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1.
Nat Commun ; 10(1): 4957, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673082

RESUMO

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

2.
BMC Cardiovasc Disord ; 19(1): 240, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664920

RESUMO

BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

3.
BMC Public Health ; 19(1): 939, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300003

RESUMO

BACKGROUND: Born in Bradford (BiB) is a prospective multi-ethnic pregnancy and birth cohort study that was established to examine determinants of health and development during childhood and, subsequently, adult life in a deprived multi-ethnic population in the north of England. Between 2007 and 2010, the BiB cohort recruited 12,453 women who experienced 13,776 pregnancies and 13,858 births, along with 3353 of their partners. Forty five percent of the cohort are of Pakistani origin. Now that children are at primary school, the first full follow-up of the cohort is taking place. The aims of the follow-up are to investigate the determinants of children's pre-pubertal health and development, including through understanding parents' health and wellbeing, and to obtain data on exposures in childhood that might influence future health. METHODS: We are employing a multi-method approach across three data collection arms (community-based family visits, school based physical assessment, and whole classroom cognitive, motor function and wellbeing measures) to follow-up over 9000 BiB children aged 7-11 years and their families between 2017 and 2021. We are collecting detailed parent and child questionnaires, cognitive and sensorimotor assessments, blood pressure, anthropometry and blood samples from parents and children. Dual x-ray absorptiometry body scans, accelerometry and urine samples are collected on subsamples. Informed consent is collected for continued routine data linkage to health, social care and education records. A range of engagement activities are being used to raise the profile of BiB and to disseminate findings. DISCUSSION: Our multi-method approach to recruitment and assessment provides an efficient method of collecting rich data on all family members. Data collected will enhance BiB as a resource for the international research community to study the interplay between ethnicity, socioeconomic circumstances and biology in relation to cardiometabolic health, mental health, education, cognitive and sensorimotor development and wellbeing.


Assuntos
Grupos Étnicos/estatística & dados numéricos , Pobreza/etnologia , Determinantes Sociais da Saúde/etnologia , Criança , Inglaterra , Feminino , Seguimentos , Humanos , Masculino , Gravidez , Estudos Prospectivos , Inquéritos e Questionários
4.
J Orthod ; 46(2): 118-125, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31060463

RESUMO

OBJECTIVE: To investigate the impact of premature extraction of primary teeth (PEPT) on orthodontic treatment need in a cohort of children participating in the Born in Bradford (BiB) longitudinal birth cohort. DESIGN: Observational, cross-sectional cohort. PARTICIPANTS: We aim to recruit 1000 children aged 7-11 years: 500 with a history of PEPT and 500 matched non-PEPT controls. METHODS: After informed consent/assent, orthodontic records will be collected, including extra and intra-oral photographs and alginate impressions for study models. Participants will also complete a measure of oral health-related quality of life (COHIP-SF 19). The records will be used to quantify space loss, identify other occlusal anomalies and assess orthodontic treatment need using the Index of Orthodontic Treatment Need. For each outcome, summary statistics will be calculated and the data for children with and without PEPT compared. The records of the children identified to be in need of orthodontic treatment will be examined by an expert orthodontic panel to judge if this treatment should be undertaken at the time of the records or delayed until the early permanent dentition. Collecting robust records in the mixed dentition provides the clinical basis to link each stage of the causal chain and enable the impact of PEPT on orthodontic need to be characterised. This study is the first to provide the foundations for future longitudinal data collection allowing the long-term impact of PEPT to be studied.

5.
Environ Int ; 123: 189-200, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30530161

RESUMO

Characterization of the "exposome", the set of all environmental factors that one is exposed to from conception onwards, has been advocated to better understand the role of environmental factors on chronic diseases. Here, we aimed to describe the early-life exposome. Specifically, we focused on the correlations between multiple environmental exposures, their patterns and their variability across European regions and across time (pregnancy and childhood periods). We relied on the Human Early-Life Exposome (HELIX) project, in which 87 environmental exposures during pregnancy and 122 during the childhood period (grouped in 19 exposure groups) were assessed in 1301 pregnant mothers and their children at 6-11 years in 6 European birth cohorts. Some correlations between exposures in the same exposure group reached high values above 0.8. The median correlation within exposure groups was >0.3 for many exposure groups, reaching 0.69 for water disinfection by products in pregnancy and 0.67 for the meteorological group in childhood. Median correlations between different exposure groups rarely reached 0.3. Some correlations were driven by cohort-level associations (e.g. air pollution and chemicals). Ten principal components explained 45% and 39% of the total variance in the pregnancy and childhood exposome, respectively, while 65 and 90 components were required to explain 95% of the exposome variability. Correlations between maternal (pregnancy) and childhood exposures were high (>0.6) for most exposures modeled at the residential address (e.g. air pollution), but were much lower and even close to zero for some chemical exposures. In conclusion, the early life exposome was high dimensional, meaning that it cannot easily be measured by or reduced to fewer components. Correlations between exposures from different exposure groups were much lower than within exposure groups, which have important implications for co-exposure confounding in multiple exposure studies. Also, we observed the early life exposome to be variable over time and to vary by cohort, so measurements at one time point or one place will not capture its complexities.


Assuntos
Exposição Ambiental , Poluição do Ar , Criança , Doença Crônica , Estudos de Coortes , Exposição Ambiental/análise , Europa (Continente) , Feminino , Humanos , Mães , Gravidez , Purificação da Água
6.
BMJ Open ; 8(9): e021311, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30206078

RESUMO

PURPOSE: Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. PARTICIPANTS: The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6-11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level). FINDINGS TO DATE: Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6-11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. FUTURE PLANS: HELIX study results will inform on the early life exposome and its association with molecular omics signatures and child health outcomes. Cohort data are accessible for future research involving researchers external to the project.

7.
Lancet Respir Med ; 6(5): 379-388, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29496485

RESUMO

BACKGROUND: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. METHODS: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4-16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2-56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1-79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. FINDINGS: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p<1·14 × 10-7) after meta-analysis. Consistently lower methylation levels were observed at all associated loci across childhood from age 4 to 16 years in participants with asthma, but not in cord blood at birth. All 14 CpG sites were significantly associated with asthma in the second replication study using whole-blood DNA, and were strongly associated with asthma in purified eosinophils. Whole-blood transcriptional signatures associated with these CpG sites indicated increased activation of eosinophils, effector and memory CD8 T cells and natural killer cells, and reduced number of naive T cells. Five of the 14 CpG sites were associated with asthma in respiratory epithelial cells, indicating cross-tissue epigenetic effects. INTERPRETATION: Reduced whole-blood DNA methylation at 14 CpG sites acquired after birth was strongly associated with childhood asthma. These CpG sites and their associated transcriptional profiles indicate activation of eosinophils and cytotoxic T cells in childhood asthma. Our findings merit further investigations of the role of epigenetics in a clinical context. FUNDING: EU and the Seventh Framework Programme (the MeDALL project).


Assuntos
Asma/genética , Ilhas de CpG , Metilação de DNA , Eosinófilos/imunologia , Epigênese Genética , Asma/sangue , Criança , Pré-Escolar , DNA/sangue , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Linfócitos T Citotóxicos
9.
Autism ; : 1362361317733182, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29113453

RESUMO

There has been recent interest in the relationship between socioeconomic status and the diagnosis of autism in children. Studies in the United States have found lower rates of autism diagnosis associated with lower socioeconomic status, while studies in other countries report no association, or the opposite. This article aims to contribute to the understanding of this relationship in the United Kingdom. Using data from the Born in Bradford cohort, comprising 13,857 children born between 2007 and 2011, it was found that children of mothers educated to A-level or above had twice the rate of autism diagnosis, 1.5% of children (95% confidence interval: 1.1%, 1.9%) compared to children of mothers with lower levels of education status 0.7% (95% confidence interval: 0.5%, 0.9%). No statistically significant relationship between income status or neighbourhood material deprivation was found after controlling for mothers education status. The results suggest a substantial level of underdiagnosis for children of lower education status mothers, though further research is required to determine the extent to which this is replicated across the United Kingdom. Tackling inequalities in autism diagnosis will require action, which could include increased education, awareness, further exploration of the usefulness of screening programmes and the provision of more accessible support services.

10.
Nat Commun ; 8(1): 303, 2017 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-28827725

RESUMO

Heterozygous mutations within homozygous sequences descended from a recent common ancestor offer a way to ascertain de novo mutations across multiple generations. Using exome sequences from 3222 British-Pakistani individuals with high parental relatedness, we estimate a mutation rate of 1.45 ± 0.05 × 10-8 per base pair per generation in autosomal coding sequence, with a corresponding non-crossover gene conversion rate of 8.75 ± 0.05 × 10-6 per base pair per generation. This is at the lower end of exome mutation rates previously estimated in parent-offspring trios, suggesting that post-zygotic mutations contribute little to the human germ-line mutation rate. We find frequent recurrence of mutations at polymorphic CpG sites, and an increase in C to T mutations in a 5' CCG 3' to 5' CTG 3' context in the Pakistani population compared to Europeans, suggesting that mutational processes have evolved rapidly between human populations.Estimates of human mutation rates differ substantially based on the approach. Here, the authors present a multi-generational estimate from the autozygous segment in a non-European population that gives insight into the contribution of post-zygotic mutations and population-specific mutational processes.


Assuntos
Genética Populacional/métodos , Genoma Humano/genética , Taxa de Mutação , Mutação , Exoma/genética , Mutação em Linhagem Germinativa , Heterozigoto , Homozigoto , Humanos , Polimorfismo Genético
11.
Prev Med ; 99: 152-163, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28232098

RESUMO

This systematic review of reviews aims to investigate how brief interventions (BIs) are defined, whether they increase physical activity, which factors influence their effectiveness, who they are effective for, and whether they are feasible and acceptable. We searched CINAHL, Cochrane database of systematic reviews, DARE, HTA database, EMBASE, MEDLINE, PsycINFO, Science Citation Index-Expanded and Social Sciences Citation Index, and Scottish Intercollegiate Guidelines Network from their inception until May 2015 to identify systematic reviews of the effectiveness of BIs aimed at promoting physical activity in adults, reporting a physical activity outcome and at least one BI that could be delivered in a primary care setting. A narrative synthesis was conducted. We identified three specific BI reviews and thirteen general reviews of physical activity interventions that met the inclusion criteria. The BI reviews reported varying definitions of BIs, only one of which specified a maximum duration of 30min. BIs can increase self-reported physical activity in the short term, but there is insufficient evidence about their long-term impact, their impact on objectively measured physical activity, and about the factors that influence their effectiveness, feasibility and acceptability. Current definitions include BIs that are too long for primary care consultations. Practitioners, commissioners and policy makers should be aware of this when interpreting evidence about BIs, and future research should develop and evaluate very brief interventions (of 5min or less) that could be delivered in a primary care consultation.


Assuntos
Exercício/fisiologia , Atenção Primária à Saúde/métodos , Encaminhamento e Consulta , Comportamentos Relacionados com a Saúde , Humanos , Assistência ao Paciente
12.
BMJ Paediatr Open ; 1(1): e000171, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29637167

RESUMO

Background: Congenital anomalies (CAs) are a common cause of infant death and disability. We linked children from a large birth cohort to a routine primary care database to detect CA diagnoses from birth to age 5 years. There could be evidence of underreporting by CA registries as they estimate that only 2% of CA registrations occur after age 1 year. Methods: CA cases were identified by linking children from a prospective birth cohort to primary care records. CAs were classified according to the European Surveillance of CA guidelines. We calculated rates of CAs by using a bodily system group for children aged 0 to <5 years, together with risk ratios (RRs) with 95% CIs for maternal risk factors. Results: Routinely collected primary care data increased the ascertainment of children with CAs from 432.9 per 10 000 live births under 1 year to 620.6 per 10 000 live births under 5 years. Consanguinity was a risk factor for Pakistani mothers (multivariable RR 1.87, 95% CI 1.46 to 2.83), and maternal age >34 years was a risk factor for mothers of other ethnicities (multivariable RR 2.19, 95% CI 1.36 to 3.54). Education was associated with a lower risk (multivariable RR 0.78, 95% CI 0.62 to 0.98). Conclusion: 98% of UK CA registrations relate to diagnoses made in the first year of life. Our data suggest that this leads to incomplete case ascertainment with a further 30% identified after age 1 year in our study. Risk factors for CAs identified up to age 1 year persist up to 5 years. National registries should consider using routine data linkage to provide more complete case ascertainment after infancy.

13.
J Public Health (Oxf) ; 39(2): e48-e55, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27412173

RESUMO

Background: The 'Five Year Forward View' (NHS England) calls for a radical upgrade in public health provision. Inequalities in maternal health may perpetuate general patterns of health inequalities across generations; therefore equitable access to general practice (GP) provision during maternity is important. This paper explores variation in GP consultation rates for disadvantaged mothers. Method: Data from the Born in Bradford cohort (around 12 000 women), combined with GP records and GP practice variables, were modelled to predict GP consultation rates, before and after adjusting for individual health and GP provision. Results: Observed GP consultation rates are higher for women in materially deprived neighbourhoods and Pakistani women. However these groups were found to consult less often after controlling for individual health. This difference, around one appointment per year, is 'explained' by the nature of GP provision. Women in practices with a low GP to patient ratio had around 09 fewer consultations over the six year period compared to women in practices with the highest ratio. Conclusions: Equitable access to GP services, particularly for women during the maternal period, is essential for tackling deep-rooted health inequalities. Future GP funding should take account of neighbourhood material deprivation to focus resources on areas of the greatest need.


Assuntos
Grupos Étnicos/estatística & dados numéricos , Medicina Geral/organização & administração , Medicina Geral/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Serviços de Saúde Materna/organização & administração , Serviços de Saúde Materna/estatística & dados numéricos , Mães/estatística & dados numéricos , Adulto , Estudos de Coortes , Inglaterra , Feminino , Humanos , Medicina Estatal/organização & administração , Medicina Estatal/estatística & dados numéricos , Adulto Jovem
14.
Lancet Diabetes Endocrinol ; 5(2): 97-105, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27908689

RESUMO

BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30). INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Análise da Randomização Mendeliana/métodos , Pró-Proteína Convertase 9/genética , Glicemia/metabolismo , Estudos de Casos e Controles , LDL-Colesterol/sangue , LDL-Colesterol/genética , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
15.
BMC Public Health ; 15: 711, 2016 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-27488369

RESUMO

BACKGROUND: Early interventions are recognised as key to improving life chances for children and reducing inequalities in health and well-being, however there is a paucity of high quality research into the effectiveness of interventions to address childhood health and development outcomes. Planning and implementing standalone RCTs for multiple, individual interventions would be slow, cumbersome and expensive. This paper describes the protocol for an innovative experimental birth cohort: Born in Bradford's Better Start (BiBBS) that will simultaneously evaluate the impact of multiple early life interventions using efficient study designs. Better Start Bradford (BSB) has been allocated £49 million from the Big Lottery Fund to implement 22 interventions to improve outcomes for children aged 0-3 in three key areas: social and emotional development; communication and language development; and nutrition and obesity. The interventions will be implemented in three deprived and ethnically diverse inner city areas of Bradford. METHOD: The BiBBS study aims to recruit 5000 babies, their mothers and their mothers' partners over 5 years from January 2016-December 2020. Demographic and socioeconomic information, physical and mental health, lifestyle factors and biological samples will be collected during pregnancy. Parents and children will be linked to their routine health and local authority (including education) data throughout the children's lives. Their participation in BSB interventions will also be tracked. BiBBS will test interventions using the Trials within Cohorts (TwiCs) approach and other quasi-experimental designs where TwiCs are neither feasible nor ethical, to evaluate these early life interventions. The effects of single interventions, and the cumulative effects of stacked (multiple) interventions on health and social outcomes during the critical early years will be measured. DISCUSSION: The focus of the BiBBS cohort is on intervention impact rather than observation. As far as we are aware BiBBS is the world's first such experimental birth cohort study. While some risk factors for adverse health and social outcomes are increasingly well described, the solutions to tackling them remain elusive. The novel design of BiBBS can contribute much needed evidence to inform policy makers and practitioners about effective approaches to improve health and well-being for future generations.


Assuntos
Desenvolvimento Infantil , Promoção da Saúde/normas , Estado Nutricional , Adulto , Pré-Escolar , Estudos de Coortes , Inglaterra , Grupos Étnicos , Feminino , Humanos , Lactente , Recém-Nascido , Desenvolvimento da Linguagem , Masculino , Mães , Obesidade , Pobreza , Gravidez , Projetos de Pesquisa , Fatores de Risco
16.
BMC Psychiatry ; 16: 99, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-27071711

RESUMO

BACKGROUND: Common mental disorders (CMD) such as anxiety and depression during the maternal period can cause significant morbidity to the mother in addition to disrupting biological, attachment and parenting processes that affect child development. Pharmacological treatment is a first-line option for moderate to severe episodes. Many women prescribed pharmacological treatments cease them during pregnancy but it is unclear to what extent non-pharmacological options are offered as replacement. There are also concerns that treatments offered may not be proportionate to need in minority ethnic groups, but few data exist on treatment disparities in the maternal period. We examined these questions in a multi-ethnic cohort of women with CMD living in Bradford, England before, during and up to one year after pregnancy. METHODS: We searched the primary care records of women enrolled in the Born in Bradford cohort for diagnoses, symptoms, signs ('identification'), referrals for treatment, non-pharmacological and pharmacological treatment and monitoring ('treatment') related to CMD. Records were linked with maternity data to classify women identified with a CMD as treated prior to, and one year after, delivery. We examined rates and types of treatment during pregnancy, and analysed potential ethnic group differences using adjusted Poisson and multinomial logistic regression models. RESULTS: We analysed data on 2,234 women with indicators of CMD. Most women were discontinued from pharmacological treatment early in pregnancy, but this was accompanied by recorded access to non-drug treatments in only 15 % at the time of delivery. Fewer minority ethnic women accessed treatments compared to White British women despite minority ethnic women being 55-70 % more likely than White British women to have been identified with anxiety in their medical record. CONCLUSIONS: Very few women who discontinued pharmacological treatment early in their pregnancy were offered other non-pharmacological treatments as replacement, and most appeared to complete their pregnancy untreated. Further investigation is warranted to replicate the finding that minority ethnic women are more likely to be identified as being anxious or having anxiety and understand what causes the variation in access to treatments.


Assuntos
Grupos Étnicos/psicologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Transtornos Mentais/terapia , Mães/psicologia , Complicações na Gravidez/terapia , Adulto , Estudos de Coortes , Inglaterra , Grupos Étnicos/estatística & dados numéricos , Feminino , Humanos , Lactente , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/psicologia , Mães/estatística & dados numéricos , Período Pós-Parto , Gravidez , Complicações na Gravidez/psicologia , Inquéritos e Questionários
17.
Science ; 352(6284): 474-7, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-26940866

RESUMO

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans.


Assuntos
Consanguinidade , Saúde , Histona-Lisina N-Metiltransferase/genética , Adulto , Análise Mutacional de DNA , Prescrições de Medicamentos , Exoma/genética , Feminino , Fertilidade , Técnicas de Inativação de Genes , Genes Letais , Loci Gênicos , Genoma Humano , Recombinação Homóloga , Homozigoto , Humanos , Masculino , Mães , Paquistão/etnologia , Fenótipo , Reino Unido
18.
Br J Psychiatry ; 208(5): 453-61, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26795424

RESUMO

BACKGROUND: There are limited data on detection disparities of common mental disorders in minority ethnic women. AIMS: Describe the natural history of common mental disorders in primary care in the maternal period, characterise women with, and explore ethnic disparities in, detected and potentially missed common mental disorders. METHOD: Secondary analyses of linked birth cohort and primary care data involving 8991 (39.4% White British) women in Bradford. Common mental disorders were characterised through indications in the electronic medical record. Potentially missed common mental disorders were defined as an elevated General Health Questionnaire (GHQ-28) score during pregnancy with no corresponding common mental disorder markers in the medical record. RESULTS: Estimated prevalence of pre-birth common mental disorders was 9.5%, rising to 14.0% 3 years postnatally. Up to half of cases were potentially missed. Compared with White British women, minority ethnic women were twice as likely to have potentially missed common mental disorders and half as likely to have a marker of screening for common mental disorders. CONCLUSIONS: Common mental disorder detection disparities exist for minority ethnic women in the maternal period.


Assuntos
Ansiedade/diagnóstico , Diagnóstico Tardio/estatística & dados numéricos , Depressão/diagnóstico , Disparidades em Assistência à Saúde/etnologia , Complicações na Gravidez/diagnóstico , Atenção Primária à Saúde/estatística & dados numéricos , Adulto , Ansiedade/etnologia , Depressão/etnologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/etnologia , Reino Unido/etnologia , Adulto Jovem
19.
Eur Child Adolesc Psychiatry ; 25(6): 601-13, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26415597

RESUMO

Observational studies indicate children whose mothers have poor mental health are at increased risk of socio-emotional behavioural difficulties, but it is unknown whether these outcomes vary by the mothers' mental health recognition and treatment status. To examine this question, we analysed linked longitudinal primary care and research data from 1078 women enrolled in the Born in Bradford cohort. A latent class analysis of treatment status and self-reported distress broadly categorised women as (a) not having a common mental disorder (CMD) that persisted through pregnancy and the first 2 years after delivery (N = 756, 70.1 %), (b) treated for CMD (N = 67, 6.2 %), or (c) untreated (N = 255, 23.7 %). Compared to children of mothers without CMD, 3-year-old children with mothers classified as having untreated CMD had higher standardised factor scores on the Strengths and Difficulties Questionnaire (d = 0.32), as did children with mothers classified as having treated CMD (d = 0.27). Results were only slightly attenuated in adjusted analyses. Children of mothers with CMD may be at risk for socio-emotional and behavioural difficulties. The development of effective treatments for CMD needs to be balanced by greater attempts to identify and treat women.


Assuntos
Transtornos do Comportamento Infantil/psicologia , Comportamento Infantil/psicologia , Mães/psicologia , Atenção Primária à Saúde , Estresse Psicológico/psicologia , Adulto , Transtornos do Comportamento Infantil/epidemiologia , Transtornos do Comportamento Infantil/terapia , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Gravidez , Atenção Primária à Saúde/tendências , Autorrelato , Estresse Psicológico/epidemiologia , Estresse Psicológico/terapia , Resultado do Tratamento
20.
J Vis Exp ; (94)2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25489745

RESUMO

Convergent Polishing is a novel polishing system and method for finishing flat and spherical glass optics in which a workpiece, independent of its initial shape (i.e., surface figure), will converge to final surface figure with excellent surface quality under a fixed, unchanging set of polishing parameters in a single polishing iteration. In contrast, conventional full aperture polishing methods require multiple, often long, iterative cycles involving polishing, metrology and process changes to achieve the desired surface figure. The Convergent Polishing process is based on the concept of workpiece-lap height mismatch resulting in pressure differential that decreases with removal and results in the workpiece converging to the shape of the lap. The successful implementation of the Convergent Polishing process is a result of the combination of a number of technologies to remove all sources of non-uniform spatial material removal (except for workpiece-lap mismatch) for surface figure convergence and to reduce the number of rogue particles in the system for low scratch densities and low roughness. The Convergent Polishing process has been demonstrated for the fabrication of both flats and spheres of various shapes, sizes, and aspect ratios on various glass materials. The practical impact is that high quality optical components can be fabricated more rapidly, more repeatedly, with less metrology, and with less labor, resulting in lower unit costs. In this study, the Convergent Polishing protocol is specifically described for fabricating 26.5 cm square fused silica flats from a fine ground surface to a polished ~λ/2 surface figure after polishing 4 hr per surface on a 81 cm diameter polisher.


Assuntos
Óptica e Fotônica/métodos , Vidro/química , Óptica e Fotônica/instrumentação , Reologia/instrumentação , Reologia/métodos
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