Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

Author affiliations: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China (J. Zhang, H. Li, K. Ma, Y. Chen, Z. Qiu, B. Li, W. Jia, M. Liao, W. Qi); National Avian Influenza Para-Reference Laboratory, Ministry of Agriculture and Rural Affairs of the Peoples Republic of China, Guangzhou (J. Zhang, H. Li, W. Jia, M. Liao, W. Qi); Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs of the Peoples Republic of China, Guangzhou (J. Zhang, W. Jia, M. Liao, W. Qi); National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, National Development and Reform Commission, Guangzhou (J. Zhang, W. Jia, M. Liao, W. Qi); Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou (J. Zhang, W. Jia, M. Liao, W. Qi); Guangzhou South China Biological Medicine Co., Ltd, Guangzhou (H. Ye, W. Qiu, Z. Liang); Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou (W. Jia, M. Liao, W. Qi)

Since emerging in China in 2013, influenza A(H7N9) viruses have continued to circulate in mainland China, sporadically causing human infection (13). As of February 2020, a total of 1,568 laboratory-confirmed human cases and 616 related deaths had been reported, for a fatality rate of 40% (http://www.fao.org/ag/againfo/programmes/en/empres/H7N9/situation_update.html). In mid-2016, a highly pathogenic avian influenza (HPAI) virus of subtype H7N9 emerged, and the number of cases in humans began to rise sharply during a fifth wave (4,5). Animal studies indicated that these HPAI H7N9 viruses are highly virulent in chickens and have gained transmissibility among ferrets (57). Also, the cocirculation of HPAI (H7N9) viruses caused high genetic diversity and host adaption (8), posing public health concerns.

Although HPAI H7N9 viruses spread widely across China in 2017 (8,9), after an influenza H5/H7 bivalent vaccine for poultry was introduced in September 2017, the prevalence of the H7N9 viruses in birds and humans decreased dramatically (6,10). In early 2019, when the novel HPAI H7N9 viruses re-emerged, the isolation of HPAI H7N9 viruses from birds revealed them to be responsible for continuous epidemics in northeastern China (11). In March 2019, a human death in Gansu, China, was confirmed to have been caused by an H7N9 virus (12). To explore the prevalence and evolution of influenza A(H7N9) viruses, we sequenced 28 hemagglutinin (HA) and neuraminidase (NA) genes of poultry-origin H7N9 viruses circulating in China during 2019.

Figure 1

Figure 1. Evolutionary history of influenza A(H7N9) viruses, China, 20172019. A) Phylogenic tree of the hemagglutinin gene of H7N9 viruses. Colors indicate reference H7N9 viruses (n = 1,038) from each wave together with...

During JanuaryDecember 2019, we conducted poultry surveillance for influenza virus at live poultry markets in 15 provinces of China (Appendix Figure 9). We isolated 28 H7N9 viruses from tracheal and cloacal swab samples of chickens in Shandong, Hebei, and Liaoning Provinces (Figure 1, panel C; Appendix Table 1). Vaccination of all chickens in China was compulsory according to the Ministry of Agriculture and Rural Affairs of the Peoples Republic of China. We sequenced the HA and NA genes of 28 H7N9 viruses and submitted the sequences to GISAID (https://www.gisaid.org) (Appendix Table 2). All H7N9 viruses had 4 continuous basic amino acids at cleavage sites (i.e., KRKRTAR/G and KRKRIAR/G), suggestive of high pathogenicity. Phylogenic analysis demonstrated that the HA and NA genes of all of these HPAI H7N9 viruses belonged to the Yangtze River Delta lineage and formed a new subclade (Figure 1, panel A), which exhibited a long genetic distance to the HPAI H7N9 viruses that persisted during 20172018. In particular, the HA and NA genes of A/chicken/northeast China/19376-E5/2019(H7N9), A/chicken/northeast China/19254/2019(H7N9), and A/chicken/northeast China/LN190408A/2019(H7N9) were genetically closely related to the human-infecting influenza A(H7N9) viruses from Gansu (Figure 1, panel B; Appendix Figures 13), implying the potential risk for the reemerged HPAI H7N9 viruses to infect humans.

Figure 2

Figure 2. Time-scaled evolution of influenza A(H7N9) viruses, China. A) Analysis of root-to-tip divergence against sampling date for the hemagglutinin gene segment (n = 189). B) Maximum clade credibility tree of the hemagglutinin...

A root-to-tip regression analysis of temporal structure revealed aspects of the clock-like structure of 189 H7N9 viruses (correlation coefficient 0.89; R2 0.95) during 20132019 (Figure 2, panel A). The epidemic HPAI H7N9 viruses had circulated in China since 2017 and can be classified into 2 sublineages, A and B. The HA and NA genes of the HPAI H7N9 viruses in 2019 belonged to a new sublineage B, whereas the HPAI H7N9 viruses circulating in 20172018 grouped into sublineage A (Figure 2, panel B; Appendix Figures 4, 5). Using the evolutionary rates of HA and NA, we estimated the times of origin (95% highest population density) of HPAI H7N9 viruses in sublineage B, which were September 2017June 2018 for HA and April 2017May 2018 for NA. Our HPAI H7N9 isolates exhibited traits of sublineages B-1 and B-2. We observed that the HPAI H7N9 viruses in eastern and northeastern China belonged to sublineage B-2 (Figure 2, panel B). However, in mid-2019, the HPAI H7N9 viruses continued to evolve and formed sublineage B-1, which suggested that the estimated times to the most recent common ancestors were May 2019 for HA genes and February 2019 for NA genes. Also, the human- and chicken-origin HPAI H7N9 viruses from Liaoning, Gansu, and Inner Mongolia clustered together in sublineage B-1. These results indicate that the poultry-origin H7N9 virus in sublineage B-1 emerged before the human spillover event in March 2019.

Although no substantial difference surfaced in the substitution rate of HA genes between H7N9 viruses during 20172018 and the viruses during 2019, the increased substitution rate occurred in the first and second codons of reemerged HPAI H7N9 viruses (Appendix Table 4). In a maximum clade credibility tree of the HA gene, 9 independently occurring mutations gave rise to the new sublineage-B circulating in 2019, including A9S, R22K, E71K, I78V, T116K, V125T, A151T, K301R, D439N (H7 numbering, https://www.fludb.org/brc/haNumbering.spg) (Figure 2, panel B), and only the V125T and A151T substitutions of the HA protein were reported as immune escape mutations (13). In addition, sublineage B-1 appeared to have acquired 3 parallel K184R, I499V, I520T (H7 numbering) mutations. The prevailing K184R substitutions of HPAI H7N9 viruses occurred during 2019. The K184R mutation was located in the antigenic site B and receptor binding region (Appendix Figure 6), suggesting that K184R was a potential mediator of viral antigenicity.

We used a hemagglutinin inhibition assay with an antigen of 15 H7N9 viruses circulating during 20172019, along with specific antiserum of 6 H7N9 viruses and 2 commonly used reassortant inactivated vaccines, H7N9-Re-2 and H7N9-rGD76, as controls. Antiserum from chickens vaccinated with H7N9-Re-2 strains showed high titers (910 log2) and with H7N9-rGD76 strains showed low titers (48 log2) to the HPAI H7N9 viruses circulating during 20182019 (Table 1). Moreover, the crosshemagglutinin inhibition assay suggested statistically significant antigenic differences between the HPAI H7N9 viruses circulating during 2017 and during 20182019 (Table 2; Appendix Figure 7), indicative of antigenic drift of the reemerged HPAI H7N9 viruses. H7N9-Re-2 and H7N9-rGD76 inactivated vaccines have been widely used in chicken populations in mainland China since 2019 (14). Of note, we found that the virus shedding of chickens vaccinated with H7N9-Re-2 and H7N9-rGD76 against HPAI H7N9 viruses during 2019 ranged from 30% to 80% (Appendix Table 3); therefore, a timely update of H7N9 vaccine is needed.

Next, we evaluated the protective efficacy of the new candidate H7N9 inactivated vaccine (H71903)that is, reverse genetic recombinant carrying HA and NA of A/chicken/east China/H7SD12/2019(H7N9) with internal genes of A/duck/Guangdong/D7/2007(H5N2)in chickens against the challenge of 4 HPAI H7N9 viruses prevailing in sublineage B in 2019. All of the control chickens challenged with the H7N9 viruses died within 6 days of challenge (Appendix Figure 8). However, virus shedding was not detected from any of the vaccinated chickens challenged with H7N9 viruses (Appendix Table 3), indicating that the new candidate H7N9 vaccine could provide sound protection for chickens against challenge with these reemerged H7N9 variants.

Our findings highlight that the HPAI H7N9 viruses that reemerged during 2019 had been cocirculating at a low level in eastern and northeastern China after the vaccination strategy was implemented. These HPAI H7N9 viruses continued to evolve and showed antigenic drift, posing a public health concern. Although vaccination can largely control the occurrence of H7N9 virus outbreaks, it can also accelerate the generation of novel variants. Therefore, comprehensive surveillance and enhancement of biosecurity precautions should be undertaken immediately to prevent the influenza virus epidemic from becoming a pandemic.

Dr. Zhang is a PhD student at South China Agricultural University, Guangzhou, China. His research interests are the epidemiology and pathogenesis of emerging and re-emerging infectious diseases.

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We acknowledge all contributors who submitted the sequence data on which this research is based to the GISAID EpiFlu Database. All submitters of data may be contacted directly through the GISAID website (http://www.gisaid.org).

This work was supported by the Key Research and Development Program of Guangdong Province (2019B020218004), the National Natural Science Foundation of China (31672586, 31830097, and 319410014), the Earmarked Fund for China Agriculture Research System (CARS-41-G16), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2018, to W.Q.), and the Young Scholars of Yangtze River Scholar Professor Program (2019, to W.Q.).

Suggested citation for this article: Zhang J, Ye H, Li H, Ma K, Qiu W, Chen Y, et al. Evolution and antigenic drift of influenza A(H7N9) viruses, China, 20172019. Emerg Infect Dis. 2020 Aug [date cited]. https://doi.org/10.3201/eid2608.200244

The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.

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Evolution and Antigenic Drift of Influenza A (H7N9) Viruses, China, 20172019 - CDC

News Release

Thursday, July 9, 2020

Comparing epigenetic differences between humans and domestic dogs provides an emerging model of aging.

One of the most common misconceptions is that one human year equals seven dog years in terms of aging. However, this equivalency is misleading and has been consistently dismissed by veterinarians. A recent study, published in the journalCell Systems, lays out a new framework for comparing dog-to-human aging. In one such comparison, the researchers found the first eight weeks of a dogs life is comparable to the first nine months of human infancy, but the ratio changes over time. The research used epigenetics, a process by which modifications occur in the genome, as a biological marker to study the aging process. By comparing when and what epigenetic changes mark certain developmental periods in humans and dogs, researchers hope to gain specific insight into human aging as well.

Researchers performed a comprehensive analysis and quantitatively compared the progression of aging between two mammals, dogs and humans. Scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and collaborators at the University of California (UC) San Diego, UC Davis and the University of Pittsburgh School of Medicine carried out the research.

All mammals experience the same overarching developmental timeline: birth, infancy, youth, puberty, adulthood and death. But researchers have long sought specific biological events that govern when such life stages take place. One means to study such a progression involves epigenetics gene expression changes caused by factors other than the DNA sequence itself. Recent findings have shown that epigenetic changes are linked to specific stages of aging and that these are shared among species.

Researchers focused on one type of epigenetic change called methylation, a process in which molecules called methyl groups are attached to particular DNA sequences, usually parts of a gene. Attaching to these DNA regions effectively turns the gene into the "off" position. So far, researchers have identified that in humans, methylation patterns change predictably over time. These patterns have allowed the creation of mathematical models that can accurately gauge the age of an individual called "epigenetic clocks."

But these epigenetic clocks have only been successful in predicting human age. They do not seem to be valid across species, such as in mice, dogs, and wolves. To see why the epigenetic clocks in these other species differed from the human version, researchers first studied the epigenetic changes over the lifetime of a domestic dog and compared the resultsobtained with humans.

Dogs are a useful model for such comparisons because much of their environment, diet, chemical exposure, and physiological and developmental patterns are similar to humans.

"Dogs experience the same biological hallmarks of aging as humans, but do so in a compressed period, around 10 to 15 years on average, versus over 70 years in humans. This makes dogs invaluable for studying the genetics of aging across mammals, including humans," said Elaine Ostrander, Ph.D., NIH Distinguished Investigator and co-author of the paper.

Dr. Ostrander and her colleagues in Trey Ideker's laboratory at UC San Diego took blood samples from 104 dogs, mostly Labrador retrievers, ranging from four weeks to 16 years of age. They also obtained previously published methylation patterns from 320 people, whose ages ranged from 1 to 103 years. The researchers then studied and compared the methylation patterns from both species.

Based on the data, researchers identified similar age-related methylation patterns, specifically when pairing young dogs with young humans or older dogs with older humans. They did not observe this relationship when comparing young dogs to older humans and vice versa.

The study also found that groups of specific genes involved in development can explain much of the similarity, which had similar methylation patterns during aging in dogs and humans.

"These results suggest that aging can, in part, be explained by a continuum of changes beginning in development," said Dr. Ideker. "The programs of development are expressed incredibly strongly at defined periods when the pup is in the womb and childhood. But equally strongly are systems that clamp down to stop it. In a sense, we are looking at aging as the residual 'afterburn' of those powerful forces."

The researchers also attempted to correlate the human epigenetic clock with dogs, using this as a proxy for converting dog years to human years.

The new formula is more complicated than the "multiply by seven" method. When dogs and humans experience similar physiological milestones, such as infancy, adolescence and aging, the new formula provided reasonable estimates of equivalent ages. For example, by using the new formula, eight weeks in dogs roughly translates to nine months in humans, which corresponds to the infant stage in both puppies and babies. The expected lifespan of senior Labrador retrievers, 12 years, correctly translates to 70 years in humans, the worldwide average life expectancy.

The group acknowledges that the dog-to-human years formula is largely based on data from Labrador retrievers alone. Hence, future studies with other dog breeds will be required to test the formula's generalizability. Because dog breeds have different life spans, the formula may be different among breeds.

Dr. Ostrander noted, "It will be particularly interesting to study long-lived breeds, a disproportionate number of which are small in size, versus breeds with a shorter lifespan, which includes many larger breeds. This will help us correlate the well-recognized relationship between skeletal size and lifespan in dogs."

The study also demonstrates that studying methylation patterns may be a useful method to quantitatively translate the age-related physiology experienced by one organism (e.g., humans) to the age at which physiology in a second organism is most similar (e.g., dogs). The group hopes that such translation may provide a useful tool for understanding aging and identifying ways to maximize healthy lifespans.

"This study, which highlights the relevance of canine aging studies, further expands the utility of the dog as a genetic system for studies that inform human health and biology," said Dr. Ostrander.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

NHGRI is one of the 27 institutes and centers at the National Institutes of Health. The NHGRI Extramural Research Program supports grants for research, and training and career development at sites nationwide. Additional information about NHGRI can be found at https://www.genome.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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Link:

NIH researchers reframe dog-to-human aging comparisons - National Institutes of Health

As 2020 wears on, Shah and others are grappling with a new and bitter reality: Because of the economic crisis, which was triggered by the current pandemic, which was worsened by a lack of public-health investment, public-health agencies will probably suffer more budget cuts in the coming years. Its not like the environmental movement or even the health care reform movement, where you have activists and lobbyists and advocates fighting to change the status quo or to secure their piece of the pie, Hearne told me. Its a lot of isolated departments across the country, saying, Oh, well just keep doing Gods work over here, and if our budget gets cut again, well just make do somehow.

To change this, Shah, Hearne and others say, the public-health community will need to muster more political will than it has in the past. In the years preceding the coronavirus outbreak, the United States faced a host of public-health disasters: a resurgence of measles and syphilis; an uptick in food-borne illness; and a continuing lead-contaminated-water crisis. None of those issues captured even a fraction of the attention that universal health care did. In fact, while the health care system was discussed relentlessly in 2019, as it tends to be almost every election season, public health was barely mentioned at all. No one is going to vote for you or name a hospital wing after you because you kept them from getting something that they didnt think they were susceptible to in the first place, Frieden says. The people who cure diseases are glorified, not the people who prevent them.

In late June, Abbott reversed course again and ordered the states bars to close and restaurants to reduce their capacity to 50 percent (they had been at 75 percent for several days). He also issued an executive order requiring all Texans in counties with more than 20 active Covid-19 cases to wear a mask in public. Scientists worried that it was too little too late, and by early July, the numbers seemed to prove them right. On July 8, the state hit a record 9,952 new coronavirus cases reported in a single day. The states positivity rate the portion of all tests done that come out positive also rose to 15.6 percent, from 7.9 percent just three weeks earlier.

Hospital beds were filling up, hospital floors reconfigured and surge units readied. Doctors and nurses, in Harris County and elsewhere, have begun a worrying and familiar census-taking of ventilators and personal protective equipment. And the same stories that played out in Wuhan and Lombardy and Seattle and New York were beginning anew. And not only in Texas. In more than 35 states, including some that had previously brought their outbreaks under control, daily case counts are rising, positivity rates are rising and new grim records are being set and then quickly surpassed. People in Texas, Florida, California and New Jersey are bracing for a second wave of outbreaks in the fall, even as the first wave has yet to fully recede. The root of this catastrophe, doctors, scientists and health historians say, is our failure to fully incorporate public health into our understanding of what it means to be a functioning society. Until we do that, we will be unable to effectively respond to crises like this one let alone prevent them.

In Harris County, Hidalgo and her advisers have created a numerical and color-coded warning system so that residents know how dire the threat level is and exactly how cautious they need to be. We needed something that was clear and concise, because the back and forth with all the orders was confusing people and causing them to tune out, she told me. I went with colors and numbers because some people like one and some people like the other, and I really just want this to stick. Right now, Harris County is at the highest threat level: one (or red), meaning that the outbreak there is severe and uncontrolled and that people should leave home only to meet essential needs. As with all things coronavirus-related, it will take a while to see if people hear the message and heed it.

In the meantime, the political and cultural battles over how to respond to the coronavirus crisis have continued unabated. The Texas Education Agency said they would withhold funding for schools that dont enable students to attend full-time, in-person, this fall. On July 8, the mayor of Houston, Sylvester Turner, prevailed on the citys convention center to cancel the state Republican convention that was scheduled for mid-July. The state party has challenged the move in court.

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Why Were Losing the Battle With Covid-19 - The New York Times

This week Summerville Medical Center is celebrating the one year anniversary of consolidating obstetric and neonatal services across Trident Health system to one location at Summerville Medical Center.

We are honored to continue providing excellent care to our Lowcountry families close to home. said Dr. Beth Cook, Womens Services Medical Director for Summerville Medical Center and a local OB/GYN.

Combining more than 170 highly qualified clinicians and board-certified physicians, a comprehensive range of services for women and children, and facility resources onto one campus signaled a landmark moment for the health system in caring for Lowcountry women and children.

In the last year, the hospital has delivered more than 2,700 babies, including 36 sets of twins, and cared for more than 400 babies in the hospitals Level II neonatal ICU (NICU).

In the 26 years Summerville Medical Center has been open, we have been embraced by our community, said Dr. Beth Cook.

In 2018, Summerville Medical Center completed a $53 million womens and neonatal expansion in advance of the consolidation that provides patients with the highest quality care and the comforts of home. The new unit features a two story tower with 30 private postpartum rooms, 12 labor and delivery rooms, a 16-bed Level II neonatal ICU, Emergency Department OB suite, C-section suite, and more than $10 million in state-of-the-art technology.

Summerville Medical Center is proud to be the only Lowcountry hospital offering NICView technology, a 24/7 secure feed for families to watch their baby on any electronic device. Other additions such as wireless fetal monitoring and 55 Apple TVs in patient rooms provides families with the comforts of home while being in the hospitals care. In addition, the hospital provides families with special touches to celebrate the occasion with a celebratory meal for mom and partner, including sparkling grape juice in champagne flutes, a high end bath robe for mom, and a special raised on sweet tea and sunshine for their little one.

The hospital also has a Maternal Fetal Medicine Clinic that provides care for high risk expecting moms on their pregnancy journey, as well as genetic counseling and fertility services for women considering starting a family. The Maternal Fetal Medicine Clinic cared for more than 1,000 families in the last year.

We are experiencing significant growth in the Lowcountry, commented Angel Bozard, AVP of Womens & Childrens Services at Summerville Medical Center. As a result, Summerville Medical Center is committed to continue growing our facility, our services and our team so that moms and babies can receive excellent care in their own community. We are honored to have the most experienced providers of maternity and newborn care here at Summerville Medical Center.

Take a virtual tour of the new unit at http://www.TridentHealthsystem.com/momandbaby.

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Summerville Medical celebrates 1 year anniversary of obstetric consolidation - Journalscene.com

HIV, shown here budding from cell, remains stubbornly resistant to cure strategies because its DNA can lie silently in host chromosomes for years.

By Jon CohenJul. 7, 2020 , 9:00 AM

A 36-year-old man in Brazil has seemingly cleared an HIV infectionmaking him the proof of principle in humans of a novel drug strategy designed to flush the AIDS virus out of all of its reservoirs in the body. After receiving an especially aggressive combination of antiretroviral (ARV) drugs and nicotinamide (vitamin B3), the man, who asks to be referred to as the So Paulo Patient to protect his privacy, went off all HIV treatment in March 2019 and has not had the virus return to his blood.

The patients story is remarkable, says Steven Deeks, an HIV/AIDS clinician at the University of California, San Franciscowho was not involved with this study. But he and others, including the study leaders, caution that the success hasnt been long or definitive enough to label it a cure. Interesting anecdotes have long driven the HIV cure field, and they should be considered largely as hypothesis-generating observations that can simulate new areas of investigation, says Deeks, who also conducts HIV cure research.

Most people who suppress HIV with ARVs and later stop treatment see it come racing back to high levels within weeks. Not only did the So Paulo Patient not experience a rebound, but his HIV antibodies also dropped to extremely low levels, hinting at the possibility he may have cleared infected cells in the lymph nodes and gut.

Ricardo Diaz of the Federal University of So Paulo, the clinical investigator running the study, says he doesnt know whether the patient is cured. He has very little antigen, Diaz says, referring to HIV proteins that trigger the production of antibodies and other immune responses. But he notes his team has not sampled the mans lymph nodes or gut for the virus since he stopped treatment. Diaz discussed the patient today at a press conference for AIDS 2020, the 23rd International AIDS Conference taking place virtually this week, and he plans to present the study in full tomorrow.

Only two people are known to have been cured of their HIV infections:Timothy Ray Brown and a man who has asked to be referred to as the London Patient; both received bone marrow transplants as part of a treatment for cancers. The transplants cleared their infections and gave them new immune systems that resist infection with the virus. But bone marrow transplants are expensive, complicated interventions that can have serious side effects, making them an impractical cure for the 38 million people now living with the AIDS virus.

Other potential HIV cure cases have received intense media attention only to see the virus return after prolonged absences. Most soberingly, a baby in Mississippi who started ARVs shortly after birth stopped treatment at 18 months and was thought to be cured until the virus suddenly resurfaced more than 2 years later. Several adults who had bone marrow transplants and appeared to have been cured were not.

HIV has proven particularly difficult to eliminate because the virus weaves its genetic material into human chromosomes, where it can lie dormant, escaping the immune surveillance that typically eliminates foreign invaders. These silently infected cells may persist, perhaps indefinitely, because they have stem cell-like properties and can make clones of themselves. Researchers have come up with several strategies to flush reservoirs of cells that harbor latent HIV infections, but none have provedeffective.

To compare different reservoir-clearing strategies, Diaz and colleagues in 2015 recruited the So Paulo Patient and other individuals who had controlled their HIV infections with ARVs. The most aggressive approach, used in this man and four others, added two ARVs to the three they were already taking, in the hopethis would rout out any HIV that might have dodged the standard treatment. On top of this intensification, the study group received nicotinamide, which can, in theory, prod infected cells to wake up the latent virus. When those cells make new HIV, they either self-destruct or are vulnerable to immune attack.

After 48 weeks on this intensified schedule, the five trial participants returned to their regular three-drug regimen for 3 years, after which they stopped all treatment. Four saw the virus quickly return, but the So Paulo Patient has now gone 66 weeks without signs of being infected. Sensitive tests that detect viral genetic material did not find HIV in his blood. An even more sensitive test, which mixed his blood with cells that are susceptible to HIV infection, produced no newly infected cells.

Intriguingly, during the intensification period with nicotinamide, this man was the only one of the five who twice had the virus detected on standard blood tests. To Diaz, this suggests that latently infected cells had been roused, leading to blips of viral production. Im always trying to be a little bit the devils advocate, but in this case, Im optimistic, Diaz says. Maybe this strategy is not good for everybody because it only worked in one out of five here. But maybe it did get rid of virus. I dont know. I think this is a possibility.

Deeks says he does not know of any report, other than the two people cured by bone marrow transplants, of decreases in HIV antibody levels after stopping treatment. One large, outstanding question, he says, is whether the man indeed stopped taking his ARVs. I have not taken any HIV medication since March 30, 2019, the So Paulo Patient says. Diaz plans to confirm this by examining the mans blood for ARVs.

Another unknown is how soon the man started ARVs after becoming infected with HIV. Studies have shown that a small percentage of people who begin ARV treatment shortly after becoming infected have a better chance of controlling the virus for prolonged periods if they cease the drugs, presumably because they never built large reservoirs of infected cells. The So Paulo Patient started treatment 2 months after being diagnosed in October 2012. As with most people who become infected with HIV, he cannot say for certain when transmission occurred, but he suspects it was in June 2012. The only certainty is that he tested negative in 2010.

Its also unclear how nicotinamide would awaken silent infected cells. HIV DNA remains latent when it tightly spools around chromosome proteins known as histones. To make viral copies, it must unspool, and Diaz points to evidence that nicotinamide can trigger this unspooling in different ways.

Sharon Lewin, an HIV cure researcher who directs the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, finds the antibody response intriguing. But she underscores it is not a convincing, controlled experiment. We need to move beyond case reports of HIV remission, Lewin says. I would be super excited to see long term remission in multiple participants in a clinical trial. This is what the field needs to really advance.

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An intriguingbut far from provenHIV cure in the 'So Paulo Patient' - Science Magazine

SAN DIEGO, July 08, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced today that two top cytogeneticists from leading institutions in The Netherlands and France presented their research data as part of a multicentric, international effort to compare data generated with Bionanos Saphyr system against gold standard cytogenetic methods consisting of karyotyping, FISH, and/or chromosomal microarray in patients with a variety of constitutional or inherited genetic disorders and in patients with leukemias. In back-to-back online presentations, each showed 100% concordance between Saphyr and standard cytogenetics along with other discoveries that extend the capabilities of the current standard of care.

Summary of data presentations:

In a webinar originally hosted by LabRoots on Friday, June 22, Dr. Laila El Khattabi from the Cochin Hospital in Paris, France discussed how Saphyr improved structural variant detection for constitutional chromosomal aberrations in her research. The data originate from an international multi-center effort between the hospitals of Paris-Cochin, Lyon and Clermont-Ferrand and the Radboud University Medical Center in the Netherlands, as part of the first international consortium to validate Saphyr for constitutional cytogenetic analysis. The consortium compared the performance of Saphyr against the combination of karyotyping, FISH and array-based methods in 85 samples with a variety of constitutional aberrations including deletions, duplications, balanced and unbalanced translocations, inversions, ring chromosomes and aneuploidies in patients with intellectual disabilities and recurrent miscarriages. Saphyr showed 100% concordance with gold standard methods in these 85 samples. Dr. El Khattabi expressed the consortiums confidence in Saphyrs potential to largely replace standard cytogenetic testing methods in the future. A manuscript describing the study results will be submitted for publication in the coming weeks.

Dr. Alexander Hoischen from Radboud University Medical Center described how Bionano genome imaging identified likely pathogenic variants in 25% of unsolved rare disease cases analyzed with Saphyr. Dr. Hoischen presented two of these research cases, which involved families with undiagnosed genetic disorders. The first case involved a rare and aggressive childhood tumor named Atypical Teratoid Rhabdoid Tumor (ATRT) in which Saphyr detected an insertion in the SMARCB1 gene in a family affected by ATRT, while MLPA and next generation sequencing were unable to identify this variant. In a family affected by intellectual disability, Saphyr identified a single de novo deletion affecting the NSF gene, undetected by chromosomal microarray, whole exome and whole genome sequencing and long read sequencing. This deletion was confirmed to be de novo in the child through PCR validation. Finally, Dr. Hoischen provided an update on his retrospective comparative study on leukemias, which he presented at ESHG 2020 and is expected to be submitted for peer-review publication in the near future. The study showed 100% concordance between Bionanos Saphyr system and standard cytogenetics in 48 leukemia patients. Additionally, Saphyr identified novel events previously undetected by traditional cytogenetic methods, many of them being rare inter-chromosomal translocations causing gene fusions never described before, opening potential new avenues of research in precision medicine and drug development. Dr. Hoischen concluded that Saphyr has value in solving unanswered rare disease cases and has the potential to replace classical cytogenetics methods.

At the ESHG 2020 conference, Dr. Uwe Heinrich, representing MVZ Martinsried, Germany presented that Bionano was able to confirm all known large rearrangements in a cohort of patients with intellectual disability, developmental disorders and chromosomal aberrations. Drs. Hoischen and Heinrich announced that their respective teams are planning to seek accreditation for the Saphyr system, to start offering Bionanos genome imaging as part of a stepwise diagnosis, and to subsequently replace chromosomal microarray with Saphyr altogether later on.

Erik Holmlin, Ph.D., CEO of Bionano Genomics commented: We previously demonstrated the notable performance of Saphyr in leukemia studies across the globe, but the international study presented by Dr. El Khattabi demonstrates that Saphyr performs equally well in genetic diseases such as intellectual disabilities and subfertility. Saphyr showed 100% concordance with traditional cytogenetic methods and made additional discoveries in both leukemia patients and in those with constitutional disorders. We believe that Saphyr is capable of replacing traditional cytogenetic methods and consolidating these outdated methods into a single digital platform that is faster, less expensive and has lower manual labor needs, while providing greater accuracy than these methods.

A recording of the presentation by Drs. El Khattabi and Hoischen can be viewed at https://bionanogenomics.com/library/webinars/

About Bionano GenomicsBionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing. Bionanos Saphyr system is a platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. For more information, visitwww.bionanogenomics.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: our intentions, beliefs, projections, outlook, analyses or current expectations concerning the Saphyr System; the intended use of Saphyr by the institutions identified in this press release; expectations regarding the rate and extent of adoption of Saphyr in research and clinical settings; and the general effectiveness and utility of Saphyr, including its ability to replace traditional cytogenetic methods and enable discoveries that can contribute to treatment of disease. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the loss of key members of management and our commercial team; and the risks and uncertainties associated withour business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

ContactsCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 (617) 430-7577arr@lifesciadvisors.com

Media Contact:Kirsten ThomasThe Ruth Group+1 (508) 280-6592kthomas@theruthgroup.com

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First Extensive Validation Study of Saphyr for Constitutional Genetic Disorders by European Consortium Shows 100% Concordance to Standard Cytogenetics...

Putting your employees and company culture first keeps the focus on inclusion and innovation, giving the company an incredible competitive advantage. At least thats the mantra at the heart of MyoKardia, a California-based biotech company that is developing precision medicine for cardiovascular diseases (CVDs).

We want to change the world for people with cardiovascular disease by taking a patient-focused, scientifically driven approach, Tassos Gianakakos, MyoKardias CEO, told BioSpace. When youre addressing hard problems, you need different opinions, approaches, and expertise at the table. That is the only way to effectively deliver on the mission.

Companies are at risk of getting it wrong when they dont focus on culture early on you need to launch out of the gate with a culture mindset, Gianakakos added. You get back what you put out there, so being a mission-driven, culture-valuing company will help draw in likeminded employees. That group genius is what enables remarkable improvements to health outcomes for society.

CVD, also called heart disease, is a blanket term used to describe many diseases that affect the heart or blood vessels. Globally, heart diseases are by far the number one killer in the world, with CVDs responsible for 17.9 million deaths worldwide. These conditions are highly prevalent throughout the population 30.3 million US adults have been diagnosed with CVDs.

Credit: WHO

We lose more people in the U.S. and around the world to cardiovascular conditions than any other disease, Gianakakos. MyoKardias entire purpose is to change that. We want to be the leading company developing precision medicine for CVDs. Our approach is different; were subtyping patient populations within these large, heterogeneous conditions so that we can identify effective, targeted therapeutics. The idea is to discover and develop medicines that have transformative potential for people.

MyoKardias late-stage pipeline focuses on two CVDs: hypertrophic cardiomyopathy (HCM), where the heart muscle becomes abnormally thick (hypertrophied), making it harder for the heart to pump blood; and dilated cardiomyopathy (DCM), where the hearts main pumping chamber (called the left ventricle) stretches and thins (dilates), making it harder for the heart to pump blood.

HCM is frequently caused by gene mutations in heart muscle proteins that cause the heart muscle to squeeze with more force than needed, leading to abnormal thickening over time. It is the most common inherited heart disease, occurring in about 1 in 500 people (over 650,000 people in the US). HCM is the most common cause of cardiac arrest (where the heart suddenly stops beating), in younger people. Although certain medications, like beta blockers and blood thinners, are used to treat some HCM symptoms, there arent any drugs that specifically address the underlying problem in HCM the genetic mutation-induced thickened heart muscle.

Positive results from a Phase III clinical trial of mavacamten, MyoKardias lead drug candidate for HCM, were announced in May. MyoKardia aims to submit a New Drug Application (NDA) submission with the FDA in the first quarter of 2021 and is planning for its first product launch.

DCMs causes may be varied in addition to genetics, a number of diseases are linked to left ventricle dilation, including diabetes, obesity, high blood pressure, infections, and drug and alcohol abuse. It is a common cause of systolic heart failure (where the heart isnt pumping blood as well as it should be). Medications such as angiotensin-converting enzyme (ACE) inhibitors, beta blockers, and blood thinners can successfully treat heart failure, but none of them are specific to the heart and have systemic side effects.

MyoKardias investigational drug danicamtiv is intended to increase heart contractions without interfering with the hearts ability to fill. The company recently reported encouraging data from their Phase IIa study of danicamtiv in chronic heart failure patients. They plan to advance into two new Phase II studies in specific patient populations: genetic DCM patients and systolic heart failure patients with paroxysmal or persistent atrial fibrillation (AFib).

BioSpace spoke to Gianakakos and Ingrid Boyes, MyoKardias Senior Vice President of Human Resources, about the companys pipeline, culture, and why building a culture of diversity and inclusion is foundational to a company.

(Boyes previously spoke to BioSpace in 2015 about what MyoKardia is looking for when theyre hiring.)

COMPANY CULTURE, DIVERSITY & INCLUSION

BioSpace: Why is company culture and diversity so important to a successful company? How do you promote diversity and inclusion at MyoKardia?

Gianakakos: The diseases we are tackling know no ethnic, gender or socioeconomic boundaries. So our company culture needs to reflect this. Our teams need to reflect this and the patients we are working to help. Its hard for us to see doing good science and achieving our mission any other way. And it goes beyond the science. To have a successful and meaningful company, we need to innovate more broadly in growth strategies, commercial models, and new ways to more effectively get our therapies to patients who need it around the world.

Im proud of how we embrace each others differences gender, ethnicity and race, orientation, socioeconomic status and beliefs -- and highlight the importance of company culture. Everyone at MyoKardia shares the same mission, the same values, but we embrace and value each persons differences. We want our employees to feel safe sharing their own voice and know that different points of view are valued and respected.

Boyes: Tassos passion for company culture is a large part of why I joined the company five years ago. As a Hispanic woman, its really important to me to create an environment where people can thrive and grow. We have fun while creating a valuable community. As employee number 50, I was able to focus on how to help build a company culture with Tassos that values diversity by building on employees experiences. We were very intentional about company culture and how we evolve it. Every voice at MyoKardia counts and every person plays an important role in improving CVD patients lives.

We actively seek input from our employees and encourage them to challenge the status quo. We also invite employees to lead activities and bring their unique perspectives to work.

Gianakakos: We want to bring great people who are passionate to the company and play to their strengths. Focusing on increasing their engagement and creating an energizing work environment allows employees to do their most creative and best work. Having people build the skills they want and need by cross-training and encouraging lifelong learning improves the connectivity and the innovation within the company.

We believe this is one of the key competitive advantages at MyoKardia connecting and supporting people to engage and excite them and ensuring they have a voice that is valued. Having diverse perspectives and a commitment to listening leads us to much better decisions and results.

What kind of diversity and engagement activities do you do both within MyoKardia and externally with the general public?

Boyes: We always strive to improve the culture by actively soliciting feedback from our employees though a number of channels, including engagement surveys. Implementing employee-led initiatives has brought great features into the companys culture, such as a womens forum that brings in external women speakers and identifies female role models, a green team focused on being more sustainable, and a community volunteer team that actively supports our community. All of these activities also help to develop valuable leadership skills regardless of title within our organization.

Gianakakos: Based on employee feedback, weve also implemented several policy changes, such as increasing the companys 401k match and giving each employee a six-week sabbatical once they have been with the company for six years.

Boyes: We want to be connected with diverse organizations and participate as much as possible externally connecting with others in the community with culture-focused passion. We are always looking to connect with driven people who share our company values.

Switching gears to the science, what does CVD drug development look like right now?

Gianakakos: In many ways, CVD is where oncology was 20 years ago there were no precision medicines and non-specific treatments such as chemotherapy and radiation were used regardless of cancer type. The number of drugs in development for CVDs is woefully low relative to its global burden. There are over 1,100 oncology drugs in development, but only 200 for cardiovascular diseases, despite CVDs killing more people annually than all cancers combined. In oncology today, precision medicine approaches have given us countless targeted therapies that have completely transformed patient care. We are making this happen today in CVD, where we feel may even have advantages over oncology given the many tools now available to monitor the heart, such as wearables and patches that measure the heart rate and rhythm.

What made you focus on precision cardiac medicine? Why now?

Gianakakos: Momentum around precision medicine in other disease areas was clearly growing and resulting in important advances when MyoKardia started eight years ago. The first cystic fibrosis drug that treated the underlying cause rather than the symptoms (ivacaftor) was just launched by Vertex and a few years prior to MyoKardia our founding investors were involved in launching several exciting new companies like Foundation Medicine, Agios and bluebird bio who were developing potentially game-changing targeted therapies.

Traditionally, CVD clinical trials are massive, expensive, and often fail. When there is a lack of understanding of the underlying disease biology and its unclear exactly what the drug is doing, that can result in a large signal-to-noise ratio. This in turn, requires larger studies which are more expensive, and the therapies have to benefit large numbers of patients for the investment to make sense. This is a recipe that doesnt lead to innovative or efficient drug discovery. Identifying smaller, more homogenous subgroups of patients who all share the same disease pathology, and targeting them with drugs designed specifically to address the underlying disease biology is so powerful. Were matching the tailored treatment to address each persons underlying condition understanding how to identify the right drugs for the right patients.

CARDIOVASCULAR DISEASE DRUG DEVELOPMENT & MYOKARDIAS PIPELINE

What are the major knowledge gaps that need to be addressed to make precision cardiac medicine achievable for many patients? What does the landscape look like right now for precision cardiac medicine?

Gianakakos: There needs to be a cultural shift in the CVD field to move away from grouping broad heterogenous patients together, to focusing on smaller, well defined patient groups treated with targeted therapies and learning as much as we can from those that respond very well and, as importantly, those that do not.

Matching patient profiles to drugs that specifically address their underlying disease is key. Leaning on existing technology, such as wearables, genetic sequencing, imaging, and biomarker profiles to subtype CVD patients and deeply understand the biological drivers of disease will lead to critically important targeted therapies and much more effective clinical trials.

In terms of other precision cardiac medicine approaches in development, gene therapies are being explored. While that technology is maturing, most gene therapies for CVDs are still in early-stage research, but eventually could be helpful for certain sub-groups of patients with CVD.

Relative to other disease areas, like oncology, it has been challenging for companies to invest in new approaches to drug discovery and development in areas like CVD and neurology. However, given the staggering medical need, and with progress being made by companies like ours, I expect interest in CVD precision medicine to increase over the next 3-5 years.

What does MyoKardias pipeline look like?

Gianakakos: Our Phase III drug, called mavacamten (MYK-461), is for HCM. HCM is a genetic disease where the heart thickens due to excessive force of contraction cause by mutations in the heart muscle proteins. There are two common subtypes of HCM: obstructive, where the thickening also occurs near the base of the aorta and prevents (obstructs) blood from flowing well out of the heart; and non-obstructive, where the thick muscle makes it challenging for the heart to relax and fill, reducing the amount of blood flow out of the heart without physically obstructing blood flow. About one-third of HCM patients have the non-obstructive type.

Mavacamten is a small molecule that targets the heart muscle protein myosin reducing the excessive force of contraction, directly addressing the underlying cause of HCM. We announced positive data from our Phase III trial (EXPLORER-HCM) of mavacemten in about 250 symptomatic obstructive HCM patients and we are now able to move full steam ahead on our first regulatory submission for approval. Encouraging results from a Phase II trial (MAVERICK-HCM) of mavacamten in about 60 participants with symptomatic non-obstructive HCM were recently presented and we are going to be moving mavacamten forward in non-obstructive patients. We are also conducting a long-term extension study is also ongoing for patients who participated in either EXPLORER-HCM or MAVERICK-HCM.

We started hyper focused in a disease with a defined genetic background and will expand in a deliberate way into adjacent diseases with similar problems, such as heart failure with preserved ejection fraction. About 3 million people in the U.S. have problems filling and relaxing their hearts and we estimate that approximately 10% of them share similar pathology to HCM. Are these disease subtypes related? Do they have similar genetic mutations? We plan to start a Phase II trial in the next few months to explore if mavacamten can help that specific heart failure population and learn much more about this devastating form of heart failure.

We also have a Phase II molecule, called danicamtiv (MYK-491), for DCM that is designed to increase the force of contraction in the heart - the opposite of what mavacamten has been created to do. Danicamtiv is a small molecule that selectively increases the number of myosin-actin cross bridges, supporting heart muscle contractions to help the heart pump more efficiently. It has recently completed a Phase Ib/IIa trial in DCM or stable heart failure patients and has shown very promising early results. We are now moving into a separate Phase II study in DCM patients with certain genetic mutations. Among the most interesting new findings from our clinical study of danicamtiv is that it appears to have a direct effect on the performance of the left atrium. We were able to confirm and learn more about these findings in nonclinical studies, which is leading us to explore danicamtiv in patients with systolic dysfunction and atrial fibrillation.

MyoKardia has gone from startup to successfully completing our first Phase III trial in eight years. In the coming months, we will be submitting our first drug to the FDA this year, which if approved will bring the first every therapy designed specifically for HCM to people with this debilitating condition.

We design our therapies with the aim of targeting the underlying disease mechanism to treat and, in some cases, reverse the problem, actually slowing down or reversing disease progression. That allows patients to live full lives, free from fear and complications. We are very excited and remain super ambitious. The magic and special sauce is really our employees and our culture.

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MyoKardia: The Precision Cardiac Medicine Company with Diversity and Inclusion at its Heart - BioSpace

Living through a global pandemic, we can take some comfort from the enormous collaborative research and development response that is taking place to find a way out from under the shadow of the COVID-19 crisis. Scientists around the world are working to find new diagnostics, treatments and vaccines to use in the fight against the coronavirus.

Nathalie Moll is the Director General of the European Federation of Pharmaceutical Industries and Associations (EFPIA).

The polar opposite of a pandemic, a rare disease may only affect a handful of patients in a particular country, but to the patient, their family, carers and clinicians, the impact of their condition can be just as devastating. Often genetic, discovered in childhood and frequently severe, rare diseases are some of the most significant scientific challenges in medicine. Typically they affect only 1 in 2,000 people, but there are more than 6000 rare diseases meaning around 30 million Europeans are living with some form of rare condition.

Rare diseases certainly dont attract the levels of media attention and interest that a public health crisis like COVID-19 does but for patients living with the 95% of rare diseases where no treatment options exist, the need for new diagnostics and medicines is every bit as real.

As the industry responsible for developing those new therapies, we are committed to achieving the crucial objective of finding new treatments for patients in areas of unmet medical need. It means supporting and strengthening the framework of incentives to drive further research into the next generation of treatments and cures for rare disease and paediatric treatments. Incentives drive investment, research and results. Results that mean new treatments and ultimately better outcomes for patients.

It is why EFPIA supports the existing European legislation on orphan medicines and paediatric medicines, while underlining the need to co-create vehicles to address issues around access to new treatments. Prior to the orphan legislation coming into force in 2000, there were just 8 treatments licensed for use to treat rare diseases, now there are 169, underlining the fundamental role that a predictable and stable incentives framework for research and development has. Any destabilisation of that framework threatens the investment in research and development in this area.

At the same time, faster, more equitable access to new rare disease treatments for patients across Europe is a shared goal and responsibility. Re-opening the Orphan Medicinal Product Regulation will not address the core challenges regarding unequal access and availability of orphan drugs within the EuropeanUnion. Addressing this challenge requires a structured dialogue with relevant stakeholders, Member States and the European Commission sensitive to their respective competence areas, to find solutions to introduce these ground-breaking treatments. That is why we reiterate the call to Member States and the Commission to set up a High-Level Forum composed of EU and national decision makers, patients, as well as the research and healthcare communities to find collaborative, multi-stakeholder solutions to these complex issues of access.

Considering the lack of innovation policy drivers in the Roadmap for the EUs Pharmaceutical Strategy, it is all the more critical that we maintain a stable and predictable incentives framework that can continue to support the development of new treatments for rare disease patients in Europe. We have to work together to ensure access to new treatments and technologies today, medical innovation in rare diseases for tomorrow and sustainable healthcare systems in a globally competitive Europe. Destabilising investment in the discovery and development of new treatments for patients living with rare diseases by re-opening a legislation, proven to be effective in stimulating the development of new treatments, cannot be the right approach.

One crystal clear lesson from the COVID-19 pandemic has been that the answer lies in medical innovation. This is equally true for patients living with rare diseases. Now is the time to re-build and re-invigorate rather than devalue Europes health research ecosystem, to make sure we address these challenges and #WeWontRest until we make treatments for rare diseases less rare.

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From pandemic to rare disease, medical innovation is the answer - EURACTIV

The roulette wheel that decides who lives and dies from the coronavirus is weighted by the type of blood coursing through the veins of victims, gifting some with innate resistance and dooming others to misery and torment.

Infectious-disease specialists say the worldwide pandemic is especially cruel to people with Type A blood, which apparently lacks certain compounds that help fight off the disease.

A study published June 17 in the New England Journal of Medicine found that people with Type A blood have a higher risk of contracting the disease and suffering complications. The analysis, conducted by an international team of scientists, also showed that people with Type O blood were at least partially protected from the virus.

It was one of several recent reports on the phenomenon, which epidemiologists say is not unique to COVID-19.

People with Type A blood ... are more likely to have severe disease and death than people with other types, said John Swartzberg, an infectious-disease specialist at UC Berkeley. It doesnt surprise me because we know that blood types are associated with other infectious diseases.

Blood type is determined by a gene that tells the body what blood cell proteins to make. The types, A, B, AB and O, have different antigens, which determine their properties, including weaknesses and strengths. A blood type that is positive means that persons red blood cells carry a protein called Rh, also known as the RhD antigen. Negative blood type does not.

Epidemiologists have long known that blood type plays a role in how peoples bodies react to infectious diseases, and Type A positive and negative appears to be among the most problematic.

For example, people with Type A blood have a higher chance of developing certain cancers, particularly stomach cancer. All the types of blood have agreeable and disagreeable qualities, but Type A is associated with higher levels of the stress hormone cortisol, according the National Institutes of Health.

Swartzberg said people with Type A blood are also more likely to contract the most virulent form of malaria, known as Plasmodium falciparum. The protozoan parasite that causes it is transmitted through the bite of a female mosquito.

On the other hand, people with Type O blood are less likely to develop inflammation during infections, suffer from heart disease, pancreatic cancer or contract parasitic diseases like P. falciparum.

The Journal of Medicine study sequenced the genomes of 1,980 COVID-19 patients in Spain and Italy who had suffered respiratory failure and compared their results with an approximately equal number of people who were not sick. The researchers concluded that people with Type A blood had as much as a 45% higher risk of getting severely ill from the coronavirus.

Another study, of more than 2,000 people in China in March, also found that blood group A had a significantly higher risk of coronavirus infection. That information aligns with other studies, most of them not yet peer reviewed.

In each case, Type O blood was linked to lower risk and less severe illness. A study by the genomics site 23andMe calculated that people with blood Type O were 9% to 18% less likely to contract COVID-19 than people with other types of blood.

Type O blood is handy in other ways. O positive is the most common blood type, and O negative is compatible with all other types of blood. Because O negative blood can be given to anybody, it is commonly used for transfusions.

Studies have shown that people with Type O blood also get fewer blood clots, a serious problem among COVID-19 patients.

SARS-CoV-2, the specific coronavirus that causes COVID-19, is essentially like a tiny parasite that uses its telltale spike proteins to latch onto the much larger human cells, like pepper on an egg. The virus uses the cells receptors to worm its way inside, where it replicates itself billions of times and spreads throughout the body.

There are a variety of factors that influence vulnerability to a coronavirus infection, including old age, underlying medical conditions and possibly race, although the high mortality rate among minorities is more likely related to poverty and a lack of medical care. A study, published Wednesday in Nature, said Latinos and African Americans are three times more likely than white people to be infected by the coronavirus and nearly twice as likely to die.

Men are hospitalized and die from the virus more often than women, a disparity that researchers have linked to testosterone, the male sex hormone.

Researchers know that the coronavirus targets ACE2 receptors, a protein on the surface of human cells that normally helps regulate blood pressure. Peter Chin-Hong, a professor of medicine and infectious diseases at UCSF, said the genes that make the ACE2 receptors are next to the genes that provide the blood type codes.

Because they are so close to each other, they influence each other in ways we dont understand, Chin-Hong said. Things are next to each other for a reason.

Nobody knows exactly how the coronavirus operates, but some scientists believe the virus, when it infects a new host, carries with it genetic coding blood type antigens from its last victim. Apparently, Type O blood adapts better to the coronavirus coding.

Swartzberg said this may have something to do with the types of carbohydrates, or sugars, on the surface of red blood cells.

The Type A carbohydrate may facilitate the entrance of the (malarial) protozoan into the red blood cell, causing more severe infection, Swartzberg said. People with Type O blood, which doesnt have any of those carbohydrates, may be somewhat protected.

George Rutherford, a UCSF infectious-disease specialist, said Caucasians of Mediterranean descent have the highest percentage of Type A blood.

Most of these (blood type) observations are from Italy and Spain, which have had horrendous COVID outbreaks, Rutherford said.

A big puzzle is that blood type doesnt seem to matter when it comes to African Americans and other people of color. Type O blood is more common among African Americans a little more than half carry that type yet African Americans have disproportionately high infection rates. The same goes for Latinos, 57% of whom carry Type O blood.

Its an indication, Rutherford said, that socioeconomic problems like poverty, obesity and stress may be bigger factors in who gets the disease and how ill they become than blood type.

Peter Fimrite is a San Francisco Chronicle staff writer. Email: pfimrite@sfchronicle.com Twitter: @pfimrite

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If you have this blood type, studies show youre at higher risk for the coronavirus - San Francisco Chronicle

A federal program trying to recruit 1 million people for medical research is launching an effort to learn more about COVID-19. WUWM's Chuck Quirmbach reports.

A federal program trying to recruit 1 million people for medical research is launching an effort to learn more about COVID-19. The Medical College of Wisconsin and some other health care outlets in the state are part of the program called All of Us.

All of Us began during the Obama administration and could cost $1.5 billion nationally over a 10-year period.

READ:In Return For Some DNA, Program Promises Medicine Eventually 'Tailored To You'

So far, the National Institutes of Health (NIH) has gotten about 280,000 people to sign up for All of Us. Volunteering means allowing NIH confidential access to online medical records and to provide researchers with blood and urine samples. The hope is to build a diverse biomedical database that will lead to more individualized, or precision, disease prevention, treatment and care.

Enrollment for All of Us has been on hold for more than three months due to the COVID-19 pandemic. But program officials are about to start conducting antibody tests of the blood samples of at least the last 10,000 people who signed up for All of Us early this year.

Dr. Jeff Whittle is a professor of Medicine and the Medical College of Wisconsin's principal investigator for All of Us. He says the tests will look for antibodies, or disease-fighting proteins that formed in people who had the coronavirus at the time of giving the blood sample.

"It won't lead directly to effect treatment. It will help us to understand who are the higher-risk individuals for infection and at higher risk for becoming ill. It may help us target resources. It may help target testing. It may help us target vaccination because when a vaccine becomes available, there will be some groups that providers will be wanting to vaccinate sooner than others, Whittle said.

Whittle also told WUWM there may be a genetic link to how humans interact with the coronavirus."There may be markers on your cells, determined by genetics, that make you more or less likely to be infected. There may be aspects of how your immune system works, that are genetically determined, that may make you able to mount a more robust or less robust response."

Whittle says All of Us volunteers, in effect, already gave permission for their submitted blood samples to be tested for research. He says after the antibody study is conducted at Vanderbilt University, some participants may eventually be contacted for follow-up.

As for recruiting nationally 720,000 more people for All of Us, Whittle says people can call to begin preliminary sign-up. He says The Medical College of Wisconsin will schedule local appointments tobegin later this month.

Support for Innovation reporting is provided by Dr. Lawrence and Mrs. Hannah Goodman.

Do you have a question about innovation in Wisconsin that you'd like WUWM's Chuck Quirmbach to explore? Submit it below.

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COVID-19 Now Research Focus Of Health Database That Has Several Wisconsin Partners - WUWM

Theres encouraging and not so encouraging news about COVID-19 testing.

The most common tests used to diagnose an infection with the novel coronavirus are almost 100 percent effective if administered correctly.

However, the same cant be said of tests to determine if youve already had the disease and have developed antibodies.

Experts say diagnostic testing is one of the most powerful public health tools for fighting the spread of the coronavirus.

The tests identify people who may need treatment. Results also trace those who have been in contact with other individuals to help prevent the transmission of the disease further. This can assist epidemiologists in determining how widely the virus has spread.

Testing makes the enemy visible, said Dr. Emily Volk, an assistant professor of pathology at the University of Texas-Health in San Antonio and president-elect of the College of American Pathologists (CAP).

There are two basic types of tests for the novel coronavirus. One type diagnoses an infection and the other tests for antibodies.

Diagnostic tests detect active infections. This is the test you want if you think youve been exposed to the coronavirus or are exhibiting symptoms of COVID-19.

There are currently two types of diagnostic tests available.

The RT-PCR nasopharyngeal tests are more widely used and more familiar. Most involve sticking a 6-inch swab deep into your nose to collect virus samples to test.

However, some more recently approved RT-PCR tests seek to avoid the discomfort associated with the nasopharyngeal swab tests by allowing samples to be collected via a shallow swab of the nose or by testing saliva for the presence of the virus.

If performed correctly, RT-PCR swab tests would be pretty close to 100 percent accurate, Volk told Healthline.

We should be diagnosing people with PCR tests because they are the most accurate, added Dr. Christina Wojewoda, a pathologist at the University of Vermont and vice chair of CAPs microbiology committee.

To get the most accurate results, RT-PCR tests should be conducted 8 days after suspected exposure or infection, to ensure that enough viral material is present to detect.

Some clinicians know that, but people who are swabbing may not be passing that information along, Wojewoda told Healthline.

Its also possible to administer the test too late, after the body has successfully fought off the disease, according to Dr. William Schaffner, professor of medicine in the division of infectious diseases at the Vanderbilt University School of Medicine in Tennessee and medical director of the National Foundation for Infectious Diseases.

The test must also be administered properly, which means inserting the swab 3 inches or so to reach the cavity where the nasal passages meet the pharynx.

If youve had this test and it wasnt uncomfortable, it wasnt done correctly, Schaffner told Healthline.

False-positive results, while rare, can occur with PCR tests, said Wojewoda, because the coronavirus genetic material may linger in the body long after recovery from an infection.

You cant tell if the person [had an infection] 3 days ago or 5 months ago, she said.

Swabs are also used to collect samples for antigen testing. These tests have the advantage of yielding faster results (hours rather than several days).

Theyre also less accurate than RT-PRC tests, mostly because they require test samples to contain large amounts of virus proteins to yield a positive result.

False-negative results from antigen tests may range as high as 20 to 30 percent.

If an antigen test is positive, you can believe it, said Wojewoda. If its negative, you have to question that.

As the name suggests, these tests look for antibodies made by your immune system in response to an infection with the new coronavirus.

Antibody tests are not diagnostic tests.

Antibodies can take several days or weeks to develop after you have an infection and may stay in your blood for several weeks after recovery, according to the Food and Drug Administration (FDA). Because of this, antibody tests should not be used to diagnose an active coronavirus infection.

Antibody tests also arent terribly useful.

Ideally, a positive antibody test would tell you that youve recovered from COVID-19 or a coronavirus infection and have immunity from future infections, allowing you to return to work, travel, and socialization without the risk of transmitting the infection or becoming sick again yourself.

However, researchers dont yet know whether the presence of antibodies means that you have immunity, whether you could still get sick from a different strain of the virus, or how long immunity lasts.

Antibody tests are problematic because they can be misused easily, said Volk. You may think if you have a positive antibody test that you dont have to wear a mask or conform to social distancing, but antibodies dont tell us that you have immunological armor against future infections.

Antibody tests also are subject to false-positive results.

The job of antibodies is to stick to things, so they can create a positive test result if they react to a different type of coronavirus, said Wojewoda.

Antibody tests show the most promise if the way the human body controls the coronavirus is with an antibody response, Wojewoda added. If not, it doesnt make any difference.

For example, she said, its T cells, not antibodies, that help the body fight an HIV infection.

Thats another piece of data that needs to be figured out before testing can be figured out, Wojewoda said.

Every COVID-19 test currently (and legally) available in the United States has been approved by the FDA under the agencys Emergency Use Authorization (EUA) protocol.

The EUA permits the FDA to allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life threatening diseases or conditions caused by chemical, biological, radiological and nuclear threat agents when there are no adequate, approved, and available alternatives.

That has allowed novel coronavirus tests to quickly hit the market without the research and testing normally required for FDA approval.

To date, the FDA has approved 130 different RT-PCR, antigen, and antibody tests for the new coronavirus.

Doing a full clinical trial takes a long time, but we need tests now, said Sherry Dunbar, PhD, senior director of global scientific affairs for Luminex Corporation, which manufactures a pair of PRC tests and has submitted an application to the FDA for emergency approval of a new antigen test.

Experts generally agree that the RT-PCR tests are more accurate and useful than antigen and antibody tests, which are better used as confirmatory tools.

Dunbar told Healthline that some testing labs are using multiple tests to anticipate shortages on testing products. Theyre also using the quicker tests when demand is high and the slower but more accurate tests on weekends or during slower times.

Wojewoda said that while some tests promise quicker results than others, the biggest limiting factor to turnaround results is shortages of reagents the chemicals used to do the testing.

Im not looking for a new test, she said. Those on the market are as accurate and fast as they need to be. We have the instruments we need to test. We just need more stuff to do it with.

As with most other things regarding the novel coronavirus, pathologists and testing labs are learning about COVID-19 on the fly, said Dunbar.

Never in my career have I seen anything like this, where the public is discussing and analyzing the data at the same time as the researchers, she said. Were basing our response on past knowledge of other viruses, but as we like to say, the bugs dont read the book. What happened in the past can help us prepare, but things will continue to evolve.

Originally posted here:

How Accurate Are the Coronavirus Diagnostic and Antibody Tests? - Healthline

LOS ANGELES, July 7, 2020 /PRNewswire/ -- The Prostate Cancer Foundation (PCF) has collaborated with a consortium of 41 leading patient advocacy organizations, professional societies and industry partners to publish a white paper detailing recommendations for the use of testing terminology in precision medicine for patient education throughout the cancer community. Use of consistent language will significantly improve patient awareness and understanding of potentially life-saving testing options available for both new cancer diagnoses and progression or recurrence of disease. In prostate cancer, testing is a crucial tool that may reveal additional treatment options and/or information for a man's family about their own cancer risk.

Research shows that despite widespread acceptance of the importance of testing, actual testing rates lag far behind best-practice recommendations for both biomarker testing for somatic (acquired) mutations and other biomarkers, and for germline genetic testing for identifying germline (inherited) mutations (also known as variants). Analysis by The Consistent Testing Terminology Working Group (Working Group) indicates that language disparity is a primary obstacle to patient communication with providers about testing for their specific cancer type. Further, development of consistent language can increase patient understanding and communication, facilitate shared decision making, support value-based care and assure concordance in policy development.

"Both types of testing biomarker testing and genetic testing for inherited cancer risk are important in the care of prostate cancer patients," said Dr. Andrea Miyahira, Director of Global Research and Scientific Communications at PCF. "One example is the very recent approval of medications for men with advanced prostate cancer and certain mutations in their tumor or inherited mutations that would be revealed through testing. Therefore, clear terminology and understanding between patients and providers is all the more vital. PCF supports this valuable collaboration across cancer types."

The Working Group is a consortium of 20 cancer patient advocacy groups representing solid tumor and hematologic malignancies, three professional societies, and 18 pharmaceutical and diagnostic companies and testing laboratories. Over the course of many years, multiple activities, led by numerous individual patient advocacy organizations and professional societies have developed the groundwork for this effort. The Working Group has launched a multi-faceted dissemination and communications effort to ensure that its recommendations and supporting materials are widely available among all key stakeholders within the cancer ecosystem, including providers, patient advocacy organizations, guidelines agencies, payers, and policymakers.

In developing its recommendations, the Working Group, first convened in 2019 by LUNGevity Foundation, identified 33 terms related to biomarker, genetic and genomic testing that were being used in patient education and clinical care within the different cancer communities. In many cases, multiple terms were used to describe the same test. Various testing modalities, the source of testing samples, and the multiplicity of gene mutations currently identifiable by testing, were contributing factors in this often-confusing overlap.

In the final analysis, three umbrella descriptor terms emerged as recommendations from the Working Group's milestone exploration: "Biomarker testing" was selected as the preferred term for tests that identify characteristics, targetable findings or other test results originating from malignant tissue and blood; "genetic testing for an inherited mutation" and "genetic testing for inherited cancer risk" were selected as consensus terms for tests used to identify germline (inherited) mutations.

"Far too many patients across all cancer types are still missing out on essential tests for biomarkers and inherited mutations indicating cancer risk," said Michelle Shiller, DO, AP/CP, MGP, Co-Medical Director of Genetics at Baylor Sammons Cancer Center and Staff Pathologist at Baylor University Medical Center. "With rates of biomarker testing and genetic testing for an inherited mutation at sub-optimal levels for numerous patient populations, patients are not benefiting from biomarker-directed care or not learning about their inherited cancer risk. Confusion around testing terms is a driving factor in this undertesting and ultimately has a detrimental impact on patient care."

"When someone is diagnosed with cancer, they're swept into a whirlwind of bewildering words and complex, pressing decisions. Our Working Group's goal is to help calm that storm of confusion with clear and consistent language that facilitates communication and medical decision-making. A unified voice and message from providers, industry and the patient advocacy community about testing is absolutely vital to optimal cancer care," said Nikki Martin, Director of Precision Medicine Initiatives at LUNGevity Foundation.

An abstract on the Working Group's recommendations was published in May 2020 as part of the American Society of Clinical Oncology (ASCO) Annual Meeting Virtual Library. The White Paper can be viewed in its entirety athttp://www.commoncancertestingterms.org/.

About LUNGevity Foundation LUNGevity Foundation is the nation's leading lung cancer organization focused on improving outcomes for people with lung cancer through research, education, policy initiatives, and support and engagement for patients, survivors, and caregivers. LUNGevity seeks to make an immediate impact on quality of life and survivorship for everyone touched by the diseasewhile promoting health equity by addressing disparities throughout the care continuum. LUNGevity works tirelessly to advance research into early detection and more effective treatments, provide information and educational tools to empower patients and their caregivers, promote impactful public policy initiatives, and amplify the patient voice through research and engagement. The organization provides an active community for patients and survivorsand those who help them live better and longer lives.

Comprehensive resources include a medically vetted and patient-centric website, a toll-free HELPLine for support, the International Lung Cancer Survivorship Conference, and an easy-to-use Clinical Trial Finder, among other tools. All of these programs are to achieve our visiona world where no one dies of lung cancer. LUNGevity Foundation is proud to be a four-star Charity Navigator organization. Please visit http://www.LUNGevity.org to learn more.

About the Prostate Cancer Foundation The Prostate Cancer Foundation (PCF) is the world's leading philanthropic organization dedicated to funding life-saving prostate cancer research. Founded in 1993 by Mike Milken, PCF has raised more than $830 million in support of cutting-edge research by more than 2,200 research projects at 220 leading cancer centers in 22 countries around the world. Thanks in part to PCF's commitment to ending death and suffering from prostate cancer, the death rate is down more than 50% and countless more men are alive today as a result. PCF research now impacts more than 73 forms of human cancer by focusing on immunotherapy, the microbiome, and food as medicine. For more information, visit PCF.org.

Media Contact: Donald Wilson Prostate Cancer Foundation (310) 428-4730 press@pcf.org

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The Prostate Cancer Foundation Collaboration With Pan-Cancer Consortium Clarifies And Promotes Consistent Use Of Common Terms For Biomarker And...

We may have mapped the human genome in 2003, but a new worldwide study has discovered the links between our genes and the conditions that ail us.

In this time of extra focus on health, allow me one more story from the brave new world of medical research. Every day, twenty American war veterans kill themselves. That is fifteen percent of the total amount of Americans who take their own lives each year; a disproportionally high number. A few weeks ago, the American Department of Veteran Affairs learnt a little more about why that might be the case.

While trauma is involved, surprisingly so is genetics. Research that looked at an astounding 200,000 veterans, concluded that quite a few of them were susceptible to anxiety and depression even before they were sent to Afghanistan or another warzone. In fact, in an astonishing number, there was a problem with a gene called MAD1C1, that is also implicated in bipolar disease and schizophrenia. On top of that, there were five other genetic variants that are linked to anxiety that were more prevalent in this group. Obviously, this is important information. Not only will it now be possible to better predict who should and shouldnt go to war, but deaths can also be prevented by teaching people how to cope before the shit hits the fan.

With 200,000 participants, this research is the largest ever study into anxiety in the world. But it is not the only mass investigation into illness that is going on at the moment. In fact, bigger is definitely better at almost all laboratories on the planet. For instance, a few months ago researchers looked closer at insomnia than had ever been possible before: 1.3 million people were involved, and 956 genes were found that could hold the key to solving a problem that a third of the general population suffers from. An issue, too, that is implicated in all manner of mental health issues, as well as diabetes and cardiovascular disease.

This kind of research is part of Genome-Wide Association Studies that are taking place from New York to Melbourne and Cape Town to Oslo. As you may remember, in 2003 the Human Genome Project was completed, and that meant that suddenly researchers could look into genetic contributions to common diseases better than ever before.

Until the human genome was mapped, the only way to look at the role genes played in illnesses was to study families. That was relatively successful if they were suffering from a single gene disorder, but not so much if it was more complicated than that. But after humanity cracked the gene code in 2003, Biobanks started springing up everywhere. At the moment, weve got forty-five in NSW alone, and the largest in the southern hemisphere is at the RPA in Camperdown. It is run by NSW Health and stores more than three million human samples for use in research. Usually, that is left-over tissue from an operation, biopsy or blood test, of course, donated with written consent. At Camperdown, researchers can apply for access to those samples, so they can investigate whatever illness they are looking at at a much larger scale than pre-2003.

These studies, as usual, involve one group of people with an illness and a control group without. But because so many samples are available, it is possible to look at enormous populations. That means you are casting a wide net, but because there is no hypothesis before you start, anything can happen. The focus, of course, is finding the genes that are associated with a particular disease. And once youve found those, you can zoom in and look a little closer. This has two consequences: first of all, that you can know more about more illnesses much faster than before. Secondly, it is laying the groundwork for personalised medicine.

In the near future, it will no longer be one size fits all (like one type of chemo for everybody with bowel cancer, for instance). Treatments will be tailored to one individual patient, because when we know more about one persons particular gene make-up it is easier to design something that will be just right for them. Not just when they are already sick, but even in the prevention of that illness. Less guesswork, less adverse reactions to treatments, fewer mistakes.

Of course, there are limitations. Not everything can be explained by looking at genes, for instance, and every person responds differently to disease, which makes treatment still complicated. Also, completing a complete genome sequencing is still expensive. And the problem with quite a few of the Biobanks is that the owners of the samples are generally white and Western. Apart from that, just knowing which genes are associated with a disease is only the beginning.

The challenge is the road from that knowledge to new drugs, diagnostics and maybe prevention. Nevertheless, so far over three thousand GWA studies have been done, into almost two thousand different diseases. We now know more about what causes heart attacks (from a study started in 2004), have found a protein that is involved in producing macular degeneration and can pinpoint genes that are related to risky behaviour, like driving too fast, smoking, drinking and having high-risk sex. We have found the genes connected to intelligence, obesity, schizophrenia, childhood aggression, antisocial behaviour, depression and all manner of other things.

There are Biobanks in NSW that specialise in melanoma, stroke, sleep, childrens cancer, gynaecological issues and problems with the brain. I know it is a little brave new world, and we need to be careful it doesnt turn into an Orwellian nightmare. But limitless possibilities, and hope for those who are sick: there is something to be said for that, isnt there?

For this story I have used the following sources:

https://nsw.biobanking.org/locator

https://www.smh.com.au/healthcare/biggest-biobank-in-the-southern-hemisphere-to-revolutionise-medical-research-in-nsw-20171113-gzk5os.html

NSW Health Statewide Biobank

https://www.researchgate.net/publication/331328430_Genome-wide_analysis_of_insomnia_in_1331010_individuals_identifies_new_risk_loci_and_functional_pathways

https://www.researchgate.net/publication/330368016_Genome-wide_association_analyses_of_risk_tolerance_and_risky_behaviors_in_over_1_million_individuals_identify_hundreds_of_loci_and_shared_genetic_influences

https://www.researchgate.net/publication/330368016_Genome-wide_association_analyses_of_risk_tolerance_and_risky_behaviors_in_over_1_million_individuals_identify_hundreds_of_loci_and_shared_genetic_influences

https://edition.cnn.com/2020/01/09/health/anxiety-genetic-association-wellness-trnd/index.html?utm_source=twCNN&utm_content=2020-01-10T05%3A09%3A03&utm_medium=social&utm_term=link

https://www.mentalhealth.va.gov/suicide_prevention/data.asp

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Worldwide genome research could change the course of medical history - The Big Smoke Australia

A combined analysis of 10 prospective trials, intended to shed light on racial disparities in percutaneous coronary intervention (PCI) outcomes, saw sharply higher risks of death and myocardial infarction (MI) for Blacks compared with Whites.

The burden of comorbidities, including diabetes, was greater for Hispanics and Blacks compared to Whites, but only in Blacks were PCI outcomes significantly worse even after controlling for such conditions and other baseline risk factors.

The analysis based on more than 22,000 patients was published July 6 in JACC: Cardiovascular Interventions, with lead author Mordechai Golomb, MD, Cardiovascular Research Foundation, New York City.

In the study based on patient-level data from the different trials, the adjusted risk of MI after PCI was increased 45% at 1 year and 55% after 5 years for Blacks compared with Whites. Their risk of death at 1 year was doubled, and their risk of major adverse cardiac events (MACE) was up by 28% at 5 years.

"Improving healthcare and outcomes for minorities is essential, and we are hopeful that our work may help direct these efforts, senior author Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York City, told theheart.org | Medscape Cardiology.

"But this won't happen without active, concerted efforts to promote change and opportunity, a task for government, regulators, payers, hospital administrators, physicians, and all healthcare providers," he said. "Understanding patient outcomes according to race and ethnicity is essential to optimize health for all patients," but "most prior studies in this regard have looked at population-based data."

In contrast, the current study used hospital source records, which are considered more accurate than administrative databases, and event coding reports, Stone said, plus angiographic core laboratory analyses for all patients, "allowing an independent assessment of the extent and type of coronary artery disease and procedural outcomes."

The analysis "demonstrated that even when upfront treatments are presumably similar [across racial groups] in a clinical trial setting, longitudinal outcomes still differ by race," Michael Nanna, MD, told theheart.org | Medscape Cardiology.

The "troubling" results "highlight the persistence of racial disparities in healthcare and the need to renew our focus on closing these gaps, [and] is yet another call to action for clinicians, researchers, and the healthcare system at large," said Nanna, of Duke University Medical Center, Durham, North Carolina, and lead author on an editorial accompanying the published analysis.

Of the 10 randomized controlled trials included in the study, which encompassed 22,638 patients, nine were stent comparisons and one compared antithrombotic regimens in patients with acute coronary syndromes (ACS), the authors note. The median follow-up was about 1100 days.

White patients made up 90.9% of the combined cohort, Black patients comprised 4.1%, Hispanics 2.1%, and Asians 1.8% figures that "confirm the well-known fact that minority groups are underrepresented in clinical trials," Stone said.

There were notable demographic and clinical differences at baseline between the four groups.

For example, Black patients tended to be younger than White, Hispanic, and Asian patients. Black and Hispanic patients were also less likely to be male compared with White patients.

Both Black and Hispanic patients had more comorbidities than Whites did at baseline, the authors observe. For example, Black and Hispanic patients had a greater body mass index compared with Whites, whereas it was lower for Asians; and they had more diabetes and more hypertension than Whites (P < .0001 for all differences).

Hispanics were more likely to have ACS at baseline compared with Whites and less likely to have stable coronary artery disease (CAD) (P < .0001 for all differences). Similar proportions of Blacks and of Whites had stable CAD, about 32% of each, and ACS, about 68% in both cases.

Rates of hyperlipidemia and stable CAD were greater and rates of ACS was lower in Asians than the other three race groups (P < .0001 for each difference).

In adjusted analysis, the risk of MACE at 5 years was significantly increased for Blacks compared with Whites (hazard ratio (HR),1.28; 95% CI, 1.05 - 1.57; P = .01). The same applied to MI (HR, 1.55; 95% CI, 1.15 - 2.09; P = .004).

At 1 year, Blacks showed higher risks for death (HR, 2.06; 95% CI, 1.26 - 3.36; P = .004) and for MI (HR, 1.45; 95% CI, 1.01 - 2.10; P = .045), compared with Whites.

No significant increases in risk for outcomes at 1 and 5 years were seen for Hispanics or Asians compared with Whites.

Covariates in the analyses included age, sex, body mass index, diabetes, current smoking, hypertension, hyperlipidemia, history of MI or coronary revascularization, clinical CAD presentation, category of stent, and race stratified by study.

Even with underlying genotypic differences between Blacks and Whites, much of the difference in risk for outcomes "should have been accounted for when the researchers adjusted for these clinical phenotypes," the editorial notes.

Some of the difference in risk must have derived from uncontrolled-for variables, and "Beyond genetics, it is clear that race is also a surrogate for other socioeconomic factors that influence both medical care and patient outcomes," they write.

The adjusted analysis, note Golomb et al, suggests "that for Hispanic patients, the excess risk for adverse clinical outcomes may have been attributable to a higher prevalence of risk factors. In contrast, the excess risk for adverse clinical outcomes for Black patients persisted even after adjustment for baseline risk factors."

As such, they agree, "The observed increased risk may be explained by differences that are not fully captured in traditional cardiovascular risk factor assessment, including socioeconomic differences and education, treatment compliance rates, and yet-to-be-elucidated genetic differences and/or other factors."

Stone said that such socioeconomic considerations may include reduced access to care and insurance coverage; lack of preventive care, disease awareness, and education; delayed presentation; and varying levels of provided care.

"Possible genetic or environmental-related differences in the development and progression of atherosclerosis and other disease processes" may also be involved.

"Achieving representative proportions of minorities in clinical trials is essential but has proved challenging," Stone said. "We must ensure that adequate numbers of hospitals and providers that are serving these patients participate in multicenter trials, and trust has to be developed so that minority populations have confidence to enroll in studies."

Stone reported holding equity options in Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestro Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix; and receiving consulting fees from Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore Ablative Solutions, Miracor, Neovasc, W-Wave, Abiomed, and others. Disclosures for the other authors are in the report. Nanna reports no relevant financial relationships; other coauthor disclosures are provided with the editorial.

JACC Cardiovasc Interv. 2020;13:1586-1595, 1596-1598. Abstract, Editorial

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Post-PCI Mortality Higher in Blacks vs Whites, Comorbidities Aside - Medscape

In January, vaccine researchers lined up on the starting blocks, waiting to hear a pistol. That shot came on January 10, when scientists in China announced the complete genetic makeup of the novel coronavirus. With that information in hand, the headlong race toward a vaccine began.

As the virus, now known as SARS-CoV-2, began to spread like wildfire around the globe, researchers sprinted to catch up with treatments and vaccines. Now, six months later, there is still no cure and no preventative for the disease caused by the virus, COVID-19, though there are glimmers of hope. Studies show that two drugs can help treat the sick: The antiviral remdesivir shortens recovery times (SN: 4/29/20) and a steroid called dexamethasone reduces deaths among people hospitalized with COVID-19 who need help breathing (SN: 6/16/20).

But the finish line in this race remains a safe and effective vaccine. With nearly 180 vaccine candidates now being tested in lab dishes, animals and even already in humans, that end may be in sight. Some experts predict that a vaccine may be available for emergency use for the general public by the end of the year even before it receives expedited U.S. Food and Drug Administration approval.

Velocity might come at the expense of safety and efficacy, some experts worry. And that could stymie efforts to convince enough people to get the vaccine in order to build the herd immunity needed to end the pandemic.

Were calling for transparency of data, says Esther Krofah, executive director of FasterCures, a Washington, D.C.-based nonprofit. We want things to accelerate meaningfully in a way that does not compromise safety or the science, but we need to see the data, she says.

Traditionally, vaccines are made from weakened or killed viruses, or virus fragments. But producing large amounts of vaccine that way can take years, because such vaccines must be made in cells (SN: 7/7/20), which often arent easy to grow in large quantities.

Getting an early good look at the coronaviruss genetic makeup created a shortcut. It let scientists quickly harness the viruss genetic information to make copies of a crucial piece of SARS-CoV-2 that can be used as the basis for vaccines.

That piece is known as the spike protein. It studs the viruss surface, forming its halo and allowing the virus to latch onto and enter human cells. Because the spike protein is on the outside of the virus, its also an easy target for antibodies to recognize.

Researchers have copied the SARS-CoV-2 version of instructions for making the spike protein into RNA or DNA, or synthesized the protein itself, in order to create vaccines of various types (see sidebar). Once the vaccine is delivered into the body, the immune system makes antibodies that recognize the virus and block it from getting into cells, either preventing infection or helping people avoid serious illness.

Using this approach, drugmakers have set speed records in devising vaccines and beginning clinical trials. FasterCures, which is part of the Milken Institute think tank, is tracking 179 vaccine candidates, most of which are still being tested in lab dishes and animals. But nearly 20 have already begun testing in people.

Some front-runners have emerged, leading the pack in a neck-and-neck race. Some have been propelled by an effort by the U.S. federal government, called Operation Warp Speed, which has picked a handful of vaccine candidates to fast-track.

First out of the starting gate was one developed by Moderna, a Cambridge, Mass.based biotech company. It inoculated the first volunteer with its candidate vaccine on March 16, just 63 days after the viruss genetic makeup was revealed. The company has since reported preliminary safety data, and some evidence that its vaccine stimulates the immune system to produce antibodies against the coronavirus (SN: 5/18/20).

That company and several others now have vaccines entering Phase III clinical trials. Moderna and the National Institute of Allergy and Infectious Diseases, in Bethesda, Md., will begin inoculating 30,000 volunteers with either the vaccine or a placebo in July to test the vaccines efficacy in large numbers of people.

Modernas vaccine requires two doses; a prime and a boost. That means it will take 28 days to get any individual person vaccinated, NIAID director Anthony Fauci said June 26 during a Milken Institute webinar. It will take weeks and months to give the full set of shots to all those people. Then it will take time to determine whether more people in the placebo group get COVID-19 than those in the vaccine group a sign that the vaccine works. Those results could come in late fall or early winter.

NIAID launched a clinical trials network July 8 to recruit volunteers at sites across the United States for phase III testing of vaccines and antibodies to prevent COVID-19. Modernas vaccine will be the first in line for testing.

Some researchers propose accelerating clinical trials even further by trying controversial challenge trials, in which vaccinated volunteers are intentionally exposed to the coronavirus (SN: 5/27/20). None of those studies have gotten the green light yet.

Three other global drug and vaccine companies have announced plans to launch similarly sized trials this summer: Johnson & Johnson; AstraZeneca, working with the University of Oxford; and Pfizer Inc., which has teamed up with the German company BioNTech. Like Moderna, all are part of Operation Warp Speed, or will be joining it.

Usually, Phase III trials are about determining efficacy. But the rush to get through earlier stages designed to make sure a drug doesnt cause harm means that scientists also will be keeping a keen eye on safety, Fauci said. Researchers will be watching, in particular, for any suggestion that antibodies generated by the vaccine might enhance infection.

That can happen when antibodies stimulated by the vaccine dont fully neutralize the virus and can aid it getting into cells and replicating, or because the vaccine alters immune cell responses in unhelpful ways. Vaccines against MERS and SARS coronaviruses made infections with the real virus worse in some animal studies.

Such enhanced infections are a worry for any unproven vaccine candidate, but some experimental vaccines in the works may be more concerning than others, says Peter Pitts, president of the Center for Medicine in the Public Interest, a nonprofit research and education organization headquartered in New York City.

For instance, China-based CanSino Biologics Inc. has developed a hybrid virus vaccine: Its made by putting the coronavirus spike protein into a common cold virus called adenovirus 5. That virus can infect humans but has been altered so that it can no longer replicate.

In a small study, reported June 13 in the Lancet, CanSinos vaccine triggered antibody production against the spike protein. But many volunteers already had preexisting antibodies to the adenovirus, raising concerns that that could weaken their response to the vaccine. A weakened response might make an infection worse when people encounter the real coronavirus, Pitts says.

Thats of particular concern because CanSino said in a June 29 statement to the Hong Kong stock exchange that its vaccine was approved by the Chinese government for temporary use by the Chinese military. Thats essentially turning soldiers into guinea pigs, Pitts says.

The type of antibodies stimulated by the vaccine will be important in determining whether the vaccine protects against disease or makes things worse, Yale University immunologists Akiko Iwasaki and Yexin Yang, warned April 21 in Nature Reviews Immunology. Some types of antibodies have been associated with more severe COVID-19.

And it will be important to monitor the ratio of neutralizing antibodies and non-neutralizing antibodies, as well as activity of other immune cells triggered by the vaccines, an international working group of scientists recommended in a conference report in the June 26 Vaccine.

Public health officials will also be tracking side effects closely. As big as the vaccine trials may be, we cant be sure that there arent rare side effects, Anne Schuchat, principal deputy director of the Centers for Disease Control and Prevention, said June 29 during a question-and-answer session with the Journal of the American Medical Association. Thats why even when we get enough to vaccinate large numbers, were going to need to be following it.

In 1976 for instance, it turned out that Guillain-Barr syndrome, a rare neurological condition in which the immune system attacks parts of the nervous system, was a rare side effect of the swine flu influenza vaccine. That didnt become obvious until the vaccine had already been rolled out to 45 million people in the United States.

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Early on, it was unclear whether scientists could devise a vaccine against the coronavirus at all. Its now a question of when rather than if well have a vaccine.

But some researchers have expressed concern that rushing clinical trials might lead federal regulators to approve a vaccine based on its ability to trigger antibody production alone. Its still unclear how well antibodies protect against reinfection with the coronavirus and how long any such immunity may last (SN: 4/28/20). The measure of whether the vaccine works should be its ability to protect against illness, not antibody production, Fauci said.

I really want to make sure that we dont have a vaccine thats distributed among the American people unless we know its safe and we know it is effective, he said. Not that we think it might be effective, but that we know its effective.

So far though, companies are measuring success by the antibody. For instance, INOVIO, a biotechnology company based in Plymouth Meeting, Pa., announced June 30 that 94 percent of participants in a small safety trial made antibodies against the coronavirus. The data, delivered via news release like that from numerous other companies rushing to show progress, had not been peer-reviewed and other details about the companys DNA-based vaccine were sparse.

Despite still having much to prove, companies are gearing up manufacturing without knowing if their product will ever reach the market. By the end of the year, companies promise they can have hundreds of millions of doses. We keep saying, Are you sure? And they keep saying yes, Fauci said. Thats pretty impressive if they can do it.

For instance, if everything goes right, a vaccine in testing now from Pfizer might be available as soon as October, Pfizer chairman and chief executive Albert Bourla said during the Milken Institute session. If we are lucky, and the product works and we do not have significant bumps on our way to manufacturing, he said, the company expects to be able to make 1 billion doses by early next year.

Pfizer released preliminary data on the safety of one of four vaccine candidates it is evaluating July 1 at medRxiv.org. In the small study of 45 people, no severe side effects were noted. Vaccination produced neutralizing antibodies at levels 1.8 to 2.8 times levels found in blood plasma from people who had recovered from COVID-19, researchers reported.

Novavax Inc., a Gaithersburg, Md.-based biotechnology company, announced July 7 that it was being award $1.6 billion from Operation Warp Speed to conduct phase III trials and to deliver 100 million doses of its vaccine as early as the end of the year.

If manufacturers can deliver a vaccine as promised, there could be another big hurdle: Theres no guarantee people will line up for shots. About a quarter of Americans said in recent polls that they would definitely or probably not get a coronavirus vaccine if one were available. Thats a pending public health crisis, Pitts says.

Krofah agrees. We need to think about the post-pandemic world in the midst of all of this, she says. We need to start building that public trust now. Tackling issues of vaccine hesitancy shouldnt be left until a vaccine is available, she says.

Whether with vaccines or treatments, we need to expedite, but not rush, Pitts says. Theres a perception that therapeutics or vaccines will be approved willy-nilly because of politics, and thats a dangerous misperception. The FDA laid out guidelines, including an accelerated approval process, on June 30 that should ensure any approved vaccines work, he says.

There is good news for those who are eagerly awaiting vaccines, Krofah and Pitts say: There wont be just one winner in the race. Instead, there may be multiple options to choose from. Thats not a luxury; it may be a necessity. Multiple vaccines may be needed to protect different segments of the population, Krofah says. For instance, elderly people may need a vaccine that prods the immune system harder to make antibodies, and children may need different vaccines than adults do.

Whats more, long-term investments in development will be needed so that vaccines can be altered if the virus mutates. We need to stay the front and not declare victory once a vaccine has been approved for emergency use, she says.

For now, vaccine makers are moving both as quickly and as carefully as possible, Bourla said. I am aware that right now that billions of people, millions of businesses, hundreds of governments are investing their hope for a solution in a handful of pharma companies.

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A COVID-19 vaccine may come soon. Will the blistering pace backfire? - Science News

Polygenic risk scores, which evaluate disease risk based on DNA variants, have previously been based almost entirely on patients who had European ancestry.

The project, Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network, will build upon work of the existing eMERGE Network, and help these institutions recruit a higher percentage of patients from diverse ethnic backgrounds. The goal is to serve patients who are typically underrepresented in clinical trials or who typically have poor clinical outcomes.

NHGRI funds eMERGE, which brings together DNA biorepositories with electronic health record (EHR) systems to allow high-throughput genetic research to advance personalized medicine. While much of this kind of work is associated with cancer research, eMERGE and the grants awarded in the new round of funding will work to advance protocols that will determine care models for diabetes and cardiovascular disease and determine who is at risk for Alzheimer disease.

The challenge of bringing diversity to clinical trials has been well-documented in the scientific literature in recent years. A 2016 workshopat the European Society of Human Genetics explored the need to address disparities by engaging communities that been historically underrepresented in genomics research; without data from these populations, interpreting genetic testing results would be difficult when these patients sought care, and pathways based on clinical trials might not produce the same outcomes in these populations.

Where the Money Goes

In addition to the $61 million to the 10 sites, $13.4 million will go to the eMERGE Network Coordinating Center at Vanderbilt University.

The 10 sites will be in 2 categories. The first group, to include Mayo Clinic, Rochester,Minnesota; Vanderbilt University Medical Center, Nashville, Tennessee; Brigham and Womens Hospital, Boston; and Northwestern University, Chicago, will seek 10,000 patients, of which at least 35% should be from underrepresented groups.

The second set of locations, called enhanced diversity clinical sites, will seek 15,000 patients, of which 75% must be from diverse groups. These are the University of Alabama, Birmingham; Icahn School of Medicine at Mount Sinai, New York City; Cincinnati Children'sHospital Medical Center; Columbia University, New York City; Childrens Hospital of Philadelphia; and University of Washington Medical Center, Seattle.

Officials for Childrens Hospital of Philadelphia (CHOP) noted the specific requirements of this round of funding called for enrolling at least 2500 new participants who had not been previously involved with the hospitals Center for Applied Genomics (CAG), of which 75% must be African American.

The Center for Applied Genomics and the National Institutes of Health have had an excellent partnership within the eMERGE Network, and we are thrilled to continue to build upon the valuable work that we have been able to achieve so far with particular emphasis on resolving diseases in diverse patient populations and minority groups, Hakon Hakonarson, MD, PhD, director of the CAG at CHOP and principal investigator of the program, said in a statement. The primary goals of this program are to identify disease risks faced by patients and their families and to determine the most appropriate actions we can take to improve health outcomes. The program specifically focuses on African American children and their families, who will constitute 75% of participants.

Polygenic risk scores, which evaluate disease risk based on DNA variants, have previously been based almost entirely on patients who had European ancestry. Investigators have seen a need to incorporate data from patients from non-European ancestry into risk scores, as well as those who have clinical and lifestyle characteristics seen in the real world, such as higher body mass index (BMI), alcohol use, elevated blood glucose levels, and other factors that affect a persons risk level.

The eMERGE Network, launched in 2007, first collected electronic health record data to address this problem. The sites that will proactively collect data over the next 5 years will add new data to incorporate into risk calculations.

The goal is to develop protocols to estimate risk for common, complex diseases, such as coronary heart disease, diabetes, or Alzheimers disease, and incorporate health management recommendations for clinicians into the EHR using the Fast Healthcare Interoperability ResourceStandard, which spells out how health information is to be shared electronically.

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NIH Funds Research to Understand How Genomics of Diverse Populations Affect Clinical Care - AJMC.com Managed Markets Network

Parasitic filarial nematodes infect hundreds of millions of people, causing diseases such as river blindness and lymphatic filariasis, which can lead to elephantiasis, a severe swelling of the limbs.

Mosquitoes spread the parasitic worms, which engage in sophisticated migrations within their insect and mammal hosts. One worm, Brugia malayi, starts in the mosquitos gut, migrates to its flight muscles, then to its mouth. In its human host, the worm travels between the lymphatic system and the blood. Researchers have little idea how the nematodes achieve these nomadic lifestyles that are crucial for their survival.

Researchers prepare to inject an anaesthetized mosquito infected with parasitic Brugia malayi nematodes with gene-disrupting molecules to study how the nematodes rely on chemical sensation to migrate within their hosts. Courtesy of Zamanian lab

In new research, University of WisconsinMadison scientists provide the first look at the genetic underpinnings of the worms migration through their hosts. They identified two genes the nematodes use to respond to cues in their host environment. When the genes are disrupted, the worms are lost and less effective at infecting their hosts.

The genes are part of the nematodes chemosensation network, a combination of chemical-sensing proteins and nerve cells that let the parasites detect and respond to molecules in their environment. Because these responses are key for the nematodes complex life cycle, theyre a potential target for future treatments.

Were hopeful that a better understanding of how worms are transmitted between hosts and move within them may lead to new approaches for parasite treatment and control, says Mostafa Zamanian, a professor of pathobiological sciences in the UWMadison School of Veterinary Medicine and senior author of the report. The work was published in June in the journal PLOS Biology.

All animals use chemosensation. Its what allows a bee to follow the scent of a flower or a human to track down the aroma of baking cookies. The Zamanian lab figured that filarial nematodes used the same system to travel to the right part of their mosquito and human hosts at the right time by following specific chemical signatures their hosts produce.

To test this idea, the researchers mined over 40 parasite genomes to identify sensory genes in filarial parasites. Then they measured the expression of chemosensory genes throughout the parasites life cycle. They looked at chemoreceptors proteins that detect a specific signal during distinct stages of the parasites life cycles within human and mosquito hosts, when the parasites migrate to different tissues.

Mostafa Zamanian

Nicolas Wheeler

We saw chemoreceptors turned on and turned off at very specific time points, likely to help the nematodes get to the right destination at the right time, says Nicolas Wheeler, a postdoctoral researcher in the Zamanian lab and lead author of the new study.

The researchers tested whether disrupting the chemosensation network would impair the worms ability to migrate within and infect their hosts. They singled out two genes known to act as messengers for chemosensation in distantly related nematodes: OSM-9 and TAX-4.

To test OSM-9s function, they exposed the nematodes to the OSM-9-disrupting chemical nicotinamide at different stages of their life cycles. When these nicotinamide-laced worms were fed to mosquitoes, the insects ended up infected with 20 to 40 percent fewer parasites. Those nematodes that did survive in the mosquitoes were worse at migrating to the insects flight muscles compared to nematodes with normally functioning OSM-9.

The researchers also extracted larvae from mosquitoes during the stage when they can infect humans and exposed them to nicotinamide. In a petri dish experiment, the larvae became less likely to move toward chemical signals in mammalian blood. The results of the nicotinamide experiments suggested that OSM-9 is key for helping the worms navigate.

The filarial nematode Brugia malayi during the larval life stage when it can infect humans, where the parasite can cause severe swelling in the limbs known as elephantiasis. Courtesy of Zamanian lab

Using another system, the research team was able to disrupt both OSM-9 and TAX-4 while the nematodes were developing within their mosquito hosts. The researchers had to inject hundreds of mosquitoes by hand with molecules tailored to disrupt each gene finicky, time-consuming work.

Because the mosquitoes were infected with the parasites and potentially able to transmit them, the researchers had to don head-to-toe protective clothing to avoid getting bitten. Then they tested how well the nematodes could respond to chemical signatures in mammals.

The filarial nematode Brugia malayi during the lifestage when it is taken up by mosquitoes feeding on infected humans. In mosquitoes, the parasite must travel from the insects gut to its flight muscles and eventually its mouth to make it back to human hosts. Courtesy of Zamanian lab

It was worth it in the end, because we were able to show both OSM-9 and TAX-4 are involved in the infective larvas ability to crawl toward (host signals in the blood), says Wheeler. These are the first two genes to be linked to migratory behavior in these parasitic nematodes.

There are effective treatments against filarial parasites, but the complex drug regimens have potentially severe side effects, and the nematodes have developed drug resistance. There is also growing evidence that sensory systems play an important role in how parasites respond to existing antiparasitic drugs. A better understanding of how the worms detect chemical signatures and find their way within hosts could one day help researchers disrupt these critical migrations, potentially bolstering treatment.

This is a starting point, says Wheeler.

This work was funded in part by the National Institutes for Health (grants K22AI125473 and R01AI151171).

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Parasitic worms use their keen senses to wriggle through their hosts - University of Wisconsin-Madison

BOSTON, July 10, 2020 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) affiliate Phoenix Tissue Repair (PTR) today announced an upcoming presentation of interim data from an ongoing Phase 1/2 study of PTR-01 (BBP-589), an intravenously-administered recombinant collagen 7 protein replacement therapy for patients with recessive dystrophic epidermolysis bullosa (RDEB). The presentation will be made during the Society for Pediatric Dermatologys (SPD) 45th Annual Meeting, to be held virtually July 10-12, 2020.

The poster presentation, which includes safety and tolerability data observed so far in patients enrolled in cohorts 1-3, will be delivered by Anna L. Bruckner, MD, associate professor of dermatology and pediatrics at University of Colorado School of Medicine. The pre-recorded presentation will be available online to meeting registrants until December 31, 2020. The poster will also be available on the Phoenix Tissue Repair website.

Details for the presentation are below:

Title: Interim update from a Phase 1/2 trial examining the safety and tolerability of PTR-01, a collagen 7 protein replacement therapy, in patients with recessive dystrophic epidermolysis bullosaPresenter: Anna L. Bruckner, MD

AboutDystrophic Epidermolysis Bullosa (DEB)DEB is a rare genetic disorder symptomatic from birth that is caused by mutations in the gene for a protein called collagen type VII (C7). The C7 protein is essential for the formation of anchoring fibrils, structures which connect the epidermis and dermisthe uppermost two layers of the skin. Patients with the recessive form of DEB (RDEB) tend to have particularly severe symptoms due to severe insufficiency of functional C7. Symptoms include extreme skin and mucosal fragility that present as recurrent, painful blistering and scarring of the skin, as well as ulcerations of the mouth, tongue and dental caries. In addition to the cutaneous and oral symptoms, severe forms are associated with erosions and scarring of mucous membranes of the eye, esophagus, genitals and anus. Joint contractures, mutilating deformities of hands and feet, malnutrition, growth retardation, recurrent infections and a significantly increased risk for squamous cell carcinoma are also common. There are currently no approved disease-modifying therapies for any form of DEB, and the standard of care focuses on wound and pain management.

About Phoenix Tissue Repair and PTR-01Phoenix Tissue Repair is aBoston-based company that is an affiliate of BridgeBio Pharma, and is focused on advancing a novel systemic treatment for recessive dystrophic epidermolysis bullosa (RDEB).PTR-01 is an investigational protein replacement therapy which uses a recombinant collagen type VII (rC7) for the treatment of RDEB. PTR-01 is designed to be systemically available through intravenous delivery. Phoenix Tissue Repair acquired worldwide rights to PTR-01 in 2017. Preclinical studies of PTR-01 have demonstrated C7 staining in basement membranes withde novoanchoring fibril formation and improved survival in models of RDEB.

PTR-01 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration and the European Medicines Agency.

About BridgeBioPharma, Inc.BridgeBio is a team of experienced drug discoverers, developers and innovators working to create life-altering medicines that target well-characterized genetic diseases at their source. BridgeBio was founded in 2015 to identify and advance transformative medicines to treat patients who suffer from Mendelian diseases, which are diseases that arise from defects in a single gene, and cancers with clear genetic drivers. BridgeBios pipeline of over 20 development programs includes product candidates ranging from early discovery to late-stage development. For more information, visit bridgebio.com.

Forward-Looking StatementsThis press release contains forward-looking statements. All statements contained herein other than statements of historical fact constitute forward-looking statements, including statements relating to expectations, plans, and prospects regarding Phoenix Tissue Repair's clinical development plan, clinical trial results, timing and completion of clinical trials, and ability to take advantage of expedited FDA review for PTR-01. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to, Phoenix Tissue Repair's ability to advance PTR-01 in clinical development in accordance with its plans, the results from any clinical trials and nonclinical studies of PTR-01, and the nature of Phoenix Tissue Repair's interactions with regulatory authorities. Moreover, Phoenix Tissue Repair operates in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of Phoenix Tissue Repair's management as of the date of this release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. All forward-looking statements in this press release are based on information available to Phoenix Tissue Repair as of the date hereof, and Phoenix Tissue Repair disclaims any obligation to update these forward-looking statements except as required by law.

Investor Relations Contact:Mike Mangone, Ph.D.Vice President, Business Development & Corporate Strategy857-449-0970info@phoenixtissuerepair.com

Media Relations Contact:Carolyn HawleyCanale Communications(619) 849-5382carolyn@canalecomm.com

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BridgeBio Pharma's Phoenix Tissue Repair to Highlight Interim Phase 1/2 Study Data in a Presentation at the Society for Pediatric Dermatology's 45th...

By The Canadian Press on July 10, 2020.

In The News is a roundup of stories from The Canadian Press designed to kickstart your day. Here is whats on the radar of our editors for the morning of July 10

What we are watching in Canada

OTTAWA The Supreme Court of Canada is slated to rule this morning on the constitutionality of a federal law that forbids companies from making people undergo genetic testing before buying insurance or other services.

The Genetic Non-Discrimination Act also outlaws the practice of requiring the disclosure of existing genetic test results as a condition for obtaining such services or entering into a contract.

The act is intended to ensure Canadians can take genetic tests to help identify health risks without fear they will be penalized when seeking life or health insurance.

The law, passed three years ago, is the result of a private members bill that was introduced in the Senate and garnered strong support from MPs despite opposition from then-justice minister Jody Wilson-Raybould.

The Quebec government referred the new law to the provincial Court of Appeal, which ruled in 2018 that it strayed beyond the federal governments jurisdiction over criminal law.

The Canadian Coalition for Genetic Fairness then challenged the ruling in the Supreme Court of Canada, which heard the appeal last October.

Also this

OTTAWA Canadian troops are being forced to hitch a ride with the British military to get to and from Latvia due to a shortage of working planes.

A CC-150 Polaris was to carry about 120 Canadian soldiers to Latvia on Wednesday and fly back with a similar number of returning troops.

Yet the Defence Department says those plans changed after a problem was found with the planes landing gear, which is when the military asked the British for help.

The Air Force has three Polaris capable of ferrying personnel to different parts of the world but the Defence Department says the other two were unavailable.

One is currently ferrying troops to and from the Middle East while the third which normally serves as the prime ministers plane is out of commission until at least January after a hangar accident last October.

Defence Department spokeswoman Jessica Lamirande says the British plane took off with the 120 departing troops on Thursday and will return with a similar number of soldiers in the coming days.

What we are watching in the U.S.

International students worried about a new immigration policy that could potentially cost them their visas say they feel stuck between being unnecessarily exposed during the coronavirus pandemic and being able to finish their studies in the United States.

The students from countries such as India, China and Brazil say they are scrambling to devise plans after federal immigration authorities notified colleges this week that international students must leave the U.S. or transfer to another college if their schools operate entirely online this fall.

Some say they are considering the possibility of returning home or moving to Canada.

What we are watching elsewhere in the world

SEOUL The sudden death of the Seoul mayor is triggering an outpouring of public sympathy but also questions about his behaviour.

Park Won-sun was found dead in the South Korean capital, hours after his daughter reported him missing.

Media reports say one of his secretaries lodged a complaint with police over his alleged sexual harassment.

Many mourn Parks death, while others worry sympathy for him could lead to a criticism of the woman who filed the complaint.

Despite gradually improvements in womens rights in recent years, South Korea remains a male-centred society.

Today in 1912

Montreals George Hodgson won Canadas first Olympic swimming gold medal. He set a world record of 22 minutes flat in the 1,500-metre freestyle at the Games in Stockholm. That record lasted 11 years. Four days later, Hodgson won the 400-metre freestyle. Canada did not capture another Olympic swimming title until 1984.

The Canadian economy

Statistics Canada is set this morning to give a snapshot of the job market as it was last month as pandemic-related restrictions eased and reopenings widened.

Economists expect the report will show a bump in employment as a result, further recouping some of the approximately three million jobs lost over March and April.

Financial data firm Refinitiv says the average economist estimate for June is for employment to increase by 700,000 jobs and the unemployment rate to fall to 12.0 per cent.

The unemployment rate in May was a record-high 13.7 per cent, a far turn from the record low of 5.5 per cent recorded in January.

The Bank of Canada and federal government say the worst of the economic pain from the pandemic is behind the country, but Canada will face high unemployment and low growth until 2021.

The economic outlook released by the Liberal government Wednesday forecasted the unemployment rate to be 9.8 per cent for the calendar year, dropping to 7.8 per cent next year based on forecasts by 13 private sector economists.

This report by The Canadian Press was first published July 10, 2020.

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Genetic testing and hitching a ride with the British; In The News for July 10 - Medicine Hat News

An emergency response team on 11 January at work in the Huanan Seafood Wholesale Market in Wuhan, China, initially said to be the source of COVID-19.

By Jon CohenJul. 10, 2020 , 4:30 PM

Science's COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

The two-person team from the World Health Organization (WHO) traveling to China today to address the origin of the COVID-19 pandemic is unlikely to come home with answers. Rather, the duoan epidemiologist and an animal health expert whose names have not been releasedwill discuss with Chinese officials the scope of alarger international mission later, according to a WHO statement.

But this initial trip offers real hope that the mystery of the virus origins, which has become a political powder keg and the subject of countless conspiracy theories, will finally be investigated more thoroughly and transparently. (A similar WHO-led mission to examine how China was handling its fight against the virus, launched after weeks of diplomatic wrangling, returned in February with a surprising wealth of information.)

Science must stay open to all possibilities about the pandemics origins, Mike Ryan, executive director of WHOs Health Emergencies Programme, said at a press conference on 7 July. We need to lay out a series of investigations that will get the answers that Im sure the Chinese government, governments around the world, and ourselves really need in order to manage the risk going forward into the future.

Questions range from hunting for animals that might harbor the virus to examining the possibility that it came from a laboratory. There are plenty of details to investigate, and it could be a long road. Origin riddles for other new infectious diseases often took years to solve, and the route to answers has involved wrong turns, surprising twists, technological advances, lawsuits, allegations of cover ups, and high-level politics. Determining how a pathogen suddenly emerges in people requires a lot of sleuthing, but past successes offer clues of where to look for new insights, as do the few data points that now exist for SARS-CoV-2, the virus that causes COVID-19.

The initial, tidy origin story told by health officials in Wuhan during the first few weeks of January was that a cluster of people connected to a seafood market developed an unusual pneumonia, and that the outbreak stopped after the market was closed and disinfected. But confusion about the origin of the novel coronavirus identified in Wuhan patients arose when researchers published the first epidemiologic studies of the citys outbreak:Four of the first five casesconfirmed to have SARS-CoV-2 infections had no link to the market.

Soon, other theories emerged. Some believe its no coincidence that the city is host to the Wuhan Institute of Virology (WIV), home to leading bat coronavirus researcher Shi Zheng-Li. Her group, one of the first to isolate and sequence SARS-CoV-2, has trapped bats in the wild for 15 years, hunting for coronaviruses to help identify pandemic threats. In theirfirst report about the new virus, the scientists described a bat coronavirus in their collection that was 96.2% similar to SARS-CoV-2.

U.S. President Donald Trump early on endorsed speculation that the virus entered humans because of an accident at WIV. Amore contentious theoryis that the lab created the virus. (Researchers at the lab insist neither scenario has any merit, and evolutionary biologists elsewhere have argued the virus shows no evidence of having been engineered.)

The most popular hypothesis is that SARS-CoV-2 spread into humans from an intermediate host, an animal species susceptible to the virus that acted as a bridge between bats and humans. In the case of severe acute respiratory syndrome (SARS), civets turned out to play that role for the responsible coronavirus. For Middle East respiratory syndrome (MERS), also a coronavirus disease, itquickly became clearcamels were the culprit because highly similar viruses were found in the animals and people caring for them.

Chinese officials have reported conducting tests for SARS-CoV-2 at the Wuhan seafood market but what they foundremains sketchy. Chinas state-run news agency, Xinhua, said environmental samples tested positive for the virus in a zone of the market that sold wildlife, but the report had no details about the results or even a list of the species for sale. Other studies have discovered similarities between SARS-CoV-2 and a coronavirus found in pangolins, an endangered species that eats ants, but the pangolin virus is more divergent genetically from SARS-CoV-2 than the closest bat virus and theres no evidence pangolins or their scalesused in traditional Chinese medicinewere sold at the market.

Some more fringe theories still suggest SARS-CoV-2 came fromsnakes,cometary debris, or aU.S. Army lab.

So, assuming WHOs team and the Chinese government work out a deal for an international mission to study the pandemics origins, where would it start? Here are some key questions that need answers.

Scientists realized camels were the source of Middle East respiratory syndrome when highly similar viruses were found in the animals and people caring for them.

Another outstanding question is whether Shis team or other researchers in Wuhan manipulated bat viruses in gain-of-function experiments that can make a virus more transmissible between humans. In 2015, Shi co-authored a paper that made a chimeric SARS virus by combining one from bats with a strain that had been adapted to mice. Butthat workwas done at the University of North Carolina, not in Wuhan, and in collaboration with Ralph Baric. Did Shis group later carry out other gain-of-function studies in Wuhanand if so, what did they find?

Finally, diplomatic cablesfrom the U.S. Embassy in Beijing in 2018 warned that a new, ultra-high security lab at WIV had a serious shortage of appropriately trained technicians and investigators. Did Shis team ever work with coronaviruses in that lab, and, if so, why?

If history repeats itself, it might take yearsor even decadesto crack this case. Scientists havent unequivocally identified Ebolas source 45 years after its discovery. But the key, time and again, to clarifying the origins of emerging infectious diseases is unearthing new data. WHOs push to organize the probe promises to, at the very least, accelerate what has been a plodding pursuit for answers.

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A WHO-led mission may investigate the pandemic's origin. Here are the key questions to ask - Science Magazine