Thermoregulatory responses to combined moderate heat stress and hypoxia

Objective: The aim of this study was to examine the cutaneous vascular and sudomotor responses to combined moderate passive heat stress and normobaric hypoxia. Method: Thirteen healthy young males, dressed in a water-perfused suit, underwent passive heating (Δcore temperature ~0.7 °C) twice (NORMOXIA; 20.9% O2 and HYPOXIA; 13% O2). Chest and forearm skin blood flow (SkBF; laser Doppler flux), local sweat rate (SR; capacitance hygrometry) and core (intestinal pill) and skin temperatures, were recorded. Results: HYPOXIA reduced baseline oxygen saturation (98±1 vs. 89±6%, P<0.001) and elevated chest (P=0.03) and forearm SkBF (P=0.03) and HR (64±9 vs. 69±8 beats.min-1, P<0.01). During heating, mean body temperature (T ̅BODY) thresholds for SkBF (P=0.41) and SR (P=0.28) elevations were not different between trials. The SkBF: T ̅BODY linear sensitivity during the initial phase of heating was lower at the Chest (P=0.035) but not different at the forearm (P=0.17) during HYPOXIA. With increasing levels of heating chest SkBF was not different (P=0.55) but forearm SkBF was lower on the forearm (P<0.01) during HYPOXIA. Chest (P=0.85) and forearm (P=0.79) SR:T ̅BODY linear sensitivities were not different between trials. Conclusion: Whilst sudomotor responses and the initiation of cutaneous blood flow elevations are unaffected, hypoxia differentially effects regional SkBF responses during moderate passive heating

Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Background Ischaemic preconditioning has well-established cardiac and vascular protective effects. Short interventions (one week) of daily ischaemic preconditioning episodes improve conduit and microcirculatory function. This study examined whether a longer (eight weeks) and less frequent (three per week) protocol of repeated ischaemic preconditioning improves vascular function. Methods Eighteen males were randomly allocated to either ischaemic preconditioning (22.4 ± 2.3 years, 23.7 ± 3.1 kg/m2) or a control intervention (26.0 ± 4.8 years, 26.4 ± 1.9 kg/m2). Brachial artery endothelial-dependent (FMD), forearm cutaneous microvascular function and cardiorespiratory fitness were assessed at zero, two and eight weeks. Results A greater improvement in FMD was evident following ischaemic preconditioning training compared with control at weeks 2 (2.24% (0.40, 4.08); p=0.02) and 8 (1.11% (0.13, 2.10); p=0.03). Repeated ischaemic preconditioning did not change cutaneous microcirculatory function or fitness. Conclusions These data indicate that a feasible and practical protocol of regular ischaemic preconditioning episodes improves endothelial function in healthy individuals within two weeks, and these effects persist following repeated ischaemic preconditioning for eight weeks

REPEATED WARM WATER IMMERSION INDUCES SIMILAR CEREBROVASCULAR ADAPTATIONS TO 8-WEEKS OF MODERATE-INTENSITY EXERCISE TRAINING IN FEMALES

Exercise training has potential to positively impact cerebrovascular function in healthy and diseased individuals. Passive heat training using warm water immersion has recently been shown to enhance systemic vascular function including the cerebrovascular response to heating. We suggest that a passive heating intervention can be a useful adjunct or alternative to exercise training. Our aim was to directly compare the effects of exercise with warm water immersion training on cerebrovascular and thermoregulatory function. 18 females (25±5y) performed 8-weeks of moderate-intensity cycling (70% HRmax) or warm-water immersion (42°C) for 30 min three times per week. Brachial artery flow-mediated dilation (FMD) and cardiorespiratory fitness were measured prior to and following both interventions. A passive heat stress was employed to obtain temperature thresholds (Tb) and sensitivities for chest and forearm sweat rate (SR) and cutaneous vasodilation (CVC). Middle cerebral artery velocity (MCAv) was measured at rest and throughout heat stress. FMD (P=0.003) and VO2peak (P<0.001) improved following both interventions. MCAv and cerebrovascular conductance were higher at rest (P<0.001 and 0.05, respectively) and during passive heating (P<0.001 and <0.001, respectively) following both interventions. Chest and forearm SR occurred at a lower Tb post-intervention with no difference between interventions. Chest and forearm SR sensitivity were increased after both interventions with no differences between interventions at the forearm but a larger increase at the chest (P<0.001) following water immersion compared to exercise training. Chest and forearm CVC occurred at a lower Tb (P<0.001) following both interventions with no differences between interventions or over time. Warm water immersion training elicits favourable and similar cerebrovascular, conduit- and thermoregulatory adaptations compared to a period of moderate-intensity exercise training over 8-weeks

EXERCISE TRAINING REDUCES THE FREQUENCY OF MENOPAUSAL HOT FLUSHES BY IMPROVING THERMOREGULATORY CONTROL

Objectives: Post-menopausal hot flushes occur due to a reduction in oestrogen production causing thermoregulatory and vascular dysfunction. Exercise training enhances thermoregulatory control of sweating, skin and brain blood flow. We aimed to determine if improving thermoregulatory control and vascular function with exercise training alleviated hot flushes. Methods: Twenty one symptomatic females completed a 7-day hot flush questionnaire and underwent brachial artery flow-mediated dilation and a cardiorespiratory fitness test. Sweat rate and skin blood flow temperature thresholds and sensitivities, and middle cerebral artery velocity (MCAv) was measured during passive heating. Females performed 16-weeks of supervised exercise training or control, and measurements were repeated. Results: There was a greater improvement in cardiorespiratory fitness (4.45 ml•kg-1•min-1 (95% CI: 1.87, 8.16; P=0.04) and reduced hot flush frequency [48 hot flushes•week (39, 56) P<0.001] following exercise compared to control. Exercise reduced basal core temperature [0.14°C (0.01, 0.27) P=0.03] and increased basal MCAv [2.8 cm/s (1.0 to 5.2) P=0.04] compared to control. Sweat rate and skin blood flow thresholds occurred ~0.19 and 0.17°C earlier, alongside improved sweating sensitivity with exercise. MCAv decreased during heating [P<0.005], but was maintained 4.5 cm/s (3.6, 5.5 P<0.005) higher during heating following exercise compared to control [0.6 cm/s (-0.4, 1.4)]. Conclusions: Exercise training that improves cardiorespiratory fitness reduces self-reported hot flushes. Improvements are likely mediated through greater thermoregulatory control in response to increases in core temperature and enhanced vascular function in the cutaneous and cerebral circulations

Characterising thermal runaway within lithium-ion cells by inducing and monitoring internal short circuits

Lithium-ion batteries are being used in increasingly demanding applications where safety and reliability are of utmost importance. Thermal runaway presents the greatest safety hazard, and needs to be fully understood in order to progress towards safer cell and battery designs. Here, we demonstrate the application of an internal short circuiting device for controlled, on-demand, initiation of thermal runaway. Through its use, the location and timing of thermal runaway initiation is pre-determined, allowing analysis of the nucleation and propagation of failure within 18 650 cells through the use of high-speed X-ray imaging at 2000 frames per second. The cause of unfavourable occurrences such as sidewall rupture, cell bursting, and cell-to-cell propagation within modules is elucidated, and steps towards improved safety of 18 650 cells and batteries are discussed

Phase transitions in contagion processes mediated by recurrent mobility patterns

Human mobility and activity patterns mediate contagion on many levels, including the spatial spread of infectious diseases, diffusion of rumors, and emergence of consensus. These patterns however are often dominated by specific locations and recurrent flows and poorly modeled by the random diffusive dynamics generally used to study them. Here we develop a theoretical framework to analyze contagion within a network of locations where individuals recall their geographic origins. We find a phase transition between a regime in which the contagion affects a large fraction of the system and one in which only a small fraction is affected. This transition cannot be uncovered by continuous deterministic models due to the stochastic features of the contagion process and defines an invasion threshold that depends on mobility parameters, providing guidance for controlling contagion spread by constraining mobility processes. We recover the threshold behavior by analyzing diffusion processes mediated by real human commuting data.Comment: 20 pages of Main Text including 4 figures, 7 pages of Supplementary Information; Nature Physics (2011

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

Population specificity of the DNAI1 gene mutation spectrum in primary ciliary dyskinesia (PCD)

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>DNAI1 </it>gene, encoding a component of outer dynein arms of the ciliary apparatus, are the second most important genetic cause of primary ciliary dyskinesia (PCD), the genetically heterogeneous recessive disorder with the prevalence of ~1/20,000. The estimates of the <it>DNAI1 </it>involvement in PCD pathogenesis differ among the reported studies, ranging from 4% to 10%.</p> <p>Methods</p> <p>The coding sequence of <it>DNAI1 </it>was screened (SSCP analysis and direct sequencing) in a group of PCD patients (157 families, 185 affected individuals), the first ever studied large cohort of PCD patients of Slavic origin (mostly Polish); multiplex ligation-dependent probe amplification (MLPA) analysis was performed in a subset of ~80 families.</p> <p>Results</p> <p>Three previously reported mutations (IVS1+2-3insT, L513P and A538T) and two novel missense substitutions (C388Y and G515S) were identified in 12 families (i.e. ~8% of non-related Polish PCD patients). The structure of background SNP haplotypes indicated common origin of each of the two most frequent mutations, IVS1+2-3insT and A538T. MLPA analysis did not reveal any significant differences between patients and control samples. The Polish cohort was compared with all the previously studied PCD groups (a total of 487 families): IVS1+2-3insT remained the most prevalent pathogenetic change in <it>DNAI1 </it>(54% of the mutations identified worldwide), and the increased global prevalence of A538T (14%) was due to the contribution of the Polish cohort.</p> <p>Conclusions</p> <p>The worldwide involvement of <it>DNAI1 </it>mutations in PCD pathogenesis in families not preselected for ODA defects ranges from 7 to 10%; this global estimate as well as the mutation profile differs in specific populations. Analysis of the background SNP haplotypes suggests that the increased frequency of chromosomes carrying A538T mutations in Polish patients may reflects local (Polish or Slavic) founder effect. Results of the MLPA analysis indicate that no large exonic deletions are involved in PCD pathogenesis.</p

Systems medicine and infection

By using a systems based approach, mathematical and computational techniques can be used to develop models that describe the important mechanisms involved in infectious diseases. An iterative approach to model development allows new discoveries to continually improve the model, and ultimately increase the accuracy of predictions. SIR models are used to describe epi demics, predicting the extent and spread of disease. Genome-wide genotyping and sequencing technologies can be used to identify the biological mechanisms behind diseases. These tools help to build strategies for disease prevention and treatment, an example being the recent outbreak of Ebola in West Africa where these techniques were deployed. HIV is a complex disease where much is still to be learnt about the virus and the best effective treatment. With basic mathematical modelling techniques, significant discoveries have been made over the last 20 years. With recent technological advances, the computation al resources now available and interdisciplinary cooperation, further breakthroughs are inevitable. In TB, modelling has traditionally been empirical in nature, with clinical data providing the fuel for this top-down approach. Recently, projects have begun to use data derived from laboratory experiments and clinical trials to create mathematical models that describe the mechanisms responsible for the disease. A systems medicine approach to infection modelling helps identify important biological questions that then direct future experiments , the results of which improve the model in an iterative cycle . This means that data from several model systems can be integrated and synthesised to explore complex biological systems .Postprin

The interplay between voluntary vaccination and reduction of risky behavior: a general behavior-implicit SIR model for vaccine preventable infections

The onset in the last 15 years of behavioral epidemiology has opened many new avenues for epidemiological modelers. In this manuscript we first review two classes of behavioral epidemiology models for vaccine preventable diseases, namely behaviour-implicit SIR models with prevalence-dependent vaccination (at birth and among older individuals), and prevalence-dependent contact rate. Subsequently, we briefly propose a general framework of behavior–dependent nonlinear and linear Forces of Infection (FoI) valid for a vast family of infectious diseases, and including delays and ‘epidemic memory’ effects. Finally and mainly, we develop a new general behavioral SIR model. This model combines the two aforementioned types of behavioral phenomena, previously considered only separately, into a single unified model for behavioral responses. The resulting model allows to develop a general phenomenological theory of the effects of behavioral responses within SIR models for endemic infections. In particular, the model allows to complete the picture about the complicate interplay between different behavioral responses acting on different epidemiological parameters in triggering sustained oscillations of vaccine coverage, risky behavior, and infection prevalence