941 resultados para Multi-Criteria Optimisation


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The prevalence of overweight and obesity has increased with alarming speed over the past twenty years. It has recently been described by the World Health Organisation as a ‘global epidemic’. In the year 2000 more than 300 million people worldwide were obese and it is now projected that by 2025 up to half the population of the United States will be obese if current trends are maintained. The disease is now a major public health problem throughout Europe. In Ireland at the present time 39% of adults are overweight and 18% are obese. Of these, slightly more men than women are obese and there is a higher incidence of the disease in lower socio-economic groups. Most worrying of all is the fact that childhood obesity has reached epidemic proportions in Europe, with body weight now the most prevalent childhood disease. While currently there are no agreed criteria or standards for assessing Irish children for obesity some studies are indicating that the numbers of children who are significantly overweight have trebled over the past decade. Extrapolation from authoritative UK data suggests that these numbers could now amount to more than 300,000 overweight and obese children on the island of Ireland and they are probably rising at a rate of over 10,000 per year. A balance of food intake and physical activity is necessary for a healthy weight. The foods we individually consume and our participation in physical activity are the result of a complex supply and production system. The growing research evidence that energy dense foods promote obesity is impressive and convincing. These are the foods that are high in fat, sugar and starch. Of these potentially the most significant promoter of weight gain is fat and foods from the top shelf of the food pyramid including spreads (butter and margarine), cakes and biscuits, and confectionery, when combined are the greatest contributors to fat intake in the Irish diet. In company with their adult counterparts Irish children are also consuming large amounts of energy dense foods outside the home. A recent survey revealed that slightly over half of these children ate sweets at least once a day and roughly a third of them had fizzy drinks and crisps with the same regularity. Sugar sweetened carbonated drinks are thought to contribute to obesity and for this reason the World Health Organisation has expressed serious concerns at the high and increasing consumption of these drinks by children. Physical activity is an important determinant of body weight. Over recent decades there has been a marked decline in demanding physical work and this has been accompanied by more sedentary lifestyles generally and reduced leisure-time activity. These observable changes, which are supported by data from most European countries and the United States, suggest that physical inactivity has made a significant impact on the increase in overweight and obesity being seen today. It is now widely accepted that adults shoud be involved in 45-60 minutes, and children should be involved in at least 60 minutes per day of moderate physical activity in order to prevent excess weight gain. Being overweight today not only signals increased risk of medical problems but also exposes people to serious psychosocial problems due mainly to widespread prejudice against fat people. Prejudice against obese people seems to border on the socially acceptable in Ireland. It crops up consistently in surveys covering groups such as employers, teachers, medical and healthcare personnel, and the media. It occurs among adolescents and children, even very young children. Because obesity is associated with premature death, excessive morbidity and serious psychosocial problems the damage it causes to the welfare of citizens is extremely serious and for this reason government intervention is necessary and warranted. In economic terms, a figure of approximately â,¬30million has been estimated for in-patient costs alone in 2003 for a number of Irish hospitals. This year about 2,000 premature deaths in Ireland will be attributed to obesity and the numbers are growing relentlessly. Diseases which proportionally more obese people suffer from than the general population include hypertension, type 2 diabetes, angina, heart attack and osteoarthritis. There are indirect costs also such as days lost to the workplace due to illness arising from obesity and output foregone as a result of premature death. Using the accepted EU environmental cost benefit method, these deaths alone may be costing the state as much as â,¬4bn per year. The social determinants of physical activity include factors such as socio-economic status, education level, gender, family and peer group influences as well as individual perceptions of the benefits of physical activity. The environmental determinants include geographic location, time of year, and proximity of facilities such as open spaces, parks and safe recreational areas generally. The environmental factors have not yet been as well studied as the social ones and this research gap needs to be addressed. Clearly there is a public health imperative to ensure that relevant environmental policies maximise opportunities for active transport, recreational physical activity and total physical activity. It is clear that concerted policy initiatives must be put in place if the predominantly negative findings of research regarding the determinants of food consumption and physical activity are to be accepted, and they must surely be accepted by government if the rapid increase in the incidence of obesity with all its negative consequences for citizens is to be reversed. So far actions surrounding nutrition policies have concentrated mostly on actions that are within the remit of the Department of Health and Children such as implementing the dietary guidelines. These are important but government must now look at the totality of policies that influence the type and supply of food that its citizens eat and the range and quality of opportunities that are available to citizens to engage in physical activity. This implies a fundamental examination of existing agricultural, industrial, economic and other policies and a determination to change them if they do not enable people to eat healthily and partake in physical activity. The current crisis in obesity prevalence requires a population health approach for adults and children in addition to effective weight-reduction management for individuals who are severely overweight. This entails addressing the obesogenic environment where people live, creating conditions over time which lead to healthier eating and more active living, and protecting people from the widespread availability of unhealthy food and beverage options in addition to sedentary activities that take up all of their leisure time. People of course have a fundamental right to choose to eat what they want and to be as active as they wish. That is not the issue. What the National Taskforce on Obesity has had to take account of is that many forces are actively impeding change for those well aware of the potential health and well-being consequences to themselves of overweight and obesity. The Taskforce’s social change strategy is to give people meaningful choice. Choice, or the capacity to change (because the strategy is all about change), is facilitated through the development of personal skills and preferences, through supportive and participative environments at work, at school and in the local community, and through a dedicated and clearly communicated public health strategy. High-level cabinet support will be necessary to implement the Taskforce’s recommendations. The approach to implementation must be characterised by joined-up thinking, real practical engagement by the public and private sectors, the avoidance of duplication of effort or crosspurpose approaches, and the harnessing of existing strategies and agencies. The range of government departments with roles to play is considerable. The Taskforce outlines the different contributions that each relevant department can make in driving its strategy forward. It also emphasises its requirement that all phases of the national strategy for healthy eating and physical activity are closely monitored, analysed and evaluated. The vision of the Taskforce is expressed as: An Irish society that enables people through health promotion, prevention and care to achieve and maintain healthy eating and active living throughout their lifespan. Its high-level goals are expressed as follows: Its recommendations, over eighty in all, relate to actions across six broad sectors: high-level government; education; social and community; health; food, commodities, production and supply; and the physical environment. In developing its recommendations the Taskforce has taken account of the complex, multisectoral and multi-faceted determinants of diet and physical activity. This strategy poses challenges for government, within individual departments, inter-departmentally and in developing partnerships with the commercial sector. Equally it challenges the commercial sector to work in partnership with government. The framework required for such initiative has at its core the rights and benefits of the individual. Health promotion is fundamentally about empowerment, whether at the individual, the community or the policy level.

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Click here to download PDF The prevalence of overweight and obesity has increased with alarming speed over the past twenty years. It has recently been described by the World Health Organisation as a ‘global epidemic’. In the year 2000 more than 300 million people worldwide were obese and it is now projected that by 2025 up to half the population of the United States will be obese if current trends are maintained. The disease is now a major public health problem throughout Europe. In Ireland at the present time 39% of adults are overweight and 18% are obese. Of these, slightly more men than women are obese and there is a higher incidence of the disease in lower socio-economic groups. Most worrying of all is the fact that childhood obesity has reached epidemic proportions in Europe, with body weight now the most prevalent childhood disease. While currently there are no agreed criteria or standards for assessing Irish children for obesity some studies are indicating that the numbers of children who are significantly overweight have trebled over the past decade. Extrapolation from authoritative UK data suggests that these numbers could now amount to more than 300,000 overweight and obese children on the island of Ireland and they are probably rising at a rate of over 10,000 per year. A balance of food intake and physical activity is necessary for a healthy weight. The foods we individually consume and our participation in physical activity are the result of a complex supply and production system. The growing research evidence that energy dense foods promote obesity is impressive and convincing. These are the foods that are high in fat, sugar and starch. Of these potentially the most significant promoter of weight gain is fat and foods from the top shelf of the food pyramid including spreads (butter and margarine), cakes and biscuits, and confectionery, when combined are the greatest contributors to fat intake in the Irish diet. In company with their adult counterparts Irish children are also consuming large amounts of energy dense foods outside the home. A recent survey revealed that slightly over half of these children ate sweets at least once a day and roughly a third of them had fizzy drinks and crisps with the same regularity. Sugar sweetened carbonated drinks are thought to contribute to obesity and for this reason the World Health Organisation has expressed serious concerns at the high and increasing consumption of these drinks by children. Physical activity is an important determinant of body weight. Over recent decades there has been a marked decline in demanding physical work and this has been accompanied by more sedentary lifestyles generally and reduced leisure-time activity. These observable changes, which are supported by data from most European countries and the United States, suggest that physical inactivity has made a significant impact on the increase in overweight and obesity being seen today. It is now widely accepted that adults shoud be involved in 45-60 minutes, and children should be involved in at least 60 minutes per day of moderate physical activity in order to prevent excess weight gain. Being overweight today not only signals increased risk of medical problems but also exposes people to serious psychosocial problems due mainly to widespread prejudice against fat people. Prejudice against obese people seems to border on the socially acceptable in Ireland. It crops up consistently in surveys covering groups such as employers, teachers, medical and healthcare personnel, and the media. It occurs among adolescents and children, even very young children. Because obesity is associated with premature death, excessive morbidity and serious psychosocial problems the damage it causes to the welfare of citizens is extremely serious and for this reason government intervention is necessary and warranted. In economic terms, a figure of approximately â,¬30million has been estimated for in-patient costs alone in 2003 for a number of Irish hospitals. This year about 2,000 premature deaths in Ireland will be attributed to obesity and the numbers are growing relentlessly. Diseases which proportionally more obese people suffer from than the general population include hypertension, type 2 diabetes, angina, heart attack and osteoarthritis. There are indirect costs also such as days lost to the workplace due to illness arising from obesity and output foregone as a result of premature death. Using the accepted EU environmental cost benefit method, these deaths alone may be costing the state as much as â,¬4bn per year. The social determinants of physical activity include factors such as socio-economic status, education level, gender, family and peer group influences as well as individual perceptions of the benefits of physical activity. The environmental determinants include geographic location, time of year, and proximity of facilities such as open spaces, parks and safe recreational areas generally. The environmental factors have not yet been as well studied as the social ones and this research gap needs to be addressed. Clearly there is a public health imperative to ensure that relevant environmental policies maximise opportunities for active transport, recreational physical activity and total physical activity. It is clear that concerted policy initiatives must be put in place if the predominantly negative findings of research regarding the determinants of food consumption and physical activity are to be accepted, and they must surely be accepted by government if the rapid increase in the incidence of obesity with all its negative consequences for citizens is to be reversed. So far actions surrounding nutrition policies have concentrated mostly on actions that are within the remit of the Department of Health and Children such as implementing the dietary guidelines. These are important but government must now look at the totality of policies that influence the type and supply of food that its citizens eat and the range and quality of opportunities that are available to citizens to engage in physical activity. This implies a fundamental examination of existing agricultural, industrial, economic and other policies and a determination to change them if they do not enable people to eat healthily and partake in physical activity. The current crisis in obesity prevalence requires a population health approach for adults and children in addition to effective weight-reduction management for individuals who are severely overweight. This entails addressing the obesogenic environment where people live, creating conditions over time which lead to healthier eating and more active living, and protecting people from the widespread availability of unhealthy food and beverage options in addition to sedentary activities that take up all of their leisure time. People of course have a fundamental right to choose to eat what they want and to be as active as they wish. That is not the issue. What the National Taskforce on Obesity has had to take account of is that many forces are actively impeding change for those well aware of the potential health and well-being consequences to themselves of overweight and obesity. The Taskforce’s social change strategy is to give people meaningful choice. Choice, or the capacity to change (because the strategy is all about change), is facilitated through the development of personal skills and preferences, through supportive and participative environments at work, at school and in the local community, and through a dedicated and clearly communicated public health strategy. High-level cabinet support will be necessary to implement the Taskforce’s recommendations. The approach to implementation must be characterised by joined-up thinking, real practical engagement by the public and private sectors, the avoidance of duplication of effort or crosspurpose approaches, and the harnessing of existing strategies and agencies. The range of government departments with roles to play is considerable. The Taskforce outlines the different contributions that each relevant department can make in driving its strategy forward. It also emphasises its requirement that all phases of the national strategy for healthy eating and physical activity are closely monitored, analysed and evaluated. The vision of the Taskforce is expressed as: An Irish society that enables people through health promotion, prevention and care to achieve and maintain healthy eating and active living throughout their lifespan. Its high-level goals are expressed as follows: Its recommendations, over eighty in all, relate to actions across six broad sectors: high-level government; education; social and community; health; food, commodities, production and supply; and the physical environment. In developing its recommendations the Taskforce has taken account of the complex, multisectoral and multi-faceted determinants of diet and physical activity. This strategy poses challenges for government, within individual departments, inter-departmentally and in developing partnerships with the commercial sector. Equally it challenges the commercial sector to work in partnership with government. The framework required for such initiative has at its core the rights and benefits of the individual. Health promotion is fundamentally about empowerment, whether at the individual, the community or the policy level.

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We evaluated the usefulness of the combination of three plasmids encoding tegumental (pECL and pSM14) and muscular (pIRV5) antigens of the Schistosoma mansoni on improving the protective immunity over the use of a single antigen as DNA vaccines. Female BALB/c mice were inoculated twice with 25 µg DNA plasmid within two weeks interval. The challenge was performed with 80 cercarias of a regional isolate of S. mansoni (SLM) one week after the last immunization. Six weeks after challenge, all mice were perfused for worm load determination. The following groups were analyzed: saline; empty vector; monovalent formulations of pECL; pSM14 and pIRV5 and also double combinations of pECL/pIRV5 and pIRV5/pSM14 and a triple combination of pECL/pIRV5/pSM14. The protection was expressed as a percentage of worm loads in each group compared with the saline group. The results obtained were 41% (p < 0.05); 52% (p < 0.05); 51% (p < 0.05); 48% (p < 0.05); 55% (p < 0.05); 45% (p < 0.05); 65% (p < 0.05) for each group respectively.

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Las aplicaciones de alineamiento de secuencias son una herramienta importante para la comunidad científica. Estas aplicaciones bioinformáticas son usadas en muchos campos distintos como pueden ser la medicina, la biología, la farmacología, la genética, etc. A día de hoy los algoritmos de alineamiento de secuencias tienen una complejidad elevada y cada día tienen que manejar un volumen de datos más grande. Por esta razón se deben buscar alternativas para que estas aplicaciones sean capaces de manejar el aumento de tamaño que los bancos de secuencias están sufriendo día a día. En este proyecto se estudian y se investigan mejoras en este tipo de aplicaciones como puede ser el uso de sistemas paralelos que pueden mejorar el rendimiento notablemente.

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AbstractPerforming publicly has become increasingly important in a variety of professions. This condition is associated with performance anxiety in almost all performers. Whereas some performers successfully cope with this anxiety, for others it represents a major problem and even threatens their career. Musicians and especially music students were shown to be particularly affected by performance anxiety.Therefore, the goal of this PhD thesis was to gain a better understanding of performance anxiety in university music students. More precisely, the first part of this thesis aimed at increasing knowledge on the occurrence, the experience, and the management of performance anxiety (Article 1). The second part aimed at investigating the hypothesis that there is an underlying hyperventilation problem in musicians with a high level of anxiety before a performance. This hypothesis was addressed in two ways: firstly, by investigating the association between the negative affective dimension of music performance anxiety (MPA) and self-perceived physiological symptoms that are known to co-occur with hyperventilation (Article 2) and secondly, by analyzing this association on the physiological level before a private (audience-free) and a public performance (Article 3). Article 4 places some key variables of Article 3 in a larger context by jointly analyzing the phases before, during, and after performing.The main results of the self-report data show (a) that stage fright is experienced as a problem by one-third of the surveyed students, (b) that the students express a considerable need for more help to better cope with it, and (c) that there is a positive association between negative feelings of MPA and the self-reported hyperventilation complaints before performing. This latter finding was confirmed on the physiological level in a tendency of particularly high performance-anxious musicians to hyperventilate. Furthermore, the psycho-physiological activation increased from a private to a public performance, and was higher during the performances than before or after them. The physiological activation was mainly independent of the MPA score. Finally, there was a low response coherence between the actual physiological activation and the self-reports on the instantaneous anxiety, tension, and perceived physiological activation.Given the high proportion of music students who consider stage fright as a problem and given the need for more help to better cope with it, a better understanding of this phenomenon and its inclusion in the educational process is fundamental to prevent future occupational problems. On the physiological level, breathing exercises might be a good means to decrease - but also to increase - the arousal associated with a public performance in order to meet an optimal level of arousal needed for a good performance.

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Purpose: Extension of retinoblastoma cells anterior to the vitreous surface is a criteria used to categorize retinoblastomas in Group E. In some cases, the assessment of anterior chamber invasion is readily visible by slit lamp examination, but in other cases, invasion of the posterior chamber is clinically difficult to determinate. Ultrasound biomicroscopy (UBM) allows high-resolution images of the anterior segment and structures normally hidden from clinical visualization such as ciliary body, zonule or posterior chamber. This prompted us to evaluate the value of UBM in the assessment of posterior and anterior chamber involvement in patients with peripheral extending retinoblastomas. Methods: We retrospectively reviewed all retinoblastoma cases that underwent enucleation in our institution from 1.1996 till 12.2009 in which UBM ( 35-MHz or 50-MHz) evaluation was available. The UBM results were compared with the histopathological data. Results: From 1.1996 till 12.2009, 146 enucleations were performed in our institution. UBM information was available in 18 cases. There were 8 males and 10 females. The mean age was 4 years old. UBM allowed correct assessement of posterior chamber invasion in 15 cases (13 cases with retinoblastoma in the posterior chamber and 2 cases without retinoblastoma in the posterior chamber). There was a significant correlation between the presence of retinoblastoma cells in the posterior chamber detected by UBM and the histopathological confirmation of posterior chamber involvement (p=0,0008). The sensitivity of UBM in the assessment of posterior chamber invasion by retinoblastoma was 81% and the specificity 100%. UBM allowed correct assessment of anterior chamber invasion in 13 cases. The sensitivity of UBM for this purpose was 50% and the specificity 60 %. Conclusions: In selected cases of advanced retinoblastoma, UBM appears to represent a valuable tool in the evaluation of the precise extension of the disease. Although our series encompasses only a limited number of cases, the sensitivity and specificity of UBM in the assessment of retinoblastoma anterior extension is interesting. Further prospective multi-centered clinical studies would be necessary to better delineate the utility of this method in the precise categorization of retinoblastoma anterior extension

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The nematode parasite Ascaris lumbricoides infects the digestive tracts of over 1.4 billion people worldwide, and its sister species, Ascaris suum, has infected a countless number of domesticated and feral pigs. It is generally thought that the putative ancestor to these worms infected either humans or pigs, but with the advent of domestication, they had ample opportunity to jump to a new host and subsequently specialize and evolve into a new species. While nuclear DNA markers decisively separate the two populations, mitochondrial sequences reveal that three major haplotypes are found in A. suum and in A. lumbricoides, indicating either occasional hybridization, causing introgression of gene trees, or retention of polymorphism dating back to the original ancestral species. This article provides an illustration of the combined contribution of parasitology, archaeoparasitology, genetics and paleogenetics to the history of ascariasis. We specifically investigate the molecular history of ascariasis in humans by sequencing DNA from the eggs of Ascaris found among ancient archeological remains. The findings of this paleogenetic survey will explain whether the three mitochondrial haplotypes result from recent hybridization and introgression, due to intensive human-pig interaction, or whether their co-occurrence predates pig husbandry, perhaps dating back to the common ancestor. We hope to show how human-pig interaction has shaped the recent evolutionary history of this disease, perhaps revealing the identity of the ancestral host.

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The authors present 10 grids which are widely used in Health Sciences for the assessment of quality in research. They proceed through a comparative thematic analysis of these grids and show which points of view are preferred. They insist on the issues that differentiate these grids from each other and suggest the analysis of their differences by distinguishing the theoretical perspectives that underpin each one of these grids. Whilst the authors of the assessment grids rarely refer to the implicit theoretical backgrounds that guide their work, findings show that these grids convey varied epistemologies and research models. This gap renders the comparison of quality assessment in qualitative research a very difficult task, unless we shift our focus on the relationship between the grids, their theoretical backgrounds and their specific research subjects.

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Multi-resistant gram-negative rods are important pathogens in intensive care units (ICU), cause high rates of mortality, and need infection control measures to avoid spread to another patients. This study was undertaken prospectively with all of the patients hospitalized at ICU, Anesthesiology of the Hospital São Paulo, using the ICU component of the National Nosocomial Infection Surveillance System (NNIS) methodology, between March 1, 1997 and June 30, 1998. Hospital infections occurring during the first three months after the establishment of prevention and control measures (3/1/97 to 5/31/97) were compared to those of the last three months (3/1/98 to 5/31/98). In this period, 933 NNIS patients were studied, with 139 during the first period and 211 in the second period. The overall rates of infection by multi-resistant microorganisms in the first and second periods were, respectively, urinary tract infection: 3.28/1000 patients/day; 2.5/1000 patients/day; pneumonia: 2.10/1000 patients/day; 5.0/1000 patients/day; bloodstream infection: 1.09/1000 patients/day; 2.5/1000 patients/day. A comparison between overall infection rates of both periods (Wilcoxon test) showed no statistical significance (p = 0.067). The use of intervention measures effectively decreased the hospital bloodstream infection rate (p < 0.001), which shows that control measures in ICU can contribute to preventing hospital infections.

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OBJECTIVES: Skin notations are used as a hazard identification tool to flag chemicals associated with a potential risk related to transdermal penetration. The transparency and rigorousness of the skin notation assignment process have recently been questioned. We compared different approaches proposed as criteria for these notations as a starting point for improving and systematizing current practice. METHODS: In this study, skin notations, dermal acute lethal dose 50 in mammals (LD(50)s) and two dermal risk indices derived from previously published work were compared using the lists of Swiss maximum allowable concentrations (MACs) and threshold limit values (TLVs) from the American Conference of Governmental Industrial Hygienists (ACGIH). The indices were both based on quantitative structure-activity relationship (QSAR) estimation of transdermal fluxes. One index compared the cumulative dose received through skin given specific exposure surface and duration to that received through lungs following inhalation 8 h at the MAC or TLV. The other index estimated the blood level increase caused by adding skin exposure to the inhalation route at kinetic steady state. Dermal-to-other route ratios of LD(50) were calculated as secondary indices of dermal penetrability. RESULTS: The working data set included 364 substances. Depending on the subdataset, agreement between the Swiss and ACGIH skin notations varied between 82 and 87%. Chemicals with a skin notation were more likely to have higher dermal risk indices and lower dermal LD(50) than chemicals without a notation (probabilities between 60 and 70%). The risk indices, based on cumulative dose and kinetic steady state, respectively, appeared proportional up to a constant independent of chemical-specific properties. They agreed well with dermal LD(50)s (Spearman correlation coefficients -0.42 to -0.43). Dermal-to-other routes LD(50) ratios were moderately associated with QSAR-based transdermal fluxes (Spearman correlation coefficients -0.2 to -0.3). CONCLUSIONS: The plausible but variable relationship between current skin notations and the different approaches tested confirm the need to improve current skin notations. QSAR-based risk indices and dermal toxicity data might be successfully integrated in a systematic alternative to current skin notations for detecting chemicals associated with potential dermal risk in the workplace. [Authors]

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This service Aims: To provide a multi-component weight management service that supports sustainable behaviour change and weight loss in adults 16 years and over with a BMI 28. To enable patients to develop the necessary personal attributes for their own long term weight management and to understand the impact of their weight on their health and co-morbidities. Objectives: To provide an evidence based, multi-component tier 2 weight management service that improves patients knowledge and skills for effective and sustainable weight loss helps patients identify their own facilitators for positive behaviour change and to address underlying barriers to long-term behaviour changeincreases patients self-efficacy and confidence in their ability to address their weight To be an integral part of the tiered approach to weight management services for the population of Stockton. To ensure equitable service provision across Stockton-on-Tees. To provide intensive group based service, one-to-one support and maintenance support. To support the service user to develop and review a personalised goal setting plan phase 2 and at discharge after phase 2. To ensure a smooth transition from the service (tier2) to tier 1 services to ensure continuity of care for service users.Recruit referrals using a variety of and appropriate methods. To establish a single point of contact for referrals into the service.Continually promote the service across a range of mediums and liaise and work in partnership with key interdependencies (refer to 2.4) To establish a robust database and data collection system in line with information governance. To ensure the access criteria, care pathway and referral process is clearly understood by all health care professionals and those who may refer into the service. To establish close links with, and signpost and/or enable service users to access suitable services where patient needs indicate this. This may include access to Tees Time to Talk (IAPT) for psychological therapies; Specialist Weight Management Service; physical activity programmes; Tier 1 services; and primary care. To provide the necessary venues, equipment and assets needed to deliver the programme, ensuring due regard is given to the quality and safety of all materials used. To collect and provide data in quarterly reports to the Commissioner to allow for continued monitoring and evaluation of the service in line with the Standard Evaluation Framework (available at www.noo.org.uk/core/SEF) and as specified by the Commissioner.

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The Genetic Investigation of Anthropometric Traits (GIANT) consortium identified 14 loci in European Ancestry (EA) individuals associated with waist-to-hip ratio (WHR) adjusted for body mass index. These loci are wide and narrowing the signals remains necessary. Twelve of 14 loci identified in GIANT EA samples retained strong associations with WHR in our joint EA/individuals of African Ancestry (AA) analysis (log-Bayes factor >6.1). Trans-ethnic analyses at five loci (TBX15-WARS2, LYPLAL1, ADAMTS9, LY86 and ITPR2-SSPN) substantially narrowed the signals to smaller sets of variants, some of which are in regions that have evidence of regulatory activity. By leveraging varying linkage disequilibrium structures across different populations, single-nucleotide polymorphisms (SNPs) with strong signals and narrower credible sets from trans-ethnic meta-analysis of central obesity provide more precise localizations of potential functional variants and suggest a possible regulatory role. Meta-analysis results for WHR were obtained from 77 167 EA participants from GIANT and 23 564 AA participants from the African Ancestry Anthropometry Genetics Consortium. For fine mapping we interrogated SNPs within ± 250 kb flanking regions of 14 previously reported index SNPs from loci discovered in EA populations by performing trans-ethnic meta-analysis of results from the EA and AA meta-analyses. We applied a Bayesian approach that leverages allelic heterogeneity across populations to combine meta-analysis results and aids in fine-mapping shared variants at these locations. We annotated variants using information from the ENCODE Consortium and Roadmap Epigenomics Project to prioritize variants for possible functionality.

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Linking the structural connectivity of brain circuits to their cooperative dynamics and emergent functions is a central aim of neuroscience research. Graph theory has recently been applied to study the structure-function relationship of networks, where dynamical similarity of different nodes has been turned into a "static" functional connection. However, the capability of the brain to adapt, learn and process external stimuli requires a constant dynamical functional rewiring between circuitries and cell assemblies. Hence, we must capture the changes of network functional connectivity over time. Multi-electrode array data present a unique challenge within this framework. We study the dynamics of gamma oscillations in acute slices of the somatosensory cortex from juvenile mice recorded by planar multi-electrode arrays. Bursts of gamma oscillatory activity lasting a few hundred milliseconds could be initiated only by brief trains of electrical stimulations applied at the deepest cortical layers and simultaneously delivered at multiple locations. Local field potentials were used to study the spatio-temporal properties and the instantaneous synchronization profile of the gamma oscillatory activity, combined with current source density (CSD) analysis. Pair-wise differences in the oscillation phase were used to determine the presence of instantaneous synchronization between the different sites of the circuitry during the oscillatory period. Despite variation in the duration of the oscillatory response over successive trials, they showed a constant average power, suggesting that the rate of expenditure of energy during the gamma bursts is consistent across repeated stimulations. Within each gamma burst, the functional connectivity map reflected the columnar organization of the neocortex. Over successive trials, an apparently random rearrangement of the functional connectivity was observed, with a more stable columnar than horizontal organization. This work reveals new features of evoked gamma oscillations in developing cortex.