High-level cognition during story listening is reflected in high-order dynamic correlations in neural activity patterns

Our thoughts arise from coordinated patterns of interactions between brain structures that change with our ongoing experiences. High-order dynamic correlations in neural activity patterns reflect different subgraphs of the brain’s functional connectome that display homologous lower-level dynamic correlations. Here we test the hypothesis that high-level cognition is reflected in high-order dynamic correlations in brain activity patterns. We develop an approach to estimating high-order dynamic correlations in timeseries data, and we apply the approach to neuroimaging data collected as human participants either listen to a ten-minute story or listen to a temporally scrambled version of the story. We train across-participant pattern classifiers to decode (in held-out data) when in the session each neural activity snapshot was collected. We find that classifiers trained to decode from high-order dynamic correlations yield the best performance on data collected as participants listened to the (unscrambled) story. By contrast, classifiers trained to decode data from scrambled versions of the story yielded the best performance when they were trained using first-order dynamic correlations or non-correlational activity patterns. We suggest that as our thoughts become more complex, they are reflected in higher-order patterns of dynamic network interactions throughout the brain

Delirium, frailty and mortality:interactions in a prospective study of hospitalized older people

AbstractBackgroundIt is unknown if the association between delirium and mortality is consistent for individuals across the whole range of health states. A bimodal relationship has been proposed, where delirium is particularly adverse for those with underlying frailty, but may have a smaller effect (perhaps even protective) if it is an early indicator of acute illness in fitter people. We investigated the impact of delirium on mortality in a cohort simultaneously evaluated for frailty.MethodsWe undertook an exploratory analysis of a cohort of consecutive acute medical admissions aged ≥70. Delirium on admission was ascertained by psychiatrists. A Frailty Index (FI) was derived according to a standard approach. Deaths were notified from linked national mortality statistics. Cox regression was used to estimate associations between delirium, frailty and their interactions on mortality.ResultsThe sample consisted of 710 individuals. Both delirium and frailty were independently associated with increased mortality rates (delirium: HR 2.4, 95%CI 1.8-3.3, p&lt;0.01; frailty (per SD): HR 3.5, 95%CI 1.2-9.9, p=0.02). Estimating the effect of delirium in tertiles of FI, mortality was greatest in the lowest tertile: tertile 1 HR 3.4 (95%CI 2.1-5.6); tertile 2 HR 2.7 (95%CI 1.5-4.6); tertile 3 HR 1.9 (95% CI 1.2-3.0).ConclusionWhile delirium and frailty contribute to mortality, the overall impact of delirium on admission appears to be greater at lower levels of frailty. In contrast to the hypothesis that there is a bimodal distribution for mortality, delirium appears to be particularly adverse when precipitated in fitter individuals.</jats:sec

Assessing the reliability of uptake and elimination kinetics modelling approaches for estimating bioconcentration factors in the freshwater invertebrate, Gammarus pulex

This study considers whether the current standard toxicokinetic methods are an accurate and applicable assessment of xenobiotic exposure in an aquatic freshwater invertebrate. An in vivo exposure examined the uptake and elimination kinetics for eight pharmaceutical compounds in the amphipod crustacean, Gammarus pulex by measuring their concentrations in both biological material and in the exposure medium over a 96 h period. Selected pharmaceuticals included two anti-inflammatories (diclofenac and ibuprofen), two beta-blockers (propranolol and metoprolol), an anti-depressant (imipramine), an anti-histamine (ranitidine) and two beta-agonists (formoterol and terbutaline). Kinetic bioconcentration factors (BCFs) for the selected pharmaceuticals were derived from a first-order one-compartment model using either the simultaneous or sequential modelling methods. Using the simultaneous method for parameter estimation, BCF values ranged from 12 to 212. In contrast, the sequential method for parameter estimation resulted in bioconcentration factors ranging from 19 to 4533. Observed toxicokinetic plots showed statistically significant lack-of-fits and further interrogation of the models revealed a decreasing trend in the uptake rate constant over time for rantidine, diclofenac, imipramine, metoprolol, formoterol and terbutaline. Previous published toxicokinetic data for 14 organic micro-pollutants were also assessed and similar trends were identified to those observed in this study. The decreasing trend of the uptake rate constant over time highlights the need to interpret modelled data more comprehensively to ensure uncertainties associated with uptake and elimination parameters for determining bioconcentration factors are minimised

Intrauterine Candida albicans infection causes systemic fetal candidiasis with progressive cardiac dysfunction in a sheep model of early pregnancy

Introduction: Several recent studies have identified a potential role for intrauterine Candida albicans in adverse pregnancy outcomes, including preterm birth. There is, however, a limited understanding of the impact of intrauterine candida infection on fetal well-being in early pregnancy. Using a sheep model of early pregnancy, the aims of this study were to determine (1) the ability of experimentally induced intrauterine C albicans to infect the fetus and (2) whether C albicans exposure in early pregnancy is associated with alterations in fetal cardiac function, as measured by spectral tissue Doppler imaging analysis of fetal cardiac function. Methods: Merino ewes carrying singleton pregnancies at 89 days’ gestation (term is ∼150 days) received C albicans (n = 8) via ultrasound-guided intra-amniotic injection. Saline-exposed fetuses served as controls (n = 6). Spectral tissue Doppler imaging echocardiography and amniotic fluid collection were performed at baseline and 24 and 72 hours after intrauterine C albicans injection. Fetal tissues were collected at postmortem for analysis of infection and inflammation. Results: Relative to saline control, intrauterine C albicans infection resulted in pronounced increases in amniotic fluid tumor necrosis factor α (TNF-α; P < .05) and cytokine/chemokine messenger RNA (interleukin [IL] 1β, IL-6, TNF-α, and monocyte chemoattractant protein 1; P < .05) in the fetal myocardium, lung, skin, and liver at 72 and 96 hours postinfection. Spectral tissue Doppler imaging showed diastolic dysfunction at 24 hours and severe biventricular diastolic dysfunction 72 hours postinfection. Conclusion: Intrauterine C albicans infection in a sheep model of early pregnancy causes systemic fetal candidiasis, which is associated with a robust systemic inflammatory response and progressive cardiac dysfunction detectable by spectral tissue Doppler imaging

Feasibility and acceptability of integrated psychological therapy versus treatment as usual for people with bipolar disorder and co-morbid alcohol use:A single blind randomised controlled trial

Background Alcohol use is a common problem in bipolar disorder (BD) and evidence indicates more promising outcomes for alcohol use than other substances. No trials have evaluated individual integrated motivational interviewing and cognitive behaviour therapy (MI-CBT) for problematic alcohol use in BD. We therefore assessed the feasibility and acceptability of a novel MI-CBT intervention for alcohol use in BD. Methods A single blind RCT was conducted to compare MI-CBT plus treatment as usual (TAU) with TAU only. MI-CBT was delivered over 20 sessions with participants followed up at 3, 6, 9 and 12 months post-randomisation. Primary outcomes were the feasibility and acceptability of MI-CBT (recruitment to target, retention to follow-up and therapy, acceptability of therapy and absence of adverse events). We also conducted preliminary analyses of alcohol and mood outcomes (frequency and severity of alcohol use and time to mood relapse). Results 44 participants were recruited with 75% retention to 6 and 12 months follow-up. Therapy participants attended a mean of 17.6 (SD 4.5) sessions. Therapy alliance and treatment fidelity were acceptable. Qualitative interviews indicated the intervention was experienced as collaborative, and helpful, in addressing mood and alcohol issues, although risk of overconfidence following therapy was also identified. Clinical outcomes did not differ between arms at 12 months follow-up. Limitations As a feasibility and acceptability trial any secondary results should be treated with caution. Conclusions Integrated MI-CBT is feasible and acceptable, but lack of clinical impact, albeit in a feasibility study, suggests need for further development. Potential adaptations are discussed

Evaluation of the MYCOPLASMA IST3 urogenital mycoplasma assay in an international multicentre trial

Objectives To evaluate the accuracy, susceptibility and specificity of MYCOPLASMA IST3, the next generation of the most popular culture-based in vitro diagnostic device designed to detect, identify and test the susceptibility of urogenital mycoplasma infections. Methods MYCOPLASMA IST3 was evaluated against culture- and molecular-based gold standard methodologies to detect, identify, enumerate and determine antimicrobial resistance for Mycoplasma hominis and Ureaplasma species in 516 clinical samples collected across France, Serbia and the UK. Sample types included vulvovaginal/endocervical or urethral swabs (dry swab or eSwab®), semen and urine samples, which included blinded analysis following addition of a panel of 80 characterized control strains. Results Overall species identification was excellent for both Ureaplasma spp. (98.4% sensitivity, 99.7% specificity) and M. hominis (95.7% sensitivity, 100% specificity) relative to combined colony morphology on agar and quantitative PCR standards. Non-dilution-based bacterial load estimation by the assay was accurate between 83.7% (M. hominis) and 86.3% (Ureaplasma spp.) of the time (increased to 94.2% and 100%, respectively, if ±10-fold variance was allowed) relative to colonies counted on agar. Resistance accuracy for Ureaplasma spp. varied from gold standards for only 11/605 of individual tests (major error rate = 1.8%) and for 14/917 individual tests for M. hominis (major error rate = 1.5%). Conclusions The redesigned MYCOPLASMA IST3 assay eliminated previous shortcomings by providing independent accurate resistance screening of M. hominis and Ureaplasma species, even in mixed infections, with CLSI-compliant thresholds. Specificity, sensitivity and enumeration estimates correlated closely with the confirmatory methods

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Adiposity in early, middle and later adult life and cardiometabolic risk markers in later life; findings from the British regional heart study.

OBJECTIVES: This research investigates the associations between body mass index (BMI) at 21, 40-59, 60-79 years of age on cardiometabolic risk markers at 60-79 years. METHODS: A prospective study of 3464 British men with BMI measured at 40-59 and 60-79 years, when cardiometabolic risk was assessed. BMI at 21 years was ascertained from military records, or recalled from middle-age (adjusted for reporting bias); associations between BMI at different ages and later cardiometabolic risk markers were examined using linear regression. Sensitive period, accumulation and mobility life course models were devised for high BMI (defined as BMI≥75th centile) and compared with a saturated BMI trajectory model. RESULTS: At ages 21, 40-59 and 60-79 years, prevalences of overweight (BMI≥25 kg/m2) were 12%, 53%, 70%, and obesity (≥30 kg/m2) 1.6%, 6.6%, and 17.6%, respectively. BMI at 21 years was positively associated with serum insulin, blood glucose, and HbA1c at 60-79 years, with increases of 1.5% (95%CI 0.8,2.3%), 0.4% (0.1,0.6%), 0.3% (0.1,0.4%) per 1 kg/m2, respectively, but showed no associations with blood pressure or blood cholesterol. However, these associations were modest compared to those between BMI at 60-79 years and serum insulin, blood glucose and HbA1c at 60-79 years, with increases of 8.6% (8.0,9.2%), 0.7% (0.5,0.9%), and 0.5% (0.4,0.7%) per 1 kg/m2, respectively. BMI at 60-79 years was also associated with total cholesterol and blood pressure. Associations for BMI at 40-59 years were mainly consistent with those of BMI at 60-79 years. None of the life course models fitted the data as well as the saturated model for serum insulin. A sensitive period at 50 years for glucose and HbA1c and sensitive period at 70 years for blood pressure were identified. CONCLUSIONS: In this cohort of men who were thin compared to more contemporary cohorts, BMI in later life was the dominant influence on cardiovascular and diabetes risk. BMI in early adult life may have a small long-term effect on diabetes risk

Simulation techniques for cosmological simulations

Modern cosmological observations allow us to study in great detail the evolution and history of the large scale structure hierarchy. The fundamental problem of accurate constraints on the cosmological parameters, within a given cosmological model, requires precise modelling of the observed structure. In this paper we briefly review the current most effective techniques of large scale structure simulations, emphasising both their advantages and shortcomings. Starting with basics of the direct N-body simulations appropriate to modelling cold dark matter evolution, we then discuss the direct-sum technique GRAPE, particle-mesh (PM) and hybrid methods, combining the PM and the tree algorithms. Simulations of baryonic matter in the Universe often use hydrodynamic codes based on both particle methods that discretise mass, and grid-based methods. We briefly describe Eulerian grid methods, and also some variants of Lagrangian smoothed particle hydrodynamics (SPH) methods.Comment: 42 pages, 16 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 12; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke