Local temperature-sensitive mechanisms are important mediators of limb tissue hyperemia in the heat-stressed human at rest and during small muscle mass exercise.

Limb tissue and systemic blood flow increases with heat stress, but the underlying mechanisms remain poorly understood. Here, we tested the hypothesis that heat stress-induced increases in limb tissue perfusion are primarily mediated by local temperature-sensitive mechanisms. Leg and systemic temperatures and hemodynamics were measured at rest and during incremental single-legged knee extensor exercise in 15 males exposed to 1 h of either systemic passive heat-stress with simultaneous cooling of a single leg (n=8) or isolated leg heating or cooling (n=7). Systemic heat-stress increased core, skin and heated leg blood (Tb) temperatures, cardiac output and heated leg blood flow (LBF, 0.6 ± 0.1 l.min(-1); P0.05). Increased heated leg deep tissue BF was closely related to Tb (R(2) = 0.50; P0.05), despite unchanged systemic temperatures and hemodynamics. During incremental exercise, heated LBF was consistently maintained ~ 0.6 l.min(-1) higher than that in the cooled leg (P<0.01), with LBF and vascular conductance in both legs showing a strong correlation with their respective local Tb (R(2) = 0.85 and 0.95, P<0.05). We conclude that local temperature-sensitive mechanisms are important mediators in limb tissue perfusion regulation both at rest and during small-muscle mass exercise in hyperthermic humans.The invasive study was partially funded by Gatorade Sports Science Institute, PepsiCo

Whole body hyperthermia, but not skin hyperthermia, accelerates brain and locomotor limb circulatory strain and impairs exercise capacity in humans

Cardiovascular strain and hyperthermia are thought to be important factors limiting exercise capacity in heat-stressed humans; however, the contribution of elevations in skin (Tsk) vs. whole body temperatures on exercise capacity has not been characterised. To ascertain their relationships with exercise capacity, blood temperature (TB), oxygen uptake (V̇O2), brain perfusion (MCA Vmean), locomotor limb haemodynamics, and haematological parameters were assessed during incremental cycling exercise with elevated skin (mild hyperthermia; HYPmild), combined core and skin temperatures (moderate hyperthermia; HYPmod), and under control conditions. Both hyperthermic conditions increased Tsk vs. control (6.2 ± 0.2 °C; P < 0.001), however, only HYPmod increased resting TB, leg blood flow and cardiac output (Q̇), but not MCA Vmean. Throughout exercise, Tsk remained elevated in both hyperthermic conditions, whereas only TB was greater in HYPmod. At exhaustion, oxygen uptake and exercise capacity were reduced in HYPmod in association with lower leg blood flow, MCA Vmean and MAP, but similar maximal heart rate and TB. The attenuated brain and leg perfusion with hyperthermia was associated with a plateau in MCA and two-legged vascular conductance (VC). Mechanistically, the falling MCA VC was coupled to reductions in PaCO2 whereas the plateau in leg vascular conductance was related to markedly elevated plasma [NA] and a plateau in plasma ATP. These findings reveal that whole-body hyperthermia, but not skin hyperthermia, compromises exercise capacity in heat-stressed humans through the early attenuation of brain and active muscle blood flow.This study was supported by a grant from the Gatorade Sports Science Institute, PepsiCo Inc, USA. The views contained within this document are those of the authors and do not necessarily reflect those of PepsiCo Inc

Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease

Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown. Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis. Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death. Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population

Patient-reported outcomes: pathways to better health, better services, and better societies

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordWhile the use of PROs in research is well established, many challenges lie ahead as their use is extended to other applications. There is consensus that health outcome evaluations that include PROs along with clinician-reported outcomes and administrative data are necessary to inform clinical and policy decisions. The initiatives presented in this paper underline evolving recognition that PROs play a unique role in adding the patient perspective alongside clinical (e.g., blood pressure) and organizational (e.g., admission rates) indicators for evaluating the effects of new products, selecting treatments, evaluating quality of care, and monitoring the health of the population. In this paper, we first explore the use of PRO measures to support drug approval and labeling claims. We critically evaluate the evidence and challenges associated with using PRO measures to improve healthcare delivery at individual and population levels. We further discuss the challenges associated with selecting from the abundance of measures available, opportunities afforded by agreeing on common metrics for constructs of interest, and the importance of establishing an evidence base that supports integrating PRO measures across the healthcare system to improve outcomes. We conclude that the integration of PROs as a key end point within individual patient care, healthcare organization and program performance evaluations, and population surveillance will be essential for evaluating whether increased healthcare expenditure is translating into better health outcomes.Jose M. Valderas was supported by an NIHR Clinician Scientist Award (NIHR/CS/010/024)

A multi-agent system framework for dialogue games in the group decision-making context

Dialogue games have been applied to various contexts in computer science and artificial intelligence, particularly to define interactions between autonomous software agents. However, in order to implement dialogue games, the developers need to deal with other important details besides what is presented in the model’s definition. This is a complex work, mostly when it is expected that the agents’ interactions correctly represent a human group behavior. In this work, we present a multi-agent system framework specifically designed to facilitate the implementation of dialogue games under the context of group decision-making in which agents interact as the humans do in face-to-face meetings. The proposed framework, named MAS4GDM, encapsulates the JADE framework and provides a layer that allows developers to easily implement their dialogue models without being concerned with some complex implementation details, such as: the communication model, the agents’ life cycle, among others. We ran an experimental evaluation and verified that the proposed framework allows to implement dialogue models in an easier way and abstract the developers from important implementation details that can compromise the application’s success.This work was supported by the GrouPlanner Project (POCI-01-0145-FEDER-29178) and by National Funds through the FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within the Projects UID/CEC/00319/2013 and UID/EEA/00760/2013

Rapid bidirectional reorganization of cortical microcircuits.

Mature neocortex adapts to altered sensory input by changing neural activity in cortical circuits. The underlying cellular mechanisms remain unclear. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to show reorganization in somatosensory cortex elicited by altered whisker sensory input. We found that there was rapid expansion followed by retraction of whisker cortical maps. The cellular basis for the reorganization in primary somatosensory cortex was investigated with paired electrophysiological recordings in the periphery of the expanded whisker representation. During map expansion, the chance of finding a monosynaptic connection between pairs of pyramidal neurons increased 3-fold. Despite the rapid increase in local excitatory connectivity, the average strength and synaptic dynamics did not change, which suggests that new excitatory connections rapidly acquire the properties of established excitatory connections. During map retraction, entire excitatory connections between pyramidal neurons were lost. In contrast, connectivity between pyramidal neurons and fast spiking interneurons was unchanged. Hence, the changes in local excitatory connectivity did not occur in all circuits involving pyramidal neurons. Our data show that pyramidal neurons are recruited to and eliminated from local excitatory networks over days. These findings suggest that the local excitatory connectome is dynamic in mature neocortex

Linking habitat quality with genetic diversity: a lesson from great bustards in Spain

P. 411-419The effects of habitat loss and fragmentation on the genetic structure and variability of wild populations have received wide empirical support and theoretical formalization. By contrast, the effects of habitat quality seem largely underinvestigated, partly due to technical difficulties in properly assessing habitat quality. In this study, we combine geographic information system (GIS)-based habitat-quality modelling with a landscape genetics approach based on mitochondrial DNA markers to evaluate the possible influence of habitat quality on the levels and distribution of genetic diversity in a range of natural populations (n = 15) of Otis tarda throughout Spain. Ninety-three percent of the population represented by our countrywide sample lives in good-quality habitats, while 4.5% and 2.5% occur respectively in intermediate and poor habitats. Habitat quality was highly correlated with patch size, population size and population density, indicating the reliability and predictive power of the habitat suitability model. Genetic diversity was significantly correlated with habitat quality, size and density of the population, but not with patch size. Three of a total of 20 existing matrilineages from the species’ current genetic pool are restricted to poor-quality habitats. This study therefore highlights the importance of considering both population genetics and habitat quality in a species of high conservation priority.S

Heart or heart-lung transplantation for patients with congenital heart disease in England

BACKGROUND: Increased longevity in patients with congenital heart disease (CHD) is associated with late complications, mainly heart failure, which may not be amenable to redo surgery and become refractory to medical therapy and so, trigger referral for transplantation. We assessed the current role and future prospects of heart and heart-lung transplantation for patients with CHD in England. METHODS: We performed a retrospective analysis of hospital episodes for England for 1997-2015, identifying patients with a CHD code (ICD-10 'Q2xx.x'), who underwent heart or heart-lung transplantation. RESULTS: In total, 469 transplants (82.2% heart and 17.8% heart-lung) were performed in 444 patients. Half of patients transplanted had mild or moderate CHD complexity, this percentage increased with time (p=0.001). While overall, more transplantations were performed over the years, the proportion of heart-lung transplants declined (p<0.0001), whereas the proportion of transplants performed in adults remained static. Mortality was high during the first year, especially after heart-lung transplantation, but remained relatively low thereafter. Older age and heart-lung transplantation were strong predictors of death. While an increase in CHD transplants is anticipated, actual numbers in England seem to lag behind the increase in CHD patients with advanced heart failure. CONCLUSIONS: The current and future predicted increase in the numbers of CHD transplants does not appear to parallel the expansion of the CHD population, especially in adults. Further investment and changes in policy should be made to enhance the number of donors and increase CHD transplant capacity to address the increasing numbers of potential CHD recipients and optimise transplantation outcomes in this growing population

Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors

Integration-deficient lentiviruses (IdLVs) deliver genes effectively to tissues but are lost rapidly from dividing cells. This property can be harnessed to express transgenes transiently to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of hematopoietic stem and progenitor cells (HSPCs) during transplantation by delivering HOXB4 and Angptl3 using IdLVs to enhance the engraftment of HSPCs. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduces this risk and those associated with unsolicited gene expression in daughter cells. Transient expression led to increased multilineage hematopoietic engraftment in in vivo competitive repopulation assays without the side effects reported in constitutive overexpression models. Adult stem cell fate has not been programmed previously using IdLVs, but we demonstrate that these transient gene expression tools can produce clinically relevant alterations or be applied to investigate basic biology

Star Formation in Satellite Galaxies

We present narrow-band observations of the H$\alpha$ emission in a sample of 31 satellite orbiting isolated giant spiral galaxies. The sample studied spans the range $-19<M_B <-15$ mag. The H$\alpha$ emission was detected in all the spiral and irregular objects with fluxes in the range $1.15-49.80\times 10^{-14}$ erg cm$^{-2}$ s$^{-1}$. The average and maximum values for the current star formation rates are 0.68 and 3.66 M_\sun yr$^{-1}$ respectively. Maps of the spatial distribution of ionized gas are presented. The star-forming regions show a rich structure in which frequently discrete complexes are imposed over more diffuse structures. In general, the current star formation rates are smaller that the mean values in the past obtained from the current stellar content; this probably indicates a declining rhythm with time in the generation of new stars. However, the reserve of gas is enough to continue fueling the current levels of star formation activity for at least another Hubble time. Four of the objects (NGC 2718b, NGC 4541e, NGC 5965a$_1$ and NGC 5965a$_2$) with higher current star formation rates show clear signs of interaction with close companions of comparable brightness at projected distances of 25, 20 and 2 kpc respectively. The only two galaxies in our sample that do not show star formation activity are members of these interacting systems, and it is unclear if this is a consequence of intrinsic properties (both are Hubble early types) or if it is related with possible disruption of the external parts due to the interaction. In the case of the pair NGC 2718a-b there are indications of gas transport between both galaxies.Comment: 25 pages, 11 figures. Accepted for publication in A