49 resultados para Generational cohorts


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Predicting metal bioaccumulation and toxicity in soil organisms is complicated by site-specific biotic and abiotic parameters. In this study we exploited tissue fractionation and digestion techniques, combined with X-ray absorption spectroscopy (XAS), to investigate the whole-body and subcellular distributions, ligand affinities, and coordination chemistry of accumulated Pb and Zn in field populations of the epigeic earthworm Lumbricus rubellus inhabiting three contrasting metalliferous and two unpolluted soils. Our main findings were (i) earthworms were resident in soils with concentrations of Pb and Zn ranging from 1200 to 27 000 mg kg(-1) and 200 to 34 000 mg kg(-1), respectively; (ii) Pb and Zn primarily accumulated in the posterior alimentary canal in nonsoluble subcellular fractions of earthworms; (iii) site-specific differences in the tissue and subcellular partitioning profiles of populations were observed, with earthworms from a calcareous site partitioning proportionally more Pb to their anterior body segments and Zn to the chloragosome-rich subcellular fraction than their acidic-soil inhabiting counterparts; (iv) XAS indicated that the interpopulation differences in metal partitioning between organs were not accompanied by qualitative differences in ligand-binding speciation, because crystalline phosphate-containing pyromorphite was a predominant chemical species in the whole-worm tissues of all mine soil residents. Differences in metal (Pb, Zn) partitioning at both organ and cellular levels displayed by field populations with protracted histories of metal exposures may reflect their innate ecophysiological responses to essential edaphic variables, such as Ca2+ status. These observations are highly significant in the challenging exercise of interpreting holistic biomarker data delivered by "omic" technologies.

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Substantial resources are used for surveillance of bovine spongiform encephalopathy (BSE) despite an extremely low detection rate, especially in healthy slaughtered cattle. We have developed a method based on the geometric waiting time distribution to establish and update the statistical evidence for BSE-freedom for defined birth cohorts using continued surveillance data. The results suggest that currently (data included till September 2004) a birth cohort of Danish cattle born after March 1999 is free from BSE with probability (power) of 0.8746 or 0.8509, depending on the choice of a model for the diagnostic sensitivity. These results apply to an assumed design prevalence of 1 in 10,000 and account for prevalence heterogeneity. The age-dependent, diagnostic sensitivity for the detection of BSE has been identified as major determinant of the power. The incorporation of heterogeneity was deemed adequate on scientific grounds and led to improved power values. We propose our model as a decision tool for possible future modification of the BSE surveillance and discuss public health and international trade implications.

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BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

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BACKGROUND: Although the peroxisome proliferator-activated receptor γ (PPARγ) pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether dietary fat has a modifying effect on the association. OBJECTIVES: We examined whether 27 single nucleotide polymorphisms (SNPs) within 4 genes in the PPARγ pathway are associated with the OR of being a BW gainer or with annual changes in anthropometry and whether intake of total fat, monounsaturated fat, polyunsaturated fat, or saturated fat has a modifying effect on these associations. METHODS: A case-noncase study included 11,048 men and women from cohorts in the European Diet, Obesity and Genes study; 5552 were cases, defined as individuals with the greatest BW gain during follow-up, and 6548 were randomly selected, including 5496 noncases. We selected 4 genes [CCAAT/enhancer binding protein β (CEBPB), phosphoenolpyruvate carboxykinase 2, PPARγ gene (PPARG), and sterol regulatory element binding transcription factor 1] according to evidence about biologic plausibility for interactions with dietary fat in weight regulation. Diet was assessed at baseline, and anthropometry was followed for 7 y. RESULTS: The ORs for being a BW gainer for the 27 genetic variants ranged from 0.87 (95% CI: 0.79, 1.03) to 1.12 (95% CI: 0.96, 1.22) per additional minor allele. Uncorrected, CEBPB rs4253449 had a significant interaction with the intake of total fat and subgroups of fat. The OR for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher total fat intake was 1.07 (95% CI: 1.02, 1.12; P = 0.008), and similar associations were found for subgroups of fat. CONCLUSIONS: Among European men and women, the influence of dietary fat on associations between SNPs in the PPARγ pathway and anthropometry is likely to be absent or marginal. The observed interaction between rs4253449 and dietary fat needs confirmation.

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In this article we present a critique of a series of public policy documents that aim at improvement in health for the general population, particularly families, but fail to recognize or appreciate the implications of gender for the everyday and the long-term experiences of family members. Drawing upon considerations of gender, families, health time and space and previous theoretical work (McKie et al, 2002), we propose the concept of healthscapes to aid the analysis and development of public policies. A healthscapes approach allows analysis of health policy within the diverse and multi-dimensional notions of time, space and gender that infuse the lifecourse. We assert that consideration of the gendered and generational project of caring particularly in relation to the (re)production of health, should involve a reflective inter-play between theory research and policy.

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This paper explores the ways that young people express their agency and negotiate complex lifecourse transitions according to gender, age and inter- and intra-generational norms in sibling-headed households affected by AIDS in East Africa. Based on findings from a qualitative and participatory pilot study in Tanzania and Uganda, I examine young people's socio-spatial and temporal experiences of heading the household and caring for their siblings following their parent's/relative's death. Key dimensions of young people's caring pathways and life transitions are discussed: transitions into sibling care; the ways young people manage changing roles within the family; and the ways that young people are positioned and seek to position themselves within the community. The research reveals the relational and embodied nature of young people's life transitions over time and space. By living together independently, young people constantly reproduce and reconfigure gendered, inter- and intra-generational norms of ‘the family’, transgressing the boundaries of ‘childhood’, ‘youth’ and ‘adulthood’. Although young people take on ‘adult’ responsibilities and demonstrate their competencies in ‘managing their own lives’, this does not necessarily translate into more equal power relations with adults in the community. The research reveals the marginal ‘in-between’ place that young people occupy between local and global discourses of ‘childhood’ and ‘youth’ that construct them as ‘deviant’. Although young people adopt a range of strategies to resist marginalisation and harassment, I argue that constraints of poverty, unequal gender and generational power relations and the emotional impacts of sibling care, stigmatisation and exclusion can undermine their ability to exert agency and control over their sexual relationships, schooling, livelihood strategies and future lifecourse transitions.

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Recent research in Sub-Saharan Africa has revealed the importance of children’s caring roles in families affected by HIV and AIDS. However, few studies have explored young caregiving in the context of HIV in the UK, where recently arrived African migrant and refugee families are adversely affected by the global epidemic. This paper explores young people’s socio-spatial experiences of caring for a parent with HIV, based on qualitative research with 37 respondents in London and other urban areas in England. In-depth semi-structured interviews were conducted with young people with caring responsibilities and mothers with HIV, who were predominantly African migrants, as well as with service providers. Drawing on their perspectives, the paper discusses the ways that young people and mothers negotiate the boundaries of young people’s care work within and beyond homespace, according to norms of age, gender, generational relations and cultural constructions of childhood. Despite close attachments within the family, the emotional effects of living with a highly stigmatised life-limiting illness, pressures associated with insecure immigration status, transnational migration and low income undermined African mothers’ and young people’s sense of security and belonging to homespace. These factors also restricted their mobility and social participation in school/college and neighbourhood spaces. While young people and mothers valued supportive safe spaces within the community, the stigma surrounding HIV significantly affected their ability to seek support. The article identifies security, privacy, independence and social mobility as key dimensions of African young people’s and mothers’ imagined futures of ‘home’ and ‘family’.

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Background and Aims: Using two parental clones of outcrossing Trifolium ambiguum as a potential model system, we examined how during seed development the maternal parent, number of seeds per pod, seed position within the pod, and pod position within the inflorescence influenced individual seed fresh weight, dry weight, water content, germinability, desiccation tolerance, hardseededness, and subsequent longevity of individual seeds. Methods: Near simultaneous, manual reciprocal crosses were carried out between clonal lines for two experiments. Infructescences were harvested at intervals during seed development. Each individual seed was weighed and then used to determine dry weight or one of the physiological behaviour traits. Key Results: Whilst population mass maturity was reached at 33–36 days after pollination (DAP), seed-to-seed variation in maximum seed dry weight, when it was achieved, and when maturation drying commenced, was considerable. Individual seeds acquired germinability between 14 and 44 DAP, desiccation tolerance between 30 and 40 DAP, and the capability to become hardseeded between 30 and 47 DAP. The time for viability to fall to 50 % (p50) at 60 % relative humidity and 45 °C increased between 36 and 56 DAP, when the seed coats of most individuals had become dark orange, but declined thereafter. Individual seed f. wt at harvest did not correlate with air-dry storage survival period. Analysing survival data for cohorts of seeds reduced the standard deviation of the normal distribution of seed deaths in time, but no sub-population showed complete uniformity of survival period. Conclusions: Variation in individual seed behaviours within a developing population is inherent and inevitable. In this outbreeder, there is significant variation in seed longevity which appears dependent on embryo genotype with little effect of maternal genotype or architectural factors.

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Oral nutrition supplements (ONS) are routinely prescribed to those with, or at risk of, malnutrition. Previous research identified poor compliance due to taste and sweetness. This paper investigates taste and hedonic liking of ONS, of varying sweetness and metallic levels, over consumption volume; an important consideration as patients are prescribed large volumes of ONS daily. A sequential descriptive profile was developed to determine the perception of sensory attributes over repeat consumption of ONS. Changes in liking of ONS following repeat consumption were characterised by a boredom test. Certain flavour (metallic taste, soya milk flavour) and mouthfeel (mouthdrying, mouthcoating) attributes built up over increased consumption volume (p 0.002). Hedonic liking data from two cohorts, healthy older volunteers (n = 32, median age 73) and patients (n = 28, median age 85), suggested such build-up was disliked. Efforts made to improve the palatability of ONS must take account of the build up of taste and mouthfeel characteristics over increased consumption volume.

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Re-introduction is a technique widely used in the conservation of threatened bird species. With advances in aviculture the use of captive-produced individuals as the release stock is becoming more commonplace, and ideally, survival of captive-produced, released individuals should be no different from their wild-bred counterparts. During the late 1980s the Critically Endangered Mauritius kestrel (Falco punctatus) was successfully re-introduced into the Bambous mountain range, Mauritius, some 30 years after its local extinction. Between 1987 and 2001 the developing population was closely monitored enabling us to construct re-sighting histories for 88 released and 284 wild-bred kestrels. We used age-structured models in the survival analysis software program MARK to determine if an individual's origin influenced its subsequent survival. Our analysis indicated no compelling evidence for reduced survival among juvenile captive-reared and released individuals, relative to their wild-bred counterparts, across the majority of cohorts and only limited evidence of a cohort-specific effect. This study illustrates that despite the lack of a formal experimental approach it is still feasible to conduct an assessment of re-introduction outcomes and techniques.

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There is a strong desire to exploit transcriptomics data from model species for the genetic improvement of non-model crops. Here, we use gene expression profiles from the commercial model Pinus taeda to identify candidate genes implicated in juvenile-mature wood transition in the non-model relative, P. sylvestris. Re-analysis of 'public domain' SAGE data from xylem tissues of P. taeda revealed 283 mature-abundant and 396 juvenile-abundant tags (P < 0.01), of which 70 and 137, respectively matched to genes with known function. Based on sequence similarity, we then isolated 16 putative homologues of genes that in P. taeda exhibited widest divergence in expression between juvenile and mature samples. Candidate expression levels in P. sylvestris were almost invariably differential between juvenile and mature woody tissue samples among two cohorts of five trees collected from the same seed source and selected for genetic uniformity by genetic distance analysis. However, the direction of differential expression was not always consistent with that described in the original P. taeda SAGE data. Correlation was observed between gene expression and juvenile-mature wood anatomical characteristics by OPLS analysis. Four candidates (alpha-tubulin, porin MIP1, lipid transfer protein and aquaporin like protein) apparently had greatest influence on the wood traits measured. Speculative function of these genes in relation to juvenile-mature wood transition is briefly explored. Thus, we demonstrate the feasibility of exploiting SAGE data from a model species to identify consistently differentially expressed candidates in a related non-model species.

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The period following the withdrawal of parental care has been highlighted as a key developmental period for juveniles. One reason for this is that juveniles cannot forage as competently as adults, potentially placing them at greater risk from environmentally-induced changes in food availability. However, no study has examined this topic. Using a long-term dataset on red foxes (Vulpes vulpes), we examined (i) dietary changes that occurred in the one-month period following the attainment of nutritional independence, (ii) diet composition in relation to climatic variation, and (iii) the effect of climatic variation on subsequent full-grown mass. Diet at nutritional independence contained increased quantities of easy-to-catch food items (earthworms and insects) when compared with pre-independence. Interannual variation in the volume of rainfall at nutritional independence was positively correlated to the proportion of earthworms in cub diet. Pre-independence cub mass and rainfall immediately following nutritional independence explained a significant proportion of variance in full-grown mass, with environmental variation affecting full-grown mass of the entire cohorts. Thus, weather-mediated availability of easy-to-catch food items at a key developmental stage has lifelong implications for the development of juvenile foxes by affecting full-grown mass, which in turn appears to be an important component of individual reproductive potential.

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This investigation deals with the question of when a particular population can be considered to be disease-free. The motivation is the case of BSE where specific birth cohorts may present distinct disease-free subpopulations. The specific objective is to develop a statistical approach suitable for documenting freedom of disease, in particular, freedom from BSE in birth cohorts. The approach is based upon a geometric waiting time distribution for the occurrence of positive surveillance results and formalizes the relationship between design prevalence, cumulative sample size and statistical power. The simple geometric waiting time model is further modified to account for the diagnostic sensitivity and specificity associated with the detection of disease. This is exemplified for BSE using two different models for the diagnostic sensitivity. The model is furthermore modified in such a way that a set of different values for the design prevalence in the surveillance streams can be accommodated (prevalence heterogeneity) and a general expression for the power function is developed. For illustration, numerical results for BSE suggest that currently (data status September 2004) a birth cohort of Danish cattle born after March 1999 is free from BSE with probability (power) of 0.8746 or 0.8509, depending on the choice of a model for the diagnostic sensitivity.

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Re-introduction is a technique widely used in the conservation of threatened bird species. With advances in aviculture the use of captive-produced individuals as the release stock is becoming more commonplace, and ideally, survival of captive-produced, released individuals should be no different from their wild-bred counterparts. During the late 1980s the Critically Endangered Mauritius kestrel (Falco punctatus) was successfully re-introduced into the Bambous mountain range, Mauritius, some 30 years after its local extinction. Between 1987 and 2001 the developing population was closely monitored enabling us to construct re-sighting histories for 88 released and 284 wild-bred kestrels. We used age-structured models in the survival analysis software program MARK to determine if an individual's origin influenced its subsequent survival. Our analysis indicated no compelling evidence for reduced survival among juvenile captive-reared and released individuals, relative to their wild-bred counterparts, across the majority of cohorts and only limited evidence of a cohort-specific effect. This study illustrates that despite the lack of a formal experimental approach it is still feasible to conduct an assessment of re-introduction outcomes and techniques. (C) 2003 Elsevier Ltd. All rights reserved.

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Nutrition science finds itself at a major crossroad. On the one hand we can continue the current path, which has resulted in some substantial advances, but also many conflicting messages which impair the trust of the general population, especially those who are motivated to improve their health through diet. The other road is uncharted and is being built over the many exciting new developments in life sciences. This new era of nutrition recognizes the complex relation between the health of the individual, its genome, and the life-long dietary exposure, and has lead to the realisation that nutrition is essentially a gene - environment interaction science. This review on the relation between genotype, diet and health is the first of a series dealing with the major challenges in molecular nutrition, analyzing the foundations of nutrition research. With the unravelling of the human genome and the linking of its variability to a multitude of phenotypes from " healthy'' to an enormously complex range of predispositions, the dietary modulation of these propensities has become an area of active research. Classical genetic approaches applied so far in medical genetics have steered away from incorporating dietary effects in their models and paradoxically, most genetic studies analyzing diet-associated phenotypes and diseases simply ignore diet. Yet, a modest but increasing number of studies are accounting for diet as a modulator of genetic associations. These range from observational cohorts to intervention studies with prospectively selected genotypes. New statistical and bioinformatics approaches are becoming available to aid in design and evaluation of these studies. This review discusses the various approaches used and provides concrete recommendations for future research.