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Impact of Global and National Coronavirus Strategy on the SLTT Response – In Public Safety

February 8th, 2020 3:46 am

By Dr. Darrell Dantzler, faculty member, Emergency and Disaster Management at American Military University

On January 30, the World Health Organization (WHO) determined the novel coronavirus, formally known as 2019-nCoV, posed an international risk and declared it a Public Health Emergency of International Concern (PHEIC) and a global health emergency, a designation only declared five times previously.

The number of diagnosed 2019-nCoV cases has surpassed SARS cases, including the first known human-to-human spread of the new virus in the United States.

[Related: CDC to Announce First Case of Wuhan Coronavirus Found in US]

The Centers for Disease Control and Prevention (CDC) expects many more cases, largely due to the viruss ability to spread from person to person.

However, despite these designations and concerns from health experts, the 2019-nCoV is not classified as a pandemic; although that is subject to change based on the rate of human-to-human transmissions and determination of the lethality of the virus.

[Related: Flu Season and Pandemic Planning: Ethical Approaches to Epidemic Response]

It is critical that state, local, tribal, and territorial (SLTT) emergency managers, public health professionals, and other public safety professionals understand global and national comprehensive emergency management strategies for handling a pandemic outbreak. They include how these strategies affect them and their SLTT emergency management initiatives.

The WHOs primary role is to direct and coordinate international health within the United Nations system. The WHOs goals during the 2019-nCoV outbreak are to strengthen global diagnostic capacity and improve surveillance, early detection, and capabilities to track the spread of disease. WHO lists the following six strategic objectives for responding to the 2019-nCoV:

WHO has implemented a three-pronged approach to enhance the diagnostic capacity for 2019-nCoV:

The U.S. Department of Health and Human Services (HHS) mission is to enhance and protect the health and well-being of Americans by providing effective health and human services and by fostering advances in medicine, public health, and social services. The secretary of HHS is vested with the authority to act to protect public health and welfare, declare a public health emergency, and prepare for and respond to public health emergencies. The CDC, within the HHS, is the nations health protection agency and the leading national public health institute in the country.

HHS developed seven domains in its Pandemic Influenza Plan to thwart a severe worldwide event. Although 2019-nCoV has not reached the pandemic threshold yet, its important to understand the Pandemic Influenza Plans seven domains, which details areas where capabilities can be optimized:

Regarding the 2019-nCoV, the CDC has accomplished the following strategic response objectives:

At this point, most SLTTs have reviewed and put into place their comprehensive emergency management plan, including the Pandemic annex and the Emergency Support Functions (ESF), including ESF #8, as well as companion ESFs.

SLTT public safety professionals should monitor the global and national climate, along with maintaining situational awareness in their jurisdiction. The director of the HHS stated, (t)he playbook for responding to an infectious disease outbreak is relatively simple: You monitor and communicate, identify cases, isolate the people, diagnose them, and treat them. Then you track down all of the contacts of the infected person, and you do the same with those people, and the same with contacts of contacts if necessary. This is often easier said than done, as virus outbreaks foster volatile, uncertain, complex, and ambiguous (VUCA) environments that require immense coordination. Communication and social distancing are among challenges that SLTT public safety official encounter.

Communication

The goal of communication before, during, and after VUCA events like 2019-nCoV is to provide and share accurate and relevant information with the public, partners, and stakeholders, so that well-informed decisions are made that protect the publics health and safety.

Social medial is a double-edged sword when communicating during disease outbreaks. Currently, hoaxes about the coronavirus have spread faster than the actual virus on platforms like Facebook, YouTube, and Twitter. Some examples include Bill Gates being responsible for the virus; the Chinese created a weaponized version of coronavirus and lost control of it; drinking bleach keeps the virus away; coronavirus will cause the zombie apocalypse; parents have abandoned their children in an airport; FEMA proposes martial law to contain the coronavirus; and the US patented a vaccine years ago for the coronavirus.

Misinformation about disease outbreaks is even harder to control because of intense public interest, fear, lack of credible information, and the unknown. The WHO has actively sought to discredit misinformation and has responded to rumors through myth busting on WHOs social media channels and website.

The CDC indicated that the right message at the right time from the right person can save lives. The health agency implemented a six-step crisis communication plan that SLTT public safety agencies can employ to improve communication:

Social Distancing

If a 2019-nCoV outbreak is found in a SLTT jurisdiction, public safety managers can mitigate person-to-person transmission through social distancing. Social distancing is when public health officials restrict when and where people can congregate in order to stop or slow down the spread of a highly contagious. These social distancing measures have a considerable effect on the community; therefore, actions must be coordinated among all stakeholders including city leaders, federal partners, police departments, business, and schools.

Below are some examples of social distancing that can be used to control the spread of 2019-nCoV. Its important for SLTT emergency managers to remember that civil liberties must be balanced with public health.

In summary, the global and national strategies for controlling and eradicating pandemics or the 2019-nCoV directly impacts the strategies at the SLTT jurisdictional levels. Public safety officials should understand the global and national climate to better prepare for, respond to, mitigate, and recover from a potential pandemic in their jurisdiction.

Additionally, SLTT public safety officials must understand crisis communication and ensure their jurisdictions have the most updated and accurate information. Lastly, when determining social distancing strategies, civil liberties must be balance with public health.

About the Author: Dr. Darrell Dantzler is a faculty member at American Military University, teaching courses in Emergency & Disaster Management. He is also the Director of the Fire Protection Analysis and Field Engineering Division within the Office of Fire Protection in the Bureau of Overseas Buildings Operations at the US Department of State. Darrell brings more than 35 years of experience in Disaster and Emergency Management Planning and Response. He is a 20-year United States Air Force Veteran and a 15-year public servant with the Department of State. At State, he conducted fire assessments, fire investigations, and special emergency management assessments in over 70 countries. Darrell graduated from the National Preparedness on Leadership Initiative, Executive Education Leadership Program at Harvard Universitys T.H. Chan School of Public Health and Harvards Kennedy School of Government. He is a Certified Emergency Manager through the International Association of Emergency Managers. Darrell holds a Ph.D. in Public Safety Leadership with a specialization in Disaster and Emergency Management. To contact the author, email IPSauthor@apus.edu. For more articles featuring insight from industry experts, subscribe to In Public Safetys bi-monthly newsletter.

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Gerald Fink awarded the Genetic Society of America’s Thomas Hunt Morgan Medal – MIT News

February 8th, 2020 3:44 am

Gerald R. Fink,Whitehead Institute founding member and former director and professor of molecular genetics in the MIT Department of Biology, has been awarded the 2020 Thomas Hunt Morgan Medal, bestowed by the Genetics Society of America (GSA). The award recognizes a distinguished scientist who has a lifetime achievement in the field of genetics and a strong history as a mentor to fellow geneticists. TheGSA is an international community of more than 5,000 scientists who advance the field of genetics.

Fink, who is also the Herman and Margaret Sokol Professor at Whitehead Institute, is a former GSA president and the 1982 recipient of the GSA Medal. In honoring him with the Thomas Hunt Morgan Medal, GSA is recognizing Finks discovery of principles central to genome organization and regulation in eukaryotic cells.

This year, the Morgan Medal will also be awarded to David Botstein, chief scientific officer for Calico Labs and professor emeritus of molecular biology at the Lewis-Sigler Institute for Integrative Genomics at Princeton University, in recognition of his multiple contributions to genetics, including the collaborative development of methods for defining genetic pathways, mapping genomes, and analyzing gene expression.

These awards to Gerry and David are richly deserved and I am so pleased they are being honored together, says Whitehead Institute DirectorDavid Page. Gerry Fink has fundamentally changed the way researchers approach biological problems, and his many discoveries have significantly shaped modern science. David Botstein has helped drive modern genetics, establishing the ground rules for human genetic mapping. Page has worked closely with both men: beginning his research career as an investigator in Botsteins lab, and collaborating with Fink for more than three decades at Whitehead Institute.

The medals will be formally presented to Fink and Botstein at the Allied Genetics Conference in April.

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New Light on the Genetic Relationship Between Three Mood Disorders – Technology Networks

February 8th, 2020 3:44 am

Researchers shed new light on the genetic relationship between three mood disorders associated with depressionmajor depression and bipolar disorder types 1 and 2, in a newstudyin the journalBiological Psychiatry, published by Elsevier.

The clearest findings are a genetic distinction between type 1 bipolar and type 2 bipolar, and the greater similarity of type 2 bipolar to major depressive disorder, said first author Jonathan Coleman, PhD, a statistical geneticist and postdoctoral fellow in the lab of senior author Gerome Breen, PhD at the Institute of Psychiatry, Neuroscience, and Psychology at Kings College London, UK.

Both types of bipolar disorder used to be referred to as manic-depressive disorder. Mania is a behavioral state associated with behavioral activation, euphoric or irritable mood, reduced need for sleep, impulsive behavior, impaired judgement, racing disorganized thoughts, impulsive behaviors, and frequently strongly held false beliefs (delusions) or hallucinations. Bipolar disorder type 1 is associated with mania and depression, while bipolar 2 is predominately associated with depression marked by mild symptoms reminiscent of mania, called hypomania.

The insights came from several extremely large datasets analyzed together. For their meta-analysis, Coleman, Breen and their co-authors combined genome-wide association studies from three large datasets of people with major depression and bipolar disorder to evaluate shared and distinct molecular genetic associations. Most of the data came from the large international Psychiatric Genomics Consortium. Additional data came from the UK Biobank, a major health resource established by the Wellcome Trust, and the online genetic service platform, 23andMe.

There are significant racial and ethnic differences in the findings from genome-wide association studies (GWAS). The findings of this study pertain only to people of European ancestry and findings might be different in other groups.

The authors also report that the genetic risk for these disorders was predictive of other traits as well. For example, the genetic risk for bipolar disorder was correlated with more educational attainment, while the heritable risk for major depressive disorder was associated with less education.

In the mouse brain, the authors also mapped the genetic risk for these disorders on to particular brain cell types using a sophisticated analytic strategy building on the pattern of genes expressed. They implicated serotonin neurons in the risk for both depression and bipolar disorder, while bipolar disorder distinctively involved GABA and glutamate neurons (nerve cell types also implicated in schizophrenia).

We have long known that mood disorders are highly heterogeneous and the boundaries between types of mood disorders are often difficult to define clinically, said John Krystal, MD, editor ofBiological Psychiatry. This new study suggests that there are aspects of genetic risk, and presumably brain function, that link forms of mood disorders, but there are also distinctions that may shed light on subtypes of depression that may have important implications for treatment.

Ultimately, the researchers want to develop clinical tools to help predict if a first episode of depression is likely to persist as a disorder or progress into bipolar disorder. Genetic data wont ever replace clinical insight, but it might be a useful addition to clinical models, said Coleman.

Reference:Coleman et al. (2019). The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. Biological Psychiatry. DOI: 10.1016/j.biopsych.2019.10.015.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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The Daily Biotech Pulse: Tonix Slumps On Failed Study, Applied Genetic Announces Offering, Beam Therapeutics, PPD Price IPOs – Yahoo Finance

February 8th, 2020 3:44 am

The following is a roundup of top developments in the biotech space over the last 24 hours:

Scaling The Peaks

(Biotech stocks that hit 52-week highsFeb. 5.)

Down In The Dumps

(Biotech stocks that hit 52-week lows Feb. 5.)

See also: The Week Ahead In Biotech: Merck, Bristol-Myers Earnings, Conference Presentations In Focus

Stocks In Focus Sanofi's Multiple Sclerosis Drug Aces Midstage Trial; Q4 Sales, Net Income Rise

Sanofi SA (NASDAQ: SNY) said a Phase 2b study that evaluated its investigational BTK inhibitor SAR442168 for multiple sclerosis met the primary endpoint, with the candidate significantly reducing disease activity associated with multiple sclerosis. The candidate was also found to be safe and well-tolerated.

Separately, the company released financial results thatshowed 6.8% net sales growth for the fourth quarter, driven by Dupixent and vaccines, and 253.5% net income growth. The company said it expects 2020 business EPS to grow 5% at constant currency.

Tonix To Stop Enrollment For Late-Stage Study Of PTSD Drug

Tonix Pharmaceuticals Holding Corp (NASDAQ: TNXP) said it has decided to stop enrollment in the Phase 3 study dubbed RECOVERY that evaluated its Tonmya 5.6mg in treating post-traumatic stress disorder, following interim analysis of data by the Independent Data Monitoring Committee.

The IDMC sought stoppage of the trial for futility as it believed the experimental drug is unlikely to demonstrate a significant improvement in the primary endpoint of overall change from baseline in the severity of PTSD symptoms between the treatment and control arm.

The shares were plunging 59.91% to 68cents in premarket trading Thursday.

Arrowhead Reports Positive Mid-Phase Results For 2 Cardiometabolic Drug Candidates

Arrowhead Pharmaceuticals Inc (NASDAQ: ARWR) announced positive interim results from ongoing Phase 1/2a studies of its two RNAi-based cardiometabolic candidates: ARO-APOC3, which is being evaluated for severe hypertriglyceridemia, and ARO-ANG3, whichbeing evaluated for dyslipidemias and metabolic diseases.

The company also released fourth-quarter results, showing a sales decline of 15% to $29.46 million and a loss of 3 cents. Analysts estimated a loss of 1 cent per share for the quarter.

The stock was trading 7.5% higher to $47 in Thursday's premarket session.

Earnings

Misonix Inc (NASDAQ: MSON) reported 17.3% revenue growth on a pro forma basis for its fiscal year second quarter, and its net loss widened year-over-year. The company reiterated its fiscal year 2020 outlook for revenue growth in excess of 20% and gross margins of about 70%.

View more earnings on IBB

The stock rose 5.97% to $19 in after-hours trading.

Cardiovascular Systems Inc (NASDAQ: CSII) reported a wider-than-expected seond-quarter loss, while revenueclimbed 13.5%. The company raised the low end of its 2020 revenue guidance.

The stock shed 1.94% to $44 in after-hours trading.

Offerings

Applied Genetic Technologies Corp (NASDAQ: AGTC) said it has commenced an underwritten public offering of 6 million shares of its common stock. All the shares are being offered by the company.

The stock slipped 9.70% to $6.33 in after-hours trading.

On The Radar Clinical Readouts

Jounce Therapeutics Inc (NASDAQ: JNCE) will present at the ASCO-SITC Symposium Phase 1/2 data for vopratelimab, codenamed JTX-2011, in solid tumors.

Earnings

IPO

Beam Therapeutics said it has priced its upsized initial public offeringof 10.59 million shares at $17 per share, at the upper end of the estimated price range of $15-$17. The shares of the company, which is engaged in developing therapies based on single-base gene editing, will begin trading on the Nasdaq under the ticker symbol "BEAM."

Contract research organization PPD priced its 60-million share IPO at $27 compared to the initially estimated range of $24-$27. The shares are to be listed on the Nasdaq under the ticker symbol "PPD."

Related Link: Attention Biotech Investors: Mark Your Calendar For These February PDUFA Dates

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News from NANS: 10kHz safe and effective for treating painful diabetic neuropathy, multicentre study finds – NeuroNews International

February 8th, 2020 3:44 am

A multicentre study across 18 centres finds 10kHz safe and effective for the treatment of painful diabetic neuropathy. Sensory improvements were observed in many patients who underwent stimulation with these parameters, as well improvements in quality of life measures. Erika Petersen, University of Arkansas for Medical Sciences, Little Rock, USA, presented these data at the North American Neuromodulation Societys (NANS) annual meeting (2326 January, Las Vegas, USA) and told delegates that the study is due to run through 24 months, with later evaluations of health economics and pain medication usage.

Our clinical trial is the largest randomised controlled trial to date, involving 216 patients randomised 1:1 to conventional medical management [n=103] alone or conventional medical management plus high frequency 10kHz stimulation [n=113], explained Petersen.

She added that all patients were evaluated by independent medical monitors before they were enrolled in study, and were required to have at least 5 of 10cm of the visual analogue scale (VAS) as well as a BMI <45 to be included. When looking at the demographics of the two arms, Petersen said, they are identical; no significant differences were observed in terms of duration of diabetes, duration of time of painful diabetic neuropathy, gender, and other factors.

Lead location was T8T11. Petersen posited that this is the typical location for addressing lower limb and lower extremity pain. She further emphasised that one of the endpoints of the study was safety. For the stimulation group, 19 adverse events [occurred] in 15 patients, two of which were rated as a serious adverse event, she acknowledged, adding that one arose due to infection, while the other was acquired at plantation.

I want to highlight our infection rate, Petersen said. People worry about diabetics having a higher risk of infection. But, what we can see for this population, is a 1.8% rate, which is comparable to the majority of studies in the literature for this population.

For the primary endpoint analysis, Petersen and her co-investigators looked at a composite of safety and effectiveness, in terms of pain reduction at three months. Those with 50% pain relief without a worsening neurological deficit from baseline were characterised at responders. Of the patients receiving SCS stimulation, 86% were considered responders at three months, compared to only 5% of patients in the conventional medicine management arm, reported Petersen, adding that the team observed a trial stimulation success rate of 94%.

She alluded to the reduction in VAS scores, which decreased from 7.6 (lower limb VAS) at baseline to 2.4 at one month, and 1.7 at three months. I hope to be able to show you think maintained at 24 months when we present those data in the future, Petersen noted. Moreover, through looking at individual pain relief between the stimulator and the conventional management group, it was revealed that 77% of stimulation patients achieved pain relief, compared to only 5% of controls.

Part of the assessment was to have each investigator assess sensory changes within the patients, Petersen explained. The team had asked patients to draw out subjective diagrams of where they perceived numbness, both at baseline and three months. We were able to perceive what seemed to be a change in sensation in the stimulator population in 72% of those patients, Petersen confirmed.

But pain relief is nothing without improving quality of life, said Petersen, alluding to the fact that investigators examined three measures of sleep, each of which saw significant improvements. They also implemented a six-minute walking test as a means of achieving an objective measure of functional improvement. Compared to the conventional medical management group, the stimulator patients walked further in six minutes at the three-month time point. When you look at this by individuals, Petersen discussed, you can see that it is not across all patients, but the average and median change allows for a longer distance walked [of 39 metres; a 17% increase] in the same amount of time.

In terms of impression of change, both patients themselves as well as the clinicians evaluating them were asked to assess their improvement. In total, 67% of the stimulator population said they are better/a great deal better than baseline, compared to a mere 2% of controls. These findings were reflected throughout a multitude of other functional indicator questionnaires, noted Petersen.

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Current and Prospective Treatment Options for Waldenstrm Macroglobulinemia – Hematology Advisor

February 8th, 2020 3:44 am

Waldenstrm macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma that mainly affects elderly patients. Complications of the disease are usually attributable to tumor load or the presence of monoclonal immunoglobulin M (IgM). With limited approved treatment options by the US Food and Drug Administration (FDA), the demand for new therapies is high.

In a review published in Blood, Meletios A Dimopoulos, MD, and Efstathios Kastritis, MD, of the department of clinical therapeutics at the University of Athens in Greece, summarized current literature surrounding the treatment of WM.1 They also reviewed several example cases using clinical data from their institution.

Diagnostic Workup and Indication for Therapy

If the presence of IgM is confirmed by immunofixation electrophoresis, and a bone marrow biopsy reveals infiltration with clonal lymphoplasmacytic cells, a diagnosis of WM is established. Indolent cases are defined as those with less than 10% clonal infiltrate, but there is no established threshold for the amount of clonal cell infiltrate required for diagnosis. Although variation in clonal morphology is high, established cell morphology and immunophenotypic criteria aid in differential diagnosis among other conditions that exhibit a similar phenotype.1

During the initial workup, ruling out other causes of presenting symptoms is important. At initial presentation, the most common symptoms are anemia and cytopenias (42%), B symptoms (25%), and hyperviscosity (17%). As a result, additional laboratory parameters should be measured, including iron studies, serum albumin, lactate dehydrogenase, and beta-2 microglobulin. The measurement of monoclonal IgM levels is also necessary, as hyperviscosity syndrome, a key marker of symptomatic disease, is related to elevated IgM levels; however, this relationship is not linear.1

Another common complication of the disease is peripheral neuropathy, which in many cases is the sole indication for treatment in asymptomatic patients. WM-associated neuropathy is often slowly progressing, sensory, and symmetrical in nature. Hence, rapidly progressing peripheral neuropathy may indicate an unrelated cause.

Because of a prolonged asymptomatic period, often exceeding 5 to 10 years, it is crucial to ensure patients have an indication for therapy. Though some clinical and laboratory indications have been proposed, clinical judgment is often necessary. Monoclonal IgM levels alone are insufficient to determine an indication for therapy. Currently, there are no data to help guide clinical decision making on whether to delay or commence therapy in asymptomatic patients. In these cases, enrollment into a clinical trial may be a suitable option.

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How integrative medicine is changing the way cancer is treated – Fox Baltimore

February 8th, 2020 3:44 am

Cancer has an impact on every part of a patient's life. At GBMC Healthcare, the fight against cancer is about more than treating the disease. Delia Chiaramonte, M.D., Medical Director of Integrative and Palliative Medicine at GBMC, is leading the charge on integrative cancer care.

"It's not just about treating the cancer. It's also about how the person is coping, what side effects they may have from the disease itself or from the treatment, and how those symptoms make their life harder to manage," she says. "Treating the whole person is a really important part of cancer care."

These symptoms can be caused by a variety of internal and external sources, and Dr. Chiaramonte says it's important to get to the root of the cause of the symptom to better treat the patient.

"We hear the patient's symptoms then make an evidence-supported treatment plan that's different for every person, based on what their symptom is and why we think their symptom is happening," she explains.

For example, one person may not be sleeping well because of a physical reaction to chemotherapy. Another may not be getting good sleep because their mind is filled with anxious thoughts about their diagnosis.

Dr. Chiaramonte says there are three main causes of symptoms, and the Integrative Medicine Program makes it easier for patients to get an evidence-based, effective treatment plan and to receive those treatments at the Sandra & Malcolm Berman Cancer Institute at GBMC.

"We pull out all the causes and then address them with the treatment that is likely to work on that particular person, and often it's not just one cause," she explains.

The mind-body connection

The sympathetic nervous system directs our body's "fight or flight" response, which can be caused by both external factors and our own thoughts.

"Because the mind and body are connected, our anxious thinking can generate the 'fight-or-flight' response, and that can result in all kinds of physical symptoms, including increased pain, palpitations, changes in GI function, sleep, and nausea," Dr. Chiaramonte says.

According to Dr. Chiaramonte, there are a variety of ways to help decrease the sympathetic nervous response system, including craniosacral therapy (a light-touch manual therapy technique that works to balance and facilitate healing in the body) and massage. These methods reduce patients' anxiety.

Cancer treatment symptoms

It's no secret that chemotherapy and radiation can be taxing on the body. Nausea, fatigue, and neuropathy (nerve pain caused by damaged nerves) are just some of the side effects of cancer treatments that integrative modalities can help alleviate.

"Some energy medicine has been shown to help chemo-induced peripheral neuropathy," Dr. Chiaramonte says. "Many people come in with fatigue, usually from a combination of poor sleep and treatments. Acupuncture, meditation and guided imagery, reiki (a stress reduction and relaxation technique involving a trained practitioner), and yoga have all been shown to help fatigue."

Physical pain

Dr. Chiaramonte reiterates that the Integrative Palliative Medicine Program is just that: an integrative medicine program and not an alternative to standardized cancer care.

"I treat pain with medicines, with different kinds of opiates and complementary medications," she says. "But acupuncture has been shown to decrease pain. Meditation and guided imagery have been shown to decrease pain. Reiki has been shown to decrease pain. Depending on the person, we may use multiple modalities to help them manage their pain."

Massage is also an oft-used modality for physical pain.

"Often, when something hurts in our body, the muscles around it contract and tighten to try to protect it, and over time it can become the actual contraction of the muscle that hurts, not necessarily the underlying factor," Dr. Chiaramonte says.

She explains this can also tie into the mind-body connection because "if you're generating a lot of anxious thinking, you're more likely to continue to have this muscle tension, and massage can help."

Integrative treatment plans will vary by patient, which Dr. Chiaramonte says is the key to taking care of the mind, body, and spirit of every individual.

"We find out the 'why' behind each patient's symptoms, pull out the causes, and then come up with a plan for that particular patient, using all the tools that work."

For more information Integrative Medicine at GBMC HealthCare, click here.

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Neuropathy Pain Treatment Market 2020 Industry Sahre, Growth, Top Manufacturers, Globally Development and Forecast to 2025 – TechNews.mobi

February 8th, 2020 3:44 am

VertexMarketInsights.com has published an innovative statistics of the market titled as Neuropathy Pain Treatment Market. To clarify the various aspects, the analyst studies and elaborates the terms by using qualitative and quantitative research techniques. Finance teams can use a variety of corporate planning applications to fulfil the budgeting, planning & financial modelling, needs of their organization, whatever its size, industry and location.

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Leading Establishments (Key Companies):PfizerDepomedEndoGrnenthal GroupArbor PharmaceuticalsEli Lilly

Different regions, such as Americas, United States, Canada, Mexico, Brazil, APAC, China, Japan, Korea, Southeast Asia, India, Australia, Europe, Germany, France, UK, Italy, Russia, Spain, Middle East & Africa, Egypt, South Africa, Israel, Turkey and GCC Countries are focused to give the summarized data about the production of Neuropathy Pain Treatment market.

The global Neuropathy Pain Treatment Market is served as a backbone for the enlargement of the enterprises. To address the challenges, the report examines different key factors such as drivers and opportunities. Restraints are considered for evaluation of risk in market.

Segments covered in the report

This report forecasts revenue growth at a global, regional & country level, and analyses the market trends in each of the sub-segments from 2015 to 2025. For the purpose of this study, VertexMarketInsights have segmented the Neuropathy Pain Treatment market on the basis of type, end-user and region:

Type Outlook (Revenue in Million USD; 20152025):Calcium channel alpha 2-delta ligandsSerotonin-norepinephrine reuptake inhibitors

End Use Outlook (Revenue in Million USD; 20152025):Retail PharmaciesHospitals

Neuropathy Pain Treatment Market Summary: This report includes the estimation of market size for value (million US$) and volume. Estimation methodology validate the market size of Neuropathy Pain Treatment industry, to estimate the size of various other dependent submarkets in the overall market. Secondary research is used to identify the top players in the market, and their market shares have been determined through primary and secondary research. Each type is studied based on classification as Sales, Neuropathy Pain Treatment Market Share (%), Revenue (Million USD), Price and Gross Margin.

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Report Objectives:

Target Audience:

Table of Content:

Global Neuropathy Pain Treatment Market Research Report 2020-2025

Chapter 1: Industry Overview

Chapter 2: Neuropathy Pain Treatment Market International and China Market Analysis

Chapter 3: Environment Analysis of Market.

Chapter 4: Analysis of Revenue by Classifications

Chapter 5: Analysis of Revenue by Regions and Applications

Chapter 6: Analysis of Neuropathy Pain Treatment Market Revenue Market Status.

Chapter 7: Analysis of Industry Key Manufacturers

Chapter 8: Conclusion of the Neuropathy Pain Treatment Market Industry 2025 Market Research Report.

Continued to TOC

For more detailed Pdf Copy of Table of Content Describing Current Value and Volume of the Market with All Other Essential Information click @ https://vertexmarketinsights.com/report/41823/world-neuropathy-pain-treatment-market-research-report-2024-covering-usa-europe-china-japan-india-and-etc/ #table-of-contents

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On the track to recovery: Pole vaulters talk about their returns from injuries – The Lafayette

February 8th, 2020 3:43 am

After facing months of rehab due to injury, pole vaulters Arielle Sclar 22 and Lulu Knowles 21 recently returned to the track and field team with the support of their teammates, coaching staff, and the sports medicine department.

In the winter of my senior year of high school I was at a pole vault meet, and I landed poorly and tore my ACL and meniscus, Sclar said. I waited the full year to come back which is protocol for ACL surgery, and then there were complications, and I had a second surgery at the start of [the] fall [2019] semester.

Sclar said that it was difficult getting back into pole vaulting after her knee injury since she was not able to do any cardio exercises during rehab. She described her recovery process as long and intensive, but noted the consistent support from her teammates.

Ive never felt disconnected from the team, she said, despite being out for most of last season.

Knowles was injured at the end of her freshman year. Her injuries led her to switch from triple jump to pole vault.

I shattered my kneecap when I was still a triple jumper, she said. I really wanted to be part of the team, and since I was a gymnast, my coach asked if I would pole vault. Sophomore year I had ulnar neuropathy, which I trained and competed through for a while, but then it got really dangerous and I had to get surgery. Ulnar neuropathy, according to Medical News Today, affects the nerve the runs along the arm along the elbow and into the fingers on the outside of the hand.

Track and field head coach Michele Curcio witnessed their recovery and said that they really embraced their rehab.

Sports medicine did a great job of making sure they were ready, Curcio said. Sometimes the student athlete gets ahead of themselves. As an athlete, you think youre going to be able to do things quicker than the normal person.

Both athletes added that not being able to physically participate on the team was challenging at times.

Sometimes its really frustrating watching people do the sport you love when you cannot take part in it, Knowles said. I had contemplated just quitting, I had so many injuries. But sitting out made me realize how much I loved being part of a team and competing. Pole vault definitely gives me that thrill that I love and being out made me love the sport even more.

Its not a great feeling watching everyone else be healthy and doing what you wish you could be doing, Sclar added. But it was easier for me when thinking of how exciting it would be to be back.

While Knowles suffered her injury in a different field event, returning to the same exercise that initially caused the injury, as was the case with Sclar, presented an additional obstacle to their recovery.

The hardest thing is to come back [and] to do that thing that made you hurt, Curcio said. You have to bring them back slowly and break that mental barrier.

The support and positive energy of their teammates played a big role in their recovery and mental toughness.

Every team member here appreciates each other and being on the team, and a lot of them have gone through the same things, so I think that type of support before and after [an injury] is important, Curcio said.

Both Knowles and Sclar are now back with the team and competed last weekend at the DeSchriver Invitational. Knowles and Sclar placed fifth and sixth, respectively, in the pole vault with marks of 2.90 and 2.75 meters. Being back with the team full-time is already having an impact on both women.

People dont recognize how many things go on to make the whole track team be functional and do well, Sclar said. Everyones coming from a very different place to make a common goal as a team unit.

I love our team dynamic, especially this year because we have some freshman who joined and brought great positive energy, Knowles added. Everyone has a different major and a different story, you just get to talk to so many different people.

Knowles, Sclar and the rest of the track and field team return to action today at the University of Albany winter classic in Staten Island, N.Y.

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Life and death in Wuhan: On the front lines fighting coronavirus – Nikkei Asian Review

February 7th, 2020 3:45 am

WUHAN, China (Caixin) -- In the coronavirus epidemic, doctors on the front lines take on the greatest risk and best understand the situation. Peng Zhiyong, director of acute medicine at the Wuhan University South Central Hospital, is one of those doctors.

In an interview on Tuesday with Caixin, Peng described his personal experiences in first encountering the disease in early January and quickly grasping its virulent potential and the need for stringent quarantine measures.

As the contagion spread and flooded his ICU, the doctor observed that three weeks seemed to determine the difference between life and death. Patients with stronger immune systems would start to recover in a couple of weeks, but in the second week some cases would take a turn for the worse.

In the third week, keeping some of these acute patients alive might require extraordinary intervention. For this group, the death rate seems to be 4% to 5%, Peng said. After working 12-hour daytime shifts, the doctor spends his evenings researching the disease and has summarized his observations in a thesis.

The doctors and nurses at his hospital are overwhelmed with patients. Once they don protective hazmat suits, they go without food, drink and bathroom breaks for their entire shifts. That's because there's aren't enough of the suits for a mid-shift change, he said.

Over the past month on the front lines of the coronavirus battle, Peng has been brought to tears many times when forced to turn away patients for lack of staffing and beds. He said what really got to him, though, was the death of an acutely ill pregnant woman when treatment stopped for lack of money -- the day before the government decided to pick up the costs of all coronavirus treatments.

Here is our interview with the ICU doctor:

Screening criteria were too tough in the beginning

Caixin: When did you encounter your first novel coronavirus patient?

Peng Zhiyong: Jan. 6, 2020. There was a patient from Huanggang who had been refused by multiple hospitals and was sent to the South Central Hospital emergency room. I attended the consultation. At the time, the patient's illness was already severe, and he had difficulty breathing. I knew right then that he had contracted this disease. We debated at length whether to accept the patient. If we didn't, he had nowhere to go; if we did, there was a high likelihood the disease would infect others. We had to do a very stringent quarantine. We decided to take the patient in the end.

I called the hospital director and told him the story, including the fact that we had to clear the hospital room of other patients and to remodel it after SARS standards by setting up a contamination area, buffer area and cleaning area while separating the living areas of the hospital staff from the patients'.

On Jan. 6, with the patient in the emergency room, we did quarantine remodeling in the emergency room and did major renovations to the intensive care unit. South Central Hospital's ICU has 66 beds in total. We kept a space dedicated to coronavirus patients. I knew the infectiousness of the disease. There were bound to be more people coming in, so we set aside 16 beds. We did quarantine renovations on the infectious diseases area because respiratory illnesses are transmitted through the air, so even air has to be quarantined so that inside the rooms the air can't escape. At the time, some said that the ICU had a limited number of beds and 16 was excessive. I said it wasn't excessive at all.

Caixin: You predicted in January that there would be person-to-person transmission and even took quarantine measures. Did you report the situation to higher-ups?

Peng: This disease really did spread very fast. By Jan. 10, the 16 beds in our ICU were full. We saw how dire the situation was and told the hospital's leadership that they had to report even higher. Our head felt it was urgent too, and reported this to the Wuhan city health committee. On Jan. 12, the department sent a team of three specialists to South Central to investigate. The specialists said that clinical symptoms really resembled SARS, but they were still talking about diagnosis criteria, that kind of stuff. We replied that those standards were too stringent. Very few people would get diagnosed based on those criteria. The head of our hospital told them this multiple times during this period. I know other hospitals were doing the same.

Before this, the specialists had already gone to Jinyintan Hospital to investigate and made a set of diagnosis criteria. You had to have had exposure to the South China Seafood Market, you needed to have had a fever and test positive for the virus. You had to meet all three criteria in order to be diagnosed. The third one was especially stringent. In reality, very few people were able to test for a virus.

On Jan. 18, the high-level specialists from the National Health Commission came to Wuhan, to South Central Hospital to inspect. I told them again that the criteria were too high. This way it was easy to miss infections. I told them this was infectious; if you made the criteria too high and let patients go, you're putting society in danger. After the second national team of specialists came, the criteria were changed. The number of diagnosed patients rose quickly.

Caixin: What made you believe the new coronavirus could be transmitted between people?

Peng: Based on my clinical experience and knowledge, I believed that the disease would be an acutely infectious one and that we needed high-level protection. The virus isn't going to change based on man's will. I felt we needed to respect it and act according to science. Heeding my requirements, South Central Hospital's ICU took strict quarantine measures, and as a result, our department only had two infections. As of Jan. 28, of the entire hospital's medical personnel, only 40 have been infected. This is way less compared with other hospitals in terms of percentage of total medical staff.

It pains us to see the coronavirus develop to such a desperate state. But the priority now is to treat people; do everything we can to save people.

Fatality rate for acute patients is 4% to 5%. Three weeks determine life and death

Caixin: Based on your clinical experience, what's the disease progression of the new coronavirus?

Peng: Lately I've been spending daytimes seeing patients in the ICU, then doing some research in the evenings. I just wrote a thesis. I drew on data from 138 cases that South Central Hospital had from Jan. 7 to Jan. 28 and attempted to summarize some patterns of the novel coronavirus.

A lot of viruses will die off on their own after a certain amount of time. We call these self-limited diseases. I've observed that the breakout period of the novel coronavirus tends to be three weeks, from the onset of symptoms to developing difficulties breathing. Basically going from mild to severe symptoms takes about a week. There are all sorts of mild symptoms: feebleness, shortness of breath, some people have fevers, some don't. Based on studies of our 138 cases, the most common symptoms in the first stage are fever (98.6% of cases), feebleness (69.6%), cough (59.4%), muscle pains (34.8%) and difficulties breathing (31.2%), while less common symptoms include headaches, dizziness, stomach pain, diarrhea, nausea and vomiting.

But some patients who enter the second week will suddenly get worse. At this stage, people should go to the hospital. Elderly with underlying conditions may develop complications; some may need machine-assisted respiration. When the body's other organs start to fail, that's when it becomes severe, while those with strong immune systems see their symptoms decrease in severity at this stage and gradually recover. So the second week is what determines whether the illness becomes critical.

The third week determines whether critical illness leads to death. Some in critical condition who receive treatment can increase their lymphocytes, a type of white blood cell, and see an improvement in their immune systems, and have been brought back, so to speak. But those whose lymphocyte numbers continue to decline, those whose immune systems are destroyed in the end, experience multiple organ failure and die.

For most, the illness is over in two weeks, whereas for those for whom the illness becomes severe, if they can survive three weeks they're good. Those that can't will die in three weeks.

Caixin: Could you give more details on clinical research? What percentage of cases develop from mild conditions to severe conditions? What percentage of serious cases develop into life-threatening ones? What is the mortality rate?

Peng: Based on my clinical observations, this disease is highly contagious, but the mortality rate is low. Those that progressed into the life-threatening stage often occurred in the elderly already with chronic diseases.

As of Jan. 28, of 138 cases, 36 were in the ICU, 28 recovered, five died. That is to say, the mortality rate of patients with severe conditions was 3.6%. Yesterday, Feb. 3, another patient died, bringing the mortality rate to 4.3%. Given patients in the ICU, it is likely to have more deaths. The mortality rate is also likely to edge up but not significantly.

Those hospitalized tend to have severe or life-threatening conditions. Patients with slight symptoms are placed in quarantine at home. We have not gathered data on the percentage of cases that progress from slight symptoms to serious symptoms. If a patient goes from serious conditions to life-threatening conditions, the patient will be sent to the ICU. Among 138 patients, 36 were transferred to the ICU, representing 26% of all patients. The percentage of deaths among life-threatening cases is about 15%. The mean period to go from slight conditions to life-threatening conditions is about 10 days. Twenty-eight patients recovered and were discharged. Right now, the recovery rate is 20.3% while other patients remain hospitalized.

It is notable that 12 cases were linked to South China Seafood Market; 57 were infected while being hospitalized, including 17 patients already hospitalized in other departments; and 40 medical staff, among 138 cases, as of Jan. 28. That demonstrates that a hospital is a high-risk zone and appropriate protection must be taken.

Caixin: What is the highest risk a seriously ill patient faces?

Peng: The biggest assault the virus launches is on a patient's immune system. It causes a fall in the count of lymphocytes, damage in the lungs and shortness of breath. Many serious patients died of choking. Others died of the failure of multiple organs following complications in their organs resulting from a collapse of the immune system.

Caixin: A 39-year-old patient in Hong Kong suffered from cardiac arrest, and he died quickly. A few patients did not have severe symptoms upon the onslaught of the virus, or in the early stages, but they died suddenly. Some experts argue that the virus triggers a cytokine storm, which ravages the stronger immune systems of young adults. Eventually excessive inflammations caused by cytokine result in the higher mortality rate. Have you seen such a phenomenon in the coronavirus outbreak?

Peng: Based on my observations, a third of patients exhibited inflammation in their whole body. It was not necessarily limited to young adults. The mechanism of a cytokine storm is about whole-body inflammation, which leads to a failure of multiple organs and quickly evolves into the terminal stage. In some fast-progressing cases, it took two to three days to progress from whole-body inflammation to the life-threatening stage.

Caixin: How do you treat serious and life-threatening cases?

Peng: For serious and life-threatening cases, our main approach is to provide oxygen, high-volume oxygen. At first noninvasive machine-pumped oxygen, followed by intubated oxygen if conditions worsen. For life-threatening cases, we use ECMO (extracorporeal membrane oxygenation, or pumping the patient's blood through an artificial lung machine). In four cases, we applied ECMO to rescue patients from the verge of death.

Currently there are no special drugs for the coronavirus. The primary purpose of the ICU is to help patients sustain the functions of their body. Different patients have different symptoms. In case of shortness of breath, we provided oxygen; in case of a kidney failure, we gave dialysis; in case of a coma, we deployed ECMO. We provide support wherever a patient needs it to sustain their life. Once the count of lymphocytes goes up and the immune system improves, the virus will be cleared. However, if the count of lymphocytes continues to fall, it is dangerous because the virus continues to replicate. Once a patient's immune system is demolished, it is hard to save a patient.

Caixin: There is news of some drugs that work. People are hopeful of U.S.-made remdesivir, which cured the first case in the United States. What do you think of the drugs?

Peng: There are no 2019 novel coronavirus-targeted drugs so far. Some patients may recover after taking some drugs along with supportive treatment. But such individual cases do not indicate the universal effect of the drugs. The effect is also related to how serious each case is and their individual health conditions. People want a cure urgently, and that is understandable. But we need to be cautious.

Caixin: Do you have any advice for coronavirus patients?

Peng: The most effective approach to the virus epidemic is to control the source of the virus, stem the spread of the virus and prevent human-to-human transmission. My advice for a patient is going to a special ward for infectious diseases, early detection, early diagnosis, early quarantine and early treatment. Once it has developed into a severe case, hospitalization is a must. It is better to contain the disease at an early stage. Once it reaches the life-threatening stage, it is way more difficult to treat it and requires more medical resources. With regard to life-threatening cases, try to save them with ICU measures to reduce the mortality rate.

Sad story of a pregnant patient

Caixin: How many patients with life-threatening conditions have you treated? How many have recovered?

Peng: As of Feb. 4, six patients in the ICU of South Central Hospital died. Eighty percent of them have been improving, a quarter are approaching their discharge and the remainder are still recovering in segregated wards.

The patient who impressed me most came from Huanggang. He was the first to be saved with the assistance of ECMO. He had contact with South China Seafood Market and was in very serious condition. He was transferred to the ICU and we saved him with ECMO. He was discharged from the hospital Jan. 28.

Caixin: What is your workload and pace like?

Peng: The ICU is overloaded. There are three patient wards with 66 beds in South Central Hospital, housing 150 patients. Since Jan. 7 when we received the first patient, no one took any leave. We took turns working in the ICU. Even pregnant medical staff did not take leave. After the epidemic got worse, none of the medical staff ever went home. We rest in a hotel near the hospital or in the hospital.

In the segregated ward, we wear level-3 protective gear. One shift is 12 hours for a doctor and eight hours for a nurse. Since protective gear is in a shortage, there is only one set for a medical staff member a day. We refrain from eating or drinking during our shift because the gear is no longer protective once we go to the washroom. The gear is thick, airtight and tough on our body. It felt uncomfortable at the beginning, but we are used to it now.

Caixin: Did you experience any danger? For example, in case of intubation, what do you do to prevent yourselves from being infected?

Peng: It is a new coronavirus. We are not sure of its nature and its path of spread. It is not true to say we are not afraid. Medical staff members do fear to some extent. But patients need us. When a patient is out of breath and noninvasive oxygen provision fails, we must apply intubation. The procedure is dangerous as the patient may vomit or spit. Medical staff are likely to be exposed to the danger of infection. We strictly require doctors and nurses to apply the highest-level protection. The biggest problem we face now is the shortage of protective gear. The protective stock for ICU staff is running low, although the hospital prioritizes the supply to us.

Caixin: Is there anything that moved you in particular? Did you cry?

Peng: I often cried because so many patients could not be admitted to the hospital. They wailed in front of the hospital. Some patients even knelt down to beg me to accept him into the hospital. But there was nothing I could do since all beds were occupied. I shed tears while I turned them down. I've run out of tears now. I have no other thoughts but to try my best to save more lives.

The most saddest thing was a pregnant woman from Huanggang. She was in very serious condition. Nearly 200,000 yuan ($28,700) was spent after more than a week in the ICU. She was from the countryside, and the money for hospitalization was borrowed from her relatives and friends. Her condition was improving after the use of ECMO, and she was likely to survive. But her husband decided to give up. He cried for his decision. I wept too because I felt there was hope for her to be saved. The woman died after we gave up. And exactly the next day, the government announced a new policy that offers free treatment for all coronavirus-infected patients. I feel so sorry for that pregnant woman.

The deputy director of our department told me one thing, and he cried too. Wuhan 7th Hospital is in a partnership with our hospital, South Central Hospital. The deputy director went there to help in their ICU. He found that two-thirds of the medical staff in the ICU were already infected. Doctors there were running "naked" as they knew they were set to be infected given the shortage of protective gear. They still worked there nonetheless. That was why ICU medical staff were almost all sickened. It is too tough for our doctors and nurses.

Read the original story here.

Caixinglobal.com is English-language online news portal of Chinese financial and business news media group Caixin. Nikkei recently agreed with the company to exchange articles in English.

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Gianficaro: Rush Limbaugh’s cancer reveal brings out the darkest side of humanity – Bucks County Courier Times

February 7th, 2020 3:45 am

Two women celebrated the cancer diagnoses affecting the others political opponent, revealing the cold, cruel side to our humanity.

In the kingdom of glass, everything is transparent, and there is no place to hide a dark heart. Vera Nazarian, author

What is it that prompts the human heart to venture into the deepest corners of darkness? To descend there willingly and zealously? To encourage death to snatch life from a foe over little more than crudeness and differing points of view? To celebrate a pending death proudly, to hope for it quickly? To rationalize it as justice being the executioner?

Just what causes humanity to become so incredibly twisted and strangled by unyielding cords of hate?

On the surface, the two women Tuesday morning appeared much like any youd see sharing a table in a coffee shop. It was only when they began to speak did their words and feelings reveal the worst of who we sometimes are.

One day earlier, right-wing radio talk show host Rush Limbaugh revealed he had been diagnosed with advanced, or metastatic, lung cancer. Last month, Rep. Jerry Nadler, a Democrat and a lead House impeachment manager urging the removal of Donald Trump from office for abuse of power and obstruction of Congress, announced he would step away from the impeachment trial to be with his wife, who has metastatic pancreatic cancer.

The women, clearly on opposite ends of the political spectrum, discussed what both men are facing in their lives. My coffee went down with ease. Their conversation did not.

Limbaughs getting what he deserves, one woman said of the often caustic, occasionally unsympathetic radio host. Hes a rotten, evil man. I hate that anyone gets cancer, but theres some justice here with him. I remember he mocked Ruth Ginsburg when she got cancer. I bet its not so funny to him now.

Getting what he deserves. Getting cancer. Celebrating a mans possible, probable death. Unfathomable. As I found the distasteful opinion hard to swallow on World Cancer Day, of all days, I thought about my 88-year-old mom battling cancer today, and how the disease and the treatment are beating her up, and how I wouldnt wish the disease on anyone, especially because they wear a red tie and I wear a blue one.

Yet into the darkness the women tread. Zealously.

And then her friend followed her into the abyss. Eagerly.

Yeah, well, that Nadler is getting his, too, the other woman said. You dont survive pancreatic cancer; look at Alex Trebek. (Nadler) was part of the whole witch hunt on the president, and now this. I guess throwing Trump out of office isnt so important to him now.

Two women drinking hot coffee and revealing frozen hearts. I was hoping for better. The thaw never came.

Across the internet and on social media, cold hearts thumped out a drum beat of inhumanity, mostly against Limbaugh.

A 2006 video was recirculated of Limbaugh accusing actor Michael J. Fox of faking his symptoms of Parkinsons disease in a video ad endorsing a Democratic candidate for Senate, Claire McCaskill, who supported embryonic stem-cell research. Limbaugh also mocked Fox on air by impersonating tremors associated with the disease and charging that Fox was exaggerating them for effect. Insensitivity does not get much lower than that.

The intended message by those recirculating Limbaughs inhumanity shortly after he disclosed his cancer diagnosis was unmistakable: Paybacks are hell.

Religious scholar Reza Aslan also attacked Limbaugh, tweeting this Monday: Ask yourself this simple question: Is the world a better place or a worse place with Rush Limbaugh in it? Azlans answer was not a mystery.

I approached the two women with cold hearts. I introduced myself, told them Id overheard their conversation, and would like to talk to them about their casual discussion of cancer and death. They chided me for eavesdropping, then, predictably, refused.

While the cold hearts revealed by those women was likely an extreme perspective, it was, without question, reflective of the widening political divide in America, one in which disagreement doesnt represent the absolute ground floor. For some, it goes much deeper.

And darker.

Columnist Phil Gianficaro can be reached at 215-345-3078, pgianficaro@theintell.com, and @philgianficaro on Twitter.

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The biology, function, and biomedical applications of exosomes – Science Magazine

February 7th, 2020 3:45 am

Clinical uses of cellular communication

Exosomes are a type of extracellular vesicle that contain constituents (protein, DNA, and RNA) of the cells that secrete them. They are taken up by distant cells, where they can affect cell function and behavior. Intercellular communication through exosomes seems to be involved in the pathogenesis of various disorders, including cancer, neurodegeneration, and inflammatory diseases. In a Review, Kalluri and LeBleu discuss the biogenesis and function of exosomes in disease, highlighting areas where more research is needed. They also discuss the potential clinical applications of exosome profiling for diagnostics and exosome-mediated delivery of therapeutics to target disease cells.

Science, this issue p. eaau6977

All cells, prokaryotes and eukaryotes, release extracellular vesicles (EVs) as part of their normal physiology and during acquired abnormalities. EVs can be broadly divided into two categories, ectosomes and exosomes. Ectosomes are vesicles that pinch off the surface of the plasma membrane via outward budding, and include microvesicles, microparticles, and large vesicles in the size range of ~50 nm to 1 m in diameter. Exosomes are EVs with a size range of ~40 to 160 nm (average ~100 nm) in diameter with an endosomal origin. Sequential invagination of the plasma membrane ultimately results in the formation of multivesicular bodies, which can intersect with other intracellular vesicles and organelles, contributing to diversity in the constituents of exosomes. Depending on the cell of origin, EVs, including exosomes, can contain many constituents of a cell, including DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins. The physiological purpose of generating exosomes remains largely unknown and needs investigation. One speculated role is that exosomes likely remove excess and/or unnecessary constituents from cells to maintain cellular homeostasis. Recent studies reviewed here also indicate a functional, targeted, mechanism-driven accumulation of specific cellular components in exosomes, suggesting that they have a role in regulating intercellular communication.

Exosomes are associated with immune responses, viral pathogenicity, pregnancy, cardiovascular diseases, central nervous systemrelated diseases, and cancer progression. Proteins, metabolites, and nucleic acids delivered by exosomes into recipient cells effectively alter their biological response. Such exosome-mediated responses can be disease promoting or restraining. The intrinsic properties of exosomes in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases, including neurodegenerative conditions and cancer. Exosomes can be engineered to deliver diverse therapeutic payloads, including short interfering RNAs, antisense oligonucleotides, chemotherapeutic agents, and immune modulators, with an ability to direct their delivery to a desired target. The lipid and protein composition of exosomes can affect their pharmacokinetic properties, and their natural constituents may play a role in enhanced bioavailability and in minimizing adverse reactions. In addition to their therapeutic potential, exosomes also have the potential to aid in disease diagnosis. They have been reported in all biological fluids, and the composition of the complex cargo of exosomes is readily accessible via sampling of biological fluids (liquid biopsies). Exosome-based liquid biopsy highlights their potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. Disease progression and response to therapy may also be ascertained by a multicomponent analysis of exosomes.

The study of exosomes is an active area of research. Ongoing technological and experimental advances are likely to yield valuable information regarding their heterogeneity and biological function(s), as well as enhance our ability to harness their therapeutic and diagnostic potential. As we develop more standardized purification and analytical procedures for the study of exosomes, this will likely reveal their functional heterogeneity. Nonetheless, functional readouts using EVs enriched for exosomes have already provided new insights into their contribution to various diseases. New genetic mouse models with the ability for de novo or induced generation of cell-specific exosomes in health and disease will likely show the causal role of exosomes in cell-to-cell communication locally and between organs. Whether exosome generation and content change with age needs investigation, and such information could offer new insights into tissue senescence, organ deterioration, and programmed or premature aging. Whether EVs and/or exosomes preceded the first emergence of the single-cell organism on the planet is tempting to speculate, and focused bioelectric and biochemical experiments in the future could reveal their cell-independent biological functions. Single-exosome identification and isolation and cryoelectron microscopy analyses have the potential to substantially improve our understanding of the basic biology of exosomes and their use in applied science and technology. Such knowledge will inform the therapeutic potential of exosomes for various diseases, including cancer and neurodegenerative diseases.

Exosomes are extracellular vesicles generated by all cells and they carry nucleic acids, proteins, lipids, and metabolites. They are mediators of near and long-distance intercellular communication in health and disease and affect various aspects of cell biology.

The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.

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The biology, function, and biomedical applications of exosomes - Science Magazine

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Maybe Memorizing the Krebs Cycle Was Worthwhile After All – Medscape

February 7th, 2020 3:44 am

Like most medical students, I struggled to memorize the Krebs cycle, the complex energy-producing process that takes place in the body's mitochondria. Rote learning of Sir Hans Krebs' eponymous cascade of reactions persists and has been cited as a waste of time in modern medical education. However, it looks like that specialized knowledge about mitochondrial structure and function may finally come in handy in the clinic.

Advances in genetics have contributed to improved diagnostic accuracy of a diverse spectrum of mitochondrial disorders. Respiratory chain, nuclear gene, and mitochondrial proteome mutations can lead to multisystem or organ-specific dysfunction.

A new potential treatment for mitochondrial disorders, elamipretide, has received orphan drug designation from the US Food and Drug Administration (FDA) and is in clinical trials sponsored by Stealth Biotherapeutics. [Dr Wilner has consulted for Stealth Biotherapeutics.] Recently I had the opportunity to interview Hilary Vernon, MD, PhD, associate professor of genetic medicine at Johns Hopkins University, Baltimore, Maryland, and an expert on mitochondrial disorders. Dr Vernon discussed her research on elamipretide as a treatment for Barth syndrome, a rare form of mitochondrial disease.

I am the director of the Mitochondrial Medicine Center at Johns Hopkins Hospital. I work with individuals from infancy through adulthood who have mitochondrial conditions. I became interested in this particular area when I was early in my pediatrics/genetics residency at Johns Hopkins and saw the toll that mitochondrial disorders took on patients' lives and the limited effective therapies. At that point, I decided to focus on patient care and research in this area.

Mitochondrial disorders can be difficult to recognize because of their inherent multisystem nature and variable presentations (even between affected members of the same family). However, there are several considerations that should raise a clinician's suspicion for a mitochondrial condition. Ascertaining a family history of disease inheritance through the maternal line can raise the suspicion for a mitochondrial DNA disorder. Identification of a combination of medical issues in different organ systems that are seemingly unrelated in an individual (ie, optic atrophy and muscle weakness or diabetes and hearing loss) can also raise suspicion for a mitochondrial condition.

Due to the nature of mitochondria as the major energy producers of the cells, high-energy-requiring tissues such as the brain and the muscles are often affected. Perhaps the best known mitochondrial diseases to neurologists are MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) as well as MERFF (myoclonic epilepsy with ragged red fibers). There is a nice body of literature on the effects of arginine and citrulline in modifying stroke-like episodes in MELAS, and this is a therapy that is in current practice.

Mitochondria are complex organelles whose structure and function are encoded in hundreds of genes originating from both the nucleus of the cell and the mitochondria themselves. Mitochondria have many key roles in cellular function, including energy production through the respiratory chain, coordination of apoptosis, nitrogen metabolism, fatty acid oxidation, and much more.

Various cofactors and vitamins can be employed to improve mitochondrial function for different reasons. For example, if a specific enzyme is dysfunctional, supplying the cofactor for that enzyme may improve its function (ie, pyruvate dehydrogenase and thiamine). Antioxidants have also been considered to help reduce the oxidant load that could potentially cause ongoing damage to the mitochondrial membrane resulting from respiratory chain dysfunction (ie, coenzyme Q-10).

It is important to remember that the highest number of individual mitochondrial disorders result from mutations in genes located in the nuclear DNA. For example, the TAZ gene that is abnormal in Barth syndrome is a nuclear gene located on the X chromosome. These genes are amenable to the "regular" approaches to gene therapy.

Targeting mitochondrial DNA for gene therapy requires a different set of approaches because the gene delivery has to overcome the barrier of the mitochondrial membranes. However, research is ongoing to overcome these obstacles.

Barth syndrome is a very rare genetic X-linked disorder that usually only affects males. The genetic defect leads to an abnormal composition of cardiolipin on the inner mitochondrial membrane. Cardiolipin is an important phospholipid involved in many mitochondrial functions, including organization of inner mitochondrial membrane cristae, involvement in apoptosis, and organization of the respiratory chain (which is responsible for producing ATP via the process of oxidative phosphorylation), and many of these functions are abnormal in Barth syndrome. Individuals with Barth syndrome typically have early-onset cardiomyopathy, myopathy, intermittent neutropenia, fatigue, poor early growth, among other health concerns.

Early in my post-residency career, I followed several patients with Barth syndrome and was quickly welcomed into the Barth syndrome community by the families and the Barth Syndrome Foundation. From there, I founded the only interdisciplinary Barth syndrome clinic in the US and began to focus a significant amount of my clinical and laboratory research on this condition.

Most commonly, these individuals come to medical attention because of cardiomyopathy, but a minority of patients do come to attention due to repeated infections and neutropenia. Patients were identified for study participation through the Barth Syndrome Foundation or because they were already patients of my study team.

All participants were known to have Barth syndrome prior to study entry, and all had confirmatory genetic testing showing a pathogenic mutation in the TAZ gene.

By binding to cardiolipin in the inner mitochondrial membrane, elamipretide is believed to stabilize cristae architecture and electron transport chain structure during oxidative stress. I thought it would be great if this could help to stabilize the abnormal cardiolipin components on the inner mitochondrial membrane in Barth syndrome.

We observed improvements in several areas across the study population in the open-label extension part of the study. This includes a significant improvement in exercise performance (as measured by the 6-minute walk test, with an average improvement of 95.9 meters at 36 weeks) and a significant improvement in muscle strength. We also observed a potential improvement in cardiac stroke volume. Most of the adverse events were local injection-site reactions and were mild to moderate in nature.

The TAZPOWER trial has an ongoing open-label extension with the same endpoints as the placebo-controlled portion evaluated on an ongoing basis. In addition, in my laboratory, we are using induced pluripotent stem cells to learn more about how cardiolipin abnormalities affect different cell types in an effort to understand the tissue specificity of disease. This will help us to understand whether different aspects of Barth syndrome would necessitate individual management or clinical monitoring strategies.

Mitochondrial inner membrane dysfunction is increasingly recognized as a major aspect of the pathology of a wide range of mitochondrial conditions. Therefore, based on the role of stabilizing mitochondrial membrane components, elamipretide has a potential role in many disorders of the mitochondria.

Yes, this is what we would call "secondary mitochondrial dysfunction" (meant to differentiate from "primary mitochondrial disease," which is caused by defects in genes that encode for mitochondrial structure and function). Approaches intended to protect the mitochondria from further damage, such as antioxidants or strategies that can bypass the mitochondria for ATP production, could overlap as treatment for primary mitochondrial disease and secondary mitochondrial dysfunction.

This is something that is much discussed as a newer consideration for families who are affected by disorders of the mitochondrial DNA, but not something I have experience with firsthand.

Yes. The United Mitochondrial Disease Foundation and the Mitochondrial Medicine Society collaborated to develop the Mito Care Network, with 19 sites identified as Mitochondrial Medicine Centers across the US.

Andrew Wilner is an associate professor of neurology at the University of Tennessee Health Science Center in Memphis, a health journalist, and an avid SCUBA diver. His latest book is The Locum Life: A Physician's Guide to Locum Tenens.

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AI, 5G, and IoT can help deliver the promise of precision medicine – VentureBeat

February 7th, 2020 3:44 am

This article is part of the Technology Insight series, made possible with funding from Intel.

When my son was a toddler, he went to his pediatrician for a routine CAT scan. Easy stuff. Just a little shot to subdue him for a few minutes. Hed be awake and finished in a jiffy.

Except my son didnt wake up. He lay there on the clinic table, unresponsive, his vitals slowly falling. The clinic had no ability to diagnose his condition. Five minutes later, he was in the back of an ambulance. My wife and I were powerless to do anything but look on, frantic with worry for our boys life.

It turned out that hed had a bad reaction to a common hydrochloride sedative. Once that was figured out, doctors quickly brought him back around, and he was fine.

But what if, through groundbreaking mixtures of compute, database, and AI technologies, a quick round of analyses on his blood and genome could have revealed his potential for such a reaction before it became a critical issue?

What if it were possible to devise a course of treatment specific to him and his bodys unique conditions, rather than accepting a cookie-cutter approach and dealing with the ill effects immediately after?

And what if that could be done with small, even portable medical devices equipped with high-bandwidth connectivity to larger resources?

In short, what if, through the power of superior computing and next-generation wireless connectivity, millions of people like my son could be quickly, accurately treated on-site rather than endure the cost and trauma of legacy medical methods?

These questions I asked about my son are at the heart of todays efforts in precision medicine. Its the practice of crafting treatments tailored to individuals based on their characteristics. Precision medicine spans an increasing number of fields, including oncology, immunology, psychiatry, and respiratory disorders, and its back end is filled with big data analytics.

Key Points:

Pairing drugs to gene characteristics only covers a fraction of the types of data that can be pooled to target specific patient care.

Consider the Montefiore Health System in the Bronx. It has deployed a semantic data lake, an architecture for collecting large, disparate volumes of data and collating them into usable forms with the help of AI. Besides the wide range of data specific to patients collected onsite (including from a host of medical sensors and devices), Montefiore healthcare professionals also collate data from sources as needed, including PharmGKB databank (genetic variations and drug responses), the National Institute of Healths Unified Medical Language System (UMLS), and the Online Mendelian Inheritance in Man (human genomic data).

Long story short, the Intel/Cloudera/Franz-based solution proved able to accurately create risk scores for patients, predict whether they would have a critical respiratory event, and advise doctors on what actions to take.

We are using information for the most critically ill patients in the institution to try and identify those at risk of developing respiratory failure (so) we can change the trajectory, noted Dr. Andrew Racine, Montefiores system SVP and chief medical officer.

Now that institutions like Montefiore can perform AI-driven analytics across many databases, the next step may be to integrate off-site communications via 5G networking. Doing so will enable physicians to contribute data from the field, from emergency sites to routine in-home visits, and receive real-time advice on how to proceed. Not only can this enable healthcare professionals to deliver faster, more accurate diagnoses, it may permit general physicians to offer specialized advice tailored to a specific patients individual needs. Enabling caregivers like this with guidance from afar is critical in a world that, researchers say, faces a shortage 15 million healthcare workers by 2030.

Enabling services like these is not trivial in any way. Consider the millions of people who might need to be genetically sequenced in order to arrive at a broad enough sample population for such diagnostics. Thats only the beginning. Different databases must be combined, often over immense distances via the cloud, without sacrificing patients rights or privacy. Despite the clear need for this, according to the Wall Street Journal, only 4% of U.S. cancer patients in clinical trials have their genomic data made available for research, leaving most treatment outcomes unknown to the research and diagnostic communities. New methods of preserving patient anonymity and data security across systems and databases should go a long way toward remedying this.

One promising example: using the processing efficiencies of Intel Xeon platforms in handling the transparent data encryption (TDE) of Epic EHR patient information with Oracle Database. Advocates say the more encryption and trusted execution technologies, such as SGX, can be integrated from medical edge devices to core data centers, the more the public will learn to allow its data to be collected and used.

Beyond security, precision medicine demands exceptional compute power. Molecular modeling and simulations must be run to assess how a drug interacts with particular patient groups, and then perhaps run again to see how that drug performs the same actions in the presence of other drugs. Such testing is why it can take billions of dollars and over a decade to bring a single drug to market.

Fortunately, many groups are employing new technologies to radically accelerate this process. Artificial intelligence plays a key role in accelerating and improving the repetitive, rote operations involved in many healthcare and life sciences tasks.

Pharmaceuticals titan Novartis, for example, uses deep neural network (DNN) technology to accelerate high-content screening, which is the analysis of cellular-level images to determine how they would react when exposed to varying genetic or chemical interactions. By updating the processing platform to the latest Xeon generation, parallelizing the workload, and using tools like the Intel Data Analytics Acceleration Library (DAAL) and Intel Caffe, Novartis realized nearly a 22x performance improvement compared to the prior configuration. These are the sorts of benefits healthcare organizations can expect from updating legacy processes with platforms optimized for acceleration through AI and high levels of parallelization.

Interestingly, such order-of-magnitude leaps in capability, while essential for taming the torrents of data flowing into medical databases, can also be applied to medical IoT devices. Think about X-ray machines. Theyre basically cameras that require human specialists (radiologists) to review images and look for patterns of health or malady before passing findings to doctors. According to GE Healthcare, hospitals now generate 50 petabytes of data annually. A staggering 90% comes from medical imaging, GE says, with more than 97% unanalyzed or unused. Beyond working to use AI to help reduce the massive volume of reject images, and thus cut reduce on multiple fronts, GE Healthcare teamed with Intel to create an X-ray system able to capture images and detect a collapsed lung (pneumothorax) within seconds.

Simply being able to detect pneumothorax incidents with AI represents a huge leap. However, part of the projects objective was to deliver accurate results more quickly and so help to automate part of the diagnostic workload jamming up so many radiology departments. Intel helped to integrate its OpenVINO toolkit, which enables development of applications that emulate human vision and visual pattern recognition. Those workloads can then be adapted for processing across CPUs, GPU, AI-specific accelerators and other processors.

With the optimization, the GE X-ray system performed inferences (image assessments) 3.3x faster than without. Completion time was less than one second per image dramatically faster than highly trained radiologists. And, as shown in the image above, GEs Optima XR240amx X-ray system is portable. So this IoT device can deliver results from a wide range of places and send results directly to doctors devices in real time over fast connections, such as 5G. A future version could feed analyzed X-rays straight into patient records. There, they become another factor in the multivariate pool that constitutes the patients dataset, which in turn, enables personalized recommendations by doctors.

By now, you see the problem/solution pattern:

The U.S. provides a solid illustration of the impact of population in this progression. According to the U.S. Centers for Disease Control (CDC), even though the rate of new cancer incidents has flattened in the last several years, the countrys rising population pushed the number of new cases diagnosed from 1.5 million in 2010 to 1.9 million in 2020, driven in part by rising rates in overweight, obesity, and infections.

The white paper Accelerating Clinical Genomics to Transform Cancer Care (below) paints a stark picture of the durations involved in traditional approaches to handling new cancer cases from initial patient visit to data-driven treatment.

At each step, delays plague the process extending patient anxiety, increasing pain, even leading to unnecessary death.

Intel created an initiative called All in One Day to create a goal for the medical industry: take a patient from initial scan(s) to precision medicine-based actions for remediation in only 24 hours. This includes genetic sequencing, analysis that yields insights into the cellular- and molecular-level pathways involved in the cancer, and identification of gene-targeted drugs able to deliver the safest, most effective remedy possible.

To make All in One Day possible, the industry will require secure, broadly trusted methods for regularly exchanging petabytes of data. (Intel notes that a typical genetic sequence creates roughly 1TB of data. Now, multiply that across the thousands of genome sequences involved in many genomic analysis operations.) The crunching of these giant data sets calls for AI and computational horsepower beyond what todays massively parallel accelerators can do. But the performance is coming.

As doctors will have to service ever-larger patient populations, expect them to need data results and visualizations delivered to wherever they may be, including in forms animated or rendered in virtual reality. This will require 5G-type wireless connectivity to facilitate sufficient data bandwidth to whatever medical IoT devices are being used.

If successful, more people will get more personalized help and relief than ever possible. The medical IoT and 5G dovetail with other trends now reshaping modern medicine and making these visions everyday reality. A 2018 Intel survey showed that 37% of healthcare industry respondents already use AI; the number should rise to 54% by 2023. Promising new products and approaches appear daily. A few recent examples are here, here and here.

As AI adoption continues and pairs with faster hardware, more diverse medical devices, and faster connectivity, perhaps we will soon reach a time when no parent ever has to watch an unresponsive child whisked away by ambulance because of adverse reactions that might have been avoided through precision medicine and next-gen technology.

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Tampa health care expert unveils health care plan using artificial intelligence, genetics, medical case management to save taxpayers $1.4 trillion per…

February 7th, 2020 3:44 am

A Tampa health care expert goes public with a plan to fix America's broken health care system.

TAMPA, Fla. (PRWEB) February 05, 2020

TAMPA, Fla. Local health care expert and medical case management consultant Paul Roberts has spent two decades working to develop more efficient ways to improve healthcare, and now the 47-year-old is attempting his most ambitious task to reform America's health care system.

"There's no question about it, our healthcare system is broken and that really is something that all Americans can get behind, regardless of their political ideologies," said Roberts. "It affects all of us and we need to address it before costs skyrocket even more."

According to Roberts, his alternative plan will save tax payers an estimated 40 percent over Medicare for All, while enhancing the overall quality of care.

Roberts calls his plan Coordinated Care for All, and while it is modeled somewhat like a single-payer government-managed healthcare system, there would be no mandate to participate. Private sector competition would continue by allowing people to opt out. The plan could also be easily adopted for use in the private sector as well.

Roberts's plan focuses on several key areas including prediction of risk, education, prevention, cost containment, efficiency, and medical case management, combining all of these target areas of focus with a centralized computer system, while utilizing artificial intelligence and voluntary genetic input to predict risk.

Coordinated Care for All would combine technology, artificial intelligence and genetics to identify and target the following:

According to Roberts, while all of this can be applied to a model for a single-payer source (Universal Healthcare), the same ideas can also be also applied to the private sector. Additionally, the allowance of pre-existing conditions and competition within the private healthcare sector are inclusive in the plan.

To promote his plan, Roberts has taken big steps. Originally, he tried working with lawmakers, but when that process resulted in slow results, he decided to invest more than $250,000 into the production of a feature-length documentary film called "Diagnosing Healthcare," which is set to be released this spring.

Since beginning his push, Roberts has been gaining momentum. The Case Management Society of America published an article focusing on his plan in their latest issue of their flagship magazine, CMSA Today. Additionally, Roberts was recently interviewed about Coordinated Care for All on American Medicine Today, and next month Roberts is scheduled to speak at the Synapse Innovation Summit at Amalie Arena in Tampa Feb 11-12.

"I realized that in order to be taken seriously, I needed to take my plan directly to the American public, so that's what I am doing," said Roberts. "At the end of the day, the focus of my plan is on improving cost-effectiveness, while also improving the quality of care delivered."

For more information on Coordinated Care for All, visit http://www.robertsccm.com.

For the original version on PRWeb visit: https://www.prweb.com/releases/tampa_health_care_expert_unveils_health_care_plan_using_artificial_intelligence_genetics_medical_case_management_to_save_taxpayers_1_4_trillion_per_year/prweb16890739.htm

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Dyne Therapeutics Expands Leadership Team with Key Hires – Business Wire

February 7th, 2020 3:44 am

WALTHAM, Mass.--(BUSINESS WIRE)--Dyne Therapeutics, a biotechnology company pioneering targeted therapies for patients with serious muscle diseases, today announced the addition of three key members to its leadership team: Oxana Beskrovnaya, Ph.D., senior vice president and head of research; Chris Mix, M.D., senior vice president, clinical development; and John Najim, vice president, chemistry, manufacturing and controls (CMC).

Dyne is establishing a leadership position in muscle disease therapeutics by combining transformative science with an organizational passion for changing the lives of patients, said Joshua Brumm, president and chief executive officer of Dyne. We are thrilled to welcome Oxana, Chris and John to our growing team. Leveraging their collective experience in the discovery and development of novel medicines, we are poised to rapidly advance our programs toward the clinic and are fully focused on execution.

Dr. Beskrovnaya is an accomplished R&D leader with a strong track record of discovering and developing first-in-class therapeutics for rare genetic diseases. Prior to joining Dyne, she served as head of musculoskeletal and renal research in Sanofis rare disease and neurological unit, where she advanced a pipeline of drug candidates using multiple therapeutic modalities, including nucleic acids, proteins and small molecules. Dr. Beskrovnaya is the author of numerous patents, invited reviews, editorials, book chapters and original research articles in major scientific journals. She received her Ph.D. in genetics from Moscow Genetics Institute, followed by postdoctoral fellowship training in neuromuscular diseases at the Howard Hughes Medical Institute at the University of Iowa.

Dr. Mix brings extensive clinical development experience to Dyne, most recently serving as vice president of rare genetic disease clinical development at Agios Pharmaceuticals, where he oversaw development across several hemolytic anemia indications. In his previous role as vice president of clinical development at Sarepta Therapeutics, he focused on advancing candidate therapies for rare neuromuscular disease. Dr. Mix received his B.A. in chemistry from Haverford College and his M.D. from the University of Massachusetts Medical School. He completed his residency in internal medicine at Tufts Medical Center, a fellowship in nephrology at the Beth Israel Deaconess Medical Center in Boston and an M.S. in clinical care research at the Tufts School of Biomedical Sciences.

Mr. Najim brings a wealth of CMC biopharmaceutical development and cGMP manufacturing experience across multiple biologic expression systems and small molecules. Mr. Najim previously held roles of increasing responsibility at Proteon Therapeutics, including most recently as vice president of manufacturing and process development, and also served as associate director of manufacturing at Dyax Corporation. He received his B.S. in biochemistry from Merrimack College and his MBA from Bentley University.

About Dyne TherapeuticsDyne Therapeutics is pioneering life-transforming therapies for patients with serious muscle diseases. The companys FORCE platform delivers oligonucleotides and other molecules to skeletal, cardiac and smooth muscle with unprecedented precision to restore muscle health. Dyne is advancing treatments for myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Dyne was founded by Atlas Venture and is headquartered in Waltham, Mass. For more information, please visit http://www.dyne-tx.com, and follow us on Twitter and LinkedIn.

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Nigerias most prominent geneticists and medical research professionals are coming together to promote genomics research and make new drug discoveries…

February 7th, 2020 3:44 am

54gene has announced the launch of the African Centre for Translational Genomics (ACTG), an initiative established to facilitate translational genomics research by African scientists.

This initiative is the coming together of leading scientists as a welcome development for leveraging talent from across Nigeria to promote genomics research scholarship.

The establishment will also re-invest in the health ecosystem by empowering the next generation of African genomic scientists through the provision and implementation of grants, fellowships, internships, and training for medical researchers, trainees, and students, the company said in a statement released on Tuesday, February 4th, 2020.

According to a 2018 National Center for Biotechnology Information (NCBI) report, Nigeria has few medical geneticists and genetic counselors in Nigeria with most genetic disorders patients seen by pediatricians.

With this first concerted effort from genetic scientists and researchers, the ACTG will be funding its first study under the Non-Communicable Diseases - Genetic Heritage Study (NCD-GHS) Consortium. The consortium will see over 100,000 Nigerians participate in the eponymous study which will seek to understand the genetic basis of the highly prevalent non-Communicable Diseases (NCDs) in Nigeria such as cancers, diabetes, Alzheimers, chronic kidney, sickle cell disease, among others.

ALSO READ: Business Insider chats with the CEO of 54gene, the company building the world's first pan-African biobank

The consortium will have a steering committee co-led by the Director-General of Nigeria Institute of Medical Research [NIMR], Prof. Babatunde Lawal Salako, the Director of National Biotechnology Development Agencys Centre for Genomics Research and Innovation [NABDA-CGRI], Prof Oyekanmi Nash, the CEO of 54gene, Dr. Abasi Ene-Obong, Dr. Segun Fatumo, Assistant Professor, London School of Hygiene and Tropical Medicine [LSHTM], and Dr. Omolola Salako, Consultant Oncologist, College of Medicine, University of Lagos [CMUL].

Speaking on the consortium launch, Dr. Abasi Ene-Obong, said, In continuation with our belief at 54gene that genetic research in Africa should be ethical and beneficial to the communities we serve, and that African scientists be at the forefront of new drug discoveries that benefit Africans and the world at large; we have set up the ACTG to harness translational genetic research across Africa. The NCD-GHS study is our pilot effort under the ACTG that has the potential to rewrite the playbook of genomics research, where African scientists will be placed at the forefront of new drug discoveries for conditions that affect the health of not only Nigerians but greater Africa and the world.

Our collaboration with scientists at NIMR and NABDA-CGRI, as a consortium, is a highly welcome initiative which we believe will be a rewarding and mutually beneficial experience for all parties. For 54gene specifically, the opportunity for us to contribute to a broader national agenda for genomics research is both inspiring and humbling, and we are committed to ensuring its success.

Joining Dr. Ene-Obong at the launch of the NCD-GHS Consortium included many of Nigerias most prominent geneticists and medical research professionals.

Professor. Babatunde Lawal Salako, Director General of the Nigeria Institute of Medical Research (NIMR), added that the consortium will engage senior scientists that have made their mark in the field of cardiometabolic research in teaching hospitals across the country to ensure representativeness and quality.

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Engineering Bugs, Resurrecting Species: The Wild World of Synthetic Biology for Conservation – Singularity Hub

February 7th, 2020 3:43 am

Imagine a world where a mosquito bite is just an itchy annoyance. No malaria. No dengue fever.

Last month, scientists announced they had taken one more step toward that vision. A paper in the journal PLOS Pathogens described how they synthetically engineered mosquitoes to stop the spread of dengue fever, a viral tropical disease that sickens as many as 100 million people each year.

Now imagine genetically tweaking an invasive species of mosquito to save native Hawaiian birds from extinction, or transferring genes from one species of endangered chestnut tree to another to help the latter resist blight. Employing the same sort of genetic engineering used to make a plant-based burger bleed, scientists are beginning to explore the ways synthetic biology could help protect biodiversity and conserve species.

Synthetic biology, or synbio, employs the latest and greatest gene-editing tools, such as the cut-and-paste technology known as CRISPR-Cas9. Combined with new techniques to digitize and automate the design and modeling of various genetic elements, scientists can now engineer organisms to produce novel food ingredients or to rewire the switches that express genes that control certain functions.

In the case of those dengue-carrying mosquitoes, scientists genetically tweaked members of the Aedes aegypti species by transferring genes from the human immune system that create an antibody to suppress dengue fever into the blood-sucking insect. The antibody is activated and expressed once the female mosquito draws blood. In effect, the mosquito is cured of dengue fever before it can transmit the disease.

The next step would be to propagate the new genetic element to confer dengue immunity through a population. Thats where a gene drive comes in. Gene drive systems, which can be natural or synthetically engineered, skew inheritance of a certain genetic element so that it will spread more quickly through generations.

The idea is to bypass normal inheritance rulesthat classic Darwinian concept that inheritance is driven by genetic variations that improve an organisms ability to compete in a dog-eat-dog worldso that re-engineered traits become dominant.

In terms of conservation, synbio could potentially address several areas of concern, such as curbing invasive species, reducing pressures from wildlife trade, improving resistance to disease, and even bringing a species back from the brink of extinction.

Biologists at the University of California San Diego (UCSD), who also led the team that wrote the PLOS Pathogens paper on mosquitoes, developed a novel gene drive system for manipulating genetic inheritance in Drosophila suzukii, a fruit fly with the common name spotted-wing drosophila.

This particular pest, native to Japan and first discovered in the US in 2008, injects its eggs into soft ripening fruit like berries. Current practices to defend against spotted-wing drosophila rely on either heavy insecticide use or early harvesting. Its estimated the pest costs the US economy as much as $700 million each year in losses.

The engineered gene drive from UCSD, dubbed Medea after the character in Greek mythology that killed her offspring, uses a synthetic toxin and a corresponding antidote function to achieve 100 percent inheritance bias in less than 20 generations.

This genetic Trojan Horse could then be used to spread elements that confer susceptibility to certain environmental factors, such as triggering the death of the modified fruit flies at a certain temperature.

UC San Diego associate professor Omar Akbari told Singularity Hub that his team is getting close to field testing some of our technologies. The furthest along for our group would be the use of [precision guided sterile insect technique] to control wild populations of D. Suzuki.

A number of companies are turning to synbio to create ingredients where the natural product is expensive, rare, or threatened. Take the well-known example of vanilla. Most products on the market use a synthetic version of vanillas main ingredient, vanillin, made from petrochemicals.

Swiss company Evolva has developed a genetically modified yeast to produce vanillin in a manner similar to brewing beer. Modern Meadow also uses DNA editing tools to engineer specialized collagen-producing yeast cells for making leather products.

In a case more directly related to wildlife conservation, Singaporean scientists engineered a synthetic replacement for horseshoe crab blood cells, which have been used in biomedical applications for decades. All four species of horseshoe crabs are considered imperiled by the International Union for Conservation of Nature (IUCN).

However, while a replacement product for horseshoe crab blood has been commercially available for more than 15 years, it has yet to be broadly adopted for various reasons. Thats finally changing, as new studies have confirmed that available synthetics are just as reliable as horseshoe crab blood for detecting endotoxins in biomedical manufacturing.

The long-lived American chestnut was once one of the dominant tree species of forests in the eastern US. A blight from Asia introduced in the late 1800s has all but wiped them out. Efforts to breed American chestnuts with disease-resistant chestnut trees in China have had limited success, as its not easy to propagate the desired traits from several genes through succeeding generations.

A project led by the College of Environmental Science and Forestry in Syracuse, New York is using synbio to produce a blight-resistant American chestnut without even harming the fungus.

The researchers have copied a single gene from wheat and transferred it into American chestnuts. The gene produces an enzyme called oxalate oxidase that doesnt kill the fungus. Instead, it breaks down the fungus toxin that attacks the trees tissue properties.

The bonus is that the fungus itself is left untouched, so the blight remains dormant and doesnt evolve resistance over time.

While bringing the dead back to life is one trick that will likely elude scientists in our lifetime, synbio researchers have been actively working to resurrect the woolly mammoth and other extinct species such as the passenger pigeon, which disappeared for good more than a century ago.

These projects arent strictly creating pure examples of these long-gone species. Rather, scientists are inserting sections of ancient DNA code into modern relatives. In the case of the woolly mammoth, researchers are attempting to create a mammoth-elephant hybrid using the Asian elephant.

Proponents of this sort of resurrection science say its less about trying to revive extinct species than about saving those that are currently at risk of disappearing. The Asian elephant (Elephas maximus) is on the IUCN Red List of Threatened Species.

A team led by George Church out of Harvard University hopes that by transferring genes in the mammoth genome to the Asian elephant it will be able to survive in the Arctic; relevant genes might include those that code for extra fat and dense hair. That would extend the animals range into regions that are already changing due to a warming climate.

Like geoengineeringmanipulating the environment to stave off the effects of climate changebioengineering has its critics and detractors. Some react viscerally to the idea of altering natural systems in any way.

One of the main arguments revolves around the concern that introducing a genetically modified species could have unintended consequences. While no one expects a Jurassic Park scenario where genetically enhanced monsters chase Jeff Goldblum through the jungle, there is a chance that genetically tweaked traits could jump species or otherwise go off script.

Kent Redford believes fostering a conversation about the possible advantages and disadvantages of the role of synbio in conservation is important regardless of where one stands on the divide.

My mission is to make sure that the conservation community knows about these technologies and has taken a considered and informed opinion on them, and tried to influence [these] technologies for the good of biodiversityto minimize harm and to increase positive outcomes, he told Singularity Hub during a phone interview.

A conservation expert who has served at the The Nature Conservancy and Wildlife Conservation Society, Redford is the chair of an IUCN task force on synthetic biology and biodiversity conservation. He was the lead editor on an assessment report, Genetic Frontiers for Conservation, which will be presented this summer at the IUCN World Conservation Congress in France.

The opinion of the IUCN matters. Its 1,300 member organizations include governments, non-governmental organizations, business associations, and scientific and academic institutions.

Redford declined to speculate as to what sort of recommendations may come out of the IUCN meeting. He did note that the intersection of synbio and conservation remains on the periphery for many in the conservation community.

Most of my colleagues dont see why they should be paying much attention to this, he said. Some of those who are aware of these emerging technologies consider them to be relevant tools to help solve some of the intractable problems in conservation. Others believe these genetic techniques have the potential to completely ruin the natural world and the lives of poor people.

Akbari agreed that the biggest challenge for synbio in conservation isnt the technology but securing regulatory approvals and public support. I think we need time, he said. As more technologies are developed and tested with positive outcomesI believe the resistance will lessen.

While the scientific community debates the potential and the pitfalls of synbio, biodiversity will continue to decline.

A report last year by the United Nations Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services issued a number of disturbing statistics. For example, the average abundance of native species in most major land-based habitats has fallen by at least 20 percent, mainly since 1900. And nearly 10 percent of all domesticated breeds of mammals humans have used for food and agriculture throughout history were extinct by 2016, with at least 1,000 more breeds still threatened.

I think the natural world is in serious trouble, Redford said. Whether synbio can be part of the answer to that problem remains a big question.

Image Credit: Image by RayNight from Pixabay

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Have humans evolved beyond nature and do we even need it? – Bywire News

February 7th, 2020 3:43 am

Manuel Berdoy, University of Oxford

UK (The Conversation) - Such is the extent of our dominion on Earth, that the answer to questions around whether we are still part of nature and whether we even need some of it rely on an understanding of what we want as Homo sapiens. And to know what we want, we need to grasp what we are.

It is a huge question but they are the best. And as a biologist, here is my humble suggestion to address it, and a personal conclusion. You may have a different one, but what matters is that we reflect on it.

Perhaps the best place to start is to consider what makes us human in the first place, which is not as obvious as it may seem.

This article is part of Lifes Big Questions The Conversations new series, co-published with BBC Future, seeks to answer our readers nagging questions about life, love, death and the universe. We work with professional researchers who have dedicated their lives to uncovering new perspectives on the questions that shape our lives.

Many years ago, a novel written by Vercors called Les Animaux dnaturs (Denatured Animals) told the story of a group of primitive hominids, the Tropis, found in an unexplored jungle in New Guinea, who seem to constitute a missing link.

However, the prospect that this fictional group may be used as slave labour by an entrepreneurial businessman named Vancruysen forces society to decide whether the Tropis are simply sophisticated animals or whether they should be given human rights. And herein lies the difficulty.

Human status had hitherto seemed so obvious that the book describes how it is soon discovered that there is no definition of what a human actually is. Certainly, the string of experts consulted anthropologists, primatologists, psychologists, lawyers and clergymen could not agree. Perhaps prophetically, it is a layperson who suggested a possible way forward.

She asked whether some of the hominids habits could be described as the early signs of a spiritual or religious mind. In short, were there signs that, like us, the Tropis were no longer at one with nature, but had separated from it, and were now looking at it from the outside with some fear.

It is a telling perspective. Our status as altered or denatured animals creatures who have arguably separated from the natural world is perhaps both the source of our humanity and the cause of many of our troubles. In the words of the books author:

All mans troubles arise from the fact that we do not know what we are and do not agree on what we want to be.

We will probably never know the timing of our gradual separation from nature although cave paintings perhaps contain some clues. But a key recent event in our relationship with the world around us is as well documented as it was abrupt. It happened on a sunny Monday morning, at 8.15am precisely.

The atomic bomb that rocked Hiroshima on August 6 1945, was a wake-up call so loud that it still resonates in our consciousness many decades later.

The day the sun rose twice was not only a forceful demonstration of the new era that we had entered, it was a reminder of how paradoxically primitive we remained: differential calculus, advanced electronics and almost godlike insights into the laws of the universe helped build, well a very big stick. Modern Homo sapiens seemingly had developed the powers of gods, while keeping the psyche of a stereotypical Stone Age killer.

We were no longer fearful of nature, but of what we would do to it, and ourselves. In short, we still did not know where we came from, but began panicking about where we were going.

We now know a lot more about our origins but we remain unsure about what we want to be in the future or, increasingly, as the climate crisis accelerates, whether we even have one.

Arguably, the greater choices granted by our technological advances make it even more difficult to decide which of the many paths to take. This is the cost of freedom.

I am not arguing against our dominion over nature nor, even as a biologist, do I feel a need to preserve the status quo. Big changes are part of our evolution. After all, oxygen was first a poison which threatened the very existence of early life, yet it is now the fuel vital to our existence.

Similarly, we may have to accept that what we do, even our unprecedented dominion, is a natural consequence of what we have evolved into, and by a process nothing less natural than natural selection itself. If artificial birth control is unnatural, so is reduced infant mortality.

I am also not convinced by the argument against genetic engineering on the basis that it is unnatural. By artificially selecting specific strains of wheat or dogs, we had been tinkering more or less blindly with genomes for centuries before the genetic revolution. Even our choice of romantic partner is a form of genetic engineering. Sex is natures way of producing new genetic combinations quickly.

Even nature, it seems, can be impatient with itself.

Advances in genomics, however, have opened the door to another key turning point. Perhaps we can avoid blowing up the world, and instead change it and ourselves slowly, perhaps beyond recognition.

The development of genetically modified crops in the 1980s quickly moved from early aspirations to improve the taste of food to a more efficient way of destroying undesirable weeds or pests.

In what some saw as the genetic equivalent of the atomic bomb, our early forays into a new technology became once again largely about killing, coupled with worries about contamination. Not that everything was rosy before that. Artificial selection, intensive farming and our exploding population growth were long destroying species quicker than we could record them.

The increasing silent springs of the 1950s and 60s caused by the destruction of farmland birds and, consequently, their song was only the tip of a deeper and more sinister iceberg. There is, in principle, nothing unnatural about extinction, which has been a recurring pattern (of sometimes massive proportions) in the evolution of our planet long before we came on the scene. But is it really what we want?

The arguments for maintaining biodiversity are usually based on survival, economics or ethics. In addition to preserving obvious key environments essential to our ecosystem and global survival, the economic argument highlights the possibility that a hitherto insignificant lichen, bacteria or reptile might hold the key to the cure of a future disease. We simply cannot afford to destroy what we do not know.

But attaching an economic value to life makes it subject to the fluctuation of markets. It is reasonable to expect that, in time, most biological solutions will be able to be synthesised, and as the market worth of many lifeforms falls, we need to scrutinise the significance of the ethical argument. Do we need nature because of its inherent value?

Perhaps the answer may come from peering over the horizon. It is somewhat of an irony that as the third millennium coincided with decrypting the human genome, perhaps the start of the fourth may be about whether it has become redundant.

Just as genetic modification may one day lead to the end of Homo sapiens naturalis (that is, humans untouched by genetic engineering), we may one day wave goodbye to the last specimen of Homo sapiens genetica. That is the last fully genetically based human living in a world increasingly less burdened by our biological form minds in a machine.

If the essence of a human, including our memories, desires and values, is somehow reflected in the pattern of the delicate neuronal connections of our brain (and why should it not?) our minds may also one day be changeable like never before.

And this brings us to the essential question that surely we must ask ourselves now: if, or rather when, we have the power to change anything, what would we not change?

After all, we may be able to transform ourselves into more rational, more efficient and stronger individuals. We may venture out further, have greater dominion over greater areas of space, and inject enough insight to bridge the gap between the issues brought about by our cultural evolution and the abilities of a brain evolved to deal with much simpler problems. We might even decide to move into a bodiless intelligence: in the end, even the pleasures of the body are located in the brain.

And then what? When the secrets of the universe are no longer hidden, what makes it worth being part of it? Where is the fun?

Gossip and sex, of course! some might say. And in effect, I would agree (although I might put it differently), as it conveys to me the fundamental need that we have to reach out and connect with others. I believe that the attributes that define our worth in this vast and changing universe are simple: empathy and love. Not power or technology, which occupy so many of our thoughts but which are merely (almost boringly) related to the age of a civilisation.

Like many a traveller, Homo sapiens may need a goal. But from the strengths that come with attaining it, one realises that ones worth (whether as an individual or a species) ultimately lies elsewhere. So I believe that the extent of our ability for empathy and love will be the yardstick by which our civilisation is judged. It may well be an important benchmark by which we will judge other civilisations that we may encounter, or indeed be judged by them.

There is something of true wonder at the basis of it all. The fact that chemicals can arise from the austere confines of an ancient molecular soup, and through the cold laws of evolution, combine into organisms that care for other lifeforms (that is, other bags of chemicals) is the true miracle.

Some ancients believed that God made us in his image. Perhaps they were right in a sense, as empathy and love are truly godlike features, at least among the benevolent gods.

Cherish those traits and use them now, Poppy, as they hold the solution to our ethical dilemma. It is those very attributes that should compel us to improve the wellbeing of our fellow humans without lowering the condition of what surrounds us.

Anything less will pervert (our) nature.

To get all of lifes big answers, join the hundreds of thousands of people who value evidence-based news by subscribing to our newsletter. You can send us your big questions by email at bigquestions@theconversation.com and well try to get a researcher or expert on the case.

More Lifes Big Questions:

Manuel Berdoy, Biologist, University of Oxford

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Have humans evolved beyond nature and do we even need it? - Bywire News

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In small study, hints of promise for ‘natural killer’ cell therapy – BioPharma Dive

February 7th, 2020 3:43 am

A new type of cancer cell therapy could avoid some of the serious side effects commonly associated with CAR-T treatments, and possibly offer an easier path to developing "off-the-shelf" treatments, suggest findings from a small study led by researchers at the MD Anderson Cancer Center in Houston, Texas.

The results, which were published Wednesday in the New England Journal of Medicine, are from just 11 patients. Other factors, such as the use of postremission therapy, limit what conclusions can be drawn about the researchers' approach, which relies on "natural killer" cells rather than the T cells used in cellular drugs like Novartis' Kymriah.

Still, the data offer a glimpse into why Japanese drugmaker Takedaagreed last November to license the CAR NK cell therapy from MD Anderson, part of the company's broader push into cell and gene treatments. Some of the data published Wednesday was previously disclosed by the pharma.

The success of cancer immunotherapy, of which CAR-T treatments are a major part, has put T cells at the center of a now decade-long research revival in oncology.

But T cells are only one component of the body's immune system, and scientists in academia and in biotech are exploring whether other cellular defenders could be similarly recruited.

Researchers at MD Anderson have turned to natural killer cells, which by design recognize and attack cancers or other invaders. Such cells have been tested as an anti-cancer treatment before,but using genetic engineering to improve their tumor-killing properties, which the MD Anderson team has done, is a newer innovation.

"To my knowledge, this is the largest body of evidence on the use of CAR NK cells in patients with cancer," said Katayoun Rezvani, the study's corresponding author and a professor of stem cell transplantation and cellular therapy at MD Anderson, in an interview.

Using NK cells derived from cord blood, Rezvani and her colleagues engineered the cells to express a receptor for a protein called CD19, commonly found on the surface of B-cell malignancies like leukemia and lymphoma. They also added a gene for interleukin-15 to boost the expansion and persistence of the infused NK cells, which without engineering would typically disappear after about two weeks.

While the CAR-T treatments Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) also target CD19, they are made from a patient's own T cells, which are extracted and then engineered outside the body. The personalized process is time-consuming and laborious, hampering the commercial uptake of both Kymriahand Yescarta.

By using cord blood, Rezvani and her team are pursuing an allogeneic, or "off-the-shelf," approach to cell treatment something many consider to be the next step for the field.

Initial data look promising. Seven of the 11 treated patients, who had either chronic lymphocytic leukemia or non-Hodgkin lymphoma, responded to treatment, with the cancers of three going into remission.Most notably, none experienced cytokine release syndrome or neurotoxicity, two severe side effects that commonly occur in patients treated with CAR-T therapy.

"The lack of toxicity is very exciting here," wrote Stephan Grupp, an oncologist at Children's Hospital of Philadelphia and a leader in the CAR-T field, in comments emailed to BioPharma Dive. He was not involved with the MD Anderson study.

"We really think that this is something inherent to the biology of the natural killer cells, which means their profile of toxicity is different than that of T cells,"Rezvanisaid.

Study participants did have blood toxicities that researchers associated with the chemotherapy given prior to infusion of the CAR NK cells.

While positive, the results are limited by several factors which make drawing broader conclusions about the ultimate potential of the treatment difficult.

Five of the seven responding patients received postremission treatment, including stem cell transplants, Rituxan (rituximab) and Revlimid (lenalidomide), so researchers did not assess the duration of response to CAR NK therapy.

Additionally, a fresh CAR NK cell product was manufactured for each patient in this study, rather than using the cord blood to produce multiple therapies as would be envisioned for a true off-the-shelf product.

"I think the potential for this approach to be 'off-the-shelf' is also a little speculative at this time," wrote Grupp.

"We would need to see multiple patients treated from the same expanded product with no HLAmatching to know if 'off-the-shelf' is going to be part of the story here," he added, referring to the process by which patients are matched to donor cells.

If cord blood-derived CAR NK cells were able to be given without matching to a patient's HLA genotype, any resulting treatment could be used more widely. Nine patients were partially matched in the MD Anderson study, while the last two were treated without consideration of HLA type.

The MD Anderson researchers plan to continue enrolling patients in the study and are working with Takeda to design a larger, multi-center trial.

The drugmaker is planning to advance the treatment, which it licensed and now calls TAK-007, into pivotal studies in two types of lymphoma and CLL by 2021, with a potential filing for approval in 2023.

"Targeting CD19 was a proof of concept and now that we've demonstrated that this CAR NK approach can work and is safe we want to use this platform to target other types of cancers," said Rezvani, indicating interest in multiple myeloma and acute myeloid leukemia.

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In small study, hints of promise for 'natural killer' cell therapy - BioPharma Dive

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