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Simulation software for spiking neuronal network models matured in the past decades regarding performance and flexibility. But the entry barrier remains high for students and early career scientists in computational neuroscience since these simulators typically require programming skills and a complex installation. Here, we describe an installation-free Graphical User Interface (GUI) running in the web browser, which is distinct from the simulation engine running anywhere, on the student's laptop or on a supercomputer. This architecture provides robustness against technological changes in the software stack and simplifies deployment for self-education and for teachers. Our new open source tool, NEST Desktop, comprises graphical elements for creating and configuring network models, running simulations, and visualizing and analyzing the results. NEST Desktop allows students to explore important concepts in computational neuroscience without the need to learn a simulator control language before. Our experiences so far highlight that NEST Desktop helps advancing both quality and intensity of teaching in computational neuroscience in regular university courses. We view the availability of the tool on public resources like the European ICT infrastructure for neuroscience EBRAINS as a contribution to equal opportunities.Significance StatementThe graphical user interface NEST Desktop makes neuronal network simulations accessible to non-programmers. It facilitates the interactive exploration of neuronal network models by integrating the whole workflow of wiring up the setup, simulating the neuronal dynamics, and analyzing the recorded activity data into a single tool. NEST Desktop effectively supports teaching the concepts and methods of computational neuroscience. Due to its installation-free web-based implementation, it is in particularly suitable for online courses.The lateral septum (LS) is implicated as a hub that regulates a variety of affects, such as reward, feeding, anxiety, fear, sociability, and memory. However, it remains unclear how the LS, previously treated as a structure of homogeneity, exhibits such multifaceted functions. Emerging evidence suggests that different functions of the LS are mediated largely by its diverse input and output connections. It has also become clear that the LS is a heterogeneous region, where its dorsal and ventral poles play dissociable and often opposing roles. This functional heterogeneity can often be explained by distinct dorsal and ventral hippocampal inputs along the LS dorsoventral axis, as well as antagonizing connections between LS subregions. Similarly, outputs from LS subregions to respective downstream targets, such as hypothalamic, preoptic, and tegmental areas, also account for this functional heterogeneity. In this review, we provide an updated perspective on LS subregion classification, connectivity, and functions. We also identify key questions that have yet to be addressed in the field.Significance StatementThe lateral septum (LS) is a major relay that connects the hippocampus with various subcortical regions; however, how the LS communicates with these regions and processes relevant information has not been well studied. The past several years has brought a number of publications using multidisciplinary approaches, including optogenetics, electrophysiology, and calcium imaging, to elucidate the neural circuitry and functions of the LS. Here, we summarize and integrate current knowledge about the LS circuitry to inspire further research. We propose that the multifaceted functions of the LS are mainly mediated by its diverse input and output connections, and that LS subregions often antagonize each other in competition for controlling behavioral outputs.

Tranexamic acid (TXA) is an antifibrinolytic drug used to prevent bleeding. It was introduced as an intervention for post-traumatic haemorrhage across emergency medical services (EMS) in the UK during 2012. However, despite strong evidence of effectiveness, prehospital TXA administration rates are low. Merestinib This study used the theoretical domains framework (TDF) to identify barriers and facilitators to the administration of TXA to trauma patients by EMS providers (paramedics) in the UK.

Interviews were completed with 18 UK paramedics from a single EMS provider organisation. link2 A convenience sampling approach was used, and interviews continued until thematic saturation was reached. Semistructured telephone interviews explored paramedics' experiences of administering TXA to trauma patients, including identifying whether or not patients were at risk of bleeding. Data were analysed inductively using thematic analysis (stage 1). Themes were mapped to the theoretical domains of the TDF to identify behavioural theory-detion to increase prehospital administration of TXA.

This study presents a behavioural theory-based approach to identifying barriers and facilitators to the prehospital administration of TXA to trauma patients in the UK. It identifies multiple influencing factors that may serve as a basis for developing an intervention to increase prehospital administration of TXA.In Atkins v. Virginia, the U.S. Supreme Court ruled that the execution of defendants with an intellectual disability is "cruel and unusual punishment" prohibited by the Eighth Amendment. In a 6 to 3 decision, the Court noted the increasing number of states that blocked the executions of persons with an intellectual disability, reflecting the country's growing consensus that defendants with an intellectual disability are less culpable for their crimes than those without such a disability. Since this milestone decision, several subsequent cases have referenced this opinion. This article reviews other cases in which the execution of persons with an intellectual disability has been called into question, concluding with the Atkins-related appeal in Fuston v. State In that case, the Oklahoma Court of Criminal Appeals considered Oklahoma statutes regarding the bright-line cutoff by which defendants meet criteria for intellectual disability, as applied to the multiple intelligence measures that were administered to Mr. Fuston. The Oklahoma Court of Criminal Appeals determined that Mr. Fuston did not meet the criteria for intellectual disability because of his performance on a single IQ measure administered when he was 12 years old, instead of the totality of his performance on subsequent intelligence measures. Mr. Fuston was also denied 14 other, unrelated propositions on appeal, and the state reaffirmed his death sentence. Implications and recommendations for forensic practice are discussed.Information on tuberculosis (TB) and COVID-19 is still limited. The aim of this study is to describe the features of the TB/COVID-19 co-infected individuals from a prospective, anonymised, multi-country register-based cohort with special focus on the determinants of mortality and other outcomes. We enrolled all patients of any age with either active TB or previous TB and COVID-19. 172 centres from 34 countries provided individual data on 767 TB-COVID-19 co-infected patients, (>50% population-based). Of 767 patients, 553/747 (74.0%) had TB before COVID-19 (including 234/747 with previous TB), 71/747 (9.5%) had COVID-19 first and 123/747 (16.5%) had both diseases diagnosed within the same week (35, 4.6% on the same day). 85/767 patients died (11.08%) (41/289 (14.2%) in Europe and 44/478 (9.2%) outside Europe; (p=0.03)) 42 (49.4%) from COVID-19, 31 (36.5%) from COVID-19 and TB, 1/85 (1.2%) from TB and 11 from other causes. In the univariate analysis on mortality the following variables reached statistical significance age, being male, having >1 comorbidity; diabetes mellitus, cardiovascular disease, chronic respiratory disease, chronic renal disease, presence of key symptoms, invasive ventilation and hospitalisation due to COVID-19. link3 The final multivariable logistic regression model included age, male gender, and invasive ventilation as independent contributors to mortality. The data suggests TB and COVID-19 are a "cursed duet" and need immediate attention. TB should be considered a risk factor for severe COVID disease and patients with TB should be prioritised for COVID-19 preventative efforts, including vaccination.

Enlarging tuberculosis (TB) preventive treatment among at-risk populations is a critical component of the End TB Strategy. It is urgently needed to develop suitable latent tuberculosis infection (LTBI) testing and treatment tools according to local TB epidemic and available resources in worldwide.

Based on an open-labeled randomised controlled trial conducted since 2015 among rural residents aged 50-70 years with LTBI, the protective efficacy of the 6-week twice-weekly regimen of rifapentine plus isoniazid was further evaluated in a 5-year follow-up survey.

A total of 1298 treated participants and 1151 untreated controls were included in the 5-year protective efficacy analysis. In the per-protocol analysis, the incidence rate was 0.49/100 person-years (95% confidence interval (CI) 0.30-0.67) in the untreated control group and 0.19/100 person-years (95% CI 0.07-0.32) in the treated group, the protection rate was 61.22%. Subgroup analysis showed that the protection rate was 76.82% in the per-protocol analysis among participants with baseline IFN-γ levels in the highest quartile (≥3.25 IU·mL

). The multiple logistic regression analysis indicated that participants with baseline BMI <18.5 kg·m

and with pulmonary fibrotic lesions had increased hazard of developing active disease with an adjusted hazard ratio (aHR) of 3.64 (95% CI 1.20-11.00) and 5.99 (95% CI 2.20-16.27), respectively. In addition, individuals with higher baseline IFN-γ levels showed an increased risk of TB occurrence (aHR 2.27, 95% CI 1.13-4.58).

Our findings suggested the 6-week twice-weekly regimen of rifapentine plus isoniazid for LTBI treatment might be an optional tool for TB control in Chinese population.

Our findings suggested the 6-week twice-weekly regimen of rifapentine plus isoniazid for LTBI treatment might be an optional tool for TB control in Chinese population.

In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission.

We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after a 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal-amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time-to-first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters.

Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) of 65 patients in nebulised liposomal-amphotericin-B group and 38 (51.3%) of 74 in placebo group (absolute difference -0.6%, 95% CI -16.8% to +15.6%, odds ratio 0.98, 95% CI 0.50 to 1.90; p=0.95). The median time-to-first severe clinical exacerbation was longer in liposomal-amphotericin-B group, 337 days (IQR, 168 to 476)

177 (64 to 288). At the end of maintenance therapy, total immunoglobulin-E and

precipitins were significantly decreased in nebulised liposomal-amphotericin-B group.

In ABPA, maintenance therapy using nebulised liposomal-amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

In ABPA, maintenance therapy using nebulised liposomal-amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

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