The modern role of antipsychotics for the treatment of agitation and psychosis in Alzheimer's disease

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordINTRODUCTION: Antipsychotics have long been the mainstay of treatment for agitation and psychosis in Alzheimer's disease. Despite their current use successive studies have shown that they only confer a modest benefit which must be balanced against their well-established serious side effects (extrapyramidal symptoms, stroke, accelerated cognitive decline and mortality). Areas covered: This review outlines the current guidance on antipsychotic usage and the evidence of their continued usage against a backdrop of emerging pharmacological treatments and an increasing emphasis on the importance of non-pharmacological interventions. Expert Commentary: The current justification for antipsychotic us in the context the changing landscape of prescribing and provide a view on the most promising alternative candidates to this class of drug are appraised

Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites

ObjectiveInhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery.Study designA subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites.ResultiNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome.ConclusioniNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments

Long-term magnetic activity of a sample of M-dwarf stars from the HARPS program II. Activity and radial velocity

Due to their low mass and luminosity, M dwarfs are ideal targets if one hopes to find low-mass planets similar to Earth by using the radial velocity (RV) method. However, stellar magnetic cycles could add noise or even mimic the RV signal of a long-period companion. Following our previous work that studied the correlation between activity cycles and long-term RV variations for K dwarfs we now expand that research to the lower-end of the main sequence. Our objective is to detect any correlations between long-term activity variations and the observed RV of a sample of M dwarfs. We used a sample of 27 M-dwarfs with a median observational timespan of 5.9 years. The cross-correlation function (CCF) with its parameters RV, bisector inverse slope (BIS), full-width-at-half- maximum (FWHM) and contrast have been computed from the HARPS spectrum. The activity index have been derived using the Na I D doublet. These parameters were compared with the activity level of the stars to search for correlations. We detected RV variations up to ~5 m/s that we can attribute to activity cycle effects. However, only 36% of the stars with long-term activity variability appear to have their RV affected by magnetic cycles, on the typical timescale of ~6 years. Therefore, we suggest a careful analysis of activity data when searching for extrasolar planets using long-timespan RV data.Comment: 20 pages, 12 figures, 3 tables, accepted for publication in Astronomy and Astophysic

Existence results for a contact problem with varying friction coefficient and nonlinear forces

We consider the rate-independent problem of a particle moving in a three - dimensional half space subject to a time-dependent nonlinear restoring force having a convex potential and to Coulomb friction along the flat boundary of the half space, where the friction coefficient may vary along the boundary. Our existence result allows for solutions that may switch arbitrarily often between unconstrained motion in the interior and contact where the solutions may switch between sticking and frictional sliding. However, our existence result is local and guarantees continuous solutions only as long as the convexity of the potential is strong enough to compensate the variation of the friction coefficient times the contact pressure. By simple examples we show that our sufficient conditions are also necessary. Our method is based on the energetic formulation of rate-independent systems as developed by Mielke and co-workers. We generalize the time-incremental minimization procedure of Mielke and Rossi for the present situation of a non-associative flow rule

Subthreshold depression as a risk indicator for major depressive disorder: a systematic review of prospective studies.

Objective: In order to examine whether the incidence of major depressive disorder (MDD) is increased in subjects with subthreshold depression, or sD (clinically relevant depressive symptoms, without meeting criteria for a full-blown MDD), we conducted a review of prospective studies examining the incidence of MDD in subjects with sD. Method: A systematic literature search was conducted. For all studies, the relative risk of developing MDD was calculated, based on person-years. Results: Twenty studies (23 comparisons) were found, based on community samples, general medical patients and high-risk subjects. Most comparisons showed that subjects with sD had a consistently larger chance of developing MDD. The studies differed considerably in the definition of sD, the recency (occurrence of the last sD) and the in-/ exclusion of lifetime MDD. Conclusion: The incidence of MDD in subjects with sD is larger than in subjects without sD. Otherwise, the concept of sD is too broad to be used. In future studies, some consensus should be reached regarding the definition of sD

Reversible vancomycin susceptibility within emerging ST1421 Enterococcus faecium strains is associated with rearranged vanA-gene clusters and increased vanA plasmid copy number

Vancomycin variable enterococci (VVE) are van-positive enterococci with a vancomycin-susceptible phenotype (VVE-S) that can convert to a resistant phenotype (VVE-R) and be selected for during vancomycin exposure. VVE-R outbreaks have been reported in Canada and Scandinavian countries. The aim of this study was to examine the presence of VVE in whole genome sequenced (WGS) Australian bacteremia Enterococcus faecium (Efm) isolates collected through the Australian Group on Antimicrobial resistance (AGAR) network. Eight potential VVEAus isolates, all identified as Efm ST1421, were selected based on the presence of vanA and a vancomycin-susceptible phenotype. During vancomycin selection, two potential VVE-S harboring intact vanHAX genes, but lacking the prototypic vanRS and vanZ genes, reverted to a resistant phenotype (VVEAus-R). Spontaneous VVEAus-R reversion occurred at a frequency of 4-6 × 10−8 resistant colonies per parent cell in vitro after 48 h and led to high-level vancomycin and teicoplanin resistance. The S to R reversion was associated with a 44-bp deletion in the vanHAX promoter region and an increased vanA plasmid copy number. The deletion in the vanHAX promoter region enables an alternative constitutive promoter for the expression of vanHAX. Acquisition of vancomycin resistance was associated with a low fitness cost compared with the corresponding VVEAus-S isolate. The relative proportion of VVEAus-R vs. VVEAus-S decreased over time in serial passages without vancomycin selection. Efm ST1421 is one of the predominant VanA-Efm multilocus sequence types found across most regions of Australia, and has also been associated with a major prolonged VVE outbreak in Danish hospitals

3D time series analysis of cell shape using Laplacian approaches

Background: Fundamental cellular processes such as cell movement, division or food uptake critically depend on cells being able to change shape. Fast acquisition of three-dimensional image time series has now become possible, but we lack efficient tools for analysing shape deformations in order to understand the real three-dimensional nature of shape changes. Results: We present a framework for 3D+time cell shape analysis. The main contribution is three-fold: First, we develop a fast, automatic random walker method for cell segmentation. Second, a novel topology fixing method is proposed to fix segmented binary volumes without spherical topology. Third, we show that algorithms used for each individual step of the analysis pipeline (cell segmentation, topology fixing, spherical parameterization, and shape representation) are closely related to the Laplacian operator. The framework is applied to the shape analysis of neutrophil cells. Conclusions: The method we propose for cell segmentation is faster than the traditional random walker method or the level set method, and performs better on 3D time-series of neutrophil cells, which are comparatively noisy as stacks have to be acquired fast enough to account for cell motion. Our method for topology fixing outperforms the tools provided by SPHARM-MAT and SPHARM-PDM in terms of their successful fixing rates. The different tasks in the presented pipeline for 3D+time shape analysis of cells can be solved using Laplacian approaches, opening the possibility of eventually combining individual steps in order to speed up computations

Comparisons of host mitochondrial, nuclear and endosymbiont bacterial genes reveal cryptic fig wasp species and the effects of Wolbachia on host mtDNA evolution and diversity

Background Figs and fig-pollinating wasp species usually display a highly specific one-to-one association. However, more and more studies have revealed that the "one-to-one" rule has been broken. Co-pollinators have been reported, but we do not yet know how they evolve. They may evolve from insect speciation induced or facilitated by Wolbachia which can manipulate host reproduction and induce reproductive isolation. In addition, Wolbachia can affect host mitochondrial DNA evolution, because of the linkage between Wolbachia and associated mitochondrial haplotypes, and thus confound host phylogeny based on mtDNA. Previous research has shown that fig wasps have the highest incidence of Wolbachia infection in all insect taxa, and Wolbachia may have great influence on fig wasp biology. Therefore, we look forward to understanding the influence of Wolbachia on mitochondrial DNA evolution and speciation in fig wasps. Results We surveyed 76 pollinator wasp specimens from nine Ficus microcarpa trees each growing at a different location in Hainan and Fujian Provinces, China. We found that all wasps were morphologically identified as Eupristina verticillata, but diverged into three clades with 4.22-5.28% mtDNA divergence and 2.29-20.72% nuclear gene divergence. We also found very strong concordance between E. verticillata clades and Wolbachia infection status, and the predicted effects of Wolbachia on both mtDNA diversity and evolution by decreasing mitochondrial haplotypes. Conclusions Our study reveals that the pollinating wasp E. verticillata on F. microcarpa has diverged into three cryptic species, and Wolbachia may have a role in this divergence. The results also indicate that Wolbachia strains infecting E. verticillata have likely resulted in selective sweeps on host mitochondrial DNA