1,930 research outputs found

    Shear-flexible finite-element models of laminated composite plates and shells

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    Several finite-element models are applied to the linear static, stability, and vibration analysis of laminated composite plates and shells. The study is based on linear shallow-shell theory, with the effects of shear deformation, anisotropic material behavior, and bending-extensional coupling included. Both stiffness (displacement) and mixed finite-element models are considered. Discussion is focused on the effects of shear deformation and anisotropic material behavior on the accuracy and convergence of different finite-element models. Numerical studies are presented which show the effects of increasing the order of the approximating polynomials, adding internal degrees of freedom, and using derivatives of generalized displacements as nodal parameters

    The stability of food intake between adolescence and adulthood: a 21-year follow-up

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    Studies of the diet of adolescents in the UK demonstrate that dietary habits known to be detrimental to health in adulthood are evident at an early age. For example, Gregory et al (2000) found 4-18 year olds in the UK to have a frequent consumption of fatty and sugary foods and low consumption of fruit and vegetables. Concerns have therefore been expressed regarding the diet of children and adolescents and the continuation of these dietary habits into adulthood (HEA, 1995; Gaziano, 1998). This study aimed to investigate the extent to which these concerns may be justified by determining the stability of food intake of a group of adolescents followed up 21 years later in adulthood. The investigation involved 202 individuals from whom dietary data were collected in 1979-80 (mean age 11.6 years) (Hackett et al. 1984) and again in 2000-1 (mean age 32.5 years). Dietary data were collected at both time-points using two 3 d estimated food diaries followed by an interview to determine portion sizes using the method considered most appropriate at the time, i.e. calibrated food models in 1979-80 and a photographic food atlas (Nelson et al. 1997) in 2000-1. Foods consumed were allocated to one, or a combination of, the five food groups of the ‘Balance of Good Health’ food selection guide (HEA, 1994) according to Gatenby et al. (1995). The weight of food eaten from each of the five food groups was calculated (percentage of total weight of food consumed) and Pearson correlation coefficients generated to provide an estimate of the stability of food intake. The HEA guide advises that a balanced diet should consist of around 33% fruit and vegetables, 33% bread, other cereals and potatoes, 8% foods containing fat and/or sugar, 12% meat, fish and alternatives and 15% milk and dairy products (Gatenby et al. 1995). A shift in the group’s food intake towards the recommendations had occurred with age, most notably with a decrease in foods containing fat and/or sugar and an increase in fruit and vegetables. Nevertheless, at both ages, intakes of foods containing fat and/or sugar, meat, fish and alternatives were higher, and fruit, vegetables, bread, other cereals and potatoes lower than currently recommended. In addition, although there was significant evidence of tracking of relative intake of bread, cereals and potatoes (P<0.01), fruit and vegetables (P<0.01), and meat, fish and alternatives (P=0.02) between 11.6 and 32.5 years, the correlations were not strong. In conclusion, food intake patterns had changed considerably from early adolescence through to adulthood in a direction more in line with the current recommendations. The predictive value of an adolescent’s food intake of their intake in adulthood was found to be significant, but not strong. Further investigations will consider the extent to which this is influenced by factors such as social class, gender and educational level, as well as assessing tracking in terms of relative nutrient intakes

    Factors that impact on the quality of life of intestinal failure patients treated with home parenteral nutrition: protocol for a multicentre, longitudinal observational study

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    \ua9 2024 BMJ Publishing Group. All rights reserved. Background: Home parenteral nutrition (HPN) refers to the intravenous administration of macronutrients, micronutrients and fluid. The aims of treatment are to increase survival and improve quality of life (QoL). However, patients struggle with physiological symptoms, time-consuming invasive therapy and an increased occurrence of depression and social isolation. Our aim is to understand how HPN impacts the QoL of patients, and the contribution played by the complications of treatment, for example, liver disease. Methods and analysis: A multicentre, longitudinal, observational study will be conducted using routinely collected clinical data. Participants will also be asked to complete three QoL questionnaires (EuroQol-5 Dimensions, Short Form 36 and HPN-QoL) at baseline and 12 months. The primary outcome is mean change in QoL scores over 12 months. Secondary outcomes include how factors including liver function, gut microbiota, number of infusions of PN per week, nutritional composition of PN and nutritional status impact on QoL scores. Ethics and dissemination: Ethical approval was obtained from HRA and Health and Care Research Wales Research Ethics Committee (21/SC/0316). The study was eligible for portfolio adoption, Central Portfolio Management System ID 50506. Results will be disseminated through peer-reviewed scientific journals and presented at national and international meetings

    Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study

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    Objective Neuroinflammation is an important pathogenic mechanism in amyotrophic lateral sclerosis (ALS), with regulatory T cells (Tregs) mediating a slower rate of disease progression. Dimethyl fumarate enhances Treg levels and suppresses pro-inflammatory T cells. The present study assessed the safety and efficacy of dimethyl fumarate in ALS. Methods Phase-2, double-blind, placebo-controlled randomised clinical trial recruited participants from May 1, 2018 to September 25, 2019, across six Australian sites. Participants were randomised (2:1 ratio) to dimethyl fumarate (480 mg/day) or matching placebo, completing visits at screening, baseline, weeks 12, 24 and 36. The primary efficacy endpoint was a change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) at week 36. Secondary outcome measures included survival, neurophysiological index (NI), respiratory function, urinary neurotrophin-receptor p75 and quality of life. Results A total of 107 participants were randomised to dimethyl fumarate (n = 72) or placebo (n = 35). ALSFRS-R score was not significantly different at week 36 (−1.12 [−3.75 to 1.52, p = 0.41]). Dimethyl fumarate was associated with a reduced NI decline week 36 (differences in the least-squares mean: (0.84 [−0.51 to 2.22, p = 0.22]). There were no significant differences in other secondary outcome measures. Safety profiles were comparable between groups. Interpretation Dimethyl fumarate, in combination with riluzole, was safe and well-tolerated in ALS. There was no significant improvement in the primary endpoint. The trial provides class I evidence for safety and lack of efficacy of dimethyl fumarate in ALS

    Estimating the impact of unsafe water, sanitation and hygiene on the global burden of disease: evolving and alternative methods.

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    The 2010 global burden of disease (GBD) study represents the latest effort to estimate the global burden of disease and injuries and the associated risk factors. Like previous GBD studies, this latest iteration reflects a continuing evolution in methods, scope and evidence base. Since the first GBD Study in 1990, the burden of diarrhoeal disease and the burden attributable to inadequate water and sanitation have fallen dramatically. While this is consistent with trends in communicable disease and child mortality, the change in attributable risk is also due to new interpretations of the epidemiological evidence from studies of interventions to improve water quality. To provide context for a series of companion papers proposing alternative assumptions and methods concerning the disease burden and risks from inadequate water, sanitation and hygiene, we summarise evolving methods over previous GBD studies. We also describe an alternative approach using population intervention modelling. We conclude by emphasising the important role of GBD studies and the need to ensure that policy on interventions such as water and sanitation be grounded on methods that are transparent, peer-reviewed and widely accepted

    Adjusting for dependent comorbidity in the calculation of healthy life expectancy

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    BACKGROUND: Healthy life expectancy – sometimes called health-adjusted life expectancy (HALE) – is a form of health expectancy indicator that extends measures of life expectancy to account for the distribution of health states in the population. The World Health Organization has estimated healthy life expectancy for 192 WHO Member States using information from health interview surveys and from the Global Burden of Disease Study. The latter estimates loss of health by cause, age and sex for populations. Summation of prevalent years lived with disability (PYLD) across all causes would result in overestimation of the severity of the population average health state because of comorbidity between conditions. Earlier HALE calculations made adjustments for independent comorbidity in adding PYLD across causes. This paper presents a method for adjusting for dependent comorbidity using available empirical data. METHODS: Data from five large national health surveys were analysed by age and sex to estimate "dependent comorbidity" factors for pairs of conditions. These factors were defined as the ratio of the prevalence of people with both conditions to the product of the two total prevalences for each of the conditions. The resulting dependent comorbidity factors were used for all Member States to adjust for dependent comorbidity in summation of PYLD across all causes and in the calculation of HALE. A sensitivity analysis was also carried out for order effects in the proposed calculation method. RESULTS: There was surprising consistency in the dependent comorbidity factors across the five surveys. The improved estimation of dependent comorbidity resulted in reductions in total PYLD per capita ranging from a few per cent in younger adult ages to around 8% in the oldest age group (80 years and over) in developed countries and up to 15% in the oldest age group in the least developed countries. The effect of the dependent comorbidity adjustment on estimated healthy life expectancies is small for some regions (high income countries, Eastern Europe, Western Pacific) and ranges from an increase of 0.5 to 1.5 years for countries in Latin America, South East Asia and Sub-Saharan Africa. CONCLUSION: The available evidence suggests that dependent comorbidity is important, and that adjustment for it makes a significant difference to resulting HALE estimates for some regions of the world. Given the data limitations, we recommend a normative adjustment based on the available evidence, and applied consistently across all countries

    Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa

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    Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammatio

    Deriving utility scores for co-morbid conditions: a test of the multiplicative model for combining individual condition scores

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    BACKGROUND: The co-morbidity of health conditions is becoming a significant health issue, particularly as populations age, and presents important methodological challenges for population health research. For example, the calculation of summary measures of population health (SMPH) can be compromised if co-morbidity is not taken into account. One popular co-morbidity adjustment used in SMPH computations relies on a straightforward multiplicative combination of the severity weights for the individual conditions involved. While the convenience and simplicity of the multiplicative model are attractive, its appropriateness has yet to be formally tested. The primary objective of the current study was therefore to examine the empirical evidence in support of this approach. METHODS: The present study drew on information on the prevalence of chronic conditions and a utility-based measure of health-related quality of life (HRQoL), namely the Health Utilities Index Mark 3 (HUI3), available from Cycle 1.1 of the Canadian Community Health Survey (CCHS; 2000–01). Average HUI3 scores were computed for both single and co-morbid conditions, and were also purified by statistically removing the loss of functional health due to health problems other than the chronic conditions reported. The co-morbidity rule was specified as a multiplicative combination of the purified average observed HUI3 utility scores for the individual conditions involved, with the addition of a synergy coefficient s for capturing any interaction between the conditions not explained by the product of their utilities. The fit of the model to the purified average observed utilities for the co-morbid conditions was optimized using ordinary least squares regression to estimate s. Replicability of the results was assessed by applying the method to triple co-morbidities from the CCHS cycle 1.1 database, as well as to double and triple co-morbidities from cycle 2.1 of the CCHS (2003–04). RESULTS: Model fit was optimized at s = .99 (i.e., essentially a straightforward multiplicative model). These results were closely replicated with triple co-morbidities reported on CCHS 2000–01, as well as with double and triple co-morbidities reported on CCHS 2003–04. CONCLUSION: The findings support the simple multiplicative model for computing utilities for co-morbid conditions from the utilities for the individual conditions involved. Future work using a wider variety of conditions and data sources could serve to further evaluate and refine the approach

    Bioinformatic interrogation of expression array data to identify nutritionally regulated genes potentially modulated by DNA methylation

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    DNA methylation occurs at CpG dinucleotide sites within the genome and is recognised as one of the mechanisms involved in regulation of gene expression. CpG sites are relatively underrepresented in the mammalian genome, but occur densely in regions called CpG islands (CGIs). CGIs located in the promoters of genes inhibit transcription when methylated by impeding transcription factor binding. Due to the malleable nature of DNA methylation, environmental factors are able to influence promoter CGI methylation patterns and thus influence gene expression. Recent studies have provided evidence that nutrition (and other environmental exposures) can cause altered CGI methylation but, with a few exceptions, the genes influenced by these exposures remain largely unknown. Here we describe a novel bioinformatics approach for the analysis of gene expression microarray data designed to identify regulatory sites within promoters of differentially expressed genes that may be influenced by changes in DNA methylation

    Global patterns of healthy life expectancy in the year 2002

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    BACKGROUND: Healthy life expectancy – sometimes called health-adjusted life expectancy (HALE) – is a form of health expectancy indicator that extends measures of life expectancy to account for the distribution of health states in the population. The World Health Organization reports on healthy life expectancy for 192 WHO Member States. This paper describes variation in average levels of population health across these countries and by sex for the year 2002. METHODS: Mortality was analysed for 192 countries and disability from 135 causes assessed for 17 regions of the world. Health surveys in 61 countries were analyzed using new methods to improve the comparability of self-report data. RESULTS: Healthy life expectancy at birth ranged from 40 years for males in Africa to over 70 years for females in developed countries in 2002. The equivalent "lost" healthy years ranged from 15% of total life expectancy at birth in Africa to 8–9% in developed countries. CONCLUSION: People living in poor countries not only face lower life expectancies than those in richer countries but also live a higher proportion of their lives in poor health
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