically human values of sexuality which require that the procreation of a human person be brought about as the fruit of the conjugal act specific to the love between spouses.

Medical efforts that assist procreation, the document states, are not to be rejected on the grounds that they are artificial. As such, they bear witness to the possibilities of the art of medicine. But they must be given a moral evaluation in reference to the dignity of the human person, who is called to realize his vocation from God to the gift of love and the gift of life.

Dr. Haas noted that Donum Vitae was not meant to be seen as a negative reaction to the use of medical technology to assist couples trying to conceive; rather, it teaches that if a given medical intervention helps or assists the marriage act to achieve pregnancy, it may be considered moral; if the intervention replaces the marriage act in order to engender life, it is not moral. For example, the church accepts NaProTechnology, a form of natural family planning that incorporates scientific research and advanced medical techniques for predicting ovulation and levels of fertility, as a valid method for assisting couples trying to conceive.

Catholics in the pews have a reputation for being somewhat cavalier regarding the churchs teachings on human sexuality and reproduction. While the church obviously does not determine the morality of an action or trend by the percentage of Catholics who perform it, one study, released in 2011 by the Guttmacher Institute, suggested that 98 percent of sexually active Catholic women in the United States between the ages of 17 and 44 had used artificial contraception at some point, in direct contravention of church teaching.

IVF, however, may cause other ethical dilemmas for the faithful. Many attempts to implant an egg into a womans uterus involve fertilizing a number of eggs and implanting a number of embryos in the uterus at once, then reducing the number of viable fetuses through abortion surgeries before the full number come to term. In many other cases, excess embryos are frozen and stored. Church teaching is that life begins at conception, and that from the moment of conception the fertilized egg is a person. For anyone who accepts this premise, the conclusion is inescapable: The selective elimination of implanted embryos is the killing of innocent human beings, and the storage of embryos in a frozen state is a violation of their human dignity.

Most studies suggest that over 90 percent of embryos conceived through IVF will dieand not just from selective abortions, as the medical process has an extremely high failure rate. To be fair, natural conception also does not always offer great odds of success: The U.S.C.C.B. estimates that 15 percent of known pregnancies end in miscarriage, while the Centers for Disease Control estimate that half of all pregnancies in the United States end in miscarriage or stillbirth, and many millions of women never know that they suffered a miscarriage.

The pastoral response to this is difficult for parish ministers and health professionals. Most couples marry with the expectation of a family. When infertility becomes an obstacle, it is not just an issue of the procreative nature of marriage but its unitive nature as wellif people marry with the assumption that children will follow, and that proves impossible, the unitive element of marriage can be badly hurt. The theologian Lisa Cahill hasargued that the church's ban on IVF even when it does not include donors or surrogates "fails to foreground its teachings about sex, love and parenthood in the actual experiences of married parents or of infertile would-be parents" (America, March 28, 1987). Many pastoral ministers know of couples who have suffered as they parsed out what it meant that one or both spouses could not conceive naturally.

As reproductive technologies improve and proliferate, the ethical dilemmas will affect more and more couples. Most American Catholics now know adults, themselves now sometimes parents, who were once upon a time called test tube babies. Their witness enters the conversation as well.

And now we move to the most difficult ethical question: What about the embryos that were frozen? The teaching of the church is that each and every one is a unique human being who deserves to be born and to flourish. So should the church allow infertile couples to become pregnant through IVF using embryos currently in storage? It might violate the principle that a child should be conceived through sex, but it could also be seen as a mercy to the embryos themselvesand a grace to childless couples seeking to live out the procreative nature of their marriage.

One problem? There are at least 400,000 frozen embryos in the United States alone. Other estimates suggest the number might approach a million.

What to do with those 400,000 or more embryos, the castoffs of a well-funded industry that carefully euphemizes what is required and lost to implant a viable embryo in a healthy uterus? Couples who choose IVF face cruel choices yearly because they are typically asked to pay $600 or more a year to keep their embryos frozen rather thanhave them discarded. But what if they could offer those embryos to parents who are struggling with conception? What if childless couples could adopt such embryos and raise them as their own?

It would require some clarification of the teachings of the Catholic Church on the issue, or at least a nuance added to existing doctrine, because Donum Vitae states that the notion that embryos could be put at the disposal of infertile couples as a treatment for infertility is not ethically acceptable and would also lead to other problems of a medical, psychological and legal nature. But with the teachings already applied to vaccinesthat what has already been created is licit to use, even if its origins were not necessarily licitmight it be possible to give childless couples the chance to bear the forgotten?

More from America:

Read: Pope Francis on the intimacy and grace of prayer

Good (and a bit clichd) Jesuit wisdom for pandemic spirituality: Just let go.

As a teen, I chose adoption. Why are stories like mine missing from the abortion debate?

See the article here:
Why does the Catholic Church object to IVF? It's more complicated than you think. - America Magazine

Today marks the end of the official 16 Days of Activism against Gender-Based Violence, which falls on International Human Rights Day. This years theme was Orange the World: Fund, Respond, Prevent, Collect! We spoke to some of our Members of the Human Rights, Refugees and Violence Against Women Committee about the activities they carried out to ensure that awareness around the theme of the 16 Days was increased and to increase commitment to the elimination of this tragedy.

Dr Diana M. Galimberti from Argentina, tells us how, alongside colleagues, they committed to addressing violence against women in Latin America.

Dr. Miguel Gutirrez Ramos and I committed to address the topic of sexual abuse and violence throughout Latin America when in Istanbul.Although in El Salvador, Guatemala and Argentina we received immediate support for our activities, the worldwide quarantine impeded continuation of this project until mid- 2021.However, Dr. Gutirrez has actively participated in several meetings that were nevertheless held: at the University of Santa Fe in October of this year, where I acted as coordinator;once at a nation-wide course for obstetricians in Peru, and he will be a speaker at a meeting on sexual and reproductive rights in Arequipa, Per shortly.He habitually represents the topic of GBV from FIGO perspective at the professional meetings he attends.

During times of war, general disruption of the normal way of life conduces to higher levels of violence in society.

Argentinais one of the most advanced countries in facing GBV against women and girls.Social programmes, judicial backing and general campaigns are forwarded by the Ministry of Health and also the Ministry of Justice and Human Rights. A federal survey for all health workers has recently been launched and, based on its results, training programs on GBV will beinstituted in all public hospitals of the country.

Dr Chiara Benedetto, Chair of the FIGO Subcommittee for Refugees, explains the current situation in Italy and what they are doing to advocate for an end to violence against women.

Winning rights for girls and women is about more than giving opportunities, it is also about changing how countries and communities work, and how the fabric of society evolves. It means investing in a fairer, more equal society, free from violence. Indeed, we are living through a trying time where Gender Based Violence (GBV) is ever more behind locked doors as the waves of the COVID Pandemic confine victims with perpetrators. In Italy, there were 91 feminicides in the first 10 months of 2020, i.e., 1 every 3 days and a 73% increase in requests for help to the various associations (Istat -TheItalian National Institute of Statistics).

In line with FIGOs declarations on Violence Against Women, we recognisethat violence against women and against girls is highly prevalent and may be exacerbated in situations of crises such as conflict, displacement and among refugees. Indeed, we are in constant contact with our migrant focus group members, also through emergency numbers and assistance. Despite the COVID Pandemic and the heavy restrictions on meetings/congresses in person, numerous initiatives have been, and will be taken in Italy to raise awareness as to GBV, including a webinar, video appeals, and a number of online meetings and initiatives.

Dr Colleen McNicholas from the United States comments on their situation and what we need to do to centre the most vulnerable.

The United States continues to provide example after example of why the work of addressing and eliminating human rights violations, especially acts committed against minority communities, is so important. The devastating revelation of forced hysterectomies and sterilisation on migrant detainees reawakened an awareness of the shameful history this country has of prioritising the fertility and reproduction of some while decimating others. When I think of the most impacted by violence against women, I cant help but acknowledge the horrific rates of murder amongst transgender women, particularly women of colour. If raising awareness about gender-based violence is to have a meaningful impact, we must centre the most vulnerable.

From Mexico, Dr Atziri Ramirez tells us about online support groups for victims of violence.

I have committed myself to an online facebookgroup called "Feminist Doctors" where we touch upon several topics one of them regarding "how to educate and disseminate the Violentometer" which is a scale where a woman can realise that she is being a subject of violence. We have concluded that a good way is by posting this information in groups and offering access to public resources (such as public telephone numbers of agencies that are supporting women who are victims of violence in their homes). Following the line of online content I also became part of a group called "Trueka Feminist" which supports victims of violence by online trade. I have disseminated this information among my peers,undergraduatestudents and trainees.

Finally, Dr Taghreed Alhaidari shared posters that were created by the Iraq Member Society which were published on social media, highlighting facts and figures on the rates of GBV.

We hope these examples inspireyou to continue to carry out this important advocacy work and help to eliminate violence against women, beyond the 16 Days of Activism. For more resources on GBV and the 16 Days, visit the UN website.

Read the original here:
16 Days of Activism What have our Members been up to? - International Federation of Gynecology and Obstetrics

A sad fact remains this Christmas 60% of children in LGBT+ families have zero legal rights to one of their parents five years on from the Marriage Equality Act of 2015.

This week, ahead of Christmas, Equality for Children have renewed their pledge to ensure that progress is made to achieve equality for all children of LGBT+ families. By Christmas 2021, the grassroots group hopes to achieve 100% parental rights for all LGBT+ families.

Sadly, this is not the case today.

This Christmas we think of all the children of LGBT+ families who have been left behindAs it stands today, only one parent can be a legal parent, which of course is perilous in the event of bereavement, illness and more, Ranae Von Meding, Equality for Children.

Currently, ONLY 40% of LGBT+ families have the same rights as heterosexual couples, leaving behind 60% of children as not having access to full legal parental rights and this is five years on from the passing of the Marriage Equality Act of 2015

For most Irish families, this is the happiest time of the year. It should be a time of joy and celebration. Yet for those who are still not considered a legal family, it can be a really difficult time full of uncertainty and pain, says Ranae von Meding, CEO of Equality for Children.

It is important to acknowledge that some LGBT+ parents in Ireland now have the same rights as heterosexual parents. This is a huge step in the right direction. However, many families still fall outside of any legal framework and in these cases only one person in an LGBT+ family can be a legal parent leaving an unknown outcome for families in the event of bereavement, illness and more.

Despite the progress being made, LGBT+ children are #stillnotequal.

The protections promised in 2015 by the government under the Children and Family and Relationships Act, dictate a very particular LGBT+ family makeup. They finally came to fruition earlier this year and the first parental orders were issued early in the summer. This has been a source of enormous relief for hundreds of families. However, it is not enough. Around 40% of children of LGBT+ families benefit from this bill. That leaves the other 60% with no legal connection to one of their parents. And that simply is not good enough.

Equality for Children recognises that progress has been made with the Assisted Human Reproduction Bill at Oireachtas Committee stage, as well as the ongoing work from the Special Rapporteur on Child Protection, Dr. Conor O Mahony, to investigate parental rights for LGBT+ families using assisted human reproduction. These are significant developments and have the potential to provide pathways to legal recognition for hundreds of more families.

Equality for Children is a grassroots campaign which was launched in October 2019 campaigning for equality for all children of LGBT+ families in Ireland. It was started by a collective of concerned parents and allies, who were tired of waiting for their families to be given the recognition they deserve.

The campaign has garnered support from people who are willing to help across social media, fundraising, lobbying, design and more, but the task group is asking people to support them through volunteering to join them in the fight for full equality.

The reason why this campaign is so important is because many children of LGBT+ parents are still on the dangerous sidelines of grey legislation. We are #StillNotEqual, and our children ultimately suffer the most, until something changes. We look forward to working with government departments in the coming months to progress these crucial issues. she commented.

To find out more or see how you can help visit their website at http://www.equalityforchildren.ie.

Originally posted here:
Only 40% of LGBT+ families have the same rights as heterosexual couples - SHEmazing

The presence of the Babinski sign has already been reported for some Renaissance paintings, and the first observations date from the beginning of the 20th century.23 More recently, several articles have highlighted paintings by Botticelli containing the Babinski sign.789 However, some other paintings with the toe phenomenon have scarcely been written about,810 and, until now, no systematic study of the Babinski sign in paintings of the Christ Child from the Renaissance period (1400-1550 CE) has been reported. We did such a study using a specific and strict method, and we observed that 30% (90/302) of the corpus of paintings portrayed the Babinski sign, with a stimulating factor in 53% (48/90) of cases.

This frequency mainly results from the artistic revolution of the 15th century. In the Middle Ages, when trying to illustrate Jesus Christ, painters often represented him as a small man, with a childs height but the body and the face of an adult. Even though this way of depicting the Christ Child is still used in some Orthodox traditions, it might be regarded as an incongruity, as highlighted by Huysmans: To make the inexpressible childhood of a God () they created a hybrid being, who is no longer a child, and who is not a God, some kind of monster.11 During the Renaissance, artists began to represent the nudity of the Christ Child to demonstrate the incarnation of Christ, who was subsequently portrayed in a very realistic form. Modern art historians postulate that the imagery of the overtly sexed Christ was an affirmation of kinship with the human condition.12

As a consequence of a growing desire for realism, most Renaissance painters no longer depicted the Christ Child as a small man but as a real infant. If they had live infants as models, they were more likely to involuntarily reproduce the Babinski sign. This realism was not merely the consequence of the Italian Renaissance revolution, as it is much more the hallmark of Flemish and Rhenish painters (particularly van der Weyden, Memling, Schongauer, and Grnewald), known for their tendency to paint precise, sometimes trivial, realistic details from everyday life. This trend towards realistic depictions is also shown by the fact that in these paintings, the infants, clothes, and general surroundings belong to the Western world contemporary to the painters and are not representative of the Middle East in the first century CE. This tendency may also explain the painters frequent reproduction of the Babinski sign as soon as representation of the infants nudity became acceptable, examples of which are given in figure 2 (A-C and E). By contrast, Italian painters tended to depict idealised human bodies, with a quest for perfect beauty, as seen in the models of antiquity. Therefore, some painters, such as Fra Angelico, Masaccio, or Tiziano, failed to reproduce the Babinski sign in paintings of the Christ Child.

The stimulating atmosphere of the Renaissance period and the need for a scientific approach and precise observation of live infants to improve likenesses has been proposed as a possible explanation of the representation of the Babinski sign in paintings of the Christ Child. The particular influence of the Renaissance led to accurate depiction of natural phenomena, especially in painting. Botticelli was an example of this new focus; 40% (12/30) of his paintings in this study depict a Babinski sign. Nevertheless, many great painters such as Raphael, known to have an eye for the finest details of their subjects, almost never depicted the Christ Child with an upgoing toe. Many Renaissance painters were aware of medical and anatomical realities; neurological abnormalities such as ulnar claw or facial dystonia appear in Renaissance paintings,1314 and some painters, such as Michelangelo and da Vinci, did anatomical dissections. However, this pursuit of anatomical knowledge seems not to have been a determining factor for the depiction of the Babinski sign in painting; da Vinci, who was an anatomist and contributed to the study of the nervous system,15 depicted the Babinski sign in only 22% (2/9) of his paintings of the Christ Child. Similarly, no Tiziano paintings portray the toe phenomenon. However, Tiziano, with his student Jan van Calcar (c1499-1545), certainly participated in the illustrations for the anatomical masterpiece De Corporis Fabrica by Andreas Vesalius (1514-64).16

To explain about 30% of the paintings displaying a Babinski sign in our study, two other mechanisms can be discussed: the master-student effect, and the copying effect. In our corpus, a master-student effect could be suspected regarding Leonardo da Vinci and his master Andrea del Verrochio. It is interesting to note that the three paintings of the Christ Child with a bilateral Babinski sign were produced by Andrea del Verrochio (The Virgin and Child with Two Angels, c1470) (fig 2, D) and Leonardo da Vinci (Madonna of the Carnation, c1479, and Madonna Benois, c1480). This hypothesis of artistic filiation is supported by the bilateral Babinski sign that was recently observed on a sculpture attributed to da Vinci (Virgin with the Laughing Child).17

The practice of copying works of art was frequent during the Renaissance, particularly for Virgin and Christ Child paintings. The painting Saint Luke Drawing the Virgin, of which many copies exist, is a clear example of this.18 However, examples of serial paintings, such as Madonna and Child with the Milk Soup by Grard David, which was reproduced in at least three versions, are rare. The Babinski sign is not present in the version of this painting exhibited in the Palazzo Bianco in Genoa, whereas it is present in the other two versions. Cranach the Elder frequently produced serial paintings of the Madonna and Child, reproducing the Babinski sign each time, but this phenomenon cannot explain the occurrence of the sign in other paintings by the same artist, such as The Virgin and Child with a Bunch of Grapes (Fig 2, E).

An alternative hypothesis is that the dorsiflexion of the toes in some of Botticellis or Cranachs infants is a Mannerist stylistic choice, as shown also by the formalised placements of the fingers.9 However, this cannot be the correct explanation, as Mannerism is an artistic style that emerged only in the later years of the Italian High Renaissance (around 1520), breaking all the codes of anatomical accuracy, proportion, and balance.19 Mannerism is clearly absent in paintings by Flemish painters such as Rogier van der Weyden or Grard David or Rhenish painters such as Martin Schongauer, who frequently depicted the Babinski sign. Examples of works containing the Babinski sign by these artists are in figure 2 (A, B, and C).

Many studies of the plantar reflex in infants have been published. These have sometimes reported contradictory findings about the flexion or extension response (Babinski sign) of this reflex. One reason for these heterogeneous results may be the interference of the grasp reflex of the toes, which is generally present during the first year of life. Taking the grasp reflex into account, the physiological response of the plantar reflex until the age of 6 months is hallux extension. The main factor in eliciting the hallux extension in infants seems to be the intensity of the stimulus.420 In our corpus, we observed stimulation of the foot in 53% (48/90) of the paintings. We obviously could not evaluate the intensity of this stimulus. Nevertheless, as already noted, in some cases the stimulus was directly applied to the lateral part of the sole, the site known to elicit the Babinski sign.7

At the age of 6 months, hallux extension usually ceases to be the manifestation of the plantar reflex.420 Nativity, Adoration of the Magi, and Presentation at the Temple paintings are supposed to be set during the first week of Jesuss life, and Madonna and Child paintings during the first year. Evidently, the age of the Christ Child as depicted in paintings does not correspond to the chronological reality of these events. We therefore cannot show a relation between the frequency of the Babinski sign and the subject matter of the paintings in our series. Even if a preoccupation with realism dominated in this artistic period, the painted Christ Child usually appears older than the reality. As determining the precise age of the model is difficult, we are not able to establish a correlation with the myelinisation of the nervous system. The use of older children as models might therefore explain the low frequency of the depiction of the Babinski sign by some painters.

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The Babinski sign in Renaissance paintingsa reappraisal of the toe phenomenon in representations of the Christ Child: observational analysis - The BMJ

The uni says the money will fund three major research projects, which includes studies on fertility and tackling climate change.

The University of East Anglia has secured over 5-point-1 million pounds in funding.

The grants from the European Research Council will be used to pay for three major research projects.

Dr Charlie Wilson, from UEAs School of Environmental Sciences has been awarded 1,598,465 to study the digitisation of daily life and its impact on climate change.

Digitalisation is a major trend that has reshaped our lives from streaming music and TV to using smart meters to reduce energy use in our homes. Dr Wilsons project will involve 80 living lab households to investigate how these changes impact carbon emissions and climate change.

Dr Simone Immler from UEAs School of Biology has been awarded 2,122,476 to research fertility.

Her project will investigate the role of selection on sperm and eggs based on their genetic make-up in determining the fitness of the resulting offspring in zebrafish. And the team hope this will one day help us understand more about human reproduction and fertility.

Dr Alexander Suh, from UEAs School of Biological Sciences, has been awarded 1,994,180 to explore the evolutionary origin and impact of germline-restricted chromosomes.

The funding is part of the EUs current research and innovation programme, Horizon 2020. With this support, the project leaders will be able to consolidate their teams and have far-reaching impact.

Prof Fiona Lettice, Pro-Vice-Chancellor for Research and Innovation at UEA, said: ERC Consolidator Grants are awarded to the most talented researchers and innovators, so I would like congratulate Simone, Charlie and Alexander for this great achievement. Their projects will improve our understanding of these important topics and will deliver significant impact and real change.

ERC President Prof Jean-Pierre Bourguignon said: This funding not only empowers bright minds from across Europe to pursue their most ambitious ideas at a critical stage of their careers, but also helps train the youngest generation of researchers as members of their ERC teams.

To prepare for the challenges of tomorrow, Europe must stick to the vision of investing in frontier research, which has proved time and again its crucial added value. That is why so many count on Europes leaders to endow the Excellent Science pillar of Horizon Europe with the resources essential to strengthen Europe as a whole.

Hear all the latest news from across the UK on the hour, every hour, on Greatest Hits Radio on DAB, at greatesthitsradio.co.uk, and on the Greatest Hits Radio app.

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UEA given millions for research funding | News - Greatest Hits Radio (Norfolk and North Suffolk) - Free Radio

By: Parenting Desk | New Delhi | December 4, 2020 4:36:51 pmIt is important to speak to your doctor/fertility expert first for any queries and advice on difficulty in conceiving and fertility options possible and available. (Source:: Pixabay)

By Dr Abha Majumdar

Often, couples and doctors use the words subfertility and infertility interchangeably, but it is imperative to realise that both the terms are quite different. In fact, the prognosis and treatment for both these conditions also differ. This is an important aspect to consider when couples seek infertility counselling. The fertility counsellor analyses the health condition of the couple, their conception issues and investigate whether it is subfertility or infertility.

What does each term describe?

When the conception takes longer than the average, but the woman and the man can conceive a child, is best described as subfertility. In this condition, couples have reduced fertility or experience delay in fertility, but the possibility of conceiving naturally still exists, even though they may take longer time to conceive than what their expectations may be.

On the other hand, infertility deals with inability to conceive naturally. There are various types and causes of infertility in both men and women. In some cases of infertility, a woman may not produce eggs at all either due to hormonal imbalance or absence of eggs in the ovary. Similarly, infertility among men deals with either complete lack of sperm creation or the absence of the entire delivery system or route for sperms to pass into semen, even though sperm production is sufficient.

ALSO READ |Early birth linked to higher risk of hospital visits: BMJ study

Factors that affect fertility negatively:

Various factors in women like hormonal problems affecting ovulation, or functional issues like obstruction in the fallopian tube or in the cavity of uterus which are severe enough and do not let pregnancy happen naturally, lead to infertility. Similarly, in men complete absence or severe deficiency of sperms in semen leads to infertility. However, if these problems are mild and only require more time or minimal assistance in the form of lifestyle modification and good sexual practices for a pregnancy to happen, then these are categorised as subfertility. For example, Polycystic Ovary Syndrome (PCOS) is quite common among women affecting ovulation and may cause irregular ovulation among women leading to subfertility. On the other hand, conditions like reduced ovarian reserve and premature menopause due to aging or pre-existing medical conditions can also affect fertility leading to infertility among women.

However, in most of the couples, the factors remain the same that lead to subfertility or infertility. It is the severity of the cause which defines the conditions. Subfertility and infertility affect both men and women and sometimes even both together.

ALSO READ |Delayed vaccination: How it may impact your child

How treatment differs

The treatment for both, subfertility and infertility, will depend on the cause found after examination and investigations, for the couples inability to conceive. The fertility evaluation will involve tests for both the man and woman.

After a thorough analysis, the fertility expert will advise treatment options for them, depending on the results of the analysis. The expert might suggest simple treatment options like lifestyle changes for example, reducing alcohol and caffeine consumption, maintaining healthy weight and adequate physical and sexual activity for most sub-fertile couples. On the other hand, one may need to resort to medical or surgical treatment or even advanced treatment options such as use of assisted reproduction techniques like IVF depending on the severity of the problem found.

Therefore, to summarise, some of the medical treatment options for men include surgery for opening the blockage in the sperm delivery system or medications for sufficient sperm production in the ejaculate. For women, some of the treatment options would include fertility enhancing drugs comprising ovulation inducing agents, surgery to restore tubal patency or In-Vitro Fertilisation (IVF).

ALSO READ |Why women with perinatal depression experience full-blown depression during pregnancy

It is important to speak to your doctor/fertility expert first for any queries and advice on difficulty in conceiving and fertility options possible and available.

(The writer is Director, Centre of Human Reproduction & IVF, Sir Gangaram Hospital)

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Subfertility and Infertility: Are these different? - The Indian Express

Anastasia E. Lennon|Standard-Times

Shark research groups and government agencies in the United States and Canada announced Tuesday the establishment of anorganization that will unite over a dozen agencies to collaborativelystudy thewhite shark.

The New England White Shark Research Consortium joinsorganizations and universities in Massachusettssuch as the New England Aquarium and University of Massachusetts Dartmouthwith researchers in Maine, Rhode Island, New Hampshire, Arizona and Canada.

The group has two primary goals: advance researchers' current understanding of thewhite shark, and enhance public education and safety within the region.

Gregory Skomal, the senior fisheries scientist for the Massachusetts Division of Marine Fisheries (which is a consortium member),said the fatal shark attack of a 63-year-old womanoff the coast of Maine this summer prompted the creation of the consortium.

"It really pointed to a need for us to coordinate research here in New England," Skomal said, noting many people were surprised by the location of the attack even though researchers knewwhite sharks are historically found in Maine waters.

In an official statement, the consortium citedgrowing sightings of great white sharks in recent years as the "perfect time"to increase public and scientific understanding of the species, which is currently listed as vulnerableby the International Union for Conservation of Nature.

"Having a better understanding of this shark, the timing of its migration, where does it go, not only along Cape Cod, but along Rhode Island, New Hampshire,Maineand the coast of Canada," Skomal said. "Thats why we established this research consortium so we can all work under the same umbrella, share ideas, share data, share equipment and work collaboratively."

Skomal said the consortium came about somewhat informally through conversations among participating organizations and agencies, many of which have regularly collaborated.

"It was really along the lines of, 'Boy, we should formalize this arrangement under a singular umbrella,'" he said.

According to an official statement, the consortium will be "unparalleled" in its scope, usinghundreds of acoustic receivers to detect white shark movements from Rhode Island to Canada. Researchers will also use acoustic transmitters, satellite-linked tags and tissue analysis to study the shark's life stages.

Researchers will continue to studymigration patterns, habitat use, reproduction, predatory behavior and factors that drive interaction with humans. What's different now is that the consortium will facilitate greater collaboration and sharing of ideas, tools and data among new and old partners.

The University of Massachusetts Dartmouth School of Marine Science and Technology (SMAST) is also a participating member.

Megan Winton, a PhD student at the school and the chief research scientist for the Atlantic Shark Conservancy (another participating member), said she along with other partnering organizations will continue using high-tech equipment to characterize the predatory behavior and habits of the sharks off Cape Cod.

"The results of all of these studies are being used to identify areas and conditions during which white sharks are most likely to overlap with recreational water users in order to provide science-based information to improve public safety practices," Winton said in an email to the Standard-Times.

She has been working with her PhD advisor, Gavin Fay, and usingstatistical modellingto better understand wherewhite sharks go and when. Fay said he didn't have a formal role in the consortium, but that he will continue to collaboratewith Winton and other members.

Steven Cadrin, another SMAST professor, noted the consortium is also a great opportunity for the school's students to apply their educationto real-world problem-solving. The consortium's findings can shape decision-making and address community concerns, such as safety from sharks.

"Weve been applying some advanced technologies and modelling approaches to fisheries resources," Cadrin said. "White sharks giveus an opportunity to apply those advanced technologies and models... with white sharks, human safety is another application."

Other participating bodies include the Rhode Island Department of Environmental Management, the Maine Department of Marine Resources, the Massachusetts Division of Marine Fisheries, the Center for Coastal Studies, Arizona State University, the Atlantic Shark Institute and the NOAA Fisheries Apex Predators Program.

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International consortium created to study the white shark - SouthCoastToday.com

Regulation 174 Information for UK healthcare professionals

This medicinal product does not have a UK marketing authorisation but has been given authorisation for temporary supply by the UK Department of Health and Social Care and the Medicines and Healthcare products Regulatory Agency for active immunization to prevent COVID-19 disease caused by SARS-CoV-2 virus in individuals aged 16 years of age and over.

As with any new medicine in the UK, this product will be closely monitored to allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

COVID-19 mRNA Vaccine BNT162b2 concentrate for solution for injection

This is a multidose vial and must be diluted before use. 1 vial (0.45 mL) contains 5 doses of 30 micrograms of BNT162b2 RNA (embedded in lipid nanoparticles).

COVID-19 mRNA Vaccine BNT162b2 is highly purified single-stranded, 5-capped messenger RNA (mRNA) produced by cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2.

Excipients with known effect: For the full list of excipients, see section 6.1.

Concentrate for solution for injection.

The vaccine is a white to off-white frozen solution.

Active immunisation to prevent COVID-19 caused by SARS-CoV-2 virus, in individuals 16 years of age and older.

The use of COVID-19 mRNA Vaccine BNT162b2 should be in accordance with official guidance.

COVID-19 mRNA Vaccine BNT162b2 is administered intramuscularly after dilution as a series of two doses (0.3 mL each) 21 days apart (see section 5.1).

There are no data available on the interchangeability of COVID-19 mRNA Vaccine BNT162b2 with other COVID-19 vaccines to complete the vaccination series. Individuals who have received one dose of COVID-19 mRNA Vaccine BNT162b2 should receive a second dose of COVID-19 mRNA Vaccine BNT162b2 to complete the vaccination series.

Individuals may not be protected until at least 7 days after their second dose of the vaccine.

For further information on efficacy, see section 5.1.

The safety and efficacy of COVID-19 mRNA Vaccine BNT162b2 in children under 16 years of age have not yet been established.

Administer the COVID-19 mRNA Vaccine BNT162b2 vaccine intramuscularly in the deltoid muscle after dilution.

Do not inject the vaccine intravascularly, subcutaneously or intradermally.

Preparation: The multidose vial is stored frozen and must be thawed prior to dilution

Frozen vials should be transferred to 2 C to 8 C to thaw. Alternatively, frozen vials may also be thawed and kept at temperatures up to 25 C for a maximum of two hours in preparation for dilution for use.

When removed from the freezer, the undiluted vaccine has a maximum shelf life of up to 5 days (120 hours) at 2 C to 8 C, and and additional 2 hours at temperatures up to 25 C in preparation for dilution.

When the thawed vial is at room temperature gently invert 10 times prior to dilution. Do not shake. Prior to dilution the vaccine should present as an off-white solution with no particulates visible. Discard the vaccine if particulates or discolouration are present.

The thawed vaccine must be diluted in its original vial with 1.8 mL sodium chloride 9 mg/mL (0.9%) solution for injection, using a 21 gauge or narrower needle and aseptic techniques.

Warning: Unpreserved sodium chloride 9 mg/mL (0.9%) solution for injection is the only diluent that should be used. This diluent is not provided in the vaccine carton.

Equalise vial pressure before removing the needle from the vial by withdrawing 1.8 mL air into the empty diluent syringe.

Gently invert the diluted solution 10 times. Do not shake.

The diluted vaccine should present as an offwhite solution with no particulates visible. Discard the diluted vaccine if particulates or discolouration are present.

The diluted vials should be marked with the dilution date and time and stored between 2 C to 25 C.

Use as soon as practically possible, and within 6 hours after dilution.

After dilution, the vial contains 5 doses of 0.3 mL. Withdraw the required 0.3 mL dose of diluted vaccine using a sterile needle and syringe and administer. Any unused vaccine should be discarded 6 hours after dilution.

After dilution, the vaccine should not be shipped (transported) by motor vehicle away from the site of dilution. Any shipping (transportation) by motor vehicle after dilution of the vial is at the risk of the Health Care Professional.

For instructions on disposal see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Any person with a history of immediate-onset anaphylaxis to a vaccine, medicine or food should not receive the COVID-19 mRNA Vaccine BNT162b2. A second dose of the COVID-19 mRNA Vaccine BNT162b2 should not be given to those who have experienced anaphylaxis to the first dose of COVID-19 mRNA Vaccine BNT162b2.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine. The administration of COVID-19 mRNA Vaccine BNT162b2 should be postponed in individuals suffering from acute severe febrile illness.

Individuals receiving anticoagulant therapy or those with a bleeding disorder that would contraindicate intramuscular injection, should not be given the vaccine unless the potential benefit clearly outweighs the risk of administration.

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the vaccine. No data are available about concomitant use of immunosuppressants.

As with any vaccine, vaccination with COVID-19 mRNA Vaccine BNT162b2 may not protect all vaccine recipients.

No data are available on the use of COVID-19 mRNA Vaccine BNT162b2 in persons that have previously received a full or partial vaccine series with another COVID-19 vaccine.

This vaccine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially potassium-free.

This vaccine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially sodiumfree.

No interaction studies have been performed.

Concomitant administration of COVID-19 mRNA Vaccine BNT162b2 with other vaccines has not been studied (see section 5.1).

Do not mix COVID-19 mRNA Vaccine BNT162b2 with other vaccines/products in the same syringe.

There are no or limited amount of data from the use of COVID-19 mRNA Vaccine BNT162b2. Animal reproductive toxicity studies have not been completed. COVID-19 mRNA Vaccine BNT162b2 is not recommended during pregnancy.

For women of childbearing age, pregnancy should be excluded before vaccination. In addition, women of childbearing age should be advised to avoid pregnancy for at least 2 months after their second dose.

It is unknown whether COVID-19 mRNA Vaccine BNT162b2 is excreted in human milk. A risk to the newborns/infants cannot be excluded. COVID-19 mRNA Vaccine BNT162b2 should not be used during breast-feeding.

It is unknown whether COVID-19 mRNA Vaccine BNT162b2 has an impact on fertility

COVID-19 mRNA Vaccine BNT162b2 has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

The safety of COVID-19 mRNA Vaccine BNT162b2 was evaluated in participants 16 years of age and older in two clinical studies conducted in the United States, Europe, Turkey, South Africa, and South America. Study BNT162-01 (Study 1) enrolled 60 participants, 18 through 55 years of age. Study C4591001 (Study 2) enrolled approximately 44,000 participants, 12 years of age or older. In Study 2, a total of 21,720 participants 16 years of age or older received at least one dose of COVID19 mRNA Vaccine BNT162b and 21,728 participants 16 years of age or older received placebo. Out of these, at the time of the analysis, 19,067 (9531 COVID-19 mRNA Vaccine BNT162b2 and 9536 placebo) were evaluated for safety 2 months after the second dose of COVID-19 mRNA Vaccine BNT162b2.

Demographic characteristics were generally similar with regard to age, gender, race and ethnicity among participants who received COVID-19 mRNA Vaccine and those who received placebo. Overall, among the participants who received COVID-19 mRNA Vaccine BNT162b2, 51.5% were male and 48.5% were female, 82.1% were White, 9.6% were Black or African American, 26.1% were Hispanic/Latino, 4.3% were Asian and 0.7% were Native American/Alaskan native.

The most frequent adverse reactions in participants 16 years of age and older were pain at the injection site (> 80%), fatigue (> 60%), headache (> 50%), myalgia (> 30%), chills (> 30%), arthralgia (> 20%) and pyrexia (> 10%) and were usually mild or moderate in intensity and resolved within a few days after vaccination. If required, symptomatic treatment with analgesic and/or anti-pyretic medicinal products (e.g. paracetamol-containing products) may be used.

Adverse reactions reported in clinical studies are listed in this section per MedDRA system organ class, in decreasing order of frequency and seriousness. The frequency is defined as follows: very common ( 1/10), common ( 1/100 to < 1/10), uncommon ( 1/1,000 to < 1/100), rare ( 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from available data).

Blood and lymphatic system disorders

Nervous system disorders

Musculoskeletal and connective tissue disorders

General disorders and administration site conditions

Gastrointestinal disorders

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Coronavirus Yellow Card reporting site or search for MHRA Yellow Card in the Google Play or Apple App Store and include the vaccine brand and batch/Lot number if available.

Participants who received 58 micrograms of COVID-19 mRNA Vaccine in clinical trials did not report an increase in reactogenicity or adverse events.

In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.

Pharmacotherapeutic group: group, ATC code: not yet assigned

The nucleoside-modified messenger RNA in COVID-19 mRNA Vaccine BNT162b2 is formulated in lipid nanoparticles, which enable delivery of the RNA into host cells to allow expression of the SARSCoV-2 S antigen. The vaccine elicits both neutralizing antibody and cellular immune responses to the spike (S) antigen, which may contribute to protection against COVID-19 disease.

The efficacy of COVID-19 mRNA Vaccine BNT162b2 was evaluated in participants 16 years of age and older in two clinical studies conducted in the United States, Europe, Turkey, South Africa and South America. Study 1 enrolled 60 participants, 18 through 55 years of age. Study 2 is a multicentre, placebo-controlled efficacy study in participants 12 years of age and older. Randomisation was stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age and older, with a minimum of 40% of participants in the 56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID-19 disease. Participants with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrolment, were included as were participants with known stable infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV). There was no requirement for prophylactic use of paracetamol or analgesics. Influenza vaccines could be administered outside a window 14 days of the vaccine doses.

In Study 2, approximately 44,000 participants 12 years of age and older were randomised equally and received 2 doses of COVID-19 mRNA Vaccine or placebo with a planned interval of 21 days. The efficacy analyses included participants that received their second vaccination within 19 to 42 days after their first vaccination. Participants are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19 disease.

The population for the analysis of the primary efficacy endpoint included, 36,621 participants 12 years of age and older (18,242 in the COVID-19 mRNA Vaccine group and 18,379 in the placebo group) who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. Demographic characteristics were generally similar with regard to age, gender, race and ethnicity among participants who received COVID-19 mRNA BNT162b2 vaccine and those who received placebo. Overall, among the participants who received COVID-19 mRNA vaccine, 51.1% were male and 48.9% were female, 82.8% were White, 8.9% were Black or African American, 26.8% were Hispanic/Latino, 4.5% were Asian and 0.6% were Native American/Alaskan native. 57.2% were aged 16-55 years, 42.6% were aged > 55 years and 21.8% were 65 years.

At the time of the analysis of Study 2, information presented is based on participants 16 years and older. Participants had been followed for symptomatic COVID-19 disease for at least 2,214 person-years for the COVID-19 mRNA Vaccine and at least 2,222 person-years in the placebo group. There were 8 confirmed COVID-19 cases identified in the COVID-19 mRNA Vaccine group and 162 cases in the placebo group, respectively. In this analysis, compared to placebo, efficacy of COVID-19 mRNA Vaccine BNT162b2 from first COVID-19 occurrence from 7 days after Dose 2 in participants without evidence of prior infection with SARS-CoV-2 was 95.0% (95% credible interval of 90.3% to 97.6%). In participants 65 years of age and older and 75 years of age and older without evidence of prior infections with SARS-CoV-2, efficacy of COVID-19 mRNA Vaccine BNT162b2 was 94.7% (two-sided 95% confidence interval of 66.7% to 99.9%) and 100% (two-sided 95% confidence interval of -13.1% to 100.0%) respectively.

In a separate analysis, compared to placebo, efficacy of COVID-19 mRNA Vaccine from first COVID-19 occurrence from 7 days after Dose 2 in participants with or without evidence of prior infection with SARS-CoV-2 was 94.6% (95% credible interval of 89.9% to 97.3%).

There were no meaningful clinical differences in overall vaccine efficacy in participants who were at risk of severe COVID-19 disease including those with one or more comorbidities that increase the risk of severe COVID-19 disease (e.g. asthma, BMI 30 kg/m2, chronic pulmonary disease, diabetes mellitus, hypertension).

Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 disease.

Not applicable.

Non-clinical data reveal no special hazard for humans based on a conventional study of repeat dose toxicity. Animal studies into potential toxicity to reproduction and development have not been completed.

This vaccine contains polyethylene glycol/macrogol (PEG) as part of ALC-0159.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6 months at -80 C to -60 C.

Store in a freezer at -80 C to -60 C.

Store in the thermal container at -90 C to -60 C.

Store in the original package in order to protect from light.

Once removed from the freezer, the undiluted vaccine can be stored for up to 5 days at 2 C to 8 C, and up to 2 hours at temperatures up to 25 C, prior to use. During storage, minimise exposure to room light, and avoid exposure to direct sunlight and ultraviolet light. Thawed vials can be handled in room light conditions.

After dilution, store the vaccine at 2 C to 25 C and use as soon as practically possible and within 6 hours. The vaccine does not contain a preservative. Discard any unused vaccine.

Once diluted, the vials should be marked with the dilution time and discarded within 6 hours of dilution.

Once thawed, the vaccine cannot be re-frozen.

Concentrate for solution for injection for 5 doses in a 2 mL clear vial (type I glass) with a stopper (bromobutyl) and a flip-off plastic cap with aluminium seal.

Pack size: 195 vials

When removed from the freezer, the vaccine has a maximum possible shelf life of up to 5 days when stored at 2-8 C (label to be added once box removed from freezer). A 195 vial pack may take 3 hours to thaw at 2-8oC.

The product can alternatively be defrosted and kept for up to 2 hours at up to 25 C before being diluted for use. This facilitates immediate thaw and use when removed directly from the freezer to 25 C. In this instance the product is to be diluted within 2 hours of removing from the freezer.

Once thawed, the vaccine cannot be refrozen.

After dilution the vaccine should be used as soon as is practically possible and within 6 hours of dilution; it can be stored at 2-25 C during this period. From a microbiological point of view, it would not normally be considered good practice to store diluted product for 6 hours at 25C before being administered. The product would ideally be used as soon as practically possible after dilution.

The vaccine does not contain a preservative. Discard any unused vaccine

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

For instructions on dose preparation of the medicinal product before administration, see section 4.2.

Not applicable.

Not applicable.

Not applicable.

Link:
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INDIANAPOLIS, Dec. 9, 2020 /PRNewswire/ --Eli Lilly and Company (NYSE: LLY) today announced additional data from a pre-planned primary outcome analysis from the Phase 3 monarchE trial that showed Verzenio (abemaciclib) in combination with standard adjuvant endocrine therapy (ET) decreased the risk of breast cancer recurrence by 28.7 percent compared to standard adjuvant ET alone for people with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) high risk early breast cancer (HR: 0.713; 95% CI: 0.583, 0.871; p = 0.0009). This statistically significant improvement corresponds to a three percent difference in the two-year rate of invasive disease-free survival (IDFS) between arms (92.3 percent in the Verzenio arm and 89.3 percent in the control arm). The data presented today during the 2020 Virtual San Antonio Breast Cancer Symposium (SABCS) included an additional 3.6 months of follow-up since the pre-planned interim analysis results announced in September 2020, and more than 1,400 patients have completed two years of treatment since the start of the study.

The timing of the primary outcome analysis was driven by the number of IDFS events observed in the intent-to-treat population across both arms as prespecified in the study's statistical analysis plan.The statistically significant benefit observed was consistent across all pre-specified subgroups. The median follow up was approximately 19.1 months.

The addition of Verzenio to ET also resulted in an improvement in distant relapse-free survival (DRFS), or time to developing breast cancer that has spread to other parts of the body. The combination reduced the risk of developing metastatic disease by 31.3 percent compared to 28.3 percent at interim analysis (HR: 0.687; 95% CI: 0.551, 0.858). Safety data from monarchE were consistent with the known safety profile of Verzenio and no new safety signals were observed. Compared to the interim analysis results, there were minimal increases in adverse events.

"As the monarchE data have matured, we have seen an improvement in the reduction of risk of recurrence for people with HR+, HER2- high risk early breast cancer," said Priya Rastogi, M.D., associate professor at the University of Pittsburgh School of Medicine, medical oncologist at UPMC Hillman Cancer Center and medical director of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation. "With more than 1,400 patients completing two years of treatment, we are pleased to see the curves continue to separate, as reflected by the numerically greater hazard ratio estimates for both invasive disease-free survival and distant relapse-free survival in the primary outcome analysis."

monarchE randomized 5,637 patients with HR+, HER2- high risk early breast cancer from more than 600 sites in 38 countries. High risk was defined by cancer that spread to the lymph nodes, a large tumor size, or high cellular proliferation (as determined by tumor grade or Ki-67 index). Patients were treated for two years (treatment period) or until meeting criteria for discontinuation. After the treatment period, all patients will continue ET for five to 10 years, as clinically indicated.

"The monarchE primary outcome data builds on the significance of the results of the interim analysis with a 28.7 percent reduction in the risk of recurrence for patients with HR+, HER2-, high risk early breast cancer," said Maura Dickler, M.D., vice president, late phase development, Lilly Oncology. "We are extremely pleased that these results continue to be strong and reinforce Verzenio as the only CDK4 & 6 inhibitor with positive results in the early breast cancer setting. We thank all those who participated in the trial and we are committed to making Verzenio available for these patients as quickly as possible."

A key secondary analysis evaluated the IDFS treatment benefit of patients enrolled in monarchE based on Ki-67 index. In patients whose tumors had high Ki-67 (20%), Verzenio with ET also significantly decreased the risk of breast cancer recurrence by 30.9 percent, compared to those who received ET alone (HR: 0.691; 95% CI: 0.519, 0.920). Ki-67 is a biomarker of high cell proliferation and increased risk of recurrence. This is the first time a prespecified threshold of 20% for Ki-67 has been used to prospectively evaluate the utility of central Ki-67 using a standardized assay in a phase III registration trial.These results suggest that Ki-67 20% could be used together with clinicopathological features of nodal involvement, tumor size, and grade, to identify patients with HR+, HER2-, early breast cancer at high risk of recurrence.

All patients on monarchE will continue to be followed to assess overall survival and other endpoints. Lilly will submit the monarchE data to regulatory authorities before the end of 2020.

About the monarchE Study monarchE is a Phase 3, multicenter, randomized, open-label trial that enrolled 5,637 patients with HR+, HER2- node-positive, high risk early breast cancer. Patients were randomized 1:1 to Verzenio (150 mg twice daily) plus standard adjuvant endocrine therapy or standard adjuvant endocrine therapy alone. Patients were treated for two years (treatment period) or until meeting criteria for discontinuation. After the treatment period, all patients will continue on endocrine therapy for five to 10 years, as clinically indicated. The primary objective is invasive disease-free survival (IDFS) defined according to the Standard Definitions for Efficacy Endpoints (STEEP) criteria. In adjuvant breast cancer trials, this includes the length of time before any cancer comes back, a new cancer develops or death. Secondary objectives include distant relapse-free survival, overall survival, safety, pharmacokinetics and health outcomes.

High risk was specifically defined as women (any menopausal status) and men with resected HR+, HER2- invasive early breast cancer with either 4 pathologically positive axillary lymph nodes (ALNs) or 1 to 3 positive ALNs and at least one of the following high-risk features: primary invasive tumor size 5 cm, histological grade 3 tumor, or central Ki-67 index 20%. If applicable, patients must have also completed adjuvant chemotherapy and radiotherapy prior to enrolling and have recovered from all acute side effects.

About Early Breast Cancer Breast cancer is the most common cancer among women worldwide.1 An estimated 90% of all breast cancer is diagnosed at an early stage.2 Approximately 70% of all breast cancers are HR+, HER2-, the most common subtype.3 Even within this subtype, HR+, HER2- breast cancer is a complex disease, and many factors such as if the cancer has spread to the lymph nodes and the biology of the tumor can impact the risk of recurrence. Approximately 30% of people diagnosed with HR+ early breast cancer are at risk of their cancer returning, potentially to incurable metastatic disease.4

About Verzenio (abemaciclib) Verzenio (abemaciclib) is an inhibitor of cyclin-dependent kinases (CDK)4 & 6, which are activated by binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4 & 6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.

In vitro, continuous exposure to Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in reduction of tumor size. Inhibiting CDK4 & 6 in healthy cells can result in side effects, some of which may be serious. Clinical evidence also suggests that Verzenio crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Verzenio and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations.

Verzenio is Lilly's first solid oral dosage form to be made using a faster, more efficient process known as continuous manufacturing. Continuous manufacturing is a new and advanced type of manufacturing within the pharmaceutical industry, and Lilly is one of the first companies to use this technology.

INDICATION Verzenio is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer:

IMPORTANT SAFETY INFORMATION FOR VERZENIO (abemaciclib)

Diarrhea occurred in 81% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 90% of patients receiving Verzenio alone in MONARCH 1. Grade 3 diarrhea occurred in 9% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 13% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 20% of patients receiving Verzenio alone in MONARCH 1. Episodes of diarrhea have been associated with dehydration and infection.

Diarrhea incidence was greatest during the first month of Verzenio dosing. In MONARCH 3, the median time to onset of the first diarrhea event was 8 days, and the median duration of diarrhea for Grades 2 and 3 were 11 and 8 days, respectively. In MONARCH 2, the median time to onset of the first diarrhea event was 6 days, and the median duration of diarrhea for Grades 2 and 3 were 9 days and 6 days, respectively. In MONARCH 3, 19% of patients with diarrhea required a dose omission and 13% required a dose reduction. In MONARCH 2, 22% of patients with diarrhea required a dose omission and 22% required a dose reduction. The time to onset and resolution for diarrhea were similar across MONARCH 3, MONARCH 2, and MONARCH 1.

Instruct patients that at the first sign of loose stools, they should start antidiarrheal therapy such as loperamide, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to Grade 1, and then resume Verzenio at the next lower dose.

Neutropenia occurred in 41% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 46% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 37% of patients receiving Verzenio alone in MONARCH 1. A Grade 3 decrease in neutrophil count (based on laboratory findings) occurred in 22% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 32% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 27% of patients receiving Verzenio alone in MONARCH 1. In MONARCH 3, the median time to first episode of Grade 3 neutropenia was 33 days, and in MONARCH 2 and MONARCH 1, was 29 days. In MONARCH 3, median duration of Grade 3 neutropenia was 11 days, and for MONARCH 2 and MONARCH 1 was 15 days.

Monitor complete blood counts prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Febrile neutropenia has been reported in <1% of patients exposed to Verzenio in the MONARCH studies. Two deaths due to neutropenic sepsis were observed in MONARCH 2. Inform patients to promptly report any episodes of fever to their healthcare provider.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with Verzenio and other CDK4/6 inhibitors. Across clinical trials (MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of Verzenio-treated patients had ILD/pneumonitis of any grade, 0.6% had Grade 3 or 4, and 0.4% had fatal outcomes. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded by means of appropriate investigations.

Dose interruption or dose reduction is recommended in patients who develop persistent or recurrent Grade 2 ILD/pneumonitis. Permanently discontinue Verzenio in all patients with grade 3 or 4 ILD/pneumonitis.

Grade 3 increases in alanine aminotransferase (ALT) (6% versus 2%) and aspartate aminotransferase (AST) (3% versus 1%) were reported in the Verzenio and placebo arms, respectively, in MONARCH 3. Grade 3 increases in ALT (4% versus 2%) and AST (2% versus 3%) were reported in the Verzenio and placebo arms respectively, in MONARCH 2.

In MONARCH 3, for patients receiving Verzenio plus an aromatase inhibitor with Grade 3 increases in ALT or AST, median time to onset was 61 and 71 days, respectively, and median time to resolution to Grade <3 was 14 and 15 days, respectively. In MONARCH 2, for patients receiving Verzenio plus fulvestrant with Grade 3 increases in ALT or AST, median time to onset was 57 and 185 days, respectively, and median time to resolution to Grade <3 was 14 and 13 days, respectively.

For assessment of potential hepatotoxicity, monitor liver function tests (LFTs) prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or Grade 3 or 4, hepatic transaminase elevation.

Venous thromboembolic events were reported in 5% of patients treated with Verzenio plus an aromatase inhibitor as compared to 0.6% of patients treated with an aromatase inhibitor plus placebo in MONARCH 3. Venous thromboembolic events were reported in 5% of patients treated with Verzenio plus fulvestrant in MONARCH 2 as compared to 0.9% of patients treated with fulvestrant plus placebo. Venous thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. Across the clinical development program, deaths due to venous thromboembolism have been reported. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate.

Verzenio can cause fetal harm when administered to a pregnant woman based on findings from animal studies and the mechanism of action. In animal reproduction studies, administration of abemaciclib to pregnant rats during the period of organogenesis caused teratogenicity and decreased fetal weight at maternal exposures that were similar to the human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Verzenio and for at least 3 weeks after the last dose. There are no data on the presence of Verzenio in human milk or its effects on the breastfed child or on milk production. Advise lactating women not to breastfeed during Verzenio treatment and for at least 3 weeks after the last dose because of the potential for serious adverse reactions in breastfed infants. Based on findings in animals, Verzenio may impair fertility in males of reproductive potential.

The most common adverse reactions (all grades, 10%) observed in MONARCH 3 for Verzenio plus anastrozole or letrozole and 2% higher than placebo plus anastrozole or letrozole vs placebo plus anastrozole or letrozole were diarrhea (81% vs 30%), neutropenia (41% vs 2%), fatigue (40% vs 32%), infections (39% vs 29%), nausea (39% vs 20%), abdominal pain (29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia (27% vs 11%), decreased appetite (24% vs 9%), leukopenia (21% vs 2%), creatinine increased (19% vs 4%), constipation (16% vs 12%), ALT increased (16% vs 7%), AST increased (15% vs 7%), rash (14% vs 5%), pruritus (13% vs 9%), cough (13% vs 9%), dyspnea (12% vs 6%), dizziness (11% vs 9%), weight decreased (10% vs 3%), influenza-like illness (10% vs 8%), and thrombocytopenia (10% vs 2%).

The most common adverse reactions (all grades, 10%) observed in MONARCH 2 for Verzenio plus fulvestrant and 2% higher than placebo plus fulvestrant vs placebo plus fulvestrant were diarrhea (86% vs 25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%), headache (20% vs 15%), dysgeusia (18% vs 3%), thrombocytopenia (16% vs 3%), alopecia (16% vs 2%), stomatitis (15% vs 10%), ALT increased (13% vs 5%), pruritus (13% vs 6%), cough (13% vs 11%), dizziness (12% vs 6%), AST increased (12% vs 7%), peripheral edema (12% vs 7%), creatinine increased (12% vs <1%), rash (11% vs 4%), pyrexia (11% vs 6%), and weight decreased (10% vs 2%).

The most common adverse reactions (all grades, 10%) observed in MONARCH 1 with Verzenio were diarrhea (90%), fatigue (65%), nausea (64%), decreased appetite (45%), abdominal pain (39%), neutropenia (37%), vomiting (35%), infections (31%), anemia (25%), thrombocytopenia (20%), headache (20%), cough (19%), leukopenia (17%), constipation (17%), arthralgia (15%), dry mouth (14%), weight decreased (14%), stomatitis (14%), creatinine increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%), dizziness (11%), and dehydration (10%).

The most frequently reported 5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 3 were neutropenia (22% vs 2%), diarrhea (9% vs 1%), leukopenia (8% vs <1%), ALT increased (7% vs 2%), and anemia (6% vs 1%).

The most frequently reported 5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 2 were neutropenia (27% vs 2%), diarrhea (13% vs <1%), leukopenia (9% vs 0%), anemia (7% vs 1%), and infections (6% vs 3%).

The most frequently reported 5% Grade 3 or 4 adverse reactions from MONARCH 1 with Verzenio were neutropenia (24%), diarrhea (20%), fatigue (13%), infections (7%), leukopenia (6%), anemia (5%), and nausea (5%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3 in 10% for Verzenio plus anastrozole or letrozole and 2% higher than placebo plus anastrozole or letrozole vs placebo plus anastrozole or letrozole were increased serum creatinine (98% vs 84%; 2% vs 0%), decreased white blood cells (82% vs 27%; 13% vs <1%), anemia (82% vs 28%; 2% vs 0%), decreased neutrophil count (80% vs 21%; 22% vs 3%), decreased lymphocyte count (53% vs 26%; 8% vs 2%), decreased platelet count (36% vs 12%; 2% vs <1%), increased ALT (48% vs 25%; 7% vs 2%), and increased AST (37% vs 23%; 4% vs <1%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2 in 10% for Verzenio plus fulvestrant and 2% higher than placebo plus fulvestrant vs placebo plus fulvestrant were increased serum creatinine (98% vs 74%; 1% vs 0%), decreased white blood cells (90% vs 33%; 23% vs 1%), decreased neutrophil count (87% vs 30%; 33% vs 4%), anemia (84% vs 33%; 3% vs <1%), decreased lymphocyte count (63% vs 32%; 12% vs 2%), decreased platelet count (53% vs 15%; 2% vs 0%), increased ALT (41% vs 32%; 5% vs 1%), and increased AST (37% vs 25%; 4% vs 4%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 were increased serum creatinine (98%; <1%), decreased white blood cells (91%; 28%), decreased neutrophil count (88%; 27%), anemia (68%; 0%), decreased lymphocyte count (42%; 14%), decreased platelet count (41%; 2%), increased ALT (31%; 3%), and increased AST (30%; 4%).

Strong and moderate CYP3A inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity. Avoid concomitant use of the strong CYP3A inhibitor ketoconazole. Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold. In patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the Verzenio dose to 100 mg twice daily with concomitant use of strong CYP3A inhibitors other than ketoconazole. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the Verzenio dose to 50 mg twice daily with concomitant use of strong CYP3A inhibitors. If a patient taking Verzenio discontinues a strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor. With concomitant use of moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing the Verzenio dose in 50 mg decrements. Patients should avoid grapefruit products.

Avoid concomitant use of strong or moderate CYP3A inducers and consider alternative agents. Coadministration of strong or moderate CYP3A inducers decreased the plasma concentrations of abemaciclib plus its active metabolites and may lead to reduced activity.

With severe hepatic impairment (Child-Pugh Class C), reduce the Verzenio dosing frequency to once daily. The pharmacokinetics of Verzenio in patients with severe renal impairment (CLcr <30 mL/min), end stage renal disease, or in patients on dialysis is unknown. No dosage adjustments are necessary in patients with mild or moderate hepatic (Child-Pugh A or B) and/or renal impairment (CLcr 30-89 mL/min).

AL HCP ISI 17SEP2019

Please see full Prescribing Information for Verzenio.

About Lilly OncologyFor more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly's commitment to people with cancer, please visit http://www.LillyOncology.com.

About Eli Lilly and CompanyLilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.com and lilly.com/newsroom.P-LLY

Lilly USA, LLC 2020. ALL RIGHTS RESERVED.

Verzenio is a trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.

Lilly Forward-Looking StatementThis press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Verzenio (abemaciclib) as a treatment for patients with breast cancer and the expected timing of regulatory submissions relating to Verzenio, and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of research, development, regulatory approval, and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date, that submission timelines will occur as planned, that Verzenio will receive additional regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

1World Health Organization. Breast cancer: prevention and control. https://www.who.int/cancer/detection/breastcancer/en/index1.html. Accessed: November 19, 2020.2Howlader N, et al. SEER Cancer Statistics Review, 1975-2013. http://seer.cancer.gov/csr/1975_2013/. Accessed: November 19, 2020.3Howlader N, Altekruse S, Li C. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5).4Reinert T and Barrios CH. Optimal Management of Hormone Receptor Positive Metastatic Breast Cancer in 2016. Ther Adv Med Oncol. 2015;7(6):304-20.

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Lilly Presents Positive Primary Outcome Data from monarchE that Builds on Previous Definitive Analysis for Verzenio - PRNewswire