StemCell Therapy

Chimeric antigen receptor (CAR) T-cell therapy targeting both BCMA and CD38 induced promising responses among patients with multiple myeloma who had been treated with at least 3 prior therapies and whose disease had spread outside of the bone marrow, supporting further exploration of the dual-targeted therapy, according to Yu Hu, MD, PhD.

This is the first clinical trial of anti-BCMA and CD38 dual-targeted CAR T-cell therapy in refractory multiple myeloma. Our study demonstrates improved efficacy and manageable safety, Hu, of Union Hospital at Huazhong University of Science and Technology in Wuhan, China, said during a presentation to an audience at the 61st Annual American Society of Hematology Annual Meeting and Exposition.

The objective response rate was 90.1%, with 12 patients achieving a stringent complete response (sCR) as their best response, meaning that no plasma cells were detected in the bone marrow. Seven patients (31.8%) had a partial response (PR), meaning that the level of M-protein in the blood or urine was reduced but still detectable, with 2 achieving a very good partial response (VGPR). One patient had a minor response. Eighteen patients (81.8%) reached bone marrow minimal residual diseasenegative status.

At the cutoff date of October 31, 2019, 19 patients were still alive with 10 still in sCR, 1 with VGPR, 4 with PRs. Three patients experienced relapse and 1 patient had progressive disease.

The median progression-free survival (PFS) had not been reached with a PFS rate at 9 months of 78.9%. For 17 patients remaining in remission at 7 months after treatment, median duration of response was 28.8 weeks.

Cytokine release syndrome (CRS) was observed in 20 out of 22 patients (90.9%), with 11 having grade 1 CRS and 4 with grade 2. Severe CRS grade 3 occurred in 5 (22.7%) and only 6 patients overall required treatment. No neurotoxicity was observed. Hepatotoxicity was seen in 3 patients (13.6%) and 1 patient experienced nephrotoxicity.

The peak time of CAR T cells in peripheral blood occurred from day 7 to day 15 after infusions in patients who achieved sCR and from day 14 to day 30 in patients without sCR. The longest duration of CAR T cells in the peripheral blood was >450 days. BM38 CAR was tested by quantitative polymerase chain reaction (qPCR) in the peripheral blood.

Eight out of 9 patients achieved complete or partial response of extramedullary disease, meaning these tumors were undetectable by CT scan.

With this dual-targeted CAR T-cell therapy, we have demonstrated a high response rate, especially a higher rate and longer duration of stringent complete response, compared with other therapies, as well as effective elimination of extramedullary lesions, with no serious neurologic adverse effects and manageable levels of other adverse effects, Hu said.

Among patients with multiple myeloma, roughly 10% will develop tumors in their organs or soft tissue known as extramedullary tumors. Patients who develop these often have poor responses to available therapies, experience a decrease in their quality of life, and have poor prognoses. According to Hu, patients treated in the study demonstrated that the novel dual-targeting CAR T-cell therapy may effectively eliminate extramedullary tumors.

This new CAR T cell [therapy] may have effects on the suppressor B cell. That means you can overcome the immunosuppression of the tumor environment, Hu said.

In total, 22 patients with a median age of 59 year (range, 49-72), half of whom were male, were treated in the dose-climbing phase I trial. All patients had multiple myeloma that had returned or not responded to at least 3 prior therapies. Nine patients (41%) had extramedullary tumors. Myeloma cells in the bone marrow were observed at a median of 9.7% (0.50%-56.1%) by flow cytometry. Seventy-three percent of patients had cytogenetic abnormalities such as 1q21 amp (54.6%) and deletion of chromosome 13q (40.9%).

All patients were treated with a 3-day chemotherapy regimen of fludarabine at 25 mg/m2 and cyclophosphamide 250 mg/m2 to make room in the immune system for engineered CAR T cells before infusion with the product. Patients were infused with CAR T cells at 0.5 106/kg to 4.0 106/kg with at least 2 patients treated at every dose level.

Investigators plan to continue follow up on these patients for 2 years. A phase II trial is being planned in both China and the United States to test the treatments efficacy in a larger number of patients.

Reference:

Mei H, Hu Y, Li C, et al. A bispecific CAR-T cell therapy targeting BCMA and CD38 for relapsed/refractory multiple myeloma: updated results from a phase 1 dose-climbing trial. Presented at: 61st Annual American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 930. https://bit.ly/38imXXG.

This article originally appeared on OncLive, titled Extramedullary Multiple Myeloma Responds to Dual-Targeting CAR T-Cell Therapy.

Link:
Promising Responses from Dual-Targeting CAR T-Cell Therapy in Myeloma Support Further Exploration - Cancer Network

There's more to this trusty festive staple thank you might think, writes Fiann Nuallin.

The only time some people partake of Brussels sprouts is in a festive scenario. Well there is much more to sprouts (Brassica oleracea, from Gemmifera group of cabbages) than the tradition of dressing the plate beside the stuffing.

Packed with antioxidants and dietary fibre they serve to mop up a lot of the junk we indulge in at this time of the year but also are worth becoming a regular in the five-a-day rota during the rest of the year.

I say the rest of the year as they freeze beautifully but in terms of fresh seasonality they are in the main, a winter crop with a season than starts in October and ends in March. Garden-grown varieties can be set up to begin producing from mid-August.

There are early and late cultivars but generally the tradition is, for early harvests to sow under cover or in a cold frame in February or March. Otherwise sow or plant plugs from late April/early May.

Pick a sheltered, sunny site, to grow on.

The sprouts are little fibre bullets supporting intestinal health and helping to lower blood sugars and high lipid accumulations from triglycerides to cholesterol. Dietary fibre is of prime importance to anyone dealing with diabetes, high cholesterol and digestive conditions.

The fibre and the stomach-strengthening phytochemistry of sprouts have seen them included in dietsto support Crohns disease, irritable bowel syndrome, and ulcerative colitis.

Brussels sprouts contain an antibacterial agent known as glucoraphanin which protectsthe stomach from bacterial overgrowth particularly good in fighting off candida and Helicobacter pylori.

They are often though of as a detox or system cleanse vegetable.

The richness of their glucosinolates have been studied as valid triggers to the detoxification and clearance of cancer-causing substances. Those sulphur-rich molecules also drive a better immune system.

The boost to the whole system is derived from the amazing quality of Brussels sprouts antioxidants.

Packed with vitamin C and beta-carotene to mop up free radical damage and protect our DNA and cellular health but also filled with fabulous flavonoid such as caffeic acid, ferulic acid, isorhamnetin, quercitin, and kaempferol all not just limiting the ageing process but working to disarm allergies and inflammation.

Brusssels sprouts are one of the bestanti-inflammatory vegetables, in part due to the high vitamin K content which regulates inflammatory responses but also via thede-inflaming action of glucosinolates one in particular glucobrassicin has shown effective in limiting rheumatoid arthritis flare-ups.

The glucobrassicin molecule converts into isothiocyanate which may be helpful in improving insulin resistance by lessening inflammation that complicates diabetes.

Sprouts contain zea-xanthin known as an eye health carotenoid beneficial to prevent age-related macular degeneration and bolster eyesight in general, those 20/20 rabbits eat more than carrots.

Sprouts also supply omega-3 fatty acids, and one of them is alpha-linolenic acid which is of benefit to the cardiovascular system and support the nervous system.

Ala is also known to lower inflammation, blood pressure and cholesterol levels.

When it comes to diets for cancer prevention and recovery, glucosinolates in cruciferous vegetables often hit the headlines. Of all the crucifers, Brussels sprouts contain the most and easily activated levels of sulforaphanes and isothiocyanates known to offer protection from colonic, prostate and endometrial cancers.

These same agents are helpful in battling viral and bacterial infections that can affect us across winter months. The trick is to leave enough sprout phytochemistry intact to do the job most effectively and thats down to how you cook.

In recent years, perhaps as a drive to boost flagging sales, the odd celebrity chef appears with a roasted sprout and chestnut dish or a roasted honey-glazed sprout.

Great and tasty but to get the best from sprouts, steam them. Years of boiling to a sulphurous sog has put many off. If you smell the cabbage aroma you have overcooked the sprout. Steaming is fast and less aromatic.

Steaming also keeps those healthy phytochemicals more integral and ready to be absorbed upon eating.

A 4-6-minute steam will do the trick. As some of the sprouts chemistry is enzymatically released, it is a good idea to slice in half or quarter and allow the chopped parts to sit for five minutes before cooking. This action lets the enzymes at the cuts do their thing.

Abacus is an easy-to-grow early tomid-season cropper. Good solid sprouts.

Bosworth is an easy-to-grow late cropper best yields after Christmas into spring.

Brigitte F1 is a favourite among Irish growers quite nutty in flavour but also a long season and disease resistance.

Crispus F1 is a mid-season, clubroot-resistant variety. Small, tight sprouts.

Chronos is a clubroot-resistant variety, grown as a mid-season.

Diablo is a mid-to-late-season cropper. Dark green sprouts.

Evesham Special is a shorter growing but long and prolific harvester from September on.

Maximus is one of the early to mid-season croppers. Plenty of mid- to dark- green sprouts.

Red Bull Also known as red ball, it yields attractive and tasty dark red sprouts.

Revenge is known as a late variety and can still be vigorous and prolific in spring.

More here:
Why sprouts earn a place on your plate all year round - Irish Examiner

Abstract

IFN- produced by T cells directly induces intestinal stem cell death upon inflammation-induced intestinal injury (see the related Research Article by Takashima et al.).

Intestinal regeneration upon tissue damage is fueled by intestinal stem cells (ISCs) residing in the crypt bottom of the epithelium and marked by the gene Lgr5 (1, 2). There is growing evidence that tissue repair is at least partially mediated by a regenerative inflammatory response (3, 4). How inflammation-induced intestinal injury influences ISCs and their microenvironment (stem cell niche) remains poorly understood. In this issue of Science Immunology, Takashima et al. (5) explore the changes in the ISC niche in vivo upon T cellmediated injury as a model of graft-versus-host disease (GVHD) and in vitro using organoid T cell cocultures. Although earlier studies already implicated interferon- (IFN-) as a negative regulator of intestinal epithelial homeostasis (68), Takashima et al. now demonstrate that IFN- directly acts on ISCs by triggering apoptosis.

In an allogeneic bone marrow transplant (BMT) model, Takashima and colleagues found that ISC numbers per intestinal crypt were markedly reduced in mice receiving bone marrow alone or bone marrow and T cells when compared with normal control mice. While the ISCs in the mice receiving only bone marrow recovered 7 days later, the ISC numbers remained reduced in those mice also transplanted with donor T cells. Of note, Paneth cell numbers were also reduced after ISC depletion. The numbers of organoids established from the intestines of mice 10 days after BMT recovered back to that of control mice, whereas the organoid forming capacity from crypts of mice after combined transplantation of bone marrow and T cells remained significantly lower. Similar in vivo and in vitro results were obtained when autoreactive T cells were transplanted, pointing to a common feature of T cellmediated intestinal injury.

As seen by three-dimensional confocal microscopy, intraepithelial T cells (CD3+ IELs) preferentially localized to the villus region, whereas lamina propriaassociated T cells (CD3+ LPLs) were equally distributed along the crypt-villus axis of control mice (Fig. 1A). Conversely, mice receiving bone marrow and allogeneic T cells showed a progressive increase in the density of both CD3+ LPLs and CD3+ IELs in the crypt region.

To identify signaling molecules that cause the loss of ISCs in this model, Takashima and colleagues performed several elegant murine and human epithelial organoid coculture experiments. Murine nave allogeneic T cells did not impair murine intestinal organoid numbers, whereas alloreactive T cells effectively reduced organoid numbers. Likewise, human allogeneic cytotoxic T cells robustly inhibited human intestinal organoid forming efficiency. Even bead-activated autologous T cells suppressed human intestinal organoid growth. The authors then proceeded to screen for potential pathways mediating cytotoxicity. Organoids cocultured with T cells in the presence of antiIFN- neutralizing antibodies showed normal growth. Although IFN- receptor (IFN-R)depleted T cells were still able to affect organoid viability, IFN-Rdepleted organoids were resistant to T cellmediated killing. Organoid toxicity by IFN- was also observed in the absence of T cells. Live imaging confirmed the progressive ISC depletion upon organoid exposure to IFN-. Treatment of organoids with the immunosuppressive JAK1/2 inhibitor ruxolitinib robustly preserved numbers of both organoids and ISCs in the presence of IFN-, irrespective of whether the organoids were cultured alone or together with T cells. The authors additionally demonstrated that JAK1-depleted organoids are resistant to IFN- treatment. Further downstream, ruxolitinib prevented STAT1 phosphorylation by IFN- in intestinal crypts, and, in line, STAT1-depleted organoids were resistant to growth suppression in response to IFN- treatment.

IFN-treated organoids showed reduced expression of ISC marker genes. ISCs underwent apoptosis in vitro in a direct response to IFN-. Next, the authors confirmed in vivo that ISC numbers did not change upon transplanting allogeneic bone marrow and T cells when treating mice with IFN- neutralizing antibodies. Likewise, ruxolitinib treatment protected ISCs from T cellmediated killing in vivo. Donor T cells, particularly T helper 1 cells, were activated and IFN-+. Transplanting IFN-depleted allogeneic T cells robustly reduced the ISC loss and allowed epithelial cell proliferation to increase.

Takashima and colleagues lastly investigated whether IFN- directly induces ISC apoptosis. Using tissue-specific depletion of IFN-R1, the authors found that epithelial loss of the receptor protects from the immune-mediated GVHD phenotype. IFN-R1 is expressed by both ISCs and Paneth cells, the epithelial component of the ISC niche (9). However, Paneth celldeficient organoids remained sensitive to both IFN- and allogeneic T cellmediated cytotoxicity. Likewise, T cells were able to reduce the number of organoids containing IFN-R1deficient Paneth cells, whereas organoids containing IFN-R1deficient ISC were protected from cytotoxicity. The authors demonstrated in further experiments that IFN- directly induces ISC apoptosis independent of Paneth cells (Fig. 1, B and C).

The study by Takashima et al. extends our knowledge on signaling between ISCs and immune cells, identifying ISCs as direct targets of IFN- secreted by T cells in immune-mediated intestinal damage (as caused by GVHD). In the 2015 study by Lindemans et al., this group already identified that interleukin-22 (IL-22) secreted by group 3 innate lymphoid cells (ILC3s) directly stimulates ISCs to proliferate and regenerate the intestinal epithelium upon inflammation-induced intestinal injury (4). Modulating the effects of T cellderived IFN- on ISC, for instance, by suppressing JAK/STAT signaling via ruxolitinib treatment, may provide a new therapeutic avenue to reducing GVHD-induced damage of the intestinal epithelium (10).

(A) ISCs maintain adult homeostasis of the intestinal epithelium. T lymphocytes patrol the intestine. (B) Takashima et al. show that in GVHD as modeled by BMT and aberrant activation of T lymphocytes, T cellderived IFN- directly acts on ISCs and induces apoptosis via JAK/STAT signaling. (C) Disease progression results in marked intestinal damage due to loss of ISCs and their niche.

Acknowledgments: Funding: K.K. is a long-term fellow of the Human Frontier Science Program Organization (LT771/2015). Competing interests: H.C. and K.K. are named inventors on patents or patents pending on Lgr5 stem cellbased organoid technology.

The rest is here:
IFN-: The T cell's license to kill stem cells in the inflamed intestine - Science

Pigs engineered to have a small amount of monkey cells have been brought to full term and were even born alive, surviving for a few days after birth. Although the piglets died, it is claimed the experiment - performed in China - marks a major milestone for the future of lab-grown organs.

"This is the first report of full-term pig-monkey chimeras," Tang Hai of the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing told New Scientist.

The research is part of an ongoing effort to develop animals - whether they are sheep or pigs - that can grow human organs we could then harvest for transplants, a process called xenogeneic organogenesis.

Research has been done on both pig and sheep embryos with transplanted human stem cells; in both cases, the embryos continued to develop until the experiment was deliberately terminated.

That's because, due to ethical concerns, these chimeras - organisms that incorporate the genetic material of another species - cannot be cultivated or studied in the later stages of embryonic development. Some scientists worry that some of the human stem cellscould end upin other parts of the animal or even in its brain, with unintended consequences.

For that reason, in this experiment the team used stem cells from crab-eating macaques (Macaca fascicularis). These were imbued with fluorescent proteins so that they would glow under fluorescent light, and derived to produce fluorescing embryonic cells.

These cells were then injected into over 4,000 five-day-old pig embryos fertilised using IVF; the modified pig embryos were subsequently implanted into sows.

This fiddly and painstaking work produced just 10 piglets that made it to full term and were born alive. And only two of these were chimeric, with between one in 1,000 and one in 10,000 functional monkey cells to pig cells.

The monkey cells had migrated to the heart, liver, lungs, spleen and skin of the piglet hosts, but were not found in other organs, such as testes and ovaries, due to the low rate of chimerism, the researchers said.

Sadly, before a week was out, the piglets died - not just the two chimeras, but the other eight normal piglets, too. Because all the pigs died, Hai told New Scientist, the cause of death likely had less to do with chimerism, and more to do with IVF - a procedure that is notoriously tricky in pigs.

The low chimerism rate is also somewhat discouraging. However, the researchers remain optimistic. Although the birth rate was low, and the pigs didn't survive, the team now has a wealth of data they can apply to future experiments.

The scientists are planning to try again, increasing the chimeric cell ratio. And they believe their data may help other scientists working in the field.

"Here, we have used monkey cells to explore the potential of reconstructing chimeric human organs in a large animal model," they wrote in their paper.

"We believe this work will facilitate the development of xenogeneic organogenesis by providing a better understanding of the processes of xenogeneic recognition, fate determination, and the proliferation and differentiation of primate stem cells during porcine development.

"The findings could pave the way toward overcoming the obstacles in the re-engineering of heterogeneous organs and achieve the ultimate goal of human organ reconstruction in a large animal."

The research has been published in Protein & Cell.

Read the rest here:
Pig-Monkey Chimeras Have Been Brought to Term For The First Time - ScienceAlert

Organ donation involves removing a healthy organ from a donor and transplanting it into the body of a recipient who has a diseased organ that has failed irreversibly. The recipients survival often depends on getting an organ transplant.

There is a large need for organs by people affected with end-stage ailments, like diseases of the liver, lung, heart and kidney. A major obstacle to treating such people is that there arent enough donated organs around the world. In many countries, including in the West, the number of patients in the waiting list for organ transplants has progressively increased compared to the number of donor organs available.

And while the number of donors per million people is very low in many parts of the world, about 20-30 per million, its many times lower than this in India: less than 0.5 donor per million. Experts have estimated that a few lakh organs are required per year in India, although no more than 2-3% of this requirement is really met. The severe shortfall may need more effective propaganda, retrieval and use of donated organs.

There are also personal, religious and cultural barriers that make it hard for people to accept the idea of organ donation. Most religions dont appear to oppose organ donation, but people are often uncertain about these recommendations and so they are reluctant to donate. Judaism and Islam prohibit the desecration of corpses and stress on a complete body, timely rituals and burial within 24 hours after death. People may not prefer to donate organs of their near and dear after death, due to the mutilating effect of dissecting the body and removing its parts.

There are often logistical issues as well. Due to a lack of awareness of the donation procedure and its consequences, most people prefer receiving organs from live, instead of recently deceased, donors.

* * *

Organ donation came to be thanks to advances in surgical procedures that allowed doctors to replace a diseased or dying organ with a healthy foreign organ. These advances reflected the rise of the exchangeability of body parts. That is, clinicians began to view the body as a collection of organs and independent entities, such that they could be removed from one body and placed in another. By contrast, the older and more traditional view of the body regarded it as a complex, indivisible whole interacting with its environment. As the idea of exchangeability gained traction, organs became commodities with market value.

Also read:The Seamy Underbelly of Organ Transplantation in India

The advent of organ transplantation was a landmark in the history of medicine. Researchers had developed transplantation surgeries for small animals such as dogs, pigs and goats well before the 20th century. The organs in the human body that doctors most transplant are the kidney, heart and liver.

Murray and Merrill performed the first kidney transplant in the 1950s, from one monozygotic twin to another. Since the twins were genetically identical, they survived and lived for eight years after the procedure.

The first heart and liver transplants were undertaken in the mid-1960s. Christian Bernard, the famous South African surgeon, performed the first heart transplant in 1967, from a 25-year-old who was brain dead after an accident and to a 50-year-old man suffering from heart failure. In the same year, other doctors performed more than 100 heart transplants around the world, but the recipients in these transplants didnt live for more than a few days after. There were problems related to the health of the transplanted organs and the aftereffects of surgery.

An American surgeon named Thomas Starzl performed the first liver transplant in the mid-1960s. The first patient died immediately and after the surgery; a few more patients who received transplanted organs also died from infections and other illnesses within a few weeks.

Corneal grafts are a very well-known and effective form of organ or tissue donation. The cornea, which is the transparent structure on the front of the eye, consists of multiple layers of cells designed to be transparent. The cornea refracts light towards the eyes lens, located just behind it. Its relatively simpler to transplant cornea because it lacks blood vessels (i.e. since one doesnt need to restore blood vessels in the grafted tissue).

Another advantage is that the cornea is in a state of immune privilege: it is relatively protected from immune responses. So persons who undergo a corneal transplant dont need lifelong treatment with systemic drugs to suppress the immune system.

Corneal donation and transplantation have continuously evolved in theory and practice, and have a high rate of success. Franz Reisinger first attempted corneal grafts in the early 19th century, trying to transplant animal corneas into humans. He failed in repeated attempts. Reisinger also coined the term keratoplasty, which means surgery to the cornea.

Also read:Why Moral Exhortations Alone Will Not Boost Organ Donation in India

Only a few years later, Samuel Bigger, an Irish surgeon, treated a gazelle that had been blinded by a corneal scar by transplanting cornea from another gazelle.

A Viennese ophthalmologist named Edward Zirm performed the first successful corneal graft between two humans in the early 20th century.

* * *

One possible reason why organ transplants often dont have long-term success is the recipient. A person who is already sick due to a failed heart or liver is not likely to respond well to major surgery, and may have difficulty recovering from it. Similarly, an older patient may not be able to withstand the effects of surgery.

Another important factor is the recipients immune system, which could reject the donated organ. In 1979, doctors who just performed a liver transplant used a drug called cyclosporine to dampen the bodys immune response and thus spare the transplanted organ from attack. This occasion was a new step in the history of liver transplants. Cyclosporine improved the survival of over 70% of patients up to at least one year after surgery, and many patients survived for up to five yrs. Doctors have followed up with newer, better drugs to improve patients health outcomes since.

A third issue relates to an ethical question that researchers have flagged: a living donor has to undergo a major surgical procedure to donate an organ, and such procedures carry their own risks. Moreover, close relatives of a patient may be under pressure to agree to donate their organs, so they may not be necessarily free to decide for themselves. Another issue regards commercialisation: its very easy to provide monetary incentives to the poor and convince them to donate an organ in return. In such circumstances, the decision to donate an organ will not have been the result of free choice where it should be.

Such a market for kidneys is all too visible in India, where one finds advertisements for the sale of kidneys with hospitals involved in the business. Often, poor people are ready to donate their organs to make a lakh or two. Apart from theft and the black market for organs, monetary compensation for organs is legal in some parts of the world.

* * *

An alternative to overcome the shortage of organs for transplants is a xenotransplant: transplanting animal organs into humans. The principal animals that can potentially donate to humans are monkeys, since theyre most closely related to humans.

However, due to differences between the sizes of monkey and human organs, researchers have also considered pigs, whose organs are closer in dimensions as well as because pigs are easy to breed. Researchers are currently exploring these procedures in experiments.

Also read:Why Does Spain Lead the World in Organ Donation?

Another alternative for intact organs is stem cells, which scientists can grow in controlled environments, such as in a laboratory, and develop into miniature organs, or organoids. Using bioengineering techniques, they removed cells from an intact organ, such as a lung or trachea, such that the cells retain a skeleton of proteins and carbohydrates. Next, they populate these cells with stem cells and maintained them in a laboratory so that different types of cells grow inside the container. For example, scientists have grown multilayered corneas in a dish using a culture of stem cells and certain biomolecules.

Such advances in preserving and engineering tissues are help plug the gap between the demand for and supply of organs.

* * *

Its very important to preserve and properly store organs to ensure theyre in the best possible condition and retain their nature following transplantation. One particular concern here stems from the time and temperature of storage, which need to be carefully controlled to remain within specific limits depending on the organ and the type of death. Maintaining the right conditions ensures the organ remains viable after the recipient has received it. A heart may be stored for up to four hours, the lungs for up to six hours and the kidneys for longer periods, up to 18 hours.

A critical question to be addressed with regard to organ donation is the distinction between brain death and cardiac, or circulatory, death. A brain-dead patient will still have a functioning heart and may be on life support. However, brain-death means brain function has been completely and irreversibly lost.

For an organ donor, a criterion of either brain death or cardiac death may be taken under the definition of death. Indian law mentions two possibilities. One is in the Registration of Births and Deaths Act and the other, in the Transplantation of Human Organs and Tissues (THOT) Act. The former defines death as the permanent disappearance of all evidence of life at any time after live-birth has taken place. The THOT Act, on the other hand, defines a deceased person as one in whom permanent disappearance of all evidence of life occurs, by reason of brain stem death or in a cardiopulmonary sense, at any time after live-birth has taken place.

In many countries, both forms of death are considered acceptable for organ donation.

Chitra Kannabiranleads research on molecular genetics at the L.V. Prasad Eye Institute, Hyderabad.

Read more here:
The Ins and Outs of Organ Donation - The Wire

BOSTON and LONDON, Dec. 08, 2019 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a leading commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies, will be presenting new registrational data from multiple programs at the 61st American Society of Hematology (ASH) Annual Meeting being held December 7-10, 2019 in Orlando, FL.

On Sunday, December 8, 2019, investigators will describe ongoing clinical progress for two lead development programs in the companys primary immune deficiencies portfolio: OTL-103, an investigational gene therapy in development for the treatment of Wiskott-Aldrich syndrome (WAS) at the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy; and OTL-101, an investigational gene therapy in development for the treatment of adenosine deaminase severe combined immunodeficiency (ADA-SCID).

In addition, on Monday, December 9, 2019, investigators will deliver an oral presentation featuring updated data from the ongoing clinical proof-of-concept study of OTL-203, an investigational gene therapy in development for the treatment of mucopolysaccharidosis type I (MPS-I) at SR-Tiget.

To learn more about Orchards approach to ex vivo, autologous, hematopoietic stem cell (HSC) based gene therapy, conference attendees can visit booth #2228 in the Exhibition Hall.

Full presentation details are below:

Poster Presentation Details

Lentiviral Hematopoietic Stem and Progenitor Cell Gene Therapy for Wiskott-Aldrich Syndrome (WAS): Up to 8 Years of Follow up in 17 Subjects Treated Since 2010Publication Number: 3346Session: 801. Gene Therapy and Transfer: Poster IIDate and time: Sunday, December 8, 6:00-8:00pm ET

Lentiviral Gene Therapy with Autologous Hematopoietic Stem and Progenitor Cells (HSPCs) for the Treatment of Severe Combined Immune Deficiency Due to Adenosine Deaminase Deficiency (ADA-SCID): Results in an Expanded CohortPublication Number: 3345Session: 801. Gene Therapy and Transfer: Poster IIDate and time: Sunday, December 8, 6:00-8:00pm ET

Oral Presentation Details

Extensive Metabolic Correction of Hurler Disease by Hematopoietic Stem Cell-Based Gene Therapy: Preliminary Results from a Phase I/II TrialPublication Number: 607Session: 801. Gene Therapy and Transfer: Gene Therapies for Non-Malignant DisordersDate and time: Monday, December 9, 7:00am ET

About ADA-SCID and OTL-101Severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID) is a rare, life-threatening, inherited disease of the immune system caused by mutations in the ADA gene resulting in a lack of, or minimal, immune system development.1-4 The first symptoms of ADA-SCID typically manifest during infancy with recurrent severe bacterial, viral and fungal infections and overall failure to thrive, and without treatment the condition can be fatal within the first two years of life. The incidence of ADA-SCID is currently estimated to be one in 500,000 live births in the United States and between one in 200,000 and one in 1 million in Europe.3 OTL-101 is an autologous, ex vivo, hematopoietic stem cell-based gene therapy for the treatment of patients diagnosed with ADA-SCID being investigated in multiple clinical trials in the United States and Europe, including a registrational trial at the University of California, Los Angeles (UCLA). OTL-101 has received orphan drug designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of ADA-SCID, and Breakthrough Therapy Designation from the FDA.

About WAS and OTL-103Wiskott-Aldrich Syndrome (WAS) is a life-threatening inherited immune disorder characterized by autoimmunity and abnormal platelet function and manifests with recurrent, severe infections and severe bleeding episodes, which are the leading causes of death in this disease. Without treatment, the median survival for WAS patients is 14 years of age. Treatment with stem cell transplant carries significant risk of mortality and morbidities. OTL-103 is an ex vivo, autologous, hematopoietic stem cell-based gene therapy developed for the treatment of WAS that Orchard acquired from GSK in April 2018 and has been developed at the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. The global incidence of WAS is estimated to be about 100-260 births per year, with a global prevalence of 2,900-4,700 patients.

About MPS-I and OTL-203Mucopolysaccharidosis type I (MPS-I) is a rare inherited neurometabolic disease caused by a deficiency of the IDUA (alpha-L-iduronidase) lysosomal enzyme required to break down glycosaminoglycans (also known as GAGs or mucopolysaccharides). The accumulation of GAGs across multiple organ systems results in the symptoms of MPS-I including neurocognitive impairment, skeletal deformity, loss of vision and hearing, hydrocephalus, and cardiovascular and pulmonary complications. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births.5 There are three subtypes of MPS-I; approximately 60 percent of MPS-I patients have the severe Hurler subtype and, when untreated, these patients rarely live past the age of 10.Id Treatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have significant limitations. Though early intervention with enzyme replacement therapy has been shown to delay or prevent some clinical features of the condition, it has only limited efficacy on neurological symptoms. OTL-203 is an ex vivo, autologous, hematopoietic stem cell-based gene therapy being studied for the treatment of MPS-I. Orchard was granted an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the gene therapy program for the treatment of MPS-I developed by the San Raffaele-Telethon Institute for Gene Therapy in Milan, Italy.

About Orchard Orchard Therapeutics is a fully integrated commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies.

Orchards portfolio of ex vivo, autologous, hematopoietic stem cell (HSC) based gene therapies includes Strimvelis, a gammaretroviral vector-based gene therapy and the first such treatment approved by the European Medicines Agency for severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID). Additional programs for neurometabolic disorders, primary immune deficiencies and hemoglobinopathies are all based on lentiviral vector-based gene modification of autologous HSCs and include three advanced registrational studies for metachromatic leukodystrophy (MLD), ADA-SCID and Wiskott-Aldrich syndrome (WAS), clinical programs for X-linked chronic granulomatous disease (X-CGD), transfusion-dependent beta-thalassemia (TDT) and mucopolysaccharidosis type I (MPS-I), as well as an extensive preclinical pipeline. Strimvelis, as well as the programs in MLD, WAS and TDT were acquired by Orchard from GSK in April 2018 and originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy initiated in 2010.

Orchard currently has offices in the UK and the U.S., including London, San Francisco and Boston.

Forward-Looking StatementsThis press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as anticipates, believes, expects, intends, projects, and future or similar expressions that are intended to identify forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release, Orchards expectations regarding the timing of regulatory submissions for approval of its product candidates, including the product candidate or candidates referred to in this release, the timing of announcement of clinical data for its product candidates and the likelihood that such data will be positive and support further clinical development and regulatory approval of these product candidates, including any cryopreserved formulations of such product candidates, and the likelihood of approval of such product candidates by the applicable regulatory authorities. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, without limitation: the risk that any one or more of Orchards product candidates, including the product candidate or candidates referred to in this release, will not be successfully developed or commercialized, the risk of cessation or delay of any of Orchards ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates, the delay of any of Orchards regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchards ability to commercialize its product candidates, if approved. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards annual report on Form 20-F for the year ended December 31, 2018 as filed with the U.S. Securities and Exchange Commission (SEC) on March 22, 2019, as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

1Orphanet. SCID due to ADA deficiency. 2Whitmore KV, Gaspar HB. Front Immunol. 2016;7:314. 3Kwan A, et al. JAMA. 2014;312:729-738. 4Sauer AV, et al. Front Immunol. 2012;3:265. 5Beck et al. The Natural History of MPS I: Global Perspectives from the MPS I Registry. Genetics in Medicine 2014, 16(10), 759.

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaMolly CameronManager, Corporate Communications+1 978-339-3378media@orchard-tx.com

Read the rest here:
Orchard Therapeutics Showcases Clinical Data at the 61st American Society of Hematology Annual Meeting - BioSpace

Black ChristmasUpdate of the 1974 holiday horror classic about sorority sisters stalked by a masked killer. With Imogen Poots, Aleyse Shannon, Lily Donoghue, Cary Elwes. Written by Sophia Takal, April Wolfe. Directed by Takal. (1:38) PG-13.

BombshellCharlize Theron, Nicole Kidman and Margot Robbie play Fox News employees whose allegations of sexual harassment help topple network founder Roger Ailes. With John Lithgow, Allison Janney, Connie Britton, Kate McKinnon. Written by Charles Randolph. Directed by Jay Roach. (1:48) R.

CunninghamDocumentary profile of influential dancer-choreographer Merce Cunningham includes archival footage plus re-creations of his works. Directed by Alla Kovgan. (1:33) PG.

The Death & Life of John F. DonovanAn actor recalls the letters he exchanged with a long-dead American television star. With Kit Harington, Natalie Portman, Jacob Tremblay, Susan Sarandon, Kathy Bates, Thandie Newton, Sarah Gadon. Written by Xavier Dolan, Jacob Tierney. Directed by Dolan. (2:03) R.

The Disappearance of My MotherWriter-director Beniamino Barrese profiles his reclusive mother, 1960s-era supermodel turned feminist activist Benedetta Barzini. In English and Italian with English subtitles. (1:34) NR.

First LoveThe brother of a famous but troubled actress is torn between selling his explosive tell-all book about their childhood or helping her after she suffers a nervous breakdown. With Annie Heise, Aaron Costa Ganis, Arye Gross, Mia Barron. Written and directed by Michael Masarof. (1:20) NR.

The Great WarAmerican soldiers during WWI go behind enemy lines to try to rescue a lost platoon. With Ron Perlman, Billy Zane, Bates Wilder. Written and directed by Steven Luke. (1:48) R.

Hell on the BorderA former slave gets a job as a lawman and goes on a manhunt in his fact-based western about the first black marshal in the Wild West. With David Gyashi, Frank Grillo, Ron Perlman. Written and directed by Wes Miller. (1:50) R.

A Hidden LifeWriter-director Terrence Malicks fact-based drama about an Austrian farmer who refused to fight for Nazis during WWII. With August Diehl, Valerie Pachner, Bruno Ganz, Matthias Schoenaerts. In English, German, Italian with English subtitles. (2:53) R.

Jumanji: The Next LevelDanny Glover and Danny DeVito join Dwayne Johnson, Jack Black, Kevin Hart and Karen Gillan in this sequel to the 2017 action adventure hit about young people trapped in a videogame. With Nick Jonas, Awkwafina. Written by Jake Kasdan, Jeff Pinkner, Scott Rosenberg; based on the book by Chris Van Allsburg. Directed by Kasdan. (1:54) PG-13.

Line of DescentAn organized-crime family in Delhi deals with threats from without and within. With Brendan Fraser, Max Beesley, Abhay Deol. In Hindi and English with English subtitles. (1:48) NR.

Midnight FamilyDocumentary about a family-run private ambulance service in Mexico City. Directed by Luke Lorentzen. In Spanish with English subtitles. (1:30) NR.

Mob TownMafia figures assemble for a summit in upstate New York in 1957 in this fact-based crime drama. With David Arquette, Jennifer Esposito, Jamie-Lynn Sigler, Robert Davi, Nick Cordero. Written by Jon Carlo and Joe Gilford. Directed by Danny A. Abeckaser. (1:30) R.

RabidA fashion designer experiences a horrifying transformation after undergoing an experimental stem-cell treatment following a car accident. With Laura Vandervoort, Benjamin Hollingsworth, Phil Brooks. Written by the Soska Sisters, John Serge; story by Serge. Directed by the Soska Sisters. (1:47) NR.

Richard JewellClint Eastwood directs this fact-based drama about the security guard falsely accused in the Centennial Park bombing during the 1996 Olympics in Atlanta. With Paul Walter Hauser, Sam Rockwell, Kathy Bates, Jon Hamm, Olivia Wilde, Ian Gomez. Written by Billy Ray; based on an article by Marie Brenner. (2:09) R.

SebergFrench New Wave actress Jean Seberg is targeted by the FBI for her political and romantic involvement with civil-rights activist Hakim Jamal during the 1960s in this fact-based drama. With Kristen Stewart, Anthony Mackie, Jack OConnell, Margaret Qualley, Zazie Beetz, Vince Vaughn. Written by Joe Shrapnel, Anna Waterhouse. Directed by Benedict Andrews. (1:36) R.

6 UndergroundRyan Reynolds stars in this Michael Bay action flick about a globe-trotting team of untraceable operatives dedicated to saving the world. With Mlanie Laurent, Corey Hawkins, Adria Arjona, Dave Franco. Written by Paul Wernick, Rhett Reese. (2:05) R.

Uncut GemsAdam Sandler stars as a desperate New York City jeweler juggling numerous deals in this crime thriller. With Lakeith Stanfield, Julia Fox, Kevin Garnett, Idina Menzel, Eric Bogosian, Judd Hirsch. Written by Josh Safdie, Benny Safdie, Ronald Bronstein. Directed by the Safdies. (2:15) R.

What She Said: The Art of Pauline KaelDocumentary on the longtime firebrand film critic of the New Yorker. With Alec Baldwin, Quentin Tarantino, David O. Russell, Francis Ford Coppola and Sarah Jessica Parker as the voice of Kael. Directed by Rob Garver. (1:38) NR.

Original post:
Movies opening in L.A. this week: 'Bombshell,' 'Jumanji: The Next Level' and more - Los Angeles Times

Data: ProQuest; Chart: Axios Visuals

Senate Intelligence Committee Chairman Richard Burr (R-N.C.) said this week that Ukraine meets the standard for election meddling that people first held Russia to. But that's not what the numbers show.

Why it matters: While Burr didn't draw a moral equivalence between Russia which committed several crimes on U.S. soil during the 2016 election and what we know about Ukraine, he muddled the debate in that direction.

What they're saying: "You considered Russia meddling with just the preference they had before you knew the rest of it," said Burr. "Apply the same standard to Ukraine."

But, but, but: Axios analyzed 1,847 news stories from 179 news sources that used the words "Russia," "election," "meddling" and their derivatives between Jan. 1, 2014, and Jan. 1, 2017. And it's pretty clear the concept of Russian election meddling didn't enter the American zeitgeist until the WikiLeaks email leaks on July 25.

Burr did not respond to a request for comment.

Go deeper:

View original post here:
The difference between Russia and Ukraine on election meddling - Axios

Vladimir Putin has contended with a nod to the chaos swirling in the West and to Russia's tumultuous history that the most precious thing a leader can offer his country is stability.

Why it matters: Putin has not made Russia rich, free or particularly happy. But he imposed stability and has maintained it for two decades through his own blend of force and skill. Putin's current term expires in 2024, and the constitution bars him from seeking another.

Zoom in: Dmitri Trenin, director of Carnegie Moscow and a former Russian military officer, does not believe Putin will change the constitution to become "president for life." Thus, he says, 2024 will be the last year that Vladimir Putin will be president of Russia."

Two specific methods have been floated, beyond a constitutional change:

1. Putin forms a commonwealth with Belarus, maintaining presidencies in both countries but placing himself above them.

2. Putin builds himself another powerful role like chair of the National Security Council and oversees a staged transition from that perch.

Where things stand: Putin will be 71 when his term expires. He told the FT in June that he had been thinking about succession "since 2000."

The big picture: The "mafia-esque structure" Putin has built requires loyalty within elite circles and support from the public, says Alina Polyakova of Brookings.

Zoom out: The Russian system collapsed twice in the 20th century, in 1917 and 19891991.

The bottom line: "This transition will never be very smooth and will never be very happy even," says Trenin. But history will judge Putin on its outcome.

Putin has left the Kremlin once before, when he first ran up against term limits in 2008 and became prime minister.

Behind the scenes: "We always had an assessment, perhaps exaggerated, that Putin was the main decision-maker and [Dmitry] Medvedev was just a figurehead," says Michael McFaul, who was Barack Obama's Russia adviser and later ambassador to Moscow.

Flash forward: We always thought Putin was coming back," McFaul continues, "but there was enough ambiguity that you could hold open the possibility that maybe Medvedev would stay.

The bottom line: [Putin], like a lot of autocrats, convinced himself that he was the indispensable player and that Russia needed his strong hand in the Kremlin," says William Burns, who was then deputy secretary of state.

McFaul originally thought Putin was exaggerating both the threat to his regime during the 2012 protests and the role he attributed to the U.S.

Behind the scenes: He had no incentive to tell [national security adviser] Tom Donilon or [Secretary of State] John Kerry that were trying to overthrow the regime. Thats supposed to be for the workers and the peasants. But in those conversations, I heard a level of suspicion he just assigned all kinds of power to the United States and especially the CIA that they dont have."

"I think psychologists would call it projection," Burns says, noting that Putin had suspicion drilled into him as a KGB officer.

Former Secretary of Defense Ash Carter is more blunt. "One of his objectives is to screw us. That, unlike Syria or nuclear proliferation, is not an area where I am willing to reach common ground."

The bottom line: "Declining powers in a lot of ways as Putin reminded us can be at least as disruptive as rising powers," says Burns.

Putin issued that reminder in 2014 when he annexed Crimea and launched the war in eastern Ukraine.

The big picture: Putin views Ukraine as firmly within Russia's sphere of influence, and he saw Kiev's sudden shift toward the West as an existential threat.

Behind the scenes: We didnt have the resources devoted to Russia that we needed to understand what Russia was doing under Putin," says Michael Morell, a former CIA deputy director, noting that the invasions of Ukraine and of Georgia in 2008 took Washington utterly by surprise.

The bottom line: Just a few years after being dismissed by Obama as a "regional power," Russia was being discussed in Washington as one of three key players in an era of "great power competition."

Two of those three powers inaugurated a 1,800-mile-long symbol of their burgeoning partnership yesterday.

Driving the news: The Power of Siberia pipeline will deliver Russian gas to China and is expected to generate $400 billion for Russian state coffers, per Reuters.

The big picture: Asked about the relationship with his giant neighbor, Putin told the FT, "We have sufficient eggs, but there are not too many baskets to put those eggs in."

Between the lines: He's squeezing everything he can out of a relationship that currently provides massive economic and strategic benefits, but is also increasingly imbalanced.

The bottom line: Right now its a pretty strong marriage of convenience," says Burns, "born of a shared interest in chipping away at an American-led order."

Putin looks at China's rise, Trump's election and Europe's identity crisis and reaches a provocative conclusion: "the liberal idea has become obsolete."

Why it matters: Putin's alternative path has been embraced by high-profile politicians and a widening slice of the European electorate:

Zoom out: Putinism is a new set of ideas that is exportable," McFaul says, noting the rise of Europe's far right. Hes not alone in this fight.

The little-known KGB veteran who thrived in the shadows, underestimated and overlooked, has grown into a giant.

He's not only one of the world's most powerful men, he may be one of the richest. Anders slund of the Atlantic Council pegs his net worth at $100 billion to $160 billion, including a $1 billion palace on the Black Sea.

After 20 years at the top of that pyramid, with all the wealth and all the enemies he's accumulated along the way, leaving power would be perilous.

Go deeper:

Subscribe to Axios World to get reports like this in your inbox.

See the rest here:
20 Years of Putin: The pinnacle of power and the fear of losing it - Axios

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome.

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

"I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email.

"Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

"But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

- Cures -

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union.

They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris.

"It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection.

"You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

- Bioterrorism -

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal -- and his excommunication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

"Not everyone is a biologist or scientist," she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops?

Charpentier thinks that technology generally tends to be used for the better.

"I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

Read the original here:
2019: the year gene therapy came of age - RTL Today

The Stem Cell Cartilage Regeneration Market 2019-2028 Analytical Reporthasrecently published byMarketresearch.bizto its massive repository. The research report has been summarized with informative and technical details of the dynamics of the market. It has been compiled by using some significant research methodologies such as primary and secondary research techniques.

The Stem Cell Cartilage Regeneration report also elaborates on the factors which are fueling or hampering the growth of the market. It gives more focus on recent trends and technologies which have been adopted by top-level industries are elaborated to get proper directions for the businesses and boosting the performance of the companies.

The Stem Cell Cartilage Regeneration report includes a comprehensive overview of the global Stem Cell Cartilage Regeneration market, which also sheds light on the scope of the product. The analysts have categorized the market into different segments on the basis of some significant market segments such as stem cell type, treatment, end user, and region. After a careful analysis of the market as per these categories, the analysts have revealed the market and production shares of several segments for the review period.

Fill Out Details to Receive Free Sample Report Copy Here @https://marketresearch.biz/report/stem-cell-cartilage-regeneration-market/request-sample

Prominent Top Key Vendors of Stem Cell Cartilage Regeneration Report:-Theracell (Laboratories), Orthocell Limited, Xintela AB (publ), CellGenix GmbH, Merck KGaA, Osiris Therapeutics Inc, BioTissue Technologies GmbH, Vericel Corporation, Smith & Nephew plc, EMD Serono Inc

The geographical segmentation of the global Stem Cell Cartilage Regeneration market allows users of the report to formulate a multilevel perspective of the market in terms of regional prominence and global expansion plans. Additionally, it throws light on leading industry key players across the global regions such as North America, Latin America, Asia-Pacific, Europe, The Middle East, and Africa. Different internal and external factors have been mentioned, which are responsible for fueling or restraining the progress of the companies. Informative information regarding the challenges faced by the industries and approaches adopted by them to overcome those threats has been included.

Geographical Segmentation:-

1.North America(United States, Canada)

2.Europe(Germany, Spain, France, UK, Russia, and Italy)

3.Asia-Pacific(China, Japan, India, Australia, and South Korea)

4.Latin America(Brazil, Mexico, etc.)

5.The Middle East and Africa(GCC and South Africa)

Stem Cell Cartilage Regeneration Market Segmentation:-

Segmentation by stem cell type:

Hematopoietic Stem Cells (HSCs)Pluripotent Stem Cells (iPSC/ESCs)Mesenchymal Stem Cells (MSCs)Segmentation by treatment:

MicrofractureOsteochondral TransplantAutologous Chondrocyte ImplantationStem Cell InjectionsSegmentation by end user:

Hospitals & ClinicsAmbulatory Surgical Centers

If you have any special requirements, please let us know and we will offer you the report as per your requirements.

Ask our Industry Experts @https://marketresearch.biz/report/stem-cell-cartilage-regeneration-market/#inquiry

The Key Points of this Stem Cell Cartilage Regeneration Market Report are:

1. To survey and forecast the market size share of Stem Cell Cartilage Regeneration, in terms of value and volume.

2. Provide detailed information concerning the Stem Cell Cartilage Regeneration major factors (opportunities, drivers, restraints, and industry-specific challenges) influencing the growth of Stem Cell Cartilage Regeneration market.

3. To study the future outlook and prospects for the Stem Cell Cartilage Regeneration market with Marketing Price (Price and Margin, Factors of Price Change, Manufacturers Gross Margin Analysis)

4. To analyze the global key regions Stem Cell Cartilage Regeneration market potential and advantage, opportunity and challenge, restraints and risks.

5. Detail Profile of the dominant players and Stem Cell Cartilage Regeneration comprehensively analyses their market status in terms of ranking and core capability along with in-depth the Stem Cell Cartilage Regeneration competitive landscape for the market leaders.

6. Study competitive developments like partnerships and joint ventures, Stem Cell Cartilage Regeneration new product developments, expansions and research and development of Stem Cell Cartilage Regeneration market.

Finally, it focuses on the beneficial opportunities for growth, which promotes a way of turning a business idea into the venture. In addition to this, it gives a detailed description of top driving factors such as Stem Cell Cartilage Regeneration Market for the studies. Restraints are also provided to study the risk factors in front of businesses.

ContactUs:

Mr. Benni Johnson

MarketResearch.Biz (Powered By Prudour Pvt. Ltd.)

420 Lexington Avenue, Suite 300, New York City, NY 10170, United States

Tel: +1 347 826 1876

Email:inquiry@marketresearch.biz

Go here to read the rest:
Global Stem Cell Cartilage Regeneration Market Current Status, Historical Analysis and Forecast 2019 to 2028 - Biz News Wire

The new dairy proofs boast a revamped genetic index for cattle lifespan, enabling milk producers to identify bulls whose offspring will be more healthy and productive will help predict more accurate longevity in additional days rather than lactations.

Previously expressed in lactations which meant very little difference between the best and worst animals, the indexs scale has now been increased to approximately -305 to +305 days enabling producers to make more precise decisions.

Marco Winters, head of animal genetics with AHDB Dairy, said: The new figures give producers a more meaningful prediction of the extra lifetime expected from a bulls daughters and make a greater distinction between individual bulls.

Lifespan reflects many contributory factors, ranging from fertility and somatic cell counts to legs, feet and udder conformation. The index has a strong correlation with an animals average daily lifetime yield, which is a key contributor to its lifetime profitability.

Producers have made progress in their cows lifespan, which has steadily increased since LS was included in AHDBs Profitable Lifetime Index (PLI) in 1999 (see graph).

By helping to differentiate individual sires and moving to a larger and more meaningful scale, we feel confident we can further increase genetic progress for this trait, so cutting a herds replacement rate and its costs of heifer rearing, he said.

Lifespan Index Q and A

1. Why is lifespan so important?

It is estimated to cost more than 1800 to rear a Holstein dairy heifer from birth to the point of calving. Around 70% of farmers pay back this investment during the animals second lactation. More precisely, the average number of days at which payback occurs is a staggering 530 after first calving! Any measures which can therefore be taken to extend an animals productive life beyond this point will help improve its return on the large initial investment. Using the Lifespan Index when breeding cattle can help producers improve their herds survival rates by hundreds of days.

2. How does the new scale work?

The new scale for Lifespan Index (LS) will run from around -305 days to +305 days, with positive figures being desirable. Daughters of a +305 Lifespan Index bull are predicted to live, on average, 305 days longer than daughters of a sire whose index is zero. Equally, they are predicted to live 610 days longer than daughters of a -305 LS bull. As with all UK genetic indexes, zero represents the average.

3. How are Lifespan Indexes calculated?

The Lifespan Index is calculated from actual daughter survival, when that information is available. When it is not, it is either calculated from the animals own genotype (if it has a genomic index), or from predictive traits such as type traits (legs, feet and udders) and Somatic Cell Count Index, all of which are correlated with lifespan. Where necessary, information on ancestors lifespan will also be included in the calculation of the index. This and all other predictors will diminish in their importance as the animal acquires progeny lifespan information of its own.

4. Arent many animals culled for low production rather than survivability?

An important feature of the Lifespan Index is that it predicts involuntary rather than voluntary culling. As there is such a strong relationship between milk production and lifespan (because low producers are generally culled earlier from the herd), Lifespan Index is corrected for milk production. This correction ensures the index is more a measure of daughters ability to survive than of their failure to produce milk, which itself would be apparent from Predicted Transmitting Abilities (PTAs) for production.

More:
Revised genetic index will help boost longevity - The Scottish Farmer

WEST LAFAYETTE, Ind. (WTHR) Researchers are looking for America's oldest dog.

They don't want to teach him new tricks, but they are hoping he could teach them a few things.

And your dog could be part of their life-long scientific study that's looking to learn from pets nationwide.

More than 40 scientists and researchers from across the United States including one from Purdue University are looking for dogs to participate the national study of the general health and wellness of dogs.

The Dog Aging Project will be looking at dogs of all breeds and mixes from across the nation. This is the first major longitudinal study involving dogs, and it's scheduled to last at least 10 years.

We are going to look at a lot of different aspects of dogs lives that affect their health and longevity, says Audrey Ruple, a veterinary epidemiologist at Purdue.

Dogs are good models for humans, she says. They have similar genetics, share our environment, and they also have similar diseases and health issues. We will be asking, How do dogs age healthfully? in order to help better understand how we can age healthfully, too.

Dogs of all age ranges, breeds and sizes are eligible to participate in the study. Owners go online to register their dogs, then create a personal profile to track health, home life, diet, environment and lifestyle.

Dogs will need to make regular veterinarian visits every year. If a dog is assigned to a specific group, the owners may get a kit for their veterinarian to collect blood, urine or other samples during the annual visit.

Participation is voluntary and there is no cost to participate.

Its important to get dogs from all parts of the U.S. because of the different environmental factors present, Ruple said. And were trying to find the oldest dog in America, as well.

All dogs registered will be eligible to participate in various studies. The group conducted a soft launch with 4,500 dogs registered earlier this fall. Recently, the researchers reached 75,000 dogs for the study.

Our study population just keeps growing and growing and growing, Ruple said.

Researchers hope to find out more details on how genetics, demographics and environmental factors such as chemical exposures and noise pollution impact health and longevity.

Ruple says one goal of the study is to not just improve the health and longevity of dogs, but also extend those findings to improve human health. By studying aging in dogs, we hope to learn how to better match human health span to life span so that we can all live longer, healthier lives, Ruple said.

Funding for the Dog Aging Project comes from the National Institute of Aging, a part of the National Institutes of Health, as well as from private donations.

Read the original:
Purdue taking part in life-long study of dogs health and aging - WTHR

Scientists researching a key aspect of biochemistry in living creatures have been taking a very close look at the tiny Caenorhabditis elegans roundworm. Their latest results show that when these nematodes get put under more biochemical stress early in their lives, they somehow tend to live longer.

This type of stress, called oxidative stress - an imbalance of oxygen-containing molecules that can result in cellular and tissue damage - seems to better prepare the worms for the strains of later life, along the same lines as the old adage that whatever doesn't kill you, makes you stronger.

You might think that worm lifespans have no bearing on human life. And surely, until we have loads more research done in this field, it would be a big leap to say the same principles of prolonging one's lifespan might hold true for human beings.

But there's good reason to put C. elegans through the paces. This model organism has proven immensely helpful for researchers trying to better understand key biological functions present in worm and human alike - and oxidative stress is one such function.

The little wriggly creatures are known to have significant variations in their lifespan even when the whole population is genetically identical and grows up in the exact same conditions. So the team went looking for other factors that affect C. elegans' longevity.

"The general idea that early life events have such profound, positive effects later in life is truly fascinating," says biochemist Ursula Jakob from the University of Michigan.

Jakob and her colleagues sorted thousands of C. elegans larvae based on the oxidative stress levels they experienced during development this stress arises when cells produce more oxidants and free radicals than they can handle. It's a normal part of the ageing process, but it's also triggered by exercise and a limited food supply.

One way to measure this stress is by the levels of reactive oxygen species (ROS) molecules an organism produces - simply put, this measurement indicates the biochemical stress an organism is under. In the case of these roundworms, the more ROS were produced during development, the longer their lifespans turned out to be.

(University of Michigan)

To explain how this effect of ROS might come about, the researchers went looking for changes in the worms' genetic regulation, specifically those genes that are known to be involved in dealing with oxidative stress.

While doing so, they detected a key difference - the nematodes exposed to more ROS during development appeared to have undergone an epigenetic change (a gene expression switch that can happen due to environmental influences) thatincreased the oxidative stress resistance of their body's cells.

There are still a lot of questions to answer, but the researchers think their results identify one of the stochastic or random influences on the lifespan of organisms; it's something that has been hypothesised in the field of the genetics of ageing. And down the line, it may turn out to be relevant for ageing humans, too.

"This study provides a foundation for future work in mammals, in which very early and transient metabolic events in life seem to have equally profound impacts on lifespan," the researchers conclude.

The study has been published in Nature.

View original post here:
Fascinating Study Finds That Stressed Out Baby Worms Tend to Live Longer - ScienceAlert

The genetic index that predicts dairy cattle lifespan has been revamped to make it more accurate and indicate longevity in additional days rather than lactations.

The change will help dairy cattle breeders identify bulls whose offspring should live more healthy, productive and longer lives in their herds.

Previously, lifespan was expressed in lactations, which meant very little difference between the best and worst animals.

The indexs scale has now been increased to about -305 to +305 days, enabling producers to make more precise decisions.

The update to the lifespan index takes effect from the December AHDB Dairy proof run, which will be published this week (3 December).

See also:How to achieve an efficient dairy breeding programme

Marco Winters, head of animal genetics with AHDB Dairy, said: The new figures give producers a more meaningful prediction of the extra lifetime expected from a bulls daughters and make a greater distinction between individual bulls.

Lifespan reflects many contributory factors, ranging from fertility and somatic cell counts to leg, feet and udder conformation. The index has a strong correlation with an animals average daily lifetime yield, which is a key contributor to its lifetime profitability.

By helping to differentiate individual sires and moving to a larger and more meaningful scale, we feel confident we can further increase genetic progress for this trait, so cutting a herds replacement rate and its costs of heifer rearing, Mr Winters added.

Why is lifespan so important?

It is estimated to cost more than 1,800 to rear a Holstein dairy heifer from birth to the point of calving. About 70% of farmers pay back this investment during the animals second lactation.

More precisely, the average number of days at which payback occurs is a staggering 530 after first calving.

So any measures that can extend an animals productive life beyond this point will help improve its return on the large initial investment.

Using the lifespan index when breeding cattle can help producers improve their herds survival rates by hundreds of days.

How does the new scale work?

The new scale for lifespan index will run from about -305 days to +305 days, with positive figures being desirable.

Daughters of a +305 lifespan index bull are predicted to live, on average, 305 days longer than daughters of a sire whose index is zero.

Equally, they are predicted to live 610 days longer than daughters of a -305 lifespan index bull. As with all UK genetic indexes, zero represents the average.

How are lifespan indexes calculated?

The index is calculated from actual daughter survival, when that information is available.

When it is not, it is either calculated from the animals own genotype (if it has a genomic index), or from predictive traits such as type traits (legs, feet and udders) and somatic cell count index, all of which are correlated with lifespan.

Where necessary, information on ancestors lifespan will also be included in the calculation of the index.

This and all other predictors will diminish in their importance as the animal acquires progeny lifespan information of its own.

Arent many animals culled for low production rather than survivability?

An important feature of the lifespan index is that it predicts involuntary rather than voluntary culling.

As there is such a strong relationship between milk production and lifespan (because low producers are generally culled earlier from the herd), lifespan index is corrected for milk production.

This correction ensures the index is more a measure of daughters ability to survive than of their failure to produce milk, which itself would be apparent from predicted transmitting abilities (PTAs) for production.

Read the original here:
Dairy lifespan index trait updated to improve accuracy - FarmersWeekly

It's that time of year with Thanksgiving just over and Christmas approaching that many of us tend to cut back on our exercise routines in order to enjoy the holidays with family and friends. So how much and how often do you need to work out to improve your health and fitness? There's not a simple answer to that question but there are several guidelines to follow that have been found through research.

First of all, it's important to accept that when it comes to moving, something is always better than nothing. Every rep, set and second that you move will get you much closer to your goals. Many research studies, most recently an August 2019 review published in the British Medical Journal, have shown that any exercise comes with a lower risk of early death. Interestingly, researchers have noted that the dose-response relationship between exercise and longevity is non-linear, meaning that going from zero to 15 minutes of exercise per day is more beneficial than going from 60 to 75 minutes. Moreover, the 2018 Physical Activity Guidelines for Americans edited its recommendation that physical activity occur in bouts of at least 10 minutes. Now, every single second of activity counts toward its weekly recommendation. That recommendation calls for at least 150 minutes a week of moderate-intensity aerobic activity (such as brisk walking), plus at least two days a week of total body strengthening activities. If activity is more intense, such as running or sprinting on a stationary bike, as little as 75 minutes may be enough. It's important to realize that these guidelines refer to the minimum amount necessary for good health, not to significantly improve fitness.

So how do you know how much your personal bare minimum is for improving fitness? That depends of several factors, including age, gender and genetics. For example, it takes less time and effort to make fitness gains when you're young, a time when your body has higher base levels of muscle, testosterone, growth hormone and bone mass. Fortunately for women, a 2011 study in the American Journal of Human Biology found that even though women have lower base levels of muscle mass, they are able to make similar percentage gains in muscle mass compared with men. In terms of genetics, it is true that some people can improve fitness faster and to a greater extent than others. Hopefully, you won that genetic lottery. It is also true that everyone has a genetic upper limit to their fitness potential. And the closer you are to that limit, the more challenging it is to continue making progress toward it.

In the first few months of a new training program, especially one focusing on strength development, you can expect to make big gains in strength quickly as your neuromuscular system learns how to execute the exercises more efficiently. It's also important to realize that during this time, despite increases in strength, muscle growth isn't as pronounced. After a couple of months though, further increases in strength are mainly due to muscle growth as the neuromuscular system adapts to your exercise routine.

Specifically, if you want to build muscle, as little as two 20 to 30 minute sessions may be enough to start to see some muscle definition. That means training each muscle group twice a week. If you want to maintain the muscle you already have, then once a week may be enough. To get the most out of each session, focus on large multi-joint movements such as squats, deadlifts, rows and push-ups rather than isolation exercises like biceps curls and leg extensions.

If your goal is to keep your heart healthy, lower blood pressure or cholesterol, then the federal guidelines' bare minimum may not be adequate. The American Heart Association recommends at least 40 minutes of moderate intensity aerobic activity three to four times a week. Before starting such a routine, it is important to check with your health care provider to make sure that it's safe to pursue this level of activity. The good news is that significant improvements in cardiovascular fitness can be expected relatively quickly, in the neighborhood of three to four weeks.

So as you contemplate your exercise routine during the holidays, keep in mind that what you do between Thanksgiving and Christmas is not as important as what you do between Christmas and Thanksgiving.

Read more from the original source:
What's the minimum amount of exercise I need to do to see results? - Richmond Register

It's easy to give thoughtless gifts. This year, give thoughtful gifts: science gifts! They're experimentally validated as wonderful*. This is Massive's 2019 holiday science shopping guide, with cool stuff from all around the science web, for Thanksgiving, Black Friday, Christmas, and beyond.

Illustrated by Matteo Farinella, Designed by Allan Lasser

Massive Science

Oh wow, so weird to see us at the top here. The coolest thing on this list is definitely the Women of Science Tarot deck we made. The deck features is itself a work of art, with beautiful original work from Matteo Farinella. Instead of the traditional face cards of many tarot decks, instead there are portraits of important women in science's history, including Mae Jemison, Rachel Carson, Marie Curie, Ada Lovelace, and more. If the the $75 price tag is too steep, there are also postcard packs with art from the deck and posters!

Genius Games

The geniuses at Genius Games make science-themed board games and card games. In Virulence, take on the role of a virus and replicate. Build atoms in Subatomic. Or, become the world's first programmers in Lovelace & Babbage. Massive has partnered with Genius Games to offer a 20% off coupon, just use the code MassiveScience20!

Courtesy of Genius Games

Two Photon

The undisputed champion of science art, pins, jewelry, and more. Our favorites include the neuroscience section, with brain pins and neuron necklaces, the virus t-shirt, and the nameplate necklaces, with options like "Scientist", "Doctor", and "Programmer."

Stitching Hew

What really sets Stitching Hew apart are their intricate stitch patterns, especially the Brainbrow Pyramidal Neuron Print, detailed enough to make Cajal blush. There are even downloadable stitch patterns or an entire beginner's science hand embroidery kit.

Rachel Ignotofsky

The prolific author and illustrator made one of our favorite books, Women in Science: 50 Fearless Pioneers Who Changed the World. But she also has other books, like Women in Art: 50 Fearless Creatives Who Changed the World, along with a whole pile of beautiful art prints to choose from.

Science On A Postcard

If you're looking for an enamel pin to signal your allegiance to a particular scientific field, then this Etsy shop is for you! Packed with notebooks, postcards, stickers and an even a pocket mirror, the Science On A Postcard shop hosts some of our favourite pins, including ones that say science communicator, future scientist and that climate change is real.

Awkward Yeti

You've undoubtedly seen their comics all over the great wide web, but Awkward Yeti's store is packed with goodies. There's tabletop games for the gamer who loves organs, some of the best stuffed organs (okay, the only stuffed organs) we've seen, like a uterus and an irritable bowel, and prints from the comic.

Courtesy of Awkward Yeti

Waterlust

You don't have to be a marine scientist to love their products. Waterlust carries leggings (with pockets!), rashguards and swim tops, board shorts, and more for people who love being in the water. Their products are great on land too the fabric is soft and stretchy, and the leggings and shorts have a wide waistband that makes them incredibly comfortable for lounging around the house or going to the gym. Each pattern is dedicated to a specific marine conservation cause (my favorite is the Floridian Aquifer collection). Their products are partially made from recycled plastic bottles and the gear is shipped in eco-friendly packaging, making Waterlust a great choice for the outdoor enthusiasts in your life!

PurpleLilacAmigurumi

This science crochet shop is run by a PhD student at the University of Toronto, so you know the plushies are accurate. Oh and they're lovely too. Take the crocheted neuron necklace, or our personal favorite, the Islets of Langerhans crochet pattern.

Skype a Scientist

Skype a Scientist is one of the best science outreach organizations we know of and they have the merch to match. If you love snakes and also Greek myths, consider this Medusa-as-a-scientist t-shirt. Or rather, if you're more of an astrobiology person, maybe the hardy tardigrade is more your speed.

The Vexed Muddler

If you're interested in science-themed underwear, this is the store for you. Consider the Maratus volans (aka the peacock spider) boxer briefs, which to be honest are kind of terrifying. If that's not your thing they also have phylogenetic tree skirts, intergalactic space dresses, and oh what the heck here's black widow underwear.

Slow Dance

Perhaps something a bit more...meditative? Slow Dance is a frame that produces slow-motion, real-time movement. The creators say it helps lower stress and is quite good for meditation (we weren't just being cute).

*data not shown

Visit link:
Watch a Dragon launch towards the International Space Station today! - Massive Science

BelleCell in London

Ive seen the future. And its unexpectedly sandwiched between those exuberant bastions of indulgence, the Ritz and Le Caprice. Rather like Harry Potters Platform 9 at Kings Cross, look carefully and theres a spiral staircase to a subterranean world. Once a cellar that housed Winston Churchills wine collection, it is now a series of neon-lit vaulted passages filled with white-coated therapists and space-age machines. This is the home of Londons first biohacking clinic.

BelleCell is the creation of Kasia Zajkowska, a Polish bioscientist and Cambridge graduate who specialised in genetics and molecular biotechnology and who looks as if she could be Bella Hadids sister. Ill have what shes having. Fifteen years ago science was focused on increasing the human life span, Zajkowska says. Now its

Want to read more?

Subscribe now and get unlimited digital access on web and our smartphone and tablet apps, free for your first month.

Follow this link:
BelleCell: the 'bio-hacking' clinic aiming to shake up wellness - The Times

Washington, DC (UroToday.com) On the final day of the Society of Urologic Oncology Meeting (SUO 2019), the six best abstracts submitted were selected for presentation. One of these highlighted studies from Memorial Sloan Kettering Cancer Center (MSKCC) evaluated the differential response of high grade non-muscle invasive bladder cancer to Bacillus Calmette-Guerin (BCG) on the basis of FGFR3 alterations. Dr. Timothy Clinton, a urologic oncology fellow at MSKCC, presented the groups findings.

Recently, the FDA approved Erdafitinib, a fibroblast growth factor receptor (FGFR)3 kinase inhibitor, for use in metastatic urothelial carcinoma on the basis of phase II results published this summer in NEJM. In that publication, Loriot et al. demonstrated a 59% response rate in patients with unresectable or metastatic urothelial carcinoma.1 These results have driven interest in expanding the use of FGFR3 kinase inhibitors and looking to FGFR3 alterations for prognostication. Specifically, FGFR3 mutations have been previously associated with lower response rates to immune checkpoint inhibition, are more commonly identified in non-muscle invasive bladder cancer which is specifically less likely to progress. For these reasons, Dr. Clinton postulated that FGFR3 alterations may be able to predict BCG response.

To that end, Dr. Clinton and colleagues identified treatment nave patients with high-grade nonmuscle invasive bladder cancer (NMIBC) enrolled in a prospective protocol that captured targeted exon sequencing on pretreatment tumor DNA and matched germline DNA. Within the MSKCC cohort there were over 1,400 bladder specimens with a quarter demonstrating genomic alterations in FGFR3. Of these patients, 119 patients with high-grade NMIBC underwent BCG treatment with 51containing aFGFR3alteration (43%); 39 patients (76%) were cTaHG and 12 (24%) were cT1HG at diagnosis. Interestingly, no patients with CIS had alterations in FGFR3.

Dr. Clinton proceeding by highlight the differential response to BCG between those who were FGFR3 wild-type and those with alterations. Overall, the median follow up was 60 months (IQR 32-75). At that time 39% of the entire cohort was free from high-grade recurrence with a significant difference between the two groups. 65% of wild-type patients were free from high-grade recurrence, were as only 39% of the FGFR3 alteration group was similarly recurrence-free(p<0.05). There was no difference in progression, however, the rate was very low in both groups. Looking more in depth into the FGFR3 altered tumors, the group looked for additional mutations that corresponded to BCG response, identifying significant co-occurrence ofFGFR3mutations with cell cycle genes includingCDKN2A(p=0.03) andMDM2(p=0.03) and noFGFR3mutated tumor contained anERBB2mutation.

Overall, Dr. Clinton concluded that while FGFR3 has been historically associated with favorable prognosis, FGFR3altered tumors are associated with high recurrence rates following BCG. Given these findings and the recent BCG shortages, patients with these alterations may benefit from alternative therapy with FGFR3 kinase inhibitors. The study represents a major step in predicting BCG response rates and FGFR3 profiling could represent a novel path for personalized medicine in the future. Clinical trials for FGFR3 in NMIBC are currently underway with results pending.

Presented by:TimothyClinton, MD, Urologic Oncology Fellow at Memorial Sloan Kettering Cancer Center

Written by: Adrien Bernstein, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PAat the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC

References:1.Loriot, Y., Necchi, A., Park, S., Garcia-Donas, J., Huddart, R., & Burgess, E. et al. (2019). Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.New England Journal Of Medicine,381(4), 338-348. doi: 10.1056/nejmoa1817323

See the original post here:
SUO 2019: Response of FGFR3 Alterations In High-Grade Non-Muscle Invasive Bladder Cancer Treated with Intravesical BCG Therapy - UroToday

In this video from SC19, Jaan Mannik from One Stop Systems describes how the company delivers AI on the Fly.

AI on the Fly puts computing and storage resources for the entire AI workflow, not in the datacenter, but on the edge near the sources of data. Applications are emerging for this new AI paradigm in diverse areas including autonomous vehicles, predictive personalized medicine, battlefield command and control, and industrial automation. The common elements of these solutions are high data rate acquisition, high speed low latency storage and efficient high performance AI training and inference computing. All of these building block elements are connected seamlessly with memory mapped PCI Express system, interconnected and customized as appropriate, to meet the specific environmental requirements of in the field installations.

AI on the Fly solutions are different than traditional datacenter centric AI infrastructure, as they must deploy in harsh and rugged environments. The solutions must meet unique criteria for shock and vibration, redundancy, large operating temperature, altitude ranges and uninterrupted power sources. Few companies have the expertise across all the technologies required for designing and delivering tightly integrated AI on the Fly platforms.

OSS is a custom manufacturer of specialized high performance computing systems for industries that are showing the largest proliferation of use cases for AI on the Fly systems. These industries include:

These edge applications have unique requirements over traditional embedded computing. There is no compromise possible in delivering high performance while maintaining efficient space, weight and power. Delivering the high performance required in edge applications necessitates PCIe interconnectivity providing the fast data highway between high speed processors, NVMe storage and compute accelerators using GPUs or application specific FPGAs. AI on the Fly high performance applications will naturally demand this capability on the edge. Additionally, these solutions often require unique space and power saving form factors and specialized rugged enclosures.

See our complete coverage of SC19

Sign up for our insideHPC Newsletter

See more here:
One Stop Systems does AI on the Fly at SC19 - insideHPC