Discovery of hundreds of genes potentially associated with ALS may steer scientists toward treatments – Stanford Medical Center Report

In addition to finding many genes that could contribute to the ALS, the researchers believe the study has settled a few important questions about the disease.

Theres a long-standing debate about where ALS originates in the cell, said Johnathan Cooper-Knock, a Stanford visiting scholar and lecturer at the University of Sheffield in the United Kingdom. This new technique has surfaced genetic evidence that really pins down the axon of motor neurons as the place of disease origin. (The axon of the neuron is a long cord that helps transmit electrical signals from one neuron to another.)

A paper describing the study was published Jan. 18 in Neuron. Snyder, the Stanford W. Ascherman, MD, FACS, Professor of Genetics, is the senior author. Zhang and Cooper-Knock are co-lead authors.

Typically, ALS researchers investigate one gene at a time, performing in-depth analyses to tease out if and how that gene might contribute to the onset of the disease. The Stanford teams approach was to cast a net far and wide for genes that may play a role in ALS. Zhang trained the algorithm to sift through millions of data points from studies known as genome-wide associated screens, which contain anonymized genetic information from thousands of patients with and without ALS. The strategy was to look for genetic mutations that often occur in people who have ALS.

The team narrowed the search further: Sorting through ALS patients data, the algorithm looked for mutations only in genes that support motor neuron function. Searching only in motor neurons allowed our approach to discover more risk genes compared with previous methods, Zhang said. The analysis spit out 690 candidate genes, some that were already known to be implicated in ALS.

We can use this information to learn more about how and why motor neurons fail in ALS, Cooper-Knock said. As an example, he added, Many of the genes we uncovered pointed to the disease originating in the axon of the cell, rather than the cell body.

Previously it was not clear if axon defects were an effect of the disease, but our results indicate these defects are likely causative, added Snyder.

One gene, which repeatedly showed up in the data analysis, caught the researchers attention: KANK1, which is involved in functions at the very end of the axon. Through a series of experiments using stem cells and gene editing, the team showed that mutations in this gene lead to loss of a protein called TDP-43 from the nucleus of motor neurons, a hallmark of ALS.

If you were to look in the brains of 100 people with ALS and analyze the motor neurons, youd see this loss of TDP in something like 98, Cooper-Knock said. Its almost the definition of ALS. If this phenomenon isnt occurring, you probably dont have ALS.

The finding is an exciting discovery, but its too early to consider KANK1 a drug target. Zhang said. More research will be needed to determine if reversing the effects of a mutated KANK1 gene can help treat the disease.

The team also plans to do some experimental work on other hits from their dataset to determine whether any of the other hundreds of genes identified in the analysis could lead to ALS pathology.

Other Stanford co-authors of the study are life science researchers Minyi Shi, PhD, and Annika Weimer, PhD.

Researchers from the University of Sheffield; UC San Francisco; the Montreal Neurological Institute; Lund University; the Weizmann Institute of Science; and the University Medical Center in Utrecht, the Netherlands, contributed to this study.

This study was funded by the European Research Council, Health~Holland, the ALS Foundation Netherlands, the National Lottery of Belgium, the KU Leuven Opening the Future Fund, the Kingsland Fellowship, the My Name5 DoddieFoundation, the Wellcome Trust and the National Institute for Health Research.

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Discovery of hundreds of genes potentially associated with ALS may steer scientists toward treatments - Stanford Medical Center Report

Ceptur Therapeutics Launches with $75M Series A Financing to Advance RNA Therapeutics Based on Proprietary U1 Adaptor Technology – Business Wire

PHILADELPHIA--(BUSINESS WIRE)--Ceptur Therapeutics, Inc. (Ceptur), a biotechnology company focused on developing targeted oligonucleotide therapeutics based on U1 Adaptor technology, today announced the completion of a $75M Series A financing. The round was co-led by venBio Partners and Qiming Venture Partners USA with participation by new investors Perceptive Xontogeny Venture (PXV) Fund, Bristol Myers Squibb and Janus Henderson Investors along with existing Seed investors Affinity Asset Advisors, Boxer Capital and LifeSci Venture Partners.

We are extremely grateful for the support of our new and existing investors, said Ceptur Therapeutics co-founder, President and CEO P. Peter Ghoroghchian, MD, PhD. In 2021, we in-licensed and internally expanded our foundational IP portfolio on U1 Adaptor technology; we further recruited a world-class scientific advisory board, comprising academic and industry leaders in oligonucleotide therapeutics. Moving forward, Ceptur will use the proceeds of this financing round to advance our broad discovery pipeline of differentiated genetic medicines.

U1 Adaptors are bivalent oligonucleotides that engage sequence-specific mRNA and the U1 small nuclear ribonuclear protein (U1 snRNP), which is a ubiquitous intracellular machine that regulates transcription and splicing. U1 Adaptor therapeutics control gene expression at the pre-mRNA level within the nucleus, affording advantageous properties for drugging difficult targets.

Therapeutic approaches that target RNA have become an essential treatment modality for patients with genetic diseases and a priority for many biopharma companies; we believe that the U1 Adaptor technology is a differentiated approach to RNA regulation that has multiple potential advantages over current technologies, said Aaron Royston, M.D., M.B.A., Managing Partner at venBio Partners. We are excited to further build out Cepturs team and capabilities, to demonstrate these unique applications, and, ultimately, to advance novel therapeutics for patients with genetic diseases.

Colin Walsh, Ph.D., Partner at Qiming Venture Partners USA, added, RNA-based drugs have already become an essential tool in our therapeutic arsenal; and, we strongly believe that this modality will continue to deliver meaningful new therapies for patients. Cepturs use of synthetic oligonucleotides that engage U1 snRNP offers the ability to co-opt this master regulator of the transcriptome to regulate mRNA in a highly targeted fashion. We are thrilled to support Cepturs next phase of growth as they apply this disruptive approach for novel therapeutic applications.

With this financing, Aaron Royston, M.D., M.B.A., and Colin Walsh, Ph.D., join Cepturs Board of Directors.

Daniel Heller, M.S., M.B.A., General Partner and Chief Investment Officer at Affinity Asset Advisors, continued, In leading the Series Seed round, we identified early the potential of U1 Adaptor technology. Over the past year, we have worked closely with Peter and the Ceptur team and are delighted at the progress that has been made towards establishing the platform. In this financing round, we have significantly expanded upon our initial commitment and are inspired to partner with our new investor syndicate to advance U1 Adaptors for unmet patient needs.

To realize the revolutionary potential of the U1 Adaptor technology, several new members join Samuel Gunderson, Ph.D., co-founder of Ceptur, Professor of Molecular Biology at Rutgers University, and a leading expert on U1 snRNP biology, on Cepturs Scientific Advisory Board:

Thomas Andresen, Ph.D.Dr. Thomas L. Andresen is the CEO of T-Cypher Bio and the former CSO of Torque Therapeutics, now Repertoire Immune Medicines. While at Torque, he led the companys cellular immunotherapy programs from early-stage discovery to CMC scaling and through to clinical development. Dr. Andresen is a serial entrepreneur, having founded several US and EU life-science companies that further include Nanovi A/S and Monta Biosciences. His company creation track record spans early discovery to commercial and maps across multiple immunotherapy approaches for oncology. Dr. Andresen sits on several boards/advisory boards, including for Tidal Therapeutics (acquired by Sanofi), Monta Biosciences, and Nanovi; in academia, hes further founded the Institute of Health Technology at the Technical University of Denmark, where he maintains a professorial position. Dr. Andresen has co-authored over >200 research articles, has been listed as an inventor on >45 patent applications, and has received multiple research prizes, including the Elite Research Price from the Danish Ministry of Science.

Dennis Benjamin, Ph.D.Dr. Dennis Benjamin is the former SVP of Research at Seagen where he was a key developer of the companys ADC technology and clinical pipeline. Prior, he worked at Praecis Pharmaceuticals and Genetics Institute, advancing DNA encoded libraries and working in protein and small molecule discovery. Over his career, he has led teams that have discovered 25 biologics and small molecules that entered clinical trials and has contributed to 4 drug approvals. He is currently an advisor and SAB member at several start-up biotechnology companies.

Steven Dowdy, Ph.D.Dr. Steven F. Dowdy is a Professor of Cellular & Molecular Medicine at the UCSD School of Medicine and a cancer biologist, specializing in the development and delivery of RNA therapeutics as well as in G1 cell cycle control in cancer. The Dowdy lab is focused on the molecular details of delivery of RNA therapeutics across the endosomal lipid bilayer as well as the synthesis of endosomal escape domains to overcome this rate-limiting and billion year-old delivery challenge; its members were the first to synthesize bioreversible, charge neutralizing phosphotriester backbone RNAi prodrug triggers that increase metabolic stability, that augment pharmacokinetics and that enhance endosomal escape. Dr. Dowdy currently serves on five Science Advisory Boards for biotech companies and is an elected member of the Oligonucleotide Therapeutics Society (OTS) Board of Directors.

Sridhar Ganesan, M.D., Ph.D.Dr. Shridar Ganesan is the Associate Director for Translational Science, Chief of the Section of Molecular Oncology, and the co-Leader of the Clinical Investigations and Precision Therapeutics Program at the Rutgers Cancer Institute of New Jersey; he is also the Omar Boraie Chair in Genomic Science and Professor of Medicine at the Rutgers Robert Wood Johnson Medical School. Dr. Ganesan is a medical oncologist with clinical expertise in triple-negative breast cancer, hereditary breast cancer and rare cancer. His research interests include the characterization of DNA repair abnormalities in cancer with a focus on the BRCA1 tumor suppressor gene, the multi-modal molecular characterizations of different cancers, and the identification of biomarkers of response and resistance in early phase clinical trials. He has authored or co-authored over 120 publications, serves on multiple national and international grant review committees and is an Associate Editor of JCO-Precision Oncology.

Adrian Krainer, Ph.D.Dr. Adrian Krainer is the St Giles Professor at Cold Spring Harbor Laboratory (CSHL) and Deputy Director of Research of the CSHL Cancer Center. A world-renowned biochemist recognized for his basic work on RNA splicing and the development of its mechanism-based therapeutic applications, his seminal work with antisense oligonucleotides in mouse models of spinal muscular atrophy led to the development of nusinersen (Spinraza), which is the first FDA-approved drug for this disease; he is also a co-founder and a member of the Board of Directors at Stoke Therapeutics (NASDAQ: STOK). Dr. Krainer is the recipient of the Life Sciences Breakthrough Prize, the RNA Societys Lifetime Achievement Award, the Reemtsma Foundation International Prize in Translational Neuroscience, the Speiser Award in Pharmaceutical Sciences, and the Ross Prize in Molecular Medicine, amongst others. He previously served as the President of the RNA Society and is a member of the National Academy of Sciences, the National Academy of Medicine, the National Academy of Inventors, and the American Academy of Arts & Sciences.

Iain Mattaj, Ph.D.Dr. Iain Mattaj is the founding Director of Fondazione Human Technopole in Milan, Italy. Dr. Mattaj has made seminal contributions to the fields of transcription, RNA metabolism, nucleocytoplasmic transport and cell division. His prominent standings in these fields are underlined by his election as the past President of the RNA Society, Fellow of the Royal Society (London), Fellow of the Royal Society of Edinburgh, elected Member of the German Academy of Sciences Leopoldina, Member of Academia Europea, Foreign Honorary Member of the American Academy of Arts and Science, Fellow of the Academy of Medical Sciences (London) and Foreign Associate of the National Academy of Sciences (US). Dr. Mattaj was previously awarded the prestigious Louis-Jeantet Prize for Medicine in 2001. He is further a member of the European Molecular Biology Organization (EMBO) and helped to make The EMBO Journal a highly successful international publication, acting as Executive Editor from 1990 to 2004. Prior to his current appointment, Dr. Mattaj was a member of EMBL Heidelberg, Germany, serving as Group Leader (1985-1990), Coordinator of the Gene Expression Unit (1990-1999), and, subsequently, as the institutes Scientific Director (1999-2005) and Director General (2005-2018).

Henrik Oerum, Ph.D.Dr. Henrik Oerum the co-founder and CSO of Civi BioPharma and has previously founded 3 other oligonucleotide companies. Dr. Oerum has over 25 years of experience in the development and commercialization of oligonucleotide therapeutics, has authored >70 peer reviewed publications, and has been listed as an inventor on numerous patents in the field. In 1993, he founded PNA Diagnostics A/S, where he was also the CSO until 1999. During his tenure at PNA, the company was sold to Boehringer Mannheim (1994) and later to Hoffman-La Roche (1997). In 1996, Dr. Oerum cofounded Exiqon A/S, a nucleic acid diagnostics company that was floated on the Copenhagen Stock Exchange in 2007 (CSE:EXQ). In 2000, he co-founded the LNA-oligotherapeutics company Santaris Pharma A/S, where he served as CSO and VP of Business Development until its acquisition by Roche in 2014. Thereafter, he worked for Roche Pharma as Global Head of RNA therapeutics until March 2016, where he left to pursue new opportunities, leading to his founding of CiVi.

Thomas Tuschl, Ph.D.Dr. Thomas Tuschl is a Professor of RNA Molecular Biology at Rockefeller University. Dr. Tuschl is world renown for his research on the regulation of RNA and has discovered small interfering RNAs (siRNAs), microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs). He is a member of the German National Academy of Sciences and the recipient of numerous awards, including the NIH Directors Transformative Research Project Award, the Ernst Jung Prize, the Max Delbrck Medal, the Molecular Bioanalytics Prize, the Meyenburg Prize, the Wiley Prize and the AAAS Newcomb Cleveland Prize. He is also the co-founder and a former Director of Alnylam Pharmaceuticals (NASDAQ: ALNY).

About Ceptur Therapeutics, Inc.Headquartered in Hillsborough New Jersey, Ceptur Therapeutics is a pre-clinical stage biotechnology company focused on developing targeted oligonucleotide therapeutics based on U1 Adaptor technology. For more information about Ceptur Therapeutics, please visit http://www.cepturtx.com or follow http://www.linkedin.com/company/ceptur-therapeutics/ on Linkedin.

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Ceptur Therapeutics Launches with $75M Series A Financing to Advance RNA Therapeutics Based on Proprietary U1 Adaptor Technology - Business Wire

EdiGene Enters Strategic R&D Collaboration with Haihe Laboratory of Cell Ecosystem to Develop Hematopoietic Stem Cell Regenerative Therapies and…

BEIJING & CAMBRIDGE, Mass., January 24, 2022--(BUSINESS WIRE)--EdiGene, Inc., a global biotechnology company focused on translating gene-editing technologies into transformative therapies for patients with serious genetic diseases and cancer, announced a research and development collaboration with Haihe Laboratory of Cell Ecosystem to develop hematopoietic stem cell regenerative therapies and platform technology by combining resources and expertise from both sides.

The Haihe Laboratory of Cell Ecosystem, run by the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, is focused on conducting fundamental research, innovation, and translation in the cell ecosystem.

Under the agreement, both parties will jointly develop hematopoietic stem cell regenerative therapies, including the development of innovative genetically-modified hematopoietic stem cell therapies and the exploration of novel biomarkers to optimize quality control for stem cell production.

"With top-notch resources and industry-university-research cooperation, well facilitate the development of cell-based medicine and therapies," said Professor Tao Cheng, Deputy Director of Haihe Laboratory of Cell Ecosystem and President of the Institute of Hematology and Blood Diseases Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College, a leading hematology researcher who has made a series of discoveries relating to the regulatory and regenerative mechanisms of hematopoietic stem cells. "Hematopoietic stem cells (HSCs) have the potential for long-term self-renewal and can differentiate into various types of mature blood cells. These stem cells can be harnessed to provide treatment for a broad range of diseases such as hematological tumors, autoimmune diseases, and hereditary blood disorders. We believe that this collaboration with EdiGene will accelerate the innovation and translation in the field of HSCs, thus enabling healthier patients with new therapies."

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Professor Cheng was awarded the second prize of the National Natural Science Award 2020 as the first author of work on basic and translational research that advanced the development of adult hematopoietic stem cells for therapeutic applications.

EdiGene is scaling up clinical translation and development of the first gene-editing hematopoietic stem cell therapy in China following the 2021 approval by the China National Medical Products Administration its IND for its investigational therapy ET-01. "Our team has extensive experience in the development and translation of cutting-edge technologies including hematopoietic stem cell and gene editing," said Dong Wei, Ph.D., CEO of EdiGene. "This collaboration with Haihe Laboratory of Cell Ecosystem will further our exploration in the field of hematopoietic stem cells. The partnership with this leading academic institute and our translational know-how enable us to move forward in bringing more innovative treatment options to patients in China and around the world."

In 2021, EdiGene initiated a Phase I multicenter clinical trial of ET-01, its gene-editing hematopoietic stem cell therapy for transfusion-dependent -thalassemia. EdiGene has enrolled the first patient at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Currently, the clinical trial is being conducted in Tianjin and Guangdong-Hong Kong-Macao Greater Bay Area (Greater Bay Area). EdiGene also presented its latest research on new surface markers and migration of hematopoietic stem cells at the 63rd Annual Meeting of the American Society of Hematology (ASH) in 2021.

About Haihe Laboratory of Cell Ecosystem

The Haihe Laboratory of Cell Ecosystem ("the Laboratory"), run by the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, is one of the five registered Haihe Laboratories approved by Tianjin Municipal People's Government. With the goal of promoting population health with cell ecosystem, the Laboratory adheres to developing technological frontier, enhancing peoples health, and promoting research, innovation, and development of cell ecosystem in five key areas: cellular ecosystem, cellular ecology and immunity, cellular ecological imbalance and major diseases, cellular ecological reconstruction and frontier technology of cellular ecological research.

About Institute of Hematology and Blood Diseases Hospital (IH), Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS/PUMC)

Founded in 1957, IH is a tertiary specialty hospital under the National Health Commission of China and is the supporting unit of the National Clinical Research Center of Hematologic Diseases and the State Key Laboratory of Experimental Hematology. It is also the main founding unit of Tianjin Base, the core base of the Chinese medical science and technology innovation system with the goal of becoming "the innovation hub of hematology in China." IH mainly engages in basic research, applied research, clinical diagnosis and treatment of hematological diseases, standard-setting, new technology research, new drug evaluation, and translation in hematology and related fields. IH is leading in the diagnosis and treatment of hematological diseases in China and a global scale and has made original achievements. Since 2010, IH has been awarded first place in the Hospital Specialty Reputation Ranking (Hematology) for 12 consecutive years. It has won first place in the Hematology Specialty Ranking for ten consecutive years since 2010 and ranked the first in hematology by the Scientific and Technological Evaluation Metrics (STEM) for Chinese hospitals for eight consecutive years since 2014.

About EdiGene, Inc

EdiGene is a global, clinical-stage biotechnology company focused on translating gene editing technologies into transformative therapies for patients with serious genetic diseases and cancer. The company has established its proprietary ex vivo genome-editing platforms for hematopoietic stem cells and T cells, in vivo therapeutic platform based on RNA base editing, and high-throughput genome-editing screening to discover novel targeted therapies. Founded in 2015, EdiGene is headquartered in Beijing, with offices in Guangzhou and Shanghai, China and Cambridge, Massachusetts, USA. More information can be found at http://www.EdiGene.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220124005428/en/

Contacts

Xiaomeng ZhangEdiGene, Inc.+86 10-80733899media@edigene.com

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EdiGene Enters Strategic R&D Collaboration with Haihe Laboratory of Cell Ecosystem to Develop Hematopoietic Stem Cell Regenerative Therapies and...

Roche revives a closely watched Huntington’s disease drug – BioPharma Dive

Dive Brief:

As 2021 began, Huntington's drug research appeared to be on the verge of turning a corner.

Both Roche and Wave Life Sciences were advancing drugs that were similarly designed to block production of a protein implicated in disease progression. For Roche, the stakes were particularly high: A successful result could've led to an approval application for the first drug that might slow the march of the deadly, inherited disease.

By the end of the first quarter, however, both companies reported negative data, raising questions about their drugs as well as researchers' understanding of Huntington's. It also dialed up pressure on companies with earlier stage projects, such as UniQure and Passage Bio.

But it turns out Roche isn't done with tominersen after all, a decision that could have implications for others. While the new clinical trial will be a small, Phase 2 test that will require follow-up studies, tominersen remains one of the most advanced disease-modifying drug in clinical development for Huntington's.

The Swiss drugmaker is in "the early stages" of designing the new trial, Ionis said, which will evaluate different doses of tominersen in younger patients with less severe disease. Roche will share the design of the trial with Huntington's disease specialists in medical meetings later this year, according to Ionis.

Ahead of the trial design presentations, Roche later this week will begin a series of webinars to discuss with Huntington's specialists the after-the-fact analysis of GENERATION-HD1 that hinted at a benefit for the younger, less severe patients.

Roche's Huntington's collaboration with Ionis dates back to 2013, when the big drugmaker acquired initial licensing rights for $30 million and promised up to $362 million in future payouts. Following positive signs in early testing, Roche paid $45 million to license tominersen and cover clinical development as well as commercial costs.

As a disease caused by an identifiable genetic defect, Huntington's seems to be a good target for a medicine that can block the mutation, which results in a flawed version of a protein called huntingtin. Tominersen is a type of medicine known as antisense oligonucleotide and works by going after the RNA that encodes for the protein.

Gene therapies are also aimed at the disease's genetic cause, but work by replacing the defective gene with what could in theory be a one-time treatment. Tominersen, by comparison, was given to patients once every eight or 16 weeks in GENERATION-HD1.

An estimated 41,000 people in the U.S. have Huntington's disease, although many are undiagnosed.

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WashU part of $65 million NIH study of schizophrenia in young people Washington University School of Medicine in St. Louis – Washington University…

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Teens, young adults needed for study aimed at improving early diagnosis

Daniel Mamah, MD, of Washington University School of Medicine in St. Louis, has received a grant as part of an international study focused on young people at high risk of schizophrenia. Mamah and his colleagues plan to characterize symptoms that can help diagnose schizophrenia early, as well as identify biomarkers in the blood and brain that may help predict risk.

Washington University School of Medicine in St. Louis is part of a major international study aimed at identifying causes and effects of the early stages of schizophrenia in young people, with the goal of improving early diagnosis and treatment.

The mental illness is characterized by alterations in thoughts, feelings and behaviors, which may include psychosis, a loss of contact with reality.

By studying young people at high risk of schizophrenia, the researchers plan to characterize the variety of symptoms that can help diagnose schizophrenia early, as well as identify biomarkers in the blood and brain that may help predict risk. Such information could help identify drug targets that have potential for treating schizophrenia early or even preventing problems, such as disordered thinking, that are associated with the disease.

For the study, the researchers are seeking adolescent and young adult volunteers, ages 12 to 30, who have experienced symptoms of psychosis such as hallucinations, delusions or intrusive disturbing thoughts suggesting they may be at risk for developing schizophrenia.

About 100,000 young people in the United States experience a first episode of psychosis every year, and over 1 million children and adolescents experience other problems in perception, thinking, mood and social functioning that put them at risk for schizophrenia, said Daniel Mamah, MD, an associate professor of psychiatry and the lead investigator at the Washington University clinical site. Those problems tend to get worse over time, especially when untreated, so the goal here is to identify problems at the earliest possible stage.

The Psychosis-Risk Outcomes Network (ProNET) study is funded by a grant of more than $65 million from the National Institute of Mental Health of the National Institutes of Health (NIH). Overall, the study will recruit 1,040 young people at high risk of schizophrenia at 26 sites around the world. There are 18 U.S. sites, with other sites in Canada, the United Kingdom, Italy, Spain, Germany, China and South Korea. About 50 patients will be enrolled in the study at the Washington University site.

The grant is a component of an NIH public-private partnership designed to meet the urgent need for early therapeutic interventions for people at high risk of developing schizophrenia. The effort brings together the NIH, the Food and Drug Administration, and a number of nonprofit and private universities and other organizations, including Washington University.

The groups involved are working toward the shared mission of discovering promising biological markers to help identify those at high risk for schizophrenia as early as possible, track the progression of their symptoms and other outcomes, and identify targets for treatment.

Schizophrenia is one of the leading causes of disability worldwide, but it often goes undiagnosed until symptoms have become disruptive in a persons life. Treatment delays can be associated with long-term problems, such as alcohol and drug abuse, difficulty holding a job and homelessness.

Just being at high risk of schizophrenia is increasingly recognized as a public health problem that affects adolescents and young adults, Mamah said. To develop more effective therapies, we must characterize the substantial variations of symptoms among those at risk, as well as untangle the roots of those differences.

Many experts think that by detecting schizophrenia earlier and starting treatment sooner, it may be possible to relieve, postpone or even prevent some of the long-term difficulties associated with the disorder.

Often, when doctors first see young patients who may have experienced a psychotic episode, its not possible to know whether they are on the path to more serious problems, partly because the early symptoms of schizophrenia can vary so much between individuals, Mamah said. By studying brain structure and function, psychopathology and cognition, genetics, behavior and other factors, this project is designed to identify patients at high risk so that when we have available treatments, they can begin receiving those treatments more quickly.

Mamah is director of the Washington Early Recognition Center, a Washington University clinic that treats young people experiencing the earliest signs of mental illness involving psychosis and those in early stages of psychotic disorders, such as schizophrenia and some forms of bipolar disorder.

The study is enrolling young people who may be at risk for schizophrenia after experiencing an episode of psychosis or other symptoms for example, a young person who previously was outgoing but suddenly becomes more introverted and withdrawn, who stops doing as well in school as in the past, or who begins to behave in a suspicious or paranoid manner or seems to respond to voices that no one else hears.

Young people experiencing such symptoms can be referred by doctors, parents or teachers who worry that the adolescent or young adult may be developing problems. Those under 18 must have a parents or guardians consent to participate in the study. Young men and women over age 18 who think they may qualify can refer themselves to the study. A short screening on the groups website gives young people the option to provide information if they might be interested in clinical services or in participating in the study.

Researchers will follow study volunteers for two years, assessing genetic and clinical biomarkers that may be linked to hallucinations or intrusive thoughts. The researchers also will conduct imaging studies of brain structure and function and collect blood and saliva samples. In addition, subjects will be assessed for psychopathology, language, speech and cognitive ability.

For more information about the study, call Carli Ryan at 314-362-5216, e-mail carli.ryan@wustl.edu, or visit the clinics website.

This work is supported by the National Institute of Mental Health of the National Institutes of Health (NIH). Grant number U01 MH124639.

Washington University School of Medicines 1,700 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, and is among the top recipients of research funding from the National Institutes of Health (NIH). Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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WashU part of $65 million NIH study of schizophrenia in young people Washington University School of Medicine in St. Louis - Washington University...

UTSW researchers take new approach to fight viral infections – UT Southwestern

An immunofluorescence micrograph of cells infected by RSV (RSV is green, cells are red)

DALLAS Jan. 24, 2022 A new approach that targets the cellular machinery that viruses need to reproduce rather than the virus itself appears to stem replication of a common childhood pathogen known as respiratory syncytial virus (RSV), UT Southwestern researchers report in a new study. The findings, published in Scientific Reports, could offer a novel strategy to fight this virus and others, including SARS-CoV-2, the virus responsible for the ongoing COVID-19 pandemic.

Jeffrey Kahn, M.D., Ph.D.

RSV is far and away the major respiratory pathogen in infants and children, said study leader Jeffrey Kahn, M.D., Ph.D., Professor of Pediatrics and Microbiology, Chief of the Division of Pediatric Infectious Disease at UT Southwestern, and Director of Infectious Diseases and Medical Director of Research at Childrens Medical Center Dallas. The approach weve discovered turns the tables on this virus and potentially others in a whole new way.

RSV is a leading cause of pediatric deaths worldwide, killing an estimated 160,000 children each year, according to the National Institute of Allergy and Infectious Diseases. But although 65 years have passed since its discovery, there are still no effective treatments or a vaccine. Although some promising antiviral drugs have been explored that target components of this and other viruses, explained Dr. Kahn, viruses inevitably evolve to develop resistance against these compounds.

Taking a completely new approach, Dr. Kahn and his colleagues used genetic and pharmacological inhibition to search for vulnerable cellular pathways that RSV hijacks to replicate itself. Their experiments showed that inhibiting various components of a protein network known as the mechanistic target of rapamycin (mTOR) pathway prevented RSV from replicating in human cells. They also showed that this same strategy inhibited OC43, a human coronavirus in the same viral subfamily as SARS-CoV-2.

Because some of the drugs shown to inhibit mTOR components and block viral replication in this study are already approved by the Food and Drug Administration, they could offer hope for quick approval as antivirals against RSV, SARS-CoV-2, and other viral infections if further research confirms their utility, Dr. Kahn said.

Dr. Kahn holds the Sarah M. and Charles E. Seay Chair in Pediatric Infectious Diseases.

Other scientists who contributed to this study include HoangDinh Huynh and Ruth Levitz of UTSW, and Rong Huang of Childrens Medical Center.

This research was funded by UTSWs Department of Pediatrics and the Sarah M. and Charles E. Seay Chair in Pediatric Infectious Diseases.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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UTSW researchers take new approach to fight viral infections - UT Southwestern

Promising ALS therapy moves closer to clinic – EurekAlert

NEW YORK, NY (Jan. 24, 2022)--An experimental drug, first tried at Columbia University Irving Medical Center as a last-ditch effort to help a 25-year-old woman withjuvenile ALS, is now being tested in ALS patients in a global, phase 3 clinical trial, based on promising results from a new study at Columbia.

The study found that the druginformally named jacifusenlowered levels of FUS, a toxic protein in the womans neurons and in mice with the disease.

The clinical trial will be pivotal in determining if the drug can slow the progression of the disease.

Though the drug was possibly too little, too late, to help the young woman who first received it, the study found that it had a profound effect, virtually eliminating the toxic proteins in the central nervous system and reducing the burden of FUS pathology dramatically, says study leader Neil Shneider, MD, PhD, the Claire Tow Associate Professor of Motor Neuron Disorders in the Department of Neurology and director of the Eleanor and Lou Gehrig ALS Center at Columbia University Vagelos College of Physicians and Surgeons.

Together with our animal data, this study suggests that the drug has the potential to delay or prevent ALS caused by mutant FUS before symptoms appear or slow clinical progression after disease onset.

The story of Jacifusen

Jacifusen gets its name from Jaci Hermstad, the first person to receive the drug, but it was already in development before Jaci was diagnosed with ALS.

ALS is usually associated with adults, but a rare and aggressive form of the disease can affect individuals, like Jaci, in their teens or 20s. The disease attacks the patients motor neurons, which control the bodys muscles, until the patient can no longer move or breathe unassisted.

Several years ago, researchers discovered that most adolescents and young adults with ALS have mutations in a gene calledFUS.

In a study of a series of mouse models with ALS-relatedFUSmutations published in 2016, and in another series in the current study, Shneider found that the mutant FUS protein is toxic to motor neurons, suggesting that lowering FUS levels by silencing the gene that makes the protein might protect neurons in ALS patients with the mutation.

In 2018, Shneider met Jaci, a young woman from Iowa whose identical twin sister had died of ALS caused by a genetic mutation in theFUSgene.Soon after, Jaci began to show signs and symptoms of ALS. Shneider immediately reached out to Ionis Pharmaceuticalsa leading developer of antisense therapeuticslooking for a drug that shuts down production of the FUS protein, which might slow the progression of Jacis disease. This led to the identification of ION363, a compound that effectively lowered FUS levels in the mouse brain and spinal cord and prevented disease onset in the mouse model of FUS-related ALS. However, this drughad never been tested in humans.

With remarkable speed, Shneider won special permission from the Food and Drug Administration to give the drug to Jaci through its compassionate use program, which makes experimental treatments available to seriously ill patients outside of clinical trials. There was no time to waste. People with these mutations usually die within a year of diagnosis, Shneider says.

Jaci received the first of several doses of the drug in 2019. We saw a significant slowdown in her functional decline, suggesting that the drug was working as intended, but sadly, her disease was already advanced by the time she began the treatment and she died about a year later, Shneider says.

New study suggests jacifusen eliminates toxic proteins

In his new study, published Jan. 24, 2022, in Nature Medicine, Shneider found that a single infusion of jacifusen at birth in a mouse model effectively silenced theFUSgene, reduced FUS protein levels in the brain and spinal cord, and delayed motor neuron degeneration in the miceall with no apparent side effects.

In Jaci, jacifusen also caused profound changes in the brain. Examination of Jacis brain tissue, donated by Jaci and the Hermstad family, found that treatment with the eponymous drug markedly reduced FUS protein clumpsa hallmark of the diseasein her brain cells. At a cellular level, jacifusen was extremely effective at doing what we hoped it would do, he said.

The findings, along with encouraging signs from 10 other patients who received jacifusen under the compassionate use program, convinced Ionis to sponsor a pivotalphase 3 clinical trialatColumbia and multiple other sites in the United States, Europe and Asia. The trial, led by Shneider, will enroll at least 64 patients.

This trial will determine if jacifusen is safe, and if it can effectively slow disease progression in symptomatic FUS-ALS patients.If approved, jacifusen would be the first treatment for this highly aggressive form of early-onset ALS, Shneider says.

Future studies will determine if jacifusen works if given to people with ALS-associated FUS mutationsbeforethey become symptomatic, as it did in the mouse studies.

This study is an example of truly personalized medicine in the 21stcentury.

More information

The study was published online [January 24, 2022] inNature Medicine.

The study is titled, Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis. The other contributors are:Vladislav A. Korobeynikov(CUIMC), Alexander K. Lyashchenko(CUIMC),Beatriz Blanco-Redondo(Columbia andLeipzig University, Leipzig, Germany), and Paymaan Jafar-nejad (Ionis Pharmaceuticals).

The study was supported by grants fromthe National Institute of Neurological Disorders and Stroke (R01NS106236) and the Tow Foundation. Support for the FUS ASO (ION363) expanded access program was provided by Project ALS and the ALS Association. Additional funding was provided by Nancy Perlman and Tom Klingenstein and the Judith and Jean Pape Adams Charitable Foundation.

The authors declare no competing interests.

###

Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the Vagelos College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Irving Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cuimc.columbia.edu or columbiadoctors.org.

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Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis

24-Jan-2022

The authors declare no competing interests.

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Promising ALS therapy moves closer to clinic - EurekAlert

5 Slides We’re Discussing: Gene therapy and the promise for rare disease – State of Reform – State of Reform

Gene therapies have yielded promising results for individuals experiencing rare diseases. However, these groundbreaking therapies come with their own unique set of challenges regarding who will be able to access them, how much they will cost, and how the policymaking and scientific processes will conflict as more and more therapies undergo clinical trials.

Get the latest state-specific policy intelligence for the health care sector delivered to your inbox.

Last week, we convened a panel of experts to address these questions and discuss potential solutions in our latest 5 Slides Were Watching conversation, led by State of Reforms DJ Wilson. The panel featured Danny Seiden, president & CEO of the Arizona Chamber of Commerce and Industry, Dr. Jennifer Hodge, U.S. DMD Gene Therapy Lead at Pfizer, Dr. Rafael Fonseca, chief innovation officer at Mayo Clinic, and Dr. Sharon Hesterlee, chief research officer at the Muscular Dystrophy Association.

Hesterlee brought a slide showing the prevalence of rare diseases in Arizona, noting that 5,500 Arizonans were estimated to be living with rare genetic neuromuscular diseases that were potentially treatable with gene therapy. She highlighted that Charcot-Marie-Tooth disease and Myotonic dystrophy were the most prominent, and that both diseases currently have gene therapy treatments in preclinical development.

She emphasized that ethics need to be an important part of the conversation, and that it will be critical to educate patients and families about the treatments irreversible implications as more and more therapies begin to launch.

Its a permanent change to someone. What we see in particular with parents of a child who has a pediatric disease, they are put in a very difficult position because they have to make a decision without always understanding all of the science and all of the implications.

So I think there is a huge requirement for the physician [who does the informed consent] to be very clear, and then the parents have to decide if it doesnt work, my child cannot be redosed, my child may not be eligible for another trial I think thats been a big challenge and something that weve tried to help our community in the neuro-muscular disease space navigate.

Seiden brought a slide displaying the economic benefits that would come with the increased prevalence of gene therapies. He noted that outdated systems of payment would not be applicable to this kind of treatment, and that these therapies would allow for one-time costs as opposed to a lifetime of treatment for patients with rare diseases.

When you deal with rare diseases, you need to look at it on an annualized basis over the cost of a lifetime, because gene therapy has the potential to save money and a lot of heartache for the patients and the families involved with it Arizona is one of a handful of states that allows for value-based purchasing when it comes to Medicaid contracts With the [Arizona Health Care Cost Containment System (AHCCCS)], which is by far the largest provider, theyve recognized that you have to look at patient outcomes. Its not just about that initial upfront cost.

Hodge presented a slide illustrating the unmet needs of individuals with rare diseases and the potential impacts that gene therapies can have on these individuals. She emphasized the urgent need for innovative treatments for these diseases, as 95% of rare diseases worldwide have limited or no approved treatment options, and 80% of those rare diseases have a genetic cause. She said this makes patients with rare disease collectively one of the most underserved communities in medicine today.

She said educating every organization involved in the process of developing these therapies on the stories of real patients affected by these diseases will be critical as gene therapies move through both scientific and legislative processes.

Its really to address the underlying cause of rare diseases at the root, meaning the genetics, not the symptoms It cant be a line item in a bill, it cant be something on a piece of paper that you hear about, it has to be someone telling their story [and] thinking about the patient and what theyre going through.

You can learn so much by just sitting and talking and just hearing their story, and little things that you didnt even know affected them We need to bring that to more of the audience thats involved in making some of these decisions so they can see it as more than just a line on a piece of paper when theyre deciding something.

Fonseca showed a slide explaining some specific uses of gene therapy that could potentially provide individualized, life-saving treatment to people with red blood cell diseases, as well as preventive genetic interventions for diseases like cancer.

When you think about this approach in looking at the rare disorders, it turns out that by extrapolation, a lot of the diseases that we consider common also become more and more individualized, and therefore, theyre more and more unique. More and more, we see approaches that have to be very, very much [a] tailored design for patients

To have someone who is born with [a red-blood cell disorder] return to normal red blood cell function is just enormous. This is a worldwide problem, its a problem thats associated with pain, serious medical problems, a shorter lifespan, and great expenditures for the health system, and so [Im very excited about where were at with this].

Wilson highlighted that while few gene therapies have been officially launched in the market, many are currently in pre-clinical and clinical trials and are expected to provide promising health solutions for the future.

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5 Slides We're Discussing: Gene therapy and the promise for rare disease - State of Reform - State of Reform

Worldwide Genomic Cancer Panel and Profiling Industry to 2024 – Next Generation Sequencing Fuels a Revolution – PRNewswire

DUBLIN, Jan. 24, 2022 /PRNewswire/ -- The "Genomic Cancer Panel and Profiling Markets by Cancer, by Application, by Tissue and by Gene Type with Screening potential Market Size, Forecasting/Analysis, and Executive and Consultant Guides" report has been added to ResearchAndMarkets.com's offering.

This report provides data that analysts and planners can use. Hundreds of pages of information including a complete list of Current 2021 United States Medicare Fee Payment Schedules to help understand test pricing in detail. Forecast demand for new testing regimes or technologies. Make research investment decisions. Existing laboratories and hospitals can use the information directly to forecast and plan for clinical facilities growth.

Cancer Gene Panels and Genomic Profiling are quickly changing the diagnosis and treatment of cancers. The market is moving out of a specialized niche and going mainstream as Oncologists begin routinely using information on the hundreds of genes related to cancer. The market is exploding as physicians use all the information they can get in the battle against cancer.

While Pharmaceutical Companies see the potential to make nearly any therapy viable. The report has data on how test volumes have grown for the biggest players. Find out how this new way of understanding cancer will change cancer diagnostics forever.

Comprehensive panels, genomic profiling, high risk breast cancer panels. Learn all about how players are jockeying for position in a market that is being created from scratch. And some players are pulling way out in front and expanding globally. It is a dynamic market situation with enormous opportunity where the right diagnostic with the right support can command premium pricing. And the science is developing at the same time creating new opportunities with regularity. And the cost of sequencing continues to fall.

Key Topics Covered:

1 Market Guides1.1 Cancer Panel Market - Strategic Situation Analysis & COVID Update1.2 Large Comprehensive Cancer Panel Market - Situation Analysis1.3 Guide for Executives, Marketing, Sales and Business Development Staff1.4 Guide for Management Consultants and Investment Advisors1.5 Market Size and Shares - Large Comprehensive

2 Introduction and Market Definition2.1 What are Cancer Gene Panels and Profiling?2.2 The Sequencing Revolution2.3 Market Definition2.3.1 Revenue Market Size2.4 Methodology2.4.1 Authors2.4.2 Sources2.5 A Spending Perspective on Clinical Laboratory Testing2.5.1 An Historical Look at Clinical Testing

3 Market Overview3.1 Players in a Dynamic Market3.1.1 Academic Research Lab3.1.2 Diagnostic Test Developer3.1.3 Instrumentation Supplier3.1.4 Distributor and Reagent Supplier3.1.5 Independent Testing Lab3.1.6 Public National/regional lab3.1.7 Hospital lab3.1.8 Physician Office Labs3.1.9 Audit Body3.1.10 Certification Body3.2 Oncogenomics3.2.1 Carcinogenesis3.2.2 Chromosomes, Genes and Epigenetics3.2.2.1 Chromosomes3.2.2.2 Genes3.2.2.3 Epigenetics3.2.3 Cancer Genes3.2.4 Germline vs Somatic3.2.5 Gene Panels, Single Gene Assays and Multiplexing3.2.6 Genomic Profiling3.2.7 The Comprehensive Assay3.2.8 Changing Clinical Role3.2.9 The Cancer Screening Market Opportunity3.3 Cancer Management vs. Diagnosis3.3.1 The Role of Risk Assessment3.3.2 Diagnosis3.3.3 Managing3.3.4 Monitoring3.4 Phases of Adoption - Looking into The Future3.5 Structure of Industry Plays a Part3.5.1 Hospital Testing Share3.5.2 Economies of Scale3.5.2.1 Hospital vs. Central Lab3.5.3 Physician Office Lab's3.5.4 Physician's and POCT3.6 Currently Available Large Comprehensive Assays3.7 Pricing Profiling vs. Whole Exome (or Genome) Sequencing3.7.1 Medicare Profile Pricing3.7.2 Whole Exome Sequencing

4 Market Trends4.1 Factors Driving Growth4.1.1 Level of Care4.1.2 Companion Dx4.1.3 Immuno-oncology4.1.4 Liability4.1.5 Aging Population4.2 Factors Limiting Growth4.2.1 State of knowledge4.2.2 Genetic Blizzard4.2.3 Protocol Resistance4.2.4 Regulation and coverage4.3 Instrumentation and Automation4.3.1 Instruments Key to Market Share4.3.2 Bioinformatics Plays a Role4.4 Diagnostic Technology Development4.4.1 Next Generation Sequencing Fuels a Revolution4.4.2 Single Cell Genomics Changes the Picture4.4.3 Pharmacogenomics Blurs Diagnosis and Treatment4.4.4 CGES Testing, A Brave New World4.4.5 Biochips/Giant magneto resistance based assay

5 Cancer Panels & Profiles Recent Developments5.1 Recent Developments - Importance and How to Use This Section5.1.1 Importance of These Developments5.1.2 How to Use This Section5.2 Dante Labs Acquires Cambridge Cancer Genomics5.3 Celemics, Strand Partner on Integrated Platform for NGS Analysis5.4 Myriad Genetics Recalibrates Breast Cancer Panel for All Ancestries5.5 Burning Rock Revenues Rise5.6 Caris Life Sciences to Expand Liquid Biopsy Testing5.7 OncoDiag Announces Multiplex Test for Bladder Cancer Recurrence5.8 Intermountain and Myriad Combine Test Offering5.9 Illumina, Geneseeq to Offer Cancer Testing Kits in China5.10 Exact Sciences to Offer End-to-End Cancer Testing5.11 Guardant Health Turns to Tumor Tissue Sequencing5.12 Tempus Inks Oncology Testing Collaboration With Bayer5.13 Biocartis Collaborating With GeneproDx, Endpoint Health on Tests for Idylla Platform5.14 Wales to Routinely Screen Cancer Patients With Yourgene Elucigene Test5.15 Metastatic Cancer Markers Identified in Clinical WGS Study5.16 Stitch Bio Bets on CRISPR Tech5.17 Bayer, LifeLabs Launch Free NTRK Genetic Testing Program5.18 Foundation Medicine Liquid Biopsy Gets FDA Approval for Multiple Companion Dx5.19 Progress, Challenges in Liquid Biopsy Reimbursement5.20 Israeli Startup Curesponse Raises $6M5.21 Invitae, ArcherDX Merge to Advance Precision Oncology Offerings5.22 MD Anderson Precision Oncology Decision Support to Use Philips' Informatics Solution5.23 NeoGenomics, Lilly Oncology Partner for Thyroid Cancer Testing Program5.24 Germline Results Guides Precision Therapy in Advanced Cancer5.25 FDA Clears Cancer Genomic Profiling Kit From Personal Genome Diagnostics5.26 ArcherDX, Premier Collaborate to Evaluate Genomic Sequencing Assay for Cancers5.27 Labs Reporting Cancer Risk Mutations from Tumor Testing5.28 Users Begin Integrating Genomics Data for Clinical Decision Support5.29 Fujitsu Improves Efficiency in Cancer Genomic Medicine5.30 Thermo Fisher's automated sequencer to offer same-day, pan-cancer test results5.31 Universal Genetic Testing for All Breast Cancer Patients5.32 Exact Sciences buys Genomic Health5.33 Multi-Gene Liquid Biopsy Breast Cancer Panel5.34 Thrive to Develop Earlier Detection of Multiple Cancer Types5.35 New Gene Panel Identifies High Risk Prostate Cancer5.36 Guardant Health Liquid Biopsy Test to be Covered by EviCore5.37 Biocept Partnership Offering for Liquid Biopsy Adds Several Key Services5.38 Natera Commercializes Tumor Whole Exome Sequencing from Plasma5.39 Inivata Completes 39.8M Series B Funding Round5.40 Bio-Rad Clinical ddPCR Test, Diagnostic System Get FDA Clearance5.41 CellMax, Medigen Biotech Partner in Colorectal Cancer Clinical Trials5.42 Biodesix Acquires Integrated Diagnostics5.43 Predicine, Kintor Pharmaceuticals Partner on Clinical Trials, CDx

6 Profiles of Key Players6.1 10x Genomics, Inc6.2 Abbott Diagnostics6.3 AccuraGen Inc6.4 Adaptive Biotechnologies6.5 Aethlon Medical6.6 Agena Bioscience, Inc6.7 Agilent/Dako6.8 Anchor Dx6.9 ANGLE plc6.10 ApoCell, Inc.6.11 ArcherDx, Inc6.12 ARUP Laboratories6.13 Asuragen6.14 AVIVA Biosciences6.15 Baylor Miraca Genetics Laboratories6.16 Beckman Coulter Diagnostics6.17 Becton, Dickinson and Company6.18 BGI Genomics Co. Ltd6.19 Bioarray Genetics6.20 Biocartis6.21 Biocept, Inc6.22 Biodesix Inc6.23 BioFluidica6.24 BioGenex6.25 BioIVT6.26 Biolidics Ltd6.27 bioMerieux Diagnostics6.28 Bioneer Corporation6.29 Bio-Rad Laboratories, Inc6.30 Bio-Reference Laboratories6.31 Bio-Techne6.32 Bioview6.33 Bolidics6.34 Boreal Genomics6.35 Bristol-Myers Squibb6.36 Burning Rock6.37 Cancer Genetics6.38 Caris Molecular Diagnostics6.39 Castle Biosciences, Inc.6.40 Celemics6.41 CellMax Life6.42 Cepheid (Danaher)6.43 Charles River Laboratories6.44 Chronix Biomedical6.45 Circulogene6.46 Clinical Genomics6.47 Cynvenio6.48 Cytolumina Technologies Corp6.49 CytoTrack6.50 Datar Cancer Genetics Limited6.51 Diagnologix LLC6.52 Diasorin S.p.A6.53 Enzo Life Sciences, Inc6.54 Epic Sciences6.55 Epigenomics AG6.56 Eurofins Scientific6.57 Exact Sciences6.58 Exosome Diagnostics6.59 Exosome Sciences6.60 Fabric Genomics6.61 Fluidigm Corp6.62 Fluxion Biosciences6.63 Foundation Medicine6.64 Freenome6.65 FUJIFILM Wako Diagnostics6.66 GeneFirst Ltd.6.67 Genetron Holdings6.68 GenomOncology6.69 GILUPI Nanomedizin6.70 Grail, Inc.6.71 Guardant Health6.72 HalioDx6.73 HansaBiomed6.74 HeiScreen6.75 Helomics6.76 Horizon Discovery6.77 HTG Molecular Diagnostics6.78 iCellate6.79 Illumina6.80 Incell Dx6.81 Inivata6.82 Integrated Diagnostics6.83 Invitae Corporation6.84 Invivogen6.85 Invivoscribe6.86 Janssen Diagnostics6.87 MDNA Life SCIENCES, Inc6.88 MDx Health6.89 Menarini Silicon Biosystems6.90 Millipore Sigma6.91 Miltenyi Biotec6.92 MIODx6.93 miR Scientific6.94 Molecular MD6.95 MyCartis6.96 Myriad Genetics/Myriad RBM6.97 NantHealth, Inc.6.98 Natera6.99 NeoGenomics6.100 New Oncology6.101 NGeneBio6.102 Novogene Bioinformatics Technology Co., Ltd.6.103 Oncocyte6.104 OncoDNA6.105 Ortho Clinical Diagnostics6.106 Oxford Nanopore Technologies6.107 Panagene6.108 Perkin Elmer6.109 Personal Genome Diagnostics6.110 Personalis6.111 Precipio6.112 PrecisionMed6.113 Promega6.114 Qiagen Gmbh6.115 Rarecells SAS6.116 RareCyte6.117 Roche Molecular Diagnostics6.118 Screencell6.119 Sense Biodetection6.120 Serametrix6.121 Siemens Healthineers6.122 Silicon Biosystems6.123 simfo GmbH6.124 Singlera Genomics Inc6.125 Singulomics6.126 SkylineDx6.127 Stratos Genomics6.128 Sysmex Inostics6.129 Tempus Labs, Inc6.130 Thermo Fisher Scientific Inc6.131 Thrive Earlier Detection6.132 Todos Medical6.133 Trovagene6.134 Variantyx6.135 Volition6.136 Vortex Biosciences

7 The Global Market for Cancer Gene Panels and Profiles

8 Global Cancer Gene Panels & Profiles Markets - By Type of Cancer

9 Global Cancer Gene Panels & Profiles Markets - By Type of Application

10 Global Cancer Gene Panels & Profiles Markets - By Tissue Type

11 Global Cancer Gene Testing Markets - Germline and Somatic11.1 Global Market Somatic11.1.1 Table Somatic - by Country11.1.2 Chart - Somatic Testing Growth11.2 Global Market Germline11.2.1 Table Germline - by Country11.2.2 Chart - Germline Testing Growth

12 Potential Market Opportunity Sizes12.1 Potential Cancer Screening by Country: Lung, Breast & Colorectal12.2 Potential Cancer Screening by Country: Prostate, Other Cancer & All Cancer12.3 Potential Market Size - Cancer Diagnosis12.4 Potential Market Size - Therapy Selection

13 Appendices

For more information about this report visit https://www.researchandmarkets.com/r/qwgvdr

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1904 Fax (outside U.S.): +353-1-481-1716

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Worldwide Genomic Cancer Panel and Profiling Industry to 2024 - Next Generation Sequencing Fuels a Revolution - PRNewswire

Genetic Research Shows Rapid Immune Response in Children Protects Them From COVID-19 – SciTechDaily

Discovery of importance of interferon response in preventing serious infection will underpin new diagnostics and therapeutics.

Fundamental differences in the immune response of adults and children can help to explain why children are much less likely to become seriously ill from SARS-CoV-2, according to new research from the Wellcome Sanger Institute, University College London, and their collaborators.

The study, published in the journal Nature, is the most comprehensive single-cell study to compare SARS-CoV-2 infection in adults and children across multiple organs. Researchers found that a stronger innate immune response in the airways of children, characterized by the rapid deployment of interferons, helped to restrict viral replication early on. In adults, a less rapid immune response meant the virus was better able to invade other parts of the body where the infection was harder to control.

As part of the Human Cell Atlas1 initiative to map every cell type in the human body, the findings will be a valuable contribution to predict personal risk from SARS-CoV-2. A nasal swab to measure the immune response in newly infected adults could be used to identify those at higher risk who may be candidates for pre-emptive monoclonal antibody treatment. Recent research has also suggested inhalation of interferons could be a viable therapy2.

The immune system that we are born with is not the same as the one we have as adults. The innate immune system of children is better able to recognize dangerous viruses or bacteria automatically, triggering nave B and T cells that can adapt to the threat. Adults have a more adaptive immune system containing a huge repertoire of memory B and T cell types, which have been trained through past exposure to respond to a particular threat3. Though the adult immune system also has an innate response, it is more active in children.

One of the key mechanisms of both immune systems is a group of proteins called interferons, which are released in the presence of viral or bacterial threats and tell nearby cells to tighten their defenses. Interferons are proteins with strong anti-viral activity and their production will typically lead to the activation of B and T cells, which kill infected cells and prevent the pathogen from spreading further.

For this study, researchers at University College London (UCL) and affiliated hospitals4 collected and processed matched airway and blood samples from 19 pediatric and 18 adult COVID-19 patients with symptoms ranging from asymptomatic to severe, as well as control samples from 41 healthy children and adults.

Single-cell sequencing of the samples was done at the Wellcome Sanger Institute to generate a dataset of 659,217 individual cells. These cells were then analyzed, revealing 59 different cell types in airways and 34 cell types in blood, including some never previously described.

Analysis showed that interferons were more strongly expressed in healthy children compared to adults, with a more rapid immune response to infection in childrens airways. This would help to restrict viral replication early on and give children an immediate advantage in preventing the virus from infecting the blood and other organs.

Because SARS-CoV-2 is a new virus, it isnt something that the adaptive immune system of adults has learned to respond to. The innate immune system of children is more flexible and better able to respond to new threats. What we see at a molecular level are high levels of interferons and a very quick immune response in children that helps to explain why they are less severely affected by COVID-19 than adults.

Dr. Masahiro Yoshida, University College London

The study also detailed how the immune system of adults, with its high numbers of killer immune cells such as B and T cells, can work against the body once SARS-CoV-2 has spread to other parts of a patient.

Compared to children, adult blood has a greater number and variety of cytotoxic immune cells, which are designed to kill infected cells to prevent an infection spreading. But it is a fine line between helping and hindering. Once the virus has spread to several areas of the body, organ damage can be caused by the immune system trying and failing to control the infection. Our study shows that not only do children respond better initially, if the virus does enter the blood the cytotoxic response is less forceful.

Dr. Marko Nikolic, University College London

Knowing exactly how and why the immune response to SARS-CoV-2 can fail to control the infection or start to harm the body provides scientists with the means to start asking why certain individuals may be at greater risk of serious illness.

These data suggest that newly diagnosed adults could be tested to check interferon levels in the airway. Higher interferon levels, similar to those found in children, would suggest a lower risk of severe disease, whereas low interferon levels would suggest higher risk. Higher risk patients could then be considered for pre-emptive treatments such as monoclonal antibodies, which are expensive and can be in limited supply.

To put it simply, the innate immune response is better at fighting COVID-19 and children have stronger innate immunity, but immunity is also a complex ballet involving many types of cells. The timing and the types of cells that are triggered will influence how an infection develops, and this will vary between individuals for all sorts of reasons in addition to age. Some of the differences we observe between children and adults may help us to think about how we gauge personal risk for adults as a way of mitigating serious illness and death.

Dr. Kerstin Meyer, Wellcome Sanger Institute

In addition, there is growing evidence of the therapeutic benefits of inhaled interferon beta 1a. Based on the study results, this should be particularly the case for patients with weak or absent interferon activation.

The results are insightful not only for addressing COVID-19, but more broadly for understanding changes in the airway and blood throughout childhood. They demonstrate the power of single-cell resolution to reveal differences in the biology of children and adults, while pointing to very different considerations when thinking about how a specific disease arises and may be treated.

Jonah Cool, Chan-Zuckerberg Initiative

Reference: Local and systemic responses to SARS-CoV-2 infection in children and adults by Masahiro Yoshida, Kaylee B. Worlock, Ni Huang, Rik G. H. Lindeboom, Colin R. Butler, Natsuhiko Kumasaka, Cecilia Dominguez Conde, Lira Mamanova, Liam Bolt, Laura Richardson, Krzysztof Polanski, Elo Madissoon, Josephine L. Barnes, Jessica Allen-Hyttinen, Eliz Kilich, Brendan C. Jones, Angus de Wilton, Anna Wilbrey-Clark, Waradon Sungnak, J. Patrick Pett, Juliane Weller, Elena Prigmore, Henry Yung, Puja Mehta, Aarash Saleh, Anita Saigal, Vivian Chu, Jonathan M. Cohen, Clare Cane, Aikaterini Iordanidou, Soichi Shibuya, Ann-Kathrin Reuschl, Ivn T. Herczeg, A. Christine Argento, Richard G. Wunderink, Sean B. Smith, Taylor A. Poor, Catherine A. Gao, Jane E. Dematte, NU SCRIPT Study Investigators, Gary Reynolds, Muzlifah Haniffa, Georgina S. Bowyer, Matthew Coates, Menna R. Clatworthy, Fernando J. Calero-Nieto, Berthold Gttgens, Christopher OCallaghan, Neil J. Sebire, Clare Jolly, Paolo de Coppi, Claire M. Smith, Alexander V. Misharin, Sam M. Janes, Sarah A. Teichmann, Marko Z. Nikolic and Kerstin B. Meyer, 22 December 2021, Nature.DOI: 10.1038/s41586-021-04345-x

This research was funded by Wellcome, the Chan Zuckerberg Initiative, Rosetrees Trust, Action Medical Research, Medical Research Council and the European Unions Horizon 2020 program.

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Genetic Research Shows Rapid Immune Response in Children Protects Them From COVID-19 - SciTechDaily

British Labs Supply the World with Genetic Information about COVID-19 – VOA Learning English

British scientists have created a fast, less costly process for genome sequencing each coronavirus case they examine.

Britain is now a world leader in COVID-19 sequencing. This helps public health officials follow the spread of new variants, develop vaccines and decide when restrictions on movement are necessary.

Researchers at the Sanger Institute in Cambridge and other laboratories in Britain have a new mission. They are sharing what they have learned with scientists around the world.

The Omicron variant now spreading in many countries shows the need for worldwide cooperation, said Ewan Harrison. He is a top researcher at Sanger.

Omicron was first found by scientists in southern Africa who quickly informed the world and gave officials time to prepare.

Since dangerous mutations of the virus can happen anywhere, scientists must continually watch its development to protect everyone, Harrison said.

We cant just kind of put a fence around an individual country or parts of the world, because thats just not going to cut it, he said.

Cambridge University Professor Sharon Peacock understood the importance of sequencing the virus early in the pandemic. She knew sequencing would be important to fighting the virus. She received British government money for a national organization of scientists, laboratories and testing centers known as the COVID-19 Genomics UK Consortium.

The consortium is now working to increase knowledge of sequencing around the world. It has built training programs for researchers in developing countries. The programs include planned online classes on information sharing and working with public health officials. The goal is to help researchers build national programs to sequence COVID-19 viruses.

There is inequity in access to sequencing worldwide, the group said, adding that it wants to end the unequal situation.

By sequencing as many cases of the virus as possible, researchers hope to identify variants of concern as quickly as possible. They can then follow their spread and give early warnings to health officials.

Britain has supplied more COVID-19 sequences to researchers around the world than any country other than the United States. It has also sequenced a bigger percentage of its cases than any large nation.

Researchers in Britain have released about 1.68 million sequences, or about 11 percent of reported cases, said GISAID. GISAID is an international organization that works for quick sharing of virus information.

Over the past two years, labs around Britain have refined the process of gathering and studying COVID-19 viruses.

This has helped cut the cost of examining each genome by 50 percent. It has also reduced the time is takes to sequence from three weeks to five days, said the research group Wellcome Sanger.

Increasing sequencing ability is like building a pipeline, said Dr. Eric Topol. He is head of innovative medicine at Scripps Research in San Diego, California. In addition to buying costly sequencing machines, countries need supplies of reactive chemicals for the machines. They also need trained people to do the work and who understand the sequences. They also need systems to share the information quickly.

Meeting those needs has been difficult for many nations, including the U.S. It is even harder for developing nations, Topol said.

Many of these low- and middle-income countries dont have the sequencing capabilities, particularly with any reasonable turnaround time, he said. So, the idea that theres a helping hand there from the Wellcome Center is terrific. We need that.

Virus samples arrive from around the country. Lab assistants carefully prepare the genetic material. It is placed into the sequencing devices that read each samples unique DNA. Scientists then examine the information and compare it with other identified genomes to follow mutations. They want to see how the virus is developing.

Because COVID-19 mutates all the time, it is important to look for new, more dangerous variants that might be resistant to vaccines, Harrison said. This information will help researchers change existing vaccines or create new ones to fight the virus.

Harrison praised South Africa for quickly informing the world about the Omicron variant. But other countries, he said, punished South Africa by restricting travel and harming its economy. All nations must be permitted to publish new variant information without fear of being punished, he said.

Im Susan Shand.

The Associated Press reported this story. Susan Shand adapted it for Learning English.

__________________________________________

genome n. the entire set of genetic instructions found in a cell

sequencing n. a process of finding out the order of the amino acids forming the genetic material of an organism

variant n. something that is different in some way from others of the same kind

mutation n. a permanent change in the genes of an organism

consortium n. a group of people or companies that agree to work together

access n. the ability to get something, enter a place or meet someone

refine v. to improve (something) by making small changes

sample n. a small amount of something that is used to give information about what it was taken from

unique adj. used to say that something or someone is unlike anything or anyone else

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British Labs Supply the World with Genetic Information about COVID-19 - VOA Learning English

Xenotransplantation and the future of medicine – Hindustan Times

Amid surging Covid-19 infections driven primarily by the Omicron variant comes news of the remarkable achievement by United States (US) surgeons who implanted a heart from a genetically modified pig into a 57-year-old recipient, David Bennett, who suffered from ventricular fibrillation (a kind of heart abnormality) and had advanced heart failure. The historic procedure performed on January 7 at the University of Maryland School of Medicine (UMSOM) is a major milestone in the field of xenotransplantation the exchange of organs among species, chiefly from pigs to humans.

According to Muhammad Mohiuddin, chief of the cardiac transplantation programme at UMSOM, Bennett urgently needed a transplant and was declared ineligible for a human organ; therefore, a decision was taken to try a xenograft from a pig. The transplant team obtained compassionate use authorisation from the US Food and Drug Administration, and the organ was made available by Revivicor, a US-based biotech company. The team already had years of experience with xenografting pig hearts into baboons with a fair degree of success and were well suited to try out the exercise in humans. In 2016, they had reported that a pig heart was kept functioning in a baboon for three years.

Xenotransplantation uses animals as a source of organs for replacement therapy in humans whose own natural organs have reached the end-stage of function. Since there is always a big gap between those needing a functioning organ (chiefly heart, kidney, liver, lungs and pancreas) and the availability of the same from humans, alternative sources of donor organs have long been an unmet need.

The most significant issue with using animals as a source of transplanted organs for humans is the spontaneous immunological rejection due to the occurrence of specific antibodies produced by the human host against certain sugars present on the surface of pig cells. These get recognised as foreign, leading to hyperacute rejection in which the recipient begins to reject the organ as soon as it is implanted.

In terms of evolution, pigs and humans are quite divergent, and the major challenges are both immunological and pathophysiological. The fundamental difference is while the human system expresses the well-known ABH blood group antigens, the pigs vascular endothelium expresses a unique protein called Galactose oligosaccharide or Gala1 or simply Gal. Humans are a natural knockout for this protein that quickly triggers anti-Gal antibodies against the transplanted organ.

In recent years, significant progress has been made to genetically modify the developing piglets, rendering their tissues and organs resistant to human immune response. The creation of Dolly the sheep as the first cloned animal in 1996 provided the much-needed stimulus to do so. In their effort to create a clinical-grade facility for raising engineered pigs, Revivicor scientists produced genetic changes in a total of 10 genes: Three in the pig and seven in humans. They successfully knocked out three genes from pigs that enable the enzymes to synthesise Gal sugars, and thus minimise the formation of anti-Gal antibodies.

Simultaneously, they engineered six genes in the human host with the aim of decreasing inflammation (two genes) and blood coagulation, thereby preventing blood vessel damage (two genes) and also silenced another two regulatory proteins that promote antibody response. The final step was something that they had learnt during baboon experimentation and this included knocking out the gene for a growth hormone that ensured that the pig organ remained matched in size with the patients chest and did not outgrow upon grafting.

Two weeks have passed and the pig heart is still functioning in Bennett, making the surgical feat a remarkable achievement. However, the question of whether we have reached the stage for regular use of pig organs for transplantation in humans is still open. More science is needed to determine which modifications are critical and perhaps inescapable. It is also not clear whether different modifications may be required for different organs. For example, could there be differences for kidney versus heart and likewise for other organs? Another major barrier with xenotransplantation is the possibility of endogenous retroviruses carried by pigs and these could create safety concerns.

The other question relates to the type and extent of immunosuppression needed for the recipient because of the possibility of excessive anti-organ-specific antibodies generated in the host. While the standard immunosuppressive regimens may or may not be effective, it would be necessary to investigate immunological tools to suppress the activity of antibody-forming B-cells and inhibit their cross-talk with helper T-cells that effectively coordinate the host immune response.

While there are several issues associated with xenotransplantation, both for the recipient and society at large, the first really successful pig-to-human heart transplant achieved through the meticulous use of the tools of genetic engineering represents a significant step forward in solving the problem of organ shortage, bringing hope to those in desperate need of a transplant.

Dr Narinder Kumar Mehra is an internationally acclaimed expert in transplant immunology and former Dean of the All India Institute of Medical Sciences, New Delhi

The views expressed are personal

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Xenotransplantation and the future of medicine - Hindustan Times

Which Drugs Will Survive Climate Change? We Investigated. – VICE

You might have to experience the end of the world sober, after all.

Thats because climate change will unleash havoc on the world of drugs. And it may be a whole lot tougher on the most mainstream stimulantsgrocery store stuff like coffee, beer and winethan on hardcore illicit narcotics like heroin, cocaine and meth.

Some of those more-powerful, more-addictive, mind-altering substances appear relatively better prepared to survive the oncoming climate crisis than the vulnerable plants responsible for producing traditionally legal recreational highs, according to a review of recent scientific studies and interviews with experts on climate and agriculture by VICE News.

Heroin, for example, is already getting a boost from climate change. One study shows that rising levels of atmospheric carbon dioxide have doubled the potency of poppies, the plant used to make the drug. Wine, by contrast, is under serious threat, as changing weather patterns and raging wildfires put celebrated vineyards in jeopardy.

All plant-based drugs, whether theyre narcotics or used for medicine, are going to change, Lewis Ziska, lead author of the poppy study and now an associate professor of environmental health sciences at Columbia Universitys Mailman School of Public Health, told VICE News. In fact, the world is changing faster than our ability to describe the changes.

Though big questions remain about how climate change will impact agriculture, and experts caution that much research remains to be done, long-term agricultural consequences are just starting to come into view.

The short version: The drug world is facing a big shake-up.

To make this easier, we put the results into an oversimplified but handy-dandy chart.

For a more detailed picture, read on.

BEER: DOUBLE THE PRICE

Get ready to pay more for brew.

Climate change might make beer twice as expensive, according to a 2018 study. In Ireland, one of the heaviest beer-drinking countries in the world, the price could triple.

Thats because the cost of a key ingredient, malted barley, could soar as global average temperatures rise and barley becomes harder to grow.

The price of a six-pack in the United States might rise by as much as $8 on average, the study found.

Pricey beer is just another way climate change will suck, tweeted Steven J. Davis, one of the authors of the study.

WINE: A HINT OF ASHTRAY

Wine is decidedly in trouble.

At least, the good stuff is: Those who savor the fine distinctions between a pinot noir and a cabernet sauvignon, or a Bordeaux and a Chateauneuf-du-pape, are going to hate the future.

The world may still be able to produce the same amount of wine as before. But the quality, taste and variety of wines will change, said Benjamin Cook, a NASA climate scientist who has studied the impact of climate change on wine-growing regions.

You can grow wine grapes almost anywhere and make wine with them. Thats why you can go to Trader Joes and get 4-buck chuck, Cook told VICE News. Wine that has these characteristics that make it famous and expensive and high value, thats where the impacts are going to potentially be very severe.

Those nuances depend on the regional mix of weather, rainfall, temperature and humidityall of which will be thrown into chaos. Warmer wine-growing regions, like Australia and California, will be particularly hard hit, Cook said.

California vineyards are especially threatened by the recent surge of climate change-linked wildfires. Grapes that escape the flames can absorb chemicals from smoke that ruin their taste, leaving the dreaded smoke taint. Some winemakers complain that smoke exposure is giving their wine an ashy finish, according to The Washington Post.

Others are reaching for solutions. Kwaw Amos, owner of New Yorks Gotham Winery, blends traditional European grapes with hardier American varieties to create hybrids with better protection against heat, fungus and early budding.

The concept of hybrids is nothing new in grape growing, Amos told VICE News. Cabernet sauvignon is a hybrid. Its just now youre thinking about the next level hybrids that were going to need given whats happening.

COFFEE: DARK TIMES

Coffee is in danger.

About half of all land now used to grow the two main species of coffee, arabica and robusta, may no longer be usable by 2050, according to one estimate. Arabica and robusta make up 99 percent of the commercial supply globally, and have a limited ability to relocate to different climates.

Another study found that six-in-ten of the known species of coffee are now under threat of extinction. Experts believe higher temperatures encourage pesky fungus growth on coffee beans. Changes in rainfall patterns may also put an added stress on the plants.

Good coffee will probably become increasingly harder to grow. And that could become a global economic issue, considering the industry employs over 125 million people, including farmers, distributors and brewers. And, like beer, coffee could also get more expensive.

U.S. consumers should expect much more expensive and lower-quality coffee because of rising temperatures, extreme rainfalls, and higher frequency of severe droughts, Titus O. Awokuse, who chairs the department of agricultural, food and resource economics at Michigan State University, recently told the LA Times.

COCAINE: FINE, THANKS

Coca, the plant responsible for cocaine, is notoriously difficult to get rid of. And that likely means it will survive pretty well compared to more-vulnerable plants.

Charles Helling, a scientist who studied the crop as a soil chemist with the U.S. Department of Agriculture, has said he thinks higher temperatures wont be harmful, and that they may just encourage the plant to grow at even higher elevations.

"Coca is kind of unique, because it's got a very heavy wax cuticle, a layer on the leaves," Helling told Scientific American. "So that tends to protect it from water loss. It's a pretty hardy shrub. It's actually a lot hardier than a typical crop plant."

Another factor in cocas favor may be genetic diversity. Plants that have been extensively cultivated in mainstream agriculture tend to become more genetically homogeneous, Ziska said. Whereas plants that have thrived in the wildnot to mention, survived sustained attempts at eradicationmay demonstrate greater genetic variability that helps them respond more flexibly to a changing environment.

Its still unclear whether coca would benefit from such an advantage.

HEROIN: AS YOU LIKE IT

Poppy plants, as noted above, have already become twice as potent in natural morphine as they were in the middle of last century, thanks to rising levels of atmospheric carbon dioxide, or C02, the gas thats principally responsible for climate change, according to one study.

That study was performed in 2008, and atmospheric C02 has only continued to rise since. Pumping even more of that gas into the air may triple morphine levels by 2050, and increase potency by a factor of 4.5 by the year 2090, according to the same study.

Ziska said the reason isnt yet completely certain. But he said one theory suggests that when a given resource becomes more prevalent in an environment, plants will tend to produce more secondary compounds that are rich in that resource, and that this dynamic explains why rising atmospheric CO2 prompts poppy plants to produce more morphine.

Poppy also has another advantage that makes the plant well-suited to a drier climate: Its particularly drought-resistant.

The poppy's hardiness has enabled growers in Afghanistan, a narcostate which provides 90% of the worlds opium, to notch record harvests over the last decade.

CANNABIS: ITS COMPLICATED

Weed will probably be okaymostly.

The plant is likely well-suited to survive a moderately hotter and drier climate, according to Olufemi Ajayi, the author of a recent study on the relative dangers posed by insect pests to cannabis in the context of climate change.

But, he cautioned, only within limits. More extreme temperatures and droughts will stunt growth, or kill plants, he said.

Another 2011 study on the impact of higher concentrations of carbon-dioxide found that the plant may be able to survive under expected harsh greenhouse effects including elevated CO2 concentration and drought conditions.

Cannabis does have an otherwise unsavory link to environmental degradation, however (as do a lot of drugs: see our previous reporting here).

Indoor growing operations have spread rapidly along with broadening legalization, and they take a lot of electricity.

One estimate states that growing one ounce of cannabis indoors can emit as much greenhouse gas as burning through a large cars entire tank of gasolineor 7 to 16 gallons.

Most U.S. cannabis is grown indoors. As the industry expands, its energy consumption is expected to rise, too. In Colorado, emissions from cannabis farms already exceed those from the states coal mining industry.

In other words, weeds relationship to global warming is complex. Even if cannabis is well-positioned to withstand a moderately warmer climate, its own energy use and outsized carbon footprint will need to be accounted for if the world ever gets serious about reducing emissions.

SYNTHETIC DRUGS: FINE

The world of synthetic, lab-based drugs will likely see hardly any impact from climate change, experts including Ziska said. This is because theyre made in a lab, not grown in a field.

This diverse galaxy of stimulantswhich includes MDMA, speed, meth, LSD, synthetic cannabinoids, mephedrone, fentanyl, carfentanyl, and many morewill be relatively unaffected because much of it is far less dependent on the growth of specific agricultural crops.

Synthetic opioids, especially, have been responsible for a tidal wave of recent overdose deaths. The U.S. Centers for Disease Control estimates that 36,000 people died from synthetic opioid overdose in the U.S. in 2019, including from fentanyl, a drug 80-to-100 times stronger than morphine.

So as you contemplate the end of the world, just remember that coffee and beer may be in ever-shorter supply and growing more expensive within a few decadesbut that the worlds supply of killer fentanyl may be just as robust as ever.

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Which Drugs Will Survive Climate Change? We Investigated. - VICE

Sema4 : The Positives (and Negatives) of Medical Testing – marketscreener.com

In its recent article, "When They Warn of Rare Disorders, These Prenatal Tests Are Usually Wrong,"The New York Times published a discussion on the performance of prenatal blood screening tests. The piece, which also looked at the potential impact of results on patients, has fueled an online debate on medical ethics and misinformation. As a patient-centered health intelligence company with deep expertise in reproductive health and medical testing, we see this as a perfect opportunity to inform our partners on population health topics to help them better understand the accuracies (and inaccuracies) of clinical testing. In this guide, we aim to educate readers about the differences between screening and diagnostic tests and, crucially, why "positive" screening results should be interpreted as "further testing is recommended" and "negative" results as "no abnormalities detected; no further testing recommended."

Screening vs. diagnostic testing

Medical tests look for answers to specific health questions. Screening tests are performed to evaluate the risk of having a disease now or in the future, while diagnostic tests are performed to pinpoint the cause of a disease process and narrow down a diagnosis. Diagnostic tests also tend to be more invasive, associated with some risk, and costly. Screening tests, on the other hand, provide a cost-effective way to identify individuals at higher risk of disease, shifting the benefit-to-risk ratio to justify diagnostic testing and invasive treatments. The goal of screening tests is early diagnosis for early intervention: they provide valuable information that can indicate when diagnostic testing is needed. After diagnostic testing, an early diagnosis can help minimize long-term adverse health outcomes and optimize potential treatment options.

Noninvasive prenatal testing, or NIPT, is a blood-based screening test for expectant mothers. It evaluates the risk of fetal anomalies caused by certain chromosomal aberrations, such as aneuploidies (extra or missing chromosomes) and microdeletions (missing portions of chromosomes). Professional medical societies like the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) recommend that all pregnant women be offered prenatal screening or diagnostic testing for common aneuploidies to provide expectant parents with information about their pregnancy's risk of a genetic condition. After informed discussions with their healthcare providers about the benefits and risks of prenatal screening, this information can help parents prepare for potential complications at birth since conditions like Patau syndrome and Edwards syndrome (trisomy 13 and 18) are usually fatal by the first year of life. Early knowledge of potential complications can enable parents to deliver at a facility equipped to deal with high-risk births and connect with specialists who can guide their child's medical care.

As with all screening tests, patients opting to undergo NIPT are evaluated in the context of a larger population, based on a pre-test probability or the disease prevalence (i.e., how often a disease is present in that specific population). For example, Edwards syndrome (or trisomy 18) is the second most common fetal aneuploidy after Down syndrome, with a prevalence of one in 5,500 live births. Therefore, one newborn in 5,500 will be expected to have the condition among affected pregnancies that make it to term without screening. However, the pre-test probability also depends on patient-specific factors like ethnic background and maternal age. As the risk of fetal aneuploidy rises with age, expectant mothers are encouraged to undergo prenatal screening to detect the potential risk of fetal genetic abnormalities.

In short, screening tests are not intended to diagnose a particular condition. Instead, they serve to better personalize a person's pre-test probability of disease and weigh the need for further invasive testing.

Evaluating test utility

Test performance is evaluated based on the ability to reliably distinguish high-risk individuals or patients with disease from healthy people. A test's sensitivity gauges how well it can detect risk or disease in people who are, in fact, at high risk or sick. We can think of test sensitivity like modern home security systems that detect unexpected entries. Screening tests will detect some level of false positive alarms (perhaps, in the case of a home security system, a visiting relative), but better to be safe than sorry. The relationship between a test's sensitivity and false negativerate (the probability that an affected person incorrectly tests 'negative' or, in this case, that an intruder is not detected) can be calculated by subtracting sensitivity from 1. Because no test is perfect, positive screening results should be followed up with diagnostic tests, which are usually more specific, to facilitate a diagnosis.

Specificity gauges how well a test identifies low-risk or unaffected people who are, in fact, truly negative. When a test result is positive, specificity helps us understand whether a positive result is likely due to that disease versus other factors. The false positive rate (the probability an unaffected person incorrectly tests positive) is calculated by subtracting specificity from 1. In an ideal world, medical tests would be both perfectly sensitive and perfectly specific so that all affected individuals reliably have positive results and all healthy individuals confidently test negative. However, adjusting one of these values will generally inversely affect the other. Think of an email spam filter: setting the filter such that all emails received are sent to the spam folder would result in a filter with 100% sensitivity but at the cost of lowering specificity to 0%, which is equivalent to a false positive rate of 100%. In this case, all vital emails would be labeled as spam. In clinical practice, we are forced to strike a balance between sensitivity and specificity.

Sensitivity and specificity help speak to the accuracy of a test. Accuracy is the ability to differentiate healthy or low-risk individuals from high-risk or sick patients. It serves to estimate the strength of association between pre-test probability and post-test probability, a person's 'updated' probability of having a disease after testing. However, even in screening tests with more than 99% sensitivity, specificity, or accuracy, "positive" or "increased risk" results only tell us that an individual falls among the true positive or false positive cases. Screening tests are tuned to have higher sensitivity to cast as broad a net as possible to capture all potentially positive events, even if it means the test has slightly lower specificity, yielding a higher false positive rate. Higher sensitivity helps to maximize the likelihood of capturing all truly positive cases. This approach contrasts with diagnostic tests that aim to diagnose or "rule out" disease with near-perfect sensitivity and specificity.

Predictive values are also highly dependent on disease prevalence (Figure 1). If a disease is highly prevalent and a person tests positive for it, a high PPV means a higher likelihood that this person truly has the disease. However, as the prevalence of a disease decreases, the PPV also decreases because we can expect more false positive results for every true positive result, even with very high sensitivity and specificity. A lower PPV also increases the NPV since, for rare diseases, we can expect more individuals who are truly negative for every false negative result.

Figure 1. PPV is dependent upon disease prevalence. For equally sensitive and specific tests, PPV decreases with decreasing disease prevalence.

Therefore, the best way to think about "positive" screening test results is to interpret the result as "further testing is recommended" and "negative" results as "no abnormalities detected; no further testing recommended."

Figure 2. Post-test risk estimate is dependent on disease prevalence. Screening tests can increase our ability to detect at-risk individuals or pregnancies beyond the pre-test risk estimation for lower prevalence diseases. Pre-test, identifying individuals at risk for a rare disease is like trying to find a needle (positive case) in a haystack (larger population). However, post-test, the pile of hay (sub-population) is much smaller, and finding the needles becomes a more manageable task.

Understanding screening test results

For rare disorders and conditions with a high disease burden, the goal is to detect as many suspected cases as possible to maximize knowledge about related health risks. Take a group of 10,000 pregnant individuals in their first trimester. In this group, suppose the prevalence of a rare disorder with a high risk of miscarriage, stillbirth, developmental disability, and poor quality of life is roughly 1% (100 out of 10,000 pregnancies). Suppose these 10,000 expectant patients undergo screening for this disorder with a 99% sensitive and 95% specific test. In this scenario, we expect 100 individuals to be truly positive. With a 1% false negative rate (1-sensitivity), 99 of these 100 individuals would correctly receive a positive result. However, one affected person would incorrectly receive a negative result. Of 9,900 unaffected pregnancies, screening would correctly identify 9,405 as true negatives, although it might incorrectly label 495 healthy pregnancies as positive. We can expect about five times as many false positives as true positives and an estimated 17% PPV despite this test's excellent sensitivity and specificity.

At first glance, the above screening test may not appear informative, but the insights gained from these results are crucial. This test has captured nearly all true positive cases at higher risk of this rare disorder. Out of 10,000 individuals with a pre-test probability of 1% of having this rare disorder, it identified a subpopulation of 594 (99 true positives plus 450 false positives) individuals as 'positive' with a 17% post-test probability (PPV). That is, the screening test identified a subpopulation that is 17-times more likely to have a severe genetic disorder than the general population that was screened. The resulting 594 "positive" individuals (5.9% of the population) are now armed with results to inform critical discussions with their healthcare providers about the need for confirmatory diagnostic testing. What is important is the degree to which a screening test reliably enriches for positive cases with respect to population prevalence, allowing for a more targeted diagnostic test in a high-risk subpopulation.

In sum, the reliability of test results depends on the test characteristics discussed above. We use screening tests, combined with an individual's medical history and population variables, to determine the risk and benefit of further testing. Medical professionals, ethicists, and society at large help determine whether screening tests with particular characteristics provide enough benefit to offset the risk of potentially more invasive but more accurate testing. These foundations help establish a screening test, such as NIPT, as a standard of care in medical practice.

Noninvasive prenatal testing (NIPT)

NIPT is one form of fetal screening in which cell-free DNA from a maternal blood sample is analyzed for potential chromosome abnormalities. These screenings can also detect microdeletion syndromes characterized by physical and intellectual impairment and a higher risk of adverse health effects. Microdeletions and aneuploidies are rare in the general population, so tests for these conditions naturally have lower PPVs. Microdeletion tests are also less sensitive than aneuploidy tests, given the rarity of microdeletions and the limitations of today's technology. Their false positive rates are higher because of this lower sensitivity. However, microdeletion tests still provide significant information from false negative rates. As these tests continue to evolve, their resolution and the trade-off between sensitivity and specificity will continue to improve.

Screening tests should always be followed up with formal diagnostic testing. Patients with positive NIPT results are encouraged to undergo diagnostic procedures like amniocentesis or chorionic villus sampling for more insight into their pregnancy's risk of a genetic condition. Because these diagnostic tests carry a small risk to the pregnancy, screening tests are essential for identifying high-risk individuals who warrant more invasive testing. In addition, we encourage all families to engage in substantiative conversations with their healthcare providers so they can be better informed of their child's health now and in the future. These conversations can help them prepare for their pregnancy and make the best-informed decisions.

Navigating NIPT with Sema4

At Sema4, we know the pregnancy journey can be a whirlwind, and we're here for you throughout that journey. We aim to provide our patients, their families, and healthcare providers with valuable information from our data-driven reproductive and generational health solutions portfolio so they can make thoughtful, well-informed decisions as partners. For patients and providers interested in genetic testing options, we offer Sema4 Elements Noninvasive Prenatal Testing, a reliable, cell-free DNA NIPT screen with more than 99% sensitivity and specificity and patient-specific PPVs. This screen can detect risk with high confidence for common aneuploidies, sex chromosome abnormalities, and microdeletions in singleton and multiple gestation pregnancies. It also detects fetal sex as early as nine weeks gestation.

Support and education are essential when undergoing NIPT. As such, Sema4 provides patients with educational materials to help them learn more about the role of genetic testing. In addition, our genetic counselors are available to offer guidance and support for patients with positive results during what can be a worrisome time. Sema4 is also heavily invested in research to advance maternal-fetal health, including predictive modeling to determine the optimal timing to receive NIPT and achieve the most accurate results.

_ _ _

For more information on Sema4 ElementsTM, our portfolio of information-driven genomic solutions, digital tools, and services that enable providers to treat patients holistically during their reproductive and generational health journey, please click here.

1) Calculated using the National Society of Genetic Counselors (NSGC) NIPT/Cell Free DNA Screening Predictive Value Calculator

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Sema4 : The Positives (and Negatives) of Medical Testing - marketscreener.com

Julian Brazier: Meet a hidden driver of a bigger state, higher taxes and more regulation the libertarian movement – ConservativeHome

Sir Julian Brazier is a former Defence Minister, and was MP for Canterbury from 1987-2017.

In the background to the unhappy struggles in the Conservative Party today is a philosophical clash in which the voices of libertarians are loudest. While (mostly) still supporting the man, their accusation is that the Johnson government has abandoned liberty.

These voices call for much that traditional small c conservatives should agree with a smaller state, lower taxes, less regulation but their message carries at its heart a deeply unhelpful strand which would be bad for the country, and calamitous for the Partys prospects of staying in power.

Our most important domestic challenge today is reining back public expenditure so we can lower taxes on struggling families. Government spending is the highest proportion of GDP since the aftermath of the Second World War.

Where I part company from my libertarian friends is that I believe it is time we acknowledged that one of the hidden drivers of runaway public spending is libertarianism itself and its left-wing cousin, the human rights lobby. Both stress freedom and gloss over the responsibilities and consequences which should come with it.

John Stuart Mill formulated the paradox of hedonism: those only are happy who have their minds fixed on some object other than their own happiness.

Similarly, the paradox of liberty is that we can only attain true freedom and a smaller state, if we focus not on selfish individualism but instead on nurturing and rebuilding those natural structures and attitudes which reduce the need for the services of the state. This requires active citizens, robust families, stronger communities and a sense of nationhood. These were themes of the late, great, Sir Roger Scruton.

One of his favourite examples were the American laws which allowed people, in most places, to build freely where they wanted, but then required the American taxpayer to expend huge sums taking roads and power to them. This has created a nightmare of ever-expanding suburbs with social black holes in town centres and heavy government spending.

More broadly, he attacked the growing wish for extending freedoms without accepting any corresponding responsibilities, even crucially where there are heavy costs to the taxpayer and wider community (including later generations).

There is a parallel with Britains NHS. The cost of NHS and social care has exploded to the point where some are claiming Britain is becoming a health and social care system with a country attached. The Party is buzzing with ideas for reform of the NHS and social care from pruning expensive bureaucrats and tackling GP contracts, to moving towards an insurance-based system. Yet there is one way we could reduce NHS spending dramatically and improve productivity in the economy: by persuading millions of obese people to lose weight and the nation to become fitter.

Scandinavian countries adopted a wide range of contrasting approaches to Covid but, with their much fitter populations, all suffered far lower rates of Covid deaths, and lower pressures on their health systems. Indeed, the Swedish approach was never an option here because our large population of obese people would have brought the NHS down.

The impact of Britains obesity, the worst in Europe (apart from Malta), goes far beyond Covid. A range of illnesses from cardiovascular conditions to arthritis to diabetes are made both more likely and more dangerous by obesity and also drive up the cost of the NHS.

Yet libertarians oppose measures to incentivise fitness, from sugar taxes to public health campaigns (what they call the Nanny State). Meanwhile the human rights lobby screams against fat-shaming even in professions (such as the Army and the Police) where fitness is self-evidently important.

So, yes to lower taxation in general. But yes also to taxes targeting unhealthy foods and to tax breaks for gym subscriptions.

A parallel example is opposition to so-called Covid passports. Most of the Covid deaths, for some time now, have been among the unvaccinated. All Conservatives should wish to raise restrictions as quickly as possible. Indeed, the noisy lobby calling until recently for the re-imposition of Covid restrictions was mostly on the Left, but the circumstances which have underpinned their case the existence of large numbers who refuse to vaccinate and get sick is ignored by libertarians and the human rights lobby.

By contrast, millions of Britons saw nothing wrong with those who choose to be refuseniks paying some price (in terms of minor inconvenience) for their potential impact on the NHS. Even as we manage to ease out of the last parts of lockdown, protecting the short-term liberties of the refusenik minority has consequences, not just for public spending, but also for many who have other life-threatening conditions over which unlike the refuseniks they have no choice. Sick refuseniks are occupying beds desperately needed by other sick people.

A broader example is attitude to the family. Individualists on left and right campaigned successfully a generation ago for the virtual end to restrictions on divorce and the end of allocation of fault as a factor in child custody and the division of assets.

Today, attempts to reinforce traditional families are bitterly opposed by many the same people. Iain Duncan-Smiths radical reforms on social welfare reintroduced incentives to work, but he was consistently blocked in trying to remove disincentives for traditional families to stay together.

Yet the result of the decline of the traditional family is not just growing misery among children, with mental health, suicide, self-harm and drug-taking all on the rise and mostly higher than other European countries. It is also extremely expensive for the taxpayer as social security spending and the requirement for police officers, social workers, prison officers and childrens mental health staff grows. Studies consistently show that stable two parent families offer on average the best outcomes for children and family breakdown has an immediate cost to the benefit system.

If the state can encourage responsible personal choices and the rebuilding of those Burkean structures, from the family to the community to a sense of shared nationhood, expenditure can fall as the use of the safety net declines. If, on the other hand, choices which lead to mounting bills for the taxpayer are protected on the basis that We are not a country which asks to see papers, the size of the state will expand as the safety net gets more and more crowded.

Scruton once commented When government creates an unaccountable class it exceeds its remit, by undermining the relation on which its own legitimacy depends. In courser terms, people hate a freeloaders charter; rights should be balanced by responsibilities.

Boris Johnson led us out of the European Union. The next moves we take should seek to re-establish that balance. So, yes to reducing regulation (such as the Clinical Trials Directive which destroyed East Kents biggest employer). Yes to making strategic choices to cut public spending and taxation (a smaller university sector, an end to the triple lock for pensions?). Yes to forging new global trade and wider partnerships.

But lets have an end to the suggestion by so many of the Prime Ministers critics that a combination of offering freedom, alongside state-funded protection from the consequences, will capture the hearts of the British people.

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Julian Brazier: Meet a hidden driver of a bigger state, higher taxes and more regulation the libertarian movement - ConservativeHome

Libertarian Democrat – Wikipedia

Ideological faction within the U.S. Democratic Party

In American politics, a libertarian Democrat is a member of the Democratic Party with political views that are relatively libertarian compared to the views of the national party.[1][2]

While other factions of the Democratic Party, such as the Blue Dog Coalition, the New Democrat Coalition and the Congressional Progressive Caucus, are organized in the Congress, the libertarian faction is not organized in such a way.

Libertarian Democrats support the majority of positions of the Democratic Party, but they do not necessarily share identical viewpoints across the political spectrum; that is, they are more likely to support individual and personal freedoms, although rhetorically within the context of Democratic values.[3]

Libertarian Democrats oppose NSA warrantless surveillance. In 2013, well over half the House Democrats (111 of 194) voted to defund the NSA's telephone phone surveillance program.[4]

Former representative and current Governor Jared Polis of Colorado, a libertarian-oriented Democrat, wrote in Reason magazine: "I believe that libertarians should vote for Democratic candidates, particularly as our Democratic nominees are increasingly more supportive of individual liberty and freedom than Republicans".[5] He cited opposition to the Stop Online Piracy Act, support for the legalization of marijuana, support for the separation of church and state, support for abortion rights and individual bodily autonomy, opposition to mass surveillance and support for tax-code reform as areas where the majority of Democrats align well with libertarian values.[5]

While maintaining a relatively libertarian ideology, they may differ with the Libertarian Party on issues such as consumer protection, health care reform, anti-trust laws and the overall amount of government involvement in the economy.[3]

After election losses in 2004, the Democratic Party reexamined its position on gun control which became a matter of discussion, brought up by Howard Dean, Bill Richardson, Brian Schweitzer and other Democrats who had won in states where Second Amendment rights are important to many voters. The resulting stance on gun control brought in libertarian minded voters, influencing other beliefs.

In the 2010s, following the revelations by Edward Snowden about NSA surveillance in 2013, the increasing advent of online decentralization and cryptocurrencies like Bitcoin, the perceived failure of the war on drugs and the police violence in places like Ferguson, Democratic lawmakers such as Senators Ron Wyden, Kirsten Gilibrand and Cory Booker and Representative Jared Polis have worked alongside libertarian Republicans like Senator Rand Paul and Representative Justin Amash to curb what is seen as government overreach in each of these areas, earning plaudits from such traditional libertarian sources as Reason magazine.[6][7][8][9] The growing political power of Silicon Valley, a longtime Democratic stronghold that is friendly to economic deregulation and strong civil liberties protections while maintaining traditionally liberal views on social issues, has also seriously affected the increasingly libertarian leanings of young Democrats.[10][11][12]

The libertarian faction has influenced the presidential level as well in the post-Bush era. Alaska Senator and presidential aspirant Mike Gravel left the Democratic Party midway through the 2008 presidential election cycle to seek the Libertarian Party presidential nomination,[13] and many anti-war and civil libertarian Democrats were energized by the 2008 and 2012 presidential campaigns of libertarian Republican Ron Paul.[14][15] This constituency arguably embraced the 2016 and 2020 presidential campaigns of independent Democrat Bernie Sanders for the same reasons.[16][17] In the state of New Hampshire, libertarians operating from the Free State Project have been elected to various offices running as a mixture of both Republicans and Democrats.[18][19] A 2015 Reuters poll found that 22% of Democratic voters identified themselves as "libertarian," more than the percentage of Republicans but less than the percentage of independents.[20]

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Libertarian Democrat - Wikipedia

Criticism of libertarianism – Wikipedia

Criticism of libertarianism includes ethical, economic, environmental and pragmatic concerns and is often focused on right-libertarianism.[1] Critics have argued that laissez-faire capitalism does not necessarily produce the best or most efficient outcome,[2] and that libertarianism's philosophy of individualism and policies of deregulation fail to prevent the abuse of natural resources.[3] Criticism of left-libertarianism is instead mainly related to anarchism and includes allegations of utopianism, tacit authoritarianism and vandalism towards feats of civilization. Left and right-libertarians also engage in criticism of each other.

The validity of right-libertarian notions of liberty and economic freedom have been questioned by critics such as Robert Lee Hale, who posits that laissez-faire capitalism is a system of aggressive coercion and restriction by property owners against others:[4]

Adam Smith's "obvious and simple system of natural liberty" is not a system of liberty at all, but a complicated network of restraints, imposed in part by individuals, but very largely by the government itself at the behest of others on the freedom of the "some". ... What in fact distinguishes this counterfeit system of "laissez-faire" (the market) from paternalism, is not the absence of restraint, but the absence of any conscious purpose of the part of the officials who administer the restraint, and of any responsibility or unanimity on the part of the numerous owners at whose discretion the restraint is administered.

Other critics, including John Rawls in Justice as Fairness, argue that implied social contracts justify government actions that violate the rights of some individuals as they are beneficial for society overall. This concept is related to philosophical collectivism as opposed to individualism.[5] In response, libertarian philosophers such as Michael Huemer have raised criticisms of the social contract theory.[6]

Critics such as Corey Robin describe right-libertarianism as fundamentally a reactionary conservative ideology united with more traditional conservative thought and goals by a desire to enforce hierarchical power and social relations:[7]

Conservatism, then, is not a commitment to limited government and libertyor a wariness of change, a belief in evolutionary reform, or a politics of virtue. These may be the byproducts of conservatism, one or more of its historically specific and ever-changing modes of expression. But they are not its animating purpose. Neither is conservatism a makeshift fusion of capitalists, Christians, and warriors, for that fusion is impelled by a more elemental forcethe opposition to the liberation of men and women from the fetters of their superiors, particularly in the private sphere. Such a view might seem miles away from the libertarian defense of the free market, with its celebration of the atomistic and autonomous individual. But it is not. When the libertarian looks out upon society, he does not see isolated individuals; he sees private, often hierarchical, groups, where a father governs his family and an owner his employees.

In his essay "From Liberty to Welfare", philosopher James P. Sterba argues that a morally consistent application of right-libertarian premises, including that of negative liberty, requires that a libertarian must endorse "the equality in the distribution of goods and resources required by a socialist state". Sterba presents the example of a typical conflict situation between the rich and poor "in order to see why libertarians are mistaken about what their ideal requires". He argues that such a situation is correctly seen as a conflict of negative liberties, saying that the right of the rich not to be interfered with in the satisfaction of their luxury needs is morally trumped by the right of the poor "not to be interfered with in taking from the surplus possessions of the rich what is necessary to satisfy their basic needs".

According to Sterba, the liberty of the poor should be morally prioritized in light of the fundamental ethical principle "ought implies can" from which it follows that it would be unreasonable to ask the poor to relinquish their liberty not be interfered with, noting that "in the extreme case it would involve asking or requiring the poor to sit back and starve to death" and that "by contrast it would not be unreasonable to ask and require the rich to sacrifice their liberty to meet some of their needs so that the poor can have the liberty to meet their basic needs". Having argued that "ought implies can" establishes the reasonability of asking the rich to sacrifice their luxuries for the basic needs of the poor, Sterba invokes a second fundamental principle, "The Conflict Resolution Principle", to argue that it is reasonable to make it an ethical requirement. He concludes by arguing that the application of these principles to the international context makes a compelling case for socialist distribution on a world scale.[8]

Jeffrey Friedman argues that natural-rights libertarianism's justification for the primacy of property is incoherent:[9]

[W]e can press on from [the observation that libertarianism is egalitarian] to ask why, if ... the liberty of a human being to own another should be trumped by equal human rights, the liberty to own large amounts of property [at the expense of others] should not also be trumped by equal human rights. This alone would seem definitively to lay to rest the philosophical case for libertarianism. ... The very idea of ownership contains the relativistic seeds of arbitrary authority: the arbitrary authority of the individual's "right to do wrong."

Philosopher Jonathan Wolff criticizes deontological libertarianism as incoherent, writing that it is incapable of explaining why harm suffered by the losers in economic competition does not violate the principle of self-ownership and that its advocates must "dishonestly smuggle" consequentialist arguments into their reasoning to justify the institution of the free market.[10]

Robert Lee Hale has argued that the concept of coercion in right-libertarian theory is applied inconsistently, insofar as it is applied to government actions, but it is not applied to the coercive acts of property owners to preserve their own private property rights.[11]

Jeffrey Friedman has criticized right-libertarians for often relying on the unproven assumption that economic growth and affluence inevitably result in happiness and increased quality of life.[12]

J. C. Lester has argued that right-libertarianism has no explicit theory of liberty.[1] He supplies a theory of liberty, briefly summarized as the absence of imposed cost. Frederick[13] criticizes Lester for smuggling in concepts not specified in the theory. Lester[14] responded. Both Lester and Frederick are proponents of critical rationalism, the epistemological approach of Karl Popper. Lester has criticized libertarians for neglecting epistemology.

Right-libertarians are accused of ignoring market failures, although not all proponents are market zealots.[15] Critics of laissez-faire capitalism, the economic system favored by right-libertarians, argue that market failures justify government intervention in the economy, that nonintervention leads to monopolies and stifled innovation, or that unregulated markets are economically unstable. They argue that markets do not always produce the best or most efficient outcome, that redistribution of wealth can improve economic health and that humans involved in markets do not always act rationally.[16][17]

Other economic criticisms concern the transition to a right-libertarian society. Jonathan Chait argues that privatizing Social Security would cause a fiscal crisis in the short-term and damage individuals' economic stability in the long-term.[18]

Reconciliation of individual rights and the advances of a free market economy with environmental degradation is a problem that few right-libertarians have addressed.[19] Political scientist and author Charles Murray has written that stewardship is what private property owners do best.[19] Environmentalists on the left who support regulations designed to reduce carbon emissions, such as cap and trade, argue that many right-libertarians currently have no method of dealing with problems like environmental degradation and natural resource depletion because of their rejection of regulation and collective control.[12] They see natural resources as too difficult to privatize as well as legal responsibility for pollution or degrading biodiversity as too difficult to trace.[5] As a result, some see the rise of right-libertarianism as popular political philosophy as partially responsible for climate change.[3]

Right-libertarians are also criticised for ignoring observation and historical fact and instead focusing on an abstract ideal.[20] Imperfection is not accounted for and they are axiomatically opposed to government initiatives to counter the effects of climate change.

Anarchism is evaluated as unfeasible or utopian by its critics, often in general and formal debate. European history professor Carl Landauer argued that social anarchism is unrealistic and that government is a "lesser evil" than a society without "repressive force". He also argued that "ill intentions will cease if repressive force disappears" is an "absurdity".[21] However, An Anarchist FAQ states the following: "Anarchy is not a utopia, [and] anarchists make no such claims about human perfection. ... Remaining disputes would be solved by reasonable methods, for example, the use of juries, mutual third parties, or community and workplace assemblies [as well as] some sort of "court" system would still be necessary to deal with the remaining crimes and to adjudicate disputes between citizens".[22][23]

In his essay On Authority, Friedrich Engels claimed that radical decentralization promoted by anarchists would destroy modern industrial civilization, citing an example of railways:[24]

Here too the co-operation of an infinite number of individuals is absolutely necessary, and this co-operation must be practised during precisely fixed hours so that no accidents may happen. Here, too, the first condition of the job is a dominant will that settles all subordinate questions, whether this will is represented by a single delegate or a committee charged with the execution of the resolutions of the majority of persona interested. In either case there is a very pronounced authority. Moreover, what would happen to the first train dispatched if the authority of the railway employees over the Hon. passengers were abolished?

John Donahue also argues that if political power were radically shifted to local authorities, parochial local interests would predominate at the expense of the whole and that this would exacerbate current problems with collective action.[25]

In the end, it is argued that authority in any form is a natural occurrence which should not be abolished.[26]

In 2013, Michael Lind observed that of the 195 countries in the world, none have fully actualized a society as advocated by right-libertarians:[27]

If libertarianism was a good idea, wouldn't at least one country have tried it? Wouldn't there be at least one country, out of nearly two hundred, with minimal government, free trade, open borders, decriminalized drugs, no welfare state and no public education system?

Furthermore, Lind has criticized right-libertarianism as being incompatible with democracy and apologetic towards autocracy.[28] In response, right-libertarian Warren Redlich argues that the United States "was extremely libertarian from the founding until 1860, and still very libertarian until roughly 1930".[29]

The anarchist tendency known as platformism has been criticized by Situationists,[30] insurrectionaries, synthesis anarchists[31][32] and others of preserving tacitly statist, authoritarian or bureaucratic tendencies.

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Criticism of libertarianism - Wikipedia

Opinion | How Being Sick Changed My Health Care Views – The New York Times

But then comes the complicating factor, the part of my experience that turned me more right-wing. Because in the second phase of my illness, once I knew roughly what was wrong with me and the problem was how to treat it, I very quickly entered a world where the official medical consensus had little to offer me. It was only outside that consensus, among Lyme disease doctors whose approach to treatment lacked any C.D.C. or F.D.A. imprimatur, that I found real help and real hope.

And this experience made me more libertarian in various ways, more skeptical not just of our own medical bureaucracy, but of any centralized approach to health care policy and medical treatment.

This was true even though the help I found was often expensive and it generally wasnt covered by insurance; like many patients with chronic Lyme, I had to pay in cash. But if I couldnt trust the C.D.C. to recognize the effectiveness of these treatments, why would I trust a more socialized system to cover them? After all, in socialized systems cost control often depends on some centralized authority like Britains National Institute for Health and Care Excellence or the controversial, stillborn Independent Payment Advisory Board envisioned by Obamacare setting rules or guidelines for the system as a whole. And if youre seeking a treatment that official expertise does not endorse, I wouldnt expect such an authority to be particularly flexible and open-minded about paying for it.

Quite the reverse, in fact, given the trade-off that often shows up in health policy, where more free-market systems yield more inequalities but also more experiments, while more socialist systems tend to achieve their egalitarian advantages at some cost to innovation. Thus many European countries have cheaper prescription drugs than we do, but at a meaningful cost to drug development. Americans spend obscene, unnecessary-seeming amounts of money on our system; America also produces an outsize share of medical innovations.

And if being mysteriously sick made me more appreciative of the value of an equalizing floor of health-insurance coverage, it also made me aware of the incredible value of those breakthroughs and discoveries, the importance of having incentives that lead researchers down unexpected paths, even the value of the unusual personality types that become doctors in the first place. (Are American doctors overpaid relative to their developed-world peers? Maybe. Am I glad that American medicine is remunerative enough to attract weird Type A egomaniacs who like to buck consensus? Definitely.)

Whatever everyday health insurance coverage is worth to the sick person, a cure for a heretofore-incurable disease is worth more. The cancer patient has more to gain from a single drug that sends the disease into remission than a single-payer plan that covers a hundred drugs that dont. Or to take an example from the realm of chronic illness, just last week researchers reported strong evidence that multiple sclerosis, a disease once commonly dismissed as a species of hysteria, is caused by the Epstein-Barr virus. If that discovery someday yields an actual cure for MS, it will be worth more to people suffering from the disease than any insurance coverage a government might currently offer them.

So if the weakness of the libertarian perspective on health insurance is its tendency to minimize the strange distinctiveness of illness, to treat patients too much like consumers and medical coverage too much like any other benefit, the weakness of the liberal focus on equalizing cost and coverage is the implicit sense that medical care is a fixed pie in need of careful divvying, rather than a zone where vast benefits await outside the realm of whats already available.

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Opinion | How Being Sick Changed My Health Care Views - The New York Times

Accomplished Scot Gordon Emslie escaped classism by immigrating to Canada – The Globe and Mail

Gordon R. Emslie: Cricketer. Psychologist. Tinkerer. Libertarian. Born June 30, 1940, in Aberbeen, Scotland; died Aug. 22, 2021, in Toronto, of Alzheimers disease; aged 81.

Gordon R. EmslieCourtesy of family

In 1963, Gordon, a 23-year-old Scotsman, was offered a lucrative teaching post at a posh English university on the condition that he accept immediately, no questions asked. Armed with three MAs German, French and psychology and a postgraduate diploma in psychology from the University of London, refusal seemed unthinkable. But Gordon, unable to ignore the administrations haughtiness, quickly declined and was told hed never teach in England. One month later he immigrated to Canada a wildly disproportionate response to a bad interview.

That was Gordon. He loved London, but the paperwork he valued the most came from Kingston, Ont.: a rent receipt for his first apartment addressed, Dear Mr. Scotch (sic) Boy; the PhD in psychology from Queens University; an obituary clipping from 1966. The Kingston Whig-Standard erroneously announced his marriage, to Judith Rosemary Cafley, under the title: Death and Funerals. The absurdity of a marriage announcement printed in the obituaries perfectly signified Gordons sensibility and demeanour. A charming libertarian, he was quick to send up anything that hinted of classism. He mocked media coverage of the Royal Family; he decried his sister Moyras voice mail. British Telecom programmed it to talk in a fancy London accent, oblivious to its locale: Aberdeen.

Gordon was a born sportsman. He captained hockey and cricket teams for Robert Gordons College and the University of Aberdeen and extended his career in both sports with Ruthrieston H.C., the Scottish Select Team and London University; and Gordonians C.C. and Aberdeenshire C.C., respectively. He dropped down to one sport when, in Canada, he discovered hockey was played on ice. In 1965, Gordon played with the Kingston Cricket Club and met Judith at one of the many team parties. He captained the team in 1968 and often led the Ottawa Valley Cricket League in scoring.

By the early 1970s, Gordon and Judith had two sons, Ritchie and Andrew. The young family moved to Guelph, Kitchener and settled in Etobicoke, where Gordon selflessly allowed Ritchie to destroy his bamboo-lined cricket pads playing road hockey. Also selfless: driving his son to hockey practice, collapsed in pain over the steering wheel, instead of going directly to the hospital. It took Gordon weeks to recover from the kidney stone surgery.

The family took several trips to Scotland to visit Gordons family perhaps to avoid picking up the phone. Gordon hated telephones. A child from a phone-less house, he was far more comfortable crafting intricate letters, dictating adventures on cassette tapes, even reciting Address to a Haggis on Burns Night.

In retirement, he was thrilled to cheer on his grandson, Luca, playing hockey and baseball. He was in constant amazement of the team spirit, athletic facilities and opportunity. His face would light up.

Gordon was a tinkerer. Old cabinet drawers, lockboxes and peanut butter jars were drilled, hinged and bolted into complex contraptions holding three generations of tools. In his workshops, wild turkey feathers were hollowed out and made into pens. Scotch bottle caps were filled with concrete and used as chess pieces. And letters were carefully burned into driftwood signs.

The latter were for the paths at the cottage, named Stonehaven. He had a panache for path making and the names he etched into the signs were more often than not in Doric, a dialect unique to the Northeast of Scotland: Ceilidh Place, Ben Doric, Bothy Brae, Union Street (a thoroughfare in Aberdeen) and Lower Union Street (in Kingston where Gordon and Judith first shared a home). There are 14 signs. At least two are missing. Every so often I find a new one and rescue it from the moss and mushrooms.

Echoing his marriage notice, the venue hosting his memorial sent an e-mail to Gordons widow congratulating her on their recent wedding engagement. Im sure Gordon somehow orchestrated this.

I can hear his laugh.

Ritchie Emslie is Gordons son.

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Lives Lived celebrates the everyday, extraordinary, unheralded lives of Canadians who have recently passed. To learn how to share the story of a family member or friend, go online to tgam.ca/livesguide

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Accomplished Scot Gordon Emslie escaped classism by immigrating to Canada - The Globe and Mail

Liz Truss: The Tufton Street Candidate Byline Times – Byline Times

Sam Bright unravels the ties between Conservative leadership hopeful Liz Truss and Westminsters network of opaque libertarian think tanks

Boris Johnsons premiership of the Conservative Party is dying. It is currently unclear how slowly or quickly the rot is taking hold, but there is little doubt that his political career is on a steep, downward trajectory.

His Downing Street team held multiple parties in breach of lockdown rules both this year and last, some of which were attended by the Prime Minister. The public backlash has been fierce, with focus groups telling former Downing Street pollster James Johnson that the Prime Minister is a coward.

There was something about him that made him a bit more personable to me, one voter in the focus group said, who backed the Conservatives for the first time in 2019. Its gone now, because weve lost that trust in him. Now hes just a buffoon He cant be trusted.

Scenting an opportunity, rivals to Johnsons throne are now encircling the Prime Minister preparing their campaigns for the moment when his leadership begins its final descent. Foreign Secretary Liz Truss is a front-runner in this pack, by virtue of her popularity among Conservative Party members.

But Truss also has another crucial constituency of support that may bolster her efforts to seize control of the Conservative Party: for years, she has developed close ties to the Tufton Street network a group of libertarian think tanks and lobbying groups, many of which are opaquely funded, that for years have exerted considerable influence on the policy decisions and the operation of the Tories.

Several of the groups are currently or were formerly based in brick-clad offices along Tufton Street in Londons Westminster, creating an association between a political ideology and the address as well as suspicions that these libertarian organisations closely coordinate their work.

Tufton Street is much like Fleet Street the former habitat of the newspaper industry. While the titles that were once based there have now scattered across London, Fleet Street is still used as a shorthand phrase for the industry much like Tufton Street and the world of libertarian politics.

Indeed, Shahmir Sanni, a Brexit whistleblower who formerly worked within the Tufton Street network, says that these groups regularly held meetings at 55 Tufton Street to agree on a single set of right-wing talking points and to [secure] more exposure to thepublic.

These organisations are bound by their support for Brexit the Vote Leave campaign was originally registered at 55 Tufton Street and their vigour for low taxes, laissez faire economics, a smaller state, and seemingly close relationship with Liz Truss.

Attempting to institutionalise a right-wing political ideology, the Conservative Party has deployed the public appointments system to install sympathetic individuals in prominent government roles.

This strategy has been adopted by Truss, seen actively during her time as International Trade Secretary from July 2019 to September 2021, which involved the awarding of public positions to Tufton Street insiders.

In October 2020, for example, the radical, right-wing website Guido Fawkes gleefully reported that Truss had appointed a swathe of free market think tankers to her refreshed Strategic Trade Advisory Group a forum of businesses and academics, which meets regularly to consider the UKs international trade policies.

These appointments included:

Lord Hannan himself was also appointed as an advisor to the Board of Trade a commercial body within the Department for International Trade in September 2020. His Initiative for Free Trade was formerly based at 57 Tufton Street, sharing an office with Colviles Centre for Policy Studies, based around the corner from the Institute of Economic Affairs.

Following these appointments to the Strategic Trade Advisory Group, former Liberal Democrat MP Tom Brake wrote to Truss, asking whether proper due diligence had taken place in the recruitment process. Brake asked her to explain what additional checks had been carried out on the organisations that employ these individuals which have a history of failing to declare their donors to ensure that they are not funded by those who might be deemed to be agents of a foreign principal.

Core members of Truss own team have also been drawn from the Tufton Street network.

Sophie Jarvis who previously worked as head of government affairs at the Adam Smith Institute has been a special advisor to Truss at the Department for International Trade and now the Foreign Office. Nerissa Chesterfield, former head of communications at the Institute of Economic Affairs, was also employed as a special advisor to Truss from August 2019 to February 2020 leaving to work for Rishi Sunak, one of Trusss main competitors for the Conservative leadership.

Truss has also recently been given responsibility for post-Brexit negotiations with the EU tasked with ensuring a diplomatic resolutions to various trade disputes. Assisting Truss in this task is Minister of State for Europe Chris Heaton-Harris who chaired the European Research Group, a network of hard-right Eurosceptic Conservative MPs, from 2010 to 2016.

In August 2019, Truss appointed eight advisors to recommend locations for new, post-Brexit freeports ports where normal tax and customs rules do not apply two of whom were senior members of Tufton Street think tanks. One was Tom Clougherty head of tax at the Centre for Policy Studies. Clougherty was previously executive director of theAdam Smith Institute, managingeditor at the libertarian Reason Foundation, and senior editor at the CatoInstitute co-founded and part-funded by the Koch brothers, two radical, right-wing American billionaires.

Truss has surrounded herself with Tufton Street figures, with her departments often relying on their policy advice. She and her ministers held a swathe of official meetings with representatives of Tufton Street think tanks and lobbying groups during her time at the Department for International Trade, departmental records show.

Controversially, two meetings between the Institute of Economic Affairs and Truss were removed from departmental records in August 2020 justified on the basis that they were personal rather than official meetings. Labour accused Truss of appearing to be evading rules designed to ensure integrity, transparency and honesty in public office, and the records were subsequently reinstated.

It was also revealed in December 2018 that Truss met with five American libertarian groups during a visit to Washington D.C. that cost taxpayers more than 5,000. The organisations included:

The majority of these organisations have been closely associated with climate change denial or policies that obstruct efforts to address climate change and its effects.

Americans for Tax Reform belongs to aninternational coalition of anti-tax, free-market campaign groups called the World Taxpayers Associations, according to DeSmog. This includes the TaxPayers Alliance an influential UK libertarian pressure group founded by Matthew Elliot, who was the CEO of the Vote Leave EU Referendum campaign.

Elliott, an authoritative figure on the right, reserved special praise for Truss after an event hosted by Policy Exchange in September 2021, in which they both participated. Truss was on great form, he said, outlining a bold, exciting vision for how boosting international trade benefits UK consumers and workers across the country.

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Truss, along with a number of her colleagues, recently signed up as a parliamentary supporter of the Free Market Forum a new free market project launched by the Institute of Economic Affairs and advised by Elliott.

The MP for South West Norfolk since 2010, she is viewed widely as a political chameleon a former Liberal Democrat and a supporter of the Remain campaign in 2016 but her libertarian convictions have been evident since entering Parliament in 2010.

At the September 2021 Policy Exchange event, the Oxford University graduate emphasised her desire to [champion] open markets and free enterprise, saying that protectionism is no way to protect peoples living standards. This could well have been a veiled swipe at her boss, Boris Johnson, who has been seen as an interventionist Prime Minister using state spending and powers to achieve his political objectives, and raising taxes as a result.

At this critical time, we need trade to curb any rise in the cost of living through the power of economic openness, Truss added.

These sentiments chime with the attitudes of the Tufton Street network, establishing Truss as the Thatcherite contender in the upcoming Conservative leadership contest whenever it may take place.

Johnson has authoritarian instincts, and is certainly not a moderate Prime Minister. However, whichever direction the Conservative Party takes in the post-Johnson era, it seems likely to be more radical particularly in relation to economics. Truss, as the Tufton Street candidate, represents the sharp end of this spear.

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Liz Truss: The Tufton Street Candidate Byline Times - Byline Times