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A central challenge in fusion energy is reconciling the high-confinement mode required for reactor performance with the intense intermittent relaxation events it produces, known as edge-localized modes. These instabilities arise in the steep pressure pedestal at the plasma edge when magnetohydrodynamic thresholds are crossed, inflicting damaging heat loads on reactor components. Here, we show that multiscale interactions between microscopic turbulence and macroscopic magnetohydrodynamic modes provide encouraging prospects for self-organized edge-localized modes regulation. Using direct quantitative measurements of multiscale modes, eddy dynamics, and turbulent flux, we show that small-scale electron drift wave turbulence actively scatters the large-scale peeling-ballooning modes. This scattering decorrelates the pressure and velocity fields of the instability, so arresting its growth. Our modeling and theoretical analysis confirm this suppression mechanism is effective even when conventional linear stability thresholds are exceeded. This work establishes a nonlinear principle for edge-localized modes stability, revealing how ambient micro-turbulence can be leveraged to maintain a macro-stable, high-performance pedestal for future fusion reactors. Edge localised modes (ELMs) in highly confined plasmas are notoriously difficult to regulate. Here, the authors analyse multiscale modes and interactions by combining experimental measurements from DIII-D and modeling, showing promising results in ELM control.

A new sightline geometry for the fast-ion D-alpha (FIDA) diagnostic on the Large Helical Device (LHD) has been confirmed to measure signals for high-energy fast ions produced by negative-ion neutral beam injection. The newly installed sightline uses a 180 keV tangential negative-ion neutral beamline as the active source. Due to the small angle between the beamline and FIDA sightline, the relative velocity between fast ions and injected neutrals is small. This allows for high-energy fast ions just below the beam injection energy to produce measurable Doppler-shifted FIDA emission. Experiments were conducted at LHD in order to compare the new sightline, which views a high-energy negative-ion tangential beamline, and the old sightline, which views a low-energy perpendicular positive-ion neutral beamline. The measured FIDA signal is validated against predictions from the synthetic fast-ion diagnostic code FIDASIM with a distribution function modelled by the 5D transport code GNET. The results of the experiment confirm that reducing the viewing angle with a tangential active beam allows FIDA diagnostic to view high-energy fast ions with a sufficient signal-to-noise ratio.

Influenza continues to cause seasonal epidemics and pandemics in humans. The burden of influenza is underestimated by traditional laboratory-based surveillance, and modelled estimates are required for influenza-attributable morbidity and mortality. We aimed to estimate the influenza-attributable hospitalisation in Australia, by influenza type. A generalised-additive regression model was used to estimate type- and age-specific influenza-attributable hospitalisation rates per 100,000 population by principal diagnosis in Australia, from 2001 through 2013. Weekly counts of laboratory-confirmed influenza notifications and by type, influenza A and B were used as covariates in the model. Main principal diagnosis categories of interest were influenza and pneumonia and respiratory admissions. A smoothing spline was used to control for unmeasured time varying factors. Results for 2009, in which the pandemic influenza A(H1N1)pdm09 virus circulated, were not included in annual averages and are reported separately. During the study period, the estimated annual average, all-age, annual respiratory hospitalisation rates attributable to seasonal influenza type A, B and total influenza were 45.4 (95% CI: 34.9, 55.9), 32.6 (95% CI: 22.8, 42.4), and 76.9 (95% CI: 73.6, 80.2) per 100,000 population, respectively. During 2009, the estimated total pandemic influenza-attributable, all-age, respiratory hospitalisation rate was 56.1 (95% CI: 47.4, 64.9) per 100,000. Older adults (≥85 years of age) experienced the highest influenza-attributable hospitalisation rates for both seasonal and 2009 pandemic influenza. Collinearity between influenza A and B time series in some years limited the ability of the model to resolve differences in influenza attribution between the two virus types. Both seasonal and pandemic influenza caused considerable morbidity in Australia during the years studied, particularly among older adults. The pandemic hospitalisation rate in 2009 was lower than the average overall annual rate for seasonal influenza, but young to middle aged adults experience a hospitalisation rate similar to that of severe seasonal influenza.

In recent years, numerous studies have highlighted the overlap between autism spectrum disorder (ASD) and catatonia, both from a clinical and pathophysiological perspective. This study aimed to investigate the relationship between the autism spectrum (autistic traits and ASD signs, symptoms, and behavioral manifestation) and Catatonia Spectrum (CS). A total sample of 376 subjects was distributed in four diagnostic groups. Subjects were assessed with the Structured Clinical Interview for DSM-5, Research Version, the Adult Autism Subthreshold Spectrum (AdAS Spectrum), and CS. In the statistical analyses, the total sample was also divided into three groups according to the degree of autism severity, based on the AdAS Spectrum total score. A statistically significant positive correlation was found between AdAS Spectrum and CS total score within the total sample, the gender subgroups, and the diagnostic categories. The AdAS Spectrum domains found to be significantly and strongly correlated with the total CS score were hyper-hypo reactivity to sensory input, verbal communication, nonverbal communication, restricted interests and rumination, and inflexibility and adherence to routine. The three groups of different autistic severity were found to be distributed across all diagnostic groups and the CS score increased significantly from the group without autistic traits to the group with ASD. Our study reports a strong correlation between autism spectrum and CS.

Immune checkpoint inhibition (ICI) is a promising therapeutic strategy for counteracting tumor immune evasion. The therapeutic response largely depends on interactions between cancer cells and the tumor immune microenvironment (TIME). This study aimed to characterize the TIME and its relationship with the immune checkpoint ligand Programmed Death-Ligand 1 (PD-L1) in canine urothelial carcinomas (UCs). UCs were retrospectively selected and tested for PD-L1 using single-antibody immunohistochemistry. Multiplex immunohistochemistry was performed using anti-CD3, -CD20, and -IBA1 antibodies, to co-localize the immune cells (ICs). Both ICs and PD-L1 expression were quantified with computer-assisted image analysis (QuPath software). Based on the spatial distribution and density of ICs, tumors were classified in three distinct immune phenotypes: immune-inflamed, immune-excluded, and immune-desert. Among the 49 UCs analyzed, 11 (22%) were PD-L1+. Forty carcinomas were classified as immune-inflamed (9 PD-L1+; 31 PD-L1-), 7 as immune-excluded (2 PD-L1+; 5 PD-L1-), and 2 as immune-desert (PD-L1-). Macrophages and T-cells were the most numerous ICs, while B-cells were significantly fewer ( p  < 0.0001). PDL1 + tumors exhibited a significantly higher number of macrophages compared to PD-L1- tumors ( p  = 0.003). Immuno-inflamed tumors showed a higher density of T cells ( p  = 0.01) and a lower macrophages-to-T lymphocytes ratio ( p  = 0.02) compared to immune-excluded and immune-desert phenotypes. In summary, most UCs were immune-inflamed and T-cell rich; a subset of tumors was PDL1 + and associated with a higher number of macrophages. Further characterization of T lymphocytes and macrophages polarization is necessary to better stratify the immune response.

Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000–500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999–2015. We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65–74 years, and ≥75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. We estimated that 291 243–645 832 seasonal influenza-associated respiratory deaths (4·0–8·8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8–16·5 per 100 000 individuals), southeast Asia (3·5–9·2 per 100 000 individuals), and among people aged 75 years or older (51·3–99·4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243–105 690 influenza-associated respiratory deaths occur annually. These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated. None.

Autism spectrum disorder (ASD) is characterized by challenges in social competence that persist in adulthood, yet few treatment options exist. A pilot randomized clinical trial (RCT) of a peer-mediated, theatre-based intervention with established efficacy in youth with ASD was examined in autistic adults. The final sample consisted of forty-seven 18-to-40-year-old participants randomized to the experimental (EXP N  = 23) or waitlist control (WLC N  = 24) condition. A multimodal, social interdependent model was employed to examine social competence changes in brain (incidental face memory (IFM) using event-related potentials), cognition (Wechsler Memory Scale-III), behavior (Contextual Assessment of Social Skills) and function (Social Responsiveness Scale (SRS); Adaptive Behavior Assessment Scale (ABAS) Social Composite). Using analysis of covariance in which pretest was controlled in the model, posttest between-group differences were observed on IFM ( p  = 0.016, η 2  = 0.139, d = 0.79) and several social and adaptive functional (SRS, ABAS) outcomes in social communication and interaction (SCI) ( p  = 0.019, η 2  = 0.121, d = -00.45), communication ( p  = 0.044 η 2  = 0.09, d = -00.31), and motivation ( p  = 0.001, η 2  = 0.229, d = -0.79) domains. At two-month follow-up, gains in social motivation remained ( p  = 0.041, η 2  = 0.100, d = -0.77). The results offer preliminary support for a unique theatre-based social skills intervention for autistic adults who have few treatment options to enhance social competence. The trial was pre-registered with ClinicalTrials.gov (Identifier: NCT04349644).

•QIV was as immunogenic as TIV against the shared three strains included in the TIV.•QIV had superior efficacy to the alternate B lineage (non-TIV B lineage).•Safety profile of QIV was tolerable. A quadrivalent influenza vaccine (QIV) includes two A strains (A/H1N1, A/H3N2) and two B lineages (B/Victoria, B/Yamagata). The presence of both B lineages eliminate potential B lineage mismatch of trivalent influenza vaccine (TIV) with the circulating strain. Electronic database searches of Medline, Embase, Cochrane Central Register of Controlled Trials (CCRCT), Scopus and Web of Science were conducted for articles published until June 30, 2015 inclusive. Articles were limited to randomised controlled trials (RCTs) in adults using inactivated intramuscular vaccine and published in English language only. Summary estimates of immunogenicity (by seroprotection and seroconversion rates) and adverse events outcomes were compared between QIV and TIV, using a risk ratio (RR). Studies were pooled using inverse variance weights with a random effect model and the I2 statistic was used to estimate heterogeneity. A total of five RCTs were included in the meta-analysis. For immunogenicity outcomes, QIV had similar efficacy for the three common strains; A/H1N1, A/H3N2 and the B lineage included in the TIV. QIV also showed superior efficacy for the B lineage not included in the TIV; pooled seroprotection RR of 1.14 (95%CI: 1.03–1.25, p=0.008) and seroconversion RR of 1.78 (95%CI: 1.24–2.55, p=0.002) for B/Victoria, and pooled seroprotection RR of 1.12 (95%CI: 1.02–1.22, p=0.01) and seroconversion RR of 2.11 (95%CI: 1.51–2.95, p<0.001) for B/Yamagata, respectively. No significant differences were found between QIV and TIV for aggregated local and systemic adverse events within 7days post-vaccination. There were no vaccine-related serious adverse events reported for either QIV or TIV. Compared to TIV, injection-site pain was more common for QIV, with a pooled RR of 1.18 (95%CI: 1.03–1.35, p=0.02). In adults, inactivated QIV was as immunogenic as seasonal TIV, with equivalent efficacy against the shared three strains included in TIV, and a superior immunogenicity against the non-TIV B lineage.

An aberrant pro-inflammatory microglia response has been associated with most neurodegenerative disorders. Identifying microglia druggable checkpoints to restore their physiological functions is an emerging challenge. Recent data have shown that microglia produce de novo neurosteroids, endogenous molecules exerting potent anti-inflammatory activity. Here, the role of neurosteroidogenesis in the modulation of microgliosis was explored in human microglia cells. In particular, CYP11A1 inhibition or TSPO pharmacological stimulation, crucial proteins involved in the rate limiting step of the neurosteroidogenic cascade, were employed. CYP11A1 inhibition led microglia to acquire a dysfunctional and hyperreactive phenotype, while selective TSPO ligands promoted the establishment of an anti-inflammatory one. Analysis of specific neurosteroid levels (neurosteroidome) identified allopregnanolone/pregnanolone as crucial metabolites allowing controlled activation of microglia. Importantly, the neurosteroid shift towards a greater androgenic/estrogenic profile supported the transition from pro-inflammatory to neuroprotective microglia, suggesting the therapeutic potential of de novo microglial neurosteroidogenesis stimulation for neuroinflammatory-related disorders.

Background Respiratory syncytial virus (RSV) and influenza are important causes of disease in children and adults. In Australia, information on the burden of RSV in adults is particularly limited. Methods We used time series analysis to estimate respiratory, acute respiratory infection, pneumonia and influenza, and bronchiolitis hospitalisations attributable to RSV and influenza in Australia during 2009 through 2017. RSV and influenza‐coded hospitalisations in <5‐year‐olds were used as proxies for relative weekly viral activity. Results From 2009 to 2017, the estimated all‐age average annual rates of respiratory hospitalisations attributable to RSV and seasonal influenza (excluding 2009) were 54.8 (95% confidence interval [CI]: 20.1, 88.8) and 87.8 (95% CI: 74.5, 97.7) per 100,000, respectively. The highest estimated average annual RSV‐attributable respiratory hospitalisation rate per 100,000 was 464.2 (95% CI: 285.9, 641.2) in <5‐year‐olds. For seasonal influenza, it was 521.6 (95% CI: 420.9, 600.0) in persons aged ≥75 years. In ≥75‐year‐olds, modelled estimates were approximately eight and two times the coded estimates for RSV and seasonal influenza, respectively. Conclusions RSV and influenza are major causes of hospitalisation in young children and older adults in Australia, with morbidity underestimated by hospital diagnosis codes.