UBC-Nepal Expedition: Acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea-level and high-altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high-altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g. shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that: 1) at rest, SNA would be elevated and FMD would be reduced at HA compared to sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344m) and HA (5050m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrodcardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n=5). Our findings were: 1) at rest, SNA was elevated (P<0.01), and absolute FMD was reduced (P=0.024), but relative FMD remained unaltered (P=0.061), at HA compared to SL, and 2) despite significantly altering SNA with LBNP (+60.3±25.5%) and LBPP (-37.2±12.7%) (P<0.01), FMD was unaltered at SL (P=0.448), and HA (P=0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA

UBC-Nepal Expedition: Acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea-level and high-altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high-altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g. shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that: 1) at rest, SNA would be elevated and FMD would be reduced at HA compared to sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344m) and HA (5050m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrodcardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n=5). Our findings were: 1) at rest, SNA was elevated (P<0.01), and absolute FMD was reduced (P=0.024), but relative FMD remained unaltered (P=0.061), at HA compared to SL, and 2) despite significantly altering SNA with LBNP (+60.3±25.5%) and LBPP (-37.2±12.7%) (P<0.01), FMD was unaltered at SL (P=0.448), and HA (P=0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA

Analysis of stellar spectra with 3D and NLTE models

Models of radiation transport in stellar atmospheres are the hinge of modern astrophysics. Our knowledge of stars, stellar populations, and galaxies is only as good as the theoretical models, which are used for the interpretation of their observed spectra, photometric magnitudes, and spectral energy distributions. I describe recent advances in the field of stellar atmosphere modelling for late-type stars. Various aspects of radiation transport with 1D hydrostatic, LTE, NLTE, and 3D radiative-hydrodynamical models are briefly reviewed.Comment: 21 pages, accepted for publication as a chapter in "Determination of Atmospheric Parameters of B, A, F and G Type Stars", Springer (2014), eds. E. Niemczura, B. Smalley, W. Pyc

The associations among objectively estimated sleep and obesity indicators in elementary schoolchildren

© 2018 Elsevier B.V. Objective: A negative linear association between sleep duration and obesity in children has been reported, but this has been predominantly based on subjective estimates of sleep duration and only one indicator of obesity. This cross-sectional study aimed to examine the relationships among objectively measured sleep parameters and a range of obesity indicators in schoolchildren. Patients/methods: Baseline data were obtained from 335 elementary schoolchildren (aged 7–12 years) recruited to the study. Five indicators of obesity were determined and two global cut-off points (WHO and International Obesity Task Force) were used to define overweight/obesity. Participants wore wrist actigraphy devices (N = 264) for seven consecutive days/nights to objectively estimate six sleep features. Results: Average weekday sleep duration was 7.6 ± 0.7 h and 42.1% of the participants were overweight/obese. After adjustment, those achieving \u3c8 h of sleep had an increased body mass index z-score (β = 0.88, p \u3c 0.001), waist circumference (β = 6.49, p \u3c 0.001), body fat percentage (β = 5.17, p \u3c 0.001), and fat mass (kg) (β = 3.23, p \u3c 0.001) compared to those sleeping ≥8 h. Based on two standardized cut-off points for overweight/obesity, sleeping \u3c8 h was associated with an increased risk of obesity (odds ratio (OR) = 3.75, 95% confidence interval (CI): 1.56–9.05; OR = 4.79 95% CI: 2.11–10.90). Conclusion: Sleep insufficiency, in addition to other lifestyle factors, is likely to play a role in childhood obesity. Lifestyle interventions should include advice regarding sleep improvement with promotion of other healthy lifestyle behaviors to tackle childhood obesity, a serious global public health problem

Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval

Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed

Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis

BACKGROUND The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. METHODOLOGY We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. PRINCIPAL FINDINGS Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. CONCLUSIONS/SIGNIFICANCE Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. PROTOCOL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42012003338

Energy expenditure during overfeeding

The large inter-individual variation in weight gain during standardized overfeeding together with a weight gain that is often less than theoretically calculated from the energy excess suggest that there are differences between persons in the capacity to regulate energy expenditure and hence metabolic efficiency. Adaptive thermogenesis is defined as the regulated production of heat in response to environmental changes in temperature and diet, resulting in metabolic inefficiency. The question is whether adaptive thermogenesis can be identified in overfeeding experiments. From the numerous human overfeeding experiments we selected those studies that applied suitable protocols and measurement techniques. Five studies claimed to have found evidence for adaptive thermogenesis based on weight gains smaller than expected or unaccounted increases in thermogenesis above obligatory costs. Results from the other 11 studies suggest there is no adaptive thermogenesis as weight gains were proportional to the amount of overfeeding and the increased thermogenesis was associated with theoretical costs of an increased body size and a larger food intake. These results show that in humans, evidence for adaptive thermogenesis is still inconsistent. However, they do not rule out the existence, but emphasize that if present, adaptive changes in energy expenditure may be too small to measure considering measurement errors, errors in assumptions made and small (day-to-day) differences in physical activity. In addition, it is not clear in which component or components of total energy expenditure adaptive changes can occur and whether components can overlap due to measurement limitations

Inhibition of Hedgehog Signaling Antagonizes Serous Ovarian Cancer Growth in a Primary Xenograft Model

Recent evidence links aberrant activation of Hedgehog (Hh) signaling with the pathogenesis of several cancers including medulloblastoma, basal cell, small cell lung, pancreatic, prostate and ovarian. This investigation was designed to determine if inhibition of this pathway could inhibit serous ovarian cancer growth.We utilized an in vivo pre-clinical model of serous ovarian cancer to characterize the anti-tumor activity of Hh pathway inhibitors cyclopamine and a clinically applicable derivative, IPI-926. Primary human serous ovarian tumor tissue was used to generate tumor xenografts in mice that were subsequently treated with cyclopamine or IPI-926.Both compounds demonstrated significant anti-tumor activity as single agents. When IPI-926 was used in combination with paclitaxel and carboplatinum (T/C), no synergistic effect was observed, though sustained treatment with IPI-926 after cessation of T/C continued to suppress tumor growth. Hh pathway activity was analyzed by RT-PCR to assess changes in Gli1 transcript levels. A single dose of IPI-926 inhibited mouse stromal Gli1 transcript levels at 24 hours with unchanged human intra-tumor Gli1 levels. Chronic IPI-926 therapy for 21 days, however, inhibited Hh signaling in both mouse stromal and human tumor cells. Expression data from the micro-dissected stroma in human serous ovarian tumors confirmed the presence of Gli1 transcript and a significant association between elevated Gli1 transcript levels and worsened survival.IPI-926 treatment inhibits serous tumor growth suggesting the Hh signaling pathway contributes to the pathogenesis of ovarian cancer and may hold promise as a novel therapeutic target, especially in the maintenance setting

Beneficial effects of word final stress in segmenting a new language: evidence from ERPs

Background: How do listeners manage to recognize words in an unfamiliar language? The physical continuity of the signal, in which real silent pauses between words are lacking, makes it a difficult task. However, there are multiple cues that can be exploited to localize word boundaries and to segment the acoustic signal. In the present study, word-stress was manipulated with statistical information and placed in different syllables within trisyllabic nonsense words to explore the result of the combination of the cues in an online word segmentation task. Results: The behavioral results showed that words were segmented better when stress was placed on the final syllables than when it was placed on the middle or first syllable. The electrophysiological results showed an increase in the amplitude of the P2 component, which seemed to be sensitive to word-stress and its location within words. Conclusion: The results demonstrated that listeners can integrate specific prosodic and distributional cues when segmenting speech. An ERP component related to word-stress cues was identified: stressed syllables elicited larger amplitudes in the P2 component than unstressed ones