Cerebral small vessel disease, medial temporal lobe atrophy and cognitive status in patients with ischaemic stroke and transient ischaemic attack

BACKGROUND AND PURPOSE: Small vessel disease (SVD) and Alzheimer's disease (AD) are two common causes of cognitive impairment and dementia, traditionally considered as distinct processes. The relationship between radiological features suggestive of AD and SVD was explored, and the association of each of these features with cognitive status at 1 year was investigated in patients with stroke or transient ischaemic attack. METHODS: Anonymized data were accessed from the Virtual International Stroke Trials Archive (VISTA). Medial temporal lobe atrophy (MTA; a marker of AD) and markers of SVD were rated using validated ordinal visual scales. Cognitive status was evaluated with the Mini Mental State Examination (MMSE) 1 year after the index stroke. Logistic regression models were used to investigate independent associations between (i) baseline SVD features and MTA and (ii) all baseline neuroimaging features and cognitive status 1 year post-stroke. RESULTS: In all, 234 patients were included, mean (±SD) age 65.7 ± 13.1 years, 145 (62%) male. Moderate to severe MTA was present in 104 (44%) patients. SVD features were independently associated with MTA (P < 0.001). After adjusting for age, sex, disability after stroke, hypertension and diabetes mellitus, MTA was the only radiological feature independently associated with cognitive impairment, defined using thresholds of MMSE ≤ 26 (odds ratio 1.94; 95% confidence interval 1.28-2.94) and MMSE ≤ 23 (odds ratio 2.31; 95% confidence interval 1.48-3.62). CONCLUSION: In patients with ischaemic cerebrovascular disease, SVD features are associated with MTA, which is a common finding in stroke survivors. SVD and AD type neurodegeneration coexist, but the AD marker MTA, rather than SVD markers, is associated with post-stroke cognitive impairment

Whole body precooling attenuates the extracellular HSP72, IL-6 and IL-10 responses after an acute bout of running in the heat

The impact of whole-body precooling on the extracellular heat shock protein 72 (eHSP72) and cytokine responses to running in the heat is undefined. The aim of this study was to determine whether precooling would attenuate post-exercise eHSP72 and cytokine responses.Eight male recreational runnerscompleted two90-minuteboutsofrunningat65% _VO2maxin32±0.9°Cand47±6%relativehumidity(RH)preceded by either 60-minutes of precooling in 20.3 ± 0.3°C water (COOL) or 60 min rest in an air-conditioned laboratory (20.2 ± 1.7°C, 60 ± 3% RH; CON). eHSP72, TNF-α, IL-6, IL-10 IL-1ra were determined before and immediately after exercise. The elevation in post-exercise eHSP72 was attenuated after COOL (+0.04 ± 0.10 ng.mL−1) compared to CON (+ 0.29 ± 0.26 ng.mL−1;P < 0.001). No changes in TNF-α were observed at any stage. COOL reduced the absolute post-exercise change in IL-6 (P = 0.011) and IL-10 (P = 0.03) compared to CON. IL-1ra followed this trend (P = 0.063). A precooling-induced attenuation of eHSP72 and proinflammatory cytokines may aid recovery during multi-day sporting events, but could be counterproductive if a training response or adaptation to environmental stress is a desired outcome

Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

BACKGROUND Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation) to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. METHODS Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD). RESULTS Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18). The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18). Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3%) and control subjects (19.1 ± 2.6%; p = 0.43). CONCLUSIONS Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.This study was funded by the Centre for Training in Clinical Cerebrovascular and Cardiovascular Research, a National Health and Medical Research Council funded Centre of Clinical Research Excellence

Weight Status as a Mediator of the Association Between Preschool Extraversion and Adolescent Restrained Eating

Objectives To determine the longitudinal association between preschool extraversion and weight/dieting outcomes in adolescence. Methods Children (N = 180) were recruited as part of a longitudinal study, with child temperament assessed in preschool (age 5.25 years), weight assessed in 2nd grade and early adolescence, and eating outcomes assessed in early adolescence (mean age = 12.02 years). Results Preschoolers high in extraversion were significantly more likely to have higher body mass index z-scores (zBMI) and more restrained eating behaviors in adolescence. zBMI was found to mediate the relationship between extraversion and restrained eating, such that children with high levels of extraversion were more likely to have higher zBMI in adolescence and, owing to this higher weight status, to engage in more restrained eating. Conclusions Temperament is an important predictor of later maladaptive weight/dieting outcomes in adolescence, making it a potentially important early factor to consider in weight management interventions

Flat Information Geometries in Black Hole Thermodynamics

The Hessian of either the entropy or the energy function can be regarded as a metric on a Gibbs surface. For two parameter families of asymptotically flat black holes in arbitrary dimension one or the other of these metrics are flat, and the state space is a flat wedge. The mathematical reason for this is traced back to the scale invariance of the Einstein-Maxwell equations. The picture of state space that we obtain makes some properties such as the occurence of divergent specific heats transparent.Comment: 14 pages, one figure. Dedicated to Rafael Sorkin's birthda

Concentrations of criteria pollutants in the contiguous U.S., 1979 – 2015: Role of model parsimony in integrated empirical geographic regression

BACKGROUND: National- or regional-scale prediction models that estimate individual-level air pollution concentrations commonly include hundreds of geographic variables. However, these many variables may not be necessary and parsimonious approach including small numbers of variables may achieve sufficient prediction ability. This parsimonious approach can also be applied to most criteria pollutants. This approach will be powerful when generating publicly available datasets of model predictions that support research in environmental health and other fields. OBJECTIVES: We aim to (1) build annual-average integrated empirical geographic (IEG) regression models for the contiguous U.S. for six criteria pollutants, for all years with regulatory monitoring data during 1979 – 2015; (2) explore the impact of model parsimony on model performance by comparing the model performance depending on the numbers or variables offered into a model; and (3) provide publicly available model predictions. METHODS: We compute annual-average concentrations from regulatory monitoring data for PM10, PM2.5, NO2, SO2, CO, and ozone at all monitoring sites for 1979-2015. We also compute ~900 geographic characteristics at each location including measures of traffic, land use, and satellite-based estimates of air pollution and landcover. We then develop IEG models, employing universal kriging and summary factors estimated by partial least squares (PLS) of independent variables. For all pollutants and years, we compare three approaches for choosing variables to include in the model: (1) no variables (kriging only), (2) a limited number of variables chosen by forward selection, and (3) all variables. We evaluate model performance using 10-fold cross-validation (CV) using conventional randomly-selected and spatially-clustered test data. RESULTS: Models using 3 to 30 variables generally have the best performance across all pollutants and years (median R2 conventional [clustered] CV: 0.66 [0.47]) compared to models with no (0.37 [0]) or all variables (0.64 [0.27]). Using the best models mostly including 3-30 variables, we predicted annual-average concentrations of six criteria pollutants for all Census Blocks in the contiguous U.S. DISCUSSION: Our findings suggest that national prediction models can be built on only a small number (30 or fewer) of important variables and provide robust concentration estimates. Model estimates are freely available online

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson &amp; Johnson and Bayer

Depinning transition and thermal fluctuations in the random-field Ising model

We analyze the depinning transition of a driven interface in the 3d random-field Ising model (RFIM) with quenched disorder by means of Monte Carlo simulations. The interface initially built into the system is perpendicular to the [111]-direction of a simple cubic lattice. We introduce an algorithm which is capable of simulating such an interface independent of the considered dimension and time scale. This algorithm is applied to the 3d-RFIM to study both the depinning transition and the influence of thermal fluctuations on this transition. It turns out that in the RFIM characteristics of the depinning transition depend crucially on the existence of overhangs. Our analysis yields critical exponents of the interface velocity, the correlation length, and the thermal rounding of the transition. We find numerical evidence for a scaling relation for these exponents and the dimension d of the system.Comment: 6 pages, including 9 figures, submitted for publicatio

Drag estimation on wedge-shaped protuberances in high-speed flows

A semi-empirical method is developed to estimate drag on wedge-shaped projections in hypersonic flow. Force balance measurements from gun tunnel tests directly measure total drag on blunt wedges, where the boundary layer and the entropy layer are weakly coupled. Detailed flowfield analysis from numerical simulations provides estimated locations of peak pressure ratio and skin friction. Schlieren images are used for detecting incipient separation in incoming flows with laminar and turbulent boundary layers. Test results indicate the presence of local hotspots at reattachment points of strong detached shocks on the wedge compression ramp, and of primary and secondary vortical structures around lateral faces. Total drag is found to decrease with decreasing bluntness but increasing slenderness in wedges tend to increase skin friction drag