StemCell Therapy

NORTH CHICAGO, Ill., Dec. 11, 2020 /PRNewswire/ --AbbVie (NYSE: ABBV) today announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended the approval of RINVOQ (upadacitinib, 15 mg), an oral, once daily selective and reversible JAK inhibitor, for the expanded use in two additional rheumatic indications: the treatment of adult patients with active psoriatic arthritis and adult patients with active ankylosing spondylitis.5 The CHMP positive opinions are based on results from three pivotal clinical studies in which RINVOQ demonstrated efficacy across multiple measures of disease activity.1-3

"The CHMP's recommendations to approve RINVOQ in both psoriatic arthritis and ankylosing spondylitis mark an important milestone. AbbVie is committed to continued research to advance treatment standards for patients living with these debilitating diseases," said Thomas Hudson, senior vice president, research and development, AbbVie. "If approved, RINVOQ will become an oral, once daily targeted treatment option across three rheumatic indications in the European Union. These recommendations pave the path towards helping more people living with psoriatic arthritis and ankylosing spondylitis find relief from their symptoms across multiple manifestations of the diseases."

In both the Phase 3 SELECT-PsA 1 and SELECT-PsA 2 clinical trials, RINVOQ met the primary endpoint of ACR20 response at week 12 versus placebo in adult patients with active psoriatic arthritis who had an inadequate response to non-biologic disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs, respectively.1,2

RINVOQ also met the primary endpoint of Assessment of Spondyloarthritis International Society (ASAS) 40 response at week 14 versus placebo in SELECT-AXIS 1, a Phase 2/3 study in patients who were nave to biologic DMARDs and had an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs).3

Safety results from SELECT-PsA 1, SELECT-PsA 2 and SELECT-AXIS 1 have been previously reported and were consistent with those observed in rheumatoid arthritis, with no new significant safety risks identified.1-4

The CHMP positive opinion is a scientific recommendation for marketing authorization to the European Commission, which authorizes marketing approval in the European Union. The Marketing Authorization would be valid in all member states of the European Union, as well as Iceland, Liechtenstein and Norway.

About Psoriatic Arthritis

Psoriatic arthritis is a heterogeneous, systemic inflammatory disease with hallmark manifestations across multiple domains including joints and skin.6,7 In psoriatic arthritis, the immune system creates inflammation that can lead to skin lesions associated with psoriasis, pain, fatigue and stiffness in the joints.6,7

About Ankylosing Spondylitis

Ankylosing spondylitis is a chronic, inflammatory musculoskeletal disease primarily affecting the spine and characterized by debilitating symptoms of pain, limited mobility, structural damage and vertebral fractures.8,9

About SELECT-PsA 11,10

SELECT-PsA 1is a Phase 3, multicenter, randomized, double-blind, parallel-group, active and placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ compared to placebo and adalimumab in adult patients with active psoriatic arthritis who have a history of inadequate response to at least one non-biologic DMARD. Patients were randomized to RINVOQ 15 mg, RINVOQ 30 mg, adalimumab 40 mg EOW or placebo at baseline. At week 24, placebo patients were switched to either RINVOQ 15 mg or RINVOQ 30 mg.

The primary endpoint was the percentage of subjects receiving RINVOQ 15 mg or RINVOQ 30 mg who achieved an ACR20 response at 12 weeks of treatment versus placebo. Key secondary endpoints included change from baseline in HAQ-DI, proportion of patients achieving ACR50 and ACR70 at week 12, proportion of patients achieving PASI 75 at week 16 and proportion of patients achieving minimal disease activity (MDA) at week 24. These are not all of the secondary endpoints. The trial is ongoing, and the long-term extension will provide data on the long-term safety, tolerability and efficacy of RINVOQ in patients who have completed the placebo-controlled period.

Top-line results from SELECT-PsA 1were previously announced in February 2020. More information on this trial can be found atwww.clinicaltrials.gov(NCT03104400).

About SELECT-PsA 22,11

SELECT-PsA 2is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ in adult patients with active psoriatic arthritis who have a history of inadequate response to at least one biologic (bDMARD). Patients were randomized to RINVOQ 15 mg, RINVOQ 30 mg or placebo followed by either RINVOQ 15 mg or RINVOQ 30 mg at week 24.

The primary endpoint was the percentage of subjects achieving an ACR20 response after 12 weeks of treatment. Key secondary endpoints included change from baseline in HAQ-DI, proportion of patients achieving ACR50 and ACR70 at week 12, proportion of patients achieving PASI 75 at week 16, as well as proportion of patients achieving MDA at week 24. These are not all of the secondary endpoints. The trial is ongoing, and the long-term extension will provide data on the long-term safety, tolerability and efficacy of RINVOQ in patients who have completed the placebo-controlled period.

Top-line results from SELECT-PsA 2were previously announced in October 2019. More information on this trial can be found atwww.clinicaltrials.gov(NCT03104374).

About SELECT-AXIS 13,12

SELECT-AXIS 1is a Phase 2/3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ in adult patients with active ankylosing spondylitis who are bDMARD-nave and had inadequate response to at least two NSAIDs or intolerance to/contraindication for NSAIDs.

Key ranked secondary endpoints included proportion of subjects achieving Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 and ASAS partial remission (PR) at week 14, as well as change from baseline in Ankylosing Spondylitis Disease Activity Scores (ASDAS), MRI Spondyloarthritis Research Consortium ofCanada(SPARCC) score (spine) and Bath Ankylosing Spondylitis Functional Index (BASFI) at week 14. Period 2 is an open-label extension period to evaluate the long-term safety, tolerability and efficacy of RINVOQ in subjects who completed Period 1.

Results from SELECT-AXIS 1were previously announced in November 2019. More information on this trial can be found atwww.clinicaltrials.gov(NCT03178487).

About RINVOQ(upadacitinib)

Discovered and developed by AbbVie scientists,RINVOQ is a JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.10-20 InAugust 2019, RINVOQ received U.S. FDA approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. InDecember 2019, RINVOQ was approved by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. The approved dose for RINVOQ in rheumatoid arthritis is 15 mg. Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.10-12,14-20

Important Safety Information about RINVOQ (upadacitinib)5

RINVOQ is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy.

Use in combination with other potent immunosuppressants is not recommended.

Serious and sometimes fatal infections have been reported in patients receiving upadacitinib. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis have been reported. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis have been reported with upadacitinib. Prior to initiating upadacitinib, consider the risks and benefits of treatment in patients with chronic or recurrent infection or with a history of a serious or opportunistic infection, in patients who have been exposed to TB or have resided or travelled in areas of endemic TB or endemic mycoses, and in patients with underlying conditions that may predispose them to infection. Upadacitinib therapy should be interrupted if a patient develops a serious or opportunistic infection. As there is a higher incidence of infections in patients 75 years of age, caution should be used when treating this population.

Patients should be screened for TB before starting upadacitinib therapy. Anti-TB therapy should be considered prior to initiation of upadacitinib in patients with previously untreated latent TB or in patients with risk factors for TB infection.

Viral reactivation, including cases of herpes zoster, were reported in clinical studies. Consider interruption of therapy if a patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed before starting and during therapy with upadacitinib.

The use of live, attenuated vaccines during, or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunizations, including prophylactic zoster vaccinations, prior to initiating upadacitinib, in agreement with current immunization guidelines.

The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Immunomodulatory medicinal products may increase the risk of malignancies, including lymphoma. The clinical data are currently limited and long-term studies are ongoing. Malignancies, including non-melanoma skin cancer (NMSC), have been reported in patients treated with upadacitinib. Consider the risks and benefits of upadacitinib treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated NMSC or when considering continuing upadacitinib therapy in patients who develop a malignancy.Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Absolute neutrophil count <1000 cells/mm3, absolute lymphocyte count <500cells/mm3, or haemoglobin levels <8g/dL were reported in<1% of patients in clinical trials. Treatment should not be initiated, or should be temporarily interrupted, in patients with these haematological abnormalities observed during routine patient management.

RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidaemia) managed as part of usual standard of care.

Upadacitinib treatment was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo. If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, upadacitinib therapy should be interrupted until this diagnosis is excluded.

Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors, including upadacitinib. Upadacitinib should be used with caution in patients at high risk for DVT/PE. Risk factors that should be considered in determining the patient's risk for DVT/PE include older age, obesity, a medical history of DVT/PE, patients undergoing major surgery, and prolonged immobilisation. If clinical features of DVT/PE occur, upadacitinib treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.

The most commonly reported adverse drug reactions are upper respiratory tract infections (13.5%), nausea (3.5%), increased blood creatine phosphokinase (2.5%), and cough (2.2%). The most common serious adverse reactions were serious infections.

Please see the full SmPC for complete prescribing information atwww.EMA.europa.eu.

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Rheumatology

For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets in order to help more people living with rheumatic diseases reach their treatment goals. For more information on AbbVie in rheumatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.html.

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at http://www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTubeand LinkedIn.

Forward-Looking Statements

Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties, including the impact of the COVID-19 pandemic on AbbVie's operations, results and financial results, that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits of the Allergan acquisition, failure to promptly and effectively integrate Allergan's businesses, significant transaction costs and/or unknown or inestimable liabilities, potential litigation associated with the Allergan acquisition, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2019 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission (SEC). AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References:

SOURCE AbbVie

https://www.abbvie.com

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CHMP Recommends the Approvals of RINVOQ (Upadacitinib) for the Treatment of Adults with Active Psoriatic Arthritis and Ankylosing Spondylitis -...

UPPER NYACK, N.Y.--(BUSINESS WIRE)--CreakyJoints, the digital arthritis community for patients and caregivers worldwide and part of the Global Healthy Living Foundation (GHLF), today announced the launch of The Gout Show, a new podcast series and digital destination to raise awareness of one of the most misunderstood and misdiagnosed forms of arthritis: gout. Hosted by Steve Clisby, a professional musician who was recently diagnosed with gout, the five-episode series features experts and fellow patients defining gout, debunking common myths, and sharing useful tips to help other patients take control of their health. In addition to the podcast, there are three bonus patient audio guides about gout diagnosis, risk factors, and the treatment landscape. The Gout Show section of the CreakyJoints website (creakyjoints.org/thegoutshow) includes a quiz about uncontrolled gout, and robust educational and support articles specific to gout. The podcast and patient audio guides are available everywhere podcasts are downloaded.

Even in 2020, there is a persistent myth that gout is a disease of the upper class, of kings, caused by indulgent consumption of rich foods and alcohol, but that generalization ignores science and the experience of gout patients, said Louis Tharp, Executive Director and Cofounder of CreakyJoints. The Gout Show explains this mythology and others, focusing on how people living with gout can recognize a flare and seek treatment to reduce their risk for pain, inflammation and joint damage, so that they can concentrate on the activities of life important to them. Too many people suffer from uncontrolled gout, and The Gout Show speaks directly to them with positive messages of hope and help.

Gout Facts, Not Fiction

It is estimated that nearly 4 percent of the U.S. population (or 9.2 million people) are living with gout, a form of arthritis that causes severe, sudden attacks of inflammation, often in the toe joints or other large joints. Attacks occur following an overproduction of urate in the blood (known as hyperuricemia), which causes uric acid crystals to build up in the joints and trigger debilitating pain. Gout is a genetic condition. While more men than women get gout, anyone is susceptible if their body doesnt properly break down uric acid before it crystallizes in the joints.

The good news is that gout is highly treatable, but in order to address it with our patients, they have to recognize their symptoms and report them to their doctor, said Payam Shakouri, MD, a nephrologist with Advanced Kidney Care of Hudson Valley in New York and a medical adviser to CreakyJoints. Not only can gout be disabling disruptive to a persons quality of life, but it can cause serious damage to joints, bones and organs. Im pleased to contribute advice on The Gout Show and encourage people living with gout to listen to the series and report any symptoms they might have to their health-provider team.

The Gout Show also includes expert advice from Theodore R. Fields, MD, a rheumatologist at the Hospital for Special Surgery and Professor of Clinical Medicine at Weill Cornell Medical College in New York City.

While physicians guide the science of the podcast, patients drive the narrative. I was surprised when at age 32 I was diagnosed with gout after experiencing pain in my knee. I thought it was a simple running injury that I could rehab, and I mistakenly thought gout started just in the big toe, said Ashley Newton, a CreakyJoints member who shares her gout story in episode one of The Gout Show. As Ive learned more about gout, Ive prioritized keeping up with my treatments, tracking my symptoms in CreakyJoints ArthritisPower Research Registry, and sharing what I know about gout with other people in the event they may be experiencing symptoms that need to be reported to a doctor.

The Gout Show is available on all major streaming platforms as well as on the CreakyJoints website. It was made possible by funding from Horizon Therapeutics.

About CreakyJoints

CreakyJoints is a digital community for millions of arthritis patients and caregivers worldwide who seek education, support, advocacy, and patient-centered research. We represent patients in English and Spanish through our popular social media channels, our websites CreakyJoints.org, CreakyJoints.org.es, CreakyJoints.org.au, and the 50-State Network, which includes more than 1,500 trained volunteer patient, caregiver, and health care activists.

As part of the Global Healthy Living Foundation, CreakyJoints also has a patient-reported outcomes registry called ArthritisPower (ArthritisPower.org) with more than 29,000 consented arthritis patients who track their disease while volunteering to participate in longitudinal and observational research. CreakyJoints also publishes the popular Raising the Voice of Patients series, which are downloadable patient-centered educational and navigational tools for managing chronic illness. It also hosts PainSpot (PainSpot.org), a digital risk assessment tool for musculoskeletal conditions and injuries, and eRheum (eRheum.org) for telehealth and virtual care support. For more information and to become a member (for free), visit CreakyJoints.org.

Find us on social media:

Facebook: facebook.com/CreakyJoints and facebook.com/GlobalHealthyLivingFoundation

Twitter: @GHLForg, @CreakyJoints, #CreakyChats

Instagram: @creaky_joints, @creakyjoints_aus, @creakyjoints_esp

YouTube: youtube.com/user/CreakyJointsInc

TikTok: globalhealthylivingfnd

LinkedIn: linkedin.com/company/ghlf

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CreakyJoints Launches The Gout Show, a New Podcast Series and Educational Campaign - Business Wire

No two patients with any condition are exactly alike. But when it comes to rheumatoid arthritis (RA), it may seem like friends or support group members are having a totally different experience with pain and symptoms than that of you or your loved one. And thats because, oftentimes, they are. Unlike other diseases where there are telltale signs that most patients feel, this autoimmune disease can really affect people differently. While some patients severely struggle, experiencing consistent pain in all their joints, others may only have minor aches in their hands and feet, says Nilanjana Bose, M.D., a rheumatologist at the Rheumatology Center of Houston in Houston.

Elena Myasoedova, M.D., Ph.D, an associate professor of medicine and a senior associate consultant in rheumatology for The Mayo Clinic in Rochester, MN, says multiple studies have been conducted to better understand why symptoms vary so much by patient and there are still many unknowns. She explains that the level of RA disease activity, the number and location of involved joints and the presence of involvement of internal organs, as well as personal perception of pain and presence of other comorbidities may all affect how person feels about his RA and what symptoms they have.

Dr. Bose explains that some patients have pain in all joints, while others have pain in a few. The most typical joints that are affected are in the wrists and fingers, but even in more severe cases those areas might be spared or only an issue during a flare. Each patient is very different in the way they present, adds Veena K. Ranganath, M.D., associate clinical professor of medicine in the division of rheumatology at the David Geffen School of Medicine at UCLA in Los Angeles. Take, for example, Mary Sophia Hawks, age 58 of Knoxville, TN, whose RA was diagnosed in 2013 after a debilitating flare up where she experienced severe swollen joints all over her body, fatigue, and balance issues.

When I have a flare, everything hurts. All my joints, my muscles, everything. I can barely get to the bathroom and back to bed on those days, she says. Since then, shes had her knee replaced (doctors found that RA had eaten away at the bone, she says) and her toes are bent and dont straighten all the way. But so far, the disease hasnt adversely affected her hands, which is a more common symptom of RA, so shes able to work as a parish nurse at a local church. A positive attitude has been key in helping her live with the disease. I still go to church and sing in the choir. That brings me incredible joy.

Dr. Ranganath also says that a patients perception of their condition and pain acuity play a critical piece in how symptomatic they are. But being more sensitive to pain isnt all bad news: It can actually mean that you get diagnosed earlier, which may lead to a better outcome long term. Those who experience pain tend to seek help more quickly, she explains, which is good since its important to get on medication that can manage inflammation and prevent joint damage as well as the cardiovascular problems that are common among RA patients. Once we get the RA under control, overall outcomes are so much better, she says. (For those not experiencing pain, its key to see your doctor and have them refer you to a rheumatologist if they see physical signs of the disease.)

Dr. Bose adds that patients with concurrent mood and/or sleep disorderslike depression, anxiety, stress and insomniatend to have a lower pain threshold and will complain of pain and fatigue more. And much of the pain an RA patient feels can be affected by confounding factors like osteoarthritis and fibromyalgia, which can cause pain.

Just as pain and symptoms may differ, how well any certain medication works to quell them can also vary. And it can take some serious trial and error to find the best fit for you. Since RA is an autoimmune disease, Dr. Ranganath says that the majority of medications address the mechanism of action by suppressing the immune system from attacking itself. But what works for one patient may not work for another, Dr. Ranganath explains, due to each individuals different genetic composition and their unique environment. You have to be patient and flexible, says Hawks, who is a moderator and contributor to rheumatoidarthritis.net. You have to realize it will take a while to determine if your medication is working and not every medication works for everybody.

Dr. Bose also makes sure to take a holistic view when deciding how to proceed, treating the person as a whole, not just their RA. For example, if someone has ongoing depression or anxiety along with RA, she says its important to discuss managing mood problems, sleep issues, stress, lack of a good diet and lack of exercise, since all these conditions potentially can lead to inflammation and cause more pain.

Despite all that doctors dont know about RA and pain, Dr. Myasoedova says theres reason to be optimistic. Over the past three decades, the number of medications available for treatment of RA has increased dramatically, she said, with over 15 different medications that have been shown to prevent and/or delay progression of joint damage in RA. And this number is increasing each year. Hawks agrees. There is a lot of room for hope, she said.

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Understanding the RA Pain Spectrum - HealthCentral.com

GlobalData projects that between 2019 and 2029, seven major markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan) will see the approval and launch of five new agents for the treatment of rheumatoid arthritis (RA). Agents include one GM-CSF-inhibiting biologic (GSKs otilimab), one IL-6-inhibiting biologic (R-Pharms olokizumab), one TNF-inhibiting biologic (Taishos ozoralizumab), one BTK inhibitor (Roche/Genentechs fenebrutinib), and one IRAK 4 inhibitor (Pfizers PF-06650833).

Ozoralizumab is an inhibitory anti-TNF- trivalent nanobody complex. Two nano-bodies target TNF- while one binds to human serum albumin, theoretically extending the drugs half-life and distribution in vivo. The drug is formulated for administration via subcutaneous (SC) injection every four weeks. Ozoralizumab was originally developed by Ablynx, which in early 2018, was acquired by Sanofi. Very limited efficacy and safety data are currently available for ozoralizumab, and thus, the drugs prospects as a sixth-to-market TNF inhibitor in Japan remain uncertain. Olokizumab is a humanised interleukin-6 (IL-6) monoclonal antibody (mAb) that acts by blocking the final assembly of IL-6 to its signalling complex.

Phase IIb clinical development targeted patients who had unsuccessful responses to anti-TNF therapy. In H2 2020, R-Pharm announced positive topline results from CREDO 2 and CREDO 3, stating that all primary and secondary endpoints were achieved and that both once per month and twice per month dosing regimens were superior to placebo and non-inferior to adalimumab. There are currently two other IL-6 inhibitors, Roche/Genentech/Chugais Actemra/RoActemra (tocilizumab) and Sanofi/Regeneron/Asahi Kaseis Kevzara (sarilumab). Otilimab is a fully human monoclonal antibody (IgG1) directed against granulocyte-macrophage colony-stimulating factor (GM-CSF) that is in Phase III development by GSK. GM-CSF is a cytokine that drives the activation and proliferation of multiple innate immune cell types and is implicated in a wide range of auto-immune diseases. KOLs were relatively enthusiastic about otilimab, particularly in the context of it being a novel MOA that could provide another option to patients who are TNF inhibitor refractory.

Finally, there are two kinase inhibitors, fenebrutinib, a small-molecule inhibitor of Brutons tyrosine kinase (BTK) in development by Roche/Genentech, and PF-06650833, a highly selective, reversible, small-molecule inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4) in development by Pfizer. Both of these agents would be small-molecule, oral therapies, which are in high need for rheumatoid arthritis due to the significant costs associated with biologics, currently dominate the market. KOLs were intrigued by these new mechanisms of action (MOAs) but believed the drugs would be most effective as part of combination therapy with TNF or JAK inhibitors.

Figure 1 outlines the key Phase III/Phase IIb trials for these promising late-stage pipeline agents.

Figure 1: Key Phase II/III Trials for the Promising Pipeline Agents that GlobalData Expects to Be Licensed for RA in the 8MM During the Forecast Period, 20192029

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Five pipeline agents vying for share in the rheumatoid arthritis market - pharmaceutical-technology.com

SEATTLE--(BUSINESS WIRE)--Having used a multitude of traditional modalities for clinical charting, including transcription services and in-person scribes, Dr. Jasen Chi was determined to find the holy grail he envisioned. Chi wanted to enter the exam room, confer with a patient in-depth, and exit knowing the SOAP note would be quickly and accurately generated based on what was said, with structured and narrative data populated directly to the electronic health record (EHR). He recently discovered that very solution with Saykara and is now seeing more patients and enjoying better, more robust documentation as a result.

Saykara is a Seattle-based health tech startup using artificial intelligence (AI) to free physicians from administrative burdens. The companys proprietary platform applies deep machine learning and long-form natural language understanding to write notes, orders, referrals and more by ambiently listening to conversations between physicians and patients.

One of the most important things the healthcare community can do to improve access to care and drive costs down is make sure physicians are consistently performing at the top of their license, says Shawn Studdard, CEO and practice director of Chi Arthritis & Rheumatology. Saddling physicians with tasks like documentation creates barriers and time constraints that our nations healthcare system needs to overcome. Adopting technology like the Saykara mobile AI voice assistant is a big step forward toward resolving this problem.

Chi Arthritis & Rheumatology is known for diagnosing difficult autoimmune conditions, protecting joints from long-term erosions and deformities, and offering aggressive treatments and plans for improved quality of life. Founder, Dr. Jasen Chi, considers the exam room a sacred space for patients and family members, and refuses to allow computer data entry during visits. I want patients to feel like they are receiving our undivided attention with no distractions, says Chi. We dont want anything standing in the way of our ability to connect with patients and earn their trust.

By using the Saykara mobile AI voice assistant, Chi is now able to see approximately 15% more new patients a week. He has completely eliminated after-hours charting and dramatically reduced the overall amount of time spent charting. SOAP notes are populated directly to the EHR, requiring only his review and signoff.

Like all physician practices, Chi Arthritis & Rheumatology is faced with conforming to the 2021 evaluation and management (E/M) coding changes. Studdard feels that by using the Saykara mobile AI voice assistant, they are aptly positioned to support the updated medical decision making (MDM) criteria. Using the Saykara mobile AI voice assistant has increased the quality and comprehensiveness of our SOAP notes, which I believe will allow us to more than adequately satisfy the level of documentation needed for new E/M coding, says Studdard. I also believe that having audio files of everything said during physician-patient visits is ideal for addressing claims-related matters that may arise, such as audits, denials or downcoding.

Access to audio files captured by Saykara also aids the orientation and education of Chi Arthritis & Rheumatologys advanced practice nurses. Having our advanced practice nurses listen to visits with complex patients is a very useful teaching tool, says Studdard. The Saykara mobile AI voice assistant is definitely helping us maximize productivity and efficiency, and with our fifth location opening soon, this is more important than ever.

About SaykaraSaykara has developed a platform that uses artificial intelligence (AI) to interpret conversations between physicians and patients, transform salient content into clinical notes, orders, referrals and more, then populate both structured and narrative data directly to electronic health record systems. This is accomplished through a voice-enabled assistant named Kara that physicians access via a mobile app. The platform is specialty agnostic, scalable across any size enterprise and available with a software-as-a-service (SaaS) subscription. It has been proven to completely eliminate after-hours charting, reduce overall time spent charting by up to 70%, and enhance documentation quality and completeness by an average of 20%. Plus, with no need for computer data entry during visits, it gives physicians more face time with their patients and fosters more personalized interactions. For additional information, visit http://www.saykara.com.

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Chi Arthritis & Rheumatology able to see more patients and support new E/M coding using mobile AI voice assistant from Saykara - Business Wire

New York, Dec. 15, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Autoinjectors Market by Therapy, Type, Route of administration, End User - Global Forecast to 2025" - https://www.reportlinker.com/p05482959/?utm_source=GNW The patent expiry of biologics is also expected to provide growth opportunities for players in the market.On the other hand, the preference for alternative routes of drug delivery such as oral diabetic agents and nasal epinephrine sprays is expected to limit the adoption of autoinjector devices.

The rheumatoid arthritis segment accounted for the largest share of the autoinjectors market in 2020Based on therapy, the autoinjectors market is segmented into rheumatoid arthritis, multiple sclerosis, anaphylaxis, diabetes, and other therapies (cardiovascular diseases, migraine treatment, anemia, and progesterone therapy).In 2019, rheumatoid arthritis accounted for the largest market share of autoinjectors market.

The large share of this segment is mainly due to the high prevalence of rheumatoid arthritis.

The subcutaneous segment is projected to grow at the highest CAGR during the forecast periodBased on route of administration, the autoinjectors market is segmented into intramuscular and subcutaneous.Patients use autoinjectors for intramuscular and subcutaneous administration of various drugs for the treatment of diseases such as rheumatoid arthritis, multiple sclerosis, anaphylaxis, diabetes, migraine, anemia, and cancer.

The subcutaneous segment is projected to grow at the highest CAGR during the forecast period. The highest CAGR of this segment can primarily be attributed to the growing number of product approvals by regulatory bodies for the treatment of chronic diseases.

North America accounted for the largest share of the autoinjectors market in 2020.The autoinjectors market is segmented into five major regions, namely, Europe, North America, the Asia Pacific, Latin America, and the Middle East & Africa.North America was the largest regional market for autoinjectors.

Growth in the North American market is majorly driven by factors such as the rising incidence of anaphylaxis and the presence of favorable reimbursements.Moreover, the US and Canada are developed economies with high awareness and adoption rates for advanced devices such as autoinjectors, which is beneficial for market growth.

Furthermore, other microeconomic indicators such as rising healthcare expenditures, high affordability rate, and the improving regulatory scenario are also major factors contributing to market growth. By Company: Tier 1: 40%, Tier 2: 35%, and Tier 3: 25% By Designation: C-level Executives: 25%, Directors: 55%, and Others: 20% By Region: North America: 40%, Europe: 25%, APAC: 20%, LATAM: 10% and MEA: 5%

Some of the key players in the autoinjectors market are AbbVie Inc. (US), Mylan (US), Eli Lilly and Company (US), Ypsomed (Switzerland), Amgen (US), Becton, Dickinson and Company (US), GlaxoSmithKline plc (UK), Johnson & Johnson (US), Teva Pharmaceutical (Israel), Antares Pharma (US), Merck KGaA (Germany), Meridian Medical Technologies, Inc. (US), Roche Diagnostics (Switzerland), Bespak (UK), Bayer (Germany), SHL Medical (Switzerland), Haselmeier (Switzerland), Owen Mumford (UK), Ravimed (Poland), Medeca Pharma AB (Sweden), Cambridge Consultants Ltd. (UK), Flex (US), SMC Ltd. (US), and Promius Pharma (US). The study includes an in-depth competitive analysis of these key players in the autoinjectors market, along with their company profiles, recent developments, and key market strategies.

Research Coverage:The market study covers the autoinjectors market across various segments.It aims at estimating the market size and the growth potential of this market across different segments by therapy, type, route of administration, end users and region.

The study also includes an in-depth competitive analysis of the key players in the market, along with their company profiles, key observations related to their product and business offerings, recent developments, and key market strategies.

Key Benefits of Buying the Report:The report will help market leaders/new entrants in this market and provide information regarding the closest approximations of the autoinjectors market and its subsegments.This report will help stakeholders understand the competitive landscape, gain insights to position their businesses better, and plan suitable go-to-market strategies.

The report will also help stakeholders understand the pulse of the market and provide information on key market drivers, restraints, opportunities and challenges.

Read the full report: https://www.reportlinker.com/p05482959/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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The global autoinjectors market is projected to reach USD 104.9 billion by 2025 from USD 46.0 billion in 2020, at a CAGR of 17.9% from 2020 to 2025 -...

Purpose:Pain and cartilage destruction caused by rheumatoid arthritis (RA) are major challenges during clinical treatment. Traditional systemic administration not only has obvious side effects but also provides limited relief for local symptoms in major joints. Local delivery of therapeutics for RA treatment is a potential strategy but is limited by rapid intraarticular release.

Materials and methods:In this study, we prepared a thermoresponsive injectable hydrogel by mixing pluronic F127 (F127) and hyaluronic acid (HA) with poly (-glutamic acid) (PGA) incorporating infliximab (IFX), a new generation monoclonal antibody drug. We investigated the biocompatibility of the hydrogel and its IFX release profile. In vivo, we studied the clinical manifestations (articular skin temperature and joint diameter), detected cytokines in the synovial fluid and cartilage, performed behavioral studies on pain relief, and evaluated the cartilage protection effect.

Results:A thermoresponsive hydrogel was successfully prepared by mixing F127, HA, and PGA with injectable properties. The F127-HA-PGA hydrogel had a porous structure with interconnected pores. The infliximab-loaded thermosensitive hydrogel exhibited good biocompatibility and biodegradability and sustained release properties. Intraarticular injection of the IFX-loaded F127-HA-PGA hydrogel could alleviate the expression of inflammatory cytokines, such as tumor necrosis factor- (TNF-), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-17 (IL-17), in the synovial fluid and cartilage as well as relieve pain and inhibit cartilage destruction in RA.

Conclusion:The double effect on pain relief and cartilage protection indicated the significant potential of the IFX-loaded injectable hydrogel for RA treatment in major joint lesions.

Keywords:control release; hydrogel; infliximab; intraarticular injection; rheumatoid arthritis.

See the original post here:
Intraarticular Injection of Infliximab-Loaded Thermosensitive Hydrogel Alleviates Pain and Protects Cartilage in Rheumatoid Arthritis - DocWire News

STOCKHOLM, Dec. 15, 2020 /PRNewswire/ -- Cyxone (publ.), a clinical stage biotech company developing first-in-class drugs for diseases of the immune system, announced today that the company has filed an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) pertaining to its drug candidate Rabeximod. The application follows on a productive pre-IND meeting with the authority, where valuable advice was received on inter alia the protocol for its imminent European Phase 2 clinical study in moderate Covid-19. The IND covers the development of Rabeximod in Covid-19 and other indications, such as rheumatoid arthritis, and is a prerequisite for a future validation of the company's five recent patent applications in the US market.

Cyxone recently held a constructive pre-IND meeting (type B meeting) with the FDA, and the authority's advice has been incorporated in the study protocol for the clinical study of Rabeximod in Covid-19, which is expected to be initiated shortly in Europe. The filing of an IND will enable participation of US medical centers in future clinical studies of Rabeximod in Covid-19, rheumatoid arthritis and potential other indications. The IND package is based upon the favorable safety profile of Rabeximod shown in previous Phase 1 and Phase 2a studies. In Covid-19, Rabeximod is positioned as an oral treatment of moderately diseased patients - a group that is not addressed by current standard of care therapeutics.

"Filing an IND with the FDA is an important step in the clinical development of Rabeximod. It is a quality stamp on our drug candidate and Covid-19 trial and would enable us to expand the clinical development to the United States. Even as vaccines are becoming available, safe and convenient treatments for Covid-19 will be required to lower the death toll of the current global health emergency and to be better prepared for future pandemics", said Cyxone's CEO, Tara Heitner.

Cyxone recently announced that the company had received regulatory approval to initiate a randomized, placebo controlled, double blind, Phase 2 clinical trial of Rabeximod in Poland. In parallel, the company has submitted a Clinical Trial Application in Slovakia and is preparing for submissions in additional countries. Rabeximod will be evaluated in patients suffering from moderate Covid-19 in need of oxygen treatment but not ventilation support. In the study, 300 patients will receive Rabeximod orally at one of two dose levels or placebo for 14 days after which Cyxone will evaluate the study outcome. Cyxone aims to announce top-line results from the study in the third quarter of 2021.

"We look forward to initiating the Phase 2 study in Covid-19 patients as soon as possible, to provide important information about the safety and efficacy of Rabeximod in an acute setting", said Cyxone's Chief Operating Officer, Malin Berthold.

Contact

Tara Heitner, CEOTel: +46 70 781 88 08Email: tara.heitner@cyxone.comAdelgatan 21211 22 Malm, Sweden

This contains such information that Cyxone AB is required to make public under the EU's Market Abuse Regulation. The information was provided under the auspices of the above contact person for publication on 15 December 2020 at 09.25 CET.

About Cyxone

Cyxone AB (publ) (Nasdaq First North Growth Market: CYXO) develops disease modifying therapies for diseases such as rheumatoid arthritis and multiple sclerosis as well as treatments for virally induced acute respiratory disorders. Rabeximod is a Phase 2 candidate drug being evaluated for the management of rheumatoid arthritis and moderate Covid-19 infections. T20K is a Phase 1 candidate drug for treatment of multiple sclerosis. Certified Adviser is Mangold Fondkommission AB, +46 (0)8 503 015 50, ca@mangold.se. For more information, please visit http://www.cyxone.com

This information was brought to you by Cision http://news.cision.com

https://news.cision.com/cyxone/r/cyxone-has-filed-an-ind-in-the-us-with-rabeximod-following-positive-feed-back-from-pre-ind-meeting-w,c3254848

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SOURCE Cyxone

Company Codes: ISIN:SE0007815428, Stockholm:CYXO

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Cyxone has filed an IND in the US with Rabeximod following positive feed-back from pre-IND meeting with the FDA - BioSpace

Objectives:Predicting serious infections (SI) in patients with rheumatoid arthritis (RA) is crucial for the implementation of appropriate preventive measures. Here we aimed to identify risk factors for SI and to validate the RA Observation of Biologic Therapy (RABBIT) risk score in real-life settings.

Methods:A multi-centre, prospective, RA cohort study in Greece. Demographics, disease characteristics, treatments and comorbidities were documented at first evaluation and one year later. The incidence of SI was recorded and compared with the expected SI rate using the RABBIT risk score.

Results:A total of 1557 RA patients were included. During follow-up, 38 SI were recorded [incidence rate ratio (IRR): 2.3/100 patient-years]. Patients who developed SI had longer disease duration, higher HAQ at first evaluation and were more likely to have a history of previous SI, chronic lung disease, cardiovascular disease and chronic kidney disease. By multivariate analysis, longer disease duration (IRR: 1.05; 95% CI: 1.005, 1.1), history of previous SI (IRR: 4.15; 95% CI: 1.7, 10.1), diabetes (IRR: 2.55; 95% CI: 1.06, 6.14), chronic lung disease (IRR: 3.14; 95% CI: 1.35, 7.27) and daily prednisolone dose 10 mg (IRR: 4.77; 95% CI: 1.47, 15.5) were independent risk factors for SI. Using the RABBIT risk score in 1359 patients, the expected SI incidence rate was 1.71/100 patient-years, not different from the observed (1.91/100 patient-years; P = 0.97).

Conclusion:In this large real-life, prospective study of RA patients, the incidence of SI was 2.3/100 patient-years. Longer disease duration, history of previous SI, comorbidities and high glucocorticoid dose were independently associated with SI. The RABBIT score accurately predicted SI in our cohort.

Keywords:comorbidities; glucocorticoids; infections; rheumatoid arthritis; risk score.

Read this article:
Incidence, risk factors and validation of the RABBIT score for serious infections in a cohort of 1557 patients with rheumatoid arthritis - DocWire...

New research published in Nature has revealed important genetic causes of the most severe forms of COVID-19 disease.

Researchers studied over 2,000 severely ill patients with COVID-19, and compared their genomes to those of healthy people from existing population studies in the UK. They found that patients were much more likely to possess variations in a small number of genes that affect anti-viral immune responses and inflammation information that suggests existing drugs could be useful treatments for severe disease.

COVID-19 has been known for almost a year now, but the variation in effects on different people remains baffling: some experience no discernible symptoms at all, others a mild or moderate illness, and some a very distinct, severe and life-threatening illness. Although certain clear risk factors have emerged for the most dangerous forms of the disease, notably older age and certain conditions such as heart disease, diabetes and severe obesity, both within and outside these groups, SARS-CoV-2 infection causes a bewildering and unpredictable range of responses.

Understanding precisely who is and is not at greater risk of dangerous forms of the disease would play a very important role in ongoing efforts to control the disease and prevent the worst effects. It would allow preventative efforts including new vaccines to be directed first towards those at greatest risk. It also offers important clues to the underlying mechanisms that drive the most severe forms of disease, and hence to potential treatments.

It has seemed likely from the beginning that genetic variation between different people accounts for some of the otherwise inexplicable variation in disease severity. It may also account for differing disease susceptibility how likely someone is to become infected; this is the case for many other infectious diseases, though it is less obvious to see and hence to study. Doctors and scientists around the world have thrown themselves into efforts to uncover the genomic factors driving severe disease.

This new paper used DNA samples from over 2,200 patients with severe COVID-19 treated in over 200 intensive care units were obtained from to major research initiatives, the GenOMICC (Genetics Of Mortality In Critical Care) and the ISARIC Coronavirus Clinical Characterisation Consortium 4C studies. Genome sequences were compared with healthy control subject genomes from the UK Biobank to identify areas of the genome where there were significant differences. Findings were checked against samples from a similar number of hospitalised cases from the COVID-19 Host Genetics Initiative.

A handful of important genes involved in severe COVID-19 were identified, of two main types. The first group were genes involved in antiviral defences; the OAS gene helps block replication and spread of the virus, whilst IFNAR2 is involved in the production of an important immune mediator, interferon, which helps to trigger immune responses to viral infections. Weak early responses to infection could help the SARS-CoV-2 virus to spread and grow in the patient.

These discoveries are in line with earlier findings that pinpointed genetic changes that impaired interferon function among severe COVID-19 patients. Whilst giving interferon to critically ill patients has not proved very effective, there is hope that early administration to people with genetic predisposition to poor interferon responses who are infected by the virus might prevent severe disease.

The second group of genes implicated in severe COVID-19 were likely to play a role in the dangerous inflammatory lung damage seen in patients in critical care. These included rare variants in the TYK2, DPP9 and CCR2 genes. TYK2 is involved in controlling immune response; a rare variant that causes excessive inflammation was common among patients. This is a positive finding, since there are already anti-inflammatory drugs that target this particular biological pathway, and could prove to be valuable new treatments. Both DPP9 and CCR2 are also involved in different aspects of inflammatory responses to infection.

The researchers expect that there are other genes that affect the risk of severe disease, and hope to uncover more of these in due course as they analyse genomes additional patients; rarer genetic changes are harder to find and require larger numbers of people in studies. They are particularly interested in additional genetic factors that might account for the increased risk of severe disease seen in certain ethnic groups.

Meanwhile, other researchers continue to employ genome sequencing of the virus itself, rather than human hosts, to aid the battle against COVID-19. The UK government recently announced an additional 12.2 million funding for the COVID-19 Genomics UK (COG-UK) Consortium to continue and expand viral genome sequencing. Combining this information with patient data helps to identify whether the virus is becoming more or less infectious, or dangerous, or amenable to new vaccines all vital information.

Tackling COVID-19 without the insights provided by genomics would be infinitely more difficult like trying to understand the virus and the disease blindfolded and would undoubtedly have hugely slowed the development of vaccines, treatments and other responses to limit the harm caused by the pandemic.

Take a look at our short animation on pandemic in the genomic era

Link:
Further genetic clues to severe COVID-19 - PHG Foundation

Humans come in a variety of heights and genetics play a key role in determining whether you will be short or tall.

Theres much more than just heredity to consider before assuming a person will automatically be the same height as their parents. Medical conditions, hormonal deficiencies, and more can all contribute to how tall you are.

Read on to learn about all of the components that contribute to a persons natural height.

Genetics are among the prominent factors that contribute to how tall youll be.

As a general rule of thumb, your height can be predicted based on how tall your parents are. If they are tall or short, then your own height is said to end up somewhere based on the average heights between your two parents.

Genes arent the sole predictor of a persons height. In some instances, a child might be much taller than their parents and other relatives. Or, perhaps, they may be much shorter.

Such key differences may be explained by other factors outside of your genes that contribute to height.

Aside from genetics, there are other factors to consider that can determine a persons height, especially during childhood and adolescence.

While eating more vegetables wont automatically make you taller, getting adequate nutrition during your growing years is critical in human development, including your height.

A diet based on whole, nutritious foods can ensure you will grow up to the height your genes might dictate. On the flip side, a poor diet could lead to a shorter stature compared to your parents.

Eating healthy isnt so simple for all families. Children of a poor socioeconomic status may be at risk of a lack of access to nutrition, along with poor access to adequate health care. This, in turn, can contribute to a shorter height.

You may notice that boys grow slower than girls at first, due to differences in puberty milestones. Overall though, adult males tend to be an average of 14 centimeters (5.5 inches) taller compared to adult females.

During puberty, hormones are essential for regulating body growth. These include thyroid hormones, human growth hormones, and sex hormones such as testosterone and estrogen.

Any abnormalities in these hormones could alter growth as well as your overall height. Children who develop hypothyroidism (low thyroid) or pituitary gland disorders may experience shorter than average height compared to their parents.

Rarely, hormonal disorders can contribute to being taller than normal. For example, gigantism is caused by too many human growth hormones produced by pituitary gland tumors.

Some conditions present at birth may dictate a persons height. For example, achondroplasia (dwarfism) is a rare bone growth disorder that runs in families.

Another congenital disorder that can cause short stature is known as Turner syndrome. This rare condition causes delays in puberty. Unlike achondroplasia, Turner syndrome doesnt run in families.

Other congenital disorders lead to a taller than normal stature. These include Marfan and Klinefelter syndromes.

Marfan syndrome is caused by connective tissue enlargements, while Klinefelter syndrome occurs when males are born with an additional copy of the X chromosome.

Overall, theres no way you can increase your height. Each person is born with genes that will help dictate how tall they become, but other factors such as inadequate nutrition or medical conditions may alter this outlook.

Hormonal conditions may be the few exceptions. If a lack of thyroid or human growth hormones is detected during childhood, then taking medications may help reverse the effects on height.

However, once you reach adulthood, taking hormonal replacements wont make you taller. At this point, your full height has already been achieved, and taking any medications or supplements wont make a difference.

Its important to focus on good nutrition during childhood, but sticking with these habits will also contribute to your overall health into adulthood and beyond regardless of your height.

Poor posture and lack of exercise can also contribute to poor stature, so correcting these items may help increase your height (or the appearance of it).

Its widely regarded that your genes will dictate how tall you become. However, there are other exceptions to this rule, including your gender, access to nutrition, and any underlying medical or congenital conditions you may have.

See a doctor if you have any concerns about your height, or if you have a child who isnt reaching their growth milestones. They can discuss nutritional issues with you, and they may help rule out the possibility of any hormonal issues.

Continue reading here:
Is Height Genetic? Why and Why Not? - Healthline

A dedicated University of WisconsinMadison clinician, educator, advocate and researcher, Renata Laxova, professor emerita of medical genetics and pediatrics, passed away recently after a brief illness. She was 89.

Laxovas lifelong interests focused on the causes of intellectual and developmental disabilities, prenatal diagnosis of genetic disorders and birth defects, cancer genetics, and above all the relationships between medical professionals and the patients and families they serve. She was especially interested in coping strategies for families in difficult situations.

Renata Laxova

Laxova obtained MD and PhD degrees from the University Medical School in Brno, in what is now the Czech Republic. Initially trained in pediatrics, she later specialized in medical genetics at University College and Guys Hospital in London. She came to the United States in 1975 and joined the UWMadison departments of Pediatrics and Medical Genetics, where she served until she retired in 2000.

A skilled educator, Laxova loved teaching and stressed the importance of making clinical care personal. Understanding that genetics could be an extremely complicated discipline, Laxova worked to build awareness and accessibility through education and experiences. She underscored the importance of the patient perspective and was one of the first on campus to invite parents and families to share with her students their experiences caring for children with genetic conditions or disabilities.

David Wargowski, a clinical geneticist in the Waisman Center Medical Genetic Clinic a clinic and program Laxova helped build says Laxova inspired him to pursue a career in genetics. He first met Laxova as a medical student at UWMadison.

I found human genetics fascinating in college and was excited to have an opportunity to learn about how it applied to the medical care of people with genetic conditions, Wargowski says.

In the mid-1980s, medical genetics was still a field which primarily addressed rare disorders that were off the radar of most physicians.I learned about many of those, but more important to my medical training was learning from Laxovas example that being a good doctor is about more than being knowledgeable. It also means being compassionate and devoted to patients.

Patient care was primary for Laxova. Her innate ability to make connections with patients and learn their story set her apart. She is remembered for asking families during clinical visits, How can we most help you? a sentiment that embodied her commitment to patient advocacy and care that also led to her work on resources and supports for families throughout the state.

Responding to concern that many genetic disorders were going unnoticed and undiagnosed, Laxova helped establish the Genetic Contact Network. Within the network, professionals throughout the state identify people in need of genetic counseling and make referrals. These efforts led to the corresponding Genetic Services Network of outreach clinics and Laxova was a driving force behind the service sites in Green Bay, La Crosse and Eau Claire, among others.

At the Waisman Center, Laxova was in charge of the medical genetics program and clinic program and all of its elements clinical, education and research long before there was a program director, says Wargowski.

In 1976, Laxova was also instrumental in establishing the masters in genetic counseling training program with founding director Joan Burns. The training program was among the first of its kind in the United States and Laxova served as its first medical director, a position she held for more than 20 years. During that time, she helped train hundreds of genetic counselors while treating patients and their families in the Waisman Medical Genetics Clinic.

Casey Reiser, director of the Genetic Counselor Training Program, was herself a student in the third class of genetic counselors. Like Wargowski, Reiser had the opportunity to work with Laxova both as a student and colleague.

She was always animated and enthusiastic when she shared her knowledge with students, says Reiser. Renata was an inspiration, a wonderful mentor, and a beloved friend. She will be missed by many.

While known for the successes of her career, Laxova is also remembered for her experiences escaping both the Holocaust and communism. Laxova twice fled her homeland of the Czech Republic (then known as Czechoslovakia). In the days leading up to World War II, she escaped from the Nazis through safe passage to Britain on the last Kindertransport, which rescued thousands of children from the Holocaust. She returned in 1946.

In the late 1960s, married to her husband Tibor, and as a young mother, doctor and researcher, she once again made her way to Britain to avoid the encroaching Russian communist regime. The couple later moved to Wisconsin, where Tibor, a veterinarian, opened a practice. She joined the faculty of UWMadison in 1975. Her lifes story is chronicled in a poignant memoir dedicated to her grandson titled Letter to Alexander.

Wargowski describes the sentiment felt by many who knew and worked with Laxova.

If you didnt know her, Im sorry you didnt have that chance, he says. She was a remarkably gracious person with an amazing life story. She was absolutely devoted to her patients, her craft and her colleagues, especially those who asked for the opportunity to learn from her. She was a remarkably compassionate person and physician who taught more than genetics. She practiced a love for her patients to which most of us can only aspire, and an intolerance of disparity and discrimination that challenges the most motivated among us.

University Archives has two oral interviews with Renata Laxova from 2004 and 2008. You can access them here: https://search.library.wisc.edu/digital/AMGNC3S2LPJZPN83

More:
Holocaust survivor, geneticist, patient advocate remembered for inspiring others - University of Wisconsin-Madison

The US Food and Drug Administration granted approval yesterday (December 14) for a genetically modified line of pigs that marks the first time a GM animal has been given the regulatory greenlight for both therapeutic development and food consumption, the agency says in a statement. The alteration knocks out alpha-gal, a sugar molecule on the surface of cells, and could help minimize allergic reactions to pork and reduce the risk of organ rejection in transplant patients.

The move represents a a tremendous milestone for scientific innovation, FDA Commissioner Stephen Hahn says in the statement. The FDA strongly supports advancing innovative animal biotechnology products that are safe for animals, safe for people, and achieve their intended results.

Pigs with the genetic modification are known as GalSafe pigs and are made by Revivicor Inc, a subsidiary of the US biotech United Therapeutics. Research in the mid-2010s indicated that the knockout made transplants from the pigs less likely to be rejected by primate recipients.

The director of the FDAs Center for Veterinary Medicine, Steven Solomon, told reporters in a conference call yesterday that developers who want to use GalSafe pigs for therapeutic purposes will still have to seek approval for their applications. I think that people need to be careful, Solomon said, STATreports. Thats why in part, its going to require further evaluation for xenotransplantation, xenograft, or the other activities by the medical products centers and FDA.

As far as food production is concerned, the statement notes that the meat is safe for consumption by the general population, adding that Revivicor intends to sell meat from GalSafe pigs by mail order, rather than in supermarkets.

The agencys evaluation also concluded that GalSafe pigs presented low risk to the environment, with an impact that is no greater than from conventional pigs. It adds that no animal safety concerns were noted for GalSafe pigs beyond those that would be expected in well-managed, commercial swine populations.

Multiple other efforts to develop genetically engineered pigs are underway around the world, including some alterations designed to make pigs grow faster, and others aimed at making the animals more resistant to lethal viruses such as porcine reproductive and respiratory syndrome virus (PRRSV).

See original here:
FDA Clears Genetic Modification in Pigs for Biomedicine and Food - The Scientist

CiBER-seq dissects genetic networks

Cells integrate environmental signals and internal states to dynamically control gene expression. Muller et al. developed a technique to dissect this cellular logic by linking targeted, genome-wide genetic perturbations with a deep-sequencing readout that quantitatively measured the expression phenotype induced by each perturbation. The method, dubbed CiBER-seq, was able to recapitulate known regulatory pathways linking protein synthesis with nutrient availability in budding yeast cells. Unexpectedly, the authors found that the cellular logic also appears to consider protein production machinery in this decision. By uncovering additional facets of this deeply conserved pathway, the findings demonstrate the utility of comprehensive and quantitative CiBER-seq profiling in mapping the gene networks underlying cellular decisions.

Science, this issue p. eabb9662

Systematically profiling the effects of genetic perturbations is a powerful approach that has revealed the molecular basis for a wide range of biological phenomena. The simple, programmable DNA recognition of CRISPR-Cas9 enables genome-wide genetic analysis in human cells and many other systems. Cas9 is guided by a short RNA to a complementary sequence in the genome, where it can introduce mutations or alter gene expression. Pooled libraries of guide RNAs (gRNAs) that individually target each gene in the genome allow us to introduce genetic perturbations systematically into a population of cells. A key challenge is measuring the phenotypic effects caused by individual guides in these pooled libraries and linking these phenotypes back to the associated gRNA, thereby finding the gene that is responsible.

Molecular phenotypes such as gene expression changes provide a clear and sensitive measure for many cellular processes. We sought a general approach to profile how the expression of a particular gene of interest changed when other genes were perturbed. We began with a library of gRNAs, each disrupting one gene, and linked these guides with an expression reporter containing a guide-specific nucleotide barcode. gRNAs that alter reporter expression will change the abundance of the expressed RNA barcode specifically associated with that guide. Deep sequencing of these expressed barcodes quantifies each of these guide-specific reporter expression effects individually within a pooled, complex population. We have implemented this strategy by combining CRISPR interference (CRISPRi) with barcoded expression reporter sequencing (CiBER-seq).

We used CiBER-seq to profile the responses of several yeast promoters tied to a range of biological functions. Each promoter yielded a distinct pattern of responses that could be understood in terms of its known function and regulation. For example, we rediscover the control of MET6 expression by regulatory ubiquitylation and connect the bud scar protein Cwp1 to other genes required for budding and cytokinesis. Our analysis of the HIS4 promoter, a well-characterized target of the integrated stress response, yielded a range of genetic perturbations that activate this pathway by causing the accumulation of uncharged transfer RNAs (tRNAs). We also uncovered a notable role for tRNA depletion in this response, as impaired tRNA biogenesis activated HIS4 expression through a distinct pathway. In order to understand this regulation, we carried out genetic interaction analysis and looked for quantitative deviations in CiBER-seq profiles caused by the introduction of a second genetic perturbation. We also developed an indirect CiBER-seq approach to measure translational and posttranslational regulation, which both play roles in the signaling pathways upstream of HIS4.

CiBER-seq produces comprehensive phenotypic profiles that offer insights into gene function and regulation. These high-throughput and quantitative phenotypic measurements are also well suited for the systematic measurement of genetic interactions, which contain rich information about the operation of biological processes. This approach can be applied to study a wide range of transcriptional, translational, and posttranslational regulatory responses, and it has the potential to shed light on many areas of biology.

CRISPR-Cas9 gRNA cassettes are linked with transcriptional reporters containing specific barcodes. The RNA-to-DNA ratio for each barcode, measured by deep sequencing, reveals the reporter expression phenotype induced by each gRNA.

To realize the promise of CRISPR-Cas9based genetics, approaches are needed to quantify a specific, molecular phenotype across genome-wide libraries of genetic perturbations. We addressed this challenge by profiling transcriptional, translational, and posttranslational reporters using CRISPR interference (CRISPRi) with barcoded expression reporter sequencing (CiBER-seq). Our barcoding approach allowed us to connect an entire library of guides to their individual phenotypic consequences using pooled sequencing. CiBER-seq profiling fully recapitulated the integrated stress response (ISR) pathway in yeast. Genetic perturbations causing uncharged transfer RNA (tRNA) accumulation activated ISR reporter transcription. Notably, tRNA insufficiency also activated the reporter, independent of the uncharged tRNA sensor. By uncovering alternate triggers for ISR activation, we illustrate how precise, comprehensive CiBER-seq profiling provides a powerful and broadly applicable tool for dissecting genetic networks.

View post:
CiBER-seq dissects genetic networks by quantitative CRISPRi profiling of expression phenotypes - Science Magazine

Genetic Testing to Establish Strong Foothold in Current and Future Healthcare System

The notable rise in the demand for hereditary genetic testing over the past few years is one of the major factors that is expected to fuel the growth of the global genetic analysis services market in the upcoming decade. Technological advancements coupled with the drive to discover new and innovative genetic analysis techniques are set to shape the overall growth trajectory of the global genetic analysis services market during the forecast period. Over the past decade, the genome testing sector has witnessed consistent developments due to which, the global genetic analysis services market is anticipated to expand at an impressive rate during the assessment period.

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Hereditary genetic testing has emerged as ideal, and a rapidly evolving technology within the genetic analysis services market. This is likely to continue, owing to advancements in technology and findings of research activities. The increasing demand for improved and cutting-edge prediction and diagnostic tools and services coupled with surge in demand for disease monitoring is anticipated to play a key role in the overall growth of the global genetic analysis services market during the assessment period.

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Healthcare experts and credible researchers around the world are of the opinion that genetic testing is expected to be the future of the healthcare ecosystem. Advancements in the biomedical field coupled with the notable rise in the number of companies that are developing new genetic-testing kits are expected to augment the global genetic analysis services market during the forecast period. Moreover, as interest levels for precision medicine continues to witness sizeable growth around the world, as a result of which the demand for genetic analysis services is projected to grow at an impressive pace.

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Uptake of Next-generation Sequencing and Multi-gene Tests to Drive Market

Advancements in the genetic technology are likely to play an instrumental role in shaping the growth trajectory of the global genetic analysis services market during the forecast period. Furthermore, due to advancements in technology, the scope of genetic testing has widened by a considerable margin due to which, the demand for genetic analysis services is increasing. While genetic analysis services in the past were largely time-consuming and cumbersome, at present, increasing speed and availability of genomic testing are anticipated to present a plethora of opportunities to the players involved in the current market landscape for genetic analysis services.

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In addition, the gradual shift in the point of access to testing is evolving, as more number of consumers can avail genetic analysis services outside the healthcare setting. Advancements in genetic medicine at the back of advancements in technology are likely to bolster the growth of the global genetic analysis services market during the assessment period.

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Research and Development Activities in Full Swing amid COVID-19 Pandemic

Research and development activities are expected to continue in full swing amid the ongoing COVID-19 pandemic. The significant rise in the demand for genetic counseling services during the ongoing COVID-19 crisis is anticipated to generate consistent revenue for the players involved in the genetic analysis services market. Furthermore, researchers and scientists are increasingly focusing on discovering genetic mechanisms that are required to prevent the spread and transmission of the novel coronavirus disease. Genetic research is estimated to unlock various intricate details of the novel coronavirus, thereby opening up new opportunities for mitigation. The ongoing research pertaining to genetics and its correlation with the ongoing pandemic is expected to provide a detailed and microscopic understanding of the overall cellular mechanisms of the virus.

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Genetic Analysis Services Market: Uptake of Next-generation Sequencing and Multi-gene Tests to Drive Market - BioSpace

From phenotype to structure

Much insight has come from structures of macromolecular complexes determined by methods such as crystallography or cryoelectron microscopy. However, looking at transient complexes remains challenging, as does determining structures in the context of the cellular environment. Braberg et al. used an integrative approach in which they mapped the phenotypic profiles of a comprehensive set of mutants in a protein complex in the context of gene deletions or environmental perturbations (see the Perspective by Wang). By associating the similarity between phenotypic profiles with the distance between residues, they determined structures for the yeast histone H3-H4 complex, subunits Rpb1-Rpb2 of yeast RNA polymerase II, and subunits RpoB-RpoC of bacterial RNA polymerase. Comparison with known structures shows that the accuracy is comparable to structures determined based on chemical cross-links.

Science, this issue p. eaaz4910; see also p. 1269

Determining the structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo quantitative measurements of genetic interactions. Genetic interactions report on how the effect of one mutation is altered by the presence of a second mutation and have proven effective for identifying groups of genes or residues that function in the same pathway. The point mutant epistatic miniarray profile (pE-MAP) platform allows for rapid measurement of genetic interactions between sets of point mutations and deletion libraries. A pE-MAP is made up of phenotypic profiles, each of which contains all genetic interactions between a single point mutant and the entire deletion library.

We observe a statistical association between the distance spanned by two mutated residues in a protein complex and the similarity of their phenotypic profiles (phenotypic similarity) in a pE-MAP. This observation is in agreement with the expectation that mutations within the same functional region (e.g., active, allosteric, and binding sites) are likely to share more similar phenotypes than those that are distant in space. Here, we explore how to use these associations for determining in vivo structures of protein complexes using integrative modeling.

We generated a large pE-MAP by crossing 350 mutations in yeast histones H3 and H4 against 1370 gene deletions (or hypomorphic alleles of essential genes). The phenotypic similarities were then used to generate spatial restraints for integrative modeling of the H3-H4 complex structure. The resulting ensemble of H3-H4 configurations is accurate and precise, as evidenced by its close similarity to the crystal structure. This finding indicates the utility of the pE-MAP data for integrative structure determination. Furthermore, we show that the pE-MAP provides a wealth of biological insight into the function of the nucleosome and can connect individual histone residues and regions to associated complexes and processes. For example, we observe very high phenotypic similarities between modifiable histone residues and their cognate enzymes, such as H3K4 and COMPASS, or H3K36 and members of the Set2 pathway. Furthermore, the pE-MAP reveals several residues involved in DNA repair and others that function in cryptic transcription.

We demonstrate that the approach is transferable to other complexes and other types of phenotypic profiles by determining the structures of two complexes of known structure: (i) subunits Rpb1 and Rpb2 of yeast RNA polymerase II, using a pE-MAP of 53 point mutants crossed against 1200 deletions and hypomorphic alleles; and (ii) subunits RpoB and RpoC of bacterial RNA polymerase, using a chemical genetics map of 44 point mutants subjected to 83 environmental stresses. The accuracy and precision of the models are comparable to those based on chemical cross-linking, which is commonly used to determine protein complex structures. Moreover, the accuracy and precision improve when using pE-MAP and cross-linking data together, indicating complementarity between these methods and demonstrating a premise of integrative structure determination.

We show that the architectures of protein complexes can be determined using quantitative genetic interaction maps. Because pE-MAPs contain purely phenotypic measurements, collected in living cells, they generate spatial restraints that are orthogonal to other commonly used data for integrative modeling. The pE-MAP data may also enable the characterization of complexes that are difficult to isolate and purify, or those that are only transiently stable. Recent advances in CRISPR-Cas9 genome editing provide a means for extending our platform to human cells, allowing for identification and characterization of functionally relevant structural changes that take place in disease alleles. Expanding this analysis to look at structural changes in host-pathogen complexes and how they affect infection will also be feasible by introducing specific mutations into the pathogenic genome and studying the phenotypic consequences using genetic interaction profiling of relevant host genes.

pE-MAPs are generated by measuring the growth of yeast colonies (left) and visualized as a heatmap (background). We present an application of pE-MAPs to determine protein complex structures, using integrative modeling, and apply it to histones H3 and H4 (right) and other complexes. H3 (purple) and H4 (teal) are highlighted in the context of the nucleosome [gray, modified Protein Data Bank (PDB) 1ID3].

Determining structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo measurements of genetic interactions. We construct phenotypic profiles for point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two profiles into an upper bound on the distance between the mutated residues. We determine the structure of the yeast histone H3-H4 complex based on ~500,000 genetic interactions of 350 mutants. We then apply the method to subunits Rpb1-Rpb2 of yeast RNA polymerase II and subunits RpoB-RpoC of bacterial RNA polymerase. The accuracy is comparable to that based on chemical cross-links; using restraints from both genetic interactions and cross-links further improves model accuracy and precision. The approach provides an efficient means to augment integrative structure determination with in vivo observations.

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Genetic interaction mapping informs integrative structure determination of protein complexes - Science Magazine

Otto von Habsburg never got to be emperor. Born in 1912, he watched as his familys grasp on political power slipped, and the dynasty that once dominated central Europe and beyond became just another surname that whispered of a greater history. A vocal participant in Europes postwar politics, he couldnt forget the legacy hed been born into: once, on being asked if he planned to watch an Austria-Hungary football match, he is said to have responded Perhaps who are we playing?

Otto, who spoke seven languages and whose heart was buried in Hungary while the rest of him reposed in Austria, was among the last of a line that can be traced at least to the 10th century, to the first Habsburg we can speak of with any certainty: Kanzelin (or possibly Lanzelin) of Altenburg, a small-time magnate in what today is Switzerland. Martyn Radys panoramic history narrates how Kanzelin and his descendants made money, territorial gains and enemies: the monks of a monastery they themselves had founded spread the idea that the earliest Habsburgs were no more than robber barons.

The family took their name from the Habichtsburg or Hawks Castle, from which heartlands they fitfully expanded their influence, until by the 15th century they were rulers of the Holy Roman empire, a great patchwork of princedoms and territories and the premier power in Europe next to France. Charles V, who became King of Spain in 1516 and was elected emperor in 1519, had as his motto plus ultra, meaning still further. In the 16th and 17th centuries Habsburg power spread across the globe, with the dynasty establishing a presence in sites from Brazil, Mexico and Peru to Goa, the Philippines and Taiwan, at the same time as their forces fought for dominance against those of the Ottoman sultans to the east. In 1700 Habsburg power came to an end in Spain and its associated territories, but the central European branch of the family would remain a pre-eminent force for two centuries yet.

The Habsburgs are often remembered for their dogged insistence on keeping power within the family. Between the 15th and the 18th century, the family branches assiduously married their young off to each other (after receiving papal permission for these incestuous unions). Rady notes that between 1450 and 1750, there were four uncle-niece marriages, 11 marriages between first cousins, four marriages between first cousins-once-removed, eight between second cousins, and many other marriages with more remote kinship. This genetic feedback loop contributed to a high incidence of mental illness, epilepsy, birth defects and other illnesses among Habsburg children, as well as the notorious Habsburg jaw, which even sympathetic portraitists struggled to conceal.

In telling a family history that spans a thousand years and almost every continent, Rady sets himself an almost impossible task. The Mbius strip of their family tree and the extent and variety of the lands and peoples they ruled over make writing any Habsburg history a kind of choose-your-own-adventure exercise, where the historians own interests and expertise will always shape the broader story. The backbone of Radys narrative is a fairly traditional chronological account, sketching the character of rulers and reigns since the end of the 10th century. Some chapters pause the action, leaving high politics to one side to allow time to discuss cultural and social questions, from the Peruvian baroque to an early 18th-century Serbian vampire craze. The effect is that of a well-polished lecture course, offering a digestible narrative of the familys rise and fall, leavened with some material that sets the central political story in its wider context. Whats missing is a sustained sense of what life was like for the millions who lived under the Habsburgs: how their wars, reforms, assassinations, and peccadilloes made themselves felt (when they did) among their subjects. What did the Habsburg story mean to those they ruled over?

Maybe its natural that historians would struggle to pin down the experience of life under the Habsburgs, since the breadth and sprawl of their lands meant that they themselves often felt as if they reigned over a paper empire. Great swathes of their lands would not see a rulers physical presence for decades or centuries, but a great central mechanism of chanceries, secretaries and civil servants toiled to record and regulate affairs. In the earliest days of the dynasty, they bolstered their power by drawing up histories and genealogies that boasted of their noble origins. When a little more was needed, they werent above faking the necessary evidence: in the 14th century, Rudolf of Habsburg had his scribes draw up fake charters that helped seal his familys claims to political power and regional control. Their paper empire would only grow, with Philip II of Spain a 16th-century royal micromanager who tried in vain to follow a global empire from his desk in Madrid. By the 1850s, about 50,000 civil servants came to work every day to track and tweak the operations of empire in a bewildering variety of languages.

From 19th-century censored texts to the royal propaganda of 400 years previously, Rady has managed to make sense of an empire and its archives in a way that its own rulers often struggled to. A real strength of this account is its attention to Habsburg stories outside Europe, from attempts to meddle in the 17th-century kingdom of Kongo, and the brief period in which emperor Franz Joseph became the colonial ruler of the Chinese port of Tianjin, to the role of Austrian ships in transporting hundreds of thousands of enslaved Africans into the eastern Mediterranean and beyond in the 19th century.

But all glory fades and when it did, the Habsburgs were a family who knew how to die. The posthumous journey of Otto von Habsburgs heart was part of a family tradition: from 1619 onwards, Habsburg rulers bodies would be divided in three, with the heart going to the Loreto chapel of the Augustinian church in Vienna, and much of the rest of the body going to the crypt of the nearby Capuchin church, while the citys imposing Stephansdom housed a growing collection of Habsburg intestines deep in its own sacred bowels. Their death throes were felt around the world, with early modern royal deaths plunging communities from Madrid to Mexico City into mourning, and inspiring the construction of towering catafalques which memorialised dead monarchs and their achievements.

Grief and loss were a part of the Habsburg experience, not least for the emperor Franz Joseph, who lost his son Rudolf to suicide, his wife Sisi to assassination by an Italian anarchist, and his brother, Maximilian, at the hands of a Mexican firing squad after four years as the countrys unlikely emperor he died with the words Viva Mexico! Viva independencia! on his lips. Maximilians nephew, the Archduke Franz Ferdinand, would be gunned down in Sarajevo in 1914: the dynastys dying days had begun. When the last emperor, Karl I, was ushered out of Viennas Schnbrunn Palace by the socialist leader Karl Renner, it was with the words: Herr Habsburg the taxi is waiting.

The Habsburgs: The Rise and Fall of a World Power is published by Allen Lane (30). To order a copy go to guardianbookshop.com. Delivery charges may apply.

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The Habsburgs by Martyn Rady review negative genetic feedback loop - The Guardian

The 1997 science fiction film Gattaca is set in a dystopic future in which the practice of eugenics selective breeding designed to pass on desired genetic traits is the norm.

In this society, couples who want to have children pursue technological reproduction rather than natural procreation. This allows them to pick which of their embryonic children they want to bear after surveying their genomes.

The moral imperative is for parents to conceive and bear the best possible child, not only with preferred physical traits or predispositions for particular talents, but also free from hereditary disease and disability.

To roll the dice and welcome whatever child you get is seen as irresponsible: Not only would you be knowingly disadvantaging your child, you would also be risking reintroducing undesirable genes back into the gene pool.

Sadly, what was science fiction just a few years ago has become a reality.

In the cover story of the December issue of The Atlantic, reporter Sarah Zhang visits Denmark, a country considered moral pioneers in the field of prenatal genetic testing, diagnosis, and decision-making.

In her conversations with families and experts, Zhang uncovers a devastating trend: more than 95% of pregnancies that have a test result showing a likelihood of Trisomy 21, known more commonly as Down syndrome, end in abortion. The phenomenon of selective abortion is gaining traction despite the fact that some results are false positives, and the fact that persons with Trisomy 21 have excellent survival rates and life expectancies.

Persons with Trisomy 21 have varying symptoms (and varying degrees of severity of symptoms), including intellectual disabilities and muscular-skeletal issues. They are more susceptible to heart problems, gastrointestinal abnormalities, and speech issues. Severe cases require significant intervention, therapy, and resources.

Yet others with Down syndrome go to college, find employment, live independently, and get married. Just like any person, their particular challenges and strengths become evident over time, in part due to their genetic makeup as well as the environment in which they develop.

Within hours of the 8,000-word articles publication online, some were praising Zhangs reporting for humanizing and giving a voice to people with Down syndrome. Others, including pro-lifers, expressed outrage: For instance, one writer at The Federalist accused the author of seeking to create sympathy and understanding for eugenics and a modern-day genocide.

But beyond the pieces implications for the pro-life and pro-choice movements, Zhang identifies an uncomfortable, telling paradox one that signals the dawn of what has been called the genetic information age. She writes:

In wealthy countries, it seems to be at once the best and the worst time for Down syndrome. Better health care has more than doubled life expectancy. Better access to education means most children with Down syndrome will learn to read and write. Few people speak publicly about wanting to eliminate Down syndrome. Yet individual choices are adding up to something very close to that.

Put in other words, the article is an invitation for the world to ask itself: How can a society that celebrates diversity, inclusion, and tolerance allow its members who have genetic differences to be systematically, surgically extracted from its population?

During an amniocentesis, a doctor punctures the abdominal wall of a pregnant woman to withdraw the fluid. The fluid is then analyzed for various chromosomal abnormalities. Today, that information can be gleaned from a mothers blood sample by the 10th week of pregnancy. (Shutterstock)

Three overlapping factors have created new moral questions around child-bearing: 1) reproductive technologies, originally designed to assist couples struggling with infertility, have proliferated in type and availability; 2) the project to map the human genome, completed in 2003, has given scientists and doctors a window into the genes of their patients as well as their patients gametes; and 3) prenatal genetic testing has become a routine part of obstetric care.

While originally developed to assist couples who were unable to conceive children through natural procreation, artificial reproductive technologies (ART) now comprise a booming fertility industry. Services like in vitro fertilization are now cheaper, less riskier to women, and more likely to be covered by insurance and thus more widely available.

Because marriage and child-bearing are increasingly delayed in wealthier nations, both infertility and the risk of chromosomal abnormalities are on the rise. This makes in vitro fertilization, now paired with genetic testing, a more desirable method of reproduction: From a consumer standpoint, getting the healthiest possible child is the best investment in terms of time, cost, and risk.

But even if a woman gets pregnant naturally, she is likely to be offered prenatal screening for major chromosomal abnormalities. In the U.S., prenatal testing was generally offered to women over 35 or those with high-risk pregnancies. As of 2019, more than 60% of OBGYNs had offered it as part of their standard care to all patients.

In Denmark, nearly all pregnant women choose to have their developing children screened for genetic abnormalities.

Prenatal testing used to be done later in the second trimester if an ultrasound revealed atypical development, or if parents knew they were carriers for genetic conditions. Today, that information as well as the sex of the baby can be gleaned from a mothers blood sample by the 10th week of pregnancy.

Genetic counselors are supposed to present findings with value neutrality, meaning their language and affect is not supposed to sway patients decision-making. But Zhang spoke to advocates for persons with Down syndrome who were actively lobbying health care providers to change their language, for fear that the increase in selective abortion was correlated to language that increased parental fear.

Even shifting language from risk to probability could help open parents up to choosing life, they argued.

In many of the cases Zhang learned about, the children were originally wanted sometimes desperately so but in one catastrophic moment, they became unwanted. Parental fears about their childs quality of life as well as disappointment over losing the family that they had hoped for swayed them toward abortion.

Suddenly, Zhang writes, a new power was thrust into the hands of ordinary people the power to decide what kind of life is worth bringing into the world.

The world that The Atlantic article describes is one shaped by what Notre Dame law and political science professor O. Carter Snead calls expressive individualism in his new book What It Means to Be Human: The Case for the Body in Public Bioethics (Harvard University Press, $39.95).

This philosophy equates being fully human with finding the unique truth within ourselves and freely constructing our individual lives to reflect it, writes Snead. It considers human relationships as transactional, formed by agreements, promises, and consent for the mutual benefits of the parties involved.

Such a philosophy, he argues, leaves us without a coherent vision of our moral obligations to one another, especially the most vulnerable. This is illustrated in Zhangs piece by a series of moral quandaries that selective abortion poses.

Pope Francis kisses Peter Lombardi, 12, of Columbus, Ohio, after the boy rode in the popemobile during his general audience in St. Peter's Square at the Vatican in 2018. (Catholic News Service/Vatican Media)

If reproductive decision-making is an individual choice, what should a society do when thousands (or millions) of individual choices result in massive demographic or sociological changes?

Is a eugenic movement brought about by a societys own choosing any less problematic than one which is forced on a people, such as the campaign to eradicate persons with disabilities designed by the Nazis or the current campaign by the Chinese government to eliminate its Uyghurs population?

Zhang uncovers what she calls the most perverse moral problem in an exchange with a Danish woman who heads the National Down Syndrome Association. The woman, who is also a mother to 18-year-old son with Down syndrome, educates expectant parents about the condition.

During one of their conversations, the teenage boy leans over and looks at his mothers phone. The title of a controversial documentary called Death to Down Syndrome was displayed on the screen, and he immediately recoiled.

The reporter realized that he was cognizant of the fact that there are people who dont want people like him to be born. Moreover, his mother supports the right to abortion, even in cases like his.

The scene illustrates the ultimate conundrum for a society that supports the unrestricted right to abortion while claiming to uphold the equality of all human beings as a foundational moral principle: A woman must convince her child that his life is valuable, dignified, and worthy of living, while also supporting the rights of others to end the life of their child with his same genetic markers.

The response of a Catholic reader to the article would seem clear-cut: Because abortion is the taking of human life in its most vulnerable stage, it violates the fundamental right of all human beings to continue their life until natural death. Abortion, as well as any reproductive technology involving the creation, testing, and destruction of embryos, must be rejected.

But Catholic teaching does not stop at the moral evaluation of the technology or the act of abortion. The Gospel goes deeper it speaks to the heart of parents who receive a devastating diagnosis. It speaks to the vocation of health care workers and geneticists to heal when they can and offer comfort when they cannot. And it speaks to families about what it means to be open to the mystery of Gods design for family life.

In a 2019 speech, Pope Francis lamented the fact that thanks to modern prenatal testing techniques, even the suspicion of an illness, and especially the certainty of a disease, changes the experience of pregnancy and causes deep distress to women and couples.

The isolation and worry about the suffering that lies ahead, the pope said, is like a silent cry, a call for help in the darkness, when faced with an illness whose outcome cannot be foreseen with certainty.

In the face of fear and isolation, parents need support from a larger community, whether through their extended family, the parish, or others who have been in their situation. Support from a community is the first antidote to the individualism and isolation of reproductive choice.

When it comes to the issue of medical language, The Atlantic article notes that while genetic counselors and obstetricians are trained and required to present genetic information in as neutral a way as possible to patients, that doesnt always happen.

Pope Francis has admonished clinicians who use the phrase incompatible with life to describe genetic conditions that correspond with short lifespans or severe physical and cognitive impairments. For one thing, where there is a living human being, there is life.

Second, he says:

No human being can ever be unfit for life, whether due to age, state of health or quality of existence. Every child who appears in a womans womb is a gift that changes a familys history, the life of fathers and mothers, grandparents and of brothers and sisters. That child needs to be welcomed, loved and nurtured.

The fact that so many parents, when faced with a diagnosis of Down syndrome or other genetic anomalies, choose abortion tells Catholics a few things about why and where the Gospel is needed.

A society that reveres health and wellness is one that will have trouble in the face of sickness, aging, and death. It needs to hear the good news that suffering has been redeemed, and that it stretches the hearts of patients, caregivers, and the people they encounter.

A scene from the movie Gattaca. (IMDB)

Being mortals, bodily decay or dysfunction will come to all of us; some members of our human family experience it more acutely or earlier than others. They should receive more care, not more marginalization, because of it.

A materialist society that reduces people to their bodies and even microscopically, to their genetic material needs to know the truth that human beings have a body and a soul. The most important quality that children have and develop is their capacity to love, something that does not depend on their physical or cognitive ability.

A consumer-driven society, one that has become accustomed to customizable, curated lifestyles, is one that considers parenthood as a fulfillment of desires or a way to construct meaning and identity. Such a society which does not pause at the ways it commodifies its children needs to be reminded to protect the little ones. And a society that has unlimited access to information desperately needs wisdom.

The opening credits of Gattaca include a cautionary line from the Book of Ecclesiastes: Consider what God has done: Who can straighten what He has made crooked?

The answer to this rhetorical question should humble us. It should also help us to see all children not as something owed, but as gifts to be received as is, with all of their challenges and strengths.

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The Genetic Information Age is here. Are we ready? - Angelus News

The lynx-hare predator-prey cycle that has existed for thousands of years in North America is increasingly under threat from climate change.

The lynx are specialist predators that rely almost exclusively on snowshoe hare for food. This has led to a tight link between the populations of the two species; as the snowshoe hare populations rise and fall over a roughly 10-year cycle, lynx populations follow suit, says Dr. Jamie Gorrell, a VIU Biology Professor. When hare abundance is at its peak, lynx have plenty of food and have high survival rates, causing population booms that match, but lag slightly behind, those of the hare.

As snowshoe hare populations begin to decline, some lynx change their behaviour and begin to travel long distances, sometimes more than 1,000 kilometres, in search of food.

To understand how this cycle, which helps maintain the biodiversity of more than a dozen species in the boreal forest, could be impacted by climate change Gorrell and Dr. Evan Hersh, a VIU post-doctoral fellow, are studying the genetics of Canada lynx.

The genetic information will help researchers and conservationists understand lynx movements and connectivity among populations to identify potential habitat corridors that are essential to ensuring lynx populations remain genetically diverse.

Genetically mixed lynx populations will in turn help lessen the impact climate change may have on the stability of the lynx-hare cycle, a process vital to the functioning of boreal and sub-boreal ecosystems, says Gorrell.

Hersh is using genomic analyses and bioinformatics to analyze DNA samples that were collected with the help of Yukon residents, fur trappers and the Yukon Community Ecological Monitoring Program. The samples were collected at multiple phases during a 10-year cycle in hare abundance.

Hersh recently finished his PhD in plant ecology and evolution at the University of British Columbia and has extensive experience in genomic techniques. He says biologists now also need to be computer programmers to be able to crunch the huge amounts of data being generated in the genomic era.

Hersh will be comparing the genetic differences between Canada lynx from different areas. He said with newer techniques, instead of comparing a few hundred genetic markers, researchers can now compare tens of thousands of genetic markers.

Were hoping this thousandfold increase in the amount of data will give us the ability to figure out what is going on with their population structure. To date, no one has really applied these cutting-edge genomic techniques that produce huge amounts of data to analyze the population structure of Canada lynx within a conservation and management context, says Hersh.

The lynx needs these huge chunks of boreal forest that are continuous, not broken into little patches. If something happens in the southern portion of the boreal region, due to human use or climate change, and the area starts getting fragmented, then lynx movement can potentially be impacted, says Hersh.

They could have trouble passing over certain regions where there isnt enough boreal forest for them to travel through, which could have cascading effects on hare populations and potentially disrupt the cycle.

Hersh said if lynx and hare populations no longer follow predictable cycles, this can have tremendous impacts on the biodiversity of Boreal forests. It is estimated that the abundances of over 25 vertebrates are also regulated by this cycle. While the exact consequences of a disruption are difficult to predict, it could alter the natural patterns of genetic variation in all species that fluctuate with the cycle, which could ultimately reduce their ability to respond to future changes in their habitat and climate.

The concern is if climate change reduces the continuity of the forest and lynx cant move as far anymore, then this could disrupt that 10-year cycle.

This relationship between predator and prey could start to fall apart, so thats a potential consequence of climate change that we might not expect to happen. No one knows whats going to happen to the lynx and hare populations, says Gorrell. Most predator-prey relationships are generally stable over time and the abundance of predators and prey will stay relatively constant, but the lynx and hare have these huge peaks and crashes that happen like clockwork and its amazing how that cyclical relationship has maintained over time.

Gorrell and Hersh will be completing their research over the next two years thanks to an Accelerate Fellowship grant for $90,000 awarded jointly from Mitacs and Bill Harrower, principal biologist at High-Country Wildlife.

-30-

MEDIA CONTACT:

Rachel Stern, Communications Officer, Vancouver Island University

C: 250.618.0373 lE: Rachel.Stern@viu.ca | T: @VIUNews

List of Project Supports/Partners

Research will be completed thanks to a grant from Mitacs and Bill Harrower, principal biologist at High-Country Wildlife.

This project is also being supported by:

The Community Ecological Monitoring project includes collaboration among researchers from:

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VIU Researchers Examining Genetics of Canada Lynx | News | Vancouver Island University | Canada - Vancouver Island University News

1.

Hold on to your crowns, royal devotees: This one's a doozy. Prince Louis, whose mother is Kate Middleton, happens to look like Michael Middleton, who is get this Kate's father. I know, we were shocked, too. In a rare public appearance over the weekend, the 2-year-old prince was photographed alongside his family, and royal fans were quick to point out the striking physical similarities between Louis and his maternal grandfather. It's unclear why commenters thought the resemblance was particularly noteworthy, although it wasn't the first time Grandpa Middleton and the royal children have proven genetics do, in fact, exist. At least we now know there's hope for a non-bald King of the United Kingdom sometime in the next century. [Daily Express]

Despite the global pandemic, Cody Simpson has been pretty busy this year. He wasn't just singing, writing poetry, working as a United Nations Ocean Advocate, and falling in and out of love with Miley Cyrus. A "silent fire" in his stomach fueled his return to competitive swimming, and after five months of training, the Australian singer secured a spot in the 2021 Australian Olympic trials for the 100-meter butterfly event. "It is my greatest ambition to expand the limit and perceived notion of what's possible for someone to achieve in a single lifetime," Simpson wrote, "and I'm here to tell you can do absolutely ANYTHING if you are willing to work for it." H/T to Simpson for inspiring us while simultaneously putting us all to shame. [People]

The accolades start coming and they don't stop coming. Nearly 20 years after Shrek was released, we can breathe a sigh of relief knowing that our favorite ogre will be remembered for a long time to come. The Library of Congress announced this year's additions to the National Film Registry (which works to "ensure the survival, conservation, and increased public availability of America's film heritage"), and Shrek made the cut, getting praise for being "entertaining and emotionally impactful at levels to be appreciated by both children and their adults." The 25 selected films also include a record number of films directed by women and people of color. "We are not trying to set records but rather to set the record straight," Librarian of Congress Carla Hayden said. Hallelujah. [Variety, Library of Congress]

Story continues

Less than three weeks until The Office leaves Netflix? No, God, please no! The classic NBC show will be removed from Netflix at the end of the year and head to NBCUniversal's streaming service Peacock, and on Monday, it was announced that users will need a paid subscription to stream most of the episodes. Starting on Jan. 1, the first two seasons of The Office will stream on Peacock for free with ads, but seasons three through nine will require a $4.99 a month Peacock Premium subscription. That's yet another streaming service fans are being asked to pay for alongside Netflix, Hulu, Disney+, HBO Max, and more enough to make you want to shout, "I declare bankruptcy!" [The Wrap, Variety]

Taylor Swift released Evermore less than a month after Netflix released season four of The Crown, so it's not entirely unreasonable to suggest every song on Swift's surprise album is actually about the monarchy. However, one song in particular seems like it really fits the narrative, leading many fans to speculate the album's fifth track, "Tolerate it," is based on the relationship between Princess Diana and Prince Charles. The song, which distressingly details a broken relationship, references themes of infidelity and mental health that are also explored on The Crown. Swift also sings about using "fancy" tableware, and we all know the monarchy is very fancy. If that weren't enough, one of the song's lyrics is "You're so much older," which, hello, Charles was 12 years Diana's senior! Wake up, America the writing is quite literally on the wall. [Insider]

More stories from theweek.comJoe Biden still doesn't get itThe Trump campaign is asking its email list if Trump should run for president in 2024Washington National Cathedral rings funeral bell for 30 minutes to mourn 300,000 COVID-19 deaths

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The daily gossip: A T-Swift lyric theory, royal genetics, and the future of The Office - Yahoo News