EQ-5D is the most commonly used generic preference-based health-related quality of life (HRQoL) measure. The current study aimed at estimating the HRQoL index scores using EQ-5D-5 L measure in the capital of I...
6h
This study aimed to compare long-term postoperative quality of life and satisfaction differences between SMILE and FS-LASIK for myopia correction.
6h
2D electron crystallography can be used to study small membrane proteins in their native environment. Obtaining highly ordered 2D crystals is difficult and time-consuming. However, 2D crystals diffracting to only 10-12 Å can be prepared relatively conveniently in most cases. We have developed image-processing algorithms allowing to generate a high resolution 3D structure from cryo-electron crystallography images of badly ordered crystals. These include movie-mode unbending, refinement over sub-tiles...
7h
Asymmetric flow field-flow fractionation is a valuable tool for the characterization of protein aggregates in biotechnology owing to its broad size range and unique separation principle. However, in practice asymmetric flow field-flow fractionation is non-trivial to use due to the major deviations from theory and the influence on separation by various factors that are not fully understood. Here we report methods to assess the non-ideal effects that influence asymmetric flow field-flow fractionation...
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Over the past decade, several excellent guidelines have been published on how to enhance the quality of PhD education in Europe. Aimed primarily at preparing students for innovative roles in their fields, they include variously structured approaches to curricular offerings, as well as other program components applicable across specialties (eg: supervisor support, scientific conduct, transferable skills). Since 2012, the interdisciplinary PhD Program in Health Sciences (PPHS) at the Faculty of Medicine...
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To examine cardiorespiratory exertion during mini trampoline exercises of different intensities in both endurance-trained athletes and overweight-obese adults.; Physically healthy participants (Group A: normal-weight, endurance-trained athletes; Group B: inactive, overweight-obese adults) participated in two measurement appointments and three training sessions in between appointments, in which participants familiarized themselves with the use of the mini trampoline and the execution of the exercises....
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The cerebellum integrates descending motor commands and sensory information to generate predictions and detect errors during ongoing behaviors. Cerebellar computation has been proposed to control motor but also non-motor behaviors, including reward expectation and cognitive flexibility. However, the organization and functional contribution of cerebellar output channels are incompletely understood. Here, we elaborate the cell-type specificity of a broad connectivity matrix from the deep cerebellar...
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Atypical habituation and aberrant exploration of novel stimuli have been related to the severity of autism spectrum disorders (ASDs), but the underlying neuronal circuits are unknown. Here we show that chemogenetic inhibition of dopamine (DA) neurons of the ventral tegmental area (VTA) attenuates exploration toward nonfamiliar conspecifics and interferes with the reinforcing properties of nonfamiliar conspecific interaction in mice. Exploration of nonfamiliar stimuli is associated with the insertion...
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The view of cerebellar functions has been extended from controlling sensorimotor processes to processing 'contextual' information and generating predictions for a diverse range of behaviors. These functions rely on the computation of the local cerebellar microcircuits and long-range connectivity that relays cerebellar output to various brain areas. In this review, we discuss recent work on two of the circuit elements, which are thought to be fundamental for a wide range of non-sensorimotor behaviors:...
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Posttranscriptional mechanisms provide powerful means to expand the coding power of genomes. In nervous systems, alternative splicing has emerged as a fundamental mechanism not only for the diversification of protein isoforms but also for the spatiotemporal control of transcripts. Thus, alternative splicing programs play instructive roles in the development of neuronal cell type-specific properties, neuronal growth, self-recognition, synapse specification, and neuronal network function. Here we discuss...
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Endocytosis is a means for the cell to sample its environment for nutrients and regulate plasma membrane (PM) composition and area. Whereas the majority of internalized cargo is recycled back to the cell surface, select material is sent to the lysosome for degradation. Endosomes further play major roles in central cell activities as diverse as establishment of cell polarity and signaling, lysosomal storage and immunity. The complexity of endosomal functions is reflected by the extensive changes to...
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Understanding molecular properties of outer membrane channels of Gram-negative bacteria is of fundamental significance as they are the entry point of polar antibiotics into bacteria. Outer membrane proteomics revealed OccK8 (OprE) to be among the five most expressed substrate specific channels of the clinically important Pseudomonas aeruginosa. The high-resolution X-ray structure and electrophysiology highlighted a very narrow pore. However, experimental in vitro methods showed the transport of natural...
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One important challenge facing the urbanization and global environmental change community is to understand the relation between urban form, energy use and carbon emissions. Missing from the current literature are scientific assessments that evaluate the impacts of different urban spatial units on energy fluxes; yet, this type of analysis is needed by urban planners, who recognize that local scale zoning affects energy consumption and local climate. Satellite-based estimation of urban energy fluxes...
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Soil organic matter carries ice-nucleating particles (INPs) the origin of which is hard to define and that are active at slight supercooling. The discovery and characterization of INPs produced by the widespread soil fungus Mortierella alpina permits a more targeted investigation of the likely origin of INPs in soils. We searched for INPs with characteristics similar to those reported for M. alpina in 20 soil samples from four areas in the northern midlatitudes and one area in the tropics. In the...
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Affinity data, such as dissociation constants (K; D; ) or inhibitory concentrations (IC; 50; ), are widely used in drug discovery. However, these parameters describe an equilibrium state, which is often not established in vivo due to pharmacokinetic effects and they are therefore not necessarily sufficient for evaluating drug efficacy. More accurate indicators for pharmacological activity are the kinetics of binding processes, as they shed light on the rate of formation of protein-ligand complexes...
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Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded...
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Angiogenesis and vascular remodeling are driven by extensive endothelial cell movements. Here, we present in vivo evidence that endothelial cell movements are associated with oscillating lamellipodia-like structures, which emerge from cell junctions in the direction of cell movements. High-resolution time-lapse imaging of these junction-based lamellipodia (JBL) shows dynamic and distinct deployment of junctional proteins, such as F-actin, VE-cadherin and ZO1, during JBL oscillations. Upon initiation,...
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The increasing nanomedicine usage has raised concerns about their possible impact on human health. Present evaluation strategies for nanomaterials rely on a case-by-case hazard assessment. They take into account material properties, biological interactions, and toxicological responses. Authorities have also emphasized that exposure route and intended use should be considered in the safety assessment of nanotherapeutics. In contrast to an individual assessment of nanomaterial hazards, we propose in...
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In the version of this article initially published, the catalog numbers for BoNT A and B were given in the Methods section as T0195 and T5644; the correct numbers are B8776 and B6403. The error has been corrected in the HTML and PDF versions of the article.
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Sedimentary plant wax H-2/H-1 ratios are important tools for understanding hydroclimate and environmental changes, but large spatial and temporal uncertainties exist about transport mechanisms from ecosystem to sediments. To assess atmospheric pathways, we collected aerosol samples for two years at four locations within a similar to 60 km radius in northern Switzerland. We measured n-alkane distributions and H-2/H-1 ratios in these samples, and from local plants, leaf litter, and soil, as well as...
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Anti-aggression and de-escalation (ADE) trainings of health-care professionals working on psychiatric inpatient wards have been shown to increase staff knowledge and confidence, which could be connected with higher subjective safety. Additionally, a potential reduction of aggressive incidents could improve ward atmosphere. Thus, the current study aimed to investigate the effects of ADE training on ward atmosphere and subjective safety. In 2015, an ADE training was established at the Psychiatric University...
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The brain-derived neurotrophic factor (BDNF) is a major proliferative agent in the nervous system. Both BDNF-deficiency and perinatal hypoxia represent genetic/environmental risk factors for schizophrenia. Moreover, a decreased BDNF response to birth hypoxia was associated with the disease. BDNF expression is influenced by neuronal activity and environmental conditions such as hypoxia. Thus, it may partake in neuroprotective and reparative mechanisms in acute or chronic neuronal insults. However,...
8h
Background:; Previous research of patients with multiple sclerosis (MS) focused prevalently on fatigue, depression, and cognitive dysfunction during the clinical course. By contrast, research on the longer-term characteristics of physical activity (PA), psychological functioning, and sleep problems is scarce. The aims of the present study were therefore to examine changes in PA, mental toughness (MT) as a proxy of psychological functioning, and sleep disturbances over a 2-year period of time after...
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Background:; Aggression in psychoses is of high clinical importance, and volumetric MRI techniques have been used to explore its structural brain correlates.; Methods:; We conducted a systematic review searching EMBASE, ScienceDirect, and PsycINFO through September 2017 using thesauri representing aggression, psychosis, and brain imaging. We calculated effect sizes for each study and mean Hedge's g for whole brain (WB) volume. Methodological quality was established using the PRISMA checklist (PROSPERO:...
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Little is known about narcissistic traits in borderline personality disorder (BPD). This exploratory study aimed to illustrate the associations between total, grandiose, and vulnerable narcissism and gender, diagnostic features of BPD and narcissistic personality disorder (NPD), and psychopathology in BPD patients.; The Pathological Narcissism Inventory and psychometric measures for impulsivity, anger, borderline symptom severity, personality organization, depression, and rejection sensitivity were...
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Implementing an open door policy is a complex intervention comprising changes in therapeutic stance, team processes, and a change from locked to open doors. Recent studies show that it can lead to a reduction of seclusion and forced medication, but the role of the physical change of door status is still unclear.; The aims of this study is to examine the transition from closed to predominantly open doors on a psychiatric intensive care unit (PICU) and its associations with the frequency of seclusion...
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Psychiatric inpatient treatment is increasingly performed in settings with locked doors. However, locked wards have well-known disadvantages and are ethically problematic. In addition, recent data challenges the hypothesis that locked wards provide improved safety over open-door settings regarding suicide, absconding and aggression. Furthermore, there is evidence that the introduction of an open-door policy may lead to short-term reductions in involuntary measures. The aim of this study was to assess...
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Lithium augmentation (LA) of antidepressants is a first-line therapy in treatment-resistant depression. Immunomodulatory effects of lithium have been described. The cytokine hypothesis of depression postulates that cytokines play a key role in the pathophysiology of depression. Concordantly, it has been shown that proinflammatory cytokine serum levels decrease during antidepressant treatment. The aim of this study was to investigate changes in cytokine serum levels during LA. Serum concentrations...
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A growing body of evidence supports the idea that drugs targeting the glutamate system may represent a valuable therapeutic alternative in major depressive disorders (MDD). The rapid and prolonged mood elevating effect of the NMDA receptor (NMDAR) antagonist ketamine has been studied intensely. However, its clinical use is hampered by deleterious side-effects, such as psychosis. Therefore, a better understanding of the mechanisms of the psychotropic effects after NMDAR blockade is necessary to develop...
9h
Francisella tularensis; is the causative agent of the life-threatening disease tularemia. However, the molecular tools to study; Francisella; are limited. Especially, expression plasmids are sparse and difficult to use, as they are unstable and prone to spontaneous loss. Most; Francisella; expression plasmids lack inducible promoters making it difficult to control gene expression levels. In addition, available expression plasmids are mainly designed for; F. tularensis; , however, genetic differences...
9h
Cytochrome P450 2D6 (CYP2D6) is an enzyme that is involved in the metabolism of roughly 25% of all marketed drugs and therefore belongs to the most important enzymes in drug metabolism. CYP2D6 features a high degree of genetic polymorphism that can significantly affect the metabolic activity of an individual. In extreme cases, structural changes at the level of single amino acids can either increase its enzymatic activity abolishing the drug therapeutic effect or completely disable the enzyme and...
9h
OBJECTIVES: To examine the immediate and sustained effects of intermittent exercise sessions at different intensities on inhibitory control and task-related heart rate variability (HRV) in adolescents. DESIGN: Using cluster-randomization, participants from six classes (n=94) were allocated to groups performing 20min of intermittent exercise at moderate (MIE) or high intensity (HIE) and a control group (CON). METHODS: Using a computer-based Flanker task, inhibitory control was assessed in a classroom...
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The alternative pathway is a continuously active surveillance arm of the complement system, and it can also enhance complement activation initiated by the classical and the lectin pathways. Various membrane-bound and plasma regulatory proteins control the activation of the potentially deleterious complement system. Among the regulators, the plasma glycoprotein factor H (FH) is the main inhibitor of the alternative pathway and its powerful amplification loop. FH belongs to a protein family that also...
9h
Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine...
9h
Pharmaceutically elegant lyophilisates are highly desirable implying a stable and robust freeze-drying process. To ensure homogenous and intact cake appearance after process scale-up and transfer, characterization of lyophilisates during formulation and cycle development is required. The present study investigates different imaging techniques to characterize lyophilisates on different levels. Cake appearance of freeze-dried bovine serum albumin formulations with different dextran/sucrose ratios was...
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Tablets for oral suspension (TOS) present a convenient alternative dosage form to conventional tablets. Dispersed in a glass of water or on a spoon, such tablets can be easily administered, which can become beneficial for pediatric or geriatric patients. The novel excipient functionalized calcium carbonate (FCC), consisting of calcium carbonate and calcium phosphate, has already shown to be suitable to produce orally disintegrating placebo tablets. In this study, the influence of formulation composition...
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Photosynthetic linear electron flow (LEF) produces ATP and NADPH, while cyclic electron flow (CEF) exclusively drives photophosphorylation to supply extra ATP. The fine-tuning of linear and cyclic electron transport levels allows photosynthetic organisms to balance light energy absorption with cellular energy requirements under constantly changing light conditions. As LEF and CEF share many electron transfer components, a key question is how the same individual structural units contribute to these...
10h
Cyclic nucleotide-gated (CNG) ion channels are non-selective cation channels key to signal transduction. The free energy difference of cyclic-nucleotide (cAMP/cGMP) binding/unbinding is translated into mechanical work to modulate the open/closed probability of the pore, i.e., gating. Despite the recent advances in structural determination of CNG channels, the conformational changes associated with gating remain unknown. Here we examine the conformational dynamics of a prokaryotic homolog of CNG channels,...
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Cryo-electron tomography allows low-resolution three-dimensional (3D) viewing of cellular organelles and macromolecular complexes present as multiple copies within a tomogram. These structures are computationally extracted and averaged in order to obtain high-resolution 3D structures, and provide a map of their spatial distribution and interaction with their biological microenvironment. To do so, we apply the user-friendly; Dynamo; software package on a tomographic data set.; Dynamo; acts as a modular...
10h
The development of X-ray free-electron lasers (XFELs) has opened the possibility to investigate the ultrafast dynamics of biomacromolecules using X-ray diffraction. Whereas an increasing number of structures solved by means of serial femtosecond crystallography at XFELs is available, the effect of radiation damage on protein crystals during ultrafast exposures has remained an open question. We used a split-and-delay line based on diffractive X-ray optics at the Linac Coherent Light Source XFEL to...
10h
Several scores are available to predict mortality and neurological outcome in cardiac arrest patients admitted to the intensive care unit (ICU). The aim of the study was to externally validate the prognostic value of four previously published risk scores.; For this observational, single-center study, we prospectively included 349 consecutive adult cardiac arrest patients upon ICU admission. We calculated two cardiac arrest specific risk scores (OHCA and CAHP) and two general severity of illness scores...
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miRNAs are small RNAs that regulate gene expression post-transcriptionally. By repressing the translation and promoting the degradation of target mRNAs, miRNAs may reduce the cell-to-cell variability in protein expression, induce correlations between target expression levels, and provide a layer through which targets can influence each other's expression as "competing RNAs" (ceRNAs). However, experimental evidence for these behaviors is limited. Combining mathematical modeling with RNA sequencing...
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Sequencing of RNA 3' ends has uncovered numerous sites that do not correspond to the termination sites of known transcripts. Through their 3' untranslated regions, protein-coding RNAs interact with RNA-binding proteins and microRNAs, which regulate many properties, including RNA stability and subcellular localization. We developed the terminal exon characterization (TEC) tool ( http://tectool.unibas.ch ), which can be used with RNA-sequencing data from any species for which a genome annotation that...
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The RNA-binding proteins Roquin-1 and Roquin-2 redundantly control gene expression and cell-fate decisions. Here, we show that Roquin not only interacts with stem-loop structures, but also with a linear sequence element present in about half of its targets. Comprehensive analysis of a minimal response element of the Nfkbid 3'-UTR shows that six stem-loop structures cooperate to exert robust and profound post-transcriptional regulation. Only binding of multiple Roquin proteins to several stem-loops...
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ABCG2 is a transporter protein of the ATP-binding-cassette (ABC) family that is expressed in the plasma membrane in cells of various tissues and tissue barriers, including the blood-brain, blood-testis and maternal-fetal barriers; 1-4; . Powered by ATP, it translocates endogenous substrates, affects the pharmacokinetics of many drugs and protects against a wide array of xenobiotics, including anti-cancer drugs; 5-12; . Previous studies have revealed the architecture of ABCG2 and the structural basis...
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The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism; Caulobacter crescentus; , PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in; C. crescentus; We...
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Branching morphogenesis is a fascinating process whereby a simple network of biological tubes increases its complexity by adding new branches to existing ones, generating an enlarged structure of interconnected tubes. Branching morphogenesis has been studied extensively in animals and much has been learned about the regulation of branching at the cellular and molecular level. Here, we discuss studies of the Drosophila trachea and of the vertebrate vasculature, which have revealed how new branches...
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The aims of this study were to (a) identify and assess the quality of reporting of published cost-effectiveness studies of bariatric surgery, (b) assess their transferability to Switzerland, and (c) adapt transferable cost-effectiveness results to Switzerland.; A systematic literature search was performed in Medline, Embase and other databases. Two reviewers independently undertook screening, extraction, assessment of reporting quality utilising the Consolidated Health Economic Evaluation Reporting...
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Angiogenesis is a dynamic process relying on endothelial cell rearrangements within vascular tubes, yet the underlying mechanisms and functional relevance are poorly understood. Here we show that PI3Kα regulates endothelial cell rearrangements using a combination of a PI3Kα-selective inhibitor and endothelial-specific genetic deletion to abrogate PI3Kα activity during vessel development. Quantitative phosphoproteomics together with detailed cell biology analyses in vivo and in vitro reveal that PI3K...
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Canonical Wnt signaling is crucial for vascularization of the central nervous system and blood-brain barrier (BBB) formation. BBB formation and modulation are not only important for development, but also relevant for vascular and neurodegenerative diseases. However, there is little understanding of how Wnt signaling contributes to brain angiogenesis and BBB formation. Here we show, using high resolution in vivo imaging and temporal and spatial manipulation of Wnt signaling, different requirements...
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To tackle the complexity of cross-reactive and pathogen-specific T cell responses against related Salmonella serovars, we used mass cytometry, unbiased single-cell cloning, live fluorescence barcoding, and T cell-receptor sequencing to reconstruct the Salmonella-specific repertoire of circulating effector CD4; +; T cells, isolated from volunteers challenged with Salmonella enterica serovar Typhi (S. Typhi) or Salmonella Paratyphi A (S. Paratyphi). We describe the expansion of cross-reactive responses...
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This paper provides an overview of stable isotope analysis (H, C, N, O, Si) of the macro- and microscopic remains from aquatic organisms found in lake sediment records and their application in (palaeo)environmental science. Aquatic organisms, including diatoms, macrophytes, invertebrates, and fish, can produce sufficiently robust remains that preserve well as fossils and can be identified in lake sediment records. Stable isotope analyses of these remains can then provide valuable insights into habitat-specific...
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A rise in the atmospheric CO2 concentration of similar to 20 parts per million over the course of the Holocene has long been recognized as exceptional among interglacials and is in need of explanation. Previous hypotheses involved natural or anthropogenic changes in terrestrial biomass, carbonate compensation in response to deglacial outgassing of oceanic CO2, and enhanced shallow water carbonate deposition. Here, we compile new and previously published fossil-bound nitrogen isotope records from...
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Ocean acidification (OA), arising from the influx of anthropogenically generated carbon, poses a massive threat to the ocean ecosystems. Our knowledge of the effects of elevated anthropogenic CO2 in marine waters and its effect on the performance of single species, trophic interactions, and ecosystems is increasing rapidly. However, our understanding of the biogeochemical cycling of nutrients such as nitrogen is less advanced and lacks a comprehensive overview of how these processes may change under...
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Nitrous oxide (N2O) is a greenhouse gas and an ozone depletion agent. Estuaries that are subject to seasonal anoxia are generally regarded as N2O sources. However, insufficient understanding of the environmental controls on N2O production results in large uncertainty about the estuarine contribution to the global N2O budget. Incubation experiments with nitrogen stable isotope tracer were used to investigate the geochemical factors controlling N2O production from denitrification in the Chesapeake...
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Aim: We provide the first European-scale geospatial training set relating the charcoal signal in surface lake sediments to fire parameters (number, intensity and area) recorded by satellite moderate resolution imaging spectroradiometer (MODIS) sensors. Our calibration is intended for quantitative reconstructions of key fire-regime parameters by using sediment sequences of microscopic (MIC from pollen slides, particles 10-500 mu m) and macroscopic charcoal (MAC from sieves, particles > 100 mu m).Location:...
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Electronic health care data contain rich information on medicine use from which adherence can be estimated. Various measures developed with medication claims data called for transparency of the equations used, predominantly because they may overestimate adherence, and even more when used with multiple medications. We aimed to operationalize a novel calculation of adherence with polypharmacy, the daily polypharmacy possession ratio (DPPR), and validate it against the common measure of adherence, the...
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Few studies have examined associations between patient knowledge of direct oral anticoagulants (DOAC) and clinical outcomes, mostly because of the lack of validated questionnaires for assessing knowledge. The aim of this study was to develop and validate a questionnaire to self-assess knowledge of DOAC.; Twelve anticoagulation experts participated in the questionnaire development process to ensure content validity. The Knowledge Of Direct Oral Anticoagulants (KODOA)-test was submitted to patients...
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To evaluate a prompt card (i.e., a post-card sized tool that lists counselling prompt information) with 5 key elements and 3 open key questions to ask patients in community pharmacies.; Community pharmacists practicing in England and accredited to perform consultations used the prompt card during a formal consultation with emphasis on patients receiving oral anticoagulation. Main outcome measure was the number of performed consultations with pharmacists' thoughts and feedbacks in writing.; During...
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To assess chlamydia knowledge, willingness to undertake pharmacy-based chlamydia testing, and facilitators and barriers to such testing in consumers and community pharmacists, in Australia (AUS) and Switzerland (CH).; Statements of interest were retrieved from literature and assembled into a 12-item online survey (English and German versions). Survey was disseminated through Facebook, pharmacies' publicly available emails and professional websites (March 2015).; Consumers and pharmacists (AUS: n;...
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Background: HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen re-exposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B cell-derived HLA antibodies (DSA-M) in renal allograft recipients with pre-transplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (ABMR) using a recently developed method. Methods: Twenty patients with Luminex single antigen bead (SAB)...
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Die Moderne hat nach der Aufklärung eine zweite Zäsur erfahren, die die Mentalität der Menschen ab der Mitte des 19. Jahrhunderts bis in die Gegenwart prägt. Sowohl der Sinn der Geschichte als auch des menschlichen Handelns sind radikal infrage gestellt durch ein neuartiges, historistisches Geschichtsverständnis einerseits und die Rationalisierung der gesamten Lebenswelt als Folge einer kapitalistischen Ökonomie andererseits. Dies betrifft die Geisteswissenschaften im Allgemeinen und die Theologie...
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We report on a new population of Vipera anatolica from the Geyik Mountain Range in eastern Antalya Province, Turkey. It represents only the second known location, and is situated in a valley about 200 km east from the terra typica at Kohu Dag in western Antalya Province. We compare both populations and, based on marked differences in morphology, habitat, genetics, and its geographically isolated location, we describe the recently discovered population as a new subspecies. Aspects of ecology, threats,...
2d
We aimed to assess the cost effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from the perspective of the Swiss health care system.; The cost-effectiveness analysis was implemented as a lifelong regression-based cohort model. We compared sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF and New York-Heart Association Functional...
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The ability to differentiate patient-specific human induced pluripotent stem cells in cardiac myocytes (hiPSC-CM) offers novel perspectives for cardiovascular research. A number of studies, that reported mainly on current-voltage curves used hiPSC-CM to model voltage-gated Na(+) channel (Nav) dysfunction. However, the expression patterns and precise biophysical and pharmacological properties of Nav channels from hiPSC-CM remain unknown. Our objective was to study the characteristics of Nav channels...
2d
Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated...
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During the last two decades, hyper-immunoglobulin (Ig)E syndromes have been characterized clinically and molecularly in patients with genetically determined primary immunodeficiencies. However, the detection of low IgE levels, defined here as below detection limit in the routine clinical immunology laboratory, has received little attention. We analysed the association of serum IgA, IgM and IgG levels (including IgG subclasses) with low, normal or high serum IgE levels in patients evaluated in a single-centre...
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Major advances have been made in understanding the pathogenesis of Erdheim-Chester disease (ECD) leading to novel treatment strategies. Targeted therapies such as BRAF inhibition have shown a significant impact on disease management, emphasizing the importance of the activated mitogen-associated protein kinase pathway in this disease. However, incomplete responsiveness, potentially limiting adverse effects, and the occurrence of treatment resistance to BRAF inhibition observed in other BRAF-mutant...
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