Science Weekly: Richard Dawkins, David Attenborough and algae

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Science Weekly: Algae make environmentally friendly fuel; science funding cuts; plus, Richard Dawkins and David Attenborough in conversation

Monitoring Reports Integrated With Target e*CRF®

As part of Target Health’s commitment to the “Paperless Clinical Trials,“ within one month, all of Target Health’s EDC applications will be fully integrated with monitoring reports. We will be able to configure any company’s monitoring reports, as well as import information directly from Target e*CRF into the monitoring reports.  It will be crystal clear what data have been reviewed at each monitoring visit and the monitoring report will be fully transparent to Sponsors and Regulators.

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. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

Neurons: Faster Than Thought and Able to Multiply

Researchers have discovered what exactly happens right before a nerve cell emits a pulse: computer simulations reveal that the process is similar to a Japanese garden “shishi odoshi“ – a reed of bamboo, open on one end, which tilts when a certain amount of rainwater has accumulated inside. (Credit: Image courtesy of Bernstein Center for Computational Neuroscience)

 

Using 1) ___ simulations of brain-like networks, researchers from Germany and Japan have discovered why nerve cells transmit information through small electrical pulses. The process not only allows the brain to process information much 2) ___ than previously thought, but also single neurons are already able to multiply, opening the door to more complex forms of computing. When nerve cells communicate with each other, they do so through 3) ___ pulses – so-called action potentials. For decades, the accepted idea was that they simply sum up the tiny potentials generated by the incoming pulses and emit an action potential themselves when a threshold is reached. For the first time, Moritz Helias and Markus Diesmann from the RIKEN Brain Science Institute (Japan) and Moritz Deger and Stefan Rotter from the Bernstein Center Freiburg (Germany) now explain what exactly happens right before a nerve cell emits a pulse. The research appears online in PLoS Computational Biology, published by the Public Library of Science.

The scientists made their discovery through simulations on high performance computers, but found the perfect image for their research subject in the tranquility of Japanese gardens: the “shishi odoshi“, a reed of 4) ___, open on one end, which tilts when a certain amount of rainwater has accumulated inside. Just as one tiny raindrop ultimately causes the device to tilt and spill the water, one small electric 5) ___ will cause a neuron to produce an impulse of its own.

Although the 6) ___ in the brain would correspond to a huge forest of bamboo, and the activity sent between them to a thunderstorm of raindrops, Helias and colleagues found a precise mathematical theory that needs to consider the detailed course of events only at the time when a neuron is about to release an action 7) ___. Not only does this theory explain why nerve cells process 8) ___ much faster than previously thought. It also became clear that neurons do more than just add up pulses: In the decisive moments, they actually multiply. The availability of this mathematical operation, write the scientists, finally explains how the 9) ___ is able to execute complex computations. These insights in the basic processes of the brain will in turn inspire more powerful processor architectures in the future.

ANSWERS: 1) computer; 2) faster; 3) electrical; 4) bamboo; 5) pulse; 6) neurons; 7) potential; 8) information; 9) brain

The Health of Johannes Brahms

 

An article in the medical journal Chest reports that composer Johannes Brahms was overweight, stored fat primarily in his upper body, and made horrible sounds when he slept. These are signs of sleep apnea, a condition that causes a person to stop breathing for more than 30 seconds many times each night.

Brahms once remarked: “If there is anyone here I have not offended, I apologize.“ Sleep apnea makes a person irritable. He died of pancreatic cancer, which is associated with diabetes and upper body obesity, common findings in sleep apnea. He never married probably because of the terrible sounds he made during sleep. Baritone George Henschel reported that Brahms’ snoring drove him from a room they shared on a concert tour. Brahms drank heavily and used to fall asleep in his theater box. His neck was so large that he couldn’t wear ties. He was commonly irritable and depressed, probably because of lack of oxygen to his brain, but he gave us the most famous lullaby in the world.

ONCOLOGY

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Adjuvant Chemotherapy With Fluorouracil Plus Folinic Acid vs. Gemcitabine Following Pancreatic Cancer Resection

Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer. As a result, a study published in the Journal of the American Medical Association (2010;304:1073-1081), was performed to determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer.

The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, was an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Australasia is a region of Oceania: Australia, New Zealand, the island of New Guinea, and neighboring islands in the Pacific Ocean. Included in ESPAC-3 version 2 were 1,088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection. Patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up.

For the study, patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m2, intravenous bolus injection, followed by fluorouracil, 425 mg/m2 intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m2 intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months. The primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life.

The final analysis was carried out on an intention-to-treat basis after there were 753 deaths. Median survival was 23.0 months for patients treated with fluorouracil plus folinic acid and 23.6 months for those treated with gemcitabine. Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups.

According to the authors, compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer.

Anti-Apolipoprotein A-1 IgG Predicts Major Cardiovascular Events in Patients with Rheumatoid Arthritis

According to an article published in Arthritis & Rheumatism (2010:62:2640-2650), a study was performed to determine whether anti-apolipoprotein A-1 (anti-Apo A-1) IgG are associated with major cardiovascular events in patients with rheumatoid arthritis (RA).

The study measured anti-Apo A-1 IgG levels and the concentrations of cytokines, oxidized low-density lipoprotein (LDL), and matrix metalloproteinase 1 (MMP-1) MMP-2, MMP-3, and MMP-9 in sera from 133 patients with RA who did not have cardiovascular disease at baseline. These patients were then longitudinally followed over a median period of 9 years. A major cardiovascular event was defined as a fatal or nonfatal stroke or acute coronary syndrome. The proinflammatory effects of anti-Apo A-1 IgG were assessed on human macrophages in vitro.

Results showed that the overall incidence of major cardiovascular events was 15% (20 of 133 patients). At baseline, anti-Apo A-1 IgG positivity was 17% and was associated with a higher incidence of major cardiovascular events (adjusted hazard ratio 4.2). Patients who experienced a subsequent major cardiovascular event had higher circulating levels of anti-Apo A-1 IgG at baseline compared with those who did not have a major cardiovascular event. Receiver operating curve analysis showed that anti-Apo A-1 IgG was the strongest of all tested biomarkers for the prediction of a subsequent major cardiovascular event, with an area under the curve value of 0.73 (P = 0.0008). At the predefined and previously validated cutoff levels, the specificity and sensitivity of anti-Apo A-1 IgG to predict major cardiovascular events were 50% and 90%, respectively. Anti-Apo A-1 IgG positivity was associated with higher median circulating levels of interleukin-8 (IL-8), oxidized LDL, and MMP-9 and higher proMMP-9 activity as assessed by zymography. On human macrophages, anti-Apo A-1 IgG induced a significant dose-dependent increase in IL-8 and MMP-9 levels and proMMP-9 activity.

According to the authors, anti-Apo A-1 IgG is an independent predictor of major cardiovascular events in RA, possibly by affecting vulnerability to atherosclerotic plaque.

Low-Carbohydrate Diets and All-Cause and Cause-Specific Mortality

Data on the long-term association between low-carbohydrate diets and mortality are sparse. As a result, a study published in the Annals of Internal Medicine (2010;153:289-298), was performed to examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men.

The investigation was a prospective cohort study of women and men, who were followed from 1980 (women) or 1986 (men) until 2006, in the Nurses’ Health Study and Health Professionals’ Follow-up Study. Study participants included 85,168 women (aged 34 to 59 years at baseline) and 44,548 men (aged 40 to 75 years at baseline) without heart disease, cancer, or diabetes. Low-carbohydrate diets were either animal-based (emphasizing animal sources of fat and protein) or vegetable-based (emphasizing vegetable sources of fat and protein), were computed from several validated food-frequency questionnaires assessed during follow-up.

The study documented 12,555 deaths (2,458 cardiovascular-related and 5,780 cancer-related) in women and 8,678 deaths (2,746 cardiovascular-related and 2,960 cancer-related) in men. The overall low-carbohydrate score was associated with a modest increase in overall mortality in a pooled analysis (hazard ratio [HR], 1.12; P for trend = 0.136). The animal low-carbohydrate score was associated with higher all-cause mortality (pooled HR, 1.23; P for trend = 0.051), cardiovascular mortality (corresponding HR, 1.14; P for trend = 0.029), and cancer mortality (corresponding HR, 1.28; P for trend = 0.089). In contrast, a higher vegetable low-carbohydrate score was associated with lower all-cause mortality (HR, 0.80; P for trend < 0.001) and cardiovascular mortality (HR, 0.77; P for trend < 0.001).

According to the authors, low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women, whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates.

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

FDA Launches New Organizational Performance Management System

The FDA has launched an innovative performance management system designed to advance the President’s commitment to transparency, public participation, and collaboration in the work of government. The system, called FDA-TRACK, will monitor more than 100 FDA program offices through data from key performance measures established each year. That data will be gathered monthly, analyzed and presented each quarter to FDA senior leadership. Importantly, the public will be able to track this data and the agency’s progress through the FDA-TRACK website.

FDA-TRACK is designed to be informative, encourage accountability among the people who work at the FDA, and make that work more transparent. It gives managers and employees a new way to measure their effectiveness in meeting goals to protect the public health and provides a way for the public to monitor agency activities.

Adapted from several successful state and local performance management models, FDA-TRACK hopes to set the standard for open government at the federal level. The system monitors performance indicators in four categories:

Common Measures – Agency-wide measures applicable to each of more than 100 program offices and may focus on the agency’s most recent priorities. Example: Increase the total number of employees who are trained in the Incident Command System, which helps the agency respond to emergencies.

Key Center Director Measures – Center-specific measures that are applicable to each Center and are central to the Center’s priorities and strategic goals. Example: Increase the FDA’s technical guidance by increasing the number of technical publications drafted, which enables the Center to better prepare industry and consumers.

Program Measures – Program office-specific measures that are applicable to the office and reflect work important to the public and to the FDA’s mission. Example: Monitor the percentage of 510(k) decisions meeting the 90-day Medical Device User Fee Act goal during a specific time period.

Key Projects – Program office-specific projects that are applicable to the office and important to the mission and objectives of the office. Performance for Key Projects is measured through achievement of the stated milestones within the project’s plan. Example: The development of a new risk-based approach for evaluating safety, effectiveness, and quality of new animal drugs.

For more information about our expertise in Medical Affairs, contact Dr. Mark Horn. For Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

Target Health (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND (eCTD), IDE, NDA (eCTD), BLA (eCTD), PMA (eCopy) and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, EDC utilizing Target e*CRF®, and Medical Writing.

Target Health has developed a full suite of eClinical Trial software including:

1) Target e*CRF® (EDC plus randomization and batch edit checks)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target Newsletter®

6) Target e*CTR™ (electronic medical record for clinical trials).

Target Health’s Pharmaceutical Advisory Dream Team assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.