North Atlantic climate far more predictable than models imply.

Quantifying signals and uncertainties in climate models is essential for the detection, attribution, prediction and projection of climate change1-3. Although inter-model agreement is high for large-scale temperature signals, dynamical changes in atmospheric circulation are very uncertain4. This leads to low confidence in regional projections, especially for precipitation, over the coming decades5,6. The chaotic nature of the climate system7-9 may also mean that signal uncertainties are largely irreducible. However, climate projections are difficult to verify until further observations become available. Here we assess retrospective climate model predictions of the past six decades and show that decadal variations in North Atlantic winter climate are highly predictable, despite a lack of agreement between individual model simulations and the poor predictive ability of raw model outputs. Crucially, current models underestimate the predictable signal (the predictable fraction of the total variability) of the North Atlantic Oscillation (the leading mode of variability in North Atlantic atmospheric circulation) by an order of magnitude. Consequently, compared to perfect models, 100 times as many ensemble members are needed in current models to extract this signal, and its effects on the climate are underestimated relative to other factors. To address these limitations, we implement a two-stage post-processing technique. We first adjust the variance of the ensemble-mean North Atlantic Oscillation forecast to match the observed variance of the predictable signal. We then select and use only the ensemble members with a North Atlantic Oscillation sufficiently close to the variance-adjusted ensemble-mean forecast North Atlantic Oscillation. This approach greatly improves decadal predictions of winter climate for Europe and eastern North America. Predictions of Atlantic multidecadal variability are also improved, suggesting that the North Atlantic Oscillation is not driven solely by Atlantic multidecadal variability. Our results highlight the need to understand why the signal-to-noise ratio is too small in current climate models10, and the extent to which correcting this model error would reduce uncertainties in regional climate change projections on timescales beyond a decade.

Dynamic contrast-enhanced magnetic resonance imaging for monitoring neovascularization during bone regeneration-a randomized in vivo study in rabbits.

OBJECTIVES: Micro-computed tomography (µ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. MATERIALS AND METHODS: Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through µ-CT and histology. RESULTS: The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and µ-CT (r =-0.101, 95% CI [-0.445; 0.268]) or histology (r = 0.305, 95% CI [-0.133; 0.644]) findings on bone regeneration were observed. CONCLUSIONS: These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.

High inter-observer reliability in standardized ultrasound measurements of subcutaneous adipose tissue in children aged three to six years.

BACKGROUND: A procedure to measure subcutaneous adipose (SAT) using brightness-mode ultrasound has recently been standardized and applied to various groups of adults including underweight, overweight and obese adults. High reliability of this procedure was found in each of the examined groups. The purpose of this study was to determine inter-observer reliability of the standardized brightness-mode ultrasound measurement of uncompressed SAT in three to six-year-old children. METHODS: Three experienced observers independently captured the ultrasound images at the eight standardized measurement sites in each of the 20 children and evaluated their images using an interactive software that detects the SAT contour and automatically measures multiple thicknesses in each image; the mean of these represents SAT thickness at a given site. The children were aged 4.9 ± 1.0 years; their body mass index ranged from 13.6-17.7 kgm- 2. Sound speed was set to 1450 ms- 1 for SAT. RESULTS: SAT thickness sums with fibrous structures included (DI) ranged from 25.7-86.4 mm, mean DI was 48.1 ± 15.5 mm. For DI, resulting from 160 measurements by each observer, the intra-class correlation coefficient was 0.998 (95% confidence interval 0.980-0.999), standard error of the estimate was 1.1 mm, and 95% limits of agreement were within ±2.1 mm. The median difference in DI was 0.8 mm, i.e. about 1.9% of mean DI. CONCLUSIONS: Inter-observer results in children are comparable to previously described high reliability in adults. This method, which provides a technical thickness measurement accuracy of about 0.1 to 0.2 mm, enables monitoring of subcutaneous adipose tissue in children with a similarly high reliability as was obtained in adults previously. TRIAL REGISTRATION: German Institute of Medical Documentation and Information, German Clinical Trials Register (DRKS) ID: DRKS00010089; Date 24/02/2016.

[Schwannoma of the inferior gluteal nerve as a rare cause of gluteal radiating chronic low back pain]. / Schwannom des Nervus gluteus inferior als seltene Ursache von nach gluteal einstrahlenden chronischen Rückenschmerzen.

This is the first report of a schwannoma of the inferior gluteal nerve (IGN) as a cause of chronic low back pain in a 43-year-old man. The patient suffered from severe pain radiating to the gluteal region. He was treated for months without pain relief and was on long-term disability. Only a targeted sonographic exam revealed a hypoechoic intrapelvic mass along the course of the IGN. By tumor resection, a schwannoma was histologically confirmed. After tumor removal the patient is free of pain with all medication discontinued. He has been fully reintegrated into his professional life.

Extremely thin layer plastification for focused-ion beam scanning electron microscopy: an improved method to study cell surfaces and organelles of cultured cells.

Since the recent boost in the usage of electron microscopy in life-science research, there is a great need for new methods. Recently minimal resin embedding methods have been successfully introduced in the sample preparation for focused-ion beam scanning electron microscopy (FIB-SEM). In these methods several possibilities are given to remove as much resin as possible from the surface of cultured cells or multicellular organisms. Here we introduce an alternative way in the minimal resin embedding method to remove excess of resin from two widely different cell types by the use of Mascotte filter paper. Our goal in correlative light and electron microscopic studies of immunogold-labelled breast cancer SKBR3 cells was to visualise gold-labelled HER2 plasma membrane proteins as well as the intracellular structures of flat and round cells. We found a significant difference (p < 0.001) in the number of gold particles of selected cells per 0.6 µm2 cell surface: on average a flat cell contained 2.46 ± 1.98 gold particles, and a round cell 5.66 ± 2.92 gold particles. Moreover, there was a clear difference in the subcellular organisation of these two cells. The round SKBR3 cell contained many organelles, such as mitochondria, Golgi and endoplasmic reticulum, when compared with flat SKBR3 cells. Our next goal was to visualise crosswall associated organelles, septal pore caps, of Rhizoctonia solani fungal cells by the combined use of a heavy metal staining and our extremely thin layer plastification (ETLP) method. At low magnifications this resulted into easily finding septa which appeared as bright crosswalls in the back-scattered electron mode in the scanning electron microscope. Then, a septum was selected for FIB-SEM. Cross-sectioned views clearly revealed the perforate septal pore cap of R. solani next to other structures, such as mitochondria, endoplasmic reticulum, lipid bodies, dolipore septum, and the pore channel. As the ETLP method was applied on two widely different cell types, the use of the ETLP method will be beneficial to correlative studies of other cell model systems and multicellular organisms.

Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women.

PURPOSE: Increased gut permeability causes the trespass of antigens into the blood stream which leads to inflammation. Gut permeability reflected by serum zonulin and diversity of the gut microbiome were investigated in this cross-sectional study involving female study participants with different activity and BMI levels. METHODS: 102 women were included (BMI range 13.24-46.89 kg m-2): Anorexia nervosa patients (n = 17), athletes (n = 20), normal weight (n = 25), overweight (n = 21) and obese women (n = 19). DNA was extracted from stool samples and subjected to 16S rRNA gene analysis (V1-V2). Quantitative Insights Into Microbial Ecology (QIIME) was used to analyze data. Zonulin was measured with ELISA. Nutrient intake was assessed by repeated 24-h dietary recalls. We used the median of serum zonulin concentration to divide our participants into a "high-zonulin" (> 53.64 ng/ml) and "low-zonulin" (< 53.64 ng/ml) group. RESULTS: The alpha-diversity (Shannon Index, Simpson Index, equitability) and beta-diversity (unweighted and weighted UniFrac distances) of the gut microbiome were not significantly different between the groups. Zonulin concentrations correlated significantly with total calorie-, protein-, carbohydrate-, sodium- and vitamin B12 intake. Linear discriminant analysis effect size (LEfSe) identified Ruminococcaceae (LDA = 4.163, p = 0.003) and Faecalibacterium (LDA = 4.151, p = 0.0002) as significantly more abundant in the low zonulin group. CONCLUSION: Butyrate-producing gut bacteria such as Faecalibacteria could decrease gut permeability and lower inflammation. The diversity of the gut microbiota in women does not seem to be correlated with the serum zonulin concentration. Further interventional studies are needed to investigate gut mucosal permeability and the gut microbiome in the context of dietary factors.

A novel immuno-gold labeling protocol for nanobody-based detection of HER2 in breast cancer cells using immuno-electron microscopy.

Immuno-electron microscopy is commonly performed with the use of antibodies. In the last decade the antibody fragment indicated as nanobody (VHH or single domain antibody) has found its way to different applications previously done with conventional antibodies. Nanobodies can be selected to bind with high affinity and specificity to different antigens. They are small (molecular weight ca. 15kDa) and are usually easy to produce in microorganisms. Here we have evaluated the feasibility of a nanobody binding to HER2 for application in immuno-electron microscopy. To obtain highest labeling efficiency combined with optimal specificity, different labeling conditions were analysed, which included nanobody concentration, fixation and blocking conditions. The obtained optimal protocol was applied for post-embedment labeling of Tokuyasu cryosections and for pre-embedment labeling of HER2 for fluorescence microscopy and both transmission and scanning electron microscopy. We show that formaldehyde fixation after incubation with the anti-HER2 nanobody, improves labeling intensity. Among all tested blocking agents the best results were obtained with a mixture of cold water fish gelatine and acetylated bovine serum albumin, which prevented a-specific interactions causing background labeling while preserving specific interactions at the same time. In conclusion, we have developed a nanobody-based protocol for immuno-gold labeling of HER2 for Tokuyasu cryosections in TEM as well as for pre-embedment gold labeling of cells for both TEM and SEM.

[Reorientation of Medical Procedures Covered by Statutory Accident Insurance]. / Neuausrichtung der Heilverfahren der Gesetzlichen Unfallversicherung.

As of 01/01/2014, the German Statutory Accident Insurance (DGUV) has reorganized inpatient medical procedures. The central element of reorientation is the reorganization of the catalogue of types of accidents and type of medical procedures of hospitalized injured patients in 3 care stages. In addition, the reorientation also concentrates on hospitals with the highest performance and the best qualification and also focuses on severe and most severe injuries.This reorientation is also based on the White Paper of the German Society for Trauma Surgery (DGU), especially on the Trauma Network DGU. The new regulations will be implemented by the state associations of the German Statutory Accident Insurance.The hierarchy of care depends on established admission criteria and the severity of injury. This structuring also refers to special competence in the field of rehabilitation and will lead to the strengthening of multidisciplinary rehabilitation management and workplace-related modules of the healthcare. Overall, the accident insurance institution will place increased demands on their network partners.

[Intraoperative parathyroid hormone measurement is the best predictor of postoperative symptomatic hypocalcemia]. / Die intraoperative Parathormonmessung als bester Indikator einer postoperativen symptomatischen Hypokalzämie.

BACKGROUND: The goal of this study is to evaluate risk factors for transient postoperative hypocalcemia (HC) and to define cutoff values for perioperative parathyroid hormone (PTH) and calcium parameters (Ca) to reduce the morbidity of symptomatic HC. MATERIALS AND METHODS: At our tertiary referral hospital (Luzerner Kantonsspital, Switzerland), a total of 353 patients underwent total thyroidectomy between 2006 and 2013 and were analyzed retrospectively in terms of HC risk. The serum values of calcium and PTH were measured at strictly defined time intervals, and patients' symptoms and the necessity of treatments were determined from patients' charts. RESULTS: The prevalence of transient postoperative HC was 43%; however, only 10% of patients were symptomatic. Significant risk factors for serum and symptomatic HC were calcium values (pre-, intra-, 4 h and 1 d postoperative), PTH values (intraoperative, 4 h and 1 d postoperative), and PTH decline. Interestingly, preoperative PTH values, patient age, weight of the thyroid gland, diagnosis, and sex were not significant risk factors. In the ROC analysis ('receiver operating characteristics'), calcium measurement 4 h postoperatively showed the best predictive ability for detecting serum HC, whereas intraoperative PTH measurements were predictive for symptomatic HC. CONCLUSION: Calcium and PTH values as well as PTH decline are significant risk factors for postoperative HC. Preoperatively, only calcium measurement is prognostically significant. Intraoperative PTH measurement is the most reasonable and sensitive factor for early recognition of temporary postoperative HC in the clinical setting.

Silexan does not cause withdrawal symptoms even when abruptly discontinued.

OBJECTIVE: Subsequent to a randomised, double-blind, double dummy clinical trial assessing the efficacy of silexan compared to placebo and paroxetine in patients suffering from generalised anxiety disorder (GAD), a 1week follow-up phase was added in order to assess possible withdrawal symptoms of silexan after abrupt discontinuation. METHODS: Participants received silexan 80 mg/d, silexan 160 mg/d, paroxetine 20 mg/d, or placebo at a ratio of 1:1:1:1. Study medication was discontinued after the 10 week active treatment phase of the original trial. Whereas paroxetine was tapered as indicated, silexan administration was discontinued abruptly. Assessment of possible withdrawal effects was done using the Physician Withdrawal Checklist questionnaire (PWC-20). RESULTS: During the 1 week down-titration phase, mean total PWC-20 scores had reduced by 0.19 in placebo, 0.23 in silexan 80, 0.65 in silexan 160, and 0.51 in paroxetine. The median change in all four groups was 0.00. In none of the treatment groups withdrawal effects occurred after discontinuation. CONCLUSIONS: Values assessed for the silexan groups indicate the absence of a dependency potential of this preparation.

Morphogenetically active scaffold for osteochondral repair (polyphosphate/alginate/N,O-carboxymethyl chitosan).

Here we describe a novel bioinspired hydrogel material that can be hardened with calcium ions to yield a scaffold material with viscoelastic properties matching those of cartilage. This material consists of a negatively charged biopolymer triplet, composed of morphogenetically active natural inorganic polyphosphate (polyP), along with the likewise biocompatible natural polymers N,O-carboxymethyl chitosan (N,O-CMC) and alginate. The porosity of the hardened scaffold material obtained after calcium exposure can be adjusted by varying the pre-processing conditions. Various compression tests were applied to determine the local (nanoindentation) and bulk mechanical properties (tensile/compression test system for force measurements) of the N,O-CMC-polyP-alginate material. Determinations of the Young's modulus revealed that the stiffness of this comparably water rich (and mouldable) material increases during successive compression cycles to values measured for native cartilage. The material not only comprises viscoelastic properties suitable for a cartilage substitute material, but also displays morphogenetic activity. It upregulates the expression of genes encoding for collagen type II and aggrecan, the major proteoglycan within the articular cartilage, in human chondrocytes, and the expression of alkaline phosphatase in human bone-like SaOS-2 cells, as revealed in RT qPCR experiments. Further, we demonstrate that the new polyP-based material can be applied for manufacturing 3D solid models of cartilage bone such as of the tibial epiphyseal plate and the superior articular cartilage surface. Since the material is resorbable and enhances the activity of cells involved in regeneration of cartilage tissue, this material has the potential to be used for artificial articular cartilage implants.

Artificial cartilage bio-matrix formed of hyaluronic acid and Mg2+-polyphosphate.

Here we show that inorganic polyphosphate (polyP), a polyanionic metabolic regulator consisting of multiple phosphate residues linked by energy-rich phosphoanhydride bonds, is present in the synovial fluid. In a biomimetic approach, to enhance cartilage synthesis and regeneration, we prepared amorphous polyP microparticles with Mg2+ as counterions. The particles were characterised by X-ray diffraction (XRD), energy-dispersive X-ray (EDX) and Fourier transformed infrared spectroscopic (FTIR) analyses. Similar particles were obtained after addition of Mg2+ ions to a solution containing hyaluronic acid, as a major component of the synovial fluid, and soluble Na-polyP. The viscous paste-like material formed, composed of globular microparticles with diameter of 400 nm, strongly promoted the adhesion of chondrocytes and caused a significant upregulation of the expression of the genes encoding collagen type 3A1, as a marker for chondrocyte differentiation, and SOX9, a transcription factor that regulates chondrocyte differentiation and proliferation. The expression level of the collagen type 3A1 gene was also enhanced by exposure of chondrocytes to synovial fluid that was found to contain polyP with a size of about 80 phosphate residues. This stimulatory effect was abolished after pre-incubation of the synovial fluid with the polyP degrading alkaline phosphatase. We propose a strategy for treatment of joint dysfunctions caused by osteoarthritis based on the application of amorphous Mg2+-polyP microparticles thatprevent calcium crystal formation in the synovial fluid using scavenging Ca2+ ions (Mg2+/Ca2+ exchange) and enhance chondrocyte function after binding of the Ca2+-polyP to hyaluronic acid at the cartilage surface.

Optimal designs for copula models.

Copula modelling has in the past decade become a standard tool in many areas of applied statistics. However, a largely neglected aspect concerns the design of related experiments. Particularly the issue of whether the estimation of copula parameters can be enhanced by optimizing experimental conditions and how robust all the parameter estimates for the model are with respect to the type of copula employed. In this paper an equivalence theorem for (bivariate) copula models is provided that allows formulation of efficient design algorithms and quick checks of whether designs are optimal or at least efficient. Some examples illustrate that in practical situations considerable gains in design efficiency can be achieved. A natural comparison between different copula models with respect to design efficiency is provided as well.

¹H- and ¹³C-NMR spectroscopy of Thy-1-APPSL mice brain extracts indicates metabolic changes in Alzheimer's disease.

Biochemical alterations underlying the symptoms and pathomechanisms of Alzheimer's disease (AD) are not fully understood. However, alterations of glucose metabolism and mitochondrial dysfunction certainly play an important role. (1)H- and (13)C-NMR spectroscopy exhibits promising results in providing information about those alterations in vivo in patients and animals, especially regarding the mitochondrial tricarboxylic acid (TCA) cycle. Accordingly, transgenic mice expressing mutant human amyloid precursor protein (APP(SL))-serving as a model of neuropathological changes in AD-were examined with in vitro 1D (1)H- and 2D (1)H-(13)C-HSQC-NMR spectroscopy after oral administration of 1-(13)C-glucose and acquisition of brain material after 30 min. Perchloric acid extracts were measured using a 500 MHz spectrometer, providing more detailed information compared to in vivo spectra achievable nowadays. Area under curve (AUC) data of metabolite peaks were obtained and normalized in relation to the creatine signal, serving as internal reference. Besides confirming well-known metabolic alterations in AD like decreased N-acetylaspartate (NAA)/Creatine (Cr) ratio, new findings such as a decrease in phosphorylcholine (PC) are presented. Glutamate (Glu) and glutamine (Gln) concentrations were decreased while γ-aminobutyric acid (GABA) was elevated in Thy1-APP(SL) mice. (13)C-NMR spectroscopy revealed a shift in the Glx-2/Glx-4-ratio-where Glx represents a combined Glu/Gln-signal-towards Glx-2 in AD. These findings correlated well with the NAA/Cr-ratio. The Gln-4/Glu-4-ratio is altered in favor of Glu. Our findings suggest that glutamine synthetase (GS), which is predominantly present in glial cells may be impaired in the brain of Thy1-APP(SL) transgenic mice. Since GS is an ATP-dependent enzyme, mitochondrial dysfunction might contribute to reduced activity, which might also account for the increased metabolism of glutamate via the GABA shunt, a metabolic pathway to bypass intra-mitochondrial α-ketoglutarate-dehydrogenase, resulting in elevated GABA levels.

Aspergillus thyroiditis: first antemortem case diagnosed by fine-needle aspiration culture in a pediatric stem cell transplant patient.

Aspergillus thyroiditis (AT) has historically been considered a postmortem diagnosis in immunocompromised patients; most have disseminated disease. This report summarizes the clinical challenge of diagnosing AT. It also highlights the value of the early use of thyroid fine-needle aspiration culture and the need for a high index of suspicion to reach the final diagnosis before disease dissemination.

Breeding density affects the movements of gull chicks, the size of their home ranges and their association with neighbours.

Colonies of ground-nesting species often have heterogeneous nest densities and their offspring experience different social conditions depending on the size and location of the breeding territory. For example, unintentional territory crossing by mobile chicks can trigger strong aggression from neighbouring adults, as observed in semi-precocial gulls. This would be expected to shape chicks' movement tendencies, exploratory behaviour and propensity for social contact through aversive feedback learning or pre-natal maternal effects, as mothers may pre-adapt their offspring's behaviour to the expected early life conditions. Therefore, we hypothesize that lesser black-backed gull chicks reared in denser areas of the breeding colony will move less, have smaller home ranges and have fewer social contacts with chicks from neighbouring nests. To test this, we first cross-fostered full clutches between and within high- and low-density parts of the colony, and then used ultra-wideband tags to track free-ranging chicks. In line with our predictions, we found that chicks reared in denser areas had a lower movement activity and smaller home ranges. However, these chicks still had more social contacts, although not necessarily with a higher number of unique individuals. Pre-natal breeding density had no significant effect on any of the parameters. We conclude that parental nest choice strongly affects the early social environment of their chicks, which can shape the development of their (social) phenotype, with potentially long-lasting consequences.

Bioarchaeology aids the cultural understanding of six characters in search of their agency (Tarquinia, ninth-seventh century BC, central Italy).

Etruria contained one of the great early urban civilisations in the Italian peninsula during the first millennium BC, much studied from a cultural, humanities-based, perspective, but relatively little with scientific data, and rarely in combination. We have addressed the unusual location of twenty inhumations found in the sacred heart of the Etruscan city of Tarquinia, focusing on six of these as illustrative, contrasting with the typical contemporary cremations found in cemeteries on the edge of the city. The cultural evidence suggests that the six skeletons were also distinctive in their ritualization and memorialisation. Focusing on the six, as a representative sample, the scientific evidence of osteoarchaeology, isotopic compositions, and ancient DNA has established that these appear to show mobility, diversity and violence through an integrated bioarchaeological approach. The combination of multiple lines of evidence makes major strides towards a deeper understanding of the role of these extraordinary individuals in the life of the early city of Etruria.

Constraints on spin-dependent short-range interaction between nucleons.

We search for a spin-dependent P- and T-violating nucleon-nucleon interaction mediated by light pseudoscalar bosons such as axions or axionlike particles. We employ an ultrasensitive low-field magnetometer based on the detection of free precession of colocated 3He and 129Xe nuclear spins using SQUIDs as low-noise magnetic flux detectors. The precession frequency shift in the presence of an unpolarized mass was measured to determine the coupling of pseudoscalar particles to the spin of the bound neutron. For boson masses between 2 and 500 µeV (force ranges between 3×1(-4) m and 10(-1) m) we improved the laboratory upper bounds by up to 4 orders of magnitude.

Antibacterial biodegradable Mg-Ag alloys.

The use of magnesium alloys as degradable metals for biomedical applications is a topic of ongoing research and the demand for multifunctional materials is increasing. Hence, binary Mg-Ag alloys were designed as implant materials to combine the favourable properties of magnesium with the well-known antibacterial property of silver. In this study, three Mg-Ag alloys, Mg2Ag, Mg4Ag and Mg6Ag that contain 1.87 %, 3.82 % and 6.00 % silver by weight, respectively, were cast and processed with solution (T4) and aging (T6) heat treatment. The metallurgical analysis and phase identification showed that all alloys contained Mg4Ag as the dominant ß phase. After heat treatment, the mechanical properties of all Mg-Ag alloys were significantly improved and the corrosion rate was also significantly reduced, due to presence of silver. Mg(OH)2 and MgO present the main magnesium corrosion products, while AgCl was found as the corresponding primary silver corrosion product. Immersion tests, under cell culture conditions, demonstrated that the silver content did not significantly shift the pH and magnesium ion release. In vitro tests, with both primary osteoblasts and cell lines (MG63, RAW 264.7), revealed that Mg-Ag alloys show negligible cytotoxicity and sound cytocompatibility. Antibacterial assays, performed in a dynamic bioreactor system, proved that the alloys reduce the viability of two common pathogenic bacteria, Staphylococcus aureus (DSMZ 20231) and Staphylococcus epidermidis (DSMZ 3269), and the results showed that the killing rate of the alloys against tested bacteria exceeded 90%. In summary, biodegradable Mg-Ag alloys are cytocompatible materials with adjustable mechanical and corrosion properties and show promising antibacterial activity, which indicates their potential as antibacterial biodegradable implant materials.

Treatment of comorbid anxiety and depression with escitalopram: results of a post-marketing surveillance study.

INTRODUCTION: In this 16-week post-marketing surveillance (PMS) study, antidepressant effects and tolerability of escitalopram was examined in 2 911 patients with comorbid depression and anxiety. METHODS: Antidepressant effects were assessed using a modified version of the Montgomery-Åsberg depression rating scale (svMADRS), the Hamilton anxiety scale (HAMA) and the hospital anxiety depression scale (HADS-D) and the clinical global impression scale (CGI-S, CGI-I). RESULTS: Treatment was completed by 2 718 patients, whose severity of depression decreased from a mean svMADRS total score of 33.0 to 8.9. At the end of the study, the remission rate (svMADRS≤12) was 72.9% and the response rate (≥50% decrease in svMADRS score) was 83.1% (LOCF). Similarly, the severity of anxiety symptoms decreased from a mean HAMA total score of 28.8-8.8; the remission rate (HAMA<10) was 63.9% and the response rate (decrease≥50%) was 80.2%. The most frequent adverse events were nausea (1.6%), agitation (1.1%) and fatigue (0.7%). DISCUSSION: Antidepressant effects and good tolerability of escitalopram were confirmed in everyday practice in patients with comorbid depression and anxiety. The high response and remission rates were within the range reported in previous RTC's of escitalopram vs. comparators or vs. placebo.