Predicting patterns of long-term adaptation and extinction with population genetics.

Population genetics struggles to model extinction; standard models track the relative rather than absolute fitness of genotypes, while the exceptions describe only the short-term transition from imminent doom to evolutionary rescue. But extinction can result from failure to adapt not only to catastrophes, but also to a backlog of environmental challenges. We model long-term adaptation to long series of small challenges, where fitter populations reach higher population sizes. The population's long-term fitness dynamic is well approximated by a simple stochastic Markov chain model. Long-term persistence occurs when the rate of adaptation exceeds the rate of environmental deterioration for some genotypes. Long-term persistence times are consistent with typical fossil species persistence times of several million years. Immediately preceding extinction, fitness declines rapidly, appearing as though a catastrophe disrupted a stably established population, even though gradual evolutionary processes are responsible. New populations go through an establishment phase where, despite being demographically viable, their extinction risk is elevated. Should the population survive long enough, extinction risk later becomes constant over time.

Validation of the quality of ultrasound imaging and competence (QUICk) score as an objective assessment tool for the FAST examination.

BACKGROUND: The Focused Assessment with Sonography for Trauma (FAST) examination has become a valuable tool in trauma resuscitation. Despite the widespread use of FAST training among traumatologists, no evidence-based guidelines exist to support optimal training requirements or to provide quantitative objective assessments of imaging capabilities. Both Task-Specific Checklist (TSC) and Global Rating Scale (GRS) have been validated as objective skill assessment tools; we developed both types of scoring checklist and assessed them for construct validity with the FAST examination. METHODS: Two scoring checklists, collectively termed the Quality of Ultrasound Imaging and Competence (QUICk) Score, were developed and subjected to a modified Delphi consensus process. Two cohorts of 12 novice and 12 expert sonographers performed the FAST examination and were evaluated by two experts according to the QUICk model. Total scores as well as anatomic subsets were compared via comparison of means, and logistic regression modeling was used to determine sensitivity and specificity. RESULTS: Experts achieved significantly higher total scores than novices on both scoring systems (17.2 vs. 11.1 of 24, p < 0.01 TSC, 29.8 vs. 18.4 of 40, p < 0.01 GRS). Sensitivity (85.7% TSC, 92.9% GRS) and specificity (75.0% TSC, 91.7% GRS) as well as area under the receiver operating characteristic curve (89.9% TSC, 97.6% GRS) were consistent with a highly discriminant tool. CONCLUSION: The QUICk Score is the first validated objective tool for assessment of the quality of FAST examination imaging. Use of this tool may be instrumental in developing an evidence-based minimum-performance standard and for assessing quality-improvement modifications in FAST examination training.

Assessment of the biological effects of welding fumes emitted from metal inert gas welding processes of aluminium and zinc-plated materials in humans.

The aim of this study was to investigate biological effects and potential health risks due to two different metal-inert-gas (MIG) welding fumes (MIG welding of aluminium and MIG soldering of zinc coated steel) in healthy humans. In a threefold cross-over design study 12 male subjects were exposed to three different exposure scenarios. Exposures were performed under controlled conditions in the Aachener Workplace Simulation Laboratory (AWSL). On three different days the subjects were either exposed to filtered ambient air, to welding fumes from MIG welding of aluminium, or to fumes from MIG soldering of zinc coated materials. Exposure was performed for 6 h and the average fume concentration was 2.5 mg m(-3). Before, directly after, 1 day after, and 7 days after exposure spirometric and impulse oscillometric measurements were performed, exhaled breath condensate (EBC) was collected and blood samples were taken and analyzed for inflammatory markers. During MIG welding of aluminium high ozone concentrations (up to 250 µg m(-3)) were observed, whereas ozone was negligible for MIG soldering. For MIG soldering, concentrations of high-sensitivity CRP (hsCRP) and factor VIII were significantly increased but remained mostly within the normal range. The concentration of neutrophils increased in tendency. For MIG welding of aluminium, the lung function showed significant decreases in Peak Expiratory Flow (PEF) and Mean Expiratory Flow at 75% vital capacity (MEF 75) 7 days after exposure. The concentration of ristocetin cofactor was increased. The observed increase of hsCRP during MIG-soldering can be understood as an indicator for asymptomatic systemic inflammation probably due to zinc (zinc concentration 1.5 mg m(-3)). The change in lung function observed after MIG welding of aluminium may be attributed to ozone inhalation, although the late response (7 days after exposure) is surprising.

Experience with protein A-immunoadsorption in treatment-resistant adult immune thrombocytopenic purpura.

Extracorporeal immunoadsorption of plasma to remove IgG and circulating immune complexes (CIC) was evaluated as a therapy for adults with treatment-resistant immune thrombocytopenic purpura (ITP). Seventy-two patients with initial platelet counts less than 50,000/microL who had failed at least two other therapies were studied. They received an average of six treatments of 0.25 to 2.0 L plasma per procedure over a 2- to 3-week period using columns of staphylococcal protein A-silica (PROSORBA immunoadsorption treatment columns; IMRE Corp, Seattle, WA). The treatments caused an acute increase in the platelet count to greater than 100,000/microL in 18 patients and to 50,000 to 100,000/microL in 15 patients. The median time to response was 2 weeks. Responses were transient (less than 1 month duration) in seven of those patients (10%), but no additional relapses were reported over a follow-up period of up to 26 months (mean of 8 months). Clinical responses were associated with significant decreases in specific serum platelet autoantibodies (including anti-glycoprotein IIb/IIIa), platelet-associated Ig, and CIC. Thirty percent of treatments were associated with transient mild to moderate side effects usually presenting as a hypersensitivity-type reaction. Continued administration of failed therapies for ITP, which always included low-dose corticosteroids (less than or equal to 30 mg/d), had no demonstrable influence on the effectiveness of immunoadsorption treatment but did depress the incidence and severity of side effects. The degree of effectiveness of protein A immunoadsorption therapy in patients with treatment-resistant ITP is promising and further controlled studies in this patient population are warranted.

Rationale and strategies for chemoprevention of cancer in humans.

The potential for chemical intervention (chemoprevention) as a means of halting or delaying the process of carcinogenesis is assessed as a strategy for reducing the incidence of human cancer. The process of carcinogenesis is dissected into its constituent steps, thereby exposing sites for intervention. These sites are then critically discussed with regard to the existence of chemicals active at these sites using data gained from the laboratory and from epidemiological studies, intrinsic problems or advantages associated with intervention at specific sites in the carcinogenic process, and practical aspects of intervention in humans. The design and potential long-term positive and negative consequences of chemoprevention clinical trials are critically discussed, with the objective of exposing the major differences that exist between clinical trials in cancer chemoprevention and those in cancer chemotherapy. Results of completed prevention trials and details of ongoing trials are presented and discussed. Based on the laboratory, epidemiological, and clinical evidence presented, it is concluded that chemoprevention offers excellent prospects as a means of reducing cancer incidence. Among currently available agents, the retinoids possess the best combination of properties. However, much more research is needed to optimize drugs and protocols and to develop interim end points for assessing response. The authors finally caution that overambitious claims for the prospects for chemoprevention may lead to reduced emphasis on the need for changes in life-style (principally in smoking and diet) that are viewed as having the greatest potential for reducing cancer incidence.