961 research outputs found

    Pre-cooling for endurance exercise performance in the heat: a systematic review.

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    PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

    Food-web structure in relation to environmental gradients and predator-prey ratios in tank-bromeliad ecosystems

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    Little is known of how linkage patterns between species change along environmental gradients. The small, spatially discrete food webs inhabiting tank-bromeliads provide an excellent opportunity to analyse patterns of community diversity and food-web topology (connectance, linkage density, nestedness) in relation to key environmental variables (habitat size, detrital resource, incident radiation) and predators: prey ratios. We sampled 365 bromeliads in a wide range of understorey environments in French Guiana and used gut contents of invertebrates to draw the corresponding 365 connectance webs. At the bromeliad scale, habitat size (water volume) determined the number of species that constitute food-web nodes, the proportion of predators, and food-web topology. The number of species as well as the proportion of predators within bromeliads declined from open to forested habitats, where the volume of water collected by bromeliads was generally lower because of rainfall interception by the canopy. A core group of microorganisms and generalist detritivores remained relatively constant across environments. This suggests that (i) a highly-connected core ensures food-web stability and key ecosystem functions across environments, and (ii) larger deviations in food-web structures can be expected following disturbance if detritivores share traits that determine responses to environmental changes. While linkage density and nestedness were lower in bromeliads in the forest than in open areas, experiments are needed to confirm a trend for lower food-web stability in the understorey of primary forests

    Paradoxical effects of JZL184, an inhibitor of monoacylglycerol lipase, on bone remodelling in healthy and cancer-bearing mice

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    Background Cancer-associated bone disease is a serious complication in bone sarcomas and metastatic carcinomas of breast and prostate origin. Monoacylglycerol lipase (MAGL) is an enzyme of the endocannabinoid system, and is responsible for the degradation of the most abundant endocannabinoid in bone, 2-arachidonoyl glycerol (2AG). Methods The effects of the verified MAGL inhibitor on bone remodelling were assessed in healthy mice and in mouse models of bone disease caused by prostate and breast cancers and osteosarcoma. Findings JZL184 reduced osteolytic bone metastasis in mouse models of breast and prostate cancers, and inhibited skeletal tumour growth, metastasis and the formation of ectopic bone in models of osteosarcoma. Additionally, JZL184 suppressed cachexia and prolonged survival in mice injected with metastatic osteosarcoma and osteotropic cancer cells. Functional and histological analysis revealed that the osteoprotective action of JZL184 in cancer models is predominately due to inhibition of tumour growth and metastasis. In the absence of cancer, however, exposure to JZL184 exerts a paradoxical reduction of bone volume via an effect that is mediated by both Cnr1 and Cnr2 cannabinoid receptors. Interpretation MAGL inhibitors such as JZL184, or its novel analogues, may be of value in the treatment of bone disease caused by primary bone cancer and bone metastasis, however, activation of the skeletal endocannabinoid system may limit their usefulness as osteoprotective agents

    International comparison of health spending and utilization among people with complex multimorbidity.

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    OBJECTIVE: The objective of this study was to explore cross-country differences in spending and utilization across different domains of care for a multimorbid persona with heart failure and diabetes. DATA SOURCES: We used individual-level administrative claims or registry data from inpatient and outpatient health care sectors compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States (US). DATA COLLECTION/EXTRACTION METHODS: Data collected by ICCONIC partners. STUDY DESIGN: We retrospectively analyzed age-sex standardized utilization and spending of an older person (65-90 years) hospitalized with a heart failure exacerbation and a secondary diagnosis of diabetes across five domains of care: hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, and outpatient drugs. PRINCIPAL FINDINGS: Sample sizes ranged from n = 1270 in Spain to n = 21,803 in the United States. Mean age (standard deviation [SD]) ranged from 76.2 (5.6) in the Netherlands to 80.3 (6.8) in Sweden. We observed substantial variation in spending and utilization across care settings. On average, England spent 10,956perpersoninhospitalcarewhiletheUnitedStatesspent10,956 per person in hospital care while the United States spent 30,877. The United States had a shorter length of stay over the year (18.9 days) compared to France (32.9) and Germany (33.4). The United States spent more days in facility-based rehabilitative care than other countries. Australia spent 421perpersoninprimarycare,whileSpain(Aragon)spent421 per person in primary care, while Spain (Aragon) spent 1557. The United States and Canada had proportionately more visits to specialist providers than primary care providers. Across almost all sectors, the United States spent more than other countries, suggesting higher prices per unit. CONCLUSION: Across 11 countries, there is substantial variation in health care spending and utilization for a complex multimorbid persona with heart failure and diabetes. Drivers of spending vary across countries, with the United States being the most expensive country due to high prices and higher use of facility-based rehabilitative care

    Differences in health outcomes for high-need high-cost patients across high-income countries.

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    ObjectiveThis study explores variations in outcomes of care for two types of patient personas-an older frail person recovering from a hip fracture and a multimorbid older patient with congestive heart failure (CHF) and diabetes.Data sourcesWe used individual-level patient data from 11 health systems.Study designWe compared inpatient mortality, mortality, and readmission rates at 30, 90, and 365 days. For the hip fracture persona, we also calculated time to surgery. Outcomes were standardized by age and sex.Data collection/extraction methodsData was compiled by the International Collaborative on Costs, Outcomes and Needs in Care across 11 countries for the years 2016-2017 (or nearest): Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States.Principal findingsThe hip sample across ranged from 1859 patients in Aragon, Spain, to 42,849 in France. Mean age ranged from 81.2 in Switzerland to 84.7 in Australia, and the majority of hip patients across countries were female. The congestive heart failure (CHF) sample ranged from 742 patients in England to 21,803 in the United States. Mean age ranged from 77.2 in the United States to 80.3 in Sweden, and the majority of CHF patients were males. Average in-hospital mortality across countries was 4.1%. for the hip persona and 6.3% for the CHF persona. At the year mark, the mean mortality across all countries was 25.3% for the hip persona and 32.7% for CHF persona. Across both patient types, England reported the highest mortality at 1 year followed by the United States. Readmission rates for all periods were higher for the CHF persona than the hip persona. At 30 days, the average readmission rate for the hip persona was 13.8% and 27.6% for the CHF persona.ConclusionAcross 11 countries, there are meaningful differences in health system outcomes for two types of patients

    Differences in health care spending and utilization among older frail adults in high-income countries: ICCONIC hip fracture persona.

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    ObjectiveThis study explores differences in spending and utilization of health care services for an older person with frailty before and after a hip fracture.Data sourcesWe used individual-level patient data from five care settings.Study designWe compared utilization and spending of an older person aged older than 65 years for 365 days before and after a hip fracture across 11 countries and five domains of care as follows: acute hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, and outpatient drugs. Utilization and spending were age and sex standardized..Data collection/extraction methodsThe data were compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries as follows: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States.Principal findingsThe sample ranged from 1859 patients in Spain to 42,849 in France. Mean age ranged from 81.2 in Switzerland to 84.7 in Australia. The majority of patients across countries were female. Relative to other countries, the United States had the lowest inpatient length of stay (11.3), but the highest number of days were spent in post-acute care rehab (100.7) and, on average, had more visits to specialist providers (6.8 per year) than primary care providers (4.0 per year). Across almost all sectors, the United States spent more per person than other countries per unit (13,622perhospitalization,13,622 per hospitalization, 233 per primary care visit, $386 per MD specialist visit). Patients also had high expenditures in the year prior to the hip fracture, mostly concentrated in the inpatient setting.ConclusionAcross 11 high-income countries, there is substantial variation in health care spending and utilization for an older person with frailty, both before and after a hip fracture. The United States is the most expensive country due to high prices and above average utilization of post-acute rehab care

    ASPASIA: A toolkit for evaluating the effects of biological interventions on SBML model behavior

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    <div><p>A calibrated computational model reflects behaviours that are expected or observed in a complex system, providing a baseline upon which sensitivity analysis techniques can be used to analyse pathways that may impact model responses. However, calibration of a model where a behaviour depends on an intervention introduced after a defined time point is difficult, as model responses may be dependent on the conditions at the time the intervention is applied. We present ASPASIA (Automated Simulation Parameter Alteration and SensItivity Analysis), a cross-platform, open-source Java toolkit that addresses a key deficiency in software tools for understanding the impact an intervention has on system behaviour for models specified in Systems Biology Markup Language (SBML). ASPASIA can generate and modify models using SBML solver output as an initial parameter set, allowing interventions to be applied once a steady state has been reached. Additionally, multiple SBML models can be generated where a subset of parameter values are perturbed using local and global sensitivity analysis techniques, revealing the model’s sensitivity to the intervention. To illustrate the capabilities of ASPASIA, we demonstrate how this tool has generated novel hypotheses regarding the mechanisms by which Th17-cell plasticity may be controlled <i>in vivo</i>. By using ASPASIA in conjunction with an SBML model of Th17-cell polarisation, we predict that promotion of the Th1-associated transcription factor T-bet, rather than inhibition of the Th17-associated transcription factor ROR<i>γ</i>t, is sufficient to drive switching of Th17 cells towards an IFN-<i>γ</i>-producing phenotype. Our approach can be applied to all SBML-encoded models to predict the effect that intervention strategies have on system behaviour. ASPASIA, released under the Artistic License (2.0), can be downloaded from <a href="http://www.york.ac.uk/ycil/software" target="_blank">http://www.york.ac.uk/ycil/software</a>.</p></div

    Visual laterality in dolphins: importance of the familiarity of stimuli

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    <p>Abstract</p> <p>Background</p> <p>Many studies of cerebral asymmetries in different species lead, on the one hand, to a better understanding of the functions of each cerebral hemisphere and, on the other hand, to develop an evolutionary history of hemispheric laterality. Our animal model is particularly interesting because of its original evolutionary path, i.e. return to aquatic life after a terrestrial phase. The rare reports concerning visual laterality of marine mammals investigated mainly discrimination processes. As dolphins are migrant species they are confronted to a changing environment. Being able to categorize new versus familiar objects would allow dolphins a rapid adaptation to novel environments. Visual laterality could be a prerequisite to this adaptability. To date, no study, to our knowledge, has analyzed the environmental factors that could influence their visual laterality.</p> <p>Results</p> <p>We investigated visual laterality expressed spontaneously at the water surface by a group of five common bottlenose dolphins (<it>Tursiops truncatus</it>) in response to various stimuli. The stimuli presented ranged from very familiar objects (known and manipulated previously) to familiar objects (known but never manipulated) to unfamiliar objects (unknown, never seen previously). At the group level, dolphins used their left eye to observe very familiar objects and their right eye to observe unfamiliar objects. However, eyes are used indifferently to observe familiar objects with intermediate valence.</p> <p>Conclusion</p> <p>Our results suggest different visual cerebral processes based either on the global shape of well-known objects or on local details of unknown objects. Moreover, the manipulation of an object appears necessary for these dolphins to construct a global representation of an object enabling its immediate categorization for subsequent use. Our experimental results pointed out some cognitive capacities of dolphins which might be crucial for their wild life given their fission-fusion social system and migratory behaviour.</p

    A methodology for identifying high-need, high-cost patient personas for international comparisons.

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    ObjectiveTo establish a methodological approach to compare two high-need, high-cost (HNHC) patient personas internationally.Data sourcesLinked individual-level administrative data from the inpatient and outpatient sectors compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States.Study designWe outline a methodological approach to identify HNHC patient types for international comparisons that reflect complex, priority populations defined by the National Academy of Medicine. We define two patient profiles using accessible patient-level datasets linked across different domains of care-hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, long-term care, home-health care, and outpatient drugs. The personas include a frail older adult with a hip fracture with subsequent hip replacement and an older person with complex multimorbidity, including heart failure and diabetes. We demonstrate their comparability by examining the characteristics and clinical diagnoses captured across countries.Data collection/extraction methodsData collected by ICCONIC partners.Principal findingsAcross 11 countries, the identification of HNHC patient personas was feasible to examine variations in healthcare utilization, spending, and patient outcomes. The ability of countries to examine linked, individual-level data varied, with the Netherlands, Canada, and Germany able to comprehensively examine care across all seven domains, whereas other countries such as England, Switzerland, and New Zealand were more limited. All countries were able to identify a hip fracture persona and a heart failure persona. Patient characteristics were reassuringly similar across countries.ConclusionAlthough there are cross-country differences in the availability and structure of data sources, countries had the ability to effectively identify comparable HNHC personas for international study. This work serves as the methodological paper for six accompanying papers examining differences in spending, utilization, and outcomes for these personas across countries

    Urinary α1-Antichymotrypsin: A Biomarker of Prion Infection

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    The occurrence of blood-borne prion transmission incidents calls for identification of potential prion carriers. However, current methods for intravital diagnosis of prion disease rely on invasive tissue biopsies and are unsuitable for large-scale screening. Sensitive biomarkers may help meeting this need. Here we scanned the genome for transcripts elevated upon prion infection and encoding secreted proteins. We found that α1-antichymotrypsin (α1-ACT) was highly upregulated in brains of scrapie-infected mice. Furthermore, α1-ACT levels were dramatically increased in urine of patients suffering from sporadic Creutzfeldt-Jakob disease, and increased progressively throughout the disease. Increased α1-ACT excretion was also found in cases of natural prion disease of animals. Therefore measurement of urinary α1-ACT levels may be useful for monitoring the efficacy of therapeutic regimens for prion disease, and possibly also for deferring blood and organ donors that may be at risk of transmitting prion infections
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