Some cool links TY WindMap: https://www.windy.com Earth WindMap: http://earth.nullschool.net GOES Satellites: https://goes.gsfc.nasa.gov SDO: http://sdo.gsfc.nasa.gov/data/ Helioviewer: http://www.helioviewer.org/ SOHO: https://sohowww.nascom.nasa.gov/ STEREO: https://stereo.gsfc.nasa.gov/cgi-bin/images BARTOL Cosmic Rays: http://neutronm.bartol.udel.edu//spaceweather/welcome.html GONG: https://gong.nso.edu/ Magnetic Maps: https://gong.nso.edu/data/magmap/ondemand.html Kiruna SWx Station: http://www2.irf.se//Observatory/?link=Magnetometers Earthquakes: https://earthquake.usgs.gov/earthquakes/map/ RSOE: http://hisz.rsoe.hu/alertmap/index2.php Moon: http://www.fourmilab.ch/earthview/pacalc.html
It's so cold in Korea that the snow is wrecking skis. "Cold weather turning skis to garbage in Pyeongchang" “One of the coaches said they are throwing the skis out after today,” Craig Randell, a start crew technician working on his third Olympics, said on a chilly morning at the Yongpyong Alpine Centre, where the slalom, giant slalom and team events will be held later this month. “You can’t do anything about it but with the cold temperatures, the snow adheres to the ski base and twists it.” “They are turning their skis to garbage real fast,” he said. Austrian Alpine skier Marcel Hirscher said snow crystals that form amid the frigid weather are the primary culprits for so many skis meeting an untimely end. “Every run is a different pair of skis, but it’s not because of hard conditions but the cold conditions,” he said. “Snow crystals get really sharp when temperatures go to -20 degrees and the base burns. It’s the same as lighting fire and burning your base because the snow crystals get such sharp edges,” said the slalom specialist who is favored to win gold in Pyeongchang. Read more https://www.reuters.com/article/us-...-skis-to-garbage-in-pyeongchang-idUSKBN1FR0F5
How to build a human brain Some steps for growing mini versions of human organs are easier than others BY INGFEI CHEN 3:30PM, FEBRUARY 20, 2018 please log in to view this image BRAIN-MAKING 101 As blobs of two types of brainlike tissue fuse, interneurons (green) migrate from the left clump to the right, linking with neurons (not stained) in the right blob. On both sides, neural support cells called glia appear in purple. PAŞCA LAB/STANFORD UNIV. Email Twitter Facebook Reddit Google+ SPONSOR MESSAGE In a white lab coat and blue latex gloves, Neda Vishlaghi peers through a light microscope at six milky-white blobs. Each is about the size of a couscous grain, bathed in the pale orange broth of a petri dish. With tweezers in one hand and surgical scissors in the other, she deftly snips one tiny clump in half. When growing human brains, sometimes you need to do some pruning. The blobs are 8-week-old bits of brainlike tissue. While they wouldn’t be mistaken for Lilliputian-sized brains, some of their fine-grained features bear a remarkable resemblance to the human cerebral cortex, home to our memories, decision making and other high-level cognitive powers. Vishlaghi created these “minibrains” at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, where she’s a research assistant. First she immersed batches of human pluripotent stem cells — which can morph into any cell type in the body — in a special mix of chemicals. The free-floating cells multiplied and coalesced into itty-bitty balls of neural tissue. Nurtured with meticulously timed doses of growth-supporting ingredients, the cell clumps were eventually transferred to petri dishes of broth laced with Matrigel, a gelatin-like matrix of proteins. On day 56, the blobs display shadowy clusters of neural “rosettes.” Under a laser scanning microscope, razor-thin slices of those rosettes reveal loose-knit layers of a variety of dividing neural stem cells and the nerve cells, or neurons, they give rise to. The layered structures look similar to the architecture of a human fetal brain at 14 weeks of gestation. please log in to view this image By eight weeks, brainlike clumps (top) show neural clusters called rosettes. Within one cluster (red box, expanded at bottom), stem cells (blue and teal) churn out layers of neural precursor cells (pink) and neurons (not stained). BOTH: M. WATANABE ET AL/CELL REPORTS 2017 Across the globe, labs such as this one, led by UCLA developmental biologist and neuroscientist Bennett Novitch, are cultivating thousands of these brainy clumps for research. Less than five years ago, a team of biologists in Austria and the United Kingdom and one in Japan wowed the world when they announced they had made rudimentary bits of 3-D human cerebral cortex in a dish. Since then, researchers have been eagerly tinkering with techniques for producing these miniature brain models, like chefs obsessively refining their favorite recipes. “It’s like making a cake: You have many different ways in which you can do it,” says Novitch, who prefers using the Japanese method with a few tweaks. “There are all sorts of little tricks that people have come up with to overcome some of the common challenges.” For instance, because the brain blobs lack a built-in blood supply, they must absorb enough oxygen and nutrients from the tissue-culture broth to remain healthy. To help, some labs circulate the broth around the tissue clumps. The UCLA researchers choose instead to grow theirs at higher oxygen levels and chop the blobs at the 35-day mark, when they are as wide as three millimeters, and then about every two weeks after. Sounds radical, but the slicing gives cells on the inside — some of which start dying — exposure to much-needed oxygen and nutrients. Those divided bits then continue growing separately. But cutting can be done only so many times before the expanding rosette structures inside are damaged. With all the experimenting, researchers have cooked up a lot of innovations, including some nifty progress reported in just the last year. Scientists have concocted tiny versions of several brain regions ranging from the hypothalamus, which regulates body temperature, thirst and hunger, to the movement-controlling basal ganglia. Electrical chatter among neurons, reflecting active brain circuits, has been detected. And research groups have recently begun linking bits of specific regions like Legos. Scientists have even observed some early developmental processes as they happen within the human brain blobs. Stem cell payoff The work is part of a broader scientific bonanza that comes from coaxing human stem cells to self-assemble into balls of organlike tissue, known as organoids, that are usually no bigger than a lentil. Although the organoids don’t grow enough to replicate entire human organs, these mini-versions can mimic the 3-D cellular infrastructure of everything from our guts to our lungs. That’s something you can’t get from studies of rodents, which have different biology than humans do. Mini-organ models promise enormous advantages for understanding basic human biology, teasing apart human disease processes, and offering an accurate testing ground for finding or vetting drug therapies. And by creating personalized organoids from the reprogrammed cells of patients, scientists could study disease in a very individualized way — or maybe even use organoid structures to replace certain damaged tissues, such as in the liver or spinal cord. “Organoids offer an unprecedented level of access into the inner workings of the human brain,” Novitch says, noting that our brains are largely off-limits to poking and cutting into for research. If scientists can study accurate models of working neural circuits in these brain bits, he and others say, researchers might finally get a handle on uniquely human neurological conditions. Such disorders, which include epilepsy and, experts theorize, schizophrenia and autism (SN Online: 7/17/15), can arise when the brain’s communication networks develop off-kilter. How to build a brain Methods for making bits of brainlike tissue tap the innate tendency of human pluripotent stem cells to form neural tissue. Here’s one group’s process. please log in to view this image T. TIBBITTS Day 0: Around 9,000 stem cells are transferred into V-shaped wells and suspended in a cocktail of vitamins, amino acids and (for the first six days) Y-27632, a chemical to prevent the stem cells from committing suicide. Within a few days, the multiplying cells self-aggregate into tiny balls of neural tissue. The broth is refreshed every two to three days. Day 18: The enlarging neural balls are moved into petri dishes of broth with CDLC, a supplement that provides fats. High oxygen levels (40 percent oxygen, 5 percent carbon dioxide) help the tissue absorb enough oxygen. Well-defined clusters, or rosettes, show early layers of various types of developing neural cells by weeks four to five. Day 35: At 2 to 3 millimeters wide, the brainlike organoids are cut in half to give cells inside more access to nutrients and oxygen. The tissue clumps are nurtured in new broth infused with growth enhancers: a gelatin-like matrix of support proteins called Matrigel, B27 vitamin supplement, heparin and the growth promoter LIF. Day 56: Organoids are again snipped in half and transferred to new petri dishes made of oxygen-permeable plastic to optimize access to oxygen for healthy growth. From here on, the organoids are halved every two weeks or so, routinely surviving as long as 150 days. Source: M. Watanabe et al/Cell Reports 2017 But the research is still in its early days. Although there’s been exciting headway, studies sometimes overstate the extent to which human brain organoids reproduce features of actual developing brain tissue, says stem cell biologist Arnold Kriegstein of the University of California, San Francisco. The minimodels still lack many basic components, including certain cell types, a blood-vessel network and inputs from other neural regions. Another stumbling block is that brain organoids can vary a lot from protocol to protocol, or even batch to batch within the same lab. “The major focus now needs to be on reproducibility, and being able to get an approach that you can rely on to give you the same outcome each time,” Kriegstein says. DIY organs For decades, biology research has relied on cell lines grown in flat sheets in petri dishes, but those sheets lack the structural complexity of living tissue. Then came pioneering work that unveiled the do-it-yourself magic of stem cells raised free-floating in broth. Organlike tissue bits can be generated from pluripotent stem cells that are either plucked from embryos or created by taking a person’s adult skin or blood cells and chemically inducing them to revert to an embryonic-like state. Starting in the mid-2000s, Yoshiki Sasai’s team at the RIKEN Center for Developmental Biology in Kobe, Japan, demonstrated how to grow brainlike structures using embryonic stem cells, first from mice and then humans. please log in to view this image In cross sections of 8-week-old brain organoids (top row), loose-knit cell layers roughly resemble the tighter bands in 14-week-old human fetal brain tissue (bottom row). The last column shows a zone of neural progenitor cells (red) and an outer layer of neurons (green). M. WATANABE ET AL/CELL REPORTS 2017 In their groundbreaking study in 2013 in Proceedings of the National Academy of Sciences, the researchers used chemical cues to direct human embryonic stem cells to form a specific region of the human cortex. (Tragically, Sasai committed suicide the next year, after two stem cell studies that he coauthored were retracted amid scientific misconduct charges against a research colleague [SN: 12/27/14, p. 25]. Before his death, Sasai was cleared of any direct involvement. The discredited studies were not related to the organoid research.) A few months before the 2013 Sasai team paper, Madeline Lancaster and Juergen Knoblich of the Institute of Molecular Biotechnology in Vienna and U.K. colleagues demonstrated their more freewheeling, landmark approach to growing brain organoids(SN: 9/21/13, p. 5). The recipe, described in Nature, allows human pluripotent stem cells to spontaneously attempt to assemble into a tiny approximation of a whole brain by making whatever brain structures the stem cells choose. Meanwhile, biologists elsewhere were whipping up other types of organoids, starting instead with adult stem cells. These rare, damage-repairing cells are found in many organs (including the brain), but the cells can transform into only a limited range of cell types. In 2009, Hans Clevers of the Hubrecht Institute in Utrecht, the Netherlands, announced that his lab unexpectedly created a miniature version of a gut while cultivating adult stem cells that the team had discovered in mouse intestinal tissue. Grown in a drop of Matrigel with a trio of growth-inducing factors, these cells coalesced into little spheres containing tiny projections that resembled the fingerlike villi that absorb nutrients in the gut. Scientists soon were concocting tiny facsimiles of human stomachs, livers, kidneys, lungs and more (SN: 12/28/13, p. 20). “We essentially are discovering the vitality of what the stem cells actually do,” says Clevers, who is president of the International Society for Stem Cell Research. “We give [the cells] a little push, and they do whatever they’re good at.” The trick is knowing exactly which ingredients to use to make different organs. For pluripotent stem cells, that means exposing them to just the right growth factors or inhibitors at just the right times, over about a month, says James Wells of the Center for Stem Cell and Organoid Medicine at Cincinnati Children’s Hospital Medical Center. Some of those essential instructions are well-known from decades of research on embryo development in fish, chickens and rodents; the same chemical cues generally work for all animals with spinal cords, including people. please log in to view this image Under a microscope, rosettes of neural cells are visible along the perimeter of an 8-week-old brain organoid. The center, where cells have died, is dark. N. VISHLAGHI/UCLA However, for many body parts, organoid makers must suss out recipe instructions from scratch. Working with Jorge Múnera and other colleagues, Wells recently produced a minimodel of a human colon using human induced pluripotent stem cells. But first, the team conducted months of experiments on frog and mouse embryos to identify the signals for forming a colon. “It took a while to figure out what the special sauce was,” Wells says. Some scientists have distant dreams of using organoid methods to grow full-size livers or kidneys in the lab for transplantation. A more attainable goal may be regenerative tissue transplants, for example, replacing dying liver cells in someone with early-stage liver disease with chunks of healthy stem cells from a personalized liver organoid. Or, in patients who’ve had part of the small intestine removed, tiny pieces of gut organoid tissue could be implanted and, after growing larger, connected to the intestine. Head games The human brain, meanwhile, is vastly more complicated than any other organ. It’s unlikely that scientists will ever be able to build a full replica. While the initial brain-making recipes were stunning for what they could achieve, they left much room for improvement. In the years since the 2013 debut of human brain organoids, research groups have worked to grow bigger brain tissue clumps and more uniform structures. The Austrian method for making whole-brain organoids, in particular, produced a random mix of neural regions laid out in a topsy-turvy manner. But bioengineering tricks may help. In a study last year, Lancaster, now at the MRC Laboratory of Molecular Biology in Cambridge, England, and Knoblich got more consistent results by adding polymer filaments as scaffoldingto guide the organization of the minibrain models. please log in to view this image With surgical scissors, a UCLA biologist prepares to snip one of those organoids in half to give inner cells more access to oxygen and nutrients from the broth in the dish. INGFEI CHEN Other scientists, following the Japanese approach, which generally gives more predictable results, have concentrated on coaxing out specific cell types or structural features of the real brain. For instance, one constraint is that the organoids form slowly, more or less sticking to the same timeline of development as does a human brain during gestation. But without a blood supply, growth is limited; the brain bits reach only a few millimeters in size. That means organoid models are often short on cell types from later development stages, such as cells called astrocytes. These star-shaped cells are crucial for creating and curating the connections between neurons, and also may help with forming memories (SN Online: 11/15/17). Astrocytes don’t fully mature in a baby’s brain until after birth. But Stanford University neuroscientist Sergiu Paşca has crafted a method for making and maintaining 4-millimeter-wide balls of human cortex–like tissue (he calls them spheroids) in 3-D culture for an extended time. Last August in Neuron, his team described organoids that survived for more than 20 months — long enough, analyses showed, for astrocytes to mature and function in ways that mimic their real-brain counterparts. Of great interest, also, are the outer radial glial (oRG) cells, neural stem cells that are pivotal for constructing the unusually big cortex that’s unique to humans; oRG cells are scarce in mouse brains. When Novitch’s lab group at UCLA tried the original Japanese and Austrian organoid-making recipes, the output of oRG cells was underwhelming. So Novitch worked with Vishlaghi and postdoctoral researcher Momoko Watanabe to refine the protocol to pump up the cells’ production and reliably generate better cerebral blobs. Among other tweaks, Novitch’s team added a dash of a molecule dubbed LIF, which recent studies by others had suggested can spur the oRGs to multiply. It worked, leading to a threefold increase in the oRG populations and enhanced growth of upper neuron layers. The researchers shared their revised protocol last October in Cell Reports. Helping hand Neural stem cells called outer radial glial (oRG) cells help fuel the expansion of the unusually big human brain. A growth factor called LIF tripled the number of oRG cells in growing minibrains by week 12. Applying a growth factor to mini brain models please log in to view this image T. TIBBITTS Source: M. Watanabe et al/Cell Reports2017 On a different front, labs have begun assembling more complex minibrain models, like playing with self-directed Legos. For two months, Paşca’s team at Stanford grew spheroids in separate sets of dishes that mimicked either cortex tissue or an adjacent underlying region known as the subpallium. Then the researchers put the different bits side-by-side and left them overnight in a culture tube. Similar to how the two regions normally connect in the developing brain, the little pieces knew what to do. “By the next day they are essentially fused to each other,” says Paşca, who announced the results in May in Nature. During the fusion process, the researchers took time-lapse videos of long, spaghetti-like cells called interneurons migrating from a spheroid of the subpallium into a cortexlike spheroid. “They don’t crawl, they actually jump,” Paşca says. The images capture aspects of a hallmark phenomenon that normally unfolds during the second and third trimester of fetal gestation. Testing ground Once on the other side, interneurons form a circuit with — and quell the activity of — excitatory neurons in the cortexlike tissue, electrophysiological tests suggest. If not quieted, excitatory neurons will trigger neighboring cells to fire. In the real brain, maintaining a proper balance in neural network activity is important; disruptions in it appear to foster disorders such as epilepsy, and perhaps schizophrenia and autism. Indeed, in the same paper, the Stanford team reported new discoveries using personalized brain spheroids derived from induced pluripotent stem cells of patients with Timothy syndrome — a rare condition caused by an overactive calcium channel found mainly in the brain and heart. Patients with the disorder have epilepsy, autism and heart problems. In the patients’ spheroids, interneurons migrated inefficiently but, by adding drugs that blocked the dysfunctional calcium channel, the researchers could reverse the problem. The brain organoids made these intriguing observations possible, Paşca says. “We couldn’t have done this in any other way.” Stunted A brain organoid infected by Zika virus at 28 days old is severely stunted two weeks later (right) compared with a healthy organoid of the same age (left). please log in to view this image XUYU QIAN ET AL/CELL 2016 When sliced open, at higher magnification, a healthy cortexlike organoid (left) shows normal structure: a rosette with visible cavity in the middle, neural stem cells (red) and neurons (green and blue). A Zika-infected organoid (right) shows collapse of the rosette, with fewer neural stem cells and neurons. please log in to view this image XUYU QIAN ET AL/CELL 2016 Organoid experiments by others have, meanwhile, helped confirm that the Zika virus targets and kills oRG cells and other neural precursor cells, contributing to small brain size in infected infants. In a 2016 study, Johns Hopkins University neuroscientists Guo-li Ming and Hongjun Song reported on their own techniques for creating brain bits that have a well-defined zone of oRG cells. After infecting these organoids with the Zika virus, the researchers observed a collapse of cortexlike tissue that may partly explain the stunted brain growth (SN: 4/2/16, p. 26). 2-D cell-culture and mouse experiments also provided key evidence of the virus’s modus operandi; although the rodent brain doesn’t harbor the full contingent of human neural stem cells, it has blood vessels and immune-system components that organoids lack. In search of Zika-fighting treatments, Ming and Song, both now at University of Pennsylvania, and their colleagues have been screening thousands of compounds in 2-D cell cultures, and then validating the most promising candidates with tests in 3-D brain organoids. The team has found several potential antiviral and neuron-protecting agents to pursue. Novitch’s UCLA lab group has likewise used its brain organoids to pinpoint additional receptors by which the virus may gain entry into neural stem cells, and identified a few other drug leads for blocking infection. Organoids may also prove valuable for tailoring treatments for patients, says David Panchision, chief of the developmental neurobiology program at the National Institute of Mental Health in Bethesda, Md. Researchers might generate personalized brain organoids from the reprogrammed skin cells of individuals with, say, schizophrenia and test which medications work best for patients with particular genetic profiles of the illness. In the Netherlands, based on research reported in 2016 in Science Translational Medicine, Clevers and colleagues are already using personalized gut organoids, derived from rectal biopsies, to test whether cystic fibrosis patients will benefit from available drugs. Tailored regenerative therapies with 3-D substructures of neural tissue may also be possible, Panchision adds, for conditions like Parkinson’s disease or spinal cord injury. Blocking infection Images show 4-week-old brain organoids with no infection (left) and with Zika infection (middle, virus is green, dead stem cells are pink). Treatment with the drug duramycin before exposure to Zika largely staves off infection and cell death (right). please log in to view this image NOVITCH LAB/UCLA Growing pains For now, though, scientists have hefty challenges to overcome. Much work remains in optimizing how faithfully the bits of tissue reproduce normal brain function and architecture, Panchision says. For one thing, the organoids are developmentally young and don’t reflect a mature brain. And researchers must figure out how to build in some core features: the necessary blood vessels, immune-system cells called microglia and connections from other brain regions, such as the thalamus and cerebellum. Not to mention steroid and thyroid hormones, which also shape brain growth. However, scientists don’t necessarily need or want to create a comprehensive replica of the human brain in a dish, Panchision and others point out. Rather, the goal is to build robust and reliable models for studying specific aspects of brain function. Thus the pressing need for standardized, reproducible organoid-making recipes. Novitch’s group and many other labs are still trying to figure out why the brain bits can vary so much in size, composition and structure. Part of the trouble is the ingredients: Subtle variations in tissue-culture chemicals and Matrigel, or in different stem cell lines and how they are grown first in 2-D culture, can have a big impact on how the organoids turn out, Novitch says. At the same time, researchers need to do a more thorough job of analyzing brain organoids to know what’s actually in them at different developmental time points, compared with actual human fetal brain tissue, says UCSF’s Kriegstein. It’s otherwise hard to say whether a brain blob truly recapitulates the neural tissue that scientists claim it does. Labs have started tackling the problem with a tool called single-cell transcriptome analysis, which gives readouts of all the genes that are active in individual cells. “Greater rigor is needed,” Kriegstein says. “And I am sure we will eventually get there.”
Pinned this for a read later, expect a scathing criticism We are not even remotely close to understanding Neurons, let alone the whole brain. Never mind growing one Yes I am a major ****, sceptical as ****
UK leads the world as 100,000 Genomes Project hits the 50,000 genomes landmark to transform NHS patient care Posted on February 20, 2018 at 10:03 am The Department of Health and Social Care, NHS England and Genomics England today announced reaching the 50,000 whole human genome sequences landmark within the 100,000 Genomes Project. please log in to view this image It is a milestone that sets the UK on track to fully realise the potential of genomic medicine, deliver better care for patients and establish the UK as the global ‘go to’ destination in the fast emerging genomics sector. Genomics England was established in 2013 as a wholly owned company of the Department of Health and Social Care by the Secretary of State, Jeremy Hunt. It is tasked with the delivery of the groundbreaking 100,000 Genomes Project, which is sequencing 100,000 genomes from 70,000 people, focused on patients with rare diseases, their families, and patients with cancer. In stimulating genomic research and discovery, Genomics England aims to improve patient care and establish the UK as the centre of the global genomics industry. Achieving the 50,000 genomes landmark has only been made possible through the generous participation of tens of thousands of patients and their families – taking part in a Project at the edge of known science. Staff in NHS Genomic Medicine Centres (GMCs), as well as those in Northern Ireland, Scotland and Wales, have worked tirelessly to not only deliver the Project, but in many cases, also pioneered totally new systems, processes and procedures to ensure that genomic medicine can become part of routine NHS care. The project is already changing the lives of patients with a rare disease – often providing diagnoses for the first time after years of uncertainty and distress (known as the diagnostic odyssey), as well as working towards reducing costs to health and social care budgets. In cancer, significant progress has been made in tackling the global challenge of extracting of DNA of sufficient quality for whole genome sequencing – leading to significant redesign of tissue handling in the NHS. The scope and scale of the 100,000 Genomes Project, unparalleled anywhere else in the world, has been made possible through the UK’s unique asset − its National Health Service. The NHS, as the single biggest integrated healthcare system in the world, is able to link lifelong healthcare information with whole genome sequencing data. It is a combination that brings benefit to patients whilst also demonstrating the UK’s competitive advantage in enhancing understanding of diseases, and developing products for earlier detection and treatment. please log in to view this image Health Secretary Jeremy Hunt said: “This incredible achievement shows once again why the UK is a world leader in genomic medicine. “We’re backing our world-leading scientists and clinicians in the NHS to push the boundaries of modern science and embrace new technology – using data to transform the lives of patients and families through quicker diagnoses and personalised treatments. “It is testimony to the hard work of the clinicians and scientists across the NHS and volunteers for the project that we can continue to harness the very best of the NHS and remain at the forefront of this pioneering field. Genomics England Executive Chair, Sir John Chisholm, said: The 100,000 Genomes Project was a stunningly ambitious project when announced by the (then) Department of Health five years ago. Since then Genomics England and NHS England (now joined by Scotland, Northern, Ireland and Wales), working with a huge number of ground-breaking partnerships, have built the infrastructure and protocols to deliver health-enhancing diagnostics from consented patients with undiagnosed rare genetic disease and common cancers, while at the same time enabling their data (in de-identified form) to provide the basis for research leading to improved therapies and treatments. Having built the platform and reached the 50,000 halfway point we are now able to operate at a scale to complete the target by the end of 2018. Professor Sue Hill OBE, Chief Scientific Officer for England and Senior Responsible Officer for Genomics at NHS England, said: This is an important milestone for the project and has only been possible because of the contribution and commitment of the participants in the project and their families. “The milestone also marks how healthcare professionals from across the NHS have come together to transform care for the future, demonstrating how this technology can be utilised as part of routine care to improve patient lives and keep the NHS a world-leader in this important area of medicine. Working together patients and professionals have achieved so much and I would like to say a personal thank you to each and every one for playing their part. “We are on track to complete recruitment to the Project this Autumn and, from then, the use of these cutting-edge genomic technologies will be embedded in the NHS through the new Genomic Medicine Service offering real benefits to patients and healthcare delivery. Francis deSouza, President and CEO of lllumina (the 100,000 Genomes Project’s sequencing partner), said: This important milestone in our partnership with Genomics England marks a significant step towards delivering whole genome sequencing at scale into the NHS and provides physicians with the data to make diagnoses based on a patient’s genome that will lead to better health outcomes.
You are a liar FYI. Crazed leftie you are not. The far left has gone so far that you are now middle left I am liberal left, and progressives are a dot to me, they have gone that to the far left, so far in fact that they are almost coming back out on other side on the far right
The microbiome represents a paradigm shift for European Pharmaceutical Regulators Published on Published onFebruary 22, 2018 please log in to view this image Magali Cordaillat-Simmons FollowFollow Magali Cordaillat-Simmons Like3 Comment0 1 Write an article Recent research on microbiomes has demonstrated the important role these communities of microorganisms play on human homeostasis. The gut microbiome is being thoroughly studied, and other microbiomes are now becoming the focus of greater attention as well as other organs of the host, due to the concept of ‘axes’, i.e. the gut-brain axis, gut-lung axis, gut-liver axis. Furthermore, as the impairment of microbial functions has been associated with numerous pathologies in humans, we now know that the composition of the microbiome could also affect the efficacy of other “regular drugs” (i.e. New Chemical Entities, Biotechnological products, etc…). One example of this inter-play is the influence of a microbiome’s composition on cancer therapy and on the responder/non-responder status. As such, two important questions for European pharmaceutical regulators have now become evident, and if we as scientists and researchers are being honest with ourselves, unavoidable: 1. How do we clarify the regulatory framework so that the specific nature of Live Biotherapeutic Products is taken into account in the assessment, and the resulting adaptations are made to the regulatory framework? Indeed, Live Biotherapeutic Products (LBPs, i.e. medicinal products containing live micro-organisms) are the only type of medicinal product which exert their action locally and through a modification of the local ecosystem and local microbial functions, which in turn exert an effect on the host homeostasis. The assessment of Pharmacokinetics, or dosage, works on a different paradigm. Moreover, safety of these products involves concerns not usually assessed for other types of drugs (i.e. antibiotic resistance, virulence). Consequently, as of today, assessment is done on a case-by-case basis and may vary on the reference member state’s own knowledge of this type of product. Harmonization and European guidelines are thus sorely needed today as more and more products are in development (reaching clinical phases) and science has demonstrated the central role that the microbiome plays in human health. Future patients deserve assessment of the utmost quality; this will necessarily require harmonization at the EU level, as well as the drafting of relevant guidelines dedicated to this type of product, and not the usual application of the “spirit” of other existing guidelines, as is often recommended. Patients’ safety will be ensured by an assessment engineered for the specific nature of the products, and by harmonization of such assessments at the EU level through specific guidelines. 2. Can we continue to ignore the importance of the microbiome in designing and developing regular drugs (i.e. new Chemical entities, Biotech products, etc…)? We know that drugs can have an influence on the microbiome, the obvious example being antimicrobials; but more importantly, the microbiome of patients may also have a strong influence on the efficacy and perhaps even safety of other types of drugs. There are alterations of microbiomes that may look benign due to their resilience, but we now know that an alteration of the microbiome caused by antibiotic treatments during infancy is associated with a higher prevalence of chronic pathologies in adults. Microbiome alteration could therefore be a ticking time bomb with severe consequences later on in life, and this should no longer be ignored when designing new drugs. On the other hand, it has been shown in cancer therapy that the composition of patients’ microbiome had an influence on the efficacy of their treatment (responders/non-responders). Characterizing the patient’s microbiome therefore seems to become a necessary factor in comprehending how to optimize drug efficacy. Administering drugs to non-responder patients is obviously a question of safety, and the understanding of the influence of the microbiome may indeed be critical in the development of safer and more efficacious drugs. In conclusion, advancements in understanding the true nature of human microbiomes represent a paradigm shift for the pharmaceutical industry and regulators, and will require them to approach the human body in an entirely different way. We are not just human, we are a symbiosis, within which bacterial cells outnumber their host’s counterparts. Therefore each of us should be considered a symbiont going forward when we work on designing and assessing drugs: either drugs exerting their effect on the microbiome itself, i.e. LBPs, or drugs exerting their effect on the human side, but which may have a detrimental influence on its microbial counterpart. We believe it is time the authorities tackle this issue head-on. Industry is generally ahead of regulator due to constant innovation, but it is unfortunate to hear such a deafening silence from European regulators on this issue, an issue which could all the same affect a large swath of new drug products coming to market in the near future. While the FDA has been working on this since 2010, Europe seems to be lagging behind; and as such, this revolution in medicine will come that much later to the care of European patients. This is particularly difficult to grasp, as Europe has been a leader in microbiome research, and is in point of fact well-positioned worldwide when it comes to understanding the mechanism of actions by which microbiomes influence human health. Once again, biotechnology companies are being created in staggering numbers in the US, while in Europe the lack of a regulatory framework impede their financing and growth. We urge European member states to comprehend the significance of this transformative shift in the field of medicine, and address this need so that Europe may start to regulate and harmonize in order to enable the emergence of this new industry; but above all, to ensure the safety and benefit of future patients.
We are told when it gets freezing cold and sets records that is is weather and not "climate" Fair enough But..when it gets warmer than average, all of a sudden it's "climate" even though "climate" is an average of weather over 30 years Cold = Weather Warm = Climate change This has nothing to do with the overall topic, just the deranged scientists and journalists claiming weather variation is "human caused". It's actually doom porn tbh, click bait doom porn
