eClinical Forum

 

Next week, a team from Target Health will be attending the eClinical Forum. The eClinical Forum was formed in 2000 by Pharmaceutical industry representatives with a vision to create a non-commercial and informal environment in which to network with peers, share ideas and experiences, and to shape the future of the clinical research environment. The group today boasts an extensive membership of global companies from the biopharmaceutical and healthcare sectors and it covers research, technology and service provision.

 

The Forum provides access to:

 

An informal environment for exchanging information, ideas and best practices, providing members with the opportunity to learn and to avoid re-inventing the wheel.  Company membership allows unlimited access to monthly teleconfrerences, discussion forum, and special-interest groups. as well as access to 4 workshops/year.

A supportive group that is representative of the industry user community and that can work cooperatively with vendors and regulators.

Information from cross-industry surveys, building a better understanding of current eClinical research data status, needs and trends.

A virtual library on electronic clinical research data capture and management, and related initiatives.

A technology- and vendor-independent environment, stressing the importance of a structured approach to eClinical initiatives that manage the integration of technology, process and people.

An unparalleled opportunity to network with members within the eclinical arena in companies across the biopharmaceutical and global spectrum

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com

 

Halloween Transgenic Cat

 

This picture of a glowing cat has not been altered in any way. The cat, on the other hand, has been altered quite a bit. A team of researchers has genetically engineered it to express green fluorescent protein (aka “GFP,” originally found in jellyfish), which makes the cat glow green under ultraviolet light, as well as an antiviral restriction factor from a rhesus macaque Credit: Mayo Clinic

 

 

 

 

How do they know the cats are carrying the monkey’s gene? They labeled it with GFP — hence the glow. (This picture shows the genetically modified cat featured up top alongside a non-genetically modified cat at five months of age.) Credit: Mayo Clinic

 

Cats that can glow in the dark from a new genetic engineering technique are helping scientists study molecules that could stop AIDS. So far, the researchers have created three genetically engineered kittens that can glow green and pass this 1) ___ onto their offspring. They explained that cats are much better models for AIDS viruses than are mice and other animals. [See Images of the Glowing Kittens, below]. In addition to opening a window into the virus in humans, the cat research may end up helping the cats themselves.

 

Devastating AIDS Pandemics

 

The world is currently facing two devastating AIDS pandemics – one in 2) ___, the other in domestic cats. The viruses responsible, human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV), are highly similar. “FIV causes AIDS with loss of infection-fighting T cells like HIV does in people, and cats get sick from virtually the same AIDS-defining opportunistic infections as humans who have untreated HIV,” said researcher Eric Poeschla, a molecular biologist and infectious disease specialist at the Mayo Clinic College of Medicine in Rochester, Minn. As such, researchers have long wanted to genetically experiment with cats to better understand how to combat AIDS. To create genetically modified animals, scientists insert genes into their 3) ___, often using benign viruses as the delivery vehicles. Investigators commonly target the earliest possible stages in an animal’s development so the gene gets installed into all of its cells – any later, and the gene can end up in some tissues but not others.

 

Tinkering with Cat Genes

 

At first scientists created genetically engineered cats using cloning, which meant injecting a gene into one cell – from the skin, for instance – and then implanting the modified nucleus of that cell into an 4) ___ cell that had its nucleus removed; the resulting cell then develops into an embryo much like a fertilized egg would. In this manner, researchers generated cats that were either fluorescent red or green, a glow-in-the-dark cat being visible proof of the genetic engineering succeeding. However, this kind of cloning is very difficult to perform, as it essentially involves delicate surgery on cells. In addition, the manhandling that both 5) ___ and egg experience and the “reprogramming” the nucleus undergoes from adult to embryonic status often leads to animals that might look normal but can have aberrations on the molecular and cellular level.

 

Now scientists have developed a new way to create genetically engineered domestic cats where they modify egg cells directly with 6) ___. The amount of genetic material they implanted within the cats was tiny – if the entire string of DNA that is the cat genome were unraveled and depicted as a highway reaching across the US from NY to LA, the inserted material would be equal in length to one of the dashed yellow lines in the middle of the highway somewhere out in Nebraska. This efficient process, the first time germ cells of a carnivore have been genetically modified, led to embryos that robustly expressed the implanted gene without all the complexities 7) ___ can involve. The result – three healthy kittens that glowed green when a blue light was shone on them and transmitted the gene to their offspring.

 

The researchers then applied this approach to investigating resistance to AIDS. “We want to see if we can protect the domestic cat against its AIDS virus, if we can protect any species, eventually including ours, against its own AIDS virus,” Poeschla said. The aim of future treatments is a gene therapy that can introduce protective genes into people that help them fight off 8) ___. To do so, they created transgenic cats that generated or expressed antiviral proteins taken from rhesus monkeys. Such molecules can block retroviruses such as HIV and FIV. Preliminary results suggested cells from these cats grown in the lab resisted replication of the feline AIDS virus FIV, keeping it from spreading. “We haven’t shown cats that are AIDS-proof,” Poeschla cautioned. “We still have to do infection studies involving whole cats. That the protection gene is expressed in the cat lymphoid organs, where AIDS virus spread and cell death mostly play out, is encouraging to us, however.”

 

Millions of cats dying

 

The researchers stress their work could also help cats themselves, not just humans. Since FIV afflicts 9) ___ cats the most, the virus causes a lot of unwitnessed, unattended and unrelieved feline suffering, with millions of cats dying annually worldwide from AIDS, often painfully and alone. “Millions more suffer with chronic illness from the virus,” Poeschla added. “Supporting this research can help cats as much as people.” Although this research on transgenic cats has so far concentrated on AIDS, there are many other diseases that cats and humans share that genetically modified felines could help shed light on in a way that mice and other experimental animals cannot.

 

“Some feline organs, such as the eye, are much more similar to humans than the same organs in mice,” Poeschla explained. “The cat brain, particularly the cerebral cortex and vision-processing parts, is the best understood of any species.” As such, 10) ___ cats “might be of help in understanding the workings of the brain and neurological diseases such as Alzheimer’s, or with genetic illnesses and major eye diseases such as glaucoma or macular degeneration,” he added.

 

The scientists detailed their findings online in the journal Nature Methods.

 

 

Normal Cats By Day … Credit: Mayo Clinic – Both of the tabby-coated cats (the genetically engineered kitten and the control cat) look the same under normal light.

 

Light-up Claws – Credit: Mayo ClinicCoat, claws, whiskers, nose, tongue and the inside of the mouth glow green under blue light; fluorescence is quenched in dark fur.

 

 

 

A N S W E R S: 1) genes; 2) humans; 3) genomes; 4) egg; 5) nucleus; 6) viruses; 7) cloning; 8) HIV; 9) feral; 10) transgenic

Beware: Death’s-head Hawkmoth Harbinger of Oncoming Disease

 

 

 

Warmer English climate has attracted flights of colorful tourists from the continent.  With wings as big as a bat’s, the Death’s-head Hawkmoth is the most extraordinary of the insect visitors.

 

Watch out. Break no mirrors. Walk under no ladders. The emblem of death has been seen again.

 

The Death’s-head Hawkmoth, Europe’s most infamous insect, which bears the likeness of a skull upon its back, has turned up in England as part of the biggest influx of continental moths for many years. Several specimens have been spotted along the south coast. The first part of October’s extraordinary heat, caused by a mass of warm air surging up from southern Europe, brought with it hundreds of moths of numerous rare species from France, Spain and even the Mediterranean. The most extraordinary of these is Acherontia atropos, named in Latin after a river in Hades over which the souls of the dead were ferried and one of the three goddesses, or Fates, who spun the thread of human destiny. With wings as big as a bat’s, and a body the size of a shrew’s, the Death’s-Head Hawkmoth has three distinctive characteristics: when disturbed it makes a noise, a mouse-like squeaking through its proboscis (no other moth does makes a sound in this way); it invades beehives with impunity and feeds on the honey; and it carries that amazing likeness of a human skull prominently upon its thorax.

 

For centuries, it has been viewed in Europe as a creature of ill-omen, presaging bad fortune, illness and death, and it occurs widely as such in art and literature; it even made its way into the Hollywood movie The Silence of The Lambs, where the serial killer being hunted by the FBI agent Clarice Starling (Jodie Foster) puts the pupa of a death’s-head hawkmoth into the mouths of his victims. It featured on the posters for the 1991 film, and, rather more grandly, it also appears in one of the best-known pre-Raphaelite paintings, Holman Hunt’s The Hireling Shepherd, where the shepherd in question is showing a death’s-head hawkmoth to a young countrywoman, with the presumed message that death comes to us all, so let’s get on with our loving.

 

The insect does not breed in Britain as its caterpillar cannot survive English winters, but it is occasionally seen as a migrant. Since last week’s great influx, sightings of the insect have been confirmed at the RSPB’s Arne nature reserve in Dorset and in Plymouth, with several more sightings reported.

 

 

The Crimson Speckled Moth

 

Other, less sensational, migrant moths have also been exciting wildlife lovers. Among these is the dazzlingly colored crimson speckled moth, which looks like a bag of sweets, and the gently elegant vestal, which you might say is wearing a toga with a pink-purple stripe. Entomologists have been particularly struck by the large numbers of flame brocades that have turned up. These are beautiful, purplish-brown moths which boast a distinctive white wing-flash and are normally found in Spain and France. “The flame brocade was resident in Sussex for at least half a century from about the mid-19th century and has been a scarce immigrant since then,” said Mark Parsons, a moth expert at the charity Butterfly Conservation. “This is the first time the moth has been seen in these numbers in this country for about 130 years. It appears to have been making an attempt to re-colonize these shores, possibly as a result of more favorable weather conditions through climate change.”

 

Here’s hoping that warmer temperatures due to climate change, plus the return of the Death’s Head Hawkmoth, are not harbingers of new strains of bacteria and virus, disease and death

German Outbreak of Escherichia coli O104:H4 Associated with Sprouts

 

 

A large outbreak of the hemolytic–uremic syndrome caused by Shiga-toxin-producing Escherichia coli O104:H4 occurred in Germany in May 2011. The source of infection at the time was undetermined. As a result, a matched case-control study and a recipe-based restaurant cohort study, along with environmental, trace-back, and trace-forward investigations was conducted to determine the source of infection. The study was published on line in the New England Journal of Medicine (26 October 2011).

 

The case–control study included 26 case subjects with the hemolytic-uremic syndrome and 81 control subjects. The outbreak of illness was associated with sprout consumption (matched odds ratio, 5.8) and with sprout and cucumber consumption. Among case subjects, 25% reported having eaten sprouts, and 88% reported having eaten cucumbers. The recipe-based study among 10 groups of visitors to restaurant K included 152 persons, among whom bloody diarrhea or diarrhea confirmed to be associated with Shiga-toxin-producing E. coli developed in 31 (20%). Visitors who were served sprouts were significantly more likely to become ill (relative risk, 14.2). Sprout consumption explained 100% of cases. Trace-back investigation of sprouts from the distributor that supplied restaurant K led to producer A. All 41 case clusters with known trading connections could be explained by producer A. The outbreak strain could not be identified on seeds from the implicated lot.

 

According to the authors, the investigation identified sprouts as the most likely outbreak vehicle, underlining the need to take into account food items that may be overlooked during subjects’ recall of consumption.

Gene Variant Increases Risk of Kidney Disease in African-Americans

 

 

When a person has kidney disease, the kidneys are unable to fully remove waste products and extra water from the blood. A common kidney disease called focal segmental glomerulosclerosis (FSGS), often progresses to end-stage kidney disease and the need for dialysis or a kidney transplant.

 

According to an article published online in the Journal of the American Society of Nephrology (13 October 2011), African-Americans with two copies of the APOL1 gene have about a 4% lifetime risk of developing FSGS. The APOL1 gene occurs in about 12% of African-Americans. African Americans who develop kidney disease tend to do so at younger ages than other FSGS patients, with 70% diagnosed with FSGS between age 15 and 39, compared to 42% in that age group for people with one or no APOL1 variants.

 

Possessing two APOL1 variants also raises the risk for African-Americans with HIV of developing HIV-associated nephropathy (HIVAN) – a type of kidney disease that develops in some people with human immunodeficiency virus – to 50% among those not getting anti-viral therapy. Anti-viral therapy appears fairly effective at preventing HIVAN. According to the authors, the much higher risk of kidney disease in patients with HIV suggests that a second hit with a virus or other unknown factor is necessary for kidney injury in people who have two APOL1 variants. This may be why most people with two APOL1 variants do not develop kidney disease.

 

FSGS patients with two APOL1 variants respond as well to steroid treatments as their counterparts who don’t have the variants, making steroids a viable treatment option. Further, it was found that kidney disease progresses more rapidly in patients with two APOL1 variants, and it has been hypothesized that aggressive therapy may be advisable.

 

In 2010, working with researchers at Harvard Medical School, the authors found some kidney disease risk is due to variants APOLI, a gene adjacent to MYH9. These variants appear to have evolved about 5,000 years ago in some regions of sub-Saharan Africa to protect against trypanosomal infection, also called African sleeping sickness, a degenerative and potentially fatal disease affecting tens of thousands of people in those regions. People from other continents do not have the APOL1 variants.

Efficacy of Etanercept in the Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)

 

 

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is a rare inherited condition characterized by recurrent fevers, abdominal pain and skin rashes. TRAPS is associated with mutations in the gene coding for tumor necrosis factor receptor 1 (TNFR1), a critical molecule in receiving inflammatory signals in the body’s immune system.

 

Etanercept, trade name Enbrel is one of a class of drugs that block tumor necrosis factor, a protein implicated in the harmful inflammation in TRAPS, as well as a number of common rheumatic diseases, including rheumatoid arthritis. While the drug has been used in the treatment of TRAPS for about 10 years, this is the first formal study to look at its effectiveness long-term.

 

The study, published in Arthritis & Rheumatism (17 October 2011), was conceived in 2001 by Keith Hull, M.D., Ph.D., then a rheumatology fellow in the NIAMS under the supervision of Daniel Kastner, M.D, Ph.D., one of the discoverers of the TNF receptor mutations in TRAPS, and now the scientific director of the NIH’s National Human Genome Research Institute. The initial study enrolled 15 patients with TRAPS. Each patient kept a daily diary of attacks, symptom severity, and use of additional medicines, and had periodic blood tests to measure acute phase reactants, proteins that are produced by the liver to fight infection and serve as markers of inflammation in the blood. While on treatment with etanercept, patients reported lower symptom scores and a greater number of symptom-free days each week. Etanercept also reduced levels of acute phase reactants, particularly during asymptomatic periods.

 

To find out whether etanercept was effective as a long-term treatment, the authors contacted all 15 patients treated with etanercept seven to nine years after the conclusion of the initial study period. Despite the overall beneficial effects of etanercept, most patients discontinued the drug during the follow-up period due to a perceived lack of efficacy or painful injection site reactions, which could be related to the skin manifestations of the disease. The three patients who remained on the drug, however, continued to report benefits, suggesting that for some, the drug can be an effective long-term treatment option. However, the study did not show whether etanercept could prevent the long-term consequences of TRAPS, chiefly a condition called amyloidosis, in which inflammatory proteins build up in the body, damaging the kidneys, heart and other organs.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.

 

 

FDA invests $2 Million in Partnerships through Centers of Excellence in Regulatory Science and Innovation

 

 

The FDA announced the award of $2 million to support two regional Centers of Excellence in Regulatory Science and Innovation (CERSI). The centers, which will be located at the University of Maryland and Georgetown University, will focus on strengthening science and training needed to modernize and improve the ways drugs and medical devices are reviewed and evaluated, a major focus within the FDA.

 

In August 2011, the agency released the strategic plan for: “Advancing Regulatory Science at FDA.” More recently, the agency announced a related innovation initiative, “Driving Biomedical Innovation: Initiatives for Improving Products for Patients.”

 

Working closely with FDA scientists, CERSI researchers will assist the FDA in driving innovation in medical product development as well as in advancing laboratory, population, behavioral, and manufacturing sciences. The agency chose to pilot the CERSIs in the Washington, D.C. area, to allow for the greatest possible face-to-face collaboration and training with FDA staff.

10/29/11 Central Park NYC Snow Storm

 

 

10/29/11 NYC Central Park Snowstorm

 

 

10/29/11  —  Central Park NYC Snowstorm

 

 

Saturday 29, 2011 – Jogging During Central Park Snow Storm

Meet the “social robot” at University of Southern California

 

 

“Outsourcing no longer means giving jobs away to humans in other countries”…..……Joyce Hays, Target Health Inc.

 

 

BBC.co.uk/technology, October 27, 2011, by Jon Stewart  —  Robots are about to invade our lives.

From performing household chores, to entertaining and educating our children, to looking after the elderly, roboticists say we will soon be welcoming their creations into our homes and workplaces.

Researchers believe we are on the cusp of a robot revolution that will mirror the explosive growth of the computer revolution from the 1980s onwards.

They are developing new laws for robot behaviour, and designing new ways for humans and robots to interact.

“I think robotics technology will change who we are, just as eyeglasses and fire changed who we were before,” says Rodney Brookes, robotics entrepreneur and former director of the MIT Computer Science and Artificial Intelligence Laboratory.

Human-like robots

Commercially available robots are already beginning to perform everyday tasks like vacuuming our floors.

Some ideas, some technologies may sound like science fiction, but they are fast becoming science fact. In our eight-part series we will be exploring ideas that are the future of technology.

The latest prototypes from Japan are able to help the elderly to get out of bed or get up after a fall. They can also remind them when to take medication, or even help wash their hair.

“Current robots are not human like. For example they are things like automated beds and wheelchairs,” says celebrated roboticist Prof Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory at Osaka University, Japan. He believes the time is coming when robots start looking less like machines, and more like us.

“Everything is becoming automatic, and that means everything is a robot. People want to have a better interface.”

“Elderly people don’t like using a computer interface, but they can talk with a robot,” says Prof Ishiguro.

“In the near future we are going to use more human-like robots, I really think so.”

Prof Maja Mataric at the University of Southern California, one of the leading proponents of social caring robots, agrees. “I’m very excited about the fact that today in robotics we have machines that are sophisticated enough to be put together with people in a daily life setting,” she says.

“A major point to keep in mind is that people will need human-machine interaction in the future.”

“People say things like ‘I prefer this robot to my husband! Can I take it home?” said Prof Maja Mataric of University of Southern California

The global population is living longer, and getting older, which presents new challenges.

“The question becomes: who will take care of everyone? While people will always be the best caregivers for people, there just aren’t enough people. That’s where robotic technology can really make a difference,” says Prof Mataric.

Her group is developing robots to work with stroke patients, and elderly people undergoing cognitive changes.

The research team has found that people react well to a robot gym instructor, and seem to get less frustrated with it than with instructions given on a computer screen. The robot can act as a perfect trainer, with infinite patience.

“In fact there’s a really important point here, that as we create these care giving technologies, we’re helping not only the people that need the care, but also the people caring for them. We can give them a break, and help them avoid burnout.”

Welcome to the machine

People are going to have to like, and importantly trust robots before they welcome them into their homes, and several groups around the world are working on making it easier to communicate with them.

 

 

Robotic gym instructors are popular with old and young people

 

 

Much of human interaction takes place unconsciously, through body language. Gestures, eye contact, and concepts of personal space are all things that robots are being taught.

In learning about how people interact with machines, researchers are also discovering new roles for robots in our lives. Robots can communicate with humans in ways that other technology can not.

“If someone finds the robot to be more persuasive, more credible, that’s going to affect how they interact with it,” says Dr Cynthia Breazeal, director of the Personal Robots Group at the Massachusetts Institute of Technology.

“We can now start to think about domains where it’s the social interaction, which is the core means by which a robot helps someone, through motivating them, or giving positive reinforcement.”

Dr Breazeal says that means robots could have applications in education, learning, and healthcare, where social support is important.

Roboticists have had impressive results with autistic children, who often find communication difficult. Children seem to be able to interact more easily with a robot ‘buddy’ than with other people.

 

It’s a robot, but not as our science fiction books know it

 

 

In control

Science fiction may have primed us for the coming robot revolution, but it has also given us an idea of the types of controls we may want to consider before welcoming robots into our lives and homes.

One of the most celebrated science fiction authors, Isaac Asimov, outlined ‘Three Laws of Robotics’ in a novel featuring human-like robots. The rules were designed to protect people from harm.

  1. A robot may not injure a human being or, through inaction, allow a human being to come to harm.
  2. A robot must obey the orders given to it by human beings, except where such orders would conflict with the First Law.
  3. A robot must protect its own existence as long as such protection does not conflict with the First or Second Laws.

“Asimov’s laws of robotics were, and remain, a fictional device” says Prof Alan Winfield from the University of the West of England.

“But if not those particular laws, then in the far future there will have to be something like Asimov’s laws.”

At present, robots are not sophisticated enough to be made to behave ethically. Prof Winfield says that means roboticists building them need to behave ethically instead.

The UK’s Engineering and Physical Sciences Research Council, together with the Arts and Humanities Research Council, has drafted a set of ethical principles for robot design – which can be summarized as follows:

  1. Robots should not be designed solely or primarily to kill or harm humans.
  2. Humans, not robots, are responsible agents. Robots are tools designed to achieve human goals.
  3. Robots should be designed in ways that assure their safety and security.
  4. Robots are artefacts; they should not be designed to exploit vulnerable users by evoking an emotional response or dependency. It should always be possible to tell a robot from a human.
  5. It should always be possible to find out who is legally responsible for a robot.

“At present this code is simply a set of ideas. It’s out for debate and discussion,” says Prof Winfield.

However he believes that they are ideas that people should be thinking about before the coming ‘robot revolution’.

“In my view the principles are less important than the debate and the awareness around the issues that they provoke.”

 

 

Pacific Ocean Behind the Beach Unbrellas

 

 

This week the first 2011 TEDMED speaker was David Agus MD, who also interviewed Lance Armstrong on the second day of the conference.  As soon as the 2011 TEDMED presentations are posted, we will post them right here on the BLOG.  For now, see below, presentations from last year’s TEDMED, which we also attended in the same beautiful setting.

 

 

David Agus MD – TEDMED  2010 – (1)

 

David Agus MD – TEDMED 2010  (2)

 

David Agus MD – TEDMED 2010 (3)

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