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UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
The present study aims to document the developmental profile of static and dynamic acoustic features of vowel productions in monolingual Mandarin-speaking children aged between three and six years in comparison to adults. Twenty-nine monolingual Mandarin children and 12 native Mandarin adults were recorded producing ten Mandarin disyllabic words containing five monophthongal vowel phonemes /a i u y ɤ/. F1 and F2 values were measured at five equidistant temporal locations (the 20–35–50–65–80% points of the vowel's duration) and normalized. Scatter plots showed clear separations between vowel categories although the size of individual vowel categories exhibited a decreasing trend as the age increased. This indicates that speakers as young as three years old could separate these five Mandarin vowels in the acoustic space but they were still refining the acoustic properties of their vowel production as they matured. Although the tested vowels were monophthongs, they were still characterized by distinctive formant movement patterns. Mandarin children generally demonstrated formant movement patterns comparable to those of adult speakers. However, children still showed positional variation and differed from adults in the magnitudes of spectral change for certain vowels. This indicates that vowel development is a long-term process which extends beyond three years of age.
Research has documented that religious minorities often face the brunt of religious discrimination. Yet formal tests, using global collections, have been lacking. Building on the religious economy theory and recent work in law and politics, we propose that minority religions face discrimination from the state because they represent unwanted competition for the state supported religion, are viewed as a threat to the state and larger culture, and lack support from an independent judiciary. Drawing on the recently collected Religion and State-Minorities collection on more than 500 minority religions, we find support for each of the propositions, though the level of support varies based on the targets of state discrimination. In general, the support is strongest when explaining discrimination against minority religion's institutions and clergy, but weakens when explaining more general discrimination against the membership.
Rice yield improvement is required to support increasing global rice demand. However, the limited genetic diversity within the cultivated rice gene pool may be a major obstacle. Australian wild rice which has been largely genetically isolated from cultivated rice might be a new source of genetic variation for use in improving rice production. The physical properties of Oryza australiensis and of the two perennial Australian Wild rice taxa-belonging to the A genome wild rice were evaluated. Seeds collected from rice in the wild were generally smaller than those from domesticated rice. The wild rice A genome collections were classified as extra-long paddy rice with grains that were long or medium, while O. australiensis was categorized as long paddy rice with a short grain. However, these wild rices were slender compared with domesticated rice. The grain colour of these wild rices varied from light red brown to dark brown compared with domesticated rice which is brighter, with less redness and more yellowness than the wild rice. The physical characteristics of the grains of the Australian wild rice indicate that these rice grains may be successfully processed using current rice processing techniques and may be a useful novel food especially in the coloured rice market.
Understanding the origin of modern communities is a fundamental goal of ecology, but reconstructing communities with durations of 103–106 years requires data from the fossil record. Early Pliocene to latest Pleistocene faunas and sediments in the Meade Basin and modern soils and rodents from the same area are used to examine the role of environmental change in the emergence of the modern community. Paleoenvironmental proxies measured on modern surface soils and paleosols are described, and faunal dynamics of fossil rodents are discussed. Mean annual precipitation (MAP) was estimated from elemental concentrations and magnetic properties, and warm-season temperature and δ18O of soil water was estimated using carbonate isotope paleothermometry on pedogenic nodules. MAP and temperature estimates from paleosols exhibit no short-term variability, no long-term trends, and generally bracket modern values. Estimated soil water δ18O values increased through time, suggesting aridification played a role in the evolution of the regional grassland ecosystem. Carbon isotope analyses of biomarkers are used to examine the abundance of C4 grasses, which suggest more C4 biomass and more variability in C4 biomass than carbonate proxies. Rodent species richness remained constant due to balanced rates of extinction and immigration, both of which show episodic spikes consistent with a balance between forcing mechanisms that result in equilibrium on long time scales. Overall, these results suggest that different mechanisms of faunal change may be acting at different time scales, although the stratigraphic resolution of paleoenvironmental proxies needs to be increased, and body size and dietary distributions of rodents need to be determined before which processes of change are most important can be decided.
This longitudinal case study documents the emergence of bilingualism in a young monolingual Mandarin boy on the basis of an acoustic analysis of his vowel productions recorded via a picture-naming task over 20 months following his enrollment in an all-English (L2) preschool at the age of 3;7. The study examined (1) his initial L2 vowel space, (2) the process of L1-L2 separation, and (3) his L1 vowel system in relation to L2. The child initially utilized his L1 base in building the L2 vowel system. The L1-L2 separation started from a drastic restructuring of his working vowel space to create maximal contrast between the two languages. Meanwhile, L1 developmental processes and influence of L2 on L1 were also in effect. The developmental profile of this child uncovered strategies sequential bilingual children may use to restructure their phonetic space and construct a new system of contrasts in L2.
This study introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (Gershon, Wagster et al., 2013) in an adult sample. This first study in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test–retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One study in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication. (JINS, 2014, 20, 1–12)
Speech intelligibility in a multitalker background can be affected by the language of both the talker and the interfering speech. This study investigated whether this interaction is modulated by dialect variations of the same language. American English listeners were presented with target sentences in either their own General American English (GAE) or a different accent (Southern American English [SAE]) masked by either GAE or SAE two-talker babble at three sound to noise ratios (SNRs): +3, 0, and –3 dB. All speech materials were produced by male talkers. Across all conditions, SAE target was more intelligible than GAE. Intelligibility of either target decreased as the level of the interfering babble noise increased. Target accent interacted with masking accent: at +3 dB SNR, GAE (and not SAE) was the more effective masker. The target-masker interaction was different as listening conditions deteriorated: at 0 and –3 dB SNR, masking accent did not affect GAE target, but when the target was SAE, the SAE masker (and not GAE) was more effective. Thus, at increased noise levels, listeners benefited from the mismatch between the target and masking accents only when the target was in a nonnative accent. These results demonstrate that dialect variation can influence listeners’ performance in a multitalker environment. The apparent asymmetry in intelligibility of accents may be in part related to dialect-specific prosodic and phonetic features.
Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes.
To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia.
A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0–13 weeks and 0–39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods.
There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively.
In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.
The pharmacokinetics of a single I.V dose of natalizumab were studied in a phase 1, dose-escalation study in 28 multiple sclerosis (MS) patients. As part of the clinical trial program to establish the pharmacokinetic/pharmacodynamic and safety profiles of natalizumab, four Phase 1, dose-finding studies were conducted. An additional Phase 2 study was conducted to evaluate the safety and efficacy of natalizumab in combination with glatiramer acetate (GA). One of the recommendations of the therapeutics and technology assessment subcommittee of the AAN about the use of natalizumab was to carefully monitor patients receiving natalizumab to establish its long-term safety i.e. the true risk of progressive multifocal leukoencephalopathy (PML). Large Phase 3 trials of natalizumab alone or in combination with interferon (IFN)β-1a show that natalizumab reduces the progression of disability, and dramatically reduces the frequency of relapses and magnetic resonance imaging (MRI) lesion formation in patients with relapsing MS.