Explore the vast range of titles available.

Background Epidemiological studies have demonstrated considerable differences in the use of coercive measures among psychiatric hospitals; however, the underlying reasons for these differences are largely unclear. We investigated to what extent these differences could be explained by institutional factors. Methods Four psychiatric hospitals with identical responsibilities within the mental health care system, but with different inpatient care organizations, participated in this prospective observational study. We included all patients admitted over a period of 24 months who were affected by mechanical restraint, seclusion, or compulsory medication. In addition to the patterns of coercive measures, we investigated the effect of each hospital on the frequency of compulsory medication and the cumulative duration of mechanical restraint and seclusion, using multivariate binary logistic regression. To compare the two outcomes between hospitals, odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated. Results Altogether, coercive measures were applied in 1542 cases, corresponding to an overall prevalence of 8%. The frequency and patterns of the modalities of coercive measures were different between hospitals, and the differences could be at least partially related to institutional characteristics. For the two hospitals that had no permanently locked wards, certain findings were particularly noticeable. In one of these hospitals, the probability of receiving compulsory medication was significantly higher compared with the other institutions (OR 1.9, CI 1.1–3.0 for patients < 65 years; OR 8.0, CI 3.1–20.7 for patients ≥65 years); in the other hospital, in patients younger than 65 years, the cumulative duration of restraint and seclusion was significantly longer compared with the other institutions (OR 2.6, CI 1.7–3.9). Conclusions The findings are compatible with the hypothesis that more open settings are associated with a more extensive use of coercion. However, due to numerous influencing factors, these results should be interpreted with caution. In view of the relevance of this issue, further research is needed for a deeper understanding of the reasons underlying the differences among hospitals.

The Small Quantum Systems instrument is one of the six operating instruments of the European XFEL, dedicated to the atomic, molecular and cluster physics communities. The instrument started its user operation at the end of 2018 after a commissioning phase. The design and characterization of the beam transport system are described here. The X‐ray optical components of the beamline are detailed, and the beamline performances, transmission and focusing capabilities are reported. It is shown that the X‐ray beam can be effectively focused as predicted by ray‐tracing simulations. The impact of non‐ideal X‐ray source conditions on the focusing performances is discussed. The soft X‐ray beam from the SASE3 source at the European XFEL is delivered to the SQS instrument by a beam transport system. The system layout and performances are reported.

Background: Long-term exposure to urban air pollution may accelerate atherogenesis, but mechanisms are still unclear. The induction of a low-grade systemic inflammatory state is a plausible mechanistic pathway. Objectives: We analyzed the association of residential long-term exposure to paniculate matter (PM) and high traffic with systemic inflammatory markers. Methods: We used baseline data from the German Heinz Nixdorf Recall Study, a populationbased, prospective cohort study of 4,814 participants that started in 2000. Fine PM [aerodynamic diameter ≤ 2.5 ¼m ($PM_{2.5} $)] exposure based on a small-scale dispersion and chemistry transport model was assigned to each home address. We calculated distances between residences and major roads. Long-term exposure to air pollution (annual$PM_{2.5} $and distance to high traffic) and concentration of inflammatory markers [high-sensitivity C-reactive protein (hs-CRP) and fibrinogen] on the day of the baseline visit were analyzed with sex-stratified multiple linear regression, controlling for individual-level risk factors. Results: In the adjusted analysis, a cross-sectional exposure difference of 3.91 ¼g/m 3 in PM2.5 (interdecile range) was associated with increases in hs-CRP of 23.9% [95% confidence interval (CI), 4.1 to 47.4%] and fibrinogen of 3.9% (95% CI, 0.3 to 7.7%) in men, whereas we found no association in women. Chronic traffic exposure was not associated with inflammatory markers. Short-term exposures to air pollutants and temperature did not influence the results markedly. Conclusions: Our study indicates that long-term residential exposure to high levels of PM 25 is associated with systemic inflammatory markers in men. This might provide a link between air pollution and coronary atherosclerosis.

Background Patients with dedifferentiated or anaplastic thyroid carcinomas currently lack appropriate treatment options. Kinase inhibitors are among the most promising new agents as alternative strategies. The BRAF- and multi-kinase inhibitor, sorafenib, has already shown antitumor effects in thyroid carcinoma patients in a phase III clinical trial. In this study we aim to better characterize molecular effects and efficacy of sorafenib against thyroid carcinoma cells with various histological origins and different BRAF mutational status. Analysis of different signaling pathways affected by sorafenib may contribute to assist a more specific therapy choice with fewer side effects. Twelve thyroid carcinoma cell lines derived from anaplastic, follicular and papillary thyroid carcinomas with wildtype or mutationally activated BRAF were treated with sorafenib. Growth inhibition, cell cycle arrest, cell death induction and inhibition of intracellular signaling pathways were then comprehensively analyzed. Methods Cell viability was analyzed by MTT assay, and the cell cycle was assessed by flow cytometry after propidium iodide staining. Cell death was assessed by lactate dehydrogenase liberation assays, caspase activity assays and subG1 peak determinations. Inhibition of intracellular pathways was analyzed in dot blot and western blot analyses. Results Sorafenib inhibited proliferation of all thyroid carcinoma cell lines tested with IC50 values ranging between 1.85 and 4.2 μM. Cells derived from papillary carcinoma harboring the mutant BRAF V600E allele were slightly more sensitive to sorafenib than those harboring wildtype BRAF . Cell cycle analyses and caspase assays showed a sorafenib-dependent induction of apoptosis in all cell lines, whereas increased lactate dehydrogenase release suggested cell membrane disruption. Sorafenib treatment caused a rapid inhibition of various MAP kinases in addition to inhibiting AKT and receptor tyrosine kinases. Conclusions Sorafenib inhibited multiple intracellular signaling pathways in thyroid carcinoma cells, which resulted in cell cycle arrest and the initiation of apoptosis. Sorafenib was effective against all thyroid carcinoma cell lines regardless of their tumor subtype origin or BRAF status, confirming that sorafenib is therapeutically beneficial for patients with any subtype of dedifferentiated thyroid cancer. Inhibition of single intracellular targets of sorafenib in thyroid carcinoma cells may allow the development of more specific therapeutic intervention with less side effects.

Wilson disease is caused by accumulation of Cu 2+ in cells, which results in liver cirrhosis and, occasionally, anemia. Here, we show that Cu 2+ triggers hepatocyte apoptosis through activation of acid sphingomyelinase (Asm) and release of ceramide. Genetic deficiency or pharmacological inhibition of Asm prevented Cu 2+ -induced hepatocyte apoptosis and protected rats, genetically prone to develop Wilson disease, from acute hepatocyte death, liver failure and early death. Cu 2+ induced the secretion of activated Asm from leukocytes, leading to ceramide release in and phosphatidylserine exposure on erythrocytes, events also prevented by inhibition of Asm. Phosphatidylserine exposure resulted in immediate clearance of affected erythrocytes from the blood in mice. Accordingly, individuals with Wilson disease showed elevated plasma levels of Asm, and displayed a constitutive increase of ceramide- and phosphatidylserine-positive erythrocytes. Our data suggest a previously unidentified mechanism for liver cirrhosis and anemia in Wilson disease.

Background In view of consistently high cardiovascular morbidity and mortality rates, international efforts are aimed at developing tools for more precise risk prediction to allow preventive treatment targeted at high-risk individuals. Direct visualization of anatomic, preclinical atherosclerotic disease has the potential for individualized risk discrimination. Further, a variety of risk factors are actively evaluated, including markers of the activity of atherosclerotic disease, thrombogenic risk, and genetic polymorphisms. Methods The Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcium and Lifestyle) study is a population-based, prospective cohort study of the comparative value of modern risk stratification techniques for “hard” cardiac events. It is designed and powered to define the relative risk associated with the specific extent of coronary atherosclerosis measured by means of electron-beam computed tomography (EBCT)-derived coronary calcium quantities for myocardial infarction and cardiac death in 5 years in 4200 males and females aged 45 to 75 years in an unselected urban population from the large, heavily industrialized Ruhr area. Additionally, the predictive values of conventional cardiovascular risk factors, new candidate and socioeconomic risk factors, certain genetic polymorphisms, and direct signs of subclinical disease are examined with the ankle-brachial index, resting and stress electrocardiograms, and determination of carotid artery intima-media thickness. Prospective clinical risk-benefit and health economic analyses are an inherent part of the study. Study findings with established clinical significance are reported to the participants, but the EBCT findings are withheld until the conclusion of the study. Conclusions The Heinz Nixdorf RECALL study will define appropriate methods for identifying high-risk subgroups in the general urban population who may derive the greatest benefit from preventive treatment. (Am Heart J 2002;144:212-8.)

We present a new experimental approach to determine the Wigner distribution function of non-separable laser beams. A rotatable toroidal mirror is employed to focus an IR laser beam at a wavelength of . For different rotation angles of the mirror, intensity profiles of the reflected beam are captured. The resulting data suffices to fully reconstruct the four-dimensional Wigner distribution from which the global degree of coherence is derived. A comparison to theoretical expectations reveals validity of the applied formalism. Since the setup dispenses with any transmissive optics it can be applied to a broad spectral range, especially to extreme UV and soft x-ray radiation.

Nanoscale multilayer thin films of W and PC (Polycarbonate) show, due to the great difference of the components' characteristics, fascinating properties for a variety of possible applications and provide an interesting research field, but are hard to fabricate with low layer thicknesses. Because of the great acoustic mismatch between the two materials, such nanoscale structures are promising candidates for new phononic materials, where phonon propagation is strongly reduced. In this article we show for the first time that W/PC-multilayers can indeed be grown with high quality by pulsed laser deposition. We analyzed the polymer properties depending on the laser fluence used for deposition, which enabled us to find best experimental conditions for the fabrication of high-acoustic-mismatch W/PC multilayers. The multilayers were analyzed by fs pump-probe spectroscopy showing that phonon dynamics on the ps time-scale can strongly be tailored by structural design. While already periodic multilayers exhibit strong phonon localization, especially aperiodic structures present outstandingly low phonon propagation properties making such 1D-layered W/PC nano-structures interesting for new phononic applications.

The effectiveness of medical therapies depends crucially on patients’ adherence. To gain deeper insight into the behavioral mechanisms underlying adherence, we present a microeconomic model of the decision-making process of an individual who is initially in an asymptomatic clinical state and to whom a prophylactic therapy is offered with the aim of preventing damage to health in the future. The focus of modeling is the optimization of an intertemporal utility function, where time-inconsistent preferences are incorporated by a quasi-hyperbolic discount function. The predictions of the model concur with experience in clinical practice. Moreover, the introduction of time-inconsistency reveals a self-control problem of the individuals where resolutions made before may be given up at a later time. A more pronounced present bias leads to a decrease in adherence and, consequently, the gain in societal welfare resulting from the prophylactic therapy declines. Developing effective strategies to improve adherence is a major challenge in health care. As an example, the impact of financial incentives offered to the patients on adherence and welfare are investigated on the basis of the model. The results are consistent with empirical findings. The approach presented contributes to a better understanding of the complex interaction of the relevant determinants for adherence, particularly regarding the individuals’ self-control problem.