Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG Task Force.

The clinical outcome of sarcoidosis is quite variable. Several scoring systems have been used to assess the level of disease and clinical outcome. The definition of clinical phenotypes has become an important goal as genetic studies have identified distinct genotypes associated with different clinical phenotypes. In addition, treatment strategies have been developed for patients with resolving versus non resolving disease. A task force was established by the World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) to define clinical phenotypes of the disease based on the clinical outcome status (COS). The committee chose to examine patients five years after diagnosis to determine the COS. Several features of the disease were incorporated into the final nine categories of the disease. These included the current or past need for systemic therapy, the resolution of the disease, and current status of the condition. Sarcoidosis patients who were African American or older were likely to have a higher COS, indicating more chronic disease. The COS may be useful in future studies of sarcoidosis.

XRISE-M: X-radiography facility for solidification and diffusion studies of alloys aboard sounding rockets.

A compact fully protected microfocus X-radiography facility (XRISE-M) is presented for the study of microstructure evolution during the solidification of thin liquid alloy samples and chemical diffusion in liquid binary alloys in situ and in real-time aboard a sounding rocket. XRISE-M presently enables the simultaneous processing of either two near-isothermal solidification furnaces or a combination of a linear-shear cell diffusion furnace and a near-isothermal solidification furnace. For optimal detector calibration shortly before flight, the furnaces can be rotated around the central beam axis and calibration images can be recorded. The facility allows preheating the samples into the liquid state prior to lift-off without leakage during the ascent phase at accelerations of up to 27 g. Macrosegregation on remelting of thin metal samples for microstructure evolution investigations is prevented by an inclinable furnace metric. The use of ion-getter pumps for vacuum generation enables us to exploit the entire available time of reduced gravity for image recording and data acquisition. With the device and currently available sample environments, microstructure formation upon solidification and chemical diffusion under purely diffusive conditions in alloys can be investigated. The facility can be used equally for other investigations such as granular matter dynamics or metal foaming, provided that suitable experiment inserts are developed in the future.

Epidemiology. Tracking the human fallout from 'mad cow disease'.

A task force here has been studying cases of variant Creutzfeldt-Jakob disease (vCJD), an incurable malady of the brain and nervous system that has been linked to eating beef or other products from cattle infected with bovine spongiform encephalopathy or "mad cow disease." The team's goal is to find out just how the patients got infected and how many of them there may ultimately be. The number of confirmed or probable vCJD cases in the United Kingdom is still relatively small--a total of 80 as Science went to press--and recent estimates of the number of potential cases are lower than was once feared. Yet the task force's own recent results show that the incidence of vCJD is rising, and researchers remain determined to try to solve the riddles posed by vCJD.

French science. New CNRS chief hopes to deliver on science.

For years, French research ministers have prodded the nation's scientists to make their research pay off for society. But that message has been slow to sink in. Last week, the government gave the assignment to a biologist who has done exactly that, but who believes that the carrot works better than the stick.

Emerging diseases. Hunt for mad cow in sheep reassuring.

Experts on brain-riddling spongiform diseases have grown steadily more uneasy over signs that so-called mad cow disease or bovine spongiform encephalopathy (BSE), which is linked to a lethal human illness, may be lurking in sheep. A study in the 10 August issue of Nature now offers evidence that BSE is not rampant in sheep after all, although scientists are far from ready to let their guard down.

European science. Bug Bastille to open under new management.

In the next few weeks, Europe's most advanced high-security pathogen lab is expected to open for business in the southern French city of Lyons, but the long-anticipated debut of this "hot" lab is not turning out to be a joyous occasion for some of those involved. Last week, the Marcel Mérieux Foundation, which paid for the lab's construction, announced that the Pasteur Institute will take over its "scientific direction" and gave Pasteur the authority to name the lab's director. The leading candidate is a Pasteur scientist, which would leave the lab's current director out in the cold.

Virology. Evolution on life's fringes.

Earlier this summer, two dozen scientists gathered here to take another crack at the question of viral origins and evolution. Fresh evidence that viruses have existed for billions of years suggests that they were on hand when the first cells arose. That has scientists wondering what role these stripped-down microbes played in the evolution of life.

Research funding. Windfall for French biomedical agency.

Researchers at France's giant biomedical research agency, INSERM, are rejoicing over a 16% hike in the organization's research budget for 2001. The windfall, announced by INSERM director-general Claude Griscelli last week, is the biggest such increase since 1983.

Malaria. Can WHO roll back malaria?

In October 1998, World Health Organization Director-General Gro Harlem Brundtland announced Roll Back Malaria, a multiagency crusade that aims to cut malaria mortality in half over the next 10 years. Brundtland might just be the one to pull it off, say numerous public health experts, although some researchers question whether the goal is realistic.

EUROPEAN SCIENCE: Pathogens Lab Chief Stripped of Duties.

Europe's most advanced high-security pathogen lab has claimed its first human casualty--and it hasn't even opened for business. On 28 June, the Marcel Mérieux Foundation, which funded the construction of the $8 million facility in Lyons, banned lab director Susan Fisher-Hoch from the premises and launched legal proceedings to dismiss her. Fisher-Hoch's most egregious offense, it appears, was speaking with the press.

EUROPEAN SCIENCE POLICY: France Rebels Against Gene-Patenting Law.

France is on a collision course with the European Union over an E.U. directive that many researchers believe would allow raw DNA sequences of human genes to be patented. On 7 June, French justice minister Elisabeth Guigou told the National Assembly that the directive--which must be enacted by each of the 15 E.U. member nations by 30 July--contradicts French bioethics laws, which forbid the patenting of any part of the human body. If France maintains its defiance, it could be fined up to $600,000 daily for each day it refuses to adopt the directive.

SPONGIFORM DISEASE: Experts Downplay New vCJD Fears.

The chilling scenario of getting "mad cow disease" from eating products of other animals besides just cows was splashed across the mainstream British press last week based on a report from a leading U.K. lab that prions--abnormal proteins linked to bovine spongiform encephalopathy and its human form, variant Creutzfeldt-Jakob disease--can jump from one species to another more easily than previously believed. Although some experts say the findings raise concern about a threat to human health, others decry the media frenzy and contend that the new research adds little to what is known about the mysterious, fatal diseases.

ARCHAEOLOGY: Paintings in Italian Cave May Be Oldest Yet.

Stone slabs bearing images of an animal and a half-human, half-beast figure were uncovered during excavations by an Italian team at the Fumane Cave northwest of Verona. The images are believed to be at least as ancient as some found in the Grotte Chauvet in southern France--the current record holder at 32,000 years--and possibly even older. More important, cave art experts say, the new paintings bolster other evidence that humans engaged in sophisticated symbolic expression much earlier than once thought.

Marijuana use among urban adults.

A relatively high proportion of young adults in San Francisco have used marijuana one or more times. The proportion in this age group who have used marijuana is as great among nonstudents as among students.

ARTEC-A furnace module for directional solidification and quenching experiments in microgravity.

A new experimental design for directional solidification experiments with high cooling rates under microgravity conditions is presented. The aerogel-based furnace module ARTEC (AeRogel TEchnology for Cast alloys) developed at DLR extends the earlier presented sounding rocket facility ARTEX by enabling a transition from low to high solidification velocities and a simultaneous operation of five independent furnaces in the same sounding rocket module. The furnaces for directional solidification are equipped with thermally insulating aerogels as a crucible material. Their optical transparency allows the control of the solidification parameters (velocity and temperature gradient) with optical methods in the lab. In ARTEC, a drastically increased solidification velocity is achieved by contacting the sample with a movable cooling-rod during processing. Therefore, a better theoretical understanding of the influence of a sudden change in solidification velocity on microstructure formation is obtained. Carrying out experiments in microgravity gives access to purely diffusive solidification conditions. Hence, convection free-growth can be compared with growth subject to natural (earth) and/or forced-convection (earth and space). Furthermore, alloys with high density differences in their alloy components and, hence, also between the primary solidifying phase and the surrounding liquid can be studied without the negative influence of fluid-flow or macrosegregation being present.

Counting, analysing and reporting exacerbations of COPD in randomised controlled trials.

BACKGROUND: Clinical trials measure exacerbations of chronic obstructive pulmonary disease (COPD) inconsistently. A study was undertaken to determine if different methods for ascertaining and analysing COPD exacerbations lead to biased estimates of treatment effects. METHODS: Information on the methods used to count, analyse and report COPD exacerbation rates was abstracted from clinical trials of long-acting bronchodilators or long-acting bronchodilator/inhaled steroid combination products published between 2000 and 2006. Data from the Canadian Optimal Therapy of COPD Trial was used to illustrate how different analytical approaches can affect the estimate of exacerbation rates and their confidence intervals. RESULTS: 22 trials (17,156 patients) met the inclusion criteria and were reviewed. None of the trials adjudicated exacerbations or determined independence of events. 14/22 studies (64%) introduced selection bias by not analysing outcome data for subjects who prematurely stopped study medications. Only 31% of trials used time-weighted analyses to calculate the mean number of exacerbations/patient-year and only 15% accounted for between-subject variation. In the Canadian Optimal Therapy of COPD Trial the rate ratio for exacerbations/patient-year was 0.85 when all data were included in a time-weighted analysis, but was overestimated as 0.79 when data for those who prematurely stopped study medications were excluded and was further overestimated as 0.46 when a time-weighted analysis was not conducted; p values ranged from 0.03 to 0.24 depending on how exacerbations were determined and analysed. CONCLUSIONS: Clinical trials have used widely different methods to define and analyse COPD exacerbations and this can lead to biased estimates of treatment effects. Future trials should strive to include blinded adjudication and assessment of the independence of exacerbation events, and trials should report time-weighted intention-to-treat analyses with adjustments for between-subject variation in COPD exacerbations.

Automated end-to-end blood testing at the point-of-care: Integration of robotic phlebotomy with downstream sample processing.

Diagnostic blood testing is the most commonly performed clinical procedure in the world, and influences the majority of medical decisions made in hospital and laboratory settings. However, manual blood draw success rates are dependent on clinician skill and patient physiology, and results are generated almost exclusively in centralized labs from large-volume samples using labor-intensive analytical techniques. This paper presents a medical device that enables end-to-end blood testing by performing blood draws and providing diagnostic results in a fully automated fashion at the point-of-care. The system couples an image-guided venipuncture robot, developed to address the challenges of routine venous access, with a centrifuge-based blood analyzer to obtain quantitative measurements of hematology. We first demonstrate a white blood cell assay on the analyzer, using a blood mimicking fluid spiked with fluorescent microbeads, where the area of the packed bead layer is correlated with the bead concentration. Next we perform experiments to evaluate the pumping efficiency of the sample handling module. Finally, studies are conducted on the integrated device - from blood draw to analysis - using blood vessel phantoms to assess the accuracy and repeatability of the resulting white blood cell assay.

Treating acute exacerbations of chronic bronchitis and community-acquired pneumonia: how effective are respiratory fluoroquinolones?

OBJECTIVE: To provide family physicians with a review of evidence supporting fluoroquinolone therapy for defined patient populations with acute exacerbations of chronic bronchitis (AECB) and community-acquired pneumonia (CAP). QUALITY OF EVIDENCE: A MEDLINE search found surveillance studies, randomized controlled trials, outcome studies, and expert consensus opinion. Descriptions of patient populations for which fluoroquinolone therapy is recommended are based on level I and level III evidence. MAIN MESSAGE: A growing body of evidence supports fluoroquinolones as first-choice agents for treatment of AECB or CAP patients with comorbidity or a recent history of antibiotic use. Judicious and targeted therapy using fluoroquinolones among patients at risk of infections of the lower respiratory tract should contribute to improved clinical outcomes and broader health care savings. CONCLUSION: Current data show clinical utility and cost-effectiveness of fluoroquinolones in lower respiratory tract infections. The most recently issued AECB and CAP guidelines now recommend these antimicrobial agents as first-choice agents for specific patient populations.

Minor tranquilizers: clinical correlates of use in an urban population.

Rapid growth in the production and prescription of minor tranquilizers has stimulated increasing concern that we live in an "overmedicated" society. Data regarding drug use from a health survey in Oakland, Calif, show that (1) 20% took a minor tranquilizer or sedative during the previous year, 10% daily for a week or more; (2) use was related directly to the amount of distress and dysfunction, to psychologic more than to other types of disturbance, but not to situational stress alone; and (3) taking tranquilizers was only one aspect of a complex pattern of coping behaviors including the almost universal use of some medication, most often a "nonpsychotropic" type.

Hospital surveys of prescribing practices with psychotherapeutic drugs. A critical examination.

Hospital surveys of psychotherapeutic drug prescribing in the United States have been generally critical of the treatment practices of physicians and have been used to support claims that psychotherapeutic drugs are overprescribed and misused. This report examined several recent multihospital surveys of psychotherapeutic drug use and concludes that the surveys have failed to provide sufficient information to determine the appropriateness of treatment practices. The limitations of these surveys and the need to develop more adequate information about physician prescribing patterns are discussed.