The frequency of photosensitizing drug dispensings in Austria and Germany: a correlation with their photosensitizing potential based on published literature.

BACKGROUND:Drug-induced photosensitivity refers to the development of cutaneous adverse events due to interaction between a pharmaceutical compound and sunlight. Although photosensitivity is a very commonly listed side-effect of systemic drugs, reliable data on its actual incidence are lacking so far. OBJECTIVES:A possible approach to evaluate the real-life extent of drug-induced photosensitivity would be an analysis of the frequency of exposure to a given photosensitizing drug combined with an indicator of its photosensitizing potential. This could serve as a basis for developing a pharmaceutical 'heatmap' of photosensitivity. METHODS:The present study investigated the number of reimbursed dispensed packages of potentially photosensitizing drugs in Germany (DE) and Austria (AT) between 2010 and 2017 based on nationwide health insurance-based databases. In addition, an indicator for the photosensitizing potential was established for each drug based on the number of reports on photosensitivity in the literature. RESULTS:This analysis includes means of 632 826 944 (+/-14 894 918) drug dispensings per year in DE and 113 270 754 (+/-1 964 690) in AT. Out of these, the mean percentage of drugs that enlist photosensitivity as a potential side-effect was 49.5% (±0.7) in DE and 48.2% (±1.2) in AT. When plotting the number of reimbursed dispensed packages vs. the number of reports on photosensitivity, two categories of drugs show high numbers for both parameters, that is diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS:Diuretics and NSAIDs appear to be responsible for the greatest part of exposure to photosensitizing drugs with potential implication on public health

Tradition and Innovation in Classical Sociology: Tenth Anniversary Report of JCS

Perhaps the very idea of ‘classical sociology’ is a contradiction in terms; sociology was originally that social science peculiarly concerned with the study of the processes of modernization and the condition of modernity, that is, with the critical examination of ‘post-traditional’ developments and hence ‘post-classical’ forms of social organization. Its concerns have broadened subsequently, but the focus of sociology remains on the exploration of the nature and development of social structure and social action in the post-traditional world. In the nineteenth century, sociologists invented new concepts and experimented with new methods to study the emergence of unprecedented social phenomena and the rise of a type of society that was variously called ‘modern society’, ‘industrial society’, and ‘capitalist society’. In the twentieth century, there was a further elaboration of key sociological concepts, and it became increasingly popular to proclaim the rise of yet another form of society, described as ‘post-industrial society’, ‘late modern society’, ‘post-modern society’, or ‘network society’. In the current century, the idea of globalization has swept everything before it, leading to the notion that ‘society’ has now been replaced by flows and networks of people, objects, and ideas. With the transition from traditional to modern societies, the integrative power of Gemeinschaft began to compete with the systemic power of Gesellschaft; with the transition from modern to late modern societies, the local horizons of our Lebenswelt appear to be increasingly shaped by the deterritorialized networks of the Weltgesellschaft. If we are ‘post-traditional’, surely we are also ‘post-classical’. It is hardly surprising, therefore, that many contemporary sociologists have some difficulty accepting the very idea of classical sociology

Nanoscale spin rectifiers controlled by the Stark effect

The control of orbital and spin state of single electrons is a key ingredient for quantum information processing, novel detection schemes, and, more generally, is of much relevance for spintronics. Coulomb and spin blockade (SB) in double quantum dots (DQDs) enable advanced single-spin operations that would be available even for room-temperature applications for sufficiently small devices. To date, however, spin operations in DQDs were observed at sub-Kelvin temperatures, a key reason being that scaling a DQD system while retaining an independent field-effect control on the individual dots is very challenging. Here we show that quantum-confined Stark effect allows an independent addressing of two dots only 5 nm apart with no need for aligned nanometer-size local gating. We thus demonstrate a scalable method to fully control a DQD device, regardless of its physical size. In the present implementation we show InAs/InP nanowire (NW) DQDs that display an experimentally detectable SB up to 10 K. We also report and discuss an unexpected re-entrant SB lifting as a function magnetic-field intensity

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Background Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease dipyridamole (ASA–ERDP) versus clopidogrel. Methods In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. Results A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). Conclusions The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.

Non-invasive characterization of transverse beam emittance of electrons from a laser-plasma wakefield accelerator in the bubble regime using betatron x-ray radiation

We propose and use a technique to measure the transverse emittance of a laser-wakefield accelerated beam of relativistic electrons. The technique is based on the simultaneous measurements of the electron beam divergence given by $v_{\perp}/v_{\parallel}$, the measured longitudinal spectrum $\gamma_\parallel$ and the transverse electron bunch size in the bubble $r_{\perp}$. The latter is obtained via the measurement of the source size of the x-rays emitted by the accelerating electron bunch in the bubble. We measure a \textit{normalised} RMS beam transverse emittance $<0.5$ $\pi$ mm$\:$mrad as an upper limit for a spatially gaussian, spectrally quasi-monoenergetic electron beam with 230 MeV energy in agreement with numerical modeling and analytic theory in the bubble regime.Comment: 4 pages, 5 figure

STRP Screening Sets for the human genome at 5 cM density

BACKGROUND: Short tandem repeat polymorphisms (STRPs) are powerful tools for gene mapping and other applications. A STRP genome scan of 10 cM is usually adequate for mapping single gene disorders. However mapping studies involving genetically complex disorders and especially association (linkage disequilibrium) often require higher STRP density. RESULTS: We report the development of two separate 10 cM human STRP Screening Sets (Sets 12 and 52) which span all chromosomes. When combined, the two Sets contain a total of 782 STRPs, with average STRP spacing of 4.8 cM, average heterozygosity of 0.72, and total sex-average coverage of 3535 cM. The current Sets are comprised almost entirely of STRPs based on tri- and tetranucleotide repeats. We also report correction of primer sequences for many STRPs used in previous Screening Sets. Detailed information for the new Screening Sets is available from our web site: . CONCLUSION: Our new human STRP Screening Sets will improve the quality and cost effectiveness of genotyping for gene mapping and other applications

Mechanism of action of probiotics

The modern diet doesn't provide the required amount of beneficial bacteria. Maintenance of a proper microbial ecology in the host is the main criteria to be met for a healthy growth. Probiotics are one such alternative that are supplemented to the host where by and large species of Lactobacillus, Bifidobacterium and Saccharomyces are considered as main probiotics. The field of probiotics has made stupendous strides though there is no major break through in the identification of their mechanism of action. They exert their activity primarily by strengthening the intestinal barrier and immunomodulation. The main objective of the study was to provide a deep insight into the effect of probiotics against the diseases, their applications and proposed mechanism of action

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation