]]> Understanding the genetic causes of rare diseases supports drug development. Credit: Shutterstock.

Developing drugs to treat rare diseases is fraught with challenges; these range from trying to recruit from tiny patient populations to fill much-need clinical trials to the complex reimbursement landscape for these innovative, and often bespoke, therapies. However, as scientists improve their understanding of the genetic causes of many rare conditions and regulators explore new reimbursement options, pharma companies and smaller biotech firms are increasingly being empowered to address more of these tricky indications.

In this context, could 2020 be a breakthrough year for patients with rare diseases? Here are three case studies of companies on the verge of having treatments for rare diseases approved Rocket and Fanconi anaemia, PTC Therapeutics and aromatic l-amino acid decarboxylase (AADC) deficiency and, finally, Amryt and epidermolysis bullosa.

Fanconi anaemia (FA) is a rare paediatric inherited diseasecharacterised by bone marrow failure and predisposition to cancer, in the words of Rocket Pharmas CEO Gaurav Shah. Caused by a mutation in the FANC genes, patients with Fanconi experience bone marrow failure as they are unable to create new blood cells.

The current standard of care for Fanconi is a stem cell transplant, but Shah explains the risks involved with these pioneering procedures.

While these transplants do prolong patients lives, the procedure is incredibly difficult and is associated with a high potential for graft-versus-host disease, he says. Stem cell transplants can also lead to an even higher risk of head and neck cancer risk for Fanconi patients; almost everyone with FA who undergoes this procedure dies in their 30s.

Rocket wants to change this situation with its lentiviral vector gene therapy, RP-L102. It is specifically for Fanconi-A, which Shah explains is the most common form of the disease. He adds that the therapy contains patient-derived haematopoietic stem cells that have been generally modified to contain a functional copy of FANCA gene, a mutation which causes Fanconi-A.

RP-L102 is currently in a global registrational Phase IIA study, which has been efficacious and safe in patients so far. The data demonstrate that a single dose of RP-L102 leads to both genetic and functional correction as measured by a progressive increase in corrected peripheral blood and bone marrow cells, says Shah. Most importantly, this treatment can be administered without a conditioning regimen [of chemotherapy and radiation]. [This] means we may be able to treat patients as a preventative measure before bone marrow failure occurs, like a vaccine, with a single dose administration early in life.

Based on these promising signals, RP-L102 has received all accelerated regulatory tools from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The company is hoping to complete its biologics license applications and marketing authorisation applications (MAA) to the two regulators within the next few years.

To overcome challenges facing Rocket in the development of RP-L102, Shah explains the company worked to improve upon its own expertise in rare diseases by working with world-class research and development partners, as well immersing itself within patient communities to learn more about their treatment needs.

Slightly further along the drug approval journey is PTC Therapeutics AADC deficiency drug, PTC-AADC, for which the company recently submitted an MAA to the EMA. The company expects full EMA approval towards the end of 2020 and to treat the first patients either in the first or second quarter of 2021.

PTC acquired PTC-AADC, alongside other gene therapy assets, when it bought rare central nervous system-focused Agilis Biotherapeutics in July 2018, PTCs EMEA and Asia Pacific senior vice-president and general manager Adrian Haigh explains.

AADC deficiency is a rare condition caused by a mutation in the DDC gene, which leads to issues with the AADC enzyme and subsequent reductions in the production of dopamine. Children suffering with AADC deficiency fail to reach neurological and development milestones and have a high risk of death early in life. The only current approach to treating the condition is through dopamine agonists, which Haigh notes are largely ineffective.

The particular approach developed by Agilis, [which is] unlike other forms of gene therapy, involves delivering a very small dose of gene therapy directly into the affected, post-mitotic cells, Haigh says. The rationale is that once youve delivered the drug to post-mitotic cells, which are not dividing, it is going to stay there for a long time.

Other advantages include a reduced chance of significant immune reaction and since the dose is smaller, the treatment could overcome some of the manufacturing issues facing other gene therapies. PTC has decided to bring PTC-AADCs manufacturing in house so they are not reliant on third parties schedules and capacities.

PTCs MAA for its AADC deficiency gene therapy is based on two clinical trials of 26 patients in total. Haigh explains the company has mapped motor milestones, and he noted that in advisory boards with payers theyve been incredibly impressed by our videos showing children progressing from lying flat on their backs to walking around.

He notes that in this case, it is certainly not ethical to drill a hole in a patients head and inject a virus containing a placebo and instead PTC has successfully completed a single-arm trial by comparing with patients natural history. Regulators need to be open to novel clinical trial design, particularly in rare diseases where you have ethical problems, Haigh argues.

The company had to abandon a previous drug in development because they could not agree an economic and deliverable clinical trial design with the FDA.

One of the main challenges that faced PTC in the development of PTC-AADC was diagnosis. Haigh explains they found a lot of patients have been misdiagnosed with either cerebral palsy or epilepsy so the company launched a free genetic testing programme. This also allowed them to find patients to recruit into the trial and estimate the number of patients with AADC deficiency who might be able to benefit from this gene therapy.

Epidermolysis bullosa (EB) is a group of rare skin conditions caused by genetic mutations in the genes that encode for the proteins of the skin, particularly in collagen VII.

There are currently no approved treatments for this condition, EB charity DEBRAs UK branch director of research Caroline Collins notes the condition is managed by regular changing of dressings and the lancing of blisters.

EB is characterised by blisters and wounds on the skin; these wounds are extremely painful and can cover huge areas of the patients body, such as their whole back or entire legs. However, Collins explains these are not like the kinds of wounds you get with ulcers or burns, and they move continuously.

As well as making it incredibly challenging for patients to deal with these never-healing wounds, it also makes it difficult for drug developers to find and establish accepted clinical trial endpoints centred on wound healing. DEBRA is therefore advocating for natural history to be considered in clinical trial designs, Collins explains.

Despite these challenges, UK drug company Amryt is hoping to submit authorisation applications to the FDA and EMA by the end of 2021 for its EB drug, AP101. The company has repurposed the topical gel created for burns wounds to treat EB. It is made from a combination of an extract from the bark of the birch tree and pure sunflower oil, the companys chief medical officer Dr Mark Sumeray explains.

AP101 is currently being studied in a Phase III study Amryt claim this is the biggest global EB trial ever undertaken and has been granted rare paediatric disease designation from the FDA.

Although the current results are blinded, Sumeray explains a recent analysis by an independent data monitoring board found that the firm only needed to increase the number of patients slightly, suggesting that at this point in time, the data would have looked encouraging. Too small a patient population makes it hard for efficacy to be statistically significant.

Since Amryts AP101 may be the first drug approved for EB, Collins emphasises it is important that the company has productive conversations with regulators about the specific challenges of EB. This will help to set the ground for others to follow and further transform the lives of EB patients.

It is clear that Amryt is committed to EB because the company in-licensed a second EB candidate, a topical gene therapy called AP103 in 2018.

Sumeray explains: We have invested a lot of time and effort in the development, not only of the lead product, but also of relationships with physicians and scientists working in EB. If we can figure out how to successfully bring products to the market and have them reimbursed, then all of that knowledge can applied again.

See original here:
Rare disease outlook 2020: three therapies set to make waves this year - pharmaceutical-technology.com

Recommendation and review posted by Bethany Smith

The road into Batlow is littered with the dead.

In the smoky, gray haze of the morning, it's hard to make out exactly what Matt Roberts' camera is capturing. Roberts, a photojournalist with the Australian Broadcasting Corporation, keeps his lens focused on the road as he rolls into the fire-ravaged town 55 miles west of Canberra, Australia's capital. At the asphalt's edge, blackened livestock carcasses lie motionless.

The grim scene, widely shared on social media, is emblematic of the impact the 2019-20 bushfire season has had on Australia's animal life. Some estimates suggest "many, many billions" of animals have been killed, populations of endemic insects could be crippled and, as ash washes into riverways, marine life will be severely impacted. The scale of the bushfires is so massive, scientists are unlikely to know the impact on wildlife for many years.

But even before bushfires roared across the country, Australia's unique native animals were in a dire fight for survival. Habitat destruction, invasive species, hunting and climate change have conspired against them. Populations of native fauna are plummeting or disappearing altogether, leaving Australia with an unenviable record: It has the highest rate of mammal extinctions in the world.

A large share of Australia's extinctions have involved marsupials -- the class of mammals that includes the nation's iconic kangaroos, wallabies, koalas and wombats. A century ago, the Tasmanian tiger still padded quietly through Australia's forests. The desert rat-kangaroo hopped across the clay pans of the outback, sheltering from the sun in dug-out nests.

Now they're gone.

Australia's 2019-20 bushfire season has been devastating for wildlife.

In a search for answers to the extinction crisis, researchers are turning to one lesser-known species, small enough to fit in the palm of your hand: the fat-tailed dunnart. The carnivorous mouse-like marsupial, no bigger than a golf ball and about as heavy as a toothbrush, has a tiny snout, dark, bulbous eyes and, unsurprisingly, a fat tail. It's Baby Yoda levels of adorable -- and it may be just as influential.

Mapping the dunnart's genome could help this little animal become the marsupial equivalent of the lab mouse -- a model organism scientists use to better understand biological processes, manipulate genes and test new approaches to treating disease. The ambitious project, driven by marsupial geneticist Andrew Pask and his team at the University of Melbourne over the last two years, will see scientists take advantage of incredible feats of genetic engineering, reprogramming cells at will.

It could even aid the creation of a frozen Noah's Ark of samples: a doomsday vault of marsupial cells, suspended in time, to preserve genetic diversity and help prevent further decline, bringing species back from the brink of extinction.

If that sounds far-fetched, it isn't. In fact, it's already happening.

Creating a reliable marsupial model organism is a long-held dream for Australian geneticists, stretching back to research pioneered by famed statistician Ronald Fisher in the mid-20th century. To understand why the model is so important, we need to look at the lab mouse, a staple of science laboratories for centuries.

"A lot of what we know about how genes work, and how genes work with each other, comes from the mouse," says Jenny Graves, a geneticist at La Trobe University in Victoria, Australia, who has worked with marsupials for five decades.

The mouse is an indispensable model organism that shares many genetic similarities with humans. It has been key in understanding basic human biology, testing new medicines and unraveling the mysteries of how our brains work. Mice form such a critical part of the scientific endeavor because they breed quickly, have large litters, and are cheap to house, feed and maintain.

The lab mouse has been indispensable in understanding physiology, biology and genetics.

In the 1970s, scientists developed a method to insert new genes into mice. After a decade of refinement, these genetically modified mice (known as "transgenic mice") provided novel ways to study how genes function. You could add a gene, turning its expression up to 11, or delete a gene entirely, shutting it off. Scientists had a powerful tool to discover which genes performed the critical work in reproduction, development and maturation.

The same capability does not exist for marsupials. "At the moment, we don't have any way of manipulating genes in a devil or a kangaroo or a possum," says Graves. Without this capability, it's difficult to answer more pointed questions about marsupial genes and how they compare with mammal genes, like those of mice and humans.

So far, two marsupial species -- the Tammar wallaby and the American opossum -- have been front and center of research efforts to create a reliable model organism, but they both pose problems. The wallaby breeds slowly, with only one baby every 18 months, and it requires vast swaths of land to maintain.

The short-tailed opossum might prove an even more complicated case. Pask, the marsupial geneticist, says the small South American marsupial is prone to eating its young, and breeding requires researchers to sift through hours of video footage, looking for who impregnated whom. Pask also makes a patriotic jab ("they're American so we don't like them") and says their differences from Australian marsupials make them less useful for the problems Australian species face.

But the dunnart boasts all the features that make the mouse such an attractive organism for study: It is small and easy to house, breeds well in captivity and has large litters.

"Our little guys are just like having a mouse basically, except they have a pouch," Pask says.

Pask (front) and Frankenberg inspect some of their dunnarts at the University of Melbourne.

A stern warning precedes my first meeting with Pask's colony of fat-tailed dunnarts.

"It smells like shit," he says. "They shit everywhere."

I quickly discover he's right. Upon entering the colony's dwellings on the third floor of the University of Melbourne's utilitarian BioSciences building, you're punched in the face by a musty, fecal smell.

Pask, a laid-back researcher whose face is almost permanently fixed with a smile, and one of his colleagues, researcher Stephen Frankenberg, appear unfazed by the odor. They've adapted to it. Inside the small room that houses the colony, storage-box-cages are stacked three shelves high. They're filled with upturned egg cartons and empty buckets, which work as makeshift nests for the critters to hide in.

Andrew Pask

Frankenberg reaches in without hesitation and plucks one from a cage -- nameless but numbered "29" -- and it hides in his enclosed fist before peeking out of the gap between his thumb and forefinger, snout pulsing. As I watch Frankenberg cradle it, the dunnart seems curious, and Pask warns me it's more than agile enough to manufacture a great escape.

In the wild, fat-tailed dunnarts are just as inquisitive and fleet-footed. Their range extends across most of southern and central Australia, and the most recent assessment of their population numbers shows they aren't suffering population declines in the same way many of Australia's bigger marsupial species are.

Move over, Baby Yoda.

As I watch 29 scamper up Frankenberg's arm, the physical similarities between it and a mouse are obvious. Pask explains that the dunnart's DNA is much more closely related to the Tasmanian devil, an endangered cat-sized carnivore native to Australia, than the mouse. But from a research perspective, Pask notes the similarities between mouse and dunnart run deep -- and that's why it's such an important critter.

"The dunnart is going to be our marsupial workhorse like the mouse is for placental mammals," Pask says.

For that to happen, Pask's team has to perfect an incredible feat of genetic engineering: They have to learn how to reprogram its cells.

To do so, they collect skin cells from the dunnart's ear or footpad and drop them in a flask where scientists can introduce new genes into the skin cell. The introduced genes are able to trick the adult cell, convincing it to become a "younger," specialized cell with almost unlimited potential.

The reprogrammed cells are known as "induced pluripotent stem cells," or iPS cells, and since Japanese scientists unraveled how to perform this incredible feat in 2006, they have proven to be indispensable for researchers because they can become any cell in the body.

"You can grow them in culture and put different sorts of differentiation factors on them and see if they can turn into nerve cells, muscle cells, brain cells, blood vessels," Pask explains. That means these special cells could even be programmed to become a sperm or an egg, in turn allowing embryos to be made.

Implanting the embryo in a surrogate mother could create a whole animal.

It took about 15 minutes to get this dunnart to sit still.

Although such a technological leap has been made in mice, it's still a long way from fruition for marsupials. At present, only the Tasmanian devil has had iPS cells created from skin, and no sperm or egg cells were produced.

Pask's team has been able to dupe the dunnart's cells into reverting to stem cells -- and they've even made some slight genetic tweaks in the lab. But that's just the first step.

He believes there are likely to be small differences between species, but if the methodology remains consistent and reproducible in other marsupials, scientists could begin to create iPS cells from Australia's array of unique fauna. They could even sample skin cells from wild marsupials and reprogram those.

Doing so would be indispensable in the creation of a biobank, where the cells would be frozen down to -196 degrees Celsius (-273F) and stored until they're needed. It would act as a safeguard -- a backup copy of genetic material that could, in some distant future, be used to bring species back from the edge of oblivion, helping repopulate them and restoring their genetic diversity.

Underneath San Diego Zoo's Beckman Center for Conservation Research lies the Frozen Zoo, a repository of test tubes containing the genetic material of over 10,000 species. Stacked in towers and chilled inside giant metal vats, the tubes contain the DNA of threatened species from around the world, suspended in time.

It's the largest wildlife biobank in the world.

"Our goal is to opportunistically collect cells ... on multiple individuals of as many species as we can, to provide a vast genetic resource for research and conservation efforts," explains Marlys Houck, curator at the Frozen Zoo.

The Zoo's efforts to save the northern white rhino from extinction have been well publicized. Other research groups have been able to create a northern white rhino embryo in the lab, combining eggs of the last two remaining females with frozen sperm from departed males. Scientists propose implanting those embryos in a surrogate mother of a closely related species, the southern white rhino, to help drag the species back from the edge of oblivion.

For the better part of a decade, conservationists have been focused on this goal, and now their work is paying off: In the "coming months," the lab-created northern white rhino embryo will be implanted in a surrogate.

Sudan, the last male northern white rhinoceros, was euthanized in 2018.

Marisa Korody, a conservation geneticist at the Frozen Zoo, stresses that this type of intervention was really the last hope for the rhino, a species whose population had already diminished to just eight individuals a decade ago.

"We only turn to these methods when more traditional conservation methods have failed," she says.

In Australia, researchers are telling whoever will listen that traditional conservation methods are failing.

"We've been saying for decades and decades, many of our species are on a slippery slope," says John Rodger, a marsupial conservationist at the University of Newcastle, Australia, and CEO of the Fauna Research Alliance, which has long advocated for the banking of genetic material of species in Australia and New Zealand.

In October, 240 of Australia's top scientists delivered a letter to the government detailing the country's woeful record on protecting species, citing the 1,800 plants and animals in danger of extinction, and the "weak" environmental laws which have been ineffective at keeping Australian fauna alive.

Institutions around Australia, such as Taronga Zoo and Monash University, have been biobanking samples since the '90s, reliant on philanthropic donations to stay online, but researchers say this is not enough. For at least a decade, they've been calling for the establishment of a national biobank to support Australia's threatened species.

John Rodger

"Our real problem in Australia ... is underinvestment," Rodger says. "You've got to accept this is not a short-term investment."

The current government installed a threatened-species commissioner in 2017 and committed $255 million ($171 million in US dollars) in funding to improve the prospects of 20 mammal species by 2020. In the most recent progress report, released in 2019, only eight of those 20 were identified as having an "improved trajectory," meaning populations were either increasing faster or declining slower compared to 2015.

A spokesperson for the commissioner outlined the $50 million investment to support immediate work to protect wildlife following the bushfires, speaking to monitoring programs, establishment of "insurance populations" and feral cat traps. No future strategies regarding biobanking were referenced.

Researchers believe we need to act now to preserve iconic Australian species like the koala.

In the wake of the catastrophic bushfire season and the challenges posed by climate change, Australia's extinction crisis is again in the spotlight. Koalas are plastered over social media with charred noses and bandaged skin. On the front page of newspapers, kangaroos bound in front of towering walls of flame.

Houck notes that San Diego's Frozen Zoo currently stores cell lines "from nearly 30 marsupial species, including koala, Tasmanian devil and kangaroo," but that's only one-tenth of the known marsupial species living in Australia today.

"Nobody in the world is seriously working on marsupials but us," Rodger says. "We've got a huge interest in maintaining these guys for tourism, national icons... you name it."

There's a creeping sense of dread in the researchers I talk to that perhaps we've passed a tipping point, not just in Australia, but across the world. "We are losing species at an alarming rate," says Korody from the Frozen Zoo. "Some species are going extinct before we even know they are there."

With such high stakes, Pask and his dunnarts are in a race against time. Perfecting the techniques to genetically engineer the tiny marsupial's cells will help enable the preservation of all marsupial species for generations to come, future-proofing them against natural disasters, disease, land-clearing and threats we may not even be able to predict right now.

Pask reasons "we owe it" to marsupials to develop these tools and, at the very least, biobank their cells if we can't prevent extinction. "We really should be investing in this stuff now," he says. He's optimistic.

In some distant future, years from now, a bundle of frozen stem cells might just bring the koala or the kangaroo back from the brink of extinction.

And for that, we'll have the dunnart to thank.

Originally published Feb. 18, 5 a.m. PT.

Originally posted here:
Building a 'doomsday vault' to save the kangaroo and koala from extinction - CNET

Recommendation and review posted by Bethany Smith

Sorry, but your browser does not support the video tag.

(BPT) - For many people with cancer and other life-threatening diseases, stem cell transplants provide hope and can impact the course of the disease, but they also come with risks. One of those risks is graftversushost disease (GVHD).

What is GVHD?

GVHD is a potentially life-threatening condition that can occur after an allogeneic stem cell transplant from a donor, in which the donated cells initiate an immune response and attack the recipient's organs and tissues. There are two major forms of GVHD, acute and chronic, that can affect multiple organ systems including the skin, gastrointestinal (digestive) tract and liver.

Although the exact incidence of GVHD is unknown, it is estimated that up to 70% of stem cell transplant recipients will develop either acute or chronic GVHD, resulting in significant morbidity and mortality. Due to these concerning statistics, health care experts and the entire GVHD community are calling for additional research and support.

People with GVHD and their caregivers face a multitude of challenges, often including limited support, minimal information and few treatment options. Its time to change the future for those living with GVHD.

New award inspires the GVHD community

The Incyte Ingenuity Award aims to encourage innovation in GVHD care and other serious diseases. As part of the award, one unique proposal that addresses a critical unmet need in the GVHD community will be awarded up to $100,000 for the proposed initiative to be developed and executed. Specific initiatives may include patient and/or professional educational programs, policy-focused activities as well as awareness and support campaigns.

Incyte wanted to create a community driven program dedicated to improving the lives of patients with serious diseases, such as GVHD, which can be difficult to treat and have a devastating impact on the lives of patients, says Barry Flannelly, Pharm.D., Executive Vice President and General Manager, U.S., Incyte. Through this award, we hope to spark creativity and innovation, resulting in impactful and actionable initiatives for the GVHD community.

Get involved to make a difference

Submissions are accepted from nonprofit 501(c)(3), patient, policy and caregiver organizations, as well as health care providers and midlevel or junior faculty who submit under their health care organizations. To apply, visit http://www.IncyteIngenuityAward.com and submit an online application featuring a summary of the proposed initiative. The application window is now open and will close April 30, 2020.

All applications will be reviewed and evaluated by an independent judging panel that will select the top three entries, who will then be asked to submit a more detailed proposal of their initiative. The final award recipient will be announced in August of 2020. Apply now!

MAT-INC-00717 02/20

Read this article:
Health insights: What is GVHD and why is innovation so critical? - Eagle & Times

Recommendation and review posted by Bethany Smith

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to enfortumab vedotin-ejfv (Padcev; Astellas Pharma and Seattle Genetics) in combination with Mercks (known as MSD outside the United States and Canada) anti-PD-1 therapy pembrolizumab (Keytruda) for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.

It is estimated that approximately 81,000 people in the U.S. will be diagnosed with bladder cancer in 2020. [1] Urothelial cancer accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter, and urethra. [2] Globally, approximately 549,000 people were diagnosed with bladder cancer in 2018, and there were approximately 200,000 deaths worldwide. [3]

The recommended first-line treatment for patients with advanced urothelial cancer is cisplatin-based chemotherapy. For patients who are unable to receive cisplatin, such as people with kidney impairment, a carboplatin-based regimen is recommended. However, fewer than half of patients respond to carboplatin-based regimens and outcomes are typically poorer compared to cisplatin-based regimens. [4]

Conditionally approvedEnfortumab vedotin-ejfv, a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer, was conditionally approved by the FDA in December 2019 based on the Accelerated Approval Program. [5][6]

Antibody-drug Conjugates or ADCs are highly targeted biopharmaceutical drugs that combine monoclonal antibodies specific to surface antigens present on particular tumor cells with highly potent anti-cancer agents linked via a chemical linker.

With seven approved drugs on the market, ADCs have become a powerful class of therapeutic agents in oncology and hematology.

Continued approval for enfortumab vedotin-ejfv in combination with pembrolizumab for the treatment of patients with advanced or metastatic urothelial cancer may be contingent upon verification and description of clinical benefit in confirmatory trials. [5]

The drug is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting.

Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis). [5]

Breakthrough therapyThe Breakthrough Therapy process is designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition. The designation is based upon preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints. In the case of enfortumab vedotin, the designation was based on the initial results from Phase Ib/II EV-103 Clinical Trial.

The FDAs Breakthrough Therapy designation reflects the encouraging preliminary evidence for the combination of enfortumab vedotin and pembrolizumab in previously untreated advanced urothelial cancer to benefit patients who are in need of effective treatment options, said Andrew Krivoshik, M.D., Ph.D., Senior Vice President, and Oncology Therapeutic Area Head, Astellas.

We look forward to continuing our work with the FDA as we progress our clinical development program as quickly as possible.

This is an important step in our investigation of enfortumab vedotin in combination with pembrolizumab as first-line therapy for patients with advanced urothelial cancer who are unable to receive cisplatin-based chemotherapy, said Roger Dansey, M.D., Chief Medical Officer, Seattle Genetics.

Based on encouraging early clinical activity, we recently initiated a phase III trial of this platinum-free combination and look forward to potentially addressing an unmet need for patients.

Clinical trialThe Breakthrough Therapy designation was granted based on results from the dose-escalation cohort and expansion cohort A of the Phase Ib/II trial, EV-103 (NCT03288545), evaluating patients with locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy-treated in the first-line setting with enfortumab vedotin-ejfv in combination with pembrolizumab.

The initial results from the trial were presented at the European Society of Medical Oncology (ESMO) 2019 Congress, and updated findings at the 2020 Genitourinary Cancers Symposium.

EV-103 is an ongoing, multi-cohort, open-label, multicenter phase Ib/II trial of PADCEV alone or in combination, evaluating the safety, tolerability, and efficacy in muscle-invasive, locally advanced and first- and second-line metastatic urothelial cancer.

Adverse eventsSerious adverse reactions occurred in 46% of patients treated with enfortumab vedotin-ejfv. The most common serious adverse reactions (3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

Discontinuing treatmentAdverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

The most common adverse reactions (20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade 3 adverse reactions (5%) were rash (13%), diarrhea (6%) and fatigue (6%).

Specific recommendations

HyperglycemiaHyperglycemia occurred in patients treated with enfortumab vedotin-ejfv, including death and diabetic ketoacidosis (DKA), in patients with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C 8% were excluded.

Physicians are recommended to closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia and, if blood glucose is elevated (>250 mg/dL), withhold the drug.

Peripheral neuropathyPeripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with enfortumab vedotin-ejf in clinical trials. Two percent (2%) of patients experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with enfortumab vedotin-ejf with or without preexisting peripheral neuropathy.

The median time to onset of Grade 2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement.

Physicians should:

Occular disordersOcular disorders occurred in 46% of the 310 patients treated with enfortumab vedotin-ejf. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with enfortumab vedotin-ejf.

The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2).

Physicians should monitor patients for ocular disorders and consider:

Skin reactionsSkin reactions occurred in 54% of the 310 patients treated with enfortumab vedotin-ejf in clinical trials. Twenty-six percent (26%) of patients had a maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3).

Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement.

Physicians should monitor patients for skin reactions, and consider:

Infusion site extravasationSkin and soft tissue reactions secondary to extravasation have been observed after the administration of enfortumab vedotin-ejf. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed.

Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation.

Physicians should ensure adequate venous access prior to starting enfortumab vedotin-ejf and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicityEnfortumab vedotin-ejf can cause fetal harm when administered to a pregnant woman.

Physicians should advise patients of the potential risk to the fetus and advise female patients of reproductive potential to use effective contraception during enfortumab vedotin-ejf treatment and for 2 months after the last dose. At the same time, they should advise male patients with female partners of reproductive potential to use effective contraception during treatment with enfortumab vedotin-ejf and for 4 months after the last dose.

Clinical trialA Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer (EV-103) NCT03288545

References[1] American Cancer Society. Cancer Facts & Figures 2020. Online. Last accessed on January 23, 2020.[2] American Society of Clinical Oncology. Bladder cancer: introduction (10-2017). Online. Last accessed on January 23, 2020.[3] International Agency for Research on Cancer. Cancer Tomorrow: Bladder. Online. Last accessed on January 23, 2020.[4] National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer. Version 4; July 10, 2019. Online. Last accessed on January 23, 2020.[5] Enfortumab vedotin-ejfv (Padcev; Astellas Pharma [package insert]. Northbrook, IL)[6] Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

A version of this article was first published in ADC Review | Journal of Antibody-drug Conjugates.

Read the original post:
Combination Enfortumab Vedotin + Pembrolizumab Granted Breakthrough Therapy in Bladder Cancer - OncoZine

Recommendation and review posted by Bethany Smith

Global Stem Cell Banking Market Report 2020comprises of data that can be quite essential when it comes to dominate the market or making a mark in the market as a new emergent. The statistics are represented in graphical format in this business research report for a clear understanding on facts and figures. The report provides market insights which help to have a more precise understanding of the market landscape, issues that may impinge on the Stem Cell Banking industry in the future, and how to position specific brands in the best way. Analysis and discussion of important industry trends, market size, and market share estimates are mentioned in the Tissue-Engineered Products Market analysis report.

For More Info, Get a Sample[emailprotected]https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-stem-cell-banking-market

The Increased Market Growth can be identified by the increasing procedures of hematopoietic stem cell transplantation (hsct), emerging technologies for stem cell processing, storage and preservation. Increasing birth rates, awareness of stem cell therapies and higher treatment done viva stem cell technology. Data Bridge Market Research has recently announced publishing of a report, titled Global Stem Cell Banking Market Industry Trends and Forecast to 2026 As per the report, Global stem cell banking market is set to witness a substantial CAGR of 11.03% in the forecast period of 2019- 2026. The Stem Cell Banking Market report provides the details related to fundamental overview, development status, latest advancements, market dominance and market dynamics. The report also presents the evaluation of the competitive landscape of the market.

Few Of The Major Competitors Currently Working In The Global Stem Cell Banking Market AreNSPERITE N.V, Caladrius, ViaCord, CBR Systems, Inc, SMART CELLS PLUS, LifeCell International, Global Cord Blood Corporation, Cryo-Cell International, Inc., StemCyte India Therapeutics Pvt. Ltd, Cordvida, ViaCord, Cryoviva India, Vita34 AG, CryoHoldco, PromoCell GmbH, Celgene Corporation, BIOTIME, Inc., BrainStorm Cell Therapeutics and others.

Market Definition: Global Stem Cell Banking Market

Stem cells are cells which have self-renewing abilities and segregation into numerous cell lineages. Stem cells are found in all human beings from an early stage to the end stage. The stem cell banking process includes the storage of stem cells from different sources and they are being used for research and clinical purposes. The goal of stem cell banking is that if any persons tissue is badly damaged the stem cell therapy is the cure for that. Skin transplants, brain cell transplantations are some of the treatments which are cured by stem cell technique.

Explore Key Industry Insights In 60 Tables And 220 Figures From The 350 Pages Of Report, Global Stem Cell Banking MarketBy Source (Placental Stem Cells (PSCs), Human Embryo-Derived Stem Cells (hESCs), Bone Marrow-Derived Stem Cells (BMSCs), o Dental Pulp-Derived Stem Cells (DPSCS), Adipose Tissue-Derived Stem Cells (ADSCs) and Other Stem Cell Sources), By Application (Personalized Storage, Clinical, Research), Service Type (Sample Collection and Transportation, Sample Processing, Sample Analysis, Sample Preservation and Storage), Geography (North America, Europe, Asia Pacific, Latin America and The Middle East and Africa) Industry Trends and Forecast to 2026.

The global Stem Cell Banking market report covers scope and product overview to define key terms and offers detailed information about market dynamics to the readers. This is followed by a regional outlook and segmental analysis. The report also consists of the facts and key values of the global Stem Cell Banking market, in terms of sales and volume, revenue and its growth rate.

One of the important factors in the global Stem Cell Banking market report is competitive analysis. The report covers all of the key parameters, such as product innovation, market strategies of the key players, market share, revenue generation, the latest research and development and market experts views.

Inquire More or Share Questions if Any before the Purchase on This Report @https://www.databridgemarketresearch.com/inquire-before-buying/?dbmr=global-stem-cell-banking-market

The report focusses on weaknesses and strengths of the global Stem Cell Banking market with a competitive landscape that includes information on some market vendors. Information presented in the report is gathered from primary and secondary research methods. The report also presents recent trends and opportunities of the market helping players strive for the lions share in the market.

Segmentation: Global Stem Cell Banking Market

By Source

By Application

Research

By Service Type

Competitive Analysis: Global Stem Cell Banking Market

The global Stem Cell Banking market is highly fragmented and the major players have used various strategies such as product (software) launches, agreements, joint ventures, partnerships, acquisitions, and others to increase their footprints in this market. The report includes market shares of Stem Cell Banking market for global, Europe, North America, Asia Pacific and South America.

Research Methodology: Global Stem Cell Banking Market

Data collection and base year analysis is done using data collection modules with large sample sizes. The market data is analysed and forecasted using market statistical and coherent models. Also market share analysis and key trend analysis are the major success factors in the market report. To know more please request an analyst call or can drop down your enquiry.

The key research methodology used by DBMR research team is data triangulation which involves data mining, analysis of the impact of data variables on the market, and primary (industry expert) validation. Apart from this, other data models include Vendor Positioning Grid, Market Time Line Analysis, Market Overview and Guide, Company Positioning Grid, Company Market Share Analysis, Standards of Measurement, Top to Bottom Analysis and Vendor Share Analysis. To know more about the research methodology, drop in an inquiry to speak to our industry experts.

Primary Respondents

Demand Side: Doctors, Surgeons, Medical Consultants, Nurses, Hospital Buyers, Group Purchasing Organizations, Associations, Insurers, Medical Payers, Healthcare Authorities, Universities, Technological Writers, Scientists, Promoters, and Investors among others.

Supply Side: Product Managers, Marketing Managers, C-Level Executives, Distributors, Market Intelligence, and Regulatory Affairs Managers among others.

Reasons to Purchase this Report

Get Direct Order of this Report @https://www.databridgemarketresearch.com/checkout/buy/enterprise/global-stem-cell-banking-market

Research Methodology: Global Stem Cell Banking Market

Data collection and base year analysis is done using data collection modules with large sample sizes. The market data is analysed and forecasted using market statistical and coherent models. Also market share analysis and key trend analysis are the major success factors in the market report. To know more please request an analyst call or can drop down your enquiry.

The key research methodology used by DBMR research team is data triangulation which involves data mining, analysis of the impact of data variables on the market, and primary (industry expert) validation. Apart from this, other data models include Vendor Positioning Grid, Market Time Line Analysis, Market Overview and Guide, Company Positioning Grid, Company Market Share Analysis, Standards of Measurement, Top to Bottom Analysis and Vendor Share Analysis. To know more about the research methodology, drop in an inquiry to speak to our industry experts.

Customization of the Report

All segmentation provided above in this report is represented at country level.

All products covered in the market, product volume and average selling prices will be included as customizable options which may incur no or minimal additional cost (depends on customization)

Table of Content: Global Stem Cell Banking Market

Continued..

Browse Complete Tables and Figures:https://www.databridgemarketresearch.com/toc/?dbmr=global-stem-cell-banking-market

About Data Bridge Market Research:

Data Bridge Market Research set forth itself as an unconventional and neoteric Market research and consulting firm with unparalleled level of resilience and integrated approaches. We are determined to unearth the best market opportunities and foster efficient information for your business to thrive in the market. Data Bridge endeavors to provide appropriate solutions to the complex business challenges and initiates an effortless decision-making process.

Contact Us:

Data Bridge Market Research

US: +1 888 387 2818

UK: +44 208 089 1725

Hong Kong: +852 8192 7475

Email:[emailprotected]

Read the original post:
Stem Cell Banking Market 2020 Climbs on Positive Outlook of Booming Sales|NSPERITE NV, Caladrius, ViaCord, CBR Systems, SMART CELLS PLUS, LifeCell...

Recommendation and review posted by Bethany Smith

On August 23, 2019, the FamilieSCN2A Foundation held their biennial SCN2A Professional and Family meeting, in Seattle, Washington. The gathering brought together 37 families of individuals with mutations in the SCN2A gene, 60 investigators, eight clinicians and five industry groups that conduct research and/or clinical work on conditions related to this genetic change. A number of SFARI scientists and staff also attended the event.

The SCN2A family meeting was one of many events that family organizations of rare, neurodevelopmental disorders organized last summer. These meetings help families connect with others similarly affected as well as professionals working to better understand these conditions and develop new therapeutics. SFARI often attends and facilitates research opportunities carried on at these events.

SCN2A is a high-confidence autism risk gene, which encodes a subunit of a sodium channel in the brain called Nav1.2. When the channel malfunctions, conditions like epilepsy and autism follow. As part of its mission to understand the genetics and neurobiological underpinnings of autism, SFARI has awarded about $3 million for research on SCN2A, and some of this research was presented at the meeting. SFARI also supports a genetics first initiative called Simons Searchlight (formerly known as Simons VIP), which enrolls people with a genetic diagnosis showing rare genetic changes associated with autism and related neurodevelopmental conditions, such as SCN2A.

Many stories that may reflect the different ways SCN2A can be disabled were told at the meeting. One child had his first seizure when he was days old, and now spends many of his days irritable and immobilized by dystonia. Another developed normally until his first seizure as a toddler, which seemed to wipe out all of his skills; his milestones are now hard won in the face of continuing seizures and an autism diagnosis. Another had a sudden regression at 1 year of age, and after a misdiagnosis and seizure medication, she goes to a school for children with autism. Still another suffered from relentless seizures, which robbed her of speech; she died last year at the age of 12.

So far, about 300 different variants of the SCN2A gene have beendocumented, and the functional consequences of many are unclear. Some researchers have developed high-throughput experiments to systematically test each of thesevariants, and to screen compounds that could normalize their function2. Another approach may use genetherapy to boostexpression of the remaining good copy of SCN2A. Either way, finding appropriate in vitro testing grounds for these SCN2A variants is essential and may help personalize treatment approaches or identify more homogeneous patient groups for drug trials.

The meeting also underscored the power of family gatherings to push the science ahead. Investigators could see multiple examples of a rare genetic condition and engage new participants in research studies such as The Investigation of Genetic Exome Research (TIGER), a project of the University of Washington that compares phenotypes of single-gene conditions. In turn, families had the opportunity to express their concerns to scientists and infuse the research proceedings with urgency.

My biggest takeaway from this years conference was the mutual inspiration between the scientists and the families, says Leah Schust, meeting organizer and executive director of the FamilieSCN2A Foundation. Her son has a mutation in SCN2A.

Meeting the researchers working on a cure for our kids motivates us to fight on, Schust says. Then the scientists all say that meeting the families inspires them to go back to their labs and work even harder.

Family focus. The family meeting helped researchers reconsider what would be meaningful clinical endpoints for potential treatments. Schust says that most researchers and industry groups had thought seizure control was the most important issue. After listening to us, they realized that quality of life, movement disorders and autonomic dysfunction are higher on our list of where we would like to see improvement, she says.

When SCN2A mutations were first linked to autism, the gene stood out because it encodes a relatively well-understood protein, unlike many of the other identified genes. Nav1.2 is a voltage-gated channel found exclusively on excitatory neurons in the brain, where it controls the flow of sodium ions into the neuron, and thus its propensity for firing action potential. Experiments have revealed detailed pictures of Nav1.2s structure3, and known drugs alter its function4.

SCN2A also stands out because of its high recurrence rate in autism: unlike other autism genes, SCN2A is mutated with somewhat regular frequency5 (Figure 1).

Just as understanding why a car wont start is critical to fixing it, researchers need to understand how these SCN2A mutations alter the Nav1.2 channel. A current model1 posits that some mutations are gain-of-function, rendering the channel too active and the brain hyperexcitable, leading to infantile epilepsy; conversely, loss-of-function mutations reduce excitability and seem associated with autism and/or intellectual disability, as well as childhood-onset (as opposed to neonatal) seizures.

Yet the functional consequences of most SCN2A mutations remain unknown, and some may not fall neatly into a loss-of-function or gain-of-function category. A way of making sense of these mutations may come from looking at the working parts of Nav1.2, said Arthur Campbell of the Broad Institute of MIT and Harvard. For example, missense SCN2A variants linked to epilepsy seem to hit the channel randomly. But when marking their location on a crystal structure model of the channel, the missense variants cluster in several places: on the voltage sensor, on the linker helix responsible for conveying voltage sensor movement to the channel pore, on an area thought to interact with the beta-subunits involved in chaperoning the channel to the right place, and on the inactivation gate, which closes the pore off from sodium ion flow. He suggested that this knowledge, combined with the structural similarities between all sodium channels, may help drug development for SCN2A-related conditions.

High-throughput systems that can assay hundreds of cells at a time are helping researchers systematically explore SCN2A mutation, explained SFARI Investigator Al George of Northwestern University. While conventional electrophysiology would require weeks of work to characterize a single SCN2A variant, Georges group uses an automated patch-clamp system that can characterize multiple variants transfected into non-neuronal cell lines in a day. Using this system, two variants associated with neonatal seizures both exhibited an exceptional willingness to activate and a slowness to inactivate, which are properties consistent with a gain-of-function interpretation.

The high-throughput set up also promises to expedite the hunt for drugs to normalize SCN2A function: George described a 384-well plate design that allows measurement of the effects of two different drugs, at four different concentrations, on the SCN2A variant and control channels simultaneously. A known drug (carbamazepine) and an experimental drug (PRX-330) shifted channel inactivation to more hyperpolarized voltages, which could help quiet channels with gain-of-function mutations.

To narrow in on potentially therapeutic compounds, Jeff Cottrell and colleagues at the Broad Institute of MIT and Harvard have come up with a two-stage screen to find small molecule activators or inhibitors of Nav1.2 channels. First, compounds are initially tested on non-neural cells transfected with Nav1.2 sodium channels and potassium channels, which enables them to spike. The cells in 384-well plates are stimulated in parallel, and voltage-sensitive dyes give a readout of spiking activity; remarkably, Cottrells system allows data collection from up to 96 wells simultaneously. Any compounds that modulate spiking would then be subjected to the second stage, in a high-throughput electrophysiology assay similar to that described by George. Compounds with helpful mechanisms would then be tested for selectivity for Nav1.2 versus other sodium channels. A selective compound would then be tested in neurons, first in vitro then in vivo. This step-wise process has identified an activating compound that makes Nav1.2 more likely to open at rest and has potent effects on action potentials in brain slices and on electroencephalogram (EEG) traces from mice engineered to carry a disabled copy of SCN2A; however, Cottrell said this particular compound is not a therapeutic candidate in part because it broadens the action potential in a way that could promote seizures. A full screen is underway, and so far has identified 378 modulators from a library of 77,000 compounds.

Beyond academia, J.P. Johnson Jr. of Xenon in Burnaby, British Columbia, discussed the companys work to create sodium channel inhibitors for treating epilepsy. To obtain selective compounds, the group targets the voltage-sensing domain because its structure is the most diverse region of sodium channels. Xenon uses a trial-and-error method to optimize sodium channel inhibitor potency and selectivity. The methodical process has yielded some interesting compounds, including both selective Nav1.6 inhibitors and dual Nav1.6 and Nav1.2 inhibitors. Both quashed spiking in mouse excitatory pyramidal neurons, which contain only Nav1.2 and Nav1.6, but they did not alter spiking in Nav1.1-containing inhibitory neurons. A Nav1.6 selective inhibitor, XEN901, is currently undergoing safety trials in humans.

Kathrin Meyer of Nationwide Childrens Hospital in Columbus, Ohio, addressed the possibility of using gene therapy to normalize malfunctioning Nav1.2 channels. Meyer has been involved in several gene-therapy trials for neuromuscular disorders, including a successful one for infant-onset spinal muscular atrophy type6. Gene therapy for brain diseases was spurred by the discovery of adeno-associated virus 9 (AAV9), which can cross the bloodbrain barrier to deliver genetic material to the central nervous system. AAV9 is small, cannot replicate, does not integrate into host DNA and seems not to cause disease in humans. In considering gene therapy for SCN2A-related conditions, Meyer emphasized an approach that adds back a working copy of the gene, thus sidestepping the need for gene editing to make mutation-specific corrections. Such a treatment would only apply to those with loss-of-function mutations.

The large size of the SCN2A gene precludes its delivery by AAV9, however. As a workaround, Meyer suggested that SCN2As mRNA transcript could be targeted in an attempt to replace only the affected area of the mRNA. So far, such strategies have not been very efficient, but there are new ideas that might address some of the difficulties. Because access to tissue samples of patients with neurological disorders is limited, the development and testing of new therapies is complicated. Meyer suggested developing gene therapies in vitro using neurons reprogrammed from skin cells of patients. This might help identify which patients would react best to a certain treatment. There is likely not a one-fit-for-all situation, she said.

SFARI deputy scientific director John Spiro underscored the need for in vitro systems, citing the organizations initiative to bank blood cells to systematically generate induced pluripotent stem cells from individuals with autism. Simons Searchlight is also a resource of many different biospecimens for researchers. So far, 186 families with SCN2A-related changes have registered, and 83 of these have completed consent, lab reports and medical histories with a large number of blood samples as well. (On the sidelines of the meeting, 18 parents, 11 of their children with SCN2A mutations, and three unaffected siblings donated blood toward this initiative.) Spiro also stressed a need to come up with more quantitative methods of phenotyping, such as wearable electronics that can monitor sleep and circadian rhythms. Data that can be collected longitudinally and at home might provide sensitive outcome measures for clinical trials.

A new role for Nav1.2 has been revealed in recent work described by SFARI Investigator Kevin Bender of the University of California, San Francisco: the channels mediate back-propagating action potentials, which travel into the dendritic trees of neurons. Mice engineered to lack one copy of SCN2A a situation that mimics people with truncating SCN2A mutations that render the resulting Nav1.2 channels useless had cortical neurons with slower action potentials, reduced dendritic excitability and immature synapses based on their shape and function7. This role for Nav1.2 was particularly important later in development: when conditional knockout mice lost an SCN2A copy later in life, their cortical neurons exhibited immature synapses, though their density remained normal. Preliminary experiments suggest that adding back a working copy of SCN2A later in life through transgenic methods or by upregulating transcription of the remaining good copy of SCN2A via CRISPR techniques can restore action potential velocity and synaptic maturity.

Bender stressed how interacting with the SCN2A family group helped focus his research on important aspects of their childrens conditions. For example, parents have noted sensory hypersensitivity in their children, leading Bender to collaborate with colleague Evan Feinberg to use an eye-tracking assay in mice to measure their visual responses. He noted that SCN2A haploinsufficient mice were more sensitive to certain visual stimuli than control mice; if the assay is robust, it could help bridge the gap between SCN2A-related phenotypes in humans and behaviors measured in mice.

As meeting attendees sorted through the new findings, therapeutic questions lingered. An important issue for any therapy, whether drug or gene, will be how early in development one will have to intervene to help someone with an SCN2A mutation. Bender noted that synaptic properties could be rescued in his mice when they were 30 days old equivalent to a 10-year-old human but these and other experiments will have to probe the time periods during which therapies will be maximally effective. To find good measures of efficacy also means understanding the full complement of conditions that beset people with SCN2A mutations. For example, though seizures afflict many, Keith Coffman of Childrens Mercy Hospital in Kansas City, Missouri, suggested that, in some cases, these represent a movement disorder rather than epilepsy. Basic descriptive knowledge like this is imperative for guiding future treatment approaches.

Another smaller SCN2A meeting is planned for this year from July 30 to August 2, in Columbus, Ohio. This will be more family focused, says Schust, and there will be opportunities to participate in research.

There is clearly a lot more work to do before all the terrific basic research that was discussed at this meeting produces meaningful results for families, but it is extremely gratifying to see how much progress has been made on so many fronts and how many new good ideas are emerging, Spiro says. And its terrific to witness firsthand the positive cycle of how families drive researchers and vice versa.

View post:
Seeing through a forest of SCN2A gene variation - SFARI News

Recommendation and review posted by Bethany Smith

FEBRUARY 19, 2020 When Lt. Col. Jason Barnhill traveled to Africa last summer, he took with him not only the normal gear of an Army officer, but also a 3D printer.

Barnhill, who is the life science program director at the U.S. Military Academy, traveled to Africa to study how 3D printers could be used for field medical care. Barnhills printer was not set up to print objects made out of plastics as the printers are frequently known for. Instead, his printer makes bioprinted items that could one day be used to save Soldiers injured in combat.

The 3D bioprinting research has not reached the point where a printed organ or meniscus can be implanted into the body, but Barnhill and a team of cadets are working to advance the research in the field.

Twenty-six firsties are doing bioprinting research across seven different projects as their capstone this year. Two teams are working on biobandages for burn and field care. Two teams are working on how to bioengineer blood vessels to enable other bioprinted items that require a blood source, such as organs, to be viable. One team is working on printing a viable meniscus and the final team is working on printing a liver.

The basic process of printing biomaterial is the same as what is used to print a plastic figurine. A model of what will be printed is created on the computer, it is digitally sliced into layers and then the printer builds it layer by layer. The difference is the ink that is used.

Instead of heating plastic, 3D bioprinting uses a bioink that includes collagen, a major part of human tissue, and cells, typically stem cells.

A lot of this has to do with the bioink that we want to use, exactly what material were using as our printer ink, if you will, Class of 2020 Cadet Allen Gong, a life science major working on the meniscus project, said. Once we have that 3D model where we want it, then its just a matter of being able to stack the ink on top of each other properly.

Cadets are researching how to use that ink to create a meniscus to be implanted into a Soldiers injured knee or print a liver that could be used to test medicine and maybe one day eliminate the shortage of transplantable organs.

The research at West Point is funded by the Uniformed Services University of Health Science and is focused on increasing Soldier survivability in the field and treating wounded warriors.

Right now, cadets on each of the teams are in the beginning stages of their research before starting the actual printing process. The first stage includes reading the research already available in their area of focus and learning how to use the printers. After spring break, they will have their first chance to start printing with cells.

For the biobandage, meniscus and liver teams, the goal is to print a tangible product by the end of the semester, though neither the meniscus or liver will be something that could be implanted and used.

There are definitely some leaps before we can get to that point, Class of 2020 Cadet Thatcher Shepard, a life science major working on the meniscus project, said of actually implanting what they print. (We have to) make sure the body doesnt reject the new bioprinted meniscus and also the emplacement. There can be difficulties with that. Right now, were trying to just make a viable meniscus. Then, well look into further research to be able to work on methods of actually placing it into the body.

The blood vessel teams are further away from printing something concrete because the field has so many unanswered questions. Their initial step will be looking at what has already been done in the field and what questions still need to be answered. They will then decide on the scope and direction of their projects. Their research will be key to allowing other areas of the field to move forward, though. Organs such as livers and pancreases have been printed, so far, they can only be produced at the micro level because they have no blood flow.

Its kind of like putting the cart before the horse, Class of 2020 Cadet Michael Deegan, a life science major working on one of the blood vessel projects, said. Youve printed it, great, but whats the point of printing it if its not going to survive inside your body? Being able to work on that fundamental step thats actually going to make these organs viable is what drew me and my teammates to be able to do this.

While the blood vessel, liver and meniscus projects have the potential to impact long-term care, the work being done by the biobandage teams will potentially have direct uses in the field during combat. The goal is to be able to take cells from an injured Soldier, specifically one who suffers burns, and print a bandage with built in biomaterial on it to jumpstart the healing process.

Medics would potentially be deployed with a 3D printer in their Humvee to enable bandages to be printed on site to meet the needs of the specific Soldier and his or her exact wound. The projects are building on existing research on printing sterile bandages and then adding a bioengineering element. The bandages would be printed with specialized skin and stem cells necessary to the healing process, jumpstarting healing faster.

Were researching how the body actually heals from burns, Class of 2020 Cadet Channah Mills, a life science major working on one of the biobandage projects, said. So, what are some things we can do to speed along that process? Introducing a bandage could kickstart that healing process. The faster you start healing, the less scarring and the more likely youre going to recover.

The meniscus team is starting with MRI images of knees and working to build a 3D model of a meniscus, which they will eventually be able to print. Unlike a liver, the meniscus doesnt need a blood flow. It does still have a complex cellular structure, though, and a large part of the teams research will be figuring out how and when to implant those cells into what theyre printing.

Of the 26 cadets working on bioprinting projects, 17 will be attending medical school following graduation from West Point. The research they are doing gives them hands-on experience in a cutting-edge area of the medical field. It also enabled them to play a role in improving the care for Soldiers in the future, which will be their jobs as Army doctors.

Being on the forefront of it and just seeing the potential in bioengineering, its pretty astounding, Gong said. But it has also been sobering just to see how much more complicated it is to 3D print biomaterials than plastic.

The bioprinting projects will be presented during the academys annual Projects Day April 30.

By Brandon OConnor

More:
Cadets Research Bioprinting to Improve Soldier Care - MilitarySpot

Recommendation and review posted by Bethany Smith

"I would take them to the clean lab and at my work station I would open them up and then I would use a swab to swab around the inside of the pots that contained the samples to recover the DNA," he said.

"Once I'd done that, I'd have an extraction tube ready and you cut the tip off the swab and put it in the extraction tube for processing."

Mr Talbot said he would have carried out the process twice, keeping AJM40 and AJM42 separatefrom AJM46 and AJM48 to prevent contamination.

"The whole point of the clean lab is to prevent contaminating your sample with extraneous DNA," he said.

"There are safety cabinets for working in so the airflow is designed to prevent contamination and the labs themselves have a positiveair pressure."

Mr Talbot then added a chemical solution to the tubes with the swabs inside and they underwent a heating and spinning process for the DNA to be extracted.

He noted that the first time he tried to extract the DNA, it failed, as some of the chemical solution - the phenol - he had added to the tubes appeared frozen or crystallised.

He then added more phenol to the samples from a new bottle and repeated the process, which successfully separated the DNA.

A further several stages of the extraction were then carried out, with Mr Talbot estimating it would have taken a "few hours" to get to the final extract.

Witnesses were present for the key stages of the extraction process, to peer review Mr Talbot's workings.

The rest is here:
Claremont killer trial LIVE: Court sits into night for UK witnesses to give evidence on breakthrough DNA moment - WAtoday

Recommendation and review posted by Bethany Smith

You might be familiar with a womens clinic that provides care and treatment specifically for womens health concerns such as pregnancy, menstrual concerns. Infertility issues and chronic disorders that involve womens reproductive health. Just like women, men also have their own medical issues and it is universal fact men and women have different medical issues concerning their reproductive health and related problems.

A typical mens clinic such as DBClinic in Singapore focuses on mens health especially on topics or health issues that most men arent comfortable to talk about. These include sexual health issues like testicular and penile concerns, fertility issues, screening and treatment for sexually transmitted diseases (STDs) and HIV infection, prostate problems and even disorders like hair loss in men.

If you and your partner have been trying to conceive but to no avail, then it is recommended that you (and your partner) undergo fertility screening to determine what causes infertility. A proper diagnosis from fertility screening will enable your doctor to devise an appropriate treatment and management plan to help you and your partner. Fertility screening is also useful for people who plan to conceive or get married to determine whether they are able to make children.

It cannot be denied that there is a stigma concerning STDs and HIV not only in Singapore but worldwide. This is why people who are affected by these infections are not very open to seeking treatment and proper diagnosis because of the fear of being exposed. A mens clinic in Singapore is a safe haven for people with STDs and HIV because they are treated with the utmost care and confidentiality.

Prostate cancer is one of the top cancers affecting men in Singapore and usually affects men at an older age (usually beyond 50). It can be manifested by urination problems, blood in urine and semen, pain during ejaculation and erection problems. Early detection of prostate cancer gives you a chance for seeking treatments as early as possible. Another type of prostate problem is called benign prostate hyperplasia (BPH) and characterized by an enlarged prostate. Hough this condition isnt cancerous, it can bring lots of negative effective effects to ones quality of life.

Medically called Androgenic Alopecia is a common occurrence in men. It can even occur in men in their early 20s and it is a condition that is influenced by genetics. Meaning, it can run in the genes. While male pattern hair loss is not a serious medical concern, it can be a serious cosmetic concern for men. Thinning hair can make you look older than you actually are and in severe cases, it can cause total baldness.

DB Clinic for Mens Health

DB Clinic is a mens health clinic in Singapore that provides expert and personalized treatments and guidance to men who are experiencing sensitive and personal medical issues. Men in general, arent really open to sharing very personal concerns because it is just part of their nature. And when dealing with personal health issues, it is good to have someone you can trust. Someone who can help you have effective treatments. The doctors at DB Clinic are trained to deal with mens health. They are experts in creating an environment where patients can freely and comfortably share their issues which ultimately, builds trust.

Like Loading...

Read this article:
Services and Treatments That You Can Receive at a Mens Clinic in Singapore - Chiang Rai Times

Recommendation and review posted by Bethany Smith

Heres the truth about serum: Its the biggest secret to having younger-looking, radiant skin.

You know all the other steps to staying healthyand showing it: wearing SPF, and applying retinol. You stay hydrated and eat healthy foods. You get lots of exercise and plenty of sleep. But, are you applying serums? They can give your skin some of the most immediate and impactful benefits.

Serum seeps into all three layers of your skin to work its magic at deeper levels than moisturizer ever could. Those moisturizing creams merely sit atop your skin. Theyre equally important, and shield skin from toxins, but they do little to reverse dark spots and smooth wrinkles. Serums, on the other hand, can correct hyperpigmentation and puffy eyes.

Serum brightens your skin complexion, and can preserve moisture levels in ways that moisturizers never could (funny, given its name). No two serums are alike in terms of ingredients and overall benefits, but almost all of them brighten your skin and smooth complexion. Here are seven of our favorite serums; apply them to clean, dried skin before moisturizers, SPFs, retinol or night creams.

If your skin suffers from redness or discoloration, then look for a corrective serum. SkinCeuticals gel serum uses thyme and cucumber extract to soothe irritation, as well as mulberry extract to even skin tone and gently hydrate the skin. If most moisturizers make your skin break out, then this is a gentle and top-notch moisturizing alternative.

Vitamin C is one of the best ingredients you can apply to skin for brighter, more even complexion. Glossiers serum is packed with it, along with magnesium, for an instant pick-me-up for tired or dull skin. Use it daily to preserve a fresh face, and to get ahead of the inevitable hangovers or early mornings.

The skin around your eyes is more sensitive than the rest of your face, and is much thinner, too hence why you quickly show signs of tiredness. (Its fluid buildup from a lack of rest, shining through your skin.) So, target the eyes with a special-blend serum that tightens and brightens at the same time. In OSEAs eye serum, hyaluronic acid preserves firmness and moisture levels, grape-seed-derived resveratrol shields this thin skin from toxins, and algae extract plumps and nourishes tired eyes (and alert eyes, if youre plenty rested already everyone benefits). It also prevents and helps reverse fine lines and other signs of aging.

Some serums are best worn during the day those that focus on hydration and pure brightening. Others, like corrective and exfoliating serums, are often best suited for bedtime so that they can sync with your bodys circadian rhythm to boost cellular turnover (and in turn guarantee that you wake up looking rested and more youthful). However, some serums cover both bases: Brickells night serum is ultra-hydrating so much so that its impact is maximized by wearing it overnight. Its loaded with plant stem cells, hyaluronic acid and vitamin C, and promises to magnify the benefits of a full nights sleep. Your friends and colleagues will notice the difference within days. (Assuming you arent pairing it with a lovely binge-drinking or chain-smoking habit.)

Theres an entire family of serums that focuses on exfoliation, by using ingredients that dissolve dead skin cells and reduce hyperpigmentation (dark spots and discoloration). Herbivores serum does so with alpha- and beta-hydroxy acids, all of which are naturally derived, despite their sciencey-sounding names. Theyre extracted from things like willow bark and sugar maple, and in turn leave skin bright, while minimizing pore size and smoothing skin texture.

Its hard to categorize Caudelies skin-brightening serum, since it uses the brands proprietary blend of ingredients (Viniferine, derived from grape vines) but they seem to deliver on their promise to brighten skin 62 times better than Vitamin C. All around the globe, this is what Caudelies spa customers pay top dollar for, and you can enjoy the same complexion-smoothing effects for less than a buck a day (assuming you just use a couple drops daily).

If your skin texture needs attention just as much as your skin tone, then look for a corrective and smoothing serum. This one from PCA Skin is pumped with peptides, and it waxes poetic on your skin to undo signs of aging (like the appearance of fine lines, wrinkles, dark spots and acne spots). It also helps skin retain moisture thanks to the inclusion of hyaluronic acid, rice bran extract, squalene, ensuring firmness and brightness.

See the rest here:
The Best Serums to Brighten and Refresh Dull, Tired Skin - gearpatrol.com

Recommendation and review posted by Bethany Smith

TOKYO and BOTHELL, Wash., Feb. 19, 2020 /PRNewswire/ --Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for PADCEV (enfortumab vedotin-ejfv) in combination with Merck's (known as MSD outside the United States and Canada) anti-PD-1 therapy KEYTRUDA (pembrolizumab) for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.

The FDA's Breakthrough Therapy process is designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition. Designation is based upon preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints.

"The FDA's Breakthrough Therapydesignation reflects the encouraging preliminary evidence for the combination of PADCEV and pembrolizumab in previously untreated advanced urothelial cancer to benefit patients who are in need of effective treatment options," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "We look forward to continuing our work with the FDA as we progress our clinical development program as quickly as possible."

"This is an important step in our investigation of PADCEV in combination with pembrolizumab as a first-line therapy for patients with advanced urothelial cancer who are unable to receive cisplatin-based chemotherapy," said Roger Dansey, M.D., Chief Medical Officer, Seattle Genetics. "Based on encouraging early clinical activity, we recently initiated a phase 3 trial of this platinum-free combination and look forward to potentially addressing an unmet need for patients."

The Breakthrough Therapy designation was granted based on results from the dose-escalation cohort and expansion cohort A of the phase 1b/2 trial,EV-103 (NCT03288545), evaluating patients with locally advanced or metastatic urothelialcancer who are unable to receive cisplatin-based chemotherapytreated in the first-line setting with PADCEV in combination with pembrolizumab. Initial results from the trial were presented at the European Society of Medical Oncology (ESMO) 2019 Congress, and updated findings at the 2020 Genitourinary Cancers Symposium. EV-103 is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 trial of PADCEV alone or in combination, evaluating safety, tolerability and efficacy in muscle invasive, locally advanced and first- and second-line metastatic urothelial cancer.

About Bladder and Urothelial CancerIt is estimated that approximately 81,000 people in the U.S. will be diagnosed with bladder cancer in 2020.1 Urothelial cancer accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.2

Globally, approximately 549,000 people were diagnosed with bladder cancer in 2018, and there were approximately 200,000 deaths worldwide.3

The recommended first-line treatment for patients withadvanced urothelial cancer is a cisplatin-based chemotherapy. For patients who are unable to receive cisplatin, such as people with kidney impairment, a carboplatin-based regimen is recommended. However, fewer than half of patients respond to carboplatin-based regimens and outcomes are typically poorer compared to cisplatin-based regimens.4

About PADCEV PADCEV (enfortumab vedotin-ejfv) was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.5

PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5,6 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).5PADCEV is co-developed by Astellas and Seattle Genetics.

Important Safety Information

Warnings and Precautions

Adverse ReactionsSerious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

The most common adverse reactions (20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade 3 adverse reactions (5%) were rash (13%), diarrhea (6%) and fatigue (6%).

Lab AbnormalitiesIn one clinical trial, Grade 3-4 laboratory abnormalities reported in 5% were: lymphocytes decreased, hemoglobin decreased, phosphate decreased, lipase increased, sodium decreased, glucose increased, urate increased, neutrophils decreased.

Drug Interactions

Specific Populations

For more information, please see the full Prescribing Information for PADCEV here.

About Astellas Astellas Pharma Inc., based in Tokyo, Japan, is a company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. For more information, please visit our website at https://www.astellas.com/en.

About Seattle Genetics Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative medicines targeting cancer to make a meaningful difference in people's lives. The company is headquartered in Bothell, Washington, and has offices in California, Switzerland and the European Union. For more information on our robust pipeline, visit http://www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

About the Astellas and Seattle Genetics CollaborationSeattle Genetics and Astellas are co-developing PADCEV (enfortumab vedotin-ejfv) under a collaboration that was entered into in 2007 and expanded in 2009. Under the collaboration, the companies are sharing costs and profits on a 50:50 basis worldwide.

About the Astellas, Seattle Genetics and Merck CollaborationSeattle Genetics and Astellas entered a clinical collaboration agreement with Merck to evaluate the combination of Seattle Genetics' and Astellas' PADCEV (enfortumab vedotin-ejfv) and Merck's KEYTRUDA (pembrolizumab), in patients with previously untreated metastatic urothelial cancer. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Astellas Cautionary NotesIn this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

Seattle Genetics Forward Looking StatementsCertain statements made in this press release are forward looking, such as those, among others, relating to the development of PADCEV in combination with pembrolizumab as a first-line therapyfor patients with advanced urothelial cancerwho are unable to receive cisplatin-based chemotherapy, and the therapeutic potential of PADCEVincluding its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibility that ongoing and subsequent clinical trials may fail to establish sufficient efficacy, that adverse events or safety signals may occur and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2019 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

1American Cancer Society. Cancer Facts & Figures 2020.https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf.Accessed 01-23-2020.2American Society of Clinical Oncology. Bladder cancer: introduction (10-2017). https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed 05-09-2019.3International Agency for Research on Cancer. Cancer Tomorrow: Bladder.http://gco.iarc.fr/tomorrow 4National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer. Version 4; July 10, 2019. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf.5PADCEV [package insert]. Northbrook, IL: Astellas, Inc.6Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

SOURCE Astellas Pharma Inc.

http://www.seattlegenetics.com

Follow this link:
Astellas and Seattle Genetics Receive FDA Breakthrough Therapy Designation for PADCEV (enfortumab vedotin-ejfv) in Combination with Pembrolizumab in...

Recommendation and review posted by Bethany Smith

New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin ligases that inhibit cell death pathways and are themselves inhibited by second mitochondria-derived activator of caspases (SMAC). SMAC mimetics (SMs), small-molecule antagonists of IAPs, are being evaluated as cancer therapies in clinical trials. IAPs are also crucial regulators of inflammatory pathways because they influence both the activation of inflammatory genes and the induction of cell death through the receptor-interacting serine-threonine protein kinases (RIPKs), nuclear factor B (NF-B)inducing kinase, and mitogen-activated protein kinases (MAPKs). Furthermore, there is an increasing interest in specifically targeting the substrates of IAP-mediated ubiquitylation, especially RIPK1, RIPK2, and RIPK3, as druggable nodes in inflammation control. Several studies have revealed an anti-inflammatory potential of RIPK inhibitors that either block inflammatory signaling or block the form of inflammatory cell death known as necroptosis. Expanding research on innate immune signaling through pattern recognition receptors that stimulate proinflammatory NF-B and MAPK signaling may further contribute to uncovering the complex molecular roles used by IAPs and downstream RIPKs in inflammatory signaling. This may benefit and guide the development of SMs or selective RIPK inhibitors as anti-inflammatory therapeutics for various chronic inflammatory conditions.

View original post here:
SMAC mimetics and RIPK inhibitors as therapeutics for chronic inflammatory diseases - Science

Recommendation and review posted by Bethany Smith

I have this really annoying habit which I know I need to work on. Despite the fact that I'm naturally a very early riser (I'm talking, *wakes up at 6:30 a.m. 365 days a yeareven on the weekends* kind of early riser), I pretty much refuse to adjust my bedtime a few hours earlierto counteract the impact of my early bird identity. I love to stay up late after a long day and binge-watch my favorite shows on Hulu, I love to read 100-page chunks of a novel, and without fail, I also love to fool around on my phone doing who even knows what. You know that feeling when you look at the clock and it's a perfectly respectable 10 p.m. and then the next time you blink it's verging on 1 a.m.?! Well, it happens to me all the time, and while I know I'd be the better for shutting down my phone, burning a candle, switching on my diffuser, and being the well-behaved beauty and wellness editor I know I should be, I really struggle to do that. And, yes, it definitely shows up on my face the next day.

I have notoriously shady under-eyes just naturally, (check out our A-list celebrity guide to dark circles, here), but my lack of sleep and consequential coffee dependence the following morning has exacerbated the situation. Luckily, my job allows me access to the newest and coolest eye creams and treatments which tout all sorts of under-eye miraclesfrom the banishment of dark circles to the erasing of puff, fine lines, and wrinkles. Spoiler: most fall flat. As in, that literally did nothing, kind of flat. However, during my 3 years as a beauty editor, I've collecteda glorified possession of creams and gels and balms that truly do work wonders on my dark circles. Regardless of whether your dark circles are sheerly caused by genetics, allergies, or not-so-stellar sleep habits (me), these shadow-targetingeye creams can lend a helping hand. Keep scrolling! I'm sharing the 15 best eye creams for dark circles I've tried since becoming a beauty editor.

Hot off of L'Occitane's French presses (it literally launched two days ago, but I received ahead of time to test-drive!), this serum has stolen my heart. It's the kid sister to the brand's best-sellingOvernight Reset Oil-in-Serum ($59) (one unit is purchased every minute!) and it uses the formula's same coveted moisture magic to do battle against telltale symptoms of fatigue like dark circles, puffiness, and expression lines. Plus, I have to say I love that you can literally see the 1,600 golden bubbles of precious Immortelle Essential Oil sitting in the stunning bottle. So stunning, right?!

Peter Thomas Roth Vital-E Microbiome Age Defense Eye Cream ($55)

Y'all, brands have really been upping the anty and cadence of eye cream launches because this is another formula for dark circles that JUST hit my vanity. (And stores everywhere.) Say goodbye to fine lines and wrinkles, dullness, uneven texture, and dark circles thanks to this protective solution designed to improve the delicate skin barrier around the eyes and support the skin's natural microbiome as well.

iS Clinical Youth Eye Complex ($105)

iS Clinical is one of the top brands chosen by the top estheticians in the industry, and this anti-aging eye cream is one of their choice formulas. Not only is it insanely creamy and hydrating (but not at all sticky or slimy like some eye creams can be!) it's a huge help in the dark circle departmentI'll apply it before bed and then again in the morning to finish off my morning skin routine. My circles are still there (obviously), but they're a lot less glaring. The key is in the mix of hyaluronic acid, peptides, and antioxidants.

111Skin Space Defence Bright Eye Lift Gel NAC Y2 ($190)

Once I found out that makeup artists use this formula from 111Skin to prep celebs' skin pre-red carpet, I was 88.5% on board. And, after a few applications when I started to notice that my under-eyes looked less shadowy and significantly firmer, tighter, and all-around less fatigued, I lept to a full 120%. Categorically, it's an eye cream, but it's formulated as a soothing, lightweight gel anyone who's against heavy, cloying creams will absolutely adore. Plus, there's the whole eye lifting effect which is pretty dang wonderful in and of itself.

EIGHTH DAY Eye Renewal Cream ($225)

If you're down to feel a little tingle (it's worth it, I promise!) this eye cream has some bite. I mean that literally because one of the reasons it quickly tightens, firms, and de-puffs is thanks to the MVP ingredient: snake venom. This has been one of my favorite formulas for a couple of years now, and it's what I reach for when my under-eyes are in a state of emergency.

RVive Skincare Intensit Complete Anti-Aging Eye Serum ($285)

Not only does the featherlight serum texture feel great underneath your eyes, but this favorite eye cream also features strategic brightening agents to help diffuse any purple circles that like to lurk. (You'll get what I mean once you see the gorgeous pearly finish.) It also looks AMAZING under makeup and concealer. It's a 10/10 if you can stomach the splurge.

By Terry Hydra-clat Eye Contour ($75)

If you have a weakness for anything lovely, French, and downright effective when it comes to your beauty product investments, you should definitely consider eye contour-improving cream from By Terry. Not only does application feel cooling and luxe thanks to the silver applicator, but it also hosts delicate ingredients like Black Rose, plant stem cells, and vitamin E to not ONLY reduce dark circles but to de-puff and soften the look of any fine lines and wrinkles. This is another one that thanks to its lightweight texture is superb under your foundation and/or concealer.

Sunday Riley Auto Correct Brightening and Depuffing Eye Contour Cream ($65)

One of my favorite eye creams of all time, this is probably the one I recommend to friends most often since it's a bit more affordable and so instantaneously affect. One swipe across your under-eyes and the mica-, caffeine-, and antioxidant-rich potion practically blurs away the look of lingering darkness. I honestly think this is Sunday Riley's absolute best product. But, that's just me.

La Prairie Skin Caviar Eye Lift Serum ($485)

Now, I wouldn't include a nearly $500 eye cream if it didn't work true sorcery against dark circles now would I? The sticker shock might be a bit gut-wrenching but this is probably THE most luxurious option for dark circles on the market. Plus, if you're consistent with use, the combination of La Prairie's iconic encapsulated caviar beads and an innovative gel-cream emulsion is probably just as effective as a pricey in-office treatment. The effect is a visual lift to the eye and brow area, less puffiness, lines, shadows, you get the idea.

Ole Henriksen Banana Bright Eye Crme ($39)

If you have dark circles, the yellow tint to this brightening elixir can definitely help with that. It's rich in vitamin C, it's anti-aging, and it even makes your concealer and foundation apply smoother. Wins all-around!

GlamGlow BRIGHTEYES Illuminating Anti-Fatigue Eye Cream ($39)

For glowing skin and under-eyes that mirror a full ten hours of sleep, try GlamGlow's new formula. It features illuminating spheres to brighten up dullness and darkness, caffeine to tighten and lift, hyaluronic acid to plump and moisturize, and last but not least peptides to diminish the appearance of fine lines and wrinkles.

Tula Skincare Glow & Get It Cooling & Brightening Eye Balm ($28)

Technically, this circle-eraser is a balm and not a cream, but please bear with meit works! Like, so, so good. You know those mornings when for whatever reason you wake up feeling like you've been hit by a freight train? Sweeping this cooling, aloe-, and caffeine-infused stick all around your eye area feels almost as good as a deep tissue marathon post-Barry's Bootcamp. (Oh, and there's also a radiance-enhancingRose Glow version FYI!)

SkinMedica Instant Bright Eye Cream ($88)

Did you know Hailey Bieber (and a slew of other celebs) is a huge fan of this brand? I don't know if miss HB has tried this brightening eye cream from SkinMedica, but if not, I personally recommend she get on that. It's brimming with tons of great ingredients like phenylethyl resorcinol (which helps to support melanin balance and correct hyperpigmentation), a hyaluronic acid blend for hydration, marine extracts to supporta healthy skin barrier, plus all the other good stuff for blue and purple under-eyes like caffeine, Persian silk tree extract, and St. Pauls Wort which aidvascular and lymphatic function for a firmer, more radiant result.

Versed Zero-G Smoothing Eye Cream ($18)

My 73-year-old mom and I agreethis affordably priced eye cream from clean skincare brand Versed, is seriously spectacular. I immediately noticed how it diminished the severity of my dark circles post-flight when I visited home recently, and my mom agreed that it reduced her puff, wrinkles, so on and so forth.

Belif Moisturizing Eye Bomb ($48)

This eye cream isn't actually touted as an eye cream for dark circles. That said, it's one of the most deeply hydrating formulas I've ever tested and due that insane moisture, I notice that my under-eys look less dried and skeletal and brighter, dewier, and plumper instead. It's a lightweight, very soothing formula that boasts a whopping 26-hour span of hydration endurance. It's one to throw in your basket the next time you find yourself wandering the aisles of Sephora.

Up next,How to Get Rid of Dark Circles Like an A-List Esthetician

This article originally appeared on Who What Wear

Read More from Who What Wear

Read the original post:
I Average 5 Hours of Sleep, But No One Knows Thanks to These 15 Eye Creams - Yahoo Lifestyle

Recommendation and review posted by Bethany Smith

Meticulous Research a leading global market research company published a research report titled In-Vitro Toxicology/Toxicity Testing Market by Product& Service, Technology (Cell Culture, OMICS), Method (Cell-based Assays, In-Silico), End-point (ADME, Genotoxicity, Organ Toxicity, Dermal Toxicity), End-user, and Geography Global Forecast to 2025.

According to this latest publication from Meticulous Research, the globalin-vitro toxicology testing marketis expected to grow at a CAGR of 9% from 2019 to reach $14.4 billion by 2025.

Download Free Sample Copy Of The Report:: https://www.meticulousresearch.com/download-sample-report/cp_id=5047

Key questions answered in the report-

Which are the high growth market segments in terms of product & service, technology, method, end-point, end-user, and region/countries?

What was the historical market size for in vitro toxicology testing across the globe?

What are the market forecasts and estimates for the period 2019-2025?

What are the major drivers, restraints, opportunities, and challenges in the global in vitro toxicology testing market?

Who are the major players in the global in vitro toxicology testing market?

How is the competitive landscape and who are the market leaders in the global in vitro toxicology testing market?

What are the recent developments in the global in vitro toxicology testing market?

What are the different strategies adopted by the major players in the global in vitro toxicology testing market?

What are the geographical trends and high growth regions/ countries?

Who are the local emerging players in the global in vitro toxicology testing market and how do they compete with the global players?

Have Any Query? Ask Our Expert https://www.meticulousresearch.com/speak-to-analyst/cp_id=5047

The growth of this market is driven by factors, such as ethical issues and pressure from animal activists groups concerning the use of animals for testing, ban on animal testing on cosmetic products, support from regulatory bodies regarding the approval of in-vitro tests, low costs associated with in-vitro toxicology testing, and advancements in in-vitro methodologies. Moreover, synergetic relationships between various stakeholders in the industry and increasing toxicology databases to facilitate the use of in-vitro test methods are expected to offer significant growth opportunities for the players operating in this market.

The global in-vitro toxicology testing market study presents historical market data in terms of value (2018), estimated current data (2019), and forecasts for 2025-by product & service (equipment, assay kits, consumables, software, services), technology (cell culture technologies, high-throughput screening technologies, OMICS technologies), method (cell-based assays, biochemical assays, in-silico, ex-vivo), end-point (ADME; skin irritation, corrosion, sensitization; genotoxicity; cytotoxicity; ocular toxicity; organ toxicity; phototoxicity; and dermal toxicity), end-user (pharmaceutical & biotechnology industries, cosmetics industry, food industry, and chemical industry). The study also evaluates industry competitors and analyzes the market at a regional and country level.

You Can Directly Buy This Report From Here:: https://www.meticulousresearch.com/buy_now.php?pformat=348&vformat=1030

(Get key industry insights spread across 189 pages with 120 market data tables & 30 figures & charts from the report)

On the basis of product, the consumables segment is estimated to dominate the overall in-vitro toxicology testing market in 2019, mainly due to increasing number of in-vitro tests being performed across the globe leading to recurrent purchase of reagents and other labware. However, the software segment is projected to grow at the highest CAGR during the forecast period. The high growth of this segment can be attributed to increasing computer models and algorithms being developed to predict toxicity of test substances.

On the basis of technology, the cell culture technologies segment is estimated to account for the largest share of the in-vitro toxicology testing market in 2019, owing to growing adoption of 3D cell culture and stem cell models for toxicity testing.

On the basis of method, the in-vitro toxicology testing market is sub-segmented into cell-based assays, biochemical assays, in silico testing, and ex vivo testing. Cell-based assays segment is estimated to command the largest share of the in-vitro toxicology testing market in 2019. Advancements in cell-based technologies such as high-content screening and label-free detection are the key factors attributed to the large share of this segment in the overall market.

On the basis of end point, the ADME segment is estimated to account for the largest share of the overall in-vitro toxicology testing market in 2019. This is primarily attributed to the increasing number of early stage in-vitro ADME screening tests to prevent failure at later stage.

On the basis of end user, the in vitro toxicology testing market is segmented into pharmaceutical and biotechnology companies, cosmetics, food industry, and chemical industry. The pharmaceutical and biotechnology companies segment is estimated to account for the largest share of the overall in-vitro toxicology testing market in 2019. This is primarily attributed to increasing drug attrition rates and growing adoption of early in-vitro preclinical safety testing to filter out molecules with a higher potential for toxicity. However, the cosmetics industry segment is expected to grow at a higher rate owing to the ban on use of animals for testing toxicity of cosmetics and its ingredients.

Here are the top Market companies in the world:: https://meticulousblog.org/top-10-companies-in-in-vitro-toxicology-toxicity-testing-market/

Key Players::

In-vitro toxicology testing market is a highly consolidated in nature, wherein 3 major players Thermo Fisher Scientific (US), Merck (Germany), and GE Healthcare (US) accounted for major share of the global in-vitro toxicity testing market. Other key players operating in this market are Bio-Rad Laboratories (US), SGS SA (Switzerland), Laboratory Corporation of America Holdings (U.S.), Qiagen N.V. (Netherlands), and Eurofins Scientific (Luxembourg), among others.

Geographical Analysis::

This research report analyzes major geographies and provides comprehensive analysis of Europe (Germany, U.K., France, Italy, Spain, and RoE), North America (U.S., Canada), Asia-Pacific (China, Japan, India,and RoAPAC), Latin America, and Middle East & Africa. Europe commanded the largest share of the global in-vitro toxicology testing market, followed by North America and Asia Pacific (APAC). The large share of this region is mainly attributed to the factors such as ban on animal testing for cosmetics and its ingredients, and government initiatives to promote the reduction of use of animals for toxicity testing. Asia-Pacific region is expected to grow at the highest CAGR during the forecast period of 2019 to 2025, owing to increasing biotech investments in this region and growing collaborations between local and foreign companies.

Download Free Sample Copy Of The Report:: https://www.meticulousresearch.com/download-sample-report/cp_id=5047

Related Reports::

1Veterinary Immunodiagnostics Market Size by Product (Analysers, Consumables), by technology (ELISA, Radioimmunoassay, Rapid tests, and others), by animal type [Livestock (Cattle, Pigs, Poultry) and Companion (Feline, Canine, Equine)], by application (Infectious diseases, autoimmune disorder, endocrinology & oncology, and bone & mineral diseases), and by End-user Global Forecasts to 2022

2 Cancer Immunotherapy Market By Type (Monoclonal Antibodies, Checkpoint Inhibitors, Immunomodulators, Vaccines, Cell Therapy), Application (Lung, Breast, Multiple Myeloma, Colorectal, Melanoma, Prostate), and End User- Global Forecast to 2024

3 Competent Cells Market by Type (Cloned Competent Cells, Agrobacterium Tumefaciens Competent Cells, and Expression Competent Cells), Treatment (Chemically Competent Cells and Electrocompetent Cells), Application (Cloning, Protein Expression, others), and by End User (Pharmaceutical and Biotechnology Industry, Academic and Research Institutes, and Contract Research Organizations) Global Forecasts to 2023

About Meticulous Research

The name of our company defines our services, strengths, and values. Since the inception, we have only thrived to research, analyze and present the critical market data with great attention to details. Meticulous Research was founded in 2010 and incorporated as Meticulous Market Research Pvt. Ltd. in 2013 as a private limited company under the Companies Act, 1956. Since its incorporation, with the help of its unique research methodologies, the company has become the leading provider of premium market intelligence in North America, Europe, Asia-Pacific, Latin America, and Middle East & Africa regions.

Contact Us:

Meticulous Research

Email-sales@meticulousresearch.com

Contact Sales- +1-646-781-8004

Connect with us on LinkedIn-https://www.linkedin.com/company/meticulous-research

This content has been distributed via WiredRelease press release distribution service. For press release service enquiry, please reach us at contact@wiredrelease.com.

View post:
In-Vitro Toxicology/Toxicity Testing Market is Expected to Grow at a CAGR of 9% From 2019 to Reach $ - PharmiWeb.com

Recommendation and review posted by Bethany Smith

Going gray is a natural part of getting older. It typically starts with a small streak of white in the hair or beard, a sign that a man has reached a certain level of maturity and is now on that steady, inevitable decline to the grave. Hell, it is even conceivable (and highly likely) that some of you might even pluck one of those pale bastards out of your pube patch one night while trying to determine if the source of a vicious case of crotch itch is the crabs or just dry skin. Listen, all were saying is dont be surprised if, within the next few years, you find yourself staring down at your junk, thinking about how that lustrous man bush of yours is starting to resemble Colonel Sanders with a skinless chicken leg dangling out of his mouth. It happens to the best of us.

But hey, getting old isnt always indicative of a silver coiffure. I knew a guy back in high school who had more gray hair on his head than my 73-year-old father does now. So, it seems that age alone isnt always the culprit. In fact, it has been long since believed that stress also plays a critical role in making some men look distinguished beyond their years. Well, come to find out, the concept of stressful events turning us into gray beasts before we are officially deemed DILFs is probably real. Only science says it really comes down to how our fight or flight response is triggered throughout the years that determine when our manes will be deprived of color.

Researchers at Harvards Stem Cell Institute believe they have found a direct correlation between stress and going gray. They recently published a study in the journal Nature, which shows that three kinds of extreme stress mild, short-term pain, psychological stress, and restricted movement has a way of bringing around the gray quicker than what would happen under natural circumstances. At least that is the conclusion reached by lead researcher Dr. Ya-Chieh Hsu and team after putting a legion of mice through the wringer and watching for their response.

The graying process happens as pigment cells called melanocytes start to fade from our hair follicles. Its just that over time, these cells become less prevalent and we begin brandishing that salt and pepper look popularized by legendary screen stars like Brad Pitt and George Clooney.

Eventually, however, all of those cells fade into extinction and our hair just goes completely white, we start receiving AARP benefits and eating apple sauce with every meal. Yet, researchers say that stress can cause these cells to fade out quicker than theyre supposed to long before we start collecting social security and yelling at the neighborhood kids to get off our lawn.

Without getting overly scientific about it, researchers found that high stress seems to produce elevated levels of a chemical in the brain known as noradrenaline. Its one of the kick-ass substances manufactured by the adrenal gland when a persons fight or flight response starts firing on all cylinders. Thats the real culprit to early aging, researchers concluded. They say that once mice were injected with this chemical, they began losing melanocytes and going gray. And the transformation didnt take long either. It turns out that stress can zap our hair color in a matter of days.

When we started to study this, I expected that stress was bad for the body but the detrimental impact of stress that we discovered was beyond what I imagined, Hsu said in a statement. After just a few days, all of the melanocyte stem cells were lost. Once theyre gone, you cant regenerate pigments anymore. The damage is permanent.

While it might be challenging to manage stress in a way that keeps us looking young forever, there is a silver-lining here, boys. Women, presumably the root of all of that premature grayness in the first place, are especially hot for this look. Seriously, a recent survey from Match.com finds that 72 percent of the women on the dating scene find men with gray hair more attractive than those with darker dos. Other studies on the subject have turned out similar results. The only caveat is that women are really only turned on by the gray as long as it doesnt make the man look old. This has something to do with them wanting to feel like a guy can provide some safety and security without having to worry about changing his diapers down the road.

Read the rest here:
Getting Gray Hair Early Actually Can Mean You Are Stressed The F*ck Out - BroBible

Recommendation and review posted by Bethany Smith

Stephanie Singleton for BuzzFeed News

Do you miss being a scientist? some people ask.

Sometimes.

When people talk about science, they usually mean people in white lab coats doing things, like solving equations on the board or preparing solutions in beakers. What they mean is science as this crude mechanism of discovery by which humans refine over decades and centuries a small kernel of knowing. What they mean is grant dollars. What they mean is wild hair. What they mean is clean, aseptic, analytical. Brainy little robot people. White.

I try to be honest about my time in science about the feeling of satisfaction I had when I plotted all of my confocal data and there was a beautiful curve depicting the drop-off in signal as one moved further down the tissue of the gonad. I think about the calculations we did on scraps of paper to check the ratios of inheritance of the genes we introduced. I think of the little side room where we took our coffee and bagels. I think of the feeling of friendship and family that comes with being in a big lab, where everyone has a place, a role, an expertise, a skill. I remember the surprise I felt when people started to come to me because I knew something, because I could help. And how rare that was for me.

For the better part of several years, I saw my labmates every day. For hours and hours. Every holiday, every break, we stayed. We worked. We supported each other. We fought. We feuded. We gossiped. We threw parties for each other. We celebrated. We said goodbye at graduations and retirements. There were people who supported me and cherished me and looked after me. People who treated me like I mattered. A lab is a family. In a way.

Science was beautiful and it was wild and it was unknowable. Science was spending days and weeks on a single experiment with no way to know if it would work and no real way to tell if it had worked. Science was like trying to find your way to a dark forest only to realize that you had always been inside of the forest and that the forest is inside of another, greater, darker forest. Science was laughing with my labmates about television the night before, about the song of the summer, about tennis, about the unruly nature of mold growing on our plates, about cheap wings at Buffalo Wild Wings. Science was being taught to think. Taught to speak. Science was a finishing school. Science was a brutal education. Science made me ruthless. Science made me understand the vast beauty of the world.

But science was also working 15 hours a day for weeks or months. Science was working weekends and holidays. Science was being called lazy for taking a break. Science was the beat of doubting silence after I answered a question put to me. Science was being told that racism was not racism. Science was being told that I was fortunate that I had running water while growing up and that I was actually privileged because there are some places that do not. Science was being told that I was mistaken for a waiter at a party because I had worn a black sweater. Science was being told that I had to work harder despite working my hardest. Science was being told that I talked too much. Science was being told that I was too loud. Science was being told that I was behind, always behind. Science was being told that I had failed but had been gifted a pass by virtue of who you are. Science was being told that I had never once been to class despite attending every session and office hour because I was mistaken for someone else.

Science was being the only black person in the program for four years. Science was saying nothing because I was tired of being corrected about the particulars of my own experience. Science was being told that I should consider moving to the other side of town where more black people live. Science was someone suggesting that I find a church in order to find community. Science was having my hair stroked and touched. Science was being told that I was articulate. Science was watching peoples eyes widen slightly in surprise when I told them what program I was in. Science was the constant humiliation of wondering if I had justified my presence or if I had made it harder for the next black person to get admitted. Science was having to worry about that in the first place.

Science was a place I ultimately left, not so much because I wanted to, but because I had to. Science is not being able to say that because I reflexively feel the rebuttal waiting on the other end of that sentence: You could have made it work if you wanted it enough. Science is not knowing whether I wanted it enough.

Does science influence your writing?

Oh, sure. I guess.

Do you write science fiction?

No, I write domestic realism.

After the above exchange, people sometimes look at me like Im joking and at any moment will drop the faade to reveal that I do in fact write and love science fiction, after all.

But no, I do not write science fiction. I think that if people knew more scientists and spent significant time in their company, they would understand that the worst possible preparation for a career as a science fiction writer is an intensive science education. My training as a scientist makes it difficult to absent myself in the way I need to in order to write good fiction. I can never turn off the part of my brain that knows about protein folding or microscopy or tissue preparation or stem cells or physics or chemistry. Writing science fiction would be an extended exercise in pedantry.

People presume that science and writing are quite different. But they are both ways of knowing. They are ways of understanding the greater mystery of the world. They are systems of knowledge and inquiry. I do not understand something until I have written it, or more accurately put, until I have written my way through it.

Science was being the only black person in the program for four years. Science was saying nothing because I was tired of being corrected about the particulars of my own experience.

I think in many ways, the best preparation for a writer is a period of prolonged and rigorous thought about a difficult and complicated question. You learn to assemble your resources. You learn to fight with yourself. You learn to quarrel on the page with your worst ideas and with the ones you hold dearest. You treat your expectations with suspicion. You demand proof. You demand evidence. You think hard about the alternate hypothesis or other explanations, and you devise strategies to root these out. You learn to live with doubt. You try to prove yourself wrong. You look for places where you have been too soft. Too vague. You eliminate language that contains falsehoods. You eliminate language that can mislead your reader. You ask questions. You pursue answers with all the energy you can muster. You try to put language to what it is you observe. You develop a stamina for iteration. You develop a thick skin. You learn to seek criticism. You treat criticism like kindness. You churn the raw material of life into something that can be understood, and when you fail, you marvel at the mystery of things.

Do you miss science?

Yes. No. Yes. No.

Sometimes, when I dont feel well, I consider the question of how to derive an expression for the degradation of a molecular species in a particular tissue under a given set of circumstances. Old calculus. I turn to YouTube lectures from MIT about thermodynamics. I think of my first winter in Madison, Wisconsin.

The first snowfall was in October. It had been a hot, rainy summer, so much so that the weather seemed to turn all at once with very little warning. I was either in the middle or at the start of my second rotation as a biochemistry graduate student, working in a biophysical chemistry lab and spending most of my day in the windowless instrument facility in the basement. My project was to deduce the effect of protein concentration on the ability of a polymer of DNA to wind itself. I spent a lot of time pipetting various liquids into each other in little cuvettes, slotting them into a machine, and then waiting for the reading. It was the kind of work to which I felt ideally suited, and I could have gone on that way forever. I had recently moved to the Midwest from Alabama to pursue a PhD, and it seemed as likely as anything else that I would go on pipetting and measuring the effect of things like DNA polymer length and protein concentration on DNA winding. It was as removed from the circumstances of my previous life as anything else, and so I didnt have a compelling reason to doubt that this would be the shape my life held.

But I remember sitting down at the desk in the lab and looking out the broad window. There was a large tree at the center of the courtyard that had recently turned yellow. Fall was there in name, but not in temperature. The labs were kept quite cold, and so I wore a sweater indoors and shucked it as soon as I got outside. But that day, I looked out of the window and saw snow drifting down. The flakes were thick and fluffy, and they seemed almost fake. It was the first time I had seen snow in years, and I was totally enamored by it. The other people in the lab were on edge because snow in October portended something dark and awful a hard winter, a long, brutal freeze. Where they saw inconvenient travel and slushy roads, I saw something beautiful if frivolous, a minor novelty. Winter came early that year, and it didnt end until the very beginning of the following summer. When I went to the lake on my birthday in early June, there was still ice in the water.

People presume that science and writing are quite different. But they are both ways of knowing.

When people ask me about my time in science, it is this day which presents itself to me in jewel-like clarity. It is the day something about my life altered irrevocably. Or perhaps it is that the snow has accumulated, the way all such moments do in life, the weight of meaning, of prophecy. Inevitability is an artifact of retrospection. It is because the snow represented a stark deviation from the previous course of events in my life, at the precise moment when my life was changing so wildly, that I remember it. It is not that the snow changed me, but it came at a point when I was starting not to resemble myself. I cannot use the snow to explain to people what my life was like in science. It has the whiff of superstition, folklore. It feels too much like a memory and not enough like an answer. I do not tell them about the snow or how it seemed a benediction at the outset of something I needed desperately to work.

It was only later that I realized this was wishful thinking, and that the snow was just snow.

Do you think youd ever go back to science?

That part of my life is over now.

Ive come to understand that what people want in such a situation is to have their own conceptions of the world confirmed. That is, they want me to say that when you leave science because you have written a novel and a book of stories and have decided to attend an MFA program in creative writing, you are doing something that is antithetical to science. People presume that it is akin to picking up and leaving your home in the middle of the night under great duress, never to return. What they want is the spectacle of the forgotten treasured item, the confirmation that something has been lost, perhaps forever.

I think if people knew what it was that I left, then theyd know better than to ask. It would be like asking someone if they were sad to have left their home with no prospect of returning. It would be like asking someone if they were sad to have left their faith behind. It would be like asking someone if they were sad to have given up some fundamental idea about who they are. It would be like asking someone if they were sad to have watched their life burn to the ground. It would be like asking someone if they were sad to have left their family and friends.

They would mind their own business if they knew.

But they do not know, and so they say things like Science, wow, thats so cool, like, do you miss it?

And I smile because that is what I have learned to do. Because explaining is too hard. Too messy. There is no clean or easy or simple way to make it known to others that I left because I had to, because it was necessary to leave that I do miss it, but I also dont because Im still that person but not that person, that every day I remind myself less of the person I was then. Its sad, like losing a memory of myself, and all those years are lost to me now, all the little tricks and habits of home dropping down and away, as I become this other person known for this other thing, and its too much in the moment to say that I miss it both more and less every day, that I become a person more capable of appreciating what is lost in the grand scheme of things but less a person who knows what it is Ive actually lost, and that there is some painful, brutal, awful misalignment in the scale of those two losses.

When people ask if I miss science, the only answer available to me is an incomplete solution to the problem: Yes. No. Sometimes. Its over now.

Brandon Taylor is the senior editor of Electric Literatures Recommended Reading and a staff writer at Literary Hub. His writing has earned him fellowships from Lambda Literary Foundation, Kimbilio Fiction, and the Tin House Summer Writer's Workshop. He holds graduate degrees from the University of Wisconsin-Madison and the University of Iowa, where he was an Iowa Arts Fellow at the Iowa Writers Workshop in fiction. Learn more about his first novel Real Life here.

Read more from the original source:
Working In Science Was A Brutal Education. Thats Why I Left. - BuzzFeed News

Recommendation and review posted by Bethany Smith

Space has been a straightforward business so far: launch it; turn it on; hope it works; avoid the stray piece of space junk; let it die. Now, a more complex space economy is on the horizon, with maintenance spacecraft, repair robots, garbage removal trucks and even orbital manufacturing depots.

Thisyear is set to see history made with the first ever servicing operation on an in-orbit satellite. Robotic orbital trouble-shooters, which are expected to pave the way for a new era of space robotics, will one day shuttle malfunctioning spacecraft back and forth, refuel them, perform basic repairs or serve as temporary propulsion and steering units.

Satellites are a crucial component of 21st-century technology infrastructure. Wedepend on them for weather forecasting and climate monitoring, telecoms, navigation and a plethora of scientific and emerging applications. Satellites are often costly to build and launch, and once in orbit, little can be done to upgrade, inspect or fix them. If all goes well, operators can get up to 20 years service from their assets. If unexpected problems occur, the investment might go to waste.

The first ever in-orbit servicing spacecraft, the Mission Extension Vehicle 1 (MEV-1), built by Space Logistics, a wholly owned subsidiary of American aerospace giant Northrup Grumman, is set to perform the first automated docking between two commercial satellites. Upon completing this manoeuvre, it willcommence the equally pioneering task of extending the life of an ageing telecommunications satellite of US operator Intelsat.

The demonstration will take place in the so-called graveyard orbit about 200km above the geostationary ring, an orbit at the altitude of 36,000km, where spacecraft appear suspended above a certain spot on Earth. Sought after by operators of meteorological and telecommunications satellites, the geostationary orbit is one of the busiest regions of space. To keep it tidy for future users, operators are obliged to move their spacecraft into the graveyard at the end of each mission.

This mission represents many industry firsts, Joe Anderson, vice president of business development and operations at Space Logistics, tells E&T. We are using many new technologies and because there are some concerns, we decided to perform the demonstration in the graveyard orbit.

MEV-1, which launched in mid-October 2019 from Russias cosmodrome Baikonur inKazakhstan, raises itself into the geostationary graveyard orbit from the so-called geostationary transfer orbit, where it has been left by the launcher, using its electric thrusters. In the graveyard orbit, the service vehicle will meet its client, Intelsats IS901. Intelsats operators have moved the craft into the graveyard orbit using its onboard propulsion system ahead of the demonstration.

IS901 is an 18-year-old veteran. Under normal circumstances, the satellite would soon reach the end of its life, but Intelsat hopes that MEV-1 could add at least five years to its mission. The servicing spacecraft, which will autonomously approach and attach itself to IS901, will first move the satellite into a new slot in the geostationary orbit and then use its thrusters to maintain its position and attitude for the duration of the mission. At the end of the five-year period, MEV-1 will push IS901 back to the graveyard orbit before disconnecting and moving on to another client.

Space Logistics, previously part of Orbital ATK, acquired by Northrop Grumman in 2018, spent ten years developing technologies for the mission at the companys Rendezvous, Proximity, Operations and Docking (RPOD) laboratory.

In this laboratory, we have a number of very large industrial robots that we are using as puppeteers for the mock-up of the MEV, says Anderson. We used that laboratory to develop prototypes and test our software algorithms and sensors that are used to do the rendezvous and docking.

Space Logistics reused some of the technologies developed by Orbital ATK originally for the Cygnus spacecraft, one of the cargo vehicles resupplying the International Space Station (ISS). Cygnus, however, doesnt dock autonomously but is captured by the stations robotic arm and berthed to the stations Harmony module. While the ISS has dedicated docking and berthing ports, MEV-1 will have to be able to attach to satellites that were not designed with orbital docking in mind.

The MEV does that by taking advantage of two features that are, according to Anderson, on 80 per cent of geostationary satellites currently in orbit the so-called liquid apogee engine and the launcher adapter ring.

Before the start of the manoeuvre, MEV-1 circles around the target a few times and inspects it with its visible, infrared and lidar sensors, Anderson explains. It then positions itself 500m behind the target and waits for a command from the ground control team to start the approach, which is very slow.

At the distance of one metre from the target, MEV-1 deploys a probe, which enters through the liquid apogee engine into the client satellite. Inside, the probe deploys its fingers in order not to slip out. MEV-1 pulls the probe back and the two satellites are brought together, with the launcher adapter ring on the client satellite pressed against three stanchions on the MEV.

We end up with a very simple push-pull tension where we are pulling at the centre of that liquid apogee engine and we are pushing against the launcher adaptor ring and thats what clasps the two vehicles together, says Anderson. From that point onward, the MEV takes over the attitude and orbit control of the combined vehicle stack.

As an idea, in-orbit servicing has been around for almost 20 years, according to Anderson. The technology, however, didnt make economic sense before. The cost was too high and the risks considerable. On top of that, operators would prefer to replace their ageing systems with modern, more efficient ones. However, the tide has turned, space has become more cluttered and cost-cutting became more of an interest. The idea of prolonging the life of existing satellites instead of building and launching new ones came to the fore.

Future developments

In-orbit servicing presents only the first step towards a future that resembles what once would have been science fiction. Robotic manufacturing in space and orbital assembly of spacecraft, too, is getting closer to reality. US company Made in Space is developing a space robot called Archinaut One that will enable manufacturing of large structures for space in space.

Made in Space received $73.7m of Nasa funding for the Archinaut pilot project, which is expected to fly to space in 2022.

Fitted with a cutting-edge space-qualified 3D printer and robotic manipulator arms, Archinaut will print, assemble and deploy its own operational solar array, which, the company says, will be five times more efficient than regular solar panels used on todays spacecraft.

In the future, such orbital robots could build various components for existing satellites such as super-powerful antennas, radar booms, extra-large solar panels and others. The robots could also assemble entire telescopes larger than those that are possible to launch from Earth. Larger telescopes mean greater advances in scientific understanding. The ability to manufacture in space means considerably lower cost since the cost of launch from Earth represents a large portion of the overall cost of space exploration and utilisation.

There have been lots of new activities behind space sustainability in the last few years and I think we will see more resources being put into resolving the potential risks in orbit, says Daniel Campbell, managing director of Effective Space, a UK-based start-up developing what they call space drones, small satellites that would provide life-extension services similar to those offered by Space Logistics.

The company is part of the Consortium for Execution of Rendezvous and Servicing Operations (CONFERS), led by the US Defense Advanced Research Projects Agency (DARPA), which aims to develop operations standards for in-orbit servicing.

Effective Space, which hopes to launch its maiden mission in 2021, relies on a 111.5m platform, designed to extend the life of a satellite by up to 18 years. Space Logistics MEV-1, for comparison, based on a standard platform for geostationary satellites, comes in a larger 3.02.12.3m package.

Just like MEV-1, Effective Spaces drones will be able to detach and serve multiple satellites within their designed lifespan.

Campbell says that in addition to the growing sustainability concerns, in-orbit servicing would be handy as satellite operators await the arrival of low Earth orbit mega-constellations a new and unproven technology for telecommunications.

Many of the operators are waiting to see the impact of these deployments on the geo business, Campbell says. That incentivises them to hold off any replacement satellites and they see life extension as a potential gap filler.

DARPA envisions that robotic in-orbit servicing technology could in the future reduce the cost of geostationary satellites, which currently need to be packed with back-up systems just to ensure the missions success. That obviously increases complexity, weight and cost. In the future,new payloads could be installed as and when required by the robotic service vehicles.

Campbell says Effective Space is also looking at the possibility of using in-orbit servicing in the low Earth orbit (LEO), the area closest to the Earth up to the altitude of 2,000km, which is the most congested and set to become even more cluttered with the arrival of mega-constellations. The business case in LEO, however, will be more difficult to prove. LEO satellites tend to be smaller, cheaper and usually designed with shorter lifespans in mind compared to the geostationary platforms.

Its part of the number-crunching that needs to make sense, Campbell adds. But perhaps the incentive to use these services will not be purely economic but part of licensing requirements that will oblige the operators to safely dispose of their satellites before deploying new ones to LEO.

Space industry consultancy Northern Sky Research predicts that the in-orbit servicing market will be worth $3bn (2.3bn) by 2028 with life extension driving most of the revenue. Chris Brunskill, head of Access to Space at UK Satellite Applications Catapult, compares the current situation in space to the worlds procrastination around climate change and plastic pollution.

At the moment, we are getting away with it, he says. Mostly, it wont be a problem during our lives, but it will be something the next generation will have to worry about. The market is first going to grow very slowly, but as we start to see larger constellations, the need to manage those is going to increasingly grow the need for commercial debris mitigation and in-orbit servicing capabilities and companies.

The UK hopes to carve a slice from the prospective in-orbit servicing pie and has recently launched what is to become the UKs National In-orbit Servicing and Operations Centre in Harwell, Oxfordshire.

There are about half a dozen companies in the UK exploring in-orbit servicing, says Brunskill. That includes start-ups but also some of the established businesses such as Airbus. We are trying to establish the UK as a global centre of excellence and capabilities for debris mitigation and in-orbit servicing. With this facility we want to remove some of the roadblocks for those companies to develop their services.

The Space Applications Catapult has developed the facility in cooperation with the Japan-headquartered start-up Astroscale, which will conduct the worlds first commercial active space debris removal mission, the End-of-Life Service by Astroscale (ELSA) mission, from here in 2020.

Northrup Grumman, in the meantime, is already developing its next-generation in-orbit servicing vehicle, which will enable larger-scale operations and lower the cost of the service. The rendezvous operations will be carried out by the Mission Robotic Vehicle (MRV), essentially an upgraded MEV fitted with a robotic arm. The actual propulsion and attitude control function for the client satellite will be provided by the Mission Extension Pods (MEP), smaller and cheaper units that will be installed by the MRV.

The more complex and expensive MRV will be able to install multiple MEPs in a short period of time as well as other augmentation payloads. Northrop Grumman says the MRV will even be able to perform simple repairs and perform detail inspections of the client spacecraft. *

Regulation

The biggest challenge for in-orbit servicing and robotic space operations is not in the engineering and technology field but rather in the legal and regulatory domain. A whole new set of regulations, licensing regimes and insurance policies will be needed for the technology to fully take off.

The regulatory environment is not developed for this type of activity in space, says Anderson. There are regulatory and licensing regimes for the remote sensing of the Earth and for telecommunications, but to do a service like this is something completely new and different.

Space insurers similarly struggle to fit this type of new commercial service into their existing schemes, Anderson adds.

The space insurance market is accustomed to insuring things like geostationary communication satellites but now when we are going to rendezvous and dock in orbit and bring these two vehicles together, it has brought a new challenge, he says. If there was a problem in orbit, who would be liable? How would one calculate what the insurance claim would be?

Brunskill adds that in the UK work is under way to fill these regulatory gaps and update regulations to match the latest technology developments.

I think that the regulatory infrastructure will probably lag behind the commercial need for this, he says. But companies operating mega-constellations will need these services to maintain their own spacecraft, otherwise they would be their own worst enemy.

Sign up to the E&T News e-mail to get great stories like this delivered to your inbox every day.

Read more:
A new era of space robotics, 36000km above Earth - E&T Magazine

Recommendation and review posted by Bethany Smith

Batteries

Published on February 18th, 2020 | by Guest Contributor

February 18th, 2020 by Guest Contributor

Photo by Zach Shahan, CleanTechnica

MILWAUKEEThe Responsible Battery Coalition (RBC) a leading coalition of companies, academics and organizations dedicated to the responsible management and environmental sustainability of batteries applauded research published today by the University of Michigan (U-M) in theJournal of Energy Storageon best practices for consumers for extending the life of lithium-ion batteries, as well as the cost savings associated with minimizing degradation. The link to the paper can be foundhere.

This research is the second phase of work conducted by U-M and supported by RBC. The first phase was published in May 2019 and outlined ten Green Principles for Vehicle Energy Storage (Green Principles)that represent a comprehensive set of recommendations to guide mobile battery deployment and technology development from an environmental perspective, particularly defining best practices for minimizing the environmental impact of electric vehicle (EV) batteries.

In the new research published today, the U-M team expands onGreen Principle #6 todesign and operate battery systems to maximize service life and limit degradation by outlining nine consumer best practices for extending battery life to decrease costs and reduce environmental burdens associated with the production of new batteries. The new best practices address material consumption, mining impacts and greenhouse gas emissions, as well as the disposal of used batteries.

As the nation and world shift to economies powered by batteries, it is paramount as responsible stewards of the environment that we extend the life of all types of batteries, particularly those in our cars and trucks, saidSteve Christensen, executive director of the Responsible Battery Coalition. This work by such a respected research institution as the University of Michigan is an important first step toward creating a generational change in how consumers use and manage batteries.

The International Energy Agency has predicted that 125 million electric vehicles will be on roads globally by 2030.The RBC seeks to develop a circular economy for batteries that ensures that they are part of the solution in creating a more sustainable environment.

Many of the recommended practices discovered by the U-M research team are related to three main variables that impact battery health: temperature, state of charge, and current. Specific recommendations in the findings include:

As the mobile electronics and EV industries continue to grow, even small improvements in lifetime extension will have significant environmental benefits, the authors of theJournal of Energy Storagepaper wrote.

By minimizing exposure to the conditions that accelerate degradation, batteries can last longer. And this has a positive environmental impact, as battery production is a source of greenhouse gas emissions and many other pollutants, said study corresponding authorGreg Keoleian, director of the U-M Center for Sustainable Systems at the School for Environment and Sustainability.

Additionally, there are significant financial incentives for users to avoid adverse conditions, as the cost of lithium-ion batteries can range from 5% to over 50% of a products cost,Keoleiansaid.

As an organization whose members include the worlds largest battery manufacturer and recycler, leading automotive aftermarket retailers, and some of the largest auto producers and transportation fleet owners, were proud to have been able to support this research to help both industry and consumers get maximum life and value out of their lithium-ion battery products, addedChristensen.

In developing its list of nine best practices for lithium-ion battery life extension, U-M researchers, supported by the RBC, based their search on a range of sources, including academic publications, manufacturers user manuals, and open-source consumer information from customer-support websites.

Research Details

In addition to the academic literature reviewed, researchers also surveyed publicly available information from manufacturers, looking for instructions, guidance, warnings or tips regarding the use and maintenance of lithium-ion batteries.

Those companies included 10 cell phone manufacturers (Apple, Google, HTC, Huawei, LG, Motorola, Nokia, Samsung, Sony and ZTE), 10 laptop manufacturers (Acer, Apple, ASUS, Dell, HP, Lenovo, LG, Microsoft, Samsung and Toshiba), four power tool manufacturers (Bosch, DeWalt, Makita and Milwaukee Tool), and 10 electric vehicle manufacturers, including RBC members Ford Motor Company and Honda.

Authors of theJournal of Energy Storagepaper, in addition to Keoleian, are Maxwell Woody, Maryam Arbabzadeh and Geoffrey M. Lewis of the U-M Center for Sustainable Systems and Anna Stefanopoulou of the U-M Energy Institute.

Read the paper: Strategies to limit degradation and maximize Li-ion battery service critical review and guidance for stakeholdershttps://www.sciencedirect.com/science/article/pii/S2352152X19314227?dgcid=author

Featured image courtesy Volkswagen

Follow CleanTechnica on Google News.It will make you happy & help you live in peace for the rest of your life.

Tags: Acer, Apple, asus, dell, Google, hp, HTC, Huawei, Lenovo, LG, microsoft, Motorola, Nokia, Responsible Battery Coalition, samsung, SONY, toshiba, U-M Center for Sustainable Systems, U-M School for Environment and Sustainability, University of Michigan, ZTE

Guest Contributor is many, many people. We publish a number of guest posts from experts in a large variety of fields. This is our contributor account for those special people. 😀

Continue reading here:
Responsible Battery Coalition Applauds University of Michigan Research on Lithium-Ion Battery Degradation Calls Research Important Step in Educating...

Recommendation and review posted by Bethany Smith

Triangle Energy (Global) Limited (ASX: TEG) is an oil production & exploration company, based in Perth, Western Australia. It is currently the registered operator of the producing Cliff Head Oil Field with a 78.75% interest, in addition to a 45% JV interest in the Xanadu-1 Joint Venture oil discovery (TP/15) and a 50% interest in the Mt Horner Production Licence (L7(R1)1). Additionally, TEG holds a 33.34% equity interest in State Gas Limited (ASX: GAS).

The Cliff Head operations, located almost 10 kilometres off the Western Australian coast at a water depth of 15-20 metres, was the first commercial oil operation to be developed in the offshore Perth basin and commenced production in May 2006. The current production license WA-31-L covers over 72km, with the field spreading more than 6km. It includes the one and only offshore Cantilevered jack-up rig and offshore Arrowsmith stabilisation plant in the underexplored Perth basin.

Increased Production: Increasing Throughput, Reduced Costs

During late-2019, the CH-13 well at the Cliff Head field recommenced production, following replacement of an electrical submersible pump, to boost up the Cliff Head field production over 1,000 bopd stable rate.

Source: Triangle Energy & Kalkine Research

Interesting Read: Triangle Energys Cliff Head Oil Field Exceeds 1,000bopd; Are the Share Prices Justified?

The anticipated rise in demand for sweeter crude has boosted margins over the Brent Crude prices in the recent quarters, considering IMO 2020, which restricted the usage of marine fuels with a sulphur content higher than 0.5%.

In July 2018, Triangle Energy (Operations) Pty Ltd, a TEG subsidiary, took over the operations as the registered operator, focussing on maximising the operating margins and the economic life of the offshore Cliff Head Alpha platform, and onshore Arrowsmith Stabilisation Plant.

Cliff Head Renewal Project

During 2019, Triangle progressed on the target identification to further expand the production capacity and economic life of Cliff Head operations. TEG prioritised prospective areas close to the Cliff Head platform with the possibility of operating them with minimum capital requirements.

As Triangle Energy enjoys stable production from Cliff Head operations after the recommencement of CH-13 well, ramping up the daily production to more than a 1,000 barrels of oil, the Company continues its quest to identify and evaluate new promising lands in and around the existing Cliff Head platform.

Several workovers, infill and satellite drilling opportunities within the range of the Cliff Head's Cantilevered jack-up rig were identified during the asset reviewal studies in the first half of 2019. A detailed evaluation for the appraisal of the opportunities followed by the investment decision (Cliff Head Renewal Project) commenced in mid-2019.

The current reserves for the Cliff Head field stand at 1.71 MMstb or Million stock tank barrels (as at 30 June 2019) and will add an additional 2C Contingent Resource of 3.13 MMstb on approval of the final investment decision for the upcoming projects.

The company launched the Cliff Head Renewal program with three prime objectives, which are-

The opportunities for Cliff Head Renewable Project include

The reprocessing of the 3D seismic data was completed at the end of December 2019, with the interpretation of the data planned during early 2020. The final investment decision of the projects would follow the validation from the geological data for which the reprocessing of 3D seismic data was completed in December with interpretation of the data to be revised soon, to build an advanced geological model of the field.

The final investment decision on the prioritised targets is still awaited and could lead to the economic life extension and increased throughput from the Cliff Head operations. The Company plans to start the Cliff Head Renewal Project development well drilling either during 4Q20 or 1Q21.

On 18 February 2020 (AEDT 02:38 PM), the stock of TEG was trading at $ 0.049, up 16.667% from its previous close. The market capitalisation of the Company stood at $ 15.15 million.

This website is a service of Kalkine Media Pty. Ltd. A.C.N. 629 651 672. The website has been prepared for informational purposes only and is not intended to be used as a complete source of information on any particular company. The above article is sponsored but NOT a solicitation or recommendation to buy, sell or hold the stock of the company (or companies) under discussion. We are neither licensed nor qualified to provide investment advice through this platform.

The rest is here:
Triangle Energys Cliff Head Renewal Project: Perth Basin First Oil Operations Targeting Economic Life Extension - Kalkine Media

Recommendation and review posted by Bethany Smith

6 Serious Health Conditions Linked To Erectile Dysfunction

There is a connection between ED and dementia, heart disease, and other diseases.

We frequently think of erectile dysfunction as a minor consequence or side effect of getting older, and that makes sense. After all, some data show that more than half of all men ages 40 to 70 have some form of erectile dysfunction. But did you know that having difficulty getting or maintaining an erection could also be a sign of other health difficulties?

Here are six diseases linked to erectile dysfunction:

1.Stroke and Heart Attack

Erectile Dysfunction is one of the earliest symptoms of blockage in arteries, which could start to a stroke or heart attack, A Heart Attack happens when blood flow to a portion of the heart is blocked, normally by a blood clot. The damage to the heart tissue normally is made by a blocked coronary artery, which then prevents oxygen from getting to the tissue muscle of the heart. A heart attack is the most common cause of death in the US. There have been many new studies showing a relationship between erectile dysfunction and a heart condition.

A stroke occurs when a blood vein feeding the brain gets clogged or bursts. He points out that the arteries which supply the penis get blocked first because they are smaller that also within 20 and 30 percent of men who have Erectile Dysfunction have some form of unknown heart disease or blockage in their blood veins if they also have at least two other risk factors for developing a heart condition. So if you are a smoker with ED and high cholesterol, for example, you might want to ask your physician to check out your heart, too.

2.Coronary Artery Disease (CAD)

Coronary artery disease occurs when some important blood veins that provide your heart with blood, oxygen, and nutrients (coronary arteries) become injured or diseased. Cholesterol-containing deposits in your veins and infection are usually to blame for coronary artery disease. Coronary artery disease (CAD) is the most common sign of heart disorder. It is the leading cause of death in the United States in both men and women.

Diseased arteries can also be an important symptom of another heart disease later on in life. One research shows having ED under the age of 45 is a major risk factor for CAD. While CAD can cause stroke and heart attack, it can also lead to heart failure and abnormal pulse. According to your physicians, presently understand that theres a link between erectile dysfunction and the lining of the blood veins, called the endothelium.

The endothelium tells the blood veins when to contract and relax, he says. The endothelium can become damaged from something like stress and tobacco usage, making it more difficult for the insulation to function accurately and for blood to reach the penis because the blood veins providing the penis are unable to relax.

3.Diabetes

Diabetes is a disease that occurs when your blood glucose, also called blood sugar, is too high. Blood glucose is your main source of power and comes from the meals you eat. Diabetes has one of the most devastating influences on erectile Dysfunction for two reasons: Not only does it affect blood flow, but it also affects the nerves.

Men among with diabetes are four to six times more hopeful to develop erectile dysfunction. Diabetes can also start to strokes and heart attacks disease.

4.Dementia

Dementia is a common term applied to explain many signs of the cognitive drop, such as forgetfulness. It is a sign of various underlying disorders and brain diseases According to a 2015 research, men among erectile dysfunction are 1.69 times more possible to improve dementia than men who dont have Erectile Dysfunction.

While this research shows a relationship among erectile dysfunction and dementia, it does not truly show that dementia causes of erectile dysfunctionor vice versa. But now, there is not sufficient research to say for sure whether one causes the other. But still, he faces out that the two diseases often have some of the related risk factorslike atherosclerosis, elevated cholesterol, and diabetes, etc.

5.Prostate cancer

Prostate disease is cancer that happens in the prostate a small walnut-shaped gland in men that produces the seminal liquid that nourishes and transports sperm. This is a difficult one: When it comes to prostate cancer, two situations are occurring. Having prostate cancer it does not cause of Erectile Dysfunction, but the treatments used to fight cancerlike surgery or radiation can. He says surgery is the most frequent cause of Erectile Dysfunction in men who have prostate cancer. Aurogra 100 medicine can also help to cure Erectile Dysfunction.

When a prostate is killed, the nerves can get damaged, resulting in erectile dysfunction, he describes. Tissues and blood veins destroyed by radiation can also cause Erectile Dysfunction. It is the second-leading disease of cancer deaths for men in the U.S. About 1 in 8 men will be diagnosed with prostate cancer in their lifetime. This year, approximately 191,000 men will be diagnosed with prostate disease.

6.Liver disease

The more complicated the liver disorder, the more serious your odds for and the importance of Erectile Dysfunction. One research shows that Erectile Dysfunction was more prevalent in people with early-stage hepatitis C-induced liver cirrhosis than people who had a chronic hepatitis B infection.

Damaged liver function in men can result in erectile dysfunction or hypogonadism or both. We examined whether existing donor liver transplantation (LDLT) results in an increase in male sexual function.

Patients with liver disorder have raised SHBG (sex hormone-binding globulin) and less albumin, and thats a bad thingbecause [these proteins decrease your free testosterone levels, and not only can low testosterone kill your sex drive, but it also makes it more challenging to achieve an erection. Also, alcohol abuse can cause the liver disorder. That men need to limit their alcohol intake.

What you can do

Approximately 75 percent of men who have Erectile Dysfunction does not try for treatment. But they are researches that show that erectile dysfunction can be entirely changed with diet and exercise. While medicines like sildenafil (Viagra), Suhagra 100, Aurogra, Fildena, tadalafil (Cialis), can treat ED, they cannot cure it.

The rest is here:
6 Serious Health Conditions Linked To Erectile Dysfunction - The African Exponent

Recommendation and review posted by Bethany Smith

CRISPR is a powerful gene-editing technology that scientists use to change the genetic blueprint of plants and animals and even humans.

Since its development about 10 years ago, its been used to change the DNA of living things in beneficial ways creating pink tomatoes and mushrooms that dont go brown, for example, and crops that resist insect attacks.

This technology operates efficiently in virtually all cell types of organisms in which its been tested, CRISPR co-inventor Jennifer Doudna, a biochemist at the University of California, Berkeley, said in an interview last May. It was really quite amazing how quickly it was possible to harness this technology once it was clear how it operated.

CRISPR (also known as CRISPR/Cas9) could also be used to create human designer babies with specific traits for example, a specific eye color or possibly enhanced intelligence. Most scientists have scrupulously avoided pursuing this controversial line of research, although a Chinese scientist stoked controversy in 2018 when he claimed to have used CRISPR to edit the genes of twin girls before their birth in order to make them immune to HIV, the virus that causes AIDS.

The name CRISPR is an acronym for clustered regularly interspaced short palindromic repeats, but you dont need to understand that brain-boggling term in order to understand how CRISPR works.

In short, it works by identifying a specific strand of DNA for example, the genetic instructions that determine eye color and replacing it by cutting" the original DNA and pasting in replacement DNA.

There are other gene-editing techniques, but they are slow and expensive in comparison to CRISPR. What used to take weeks or months can now be done in days with CRISPR.

Some modern CRISPR gene-editing kits, consisting of a few petri dishes, pipettes and bottles of special proteins, are small enough to keep on a shelf in the fridge and it can take as little as two days to see results.

Beyond creating better crops and hardier farm animals, CRISPR offers the tantalizing prospect of revolutionizing human health by bringing cures for genetic diseases: We are really on the threshold of a technology that is going to enable that to treat it at its source, by correcting the code in the DNA, Doudna said in a recent video.

In a series of experiments conducted a few years ago at the Broad Institute, a biomedical institute of MIT and Harvard in Cambridge, Massachusetts, scientists used CRISPR to improve hearing in mice with a certain form of hereditary deafness.

And in experiments at several University of California campuses published in 2016, researchers fixed defective bone marrow cells in a way that could offer a cure for sickle-cell anemia, a potentially deadly condition that affects an estimated 250 million people around the world.

Scientists are also using CRISPR in an effort to wipe out malaria by creating malaria-resistant mosquitoes, which would replace the wild populations of mosquitoes that spread the disease.

Though scientists see huge potential in CRISPR technology for treating human genetic diseases, theyve generally avoided using CRISPR to edit the genes of human embryos, citing the potential dangers of the technology and the ethical issues that surround its use for that purpose.

The actions of the Chinese researcher, He Jiankui, have drawn stern criticism from scientists and bioethicists, who called the work dangerous, unethical and even amateur. They point out that scientific knowledge of CRISPR and human genetics is far from perfect and that the twin girls could suffer as they grow up from genetic problems created by the CRISPR editing of their genes.

FOLLOW NBC NEWS MACH ON TWITTER, FACEBOOK, AND INSTAGRAM.

Link:
What is CRISPR? - NBC News

Recommendation and review posted by Bethany Smith

Given that just two genes are responsible for making cats a problem for many people, it seemed like a no-brainer to engineer cats that lacked those genes, or to simply breed cats with versions of the genes that made the animals less allergenic.

But so far, itchy-eyed cat lovers have been left disappointed.

But for all those who havent given up hope, there may be new options around the corner. An allergic owner might pop open a can of allergy-fighting food for the cat. Or maybe vaccinate the cat to produce fewer allergens. And allergy shots for owners might shift from burdensome weekly or monthly injections to a shot that offers immediate relief.

The new gene-editing technology called CRISPR/Cas9 might even come to the rescue, delivering the ultimate dream to those who can afford it: a cat that doesnt produce allergens at all. One company has made some progress applying CRISPR/Cas9 to cats.

Success in taming cat allergies could bring good news for people whose allergies have nothingto do with cats. If any of the cat allergyfighting measures prove safe and effective, they could be deployed against other allergens, especially airborne ones like pollen, dog dander or dust mites.

Read the original post

Visit link:
Dreaming of hypoallergenic cats and how CRISPR could 'come to the rescue' - Genetic Literacy Project

Recommendation and review posted by Bethany Smith

In August of 2011, Carl June and his team published a landmark paper showing their CART treatment had cleared a patient of cancer. A year-to-the-month later, Jennifer Doudna made an even bigger splash when she published the first major CRISPR paper, setting off a decade of intense research and sometimes even more intense public debate over the ethics of what the gene-editing tool could do.

Last week, June, whose CART work was eventually developed by Novartis into Kymriah, published in Sciencethe first US paper showing how the two could be brought together. It was not only one of the first time scientists have combined the groundbreaking tools, but the first peer-reviewed American paper showing how CRISPR could be used in patients.

June used CRISPR to edit the cells of three patients with advanced blood cancer, deleting the traditional T cell receptor and then erasing the PD1 gene, a move designed to unleash the immune cells. The therapy didnt cure the patients, but the cells remained in the body for a median of 9 months, a major hurdle for the therapy.

Endpoints caught up with June about the long road both he and the field took to get here, if the treatment will ever scale up, and where CRISPR and other advancements can lead it.

The interview has been condensed and edited.

Youve spoken in the past about howyou started working in this field in the mid-90s after your wife passed away from cancer. What were some of those early efforts? How did you start?

Well, I graduated from high school and had a low draft number [for the Vietnam War] and was going to go to study engineering at Stanford, but I was drafted and went into the Naval Academy in 1971, and I did that so I wouldnt have to go to the rice fields.

The war ended in 73, 74, so when I graduated in 1975, I was allowed to go to medical school, and then I had a long term commitment to the Navy because they paid for the Acadamy and Medical school. And I was interested in research and at the time, what the Navy cared about was a small scale nuclear disaster like in a submarine, and like what happened at Chernobyl and Fukushima. So they sent me to the Fred Hutchinson Cancer Center where I got trained in cancer, as a medical oncologist. I was going to open a bone marrow transplant center in Bethesda because the Navy wanted one in the event of a nuclear catastrophe.

And then in 1989, the Berlin Wall came down and there was no more Cold War. I had gone back to the Navy in 86 for the transplant center, which never happened, so then I had to work in the lab full time. But in the Navy, all the research has to be about combat and casualty. They care about HIV, so my first papers were on malaria and infectious disease. And the first CAR-T trials were on HIV in the mid-90s.

In 96, my wife got diagnosed with ovarian cancer and she was in remission for 3-4 years. I moved to the University of Pennsylvania in 1999 and started working on cancer because I wasnt allowed to do that with the Navy. My wife was obviously a lot of motivation to do that. She passed away in 2001. Then I started working with David Porter on adoptive transfer T cells.

I got my first grant to do CAR-T cells on HIV in 2004, and I learned a whole lot. I was lucky to have worked on HIV because we did the first trials using lentiviruses, which is an engineered HIV virus.

I was trained in oncology, and then because of the Navy forced to work on HIV. It was actually a blessing in disguise.

So if you hadnt been drafted, you wouldve become an engineer?

Yes. Thats what I was fully intending. My dad was a chemical engineer, my brother is an engineer. Thats what I thought I was going to do. No one in my family was ever a physician. Its one of those many quirks of fate.

Back then, we didnt have these aptitude tests. It was just haphazard. I applied to three schools Berkeley, Stanford and Caltech and I got into all three. It was just luck, fate.

And it turned out when I went to the Naval Academy, they had added a pre-med thing onto the curriculum the year before, so thats what I did when I started, I did chemistry.

I wouldve [otherwise] been in nuclear submarines. The most interesting thing in the Navy then was the nuclear sub technology.

You talked about doing the first CAR-T trials on HIV patients because thats where the funding was. Was it always in your head that this was eventually going to be something for cancer?

So I got out of the Navy in 99 and moved to Penn. I started in 98 working on treating leukemia, and then once I got to Penn, I continued working one day a week on HIV.

Its kind of a Back-to-the-Future thing because now cancer has paved out a path to show that CART cells can work and put down the manufacturing and its going to be a lot cheaper making it for HIV. I still think thats going to happen.

Jim Riley, who used to be a postdoc in my lab, has some spectacular results in monkeys with HIV models. They have a large NIH and NIAID research program.

So were going to see more and more of that. The CAR technology is going to move outside of cancer, and into autoimmune and chronic infections.

I want to jump over to cytotoxic release syndrome (CRS)because a big part of the CRISPR study was that it didnt provoke this potentially deadly adverse effect. When did you first become aware that CRS was going to be a problem?

I mean we saw it in the very first patient we treated but in all honesty, we missed it. Im an MD, but I dont see the patient and David Porter tookcare of the first three patients and our first pediatric patient,Emily Whitehead.

In our first patients, 2 out of 3, had complete remission and there were fevers and it was CRS but we thought it was just an infection, and we treated with antibiotics for 3 weeks and[eventually] it went away. And sort of miraculously he was in remission and is still in remission, 9 years later.

And then when we treated Emily. She was at a 106-degree fever over three days, and there was no infection.

Ive told this story before. My daughter has rheumatoid arthritis, and I had been president of the Clinical Immunologists Society from 2009 to 2010, and the first good drug for juvenile rheumatoid arthritisthat came out. I was invited to give the Japanese scientist Tadamitsu Kishimoto the presidential award for inventing the drug.

Then in 2012, Emily Whitehead was literally dying from CRS, she had multiple organ failures. And her labs came back and IL-6 levels were 1000x normal. It turns out the drug I was looking at for my daughter, it blocks IL-6 levels. I called the physician and I said, listen theres something actionable here, since its in your formulary to give it to her off-label.

And she gave her the appropriate dose for rheumatoid arthritis. It was miraculous. She woke up very rapidly.

Now its co-labeled. When the FDA approvedKymriah, it was co-labeled. It kind of saved the field.

How were you feeling during this time? Did you have any idea what was happening to her?

No, not until we got the cytokine levels, and then it was really clear. The cytokine levels go up and it exactly coincided. Then we retroactively checked out adults and they had adverse reactions and it easy to see. We hadnt been on the lookout because it wasnt in our mouse models.

And it appeared with those who got cured. Its one of the first on-target toxicities seen in cancer, a toxicity that happens when you get better. All the toxicities from chemotherapy are off-target: like leukopenia or hair loss.

I had a physician who had a fever of 106, I saw him on a fever when he was starting to get CRS. When the nurse came in and it said 106, they thought the thermometer must be broken. On Monday, I saw him, and said how are you feeling and he said fine. And I looked at the thermometer and histemperature was still 102.

People will willingly tolerate on-target toxicity thats very different from chemotherapy if they know it helps get them better. Thats a new principle in cancer therapy.

You had these early CART results almost at the same time that Doudna publishes the first CRISPR papers, then still in bacteria. When did you first start thinking about combining the two?

Yeah, it was published inSciencein 2012 and thats when Emily Whitehead got treated. Its an amazing thing.

Thats something so orthogonal. You think how in the heck can that ever benefit CART cells? but my lab had done the first edited cells in patients, published in 2012. And we used zinc-fingered nucleases, which were the predecessors to CRISPR. It knocked out one gene at a time, but we showed it was safe.

I was already into gene editing because it could make T cells resistant to HIV. So it was pretty obvious that there were candidates in T cells that you can knock out. And almost every lab started working on some with CRISPR, cause it was much easier.

We were the first to get full approval by the FDA, so we worked on it from 2012, had all the preclinical data by 2016, and then it takes a while to develop a lot of new assays for this as we were very cautious to optimize safety and it took longer than we wanted, but in the end, we learned a tremendous amount.

So what did we learn?

First of all our patients had advanced metastatic cancer and had had a lot of chemotherapy. The first patient had had 3 bone marrow transplants.

One thing is feasibility: could you really do all the complex engineering? So we found out we could. feasibility was passed.

Another was the fact that cas9 came out of bacteria, forms of strep and staph. Everyone has pre-existing immunity to Cas9 and we had experience from the first trial with Sangamo[with zinc-finger nucleases] where some patients had a very high fever. In that case, we had used adenoviruses, and it turned out our patients had very high levels of baseline immune response to adenoviruses, so we were worried that would happen with CRISPR, and it did not happen.

It did not have any toxicity. If it had, it would have really set the field back. If there was animmune response to cas9 and CRISPR, there couldve been a real barrier to the field.

And then, the cells survived in the patients. The furthest on, it was 9 months. The cells had a very high level of survival. In the previous trials, the cells survived less than 7 days. In our case, the half-life was 85 days. We dont know the mechanism yet.

And we found very big precision in the molecular scissors, and that was a good thing for the field. You could cut 3 different genes on 3 different chromosomes and have such high fidelity.

It [CRISPR] is living up to the hype. Its going to fix all these diseases.

Whats the potential in CAR-T, specifically?

Well theres many many genes that you can add. There are many genes that knocking outwill make the cells work better. We started with the cell receptor. There are many, I think, academics and biotechs doing this now and it should make the cells more potent and less toxic.

And more broadly, what else are you looking at for the future of CART? The week before your paper, there were the results from MD Anderson on natural killer cells.

Different cell types, natural killer cells, stem cells putting CAR molecules into stem cells, macrophages. One of my graduate students started a company to do CAR macrophages and macrophages actually eat tumor cells, as opposed to T cells that punch holes in them.

There will be different cell types and there will be many more ways to edit cells. The prime editing and base editing. All different new variations.

Youve talked about how people used to think the immuno-oncology, if it ever worked, would nevertheless be a boutique treatment. Despite all the advancements, Novartis and Gilead still have not met the sales they once hoped to grab from their CART treatments. Are you confident CART will ever be widely accessible?

Oh yeah, Novartis sales are going up. They had a hiccup launching.

Back in 96 or 97, when Genentech launched Herceptin, their commercial antibody, they couldnt meet the demand either and then they scaled up and learned how to do better cultures. So right now Novartis is using tech invented in my lab in the 1990s culture tech thats complex and requires a lot of labor, so the most expensive part is human labor. A lot can be made robotic. The scale problem will be much easier.

Thats an engineering problem that will become a thing of the past. The manufacturing problem will get a lot cheaper. Here in the US, we have a huge problem with how drugs are priced. We have a problem with pricing. Thats a political issue.

But in cell therapy, its just kind of the growth things you see in a new industry. Itll get worked out.

This article has been updated to reflect that Jim Riley conducted work on CAR in HIV.

Originally posted here:
Carl June on CRISPR, CART and how the Vietnam War dropped him into medicine - Endpoints News

Recommendation and review posted by Bethany Smith

Key point: Humanity isn't ready for gene editing.

More than a year ago, the world was shocked by Chinese biophysicist He Jiankuis attempt to use CRISPR technology to modify human embryos and make them resistant to HIV, which led to the birth of twins Lulu and Nana.

Now, crucial details have been revealed in a recent release of excerpts from the study, which have triggered a series of concerns about how Lulu and Nanas genome was modified.

How CRISPR works

CRISPR is a technique that allows scientists to make precise edits to any DNA by altering its sequence.

When using CRISPR, you may be trying to knock out a gene by rendering it inactive, or trying to achieve specific modifications, such as introducing or removing a desired piece of DNA.

Read more: What is CRISPR gene editing, and how does it work?

Gene editing with the CRISPR system relies on an association of two molecules. One is a protein, called Cas9, that is responsible for cutting the DNA. The other molecule is a short RNA (ribonucleic acid) molecule which works as a guide that brings Cas9 to the position where it is supposed to cut.

The system also needs help from the cells being edited. DNA damage is frequent, so cells regularly have to repair the DNA lesions. The associated repair mechanisms are what introduce the deletions, insertions or modifications when performing gene editing.

How the genomes of Lulu and Nana were modified

He Jiankui and his colleagues were targeting a gene called CCR5, which is necessary for the HIV virus to enter into white blood cells (lymphocytes) and infect our body.

One variant of CCR5, called CCR5 32, is missing a particular string of 32 letters of DNA code. This variant naturally occurs in the human population, and results in a high level of resistance to the most common type of HIV virus.

The team wanted to recreate this mutation using CRISPR on human embryos, in a bid to render them resistant to HIV infection. But this did not go as planned, and there are several ways they may have failed.

First, despite claiming in the abstract of their unpublished article that they reproduced the human CCR5 mutation, in reality the team tried to modify CCR5 close to the 32 mutation.

As a result, they generated different mutations, of which the effects are unknown. It may or may not confer HIV resistance, and may or may not have other consequences.

Worryingly, they did not test any of this, and went ahead with implanting the embryos. This is unjustifiable.

A second source of errors could have been that the editing was not perfectly efficient. This means that not all cells in the embryos were necessarily edited.

When an organism has a mixture of edited and unedited cells, it is called a mosaic. While the available data are still limited, it seems that both Lulu and Nana are mosaic.

This makes it even less likely that the gene-edited babies would be resistant to HIV infection. The risk of mosaicism should have been another reason not to implant the embryos.

Read more: 'Designer' babies won't be common anytime soon despite recent CRISPR twins

Moreover, editing can have unintended impacts elsewhere in the genome.

When designing a CRISPR experiment, you choose the guide RNA so that its sequence is unique to the gene you are targeting. However, off-target cuts can still happen elsewhere in the genome, at places that have a similar sequence.

He Jiankui and his team tested cells from the edited embryos, and reported only one off-target modification. However, that testing required sampling the cells, which were therefore no longer part of the embryos - which continued developing.

Thus, the remaining cells in the embryos had not been tested, and may have had different off-target modifications.

This is not the teams fault, as there will always be limitations in detecting off-target and mosaicism, and we can only get a partial picture.

However, that partial picture should have made them pause.

A bad idea to begin

Above, we have described several risks associated with the modifications made on the embryos, which could be passed on to future generations.

Embryo editing is only ethically justifiable in cases where the benefits clearly outweigh the risks.

Technical issues aside, the researchers did not even address an unmet medical need.

While the twins father was HIV-positive, there is already a well-established way to prevent an HIV-positive father from infecting embryos. This sperm washing method was actually used by the team.

The only benefit of the attempted gene modification, if proven, would have been a reduced risk of HIV infection for the twins later in life.

But there are safer existing ways to control the risk of infection, such as condoms and mandatory testing of blood donations.

Implications for gene editing as a field

Gene editing has endless applications. It can be used to make plants such as the Cavendish banana more resistant to devastating diseases. It can play an important role in the adaptation to climate change.

In health, we are already seeing promising results with the editing of somatic cells (that is, non-heritable modifications of the patients own cells) in beta thalassemia and sickle cell disease.

However, we are just not ready for human embryo editing. Our techniques are not mature enough, and no case has been made for a widespread need that other techniques, such as preimplantation genetic testing, could not address.

Read more: Experts call for halt to CRISPR editing that allows gene changes to pass on to children

There is also much work still needed on governance. There have been individual calls for a moratorium on embryo editing, and expert panels from the World Health Organisation to UNESCO.

Yet, no consensus has emerged.

It is important these discussions move in unison to a second phase, where other stakeholders, such as patient groups, are more broadly consulted (and informed). Engagement with the public is also crucial.

Correction: this article originally described RNA (ribonucleic acid) as a protein, rather than a molecule.

Dimitri Perrin, Senior Lecturer, Queensland University of Technology and Gaetan Burgio, Geneticist and Group Leader, The John Curtin School of Medical Research, Australian National University

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

Image: Reuters

Link:
Gene Editing Might Let China Create The Perfect Human Being - The National Interest Online

Recommendation and review posted by Bethany Smith

A revolution is taking place in the knowledge base for life sciences and biotechnology, opening up new applications in healthcare, agriculture, and environmental protection. Political awareness of this potential dates back to 2001, when the European Commission recognized life sciences and biotech through the adoption of its life science and biotechnology strategy.

With the European Green Deal, the new European Commission has set out an ambitious roadmap towards a climate neutral continent in 2050. With that, Europe strives to become a global frontrunner and lead the way in tackling the climate crisis. Taking the potential of biotechnology and life sciences in benefiting people and planet, a renewed focus and impetus on life sciences and biotechnology are all the more necessary. Regaining leadership in the sector should be a fundamental priority for the EU.

In agriculture, biotechnology offers sustainable food solutions through applying newest technologies. Biotechnology, (including genetic modification of crops), has increased farmers yields and incomes while reducing CO2 emissions, and the need for farmer inputs. Meanwhile, a science-based, risk-proportionate and non-discriminatory regulatory framework that allows for gene editing in crops could pave the way for products which offer health and consumer benefits ..

Read the original post

Read the rest here:
Viewpoint: If Europe wants to be 'carbon neutral,' it needs to embrace biotechnologyGMO and CRISPR crops included - Genetic Literacy Project

Recommendation and review posted by Bethany Smith