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Sahota I.S.,Office of Development Research | Panwar N.S.,Development Research
Indian Journal of Occupational and Environmental Medicine | Year: 2013

Background: Hemkund Sahib is a popular pilgrimage located at 4,330 m in the Garhwal range of the Indian Himalayas. Many travelers to the region have observed pilgrims exhibiting Acute Mountain Sickness (AMS)-like symptoms. However, no systematic study on its prevalence at Hemkund has been conducted. Materials and Methods: We surveyed 25 adults. AMS rates were determined using a standard Lake Louise Score (LLS). Responses to questions related to awareness of AMS, the perceived difficulty of the trek, and physiological data including arterial oxygen saturation (SpO 2) and pulse rate, amongst others, were collected. Results: Overall prevalence of AMS was 28% (mild AMS 20%, severe AMS 8%). Borg Rating of Perceived Exertion (RPE) was 3.9/10. Water consumption for the 4-5 hour trek to Hemkund was only 0.9 L and 20% of pilgrims consumed no water at all. Nine pilgrims claimed to be aware of AMS although only one had taken prophylactic medication. SpO 2 was 82.2 ± 1.2% and pulse rate was 106.5 ± 2.9 bpm (mean ± SEM). There were no differences in non-LLS-related parameters when pilgrims were subdivided by presence or absence of AMS. Conclusion: This pilot study has, for the first time, documented the prevalence of AMS amongst pilgrims to Hemkund Sahib in the Indian Himalayas.

Konuma K.,Tokyo Medical and Dental University | Itoh M.,Tokyo Medical and Dental University | Suganami T.,Tokyo Medical and Dental University | Suganami T.,Japan Science and Technology Agency | And 9 more authors.
PLoS ONE | Year: 2015

Many attempts have been made to find novel therapeutic strategies for non-alcoholic steatohepatitis (NASH), while their clinical efficacy is unclear. We have recently reported a novel rodent model of NASH using melanocortin 4 receptor-deficient (MC4R-KO) mice, which exhibit the sequence of events that comprise hepatic steatosis, liver fibrosis, and hepatocellular carcinoma with obesity-related phenotypes. In the liver of MC4R-KO mice, there is a unique histological feature termed hepatic crown-like structures (hCLS), where macrophages interact with dead hepatocytes and fibrogenic cells, thereby accelerating inflammation and fibrosis. In this study, we employed MC4R-KO mice to examine the effect of highly purified eicosapentaenoic acid (EPA), a clinically available n-3 polyunsaturated fatty acid, on the development of NASH. EPA treatment markedly prevented the development of hepatocyte injury, hCLS formation and liver fibrosis along with lipid accumulation. EPA treatment was also effective even after MC4R-KO mice developed NASH. Intriguingly, improvement of liver fibrosis was accompanied by the reduction of hCLS formation and plasma kallikrein-mediated transforming growth factor-β activation. Moreover, EPA treatment increased the otherwise reduced serum concentrations of adiponectin, an adipocytokine with anti-inflammatory and anti-fibrotic properties. Collectively, EPA treatment effectively prevents the development and progression of NASH in MC4R-KO mice along with amelioration of hepatic steatosis. This study unravels a novel anti-fibrotic mechanism of EPA, thereby suggesting a clinical implication for the treatment of NASH. © 2015 Konuma et al.

News Article | April 19, 2016
Site: motherboard.vice.com

When Paolo Gaudiano’s daughter, who’s now 26, was in junior high school, she was “incredibly bright” in math and physics. But her father noticed she seemed to shy away from technical fields, instead favoring the liberal arts, because she “didn’t see herself fitting in.” “She would look around and see the role models were not there,” he told Motherboard during a recent interview at his Manhattan co-working space. Gaudiano, CTO of the predictive analytics firm Icosystem, has spent decades developing software to simulate and test the everyday operations of organizations like the US Navy, the French shipping company La Poste, and the insurance company Humana. His daughter’s experience got him thinking about a new aspect of a company’s operations: gender balance. Studies show increased female participation in the workforce results in faster economic growth, greater return on sales, and higher profits. American corporations are slowly starting to catch on, and some are scrambling to attract top female talent by pumping cash into recruitment efforts, beefing up their maternity leave policies, and adding nursing facilities for new mothers. But once you get women in the door, you also have to retain them. Women are most likely to leave jobs because they don’t feel challenged, because they aren’t being paid enough, and because they don’t feel like they’re being provided with opportunities to succeed, according to a 2016 study by the International Consortium for Executive Development Research. According to Gaudiano, the problem with addressing those hard-to-pin-down concerns is that gender balance is a “black box.” Corporations may know where they want to be, but they have no real idea how to get there. That’s where Icosystem comes in. The software simulates the complex workings of any given organization by mimicking the behaviors and interactions of individual employees, like a custom-built Sims universe, in order to predict how slight changes in one area, like a call operator’s time on the phone, might impact another, like customer satisfaction. Gaudiano has enlisted the help of former SUNY Levin Institute director Ellen Hunt to apply that modeling technique to the problem of gender inequality, to try to simulate how targeted strategies to recruit and keep women might actually play out in the context of an entire company. “All this talk right now is about, ‘Oh women don’t get promoted right now because they’re less aggressive about asking for things.’ So let’s simulate it,” said Gaudiano. “What if you could get every woman on the planet to increase her aggressiveness by 2 percent? What would be the impact? Is that an assumption that I can validate?” After the financial crisis, Hunt began mentoring C-suite women who had been pushed out of the financial services industry and wanted to reimagine their careers. That’s how she was picked up by the Levin Institute to head its Women Entrepreneurs & Investors Program. In her ideal scenario, Hunt says companies will focus only on peak performance and gender will be a “non-issue.” But until then, corporate America still has a lot of work to do to build on the current groundswell of support for equality in the workplace. “I think if we can push this we can hit a tipping point, and if there are enough women in senior management, it’ll be like sliding down the slope,” she said. According to Gaudiano, current efforts to level the playing field are failing because corporations view their culture as a separate arena, not as something that emerges from the way employees share resources, eat lunch, or interact with competitors and the economy at large. That so-called emergent culture is what Icosystem aims to capture with its models. For example, far too many companies concentrate their gender balance efforts on recruitment, even though the recruitment phase is “miniscule” compared to the time a new employee ultimately spends working, according to Gaudiano. “People take this sort of reductionist approach,” he explained He sees Icosystem’s modeling software as the next logical step beyond statistics, which he thinks are outdated. “With faster computers, people just crunch bigger and bigger data sets, which gives them an impression of accuracy,” he said. “But you’re still using statistics to give you a snapshot of something that happened in the past. And it hides all the details.” On top of simulating the day-to-day operations of any given organization, he said Icosystem’s models can also be used to simulate typically "female" and "male” attributes to see how putting women in leadership positions might help firms lower HR costs or boost sales. Hunt likens Icosystem’s software to a sound studio, where companies can create possible scenarios like music producers adjust faders on a mixing board: “Which ones do you move up or down to create the perfect harmony?” To the extent any data show different male and female distributions for collaboration style, communication style, or the probability of showing up to work on time, Gaudiano says he can build them into the simulation. He stressed that the company isn’t confirming or denying those assumptions. Rather, it’s providing a platform to test how they might impact possible scenarios, like a new competitor entering the scene, or a tripling of the number of female executives. Once a client signs on, Icosystem only needs a few months to get a simulation up and running, Gaudiano said. That time is mostly spent interviewing executives and employees while gathering data relevant to the company and its industry. A model is then built to simulate the every-day interactions of each employee. All this sounds very promising for employers concerned about gender equality. However, the tool has yet to be used in this way, so there is no client data to back up Gaudiano’s claims. He and Hunt plan to spend the next few months talking to potential clients and fine-tuning their marketing strategy. Furthermore, there may be a limit to what models can tell us about the complex world of human resources. Any predictions must be “kept in appropriate perspective” because they come from models and may not include “soft” variables like emotion, conflict and “seemingly irrational behaviors,” said Dr. Sue Moon, who teaches organizational behavior with a focus on gender relations at Long Island University. “Simulation technology may be more useful as a complement—but not necessarily replacement—for real world observation and learning,” she said. No matter how accurate Icosystem’s software purports to be, companies shouldn’t depend on it to bring change. Guadiano doesn’t disagree. Though he stands behind the predictive power of his simulations, he doesn’t treat them as a magic wand. “The point here is not to put a crystal ball up and tell you exactly what will happen,” said Gaudiano. “It’s to say, ‘OK here’s 50 things you’re considering. 20 will be a complete disaster, 20 will be so-so, and 10 of them are likely to be really good.’ Exactly how good they’ll be, we don’t know, but we have a very good idea.” Silicon Divide is a series about gender inequality in tech and science. Follow along here.

While wildlife enriches daily life, strengthens ecosystems and attracts visitors, it can also damage crops and carry disease. Densely populated and rapidly changing places such as Sri Lanka – where human settlements, domestic animals and wildlife mingle closely – need effective ways to manage these benefits and risks. Recent epidemics have shown the critical role that wildlife health monitoring can play. But like many low- and middle-income countries, Sri Lanka lacks the needed infrastructure and expertise. Since 2011, Sri Lanka has had its own national wildlife health centre, co-managed by three government agencies and the University of Peradeniya, and mentored by the Canadian Wildlife Health Cooperative. With support from Canada's International Development Research Centre, a four-year collaboration between the University of Peradeniya and the University of Saskatchewan now aims to build the expertise needed for a national program of research and surveillance to help detect and manage health issues linked to interactions between wildlife and humans. Research co-leader Dr Ted Leighton stresses the need to go beyond cataloguing wildlife and disease. "The human and social dimensions of managing health issues at the human-wildlife interface are severely neglected," he says. "Finding pathogens is relatively easy. The key is knowing how to communicate, educate and motivate risk-reducing behavioural change in human communities at risk." In a first phase of the research, the team identified six study sites where local communities live near protected areas. The sites represent a range of wildlife habitats and agro-ecological conditions. Researchers worked with villagers – including indigenous Adivasi or Vedda communities – to explore their beliefs, perceptions and contact with wild animals and to identify related conflicts or health risks. These explorations showed that, while some misconceptions exist, villagers are quite knowledgeable about the risks of transmittable diseases such as rabies, leptospirosis and Japanese encephalitis. Some villages raised concerns that merit further investigation, such as abnormal jackal behaviour and cases of anaemic sambar deer. The chief aim, however, is to build a critical mass of Sri Lankan scientists able to bridge animal and human health and development. According to Dr Oswin Perera, director of the Sri Lanka Wildlife Health Centre, "The project is making an important contribution to training, capacity building and networking among staff and students from the university and government agencies." Graduate students in veterinary and social sciences are taking part in the research and gaining expertise in areas such as veterinary pathology, epidemiology and community dynamics. Government officials and field staff from the wildlife, veterinary, human health and administrative sectors are helping to set project priorities, taking part in research and incorporating their new capacity in wildlife health into their programs. While building expertise in Sri Lanka, the joint effort is developing organisational models and training and evaluation tools for wildlife health research that may help other countries grappling with emerging diseases and increasing land use conflicts.

News Article | April 18, 2016
Site: www.biosciencetechnology.com

Thanks in part to the efforts of one dedicated mother, who took to Facebook to document her son’s mysterious developmental disability, an international team of researchers led by scientists at UC San Francisco and Baylor College of Medicine in Houston has now identified a new genetic syndrome that could help illuminate the biological causes of one of the most common forms of intellectual disability. In a study of 10 children published online in the American Journal of Human Genetics on April 14, the researchers linked a constellation of birth defects affecting the brain, eye, ear, heart and kidney to mutations in a single gene, called RERE. The discovery is likely to aid researchers striving to understand the cause of birth defects more broadly, the study’s authors said, but it is also a boon to families who know for the first time the reason their children share this group of developmental disabilities. “Just having an answer can be hugely beneficial for families,” said co-senior author Elliott Sherr, M.D., Ph.D., a UCSF pediatric neurologist who directs the Brain Development Research Program and the Comprehensive Center for Brain Development at UCSF. “Of course, getting a genetic answer is just the first step, but for the longest time we didn’t even have that much. It gives these families hope that we can move forward.” Finding could speed search for answers in more common genetic syndrome In their paper, the researchers demonstrate that the developmental disabilities suffered by children with RERE mutations correspond almost perfectly to the well-known pattern of intellectual disabilities, heart defects, craniofacial abnormalities, and hearing and vision problems seen in 1p36 deletion syndrome, one of the most common sources of intellectual disability in children. This syndrome occurs in approximately 1 in 5,000 newborns, and is caused by a much larger (and harder to study) pattern of genetic damage in the so-called 1p36 region at the tip of human chromosome 1. The research group of Daryl Scott, MD, PHD, an associate professor of molecular and human genetics at Baylor College of Medicine, has been working for many years to identify the specific genes that cause the medical problems in children with 1p36 deletion syndrome. “Previous research had narrowed it down to two smaller ‘critical regions’ within the 1p36 region, but even these smaller regions contain dozens of different genes,” said Scott, who was co-senior author on the new study. Scott’s group had focused on the RERE gene, which lies within one of these 1p36 critical regions, because it plays a role in retinoic acid (vitamin A) signaling, an important pathway regulating the development of many organs, including the brain, eye and heart. The Baylor researchers found that mice with Rere mutations had birth defects that were very similar to the children with 1p36 deletions, but had initially been unable to prove that damage to this gene was sufficient produce the same developmental problems in humans. Sherr and Scott credit the genesis of their collaboration to Chauntelle Trefz, the mother of one of Sherr’s patients who connected the two researchers after discovering Scott’s work on mice with Rere mutations online and whose Facebook page about her son, Harrison, became a hub for identifying other children with the same condition. Trefz says that getting the whole exome sequencing results from Sherr and learning that a single gene mutation was responsible for her son’s dizzying array of symptoms — which include global developmental delay, vision problems, hearing problems, weak muscles, and constant acid reflux — was “a game-changer.” “Learning about the mutation was like a huge weight had been lifted,” she said. “When you bring a child with special needs into the world you feel so guilty, like you’ve done something wrong. Hope can be a hard thing to find. Dr. Sherr gave us hope.” Trefz started a Facebook page documenting the joys and challenges of raising and caring for Harrison, who is now 4, hoping to find other families whose children had the same condition. “Harrison is such a happy kid, and he seems normal in many ways, but he’s really not,” she said. “I could see a lot of kids falling through the cracks without the right diagnosis. I wanted other parents to see this and say, ‘that sounds like my son.’” Soon Sherr and Scott had identified 10 children with RERE mutations through collaborators around the US, as well as several from the Netherlands who had found the researchers through Trefz’s Facebook page. The researchers began a thorough comparison of these 10 children with a cohort of 31 patients with the more common 1p36 deletion syndrome, and found that RERE mutations alone produced almost exactly the same pattern of symptoms as 1p36 syndrome, with the exception of a few of the craniofacial abnormalities and cardiomyopathies often seen in that more common syndrome. Additional experiments showed that unique brain and eye problems first observed in human patients were also seen in the mice with Rere mutations. “It’s still a shock that [a mutation in] one gene is capable of causing all these different problems,” Scott said. “But this finding really brings everything together, from molecular studies to mouse experiments and all the way to human patients. We’ve finally proved what we’ve been talking about for all these years.” Though much more study is needed to understand the syndrome fully, Scott said, RERE mutations may be capable of inducing a diverse set of developmental problems because the protein encoded by the gene interacts with important developmental processes in many organs throughout the body, such as the retinoic acid signaling crucial for proper eye and heart development. When RERE doesn’t function properly, the development of all of these organs is affected. Sherr acknowledges that the current sample of just 10 patients with RERE mutations, who each experience slightly different symptoms with notably different levels of severity, is too small to give a complete portrait of the new syndrome. “Now that we’ve seen the first 10 cases, we want to know what the next 10, the next 20 look like,” he said. “That may not take very long. Before we’d even published the paper, we’d already gotten calls from more clinics around the country whose patients have similar mutations. We suspect this syndrome may be significantly more common than we previously appreciated.” The empowerment of families through social media and the plummeting cost of of gene sequencing technologies have produced a revolution in the pace of discovery about rare genetic conditions, Sherr said. “In the last five years alone there’s been a huge explosion in the number of conditions we can decipher genetically – we can take a few kids with developmental disabilities, come up with a coherent genetic explanation for what has happened and use that as first step for how to move forward” he said. “When I started working in child neurology as a fellow back in the late ‘90s, we understood just a few of these super-rare genetic disorders but now there are hundreds. And we’re just getting started.” The authors acknowledge the following industry ties: Sherr is a member of the clinical advisory board of genetic testing company InVitae and consults for Personalis. Four of the authors are employees of GeneDx, which provides exome sequencing on a clinical basis. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from clinical laboratory testing conducted at Baylor Miraca Genetics Laboratories, which provides exome sequencing on a clinical basis.

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