Cannabis use and risk of schizophrenia: a Mendelian randomization study.

Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent. Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09-1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19-1.67; P-value for heterogeneity =0.76). The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09-1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences

Green nanosilicas for monoaromatic hydrocarbons removal from air

We demonstrate a novel application of green nanosilicas (GN), prepared via an environmentally friendly route, in removing volatile organic compounds (VOCs). Herein, we aim to establish GN as viable alternatives to traditional mesoporous silicas for the removal of monoaromatic hydrocarbons (MAHC). The results show that the GN have high extraction efficiencies comparable to those previously reported for mesoporous silicas. It was demonstrated that bespoke GN can be syntheised readily with the ability to tailor their physical properties and MAHC adsorption. In order to understand the MAHC adsorption by GN, their porosity, morphology and pore structure were characterised. It was observed that the combination of broad pore size distribution and, in particular, the presence of meso- and micro-porosity in GN contributed to high MAHC extraction efficiencies and selectivity. Although from a commercial viewpoint, further optimisation of GN is desirable in order to replace traditional sorbents, this work clearly highlights a new family of “green” sorbents, which can be prepared with a substantial reduction in secondary pollution with potential applications in selective gas separation

Analysis of a spatial Lotka-Volterra model with a finite range predator-prey interaction

We perform an analysis of a recent spatial version of the classical Lotka-Volterra model, where a finite scale controls individuals' interaction. We study the behavior of the predator-prey dynamics in physical spaces higher than one, showing how spatial patterns can emerge for some values of the interaction range and of the diffusion parameter.Comment: 7 pages, 7 figure

Spatial representation of temporal information through spike timing dependent plasticity

We suggest a mechanism based on spike time dependent plasticity (STDP) of synapses to store, retrieve and predict temporal sequences. The mechanism is demonstrated in a model system of simplified integrate-and-fire type neurons densely connected by STDP synapses. All synapses are modified according to the so-called normal STDP rule observed in various real biological synapses. After conditioning through repeated input of a limited number of of temporal sequences the system is able to complete the temporal sequence upon receiving the input of a fraction of them. This is an example of effective unsupervised learning in an biologically realistic system. We investigate the dependence of learning success on entrainment time, system size and presence of noise. Possible applications include learning of motor sequences, recognition and prediction of temporal sensory information in the visual as well as the auditory system and late processing in the olfactory system of insects.Comment: 13 pages, 14 figures, completely revised and augmented versio

Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population). The primary reason for not completing treatment was > or =1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm(3), respectively; P=0.16 to 0.72). CONCLUSIONS: Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae

COVID-19: how has a global pandemic changed manual therapy technique education in chiropractic programs around the world?

Background Manual therapy is a cornerstone of chiropractic education, whereby students work towards a level of skill and expertise that is regarded as competent to work within the field of chiropractic. Due to the COVID-19 pandemic, chiropractic programs in every region around the world had to make rapid changes to the delivery of manual therapy technique education, however what those changes looked like was unknown. Aims The aims of this study were to describe the immediate actions made by chiropractic programs to deliver education for manual therapy techniques and to summarise the experience of academics who teach manual therapy techniques during the initial outbreak of COVID-19 pandemic. Methods A qualitative descriptive approach was used to describe the immediate actions made by chiropractic programs to deliver manual therapy technique education during the COVID-19 pandemic. Chiropractic programs were identified from the webpages of the Councils on Chiropractic Education International and the Council on Chiropractic Education – USA. Between May and June 2020, a convenience sample of academics who lead or teach in manual therapy technique in those programs were invited via email to participate in an online survey with open-ended questions. Responses were entered into the NVivo software program and analysed using a reflexive thematic analysis by a qualitative researcher independent to the data collection. Results Data from 16 academics in 13 separate chiropractic programs revealed five, interconnected themes: Immediate response; Move to online delivery; Impact on learning and teaching; Additional challenges faced by educators; and Ongoing challenges post lockdown. Conclusion This study used a qualitative descriptive approach to describe how some chiropractic programs immediately responded to the initial outbreak of the COVID-19 pandemic in their teaching of manual therapy techniques. Chiropractic programs around the world provided their students with rapid, innovative learning strategies, in an attempt to maintain high standards of chiropractic education; however, challenges included maintaining student engagement in an online teaching environment, psychomotor skills acquisition and staff workload

Implementation of a pharmacogenomics consult service to support the INGENIOUS trial

Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding

Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation

Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD. Therefore, we investigated neuroinflammation in our CHMP2B mutant mice. We observed very early microglial proliferation that develops into a clear pro-inflammatory phenotype at late stages. Importantly, we also observed a similar inflammatory profile in CHMP2B patient frontal cortex. Aberrant microglial function has also been implicated in FTD caused by GRN, MAPT and C9orf72 mutations. The presence of early microglial changes in our CHMP2B mutant mice indicates neuroinflammation may be a contributing factor to the neurodegeneration observed in FTD