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1.
Mol Psychiatry ; 21(6): 758-67, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27046643

RESUMO

People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal-numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal-numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia.


Assuntos
Cognição/fisiologia , Inteligência/genética , Idoso , Bancos de Espécimes Biológicos , Escolaridade , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Polimorfismo de Nucleotídeo Único/genética , Reino Unido
2.
Mol Psychiatry ; 21(11): 1624-1632, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26809841

RESUMO

Causes of the well-documented association between low levels of cognitive functioning and many adverse neuropsychiatric outcomes, poorer physical health and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular-metabolic, neuropsychiatric, physiological-anthropometric and cognitive traits in the participants of UK Biobank, a very large population-based sample (N=112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics and to the method of linkage disequilibrium score regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.


Assuntos
Cognição , Estudos de Associação Genética/métodos , Saúde , Adulto , Idoso , Bancos de Espécimes Biológicos , Cognição/fisiologia , Bases de Dados Factuais , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Desequilíbrio de Ligação/genética , Masculino , Saúde Mental , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética
3.
Br J Dermatol ; 174(4): 853-61, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26686685

RESUMO

BACKGROUND: The Children's Dermatology Life Quality Index (CDLQI) is the most widely used instrument for measuring the impact of skin disease on quality of life (QoL) in children. OBJECTIVES: To provide a meta-analysis of all published QoL scores for a range of childhood skin conditions. METHODS: Studies using the CDLQI questionnaire to measure QoL in skin conditions were identified by searching Medline and Embase from January 1995 (CDLQI creation) to December 2014. Studies were grouped according to condition and baseline scores were combined using meta-analysis. RESULTS: Sixty-seven studies using the CDLQI met the inclusion criteria. The overall estimated CDLQI scores for conditions reported more than once were [point estimate (95% confidence interval, CI), number of studies (n), score range]: atopic eczema [8·5 (7·1-9·8), n = 38, 0-29], acne [5·3 (1·9-8·5), n = 5, 0-30], alopecia [3·1 (0-7·7), n = 2, 0-6], molluscum contagiosum [3·5 (0·6-6·7), n = 5, 0-27], psoriasis [8·0 (3·9-12·1), n = 6, 0-29], scabies [9·2 (0·0-20·3), n = 2, 1-26], urticaria [7·1 (0-15·4), n = 2, 0-22], vitiligo [6·5 (0·7-12·2), n = 2, 0-20] and warts [2·9 (0-5·8), n = 4, 0-16]. Overall, the mean effect on QoL [weighted average CDLQI score 4·6 (95% CI 3·9-5·4)] for children with these conditions was small. However, many children were found to experience a very large impact on QoL (34% of children with atopic eczema, 10% with molluscum contagiosum and 1-5% with acne) in studies where the distributions of scores were provided. CONCLUSIONS: Most skin conditions in children have a 'small' mean effect on QoL. However, the range is large and a significant proportion of children with many common skin conditions will experience a very large effect on quality of life.


Assuntos
Qualidade de Vida , Dermatopatias/psicologia , Adolescente , Criança , Pré-Escolar , Humanos , Satisfação do Paciente , Índice de Gravidade de Doença , Inquéritos e Questionários
4.
J Environ Manage ; 183: 280-293, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27600332

RESUMO

Marine Protected Areas (MPAs), marine areas in which human activities are restricted, are implemented worldwide to protect the marine environment. However, with a large proportion of these MPAs being no more than paper parks, it is important to be able to evaluate MPA success, determined by improvements to biophysical, socio-economic and governance conditions. In this study a systematic literature review was conducted to determine the most frequently used indicators of MPA success. These were then applied to a case study to demonstrate how success can be evaluated. The fifteen most frequently used indicators included species abundance, level of stakeholder participation and the existence of a decision-making and management body. Using the indicator framework with a traffic light system, we demonstrate how an MPA can be evaluated in terms of how well it performs against the indicators using secondary data from the literature. The framework can be used flexibly. For example, where no MPA data currently exist, the framework can be populated by qualitative data provided by local stakeholder knowledge. This system provides a cost-effective and straightforward method for managers and decision-makers to determine the level of success of any MPA and identify areas of weakness. However, given the variety of motivations for MPA establishment, this success needs to be determined in the context of the original management objectives of the MPA with greater weighting being placed on those objectives where appropriate.


Assuntos
Conservação dos Recursos Naturais/métodos , Ecossistema , Fenômenos Biofísicos , Análise Custo-Benefício , Bases de Dados Factuais , Tomada de Decisões , Inglaterra , Oceanos e Mares , Fatores Socioeconômicos
5.
Psychol Med ; 45(13): 2771-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25936473

RESUMO

BACKGROUND: Major depressive disorder and subthreshold depression have been associated with premature mortality. We investigated the association between depressive symptoms and mortality across the full continuum of severity. METHOD: We used Cox proportional hazards models to examine the association between depressive symptom severity, assessed using the eight-item Center for Epidemiological Studies Depression Scale (CES-D; range 0-8), and the risk of all-cause mortality over a 9-year follow-up, in 11 104 members of the English Longitudinal Study of Ageing. RESULTS: During follow-up, one fifth of study members died (N = 2267). Depressive symptoms were associated with increased mortality across the full range of severity (p trend < 0.001). Relative to study members with no symptoms, an increased risk of mortality was found in people with depressive symptoms of a low [hazard ratio (HR) for a score of 2 was 1.59, 95% confidence interval (CI) 1.40-1.82], moderate (score of 4: HR 1.80, 95% CI 1.52-2.13) and high (score of 8: HR 2.27, 95% CI 1.69-3.04) severity, suggesting risk emerges at low levels but plateaus thereafter. A third of participants (36.4%, 95% CI 35.5-37.3) reported depressive symptoms associated with an increased mortality risk. Adjustment for physical activity, physical illnesses, and impairments in physical and cognitive functioning attenuated this association (p trend = 0.25). CONCLUSIONS: Depressive symptoms are associated with an increased mortality risk even at low levels of symptom severity. This association is explained by physical activity, physical illnesses, and impairments in physical and cognitive functioning.


Assuntos
Envelhecimento/psicologia , Depressão/diagnóstico , Depressão/mortalidade , Idoso , Causas de Morte , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Fatores de Risco , Índice de Gravidade de Doença
6.
Sci Rep ; 12(1): 14700, 2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038622

RESUMO

The association between adversity and cognition varies according to the specific adversity, when the adversity was experienced, and the cognitive domains investigated. Disentangling the effect of adversity and the underlying mechanistic pathway is therefore difficult. The association between adversity (i.e., maltreatment) accumulated over the life course and cognitive flexibility, as well as two potential mediators (i.e., intra-individual variability in reaction time and depression) of this association, were investigated. Data stem from the baseline population of the UK Biobank study (N = 73,489, Mdnage = 56, SDage = 7.628, 55.740% of women). Cumulative life course adversity (specifically maltreatment) was measured with items based on the Childhood Trauma Questionnaire (CTS-5) and items adapted from the British Crime Survey. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9). Intra-individual variability in reaction time was measured with a reaction time test "snap game" and the Trail Making Test A and B were used as a measure of cognitive flexibility. A path analysis was performed on these data. Higher cumulative adverse experiences were associated with lower performance in cognitive flexibility (ß = .016, p < .001, 95% CI [0.009, 0.024]), and this effect was partly mediated by the level of depression (22.727% of the total effect of cumulative life course adversity on cognitive flexibility was mediated by depression (ß = .005, p < .001, 95% CI [0.004, 0.007])). No association between cumulative life course adverse experiences and intra-individual variability in reaction time was found, nor was any indirect association between cumulative life course adversity and performance in cognitive flexibility via intra-individual variability in reaction time. The association between cumulative life course adversity, depression, and performance in cognitive flexibility has been highlighted. In contrast, no indirect effect between cumulative life course adversity and performance in cognitive flexibility via intra-individual variability in reaction time was found, suggesting that it is not a potential mechanism underlying the association between cumulative life course adversity and executive function.


Assuntos
Cognição/fisiologia , Acontecimentos que Mudam a Vida , Saúde Mental , Adulto , Rotas de Resultados Adversos , Criança , Maus-Tratos Infantis/psicologia , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Função Executiva/fisiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Reino Unido/epidemiologia
7.
Psychol Med ; 41(10): 2057-73, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21349224

RESUMO

BACKGROUND: Symptoms of anxiety and depression are common in older people, but the relative importance of factors operating in early and later life in influencing risk is unclear, particularly in the case of anxiety. METHOD: We used data from five cohorts in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme: the Aberdeen Birth Cohort 1936, the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study and the Lothian Birth Cohort 1921. We used logistic regression to examine the relationship between factors from early and later life and risk of anxiety or depression, defined as scores of 8 or more on the subscales of the Hospital Anxiety and Depression Scale, and meta-analysis to obtain an overall estimate of the effect of each. RESULTS: Greater neuroticism, poorer cognitive or physical function, greater disability and taking more medications were associated in cross-sectional analyses with an increased overall likelihood of anxiety or depression. Associations between lower social class, either in childhood or currently, history of heart disease, stroke or diabetes and increased risk of anxiety or depression were attenuated and no longer statistically significant after adjustment for potential confounding or mediating variables. There was no association between birth weight and anxiety or depression in later life. CONCLUSIONS: Anxiety and depression in later life are both strongly linked to personality, cognitive and physical function, disability and state of health, measured concurrently. Possible mechanisms that might underlie these associations are discussed.


Assuntos
Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Estudos de Coortes , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Transtornos Neuróticos/epidemiologia , Transtornos Neuróticos/psicologia , Fatores de Risco , Distribuição por Sexo , Classe Social , Reino Unido/epidemiologia
8.
Phys Rev Lett ; 104(8): 084802, 2010 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-20366938

RESUMO

Laser-plasma wakefield-based electron accelerators are expected to deliver ultrashort electron bunches with unprecedented peak currents. However, their actual pulse duration has never been directly measured in a single-shot experiment. We present measurements of the ultrashort duration of such electron bunches by means of THz time-domain interferometry. With data obtained using a 0.5 J, 45 fs, 800 nm laser and a ZnTe-based electro-optical setup, we demonstrate the duration of laser-accelerated, quasimonoenergetic electron bunches [best fit of 32 fs (FWHM) with a 90% upper confidence level of 38 fs] to be shorter than the drive laser pulse, but similar to the plasma period.

9.
Nature ; 431(7008): 535-8, 2004 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-15457251

RESUMO

High-power lasers that fit into a university-scale laboratory can now reach focused intensities of more than 10(19) W cm(-2) at high repetition rates. Such lasers are capable of producing beams of energetic electrons, protons and gamma-rays. Relativistic electrons are generated through the breaking of large-amplitude relativistic plasma waves created in the wake of the laser pulse as it propagates through a plasma, or through a direct interaction between the laser field and the electrons in the plasma. However, the electron beams produced from previous laser-plasma experiments have a large energy spread, limiting their use for potential applications. Here we report high-resolution energy measurements of the electron beams produced from intense laser-plasma interactions, showing that--under particular plasma conditions--it is possible to generate beams of relativistic electrons with low divergence and a small energy spread (less than three per cent). The monoenergetic features were observed in the electron energy spectrum for plasma densities just above a threshold required for breaking of the plasma wave. These features were observed consistently in the electron spectrum, although the energy of the beam was observed to vary from shot to shot. If the issue of energy reproducibility can be addressed, it should be possible to generate ultrashort monoenergetic electron bunches of tunable energy, holding great promise for the future development of 'table-top' particle accelerators.

10.
Int J Popul Data Sci ; 5(1): 1121, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32935048

RESUMO

INTRODUCTION: The rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during clinical care. OBJECTIVES: We aimed to apply reproducible methods to create the SAIL dementia e-cohort (SAIL-DeC). We created SAIL-DeC with a view to maximising its utility for a broad range of research questions whilst minimising duplication of effort for researchers. METHODS: SAIL contains individual-level, linked primary care, hospital admission, mortality and demographic data. Data are currently available until 2018 and future updates will extend participant follow-up time. We included participants who were born between 1st January 1900 and 1st January 1958 and for whom primary care data were available. We applied algorithms consisting of International Classification of Diseases (versions 9 and 10) and Read (version 2) codes to identify participants with and without all-cause dementia and dementia subtypes. We also created derived variables for comorbidities and risk factors. RESULTS: From 4.4 million unique participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia, with 77,978 (60%) having dementia subtype codes. Alzheimer's disease was the most common subtype diagnosis (62%). Among the dementia cases, the median duration of observation time was 14 years. CONCLUSION: We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research.

11.
Endocrine ; 68(2): 261-264, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32472423

RESUMO

Studies on the TSH receptor (TSHR) have numerous practical applications in vitro and in vivo. For example human monoclonal autoantibodies (MAbs) to the TSHR are useful reagents for in vitro diagnostics. Measurement of TSHR autoantibodies (TRAbs) is helpful in diagnosis and management of autoimmune thyroid disease. Currently available highly sensitive and specific assays to measure TRAbs use the human TSHR MAb M22 instead of the TSH. Furthermore, preparations of the human TSHR MAb M22 are useful as the World Health Organisation International Standard for thyroid stimulating antibody and for calibration of the assays for measuring TRAbs. Preparations of thermostabilised TSHR extracellular domain have recently become available and this is likely to have an impact on improvements in specificity testing for TRAb assays. In addition the stable TSHR preparations have practical application for specific immunoadsorption of patient serum TRAbs. Human TSHR MAbs also have promising prospects as new therapeutics. Autoantibodies with TSHR antagonistic activities are "natural" inhibitors of TSHR stimulation and are expected to be helpful in controlling TSHR activity in patients with Graves' disease, Graves' ophthalmopathy and thyroid cancer.


Assuntos
Doença de Graves , Receptores da Tireotropina , Anticorpos Monoclonais , Autoanticorpos , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide
12.
Clin Endocrinol (Oxf) ; 70(3): 484-92, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18681859

RESUMO

OBJECTIVE: Low thyroid function has been associated with depression in clinical populations. We have examined whether thyroid function in the normal range is associated with minor psychiatric morbidity. DESIGN: Prospective cohort study of 2269 middle aged men (45-59 years) with thyroid function (total T(4) only, TSH unavailable) measured between 1979 and 1983 and with repeat measures of minor psychiatric morbidity (GHQ-30) over a mean of 12.3 years follow-up. We also undertook a systematic review and meta-analysis of population-based studies examining thyroid function and mood. RESULTS: There was a positive association between total T(4) and chronic psychiatric morbidity (odds ratio 1.21, 95% CI 1.02-1.43, P= 0.03), but this was consistent with chance after adjusting for social class, alcohol and smoking behaviours. The association with incident and recovery from psychiatric morbidity was weaker and consistent with chance. We identified seven eligible studies, from our systematic review and included six studies, including our own, in a meta-analysis. The pooled estimate showed a positive association (odds ratio 1.12, 95% CI 1.02-1.22, P-value = 0.01) between depression and T(4) and an inverse association with TSH (odds ratio 0.92, 95% CI 0.88-0.97, P= 0.0007) with no evidence of heterogeneity or publication bias. CONCLUSION: The results from CaPS and our meta-analysis are consistent and suggest that, if anything, higher levels of thyroxine in the normal range are associated with increased risk of depression. The effects of thyroid hormone on mood may differ in normal populations and patients with clinical thyroid dysfunction.


Assuntos
Depressão/epidemiologia , Glândula Tireoide/fisiopatologia , Estudos de Coortes , Depressão/sangue , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/psicologia , Tiroxina/sangue , País de Gales
13.
PLoS One ; 14(9): e0222212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31536538

RESUMO

The path signature is a means of feature generation that can encode nonlinear interactions in data in addition to the usual linear terms. It provides interpretable features and its output is a fixed length vector irrespective of the number of input points or their sample times. In this paper we use the path signature to provide features for identifying people whose diagnosis subsequently converts to Alzheimer's disease. In two separate classification tasks we distinguish converters from 1) healthy individuals, and 2) individuals with mild cognitive impairment. The data used are time-ordered measurements of the whole brain, ventricles and hippocampus from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We find two nonlinear interactions which are predictive in both cases. The first interaction is change of hippocampal volume with time, and the second is a change of hippocampal volume relative to the volume of the whole brain. While hippocampal and brain volume changes are well known in Alzheimer's disease, we demonstrate the power of the path signature in their identification and analysis without manual feature selection. Sequential data is becoming increasingly available as monitoring technology is applied, and the path signature method is shown to be a useful tool in the processing of this data.


Assuntos
Doença de Alzheimer/diagnóstico , Aprendizado de Máquina , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Neuroimagem
14.
PLoS One ; 14(2): e0211558, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30763336

RESUMO

Time-dependent data collected in studies of Alzheimer's disease usually has missing and irregularly sampled data points. For this reason time series methods which assume regular sampling cannot be applied directly to the data without a pre-processing step. In this paper we use a random forest to learn the relationship between pairs of data points at different time separations. The input vector is a summary of the time series history and it includes both demographic and non-time varying variables such as genetic data. To test the method we use data from the TADPOLE grand challenge, an initiative which aims to predict the evolution of subjects at risk of Alzheimer's disease using demographic, physical and cognitive input data. The task is to predict diagnosis, ADAS-13 score and normalised ventricles volume. While the competition proceeds, forecasting methods may be compared using a leaderboard dataset selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and with standard metrics for measuring accuracy. For diagnosis, we find an mAUC of 0.82, and a classification accuracy of 0.73 compared with a benchmark SVM predictor which gives mAUC = 0.62 and BCA = 0.52. The results show that the method is effective and comparable with other methods.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador , Aprendizado de Máquina , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Reconhecimento Automatizado de Padrão
15.
Neuroepidemiology ; 30(1): 25-33, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18259098

RESUMO

BACKGROUND/AIMS: The prevalence of dementia and cognitive impairment not dementia was investigated in the Caerphilly Prospective Study cohort (men currently aged 65-84 years). METHODS: Of 1,633 men eligible for cognitive screening, 1,225 (75%) were seen, with those failing the screening criteria (CAMCOG <83 or decline in CAMCOG >9) being neurologically examined. RESULTS: For dementia, diagnosed by DSM-IV criteria, the population prevalence was 5.2% rising to 6.1% in the screened population. For cognitive impairment not dementia, the prevalence in the screened population was 15.6% giving an overall prevalence of cognitive impairment of 21.8%. Prevalence rose fivefold between ages of 65 and 84 years to reach over 50%. CONCLUSION: These figures are likely to underestimate actual prevalence in this population, and developing effective interventions should be a public health priority.


Assuntos
Transtornos Cognitivos/epidemiologia , Características de Residência/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Estudos de Coortes , Demência/diagnóstico , Demência/epidemiologia , Demência/psicologia , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/psicologia , Programas de Rastreamento/estatística & dados numéricos , Testes Neuropsicológicos/estatística & dados numéricos , Prevalência , Estudos Prospectivos , País de Gales/epidemiologia
17.
J Epidemiol Community Health ; 59(2): 130-3, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15650144

RESUMO

STUDY OBJECTIVE: There is evidence suggesting that artificial feeding is associated with a reduction in cognitive function in infants and children, in contrast with breast feeding, but the available evidence suffers from confounding by social and educational factors. An opportunity arose in the Caerphilly cohort study to examine relations between cognitive function in older men and their feeding as infants, when breast feeding was usual. DESIGN: A prospective cohort study. SETTING: Caerphilly, South Wales, UK, was a deprived coal mining community when the men had been born in 1920-35. Most had been breast fed as infants. PARTICIPANTS: 779 men aged 60-74 years when tested. The men had earlier been asked to obtain from their mothers their birth weight, and how they had been fed as infants. RESULTS: Complete data were obtained for 779 men. In those whose birth weight had been at or above the median, the adjusted mean cognitive function was only slightly and non-significantly lower in those who had been artificially fed. In the men whose birth weight had been below the median, having been artificially fed was associated with significantly lower results in both a test of reasoning (the AH4) and word power (the national adult reading test (NART)). Two standard deviations below the median birth weight, artificial feeding was associated with a reduction of six points (70% of a SD) on word power (the NART). CONCLUSIONS: In men whose birth weight had been low, having been artificially fed is associated with poorer cognitive function in late adult life.


Assuntos
Aleitamento Materno/psicologia , Cognição , Idoso , Peso ao Nascer , Alimentação com Mamadeira/psicologia , Alimentação com Mamadeira/estatística & dados numéricos , Aleitamento Materno/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos
18.
Oncogene ; 34(7): 922-31, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-24632604

RESUMO

Tuberous sclerosis (TSC) is an inherited syndrome in which tumours in multiple organs are characterised by activation of mammalian target of rapamycin complex 1 (mTORC1). Previous work suggests that mTORC1 activation is associated with feedback inhibition of Akt, a substrate of mTORC2. This could limit TSC-associated tumour growth but lead to paradoxical promotion of tumour cell survival upon treatment with mTOR inhibitors. However, Akt/mTOR signalling has not been fully investigated in TSC-associated tumours and it has been uncertain whether mTOR inhibition can prevent TSC-associated renal tumourigenesis. In this study, we investigated Akt/mTOR signalling in renal tumours using a Tsc2(+/-) mouse model and tested whether mTOR inhibition could prevent renal tumourigenesis. We found that all renal lesions including cysts, adenomas and carcinomas exhibited activation of both Akt and mTORC1 as evidenced by increased protein expression and phosphorylation of Akt and mTOR and their downstream targets. Protein kinase Cα was also highly expressed and phosphorylated in these lesions, consistent with activation of mTORC2. Surprisingly, IRS proteins were highly expressed, in contrast to a striking decrease seen in cultured Tsc2(-/-) mouse embryonic fibroblasts, suggesting one mechanism through which loss of feedback inhibition of Akt may occur in mTORC1 hyperactivated Tsc-associated tumours. Long-term treatment with rapamycin reduced both Akt and mTORC1 activity in normal kidney tissues and blocked the development of all types of renal lesions. In conclusion, in contrast to previous studies, we found that Akt signalling is not inhibited in Tsc-associated renal lesions and that by partially inhibiting the Akt/mTOR pathway, rapamycin is highly effective in preventing Tsc-associated tumours.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias Renais , Neoplasias Experimentais , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Proteínas Supressoras de Tumor , Animais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/prevenção & controle , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Camundongos Mutantes , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Experimentais/prevenção & controle , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
19.
Eur Psychiatry ; 30(8): 950-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26647871

RESUMO

BACKGROUND: This study investigated differences in cognitive performance between middle-aged adults with and without a lifetime history of mood disorder features, adjusting for a range of potential confounders. METHODS: Cross-sectional analysis of baseline data from the UK Biobank cohort. Adults aged 40-69 (n=143,828) were assessed using measures of reasoning, reaction time and memory. Self-reported data on lifetime features of major depression and bipolar disorder were used to construct groups for comparison against controls. Regression models examined the association between mood disorder classification and cognitive performance, adjusting for sociodemographic, lifestyle and clinical confounders. RESULTS: Inverse associations between lifetime history of bipolar or severe recurrent depression features and cognitive performance were attenuated or reversed after adjusting for confounders, including psychotropic medication use and current depressive symptoms. Participants with a lifetime history of single episode or moderate recurrent depression features outperformed controls to a small (but statistically significant) degree, independent of adjustment for confounders. There was a significant interaction between use of psychotropic medication and lifetime mood disorder features, with reduced cognitive performance observed in participants taking psychotropic medication. CONCLUSIONS: In this general population sample of adults in middle age, lifetime features of recurrent depression or bipolar disorder were only associated with cognitive impairment within unadjusted analyses. These findings underscore the importance of adjusting for potential confounders when investigating mood disorder-related cognitive function.


Assuntos
Transtorno Bipolar/psicologia , Transtornos Cognitivos/psicologia , Cognição , Transtorno Depressivo Maior/psicologia , Adulto , Idoso , Transtorno Bipolar/epidemiologia , Transtornos Cognitivos/epidemiologia , Estudos de Coortes , Estudos Transversais , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/psicologia , Prevalência
20.
Int J Epidemiol ; 24(2): 321-30, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7635592

RESUMO

BACKGROUND: The Health Attitude Inventory (HAI) is developed to assess attitudes, beliefs and values towards coronary-related behaviour in epidemiological studies. It comprises a 76-item self-administered questionnaire which can be completed in under 10 minutes by most adults. METHODS: The HAI was administered to 2100 men aged 50-64 years along with measures of ischaemic heart disease risk factors, including the following coronary-related behaviours: smoking, exercise, type A behaviour and the consumption of fried food, dairy produce, wholemeal bread and vegetables. RESULTS: Cross-sectional analyses using linear regression showed attitudes, beliefs and values to explain between 8% and 27% of the variance in the dietary coronary-related behaviour. For exercise 13% of the variance was explained, and for type A behaviour 18%. Similar analysis for smoking using logistic regression (non-smoker versus current smoker) showed a predictive concordance of 95%. CONCLUSIONS: The HAI has demonstrated the assessment of attitudes, beliefs and values in an epidemiological setting to show associations with a range of coronary risk behaviours. This finding has potential public health as well as aetiological application in that influential attitudes, values and beliefs can be identified to aid increasing healthy as well as reducing risky coronary-related behaviour.


Assuntos
Atitude Frente a Saúde , Isquemia Miocárdica/epidemiologia , Psicometria , Dieta , Exercício Físico , Comportamentos Relacionados com a Saúde , Humanos , Funções Verossimilhança , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estresse Fisiológico , Inquéritos e Questionários , País de Gales/epidemiologia
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