Cognitive Efficacy of Quetiapine in Early-Onset First-Episode Psychosis: A 12-Week Open Label Trial

Twenty-three adolescents with psychotic disorders, aged from 13 to 18years, participated in a 12-week open label trial (17 adolescents completed the study) in order to examine the impact of quetiapine on clinical status and cognitive functions (encompassing processing speed, attention, short-term memory, long-term memory and executive function). An improvement in Clinical Global Impression and Positive and Negative Symptom Scale (P's≤0.001) was observed. In addition, after controlling for amelioration of symptoms, a significant improvement was observed on one executive function (P=0.044; Trail Making Part B). The remaining cognitive abilities showed stability. In addition, we observed an interaction between quetiapine doses (>300mg/day or <300mg/day) and time, where lower doses showed more improvement in verbal short-term memory (P=0.048), inhibition abilities (P=0.038) and positive symptoms (P=0.020). The neuropsychological functioning of adolescents with psychotic disorders remained mainly stable after 12weeks of treatment with quetiapine. However, lower doses seemed to have a better impact on two components of cognition (inhibition abilities and verbal short-term memory) and on positive symptom

Singly-resonant sum frequency generation of visible light in a semiconductor disk laser

In this paper a generic approach for visible light generation is presented. It is based on sum frequency generation between a semiconductor disk laser and a solid-state laser, where the frequency mixing is achieved within the cavity of the semiconductor disk laser using a singlepass of the solid-state laser light. This exploits the good beam quality and high intra-cavity power present in the semiconductor disk laser to achieve high conversion efficiency. Combining sum frequency mixing and semiconductor disk lasers in this manner allows in principle for generation of any wavelength within the visible spectrum, by appropriate choice of semiconductor material and single-pass laser wavelength

Characterization of Irradiation Damage Using X-Ray Diffraction Line-Profile Analysis

During operation, structural components made of zirconium alloys are subject toneutron irradiation, which leads to the displacement of zirconium atoms fromtheir lattice sites, the production of self-interstitials and vacancies, and eventually dislocation loops. This process can lead to deleterious effects such as irradiation growth, creep, and embrittlement as well as accelerated aqueous corrosion. Quantitative analysis of dislocation line densities is seen as an importantpathway for distinguishing between the irradiation response of different alloys.The analysis of irradiation damage using X-ray diffraction (XRD) line-profile analysis has proven to be a powerful complementary technique to transmissionelectron microscopy, which samples a comparatively large volume and is lessaffected by the subjectivity of image analysis. In this paper we present andanalyze three different types of XRD experiments, describing their purpose andthe new insight achieved using each technique. First, we present work carriedout on neutron-irradiated samples, comparing dislocation line densities measured by XRD with macroscopic growth measurements. A second experimentusing a synchrotron-based X-ray microbeam enabled the mapping of dislocationline densities as a function of depth from the surface of proton-irradiated zirconium alloys. These data are compared with calculated damage profiles, providingnew insight into the early saturation of damage. Finally, the last example presented here focuses on synchrotron-based 3D XRD measurements, for whichdislocation-loop line densities were analyzed in hundreds of individual grains,providing excellent statistics about the grain-to-grain variability of line densities

Completeness of tuberculosis case notifications in Germany in 2013–2017: first results of an inventory study

Background Evaluating the completeness of tuberculosis (TB) notification data is important for monitoring of TB surveillance systems. We conducted an inventory study to calculate TB underreporting in Germany in 2013–2017. Methods Acquisition of two pseudonymized case-based data sources (national TB notification data and antibiotic resistance surveillance data) was followed by two-source Capture-recapture (CRC) analysis, as case-based data from a third source was unavailable. Aggregated data on consumption of a key anti-TB drug (pyrazinamide [PZA]) was compared to an estimated need for PZA based on TB notification data to obtain an independent underreporting estimation. Additionally, notified TB incidence was compared to TB rate in an aggregated health insurance fund dataset. Results CRC and PZA-based approaches indicated that between 93 and 97% (CRC) and between 91 and 95% (PZA) of estimated cases were captured in the national TB notification data in the years 2013–2017. Insurance fund dataset did not indicate TB underreporting on the national level in 2017. Conclusions Our results suggest that more than 90% of estimated TB cases are captured within the German TB surveillance system, and accordingly the TB notification rate is likely a good proxy of the diagnosed TB incidence rate. An increase in underreporting and discrepancies however should be further investigated.Peer Reviewe

Tracing responsibilities in food production with animals

This paper summarises some results of the final report of the research project ‘Systematics of Responsibilities for Animal Welfare in the Livestock Sector’ (2018-2020). The project focused on the question who is fundamentally responsible for the treatment of farm animals. This question is largely and to some extent pointlessly discussed in the public. The study was commissioned by the German Federal Ministry of Agriculture (BMEL). It is based on a systematic examination of the term ‘responsibility’. Responsibility means that agents (who have the necessary means) act accordingly to their value preferences and cause consequences. In this respect, it must be taken into account that animal welfare (as based on altruistic reasoning) is not always given overriding priority in decision-making. This result becomes more plausible when analysing concrete examples of how real decisions were made. The report establishes a characteristic pattern that re-occurs in many discussions on problems in farm animal husbandry: There is an enormous gap between partakers ascribing responsibility to themselves or unto others. The report in contrast uses and extends well established ethical models and principles to create a matrix that makes it possible to say more precisely who is in fact responsible, and why. The report offers a detailed and rather extensive map of possible agents and stakeholders involved in animal husbandry based on the criteria of the matrix. This will lead to a much more distinguished judgement on responsibilities. The project has also developed a database tool in order to locate players in regards to certain characteristics. One result is to filter out those agents who may be called big players in the game at hand. The big food retailers and political bodies are prime candidates. The model can prove why they have indeed an enormous share of responsibility. The role of ‘the consumer’ is in turn to be reconsidered on this basis. The report finally offers an explanation on how responsibility and reliability are interconnected: It is much easier to stick to one’s own responsibilities if other players reliably stick to theirs. In turn, confidence in the system and its elements can be boosted whenever agents evidentially take up their responsibility and do ‘their jobs

Heterogeneity of cell surface glutamate and GABA receptor expression in Shank and CNTN4 autism mouse models

Autism spectrum disorder (ASD) refers to a large set of neurodevelopmental disorders, which have in common both repetitive behavior and abnormalities in social interactions and communication. Interestingly, most forms of ASD have a strong genetic contribution. However, the molecular underpinnings of this disorder remain elusive. The SHANK3 gene (and to a lesser degree SHANK2) which encode for the postsynaptic density (PSD) proteins SHANK3/SHANK2 and the CONTACTIN 4 gene which encodes for the neuronal glycoprotein CONTACTIN4 (CNTN4) exhibit mutated variants which are associated with ASD. Like many of the other genes associated with ASD, both SHANKs and CNTN4 affect synapse formation and function and are therefore related to the proper development and signaling capability of excitatory and inhibitory neuronal networks in the adult mammal brain. In this study we used mutant/knock-out mice of Shank2 (Shank2-/-), Shank3 (Shank3αβ-/-), and Cntn4 (Cntn4-/-) as ASD-models to explore whether these mice share a molecular signature in glutamatergic and GABAergic synaptic transmission in ASD-related brain regions. Using a biotinylation assay and subsequent western blotting we focused our analysis on cell surface expression of classical several ionotropic glutamate and GABA receptor subunits: GluA1, GluA2, and NR1GluN1 were analyzed for excitatory synaptic transmission, and the α1 subunit of the GABAA receptor was analyzed for inhibitory synaptic transmission. We found that both Shank2-/- and Shank3αβ-/- mice exhibit reduced levels of several cell surface glutamate receptors in most of the analyzed brain regions – especially in the striatum and thalamus – when compared to wildtype controls. Interestingly, even though Cntn4-/- mice also show reduced levels of some cell surface glutamate receptors in the cortex and hippocampus, increased levels of cell surface glutamate receptors were found in the striatum. Moreover, Cntn4-/- mice do not only show brain region-specific alterations in cell surface glutamate receptors but also a downregulation of cell surface GABA receptors in several of the analyzed brain regions. The results of this study suggest that even though mutations in defined genes can be associated with ASD this does not necessarily result in a common molecular phenotype in surface expression of glutamatergic and GABAergic receptor subunits in defined brain regions