MDMA and brain activity during neurocognitive performance: An overview of neuroimaging studies with abstinent 'Ecstasy' users.

MDMA/Ecstasy has had a resurgence in popularity, with recent supplies comprising higher strength MDMA, potentially leading to increased drug-related harm. Neurocognitive problems have been widely reported in ecstasy users, equally some studies report null findings, and it remains unclear which factors underlie the development of neurocognitive impairments. This review covers the empirical research into brain activity during neurocognitive performance, using fMRI, fNIRS, and EEG. Our main conclusion is that chronic repeated use of recreational ecstasy can result in haemodynamic and electrophysiological changes that reflect recruitment of additional resources to perform cognitive tasks. Findings are consistent with serotonergic system changes, although whether this reflects neurotoxicity or neuroadaptation, cannot be answered from these data. There is a degree of heterogeneity in the methodologies and findings, limiting the strengths of current conclusions. Future research with functional neuroimaging paired with molecular imaging, genetics or pharmacological challenges of the serotonin system may help to decipher the link between serotonergic and cognitive changes in ecstasy users

Modelling spatio-temporal data with multiple seasonalities: the NO2 portuguese case

This study aims at characterizing the spatial and temporal dynamics of spatio-temporal data sets, characterized by high resolution in the temporal dimension which are becoming the norm rather than the exception in many application areas, namely environmental modelling. In particular, air pollution data, such as NO2 concentration levels, often incorporate also multiple recurring patterns in time imposed by social habits, anthropogenic activities and meteorological conditions. A two-stage modelling approach is proposed which combined with a block bootstrap procedure correctly assesses uncertainty in parameters estimates and produces reliable confidence regions for the space-time phenomenon under study. The methodology provides a model that is satisfactory in terms of goodness of fit, interpretability, parsimony, prediction and forecasting capability and computational costs. The proposed framework is potentially useful for scenario drawing in many areas, including assessment of environmental impact and environmental policies, and in a myriad applications to other research fields. (C) 2017 Elsevier B.V. All rights reserved.- The authors acknowledge Foundation FCT (Fundacao para a Ciencia e Tecnologia) for funding through Individual Scholarship Ph.D. PD/BD/105743/2014, Centre of Mathematics of Minho University within project UID/MAT/00013/2013 and Center for Research & Development in Mathematics and Applications of Aveiro University within project UID/MAT/04106/2013.info:eu-repo/semantics/publishedVersio

Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

Clinical Adjudication of Hemodialysis Catheter-Related Bloodstream Infections: Findings from the REDUCCTION Trial.

KEY POINTS: The inter-rater reliability of reporting hemodialysis catheter-related infectious events between site investigators and trial adjudicators in Australia and New Zealand was substantial. The high concordance level in reporting catheter infections improves confidence in using site-level bacteremia rates as a clinical metric for quality benchmarking and future pragmatic clinical trials. A rigorous adjudication protocol may not be needed if clearly defined criteria to ascertain catheter-associated bacteremia are used. BACKGROUND: Hemodialysis catheter-related bloodstream infection (HD-CRBSI) are a significant source of morbidity and mortality among dialysis patients, but benchmarking remains difficult because of varying definitions of HD-CRBSI. This study explored the effect of clinical adjudication process on HD-CRBSI reporting. METHODS: The REDUcing the burden of Catheter ComplicaTIOns: a National approach trial implemented an evidence-based intervention bundle using a stepped-wedge design to reduce HD-CRBSI rates in 37 Australian kidney services. Six New Zealand services participated in an observational capacity. Adult patients with a new hemodialysis catheter between December 2016 and March 2020 were included. HD-CRBSI events reported were compared with the adjudicated outcomes using the end point definition and adjudication processes of the REDUcing the burden of Catheter ComplicaTIOns: a National approach trial. The concordance level was estimated using Gwet agreement coefficient (AC1) adjusted for service-level effects and implementation tranches (Australia only), with the primary outcome being the concordance of confirmed HD-CRBSI. RESULTS: A total of 744 hemodialysis catheter-related infectious events were reported among 7258 patients, 12,630 catheters, and 1.3 million catheter-exposure days. The majority were confirmed HD-CRBSI, with 77.9% agreement and substantial concordance (AC1=0.77; 95% confidence interval [CI], 0.73 to 0.81). Exit site infections have the highest concordance (AC1=0.85; 95% CI, 0.78 to 0.91); the greatest discordance was in events classified as other (AC1=0.33; 95% CI, 0.16 to 0.49). The concordance of all hemodialysis catheter infectious events remained substantial (AC1=0.80; 95% CI, 0.76 to 0.83) even after adjusting for the intervention tranches in Australia and overall service-level clustering. CONCLUSIONS: There was a substantial level of concordance in overall and service-level reporting of confirmed HD-CRBSI. A standardized end point definition of HD-CRBSI resulted in comparable hemodialysis catheter infection rates in Australian and New Zealand kidney services. Consistent end point definition could enable reliable benchmarking outside clinical trials without the need for independent clinical adjudication

The European Hematology Association Roadmap for European Hematology Research: a consensus document

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients