Identifying critically important vascular access outcomes for trials in haemodialysis : an international survey with patients, caregivers and health professionals

BACKGROUND: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes. METHOD: Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically. RESULTS: The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle. CONCLUSIONS: Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD

Toward Fulfilling the Promise of Molecular Medicine in Fragile X

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and a leading known cause of autism. It is caused by loss of expression of the fragile X mental retardation protein (FMRP), an RNA-binding protein that negatively regulates protein synthesis. In neurons, multiple lines of evidence suggest that protein synthesis at synapses is triggered by activation of group 1 metabotropic glutamate receptors (Gp1 mGluRs) and that many functional consequences of activating these receptors are altered in the absence of FMRP. These observations have led to the theory that exaggerated protein synthesis downstream of Gp1 mGluRs is a core pathogenic mechanism in FXS. This excess can be corrected by reducing signaling by Gp1 mGluRs, and numerous studies have shown that inhibition of mGluR5, in particular, can ameliorate multiple mutant phenotypes in animal models of FXS. Clinical trials based on this therapeutic strategy are currently under way. FXS is therefore poised to be the first neurobehavioral disorder in which corrective treatments have been developed from the bottom up: from gene identification to pathophysiology in animals to novel therapeutics in humans. The insights gained from FXS and other autism-related single-gene disorders may also assist in identifying molecular mechanisms and potential treatment approaches for idiopathic autism.Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.)National Institute of Mental Health (U.S.)FRAXA Research Foundatio

Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity

Recommendations for accurate CT diagnosis of suspected acute aortic syndrome (AAS)-on behalf of the British Society of Cardiovascular Imaging (BSCI)/British Society of Cardiovascular CT (BSCCT)

Accurate and timely assessment of suspected acute aortic syndrome is crucial in this life-threatening condition. Imaging with CT plays a central role in the diagnosis to allow expedited management. Diagnosis can be made using locally available expertise with optimized scanning parameters, making full use of recent advances in CT technology. Each imaging centre must optimize their protocols to allow accurate diagnosis, to optimize radiation dose and in particular to reduce the risk of false-positive diagnosis that may simulate disease. This document outlines the principles for the acquisition of motion-free imaging of the aorta in this context.published_or_final_versio

Genetic characterisation of farmed rainbow trout in Norway: intra- and inter-strain variation reveals potential for identification of escapees

<p>Abstract</p> <p>Background</p> <p>The rainbow trout (<it>Oncorhynchus mykiss</it>) is one of the most important aquaculture species in the world, and Norway is one of the largest producers. The present study was initiated in response to a request from the Norwegian police authority to identify the farm of origin for 35 escaped rainbow trout captured in a fjord. Eleven samples, each consisting of approximately 47 fish, were collected from the three farms operating in the fjord where the escapees were captured. In order to gain a better general understanding of the genetic structure of rainbow trout strains used in Norwegian aquaculture, seven samples (47 fish per sample) were collected from six farms located outside the region where the escapees were captured. All samples, including the escapees, were genotyped with 12 microsatellite loci.</p> <p>Results</p> <p>All samples displayed considerable genetic variability at all loci (mean number of alleles per locus per sample ranged from 5.4–8.6). Variable degrees of genetic differentiation were observed among the samples, with pair-wise <it>F</it>_STvalues ranging from 0–0.127. Self-assignment tests conducted among the samples collected from farms outside the fjord where the escapees were observed gave an overall correct assignment of 82.5%, demonstrating potential for genetic identification of escapees. In the "real life" assignment of the 35 captured escapees, all were excluded from two of the samples included as controls in the analysis, and 26 were excluded from the third control sample. In contrast, only 1 of the escapees was excluded from the 11 pooled samples collected on the 3 farms operating in the fjord.</p> <p>Conclusion</p> <p>Considerable genetic variation exists within and among rainbow trout strains farmed in Norway. Together with modern statistical methods, this will provide commercial operators with a tool to monitor breeding and fish movements, and management authorities with the ability to identify the source of escapees. The data generated in this study were used by the Norwegian police to initiate an investigation of the company operating the three farms in the fjord where escapees were observed.</p

Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

Peer reviewedPublisher PD

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; &lt;4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

The genomic evolution of human prostate cancer.

Prostate cancers are highly prevalent in the developed world, with inheritable risk contributing appreciably to tumour development. Genomic heterogeneity within individual prostate glands and between patients derives predominantly from structural variants and copy-number aberrations. Subtypes of prostate cancers are being delineated through the increasing use of next-generation sequencing, but these subtypes are yet to be used to guide the prognosis or therapeutic strategy. Herein, we review our current knowledge of the mutational landscape of human prostate cancer, describing what is known of the common mutations underpinning its development. We evaluate recurrent prostate-specific mutations prior to discussing the mutational events that are shared both in prostate cancer and across multiple cancer types. From these data, we construct a putative overview of the genomic evolution of human prostate cancer

Competition and educational quality: evidence from the Netherlands

Little evidence is available for the effect of competition on educational quality as only a few countries allow large-scale competition. In the Netherlands, free parental choice has been present since the beginning of the twentieth century and can be characterized as a full voucher program with 100 % funding. Based on micro panel data for the Netherlands, we show that there is a relation between competition and educational outcomes in secondary education, but that it is often negative and small, sometimes insignificant but never positive. This effect is larger for small and medium-sized schools and for schools that do not have a Protestant or Catholic denomination

XML-BSPM: an XML format for storing Body Surface Potential Map recordings

<p>Abstract</p> <p>Background</p> <p>The Body Surface Potential Map (BSPM) is an electrocardiographic method, for recording and displaying the electrical activity of the heart, from a spatial perspective. The BSPM has been deemed more accurate for assessing certain cardiac pathologies when compared to the 12-lead ECG. Nevertheless, the 12-lead ECG remains the most popular ECG acquisition method for non-invasively assessing the electrical activity of the heart. Although data from the 12-lead ECG can be stored and shared using open formats such as SCP-ECG, no open formats currently exist for storing and sharing the BSPM. As a result, an innovative format for storing BSPM datasets has been developed within this study.</p> <p>Methods</p> <p>The XML vocabulary was chosen for implementation, as opposed to binary for the purpose of human readability. There are currently no standards to dictate the number of electrodes and electrode positions for recording a BSPM. In fact, there are at least 11 different BSPM electrode configurations in use today. Therefore, in order to support these BSPM variants, the XML-BSPM format was made versatile. Hence, the format supports the storage of custom torso diagrams using SVG graphics. This diagram can then be used in a 2D coordinate system for retaining electrode positions.</p> <p>Results</p> <p>This XML-BSPM format has been successfully used to store the Kornreich-117 BSPM dataset and the Lux-192 BSPM dataset. The resulting file sizes were in the region of 277 kilobytes for each BSPM recording and can be deemed suitable for example, for use with any telemonitoring application. Moreover, there is potential for file sizes to be further reduced using basic compression algorithms, i.e. the deflate algorithm. Finally, these BSPM files have been parsed and visualised within a convenient time period using a web based BSPM viewer.</p> <p>Conclusions</p> <p>This format, if widely adopted could promote BSPM interoperability, knowledge sharing and data mining. This work could also be used to provide conceptual solutions and inspire existing formats such as DICOM, SCP-ECG and aECG to support the storage of BSPMs. In summary, this research provides initial ground work for creating a complete BSPM management system.</p