939 resultados para bound statement
Resumo:
Challenging environmental conditions, including heat and humidity, cold, and altitude, pose particular risks to the health of Olympic and other high-level athletes. As a further commitment to athlete safety, the International Olympic Committee (IOC) Medical Commission convened a panel of experts to review the scientific evidence base, reach consensus, and underscore practical safety guidelines and new research priorities regarding the unique environmental challenges Olympic and other international-level athletes face. For non-aquatic events, external thermal load is dependent on ambient temperature, humidity, wind speed and solar radiation, while clothing and protective gear can measurably increase thermal strain and prompt premature fatigue. In swimmers, body heat loss is the direct result of convection at a rate that is proportional to the effective water velocity around the swimmer and the temperature difference between the skin and the water. Other cold exposure and conditions, such as during Alpine skiing, biathlon and other sliding sports, facilitate body heat transfer to the environment, potentially leading to hypothermia and/or frostbite; although metabolic heat production during these activities usually increases well above the rate of body heat loss, and protective clothing and limited exposure time in certain events reduces these clinical risks as well. Most athletic events are held at altitudes that pose little to no health risks; and training exposures are typically brief and well-tolerated. While these and other environment-related threats to performance and safety can be lessened or averted by implementing a variety of individual and event preventative measures, more research and evidence-based guidelines and recommendations are needed. In the mean time, the IOC Medical Commission and International Sport Federations have implemented new guidelines and taken additional steps to mitigate risk even further.
Resumo:
Rapid neurotransmitter release depends on the ability to arrest the SNAP receptor (SNARE)-dependent exocytosis pathway at an intermediate "cocked" state, from which fusion can be triggered by Ca(2+). It is not clear whether this state includes assembly of synaptobrevin (the vesicle membrane SNARE) to the syntaxin-SNAP-25 (target membrane SNAREs) acceptor complex or whether the reaction is arrested upstream of that step. In this study, by a combination of in vitro biophysical measurements and time-resolved exocytosis measurements in adrenal chromaffin cells, we find that mutations of the N-terminal interaction layers of the SNARE bundle inhibit assembly in vitro and vesicle priming in vivo without detectable changes in triggering speed or fusion pore properties. In contrast, mutations in the last C-terminal layer decrease triggering speed and fusion pore duration. Between the two domains, we identify a region exquisitely sensitive to mutation, possibly constituting a switch. Our data are consistent with a model in which the N terminus of the SNARE complex assembles during vesicle priming, followed by Ca(2+)-triggered C-terminal assembly and membrane fusion.
Resumo:
Human Fas ligand (L) (CD95L) and tumor necrosis factor (TNF)-alpha undergo metalloproteinase-mediated proteolytic processing in their extracellular domains resulting in the release of soluble trimeric ligands (soluble [s]FasL, sTNF-alpha) which, in the case of sFasL, is thought to be implicated in diseases such as hepatitis and AIDS. Here we show that the processing of sFasL occurs between Ser126 and Leu127. The apoptotic-inducing capacity of naturally processed sFasL was reduced by >1,000-fold compared with membrane-bound FasL, and injection of high doses of recombinant sFasL in mice did not induce liver failure. However, soluble FasL retained its capacity to interact with Fas, and restoration of its cytotoxic activity was achieved both in vitro and in vivo with the addition of cross-linking antibodies. Similarly, the marginal apoptotic activity of recombinant soluble TNF-related apoptosis-inducing ligand (sTRAIL), another member of the TNF ligand family, was greatly increased upon cross-linking. These results indicate that the mere trimerization of the Fas and TRAIL receptors may not be sufficient to trigger death signals. Thus, the observation that sFasL is less cytotoxic than membrane-bound FasL may explain why in certain types of cancer, systemic tissue damage is not detected, even though the levels of circulating sFasL are high.
Resumo:
An ab initio structure prediction approach adapted to the peptide-major histocompatibility complex (MHC) class I system is presented. Based on structure comparisons of a large set of peptide-MHC class I complexes, a molecular dynamics protocol is proposed using simulated annealing (SA) cycles to sample the conformational space of the peptide in its fixed MHC environment. A set of 14 peptide-human leukocyte antigen (HLA) A0201 and 27 peptide-non-HLA A0201 complexes for which X-ray structures are available is used to test the accuracy of the prediction method. For each complex, 1000 peptide conformers are obtained from the SA sampling. A graph theory clustering algorithm based on heavy atom root-mean-square deviation (RMSD) values is applied to the sampled conformers. The clusters are ranked using cluster size, mean effective or conformational free energies, with solvation free energies computed using Generalized Born MV 2 (GB-MV2) and Poisson-Boltzmann (PB) continuum models. The final conformation is chosen as the center of the best-ranked cluster. With conformational free energies, the overall prediction success is 83% using a 1.00 Angstroms crystal RMSD criterion for main-chain atoms, and 76% using a 1.50 Angstroms RMSD criterion for heavy atoms. The prediction success is even higher for the set of 14 peptide-HLA A0201 complexes: 100% of the peptides have main-chain RMSD values < or =1.00 Angstroms and 93% of the peptides have heavy atom RMSD values < or =1.50 Angstroms. This structure prediction method can be applied to complexes of natural or modified antigenic peptides in their MHC environment with the aim to perform rational structure-based optimizations of tumor vaccines.
Resumo:
CEA as well as normal cross-reacting antigens (NCA) are fixed to the cell membrane via phosphatidylinositol (PI). To find out whether these antigens are internalized after antibody contact, acid pH desorption was compared to phospholipase C (PLC)-mediated cleavage of the antigen anchor. With the former procedure, marked differences in the desorbability of individual MAbs were noted, while PLC was able to cleave off surface-bound immune complexes irrespective of the MAb involved. From this it is concluded that internalization of MAb complexes of CEA/NCA, if occurring at all, is a low efficiency process.
Resumo:
"Vegeu el resum a l'inici del document del fitxer adjunt"
Resumo:
Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.
Resumo:
The Institute of Public Health in Ireland (IPH) aims to improve health on the island of Ireland by working to combat health inequalities and influence public policies in favour of health. The Institute promotes cooperation between Northern Ireland and the Republic of Ireland in public health research, training and policy advice. IPH acknowledge that health is influenced by a wide range of social determinants, including economic, environmental, social and biological factors. Housing and residential areas are identified as key determinants of health and IPH welcomes the opportunity to comment on the Department of the Environment (DoE), Draft Addendum to Planning Policy Statement 7.
Resumo:
In responding, IPH identify a number of potential health impacts including providing employment opportunities through farm diversification. Other issues include access to open space and housing located close to traditional focal points. The Institute of Public Health in Ireland (IPH) is an all-island body which aims to improve health in Ireland, by working to combat health inequalities and influence public policies in favour of health. IPH promotes co-operation in research, training, information and policy in order to contribute to policies which tackle inequalities in health. IPH is particularly interested in the Draft Planning Policy Statement 21 due to the impact on the countryside and potential implications on health for the population of Northern Ireland. IPH conducted a Health Impact Assessment on the proposed West Tyrone Area Plan 2019 and through this work has developed extensive knowledge when looking at health and rural issues.
Resumo:
IPH welcomes the Planning Policy Statement 18 Renewable Energy (PPS18) and the opportunity to comment on the publication. IPH applies a holistic model of health which emphasises a wide range of social determinants, including economic, environmental, social and biological factors. IPH considers that the health impacts of renewable energy should be considered as part of PPS18. We wish to make the following general observations in relation to the Proposed Plan: IPH welcomes the sustainable approach by the Department of the Environment to encourage and facilitate the provision of renewal energy in Northern Ireland. PPS18 can support the move to reduce pollutants entering the environment. However there is a need to consider wider public health concerns in the adoption of PPS18. Encouraging renewable energy (while balancing this with environmental and conservation concerns) will benefit health locally, and on a global scale. Climate change has been identified as one of the most important public health challenges of the 21st Century and therefore any policy which seeks to address this major issue is welcomed.
Resumo:
The Department of Health and Children Statement of Strategy will map out in broad terms the Department’s key areas of strategic action in the coming three years and act as the backdrop against which the Business Plans of each division of the Department will be prepared. The Institute’s recent submission on the Department’s Strategy Statement proposes that tackling inequalities in health form a key area of strategic action across all divisions within the Department in the coming three years. The Institute called for the Department to make additional commitments to tackle health inequalities at their root causes, in addition to developing services to meet the needs of poor and vulnerable members of society. The submission states that the full implementation of the National Health Information Strategy is now a matter of urgency and also strongly recommends that the Department makes the achievement of the recommendations of the recent A Strategy for Cancer Control in Ireland a priority in the coming years within its enhanced policy evaluation and analysis role. A stronger leadership role to advance the vision set out in the Primary Care Strategy is encouraged. The submission also recommends the development of a new set of high-level long-term targets relating to the reduction of inequalities to provide an overarching policy context against which related policies and the HSE operations could be structured.
Resumo:
This document states the Institute of Public Health in Ireland’s (IPH) commitment to an Open Access policy and outlines how it implements that policy. "Open Access is the immediate, online, free availability of research outputs without restrictions on use commonly imposed by publisher copyright agreements. Open Access includes the outputs that scholars normally give away for free for publication; it includes peer-reviewed journal articles, conference papers and data of various kinds."1 The Open Access (OA) movement aims to: Provide access to scientific outputs in publications that are freely available Foster the adoption of open access publication models
Resumo:
Research and Development in the Professions Allied to Medicine within NI
Resumo:
The Vision for ICT to Support Health and Social Care Services