Top-down control of visual sensory processing during an ocular motor response inhibition task

The study addressed whether top-down control of visual cortex supports volitional behavioral control in a novel antisaccade task. The hypothesis was that anticipatory modulations of visual cortex activity would differentiate trials on which subjects knew an anti- versus a pro-saccade response was required. Trials consisted of flickering checkerboards in both peripheral visual fields, followed by brightening of one checkerboard (target) while both kept flickering. Neural activation related to checkerboards before target onset (bias signal) was assessed using electroencephalography. Pretarget visual cortex responses to checkerboards were strongly modulated by task demands (significantly lower on antisaccade trials), an effect that may reduce the predisposition to saccade generation instigated by visual capture. The results illustrate how top-down sensory regulation can complement motor preparation to facilitate adaptive voluntary behavioral control

On the alert: future priorities for alerts in clinical decision support for computerized physician order entry identified from a European workshop

Background: Clinical decision support (CDS) for electronic prescribing systems (computerized physician order entry) should help prescribers in the safe and rational use of medicines. However, the best ways to alert users to unsafe or irrational prescribing are uncertain. Specifically, CDS systems may generate too many alerts, producing unwelcome distractions for prescribers, or too few alerts running the risk of overlooking possible harms. Obtaining the right balance of alerting to adequately improve patient safety should be a priority. Methods: A workshop funded through the European Regional Development Fund was convened by the University Hospitals Birmingham NHS Foundation Trust to assess current knowledge on alerts in CDS and to reach a consensus on a future research agenda on this topic. Leading European researchers in CDS and alerts in electronic prescribing systems were invited to the workshop. Results: We identified important knowledge gaps and suggest research priorities including (1) the need to determine the optimal sensitivity and specificity of alerts; (2) whether adaptation to the environment or characteristics of the user may improve alerts; and (3) whether modifying the timing and number of alerts will lead to improvements. We have also discussed the challenges and benefits of using naturalistic or experimental studies in the evaluation of alerts and suggested appropriate outcome measures. Conclusions: We have identified critical problems in CDS, which should help to guide priorities in research to evaluate alerts. It is hoped that this will spark the next generation of novel research from which practical steps can be taken to implement changes to CDS systems that will ultimately reduce alert fatigue and improve the design of future systems

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required

Characterization of childhood trauma, hippocampal mediation and Cannabis use in a large dataset of psychosis and non-psychosis individuals

Background Cannabis use (CA) and childhood trauma (CT) independently increase the risk of earlier psychosis onset; but their interaction in relation to psychosis risk and association with endocannabinoid-receptor rich brain regions, i.e. the hippocampus (HP), remains unclear. The objective was to determine whether lower age of psychosis onset (AgePsyOnset) is associated with CA and CT through mediation by the HP volumes, and genetic risk, as measured by schizophrenia polygene scores (SZ-PGRS). Methods Cross-sectional, case-control, multicenter sample from 5 metropolitan US regions. Participants (n = 1185) included 397 controls not affected by psychosis (HC); 209 participants with bipolar disorder type-1; 279 with schizoaffective disorder; and 300 with schizophrenia (DSM IV-TR). CT was assessed using the Childhood Trauma Questionnaire (CTQ); CA was assessed by self-reports and trained clinical interviewers. Assessment included neuroimaging, symptomatology, cognition and calculation of the SZ polygenic risk score (SZ-PGRS). Results In survival analysis, CT and CA exposure interact to be associated with lower AgePsyOnset. At high CT or CA, CT or CA are individually sufficient to affect AgePsyOnset. CT relation with AgePsyOnset is mediated in part by the HP in CA users before AgePsyOnset. CA before AgePsyOnset is associated with higher SZ-PGRS and correlated with younger age at CA usage. Discussion CA and CT interact to increase risk when moderate; while severe CT and/or CA abuse/dependence are each sufficient to affect AgePsyOnset, indicating a ceiling effect. Probands with/out CA before AgePsyOnset differ on biological variables, suggesting divergent pathways to psychosis

A Beautiful Thing: A Service Learning Partnership Develops

This roundtable presents multiple perspectives on a multi-year partnership between an urban school and its university neighbor. Building and nurturing a thriving mutually beneficial partnership between an urban Pre-K-8 school and its neighboring university is, as the principal of Cesar Batalla School often says, “a beautiful thing.” Cesar Batalla, serving 800 students and families from a multilingual, multiethnic community in a low-income neighborhood, is located a stone’s throw from a mid-sized suburban, private university that attracts undergraduate and graduate students with little personal firsthand experience with racial, ethnic and linguistic diversity, or of poverty and its challenges. “Geographical neighbors, yet worlds apart” would aptly describe the university school juxtaposition before we embarked upon our partnership. Transforming a coincidental proximity into a deep partnership has been a journey of many discoveries

"Do I really want to do this?" Longitudinal cohort study participants' perspectives on postal survey design: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Randomised controlled trials have investigated aspects of postal survey design yet cannot elaborate on reasons behind participants' decision making and survey behaviour. This paper reports participants' perspectives of the design of, and participation in, a longitudinal postal cohort survey. It describes strengths and weaknesses in study design from the perspectives of study participants and aims to contribute to the: 1) design of future cohort surveys and questionnaires generally and, 2) design of cohort surveys for people with musculoskeletal disorders (MSDs) specifically.</p> <p>Methods</p> <p>In-depth interviews explored the design of postal surveys previously completed by participants. Interviews used open ended questioning with a topic guide for prompts if areas of interest were not covered spontaneously. Thematic data analysis was undertaken based on the framework method. A second researcher verified all coding.</p> <p>Results</p> <p>Data from fourteen interviews were analysed within three main themes; participation, survey design and survey content. One of the main findings was the importance of clear communication aimed at the correct audience both when inviting potential participants to take part and within the survey itself. Providing enough information about the study, having a topic of interest and an explanation of likely benefits of the study were important when inviting people to participate. The neutrality of the survey and origination from a reputable source were both important; as was an explanation about why information was being collected within the survey itself. Study findings included participants' impressions when invited to take part, why they participated, the acceptability of follow-up of non-responders and why participants completed the follow-up postal survey. Also discussed were participants' first impression of the survey, its length, presentation and participants' views about specific questions within the survey.</p> <p>Conclusions</p> <p>Ideas generated in this study provide an insight into participants' decision making and survey behaviour and may enhance the acceptability of future surveys to potential participants. As well as clear communication, participants valued incentives and survey questions that were relevant to them. However, opinions varied as to the preferred format for responses with some advising more opportunity for open-ended feedback. We also found that some standard format questions can raise quandaries for individual participants.</p

Ideas and perspectives: strengthening the biogeosciences in environmental research networks

Many scientific approaches are improving our understanding and management of the rapidly changing environment. Long-term environmental research networks are one approach to advancing local, regional, and global environmental science and education. A remarkable number and wide variety of environmental research networks operate around the world today. These are diverse in funding, infrastructure, motivating questions, scientific strengths, and the sciences that birthed and maintained the networks. Some networks have individual sites that were selected because they had produced invaluable long-term data, while other networks have new sites selected to span ecological gradients. However, all long-term environmental networks share two challenges. Networks must keep pace with scientific advances and interact with both the scientific community and society at large. If networks fall short of successfully addressing these challenges, they risk becoming irrelevant. The objective of this paper is to assert that the biogeosciences offer environmental research networks a number of opportunities to expand scientific impact and public engagement. We explore some of these opportunities with four networks: the International Long Term Ecological Research programs (ILTERs), the Critical Zone Observatories (CZOs), the Earth and Ecological Observatory networks (EONs), and the FLUXNET program of eddy flux sites. While these networks were founded and grown by interdisciplinary scientists, the preponderance of expertise and funding have gravitated activities of ILTERs and EONs toward ecology and biology, CZOs toward the Earth sciences and geology, and FLUXNET toward ecophysiology and micrometeorology. Our point is not to homogenize networks, nor to diminish disciplinary science. Rather, we argue that by more fully incorporating the integration of biology and geology in long-term environmental research networks, scientists can better leverage network assets, keep pace with the ever-changing science of the environment, and engage with larger scientific and public audiences

The Chromatin Remodelling Factor dATRX Is Involved in Heterochromatin Formation

Despite extensive study of heterochromatin, relatively little is known about the mechanisms by which such a structure forms. We show that the Drosophila homologue of the human α-thalassemia and mental retardation X-linked protein (dATRX), is important in the formation or maintenance of heterochromatin through modification of position effect variegation. We further show that there are two isoforms of the dATRX protein, the longer of which interacts directly with heterochromatin protein 1 (dHP-1) through a CxVxL motif both in vitro and in vivo. These two proteins co-localise at heterochromatin in a manner dependent on this motif. Consistent with this observation, the long isoform of the dATRX protein localises primarily to the heterochromatin at the chromocentre on salivary gland polytene chromosomes, whereas the short isoform binds to many sites along the chromosome arms. We suggest that the establishment of a regular nucleosomal organisation may be common to heterochromatin and transcriptionally repressed chromatin in other locations, and may require the action of ATP dependent chromatin remodelling factors

Corticosteroid responsiveness following mepolizumab in severe eosinophilic asthma—a randomized, placebo-controlled crossover trial (MAPLE)

Mepolizumab inhibits interleukin-5 (IL-5) activity, reduces exacerbation frequency and maintenance oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma (SEA). Some patients remain dependent on OCS despite anti-IL-5 treatment suggesting residual corticosteroid responsive mechanisms. We aimed to determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab. We conducted a randomised, triple-blind, placebo-controlled crossover trial of prednisolone (0.5mg/kg/day, maximum 40mg/day, for 14±2 days) in adults with SEA after ≥12 weeks of mepolizumab. We compared change in asthma symptoms, quality of life, lung function measured by spirometry and airwave oscillometry, FeNO, and blood and sputum eosinophil cell count after prednisolone and placebo. 27 patients completed the study. Prednisolone did not improve ACQ-5 (mean difference in change for prednisolone vs placebo -0.23, 95% CI -0.58 to 0.11), mini-AQLQ (0.03, 95% CI -0.26 to 0.42), SGRQ (0.24, 95% CI -3.20 to 3.69) or VAS scores for overall asthma symptoms (0.11, 95% CI -0.58 to 0.80). The mean difference for FEV in favour of prednisolone was 105ml (95% CI -4 to 213 ml); FEF 484ml/s (95% CI 151 to 816 ml/s); FeNO reduction 41% (95% CI 25 to 54%); blood eosinophil count reduction 49% (95% CI 31 to 62%); and percentage of sputum eosinophil reduction 71% (95% CI 26 to 89%). OCS improved small airway obstruction and reduced biomarkers of type 2 inflammation but had no significant effect on symptoms or quality of life in patients with severe eosinophilic asthma receiving treatment with mepolizumab. [Abstract copyright: Copyright © 2022. Published by Elsevier Inc.