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Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.
Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.
We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.
Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.
The Passive Surveillance Stroke Severity (PaSSV) Indicator was derived to estimate stroke severity from variables in administrative datasets but has not been externally validated.
We used linked administrative datasets to identify patients with first hospitalization for acute stroke between 2007-2018 in Alberta, Canada. We used the PaSSV indicator to estimate stroke severity. We used Cox proportional hazard models and evaluated the change in hazard ratios and model discrimination for 30-day and 1-year case fatality with and without PaSSV. Similar comparisons were made for 90-day home time thresholds using logistic regression. We also linked with a clinical registry to obtain National Institutes of Health Stroke Scale (NIHSS) and compared estimates from models without stroke severity, with PaSSV, and with NIHSS.
There were 28,672 patients with acute stroke in the full sample. In comparison to no stroke severity, addition of PaSSV to the 30-day case fatality models resulted in improvement in model discrimination (C-statistic 0.72 [95%CI 0.71–0.73] to 0.80 [0.79–0.80]). After adjustment for PaSSV, admission to a comprehensive stroke center was associated with lower 30-day case fatality (adjusted hazard ratio changed from 1.03 [0.96–1.10] to 0.72 [0.67–0.77]). In the registry sample (N = 1328), model discrimination for 30-day case fatality improved with the inclusion of stroke severity. Results were similar for 1-year case fatality and home time outcomes.
Addition of PaSSV improved model discrimination for case fatality and home time outcomes. The validity of PASSV in two Canadian provinces suggests that it is a useful tool for baseline risk adjustment in acute stroke.
This paper investigates the rational and emotional functions of symbols in organizational change and how collective sensemaking and acceptance of organizational changes are facilitated by the emotional functioning of executive symbolism. Evidence from archived data, news reports, reviews, and case studies are used to support our theoretical analysis. Our opinion is that the CEO can incorporate symbols into not only the rational calculation process to convey the benefits and losses of organizational changes but also the emotional identification process to create new emotional connections and reduce the resistance of the members to organizational changes. We describe why and when the implementation of symbolism will gain the acceptance of members toward organizational change and explain the scenarios that apply for the two functions.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
We examined the accuracy of International Classification of Disease 10th iteration (ICD-10) diagnosis codes within Canadian administrative data in identifying cerebral venous thrombosis (CVT). Of 289 confirmed cases of CVT admitted to our comprehensive stroke center between 2008 and 2018, 239/289 were new diagnoses and 204/239 were acute events with only 75/204 representing symptomatic CVTs not provoked by trauma or structural processes. Using ICD-10 codes in any position, sensitivity was 39.1% and positive predictive value was 94.2% for patients with a current or history of CVT and 84.0% and 52.5% for acute and symptomatic CVTs not provoked by trauma or structural processes.
Despite its efficacy in treating comorbid insomnia and depression, cognitive behavioral therapy for insomnia (CBT-I) is limited in its accessibility and, in many countries, cultural compatibility. Smartphone-based treatment is a low-cost, convenient alternative modality. This study evaluated a self-help smartphone-based CBT-I in alleviating major depression and insomnia.
A parallel-group randomized, waitlist-controlled trial was conducted with 320 adults with major depression and insomnia. Participants were randomized to receive either a 6-week CBT-I via a smartphone application, proACT-S, or waitlist condition. The primary outcomes included depression severity, insomnia severity, and sleep quality. The secondary outcomes included anxiety severity, subjective health, and acceptability of treatment. Assessments were administered at baseline, post-intervention (week 6) follow-up, and week 12 follow-up. The waitlist group received treatment after the week 6 follow-up.
Intention to treat analysis was conducted with multilevel modeling. In all but one model, the interaction between treatment condition and time at week 6 follow-up was significant. Compared with the waitlist group, the treatment group had lower levels of depression [Center for Epidemiologic Studies Depression Scale (CES-D): Cohen's d = 0.86, 95% CI (−10.11 to −5.37)], insomnia [Insomnia Severity Index (ISI): Cohen's d = 1.00, 95% CI (−5.93 to −3.53)], and anxiety [Hospital Anxiety and Depression Scale – Anxiety subscale (HADS-A): Cohen's d = 0.83, 95% CI (−3.75 to −1.96)]. They also had better sleep quality [Pittsburgh Sleep Quality Index (PSQI): Cohen's d = 0.91, 95% CI (−3.34 to −1.83)]. No differences across any measures were found at week 12, after the waitlist control group received the treatment.
proACT-S is an efficacious sleep-focused self-help treatment for major depression and insomnia.
ABSTRACT IMPACT: Given the association between lower time to treatment and better clinical outcomes in stroke patients, identifying factors correlated with reduced proximity and thus greater time to stroke care can aid efforts to reduce disparities in stroke outcomes. OBJECTIVES/GOALS: The objective of this study is to quantify the relationship between distance to the nearest certified stroke hospital and census-derived demographics of age, race/ethnicity, income, and insurance status. METHODS/STUDY POPULATION: This is a cross-sectional study. Population data for all census tracts in the contiguous United States were obtained from the US Census Bureau’s 2014-2018 American Community Survey. Stroke hospitals were identified from national or state level certification databases and were required to offer at least IV tPA. The main outcome is driving distance in kilometers from each census tract to the nearest certified stroke center, which was calculated using OSMnx, a Python package to retrieve, model and analyze real-world street networks. Quantile regression analysis was used to compare relationships between distances and tract-level demographics of age, race/ethnicity, income, and insurance status. RESULTS/ANTICIPATED RESULTS: 2,423 stroke centers and 71,929 census tracts containing 316,995,649 individuals were included. 49,918 (69%) tracts were urban. Demographic disparities in proximity to certified stroke care were greater in non-urban areas than in urban areas. Higher representation of individuals with age ≤65 years were associated with increased median distance to a certified stroke center in non-urban areas, but not urban areas. Median distance was greater with greater representation of American Indian or uninsured populations in urban and non-urban census tracts. Higher median income was associated with decreased median distance in non-urban census tracts and greater median distance in urban census tracts. DISCUSSION/SIGNIFICANCE OF FINDINGS: Reduced proximity to stroke care exists in areas with greater representation of elderly, American Indian, or uninsured persons; and low median income. These disparities are magnified in non-urban settings. Such knowledge can aid efforts to address and reduce disparities in stroke outcomes.
The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at −15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (−15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.
Maternal migraine may contribute to mental heath problems in offspring but empirical evidence has been available only for bipolar disorders. Our objective was to examine the association between maternal migraine and the risk of any and specific psychiatric disorders in offspring.
This population-based cohort study used individual-level linked Danish national health registers. Participants were all live-born singletons in Denmark during 1978–2012 (n = 2 069 785). Follow-up began at birth and continued until the onset of a psychiatric disorder, death, emigration or 31 December 2016, whichever came first. Cox proportional hazards model was employed to calculate the hazard ratios (HRs) of psychiatric disorders.
Maternal migraine was associated with a 26% increased risk of any psychiatric disorders in offspring [HR, 1.26; 95% confidence interval (CI), 1.22–1.30]. Increased rates of psychiatric disorders were seen in all age groups from childhood to early adulthood. Increased rates were also observed for most of the specific psychiatric disorders, in particular, mood disorders (HR, 1.53; 95% CI, 1.39–1.67), neurotic, stress-related and somatoform disorders (HR, 1.44; 95% CI, 1.37–1.52) and specific personality disorders (HR, 1.47; 95% CI, 1.27–1.70), but not for intellectual disability (HR, 0.84; 95% CI, 0.71–1.00) or eating disorders (HR, 1.10; 95% CI, 0.93–1.29). The highest risk was seen in the offspring of mothers with migraine and comorbid psychiatric disorders (HR, 2.13; 95% CI, 1.99–2.28).
Maternal migraine was associated with increased risks of a broad spectrum of psychiatric disorders in offspring. Given the high prevalence of migraine, our findings highlight the importance of better management of maternal migraine at childbearing ages for early prevention of psychiatric disorders in offspring.
To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission.
Design, setting, and participants:
This cohort study was conducted during March 22–May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California.
Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription–polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.
Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages.
Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Soft magnetic metal amorphous nanocomposite alloys are produced through rapid solidification and thermal annealing yielding nanocrystals embedded within an amorphous precursor. Similar free energies in Co-rich and FeNi-based alloy systems result in multiple nanocrystalline phases being formed during devitrification. Studies of multi-phase crystallization processes have been reported for Co-rich alloys but relatively few have investigated FeNi-based systems. A detailed characterization of compositional partitioning and microstructure of an optimally annealed FeNi-based MANC (Fe70Ni30)80Nb4Si2B14 alloy is presented through complementary high-resolution transmission electron microscopy (HRTEM) and atom probe tomography (APT). HRTEM demonstrates orientation relationships between FCC and BCC nanocrystals, suggesting heterogeneous nucleation of nanocrystals in the amorphous matrix or a cooperative mechanism of nucleation between BCC and FCC nanocrystallites. APT results show evidence for (i) the segregation of Fe and Ni between nanocrystals of different phases, (ii) B partitioning to the amorphous phase, and (iii) an Nb-enriched shell surrounding nanocrystals.
In support of the ICRF experiments planned on the Wendelstein 7-X (W7-X) stellarator, i.e. fast ion generation, wall conditioning, target plasma production and heating, a first experimental study on plasma production has been made in the Uragan-2M (U-2M) stellarator using W7-X-like two-strap antenna. In all the experiments, antenna monopole phasing was used. The W7-X-like antenna operation with launched radiofrequency power of ~100 kW have been performed in helium (p = (4–14) × 10−2 Pa) with the vacuum vessel walls pre-loaded with hydrogen. Production of plasma with a density higher than 1012 cm−3 was observed near the first harmonic of the hydrogen cyclotron frequency. Operation at first hydrogen harmonic is feasible in W7-X future ICRF experiments.
Improvements in management of transient ischemic attack (TIA) have decreased stroke and mortality post-TIA. Studies examining trends over time on a provincial level are limited. We analyzed whether efforts to improve management have decreased the rate of stroke and mortality after TIA from 2003 to 2015 across an entire province.
Using administrative data from the Canadian Institute for Health Information’s (CIHI) databases from 2003 to 2015, we identified a cohort of patients with a diagnosis of TIA upon discharge from the emergency department (ED). We examined stroke rates at Day 1, 2, 7, 30, 90, 180, and 365 post-TIA and 1-year mortality rates and compared trends over time between 2003 and 2015.
From 2003 to 2015 in Ontario, there were 61,710 patients with an ED diagnosis of TIA. Linear regressions of stroke after the index TIA showed a significant decline between 2003 and 2015, decreasing by 25% at Day 180 and 32% at 1 year (p < 0.01). The 1-year stroke rate decreased from 6.0% in 2003 to 3.4% in 2015. Early (within 48 h) stroke after TIA continued to represent approximately half of the 1-year event rates. The 1-year mortality rate after ED discharge following a TIA decreased from 1.3% in 2003 to 0.3% in 2015 (p < 0.001).
At a province-wide level, 1-year rates of stroke and mortality after TIA have declined significantly between 2003 and 2015, suggesting that efforts to improve management may have contributed toward the decline in long-term risk of stroke and mortality. Continued efforts are needed to further reduce the immediate risk of stroke following a TIA.