Target Health Presentations 2012

 

 

Target Health is pleased to announce that it will be presenting at the following meetings this year. Details to follow as we get closer:

 

1. Risk-Based Approaches to Clinical Investigation – April 10-12 – Philadelphia

2. Encouraging Development of Therapeutics for Neglected Diseases – May 12-13 – Philadelphia

3. DIA Annual Meeting – June 25-27 – Philadelphia

4. Disruptive Innovations – Boston – September 13-14

 

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

 

 

On the Hunt for Universal Intelligence

 

On the hunt for the universal intelligence test. (Credit: SINC)

 

 

 

How do you use a scientific method to 1) ___ the intelligence of a human being, an animal, a machine or an extra-terrestrial? So far this has not been possible, but a team of Spanish and Australian researchers have taken a first step towards this by presenting the foundations to be used as a basis for this method in the journal Artificial Intelligence, and have also put forward a new intelligence test.

 

We have developed an “anytime” intelligence 2) ___, in other words a test that can be interrupted at any time, but that gives a more accurate idea of the intelligence of the test subject if there is a longer time available in which to carry it out,” José Hernandez-Orallo, a researcher at the Polytechnic University of Valencia (UPV), said. This is just one of the many determining factors of the universal 3) ___ test. “The others are that it can be applied to any subject — whether biological or not — at any point in its development (child or adult, for example), for any system now or in the future, and with any level of intelligence or speed,” points out Hernández-Orallo.

 

Orallo, along with his colleague David L. Dowe of the Monash University, Clayton (Australia), has suggested the use of 4) ___ and computational concepts in order to encompass all these conditions. The study forms part of the “Anytime Universal Intelligence” project, in which other scientists from the UPV and the Complutense University of Madrid are taking part.

 

The authors have used interactive 5) ___exercises in settings with a difficulty level estimated by calculating the so-called “Kolmogorov complexity” (they measure the number of computational resources needed to describe an object or a piece of information). This makes them different from traditional psychometric tests and artificial intelligence tests (Turing test).

 

Use in Artificial Intelligence

 

The most direct application of this study is in the field of 6) ___ intelligence. Until now there has not been any way of checking whether current systems are more intelligent than the ones in use 20 years ago, “but the existence of tests with these characteristics may make it possible to systematically evaluate the progress of this discipline,” says Hernández-Orallo. And what is even “more important” is that there were no theories or tools to evaluate and compare future intelligent systems that could demonstrate intelligence greater than 7) ___ intelligence.

 

The implications of a universal intelligence test also impact on many other disciplines. This could have a significant impact on most cognitive sciences, since any discipline depends largely on the specific techniques and systems used in it and the mathematical basis that underpins it. The authors conclude that “The universal and unified evaluation of intelligence, be it human, non-human animal, artificial or extraterrestrial, has not been approached from a 8) ___ viewpoint before, and this is a first step.”

 

ANSWERS: 1) measure; 2) test; 3) intelligence; 4) mathematical; 5) exercises; 6) artificial; 7) human; 8) scientific

Evolution Is Written All Over Your Face

 

 

Primates from Central and South America. (Credit: Image courtesy of University of CaliforniaLos Angeles)

 

 

Why are the faces of primates so dramatically different from one another? UCLA biologists working as “evolutionary detectives” studied the faces of 129 adult male primates from Central and South America, and they offer some answers in research published on 11 January 2011, in the early online edition of the journal Proceedings of the Royal Society B. The faces they studied evolved over at least 24 million years.

 

“If you look at New World primates, you’re immediately struck by the rich diversity of faces,” said Michael Alfaro, a UCLA associate professor of ecology and evolutionary biology and the senior author of the study. “You see bright red faces, moustaches, hair tufts and much more. There are unanswered questions about how faces evolve and what factors explain the evolution of facial features. We’re very visually oriented, and we get a lot of information from the face.” Some of the primate species studied are solitary, while others live in groups that can include dozens or even hundreds of others.

 

Each face was divided into 14 regions; coded the color of each part, including the hair and skin; studied the patterns and anatomy of the faces; and gave each a “facial complexity” score. The authors studied how the complexity of primate faces evolved over time and examined the primates’ social systems. To assess how facial colors are related to physical environments, they analyzed environmental variables, using the longitude and latitude of primates’ habitats as a proxy for sun exposure and temperature. They also used statistical methods to analyze the evolutionary history of the primate groups and when they diverged from one another.

 

“We found very strong support for the idea that as species live in larger groups, their faces become more simple, more plain,” said lead author Sharlene Santana, a UCLA postdoctoral scholar in ecology and evolutionary biology and a postdoctoral fellow with UCLA’s Institute for Society and Genetics. “We think that is related to their ability to communicate using facial expressions. A face that is more plain could allow the primate to convey expressions more easily.

 

The finding that faces are more simple in larger groups came as a surprise. “Initially, we thought it might be the opposite,” Santana said. “You might expect that in larger groups, faces would vary more and have more complex parts that would allow one individual to identify any member of that group. That is not what we found. Species that live in larger groups live in closer proximity to one another and tend to use facial expressions more than species in smaller groups that are more spread out. Being in closer proximity puts a stronger pressure on using facial expressions.”

 

“This finding suggests that facial expressions are increasingly important in large groups,” said co-author Jessica Lynch Alfaro, associate director of the UCLA Institute for Society and Genetics. “If you’re highly social, then facial expressions matter more than having a highly complex pattern on your face. ” The authors also found that when primates live in environment with more species that are closely related, their faces are more complex, regardless of their group size. This finding is consistent with their need to recognize individuals of other closely related species that live in the same habitat to avoid interbreeding, Santana said.

 

The study presented the first quantitative evidence linking social behavior to the evolution of facial diversity and complexity in primates, and how ecology controls aspects of facial patterns. As species live closer to the equator, the skin and hair around their eyes get darker. It was also found that regions of the face around the nose and mouth get darker when species live in humid environments and denser forests and that facial hair gets longer as species live farther from the equator and the climate gets colder, which may be related to regulating body temperature.

 

In the future, the authors may use computer facial-recognition software to help quantify the faces in a more sophisticated way. They also plan to study the faces of carnivores, including big cats. Previous studies have found that primate species with moustaches and beards tend to look poker-faced; they don’t move their faces much when they communicate, compared with other species.

 

The authors also devised a way to test a theory that has been in the biological literature for decades but had never been tested before. As a lineage diverges and species accumulate, a series of changes in facial coloration and body coloration emerges. The theory suggests that once a species evolves to have a certain color, such as hair color, the change is irreversible and it cannot evolve back to a previous color in its lineage. This theory was found to be wrong.

 

Lessons for human faces?

 

The findings do suggest that an important factor in shaping human faces is the premium on making unambiguous facial expressions. “Humans don’t have all these elaborate facial ornamentations, but we do have the ability to communicate visually with facial expressions,” Alfaro said. “Does reduced coloration complexity create a blank palate for visual expressions that can be conveyed more easily? That is an idea we are testing.”

 

The nature and origins of hominid intelligence is a much-studied and much-debated topic, of natural interest to humans as the most successful and intelligent hominid species. There is no universally accepted definition of intelligence, one definition is “the ability to reason, plan, solve problems, think abstractly, comprehend ideas and language, and learn.” The evolution of hominid intelligence can be traced over its course for the past 10 million years, and attributed to specific environmental challenges.

 

It is a misunderstanding of evolutionary theory, however, to see this as a necessary process, and an even greater misunderstanding to see it as one directed to a particular outcome. There are primate species which have not evolved any greater degree of intelligence than they had 10 million years ago: this is because their particular environment has not demanded this particular adaptation of them. Intelligence as an adaptation to the challenge of natural selection is no better or worse than any other adaptation, such as the speed of the cheetah or the venomous bite of the cobra. It is, however, the only adaptation which has allowed a species to establish complete domination over the rest of the natural world.

 

Whether our species has yet acquired sufficient intelligence to manage this responsibility is a matter for debate.

Vitamin D May Improve Bone Health in Those Taking Anti-HIV Drug

 

 

Vitamin D helps the body absorb calcium to build bones. When the body is deficient in vitamin D, levels of a hormone called parathyroid hormone rise. This rise triggers activity that draws calcium from bones. As a result, the bones become more fragile and can break more easily.

 

Tenofovir is widely used to treat HIV infection. However, the drug causes symptoms that resemble those of vitamin D deficiency, causing bones to lose calcium and reducing bone density. Parathyroid hormone also tends to be elevated in people taking tenofovir, whether or not they have sufficient vitamin D. Because parathyroid hormone levels are elevated in people taking tenofovir in much the same way as they are in people with vitamin D deficiency, a study was performed to see if vitamin D could counteract the bone-depleting effects of tenofovir. The study, published online in Clinical Infectious Diseases (11 January 2012), found that large monthly doses of vitamin D reduced blood levels of parathyroid hormone and that Vitamin D may help prevent hormonal changes that can lead to bone loss among those being treated for HIV with tenofovir.

 

About 200 18- to 25-year-olds on antiretroviral therapy took part in the study. Study participants included young adults taking tenofovir and those receiving other forms of anti-HIV treatment. Each month, the study participants took a 50,000-unit dose of vitamin D or placebo. Results showed that at the end of three months, parathyroid hormone levels had fallen about 14% among participants taking tenofovir and vitamin D, but remained unchanged in participants taking other kinds of anti-HIV medication. However, those taking tenofovir still had higher parathyroid hormone levels than those on other anti-HIV drugs. It is not known if longer treatment with vitamin D would further reduce parathyroid hormone levels. The recommended daily dose of vitamin D is 600 units and the authors noted that they observed no adverse effects from the vitamin D treatment during the 3 months of this study.

 

The authors are now making plans for a two-year follow-up study to examine the longer-term safety of vitamin D in a similar group of HIV-infected subjects taking antiretroviral regimens containing tenofovir, and to determine if the changes in parathyroid hormone result in improvements in bone density.

Study Initiated for the Treatment of Fatty Liver Disease in Children

 

 

Fatty liver disease affects about 17% of children in the US. This rise in the number of children with Nonalcoholic fatty liver disease (NAFLD) most likely mirrors the increase in obesity, which affects more than 16% of American children and teens. NAFLD covers a range of severity from simple liver disease without injury, called steatosis, to the more concerning nonalcoholic steatohepatitis, or NASH, which includes fat accumulation, inflammation, and liver injury. Most children with fatty liver disease are overweight and resistant to insulin, a hormone that regulates energy. The only way to distinguish NASH from other forms of fatty liver disease is with a liver biopsy.

 

NAFLD can be a precursor to NASH, which may progress to cirrhosis, liver failure and liver cancer. NAFLD may also increase a patient’s risk of developing heart disease. A healthy liver helps the body remove harmful chemicals from the blood, fight infection and digest food. If too much scar tissue forms, the liver could fail. Then a liver transplant is required.

 

NIH has launched of a new clinical trial to determine whether treating children diagnosed with the most severe form of fatty liver disease with a drug called cysteamine will help improve the liver. The trial, called Cysteamine Bitartrate Delayed-Release for the Treatment of Nonalcoholic Fatty Liver Disease in Children (CyNCh),will enroll 160 boys and girls ages 8 to 17 with NAFLD. The participants will receive cysteamine or placebo by mouth twice a day for a year. There are no weight cutoffs or percentiles for the children participating in CyNCh. However, more than 90% of the children are expected to be overweight or obese. Participants need a baseline biopsy that confirms severe NAFLD to be eligible for the study. Children with poorly managed diabetes, heart disease, and other chronic liver diseases will be excluded.

 

Results from a small pilot study using cysteamine in 11 children with NASH suggested that it may improve liver enzymes by reducing toxins that can damage the liver. Cysteamine is approved to treat cystinosis, a genetic disease that causes the amino acid cystine to accumulate in the kidneys, liver, eyes, brain, and white blood cells. Modest weight loss through diet and physical activity may help some children with fatty liver disease, but it is a treatment option that seldom helps people meet their goals.

GENETICS

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Genetic Mutation Identified for Cold Urticaria

 

 

Cold-induced urticaria is a unique inflammatory phenotype that is characterized by mast-cell degranulation and triggered by exposure to cold stimuli, a condition that can culminate in life-threatening anaphylaxis. There are various forms of cold urticaria that differ with respect to the mode of inheritance, ages at onset and resolution, and responses to a range of cold provocative testing. Although mast cells have been clearly implicated in the pathogenesis of cold urticaria, the processes leading to the degranulation of such cells are poorly understood.

 

Cold Urticaria is an allergy where hives (urticaria) or large red welts form on the skin after exposure to a cold stimulus. The welts are usually itchy and often the hands and feet will become itchy and swollen as well. Hives vary in size from about the size of a pencil eraser (7 mm diam.) to as big as a fifty cent piece (27 mm diam.) or larger. The disease is classified as chronic when hives appear for longer than 6 weeks, though their course is often unpredictable. This disorder, or perhaps two disorders with the same clinical manifestations, can be inherited (familial cold urticaria) or acquired (primary acquired cold urticaria). The acquired form is most likely to occur between ages 18–25.

 

Investigators at the National Institutes of Health have identified a genetic mutation in three unrelated families that causes cold urticaria. The study, published online in the New England Journal of Medicine (11 January 2012), was led by Joshua Milner, M.D., in the Laboratory of Allergic Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), and Daniel Kastner, M.D., Ph.D., scientific director at the National Human Genome Research Institute (NHGRI). The mutation discovered occurs in a gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in the activation of immune cells. The investigators have named the condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID.

 

The NIH study involved 29 people from three separate families. Blood sample analysis revealed that many patients produced antibodies to their own cells and tissues (autoantibodies), making them more susceptible to developing autoimmune disease. More than half had a history of recurrent infections, and laboratory tests revealed that most had low levels of infection-fighting antibodies and low numbers and reduced activity of circulating immune B cells – all symptoms of immune deficiency disease. In three cases, patients had common variable immunodeficiency, a disease that requires frequent intravenous infusions of immune globulin to prevent severe infections. Seven patients suffered from granulomas, inflamed masses of tissue, which formed on their fingers, ears, nose and other parts of their skin.

 

The NIAID investigators teamed up with gene hunting experts in Dr. Kastner’s laboratory and found the PLCG2 mutation after performing gene analysis and DNA sequencing studies. The mutation caused the PLCG2 enzyme to function without shutting off. Despite the fact that the enzyme was constantly turned on, immune cells ignored its signaling and did not activate normally.

 

The authors then performed a series of laboratory experiments to understand how the PLCG2 mutation affects B cells and mast cells, immune cells that contain histamine and other chemicals that are released during an allergic response. Patients’ B cells containing the mutated gene fail to turn on normally, leading to their inability to produce antibody, but also an inability to sense when they are producing autoantibodies. Laboratory-developed mast cells containing the mutated gene released chemicals on exposure to cool temperatures, which could explain why the patients developed cold-induced hives.

 

According to the investigators, their findings suggest that inhibiting PLCG2 activity could be a therapeutic strategy to treat cold-induced hives, autoimmunity and immune deficiency in people with PLAID, but more studies are needed. The study findings also suggest that people previously diagnosed with common variable immunodeficiency disease or with granulomatous diseases could have a PLCG2 gene mutation. Further study is needed to understand PLAID and how mutations in PLCG2 could contribute to other allergic and immunologic disorders.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.

 

 

FDA Completes Work on Three Drug User Fee Programs

 

 

Under a user fee program, industry agrees to pay fees to help fund a portion of the FDA’s drug review activities while the FDA agrees to overall performance goals such as reviewing a certain percentage of applications within a particular time frame.

 

The FDA has completed its recommendations for three user fee programs that will help speed safe and effective drugs and lower-cost generic drug and biosimilar biological products to patients. The recommendations were transmitted to Congress today by Health and Human Services Secretary Kathleen Sebelius. The programs include the fifth authorization of the Prescription Drug User Fee Act (PDUFA), and new user fee programs for human generic drugs and biosimilar biological products.

 

PDUFA was created by Congress in 1992 and must be reauthorized every five years. The current program, known as PDUFA IV, will expire on Sept. 30, 2012, unless reauthorized by Congress. FDA’s recommendations for PDUFA V were developed in consultation both with drug industry representatives and with patient and consumer advocates.

 

Under the recommendations, fees paid by industry would support continued timely review of critical prescription drugs, as well as advance the development of drugs for rare diseases, provide for enhanced communication with small or emerging companies, increase the use of standardized electronic data to improve quality and efficiency, and foster the use of new clinical endpoints that improve drug development times and help address unmet medical needs.

 

The proposed new Generic Drug User Fee program would provide the FDA with needed funding at a time when generic drug applications are on the rise. Generic drug user fees would help ensure consumers timely access to safe, high-quality and effective generic drugs, which account for two-thirds of all prescriptions dispensed in the U.S.

 

The FDA receives 800 to 900 new generic-drug-related applications annually. These applications are increasingly complex and frequently involve products manufactured outside of the U.S. In exchange for fees on facilities and product applications, the proposal includes performance metrics such as review timeframes and a commitment to achieve parity between surveillance inspections of foreign and domestic establishments by the 2017 fiscal year. As a result, FDA expects that the proposal would effectively eliminate the review backlog and significantly reduce review times.

 

A biosimilar is a biological product that is highly similar to a U.S.-licensed reference biological product notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product. The proposed Biosimilar and Interchangeable Products User Fee program is intended for products approved under a new abbreviated approval pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological product. The Affordable Care Act of 2010 contains a subtitle called the Biologics Price Competition and Innovation Act (BPCI) of 2009, which established this pathway.

 

Prior to it becoming law, competition in the biologic drug market was stifled. Enactment of BPCI will spark the development of a new segment of the industry, where companies will be able to develop alternative products. This will help spur innovation, improve consumer choice and drive down costs.

 

The recommended user fee program for biosimilars includes fees for products in development to generate revenue in the near-term and to provide FDA with the resources needed to support development-phase meetings with sponsors of biosimilar biological product candidates.