51 research outputs found

    The transient response of ice volume to orbital forcing during the warm Late Pliocene

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    Examining the nature of ice sheet and sea level response to past episodes of enhanced greenhouse gas forcing may help constrain future sea level change. Here, for the first time, we present the transient nature of ice sheets and sea level during the late Pliocene. The transient ice sheet predictions are forced by multiple climate snapshots derived from a climate model set up with late Pliocene boundary conditions, forced with different orbital forcing scenarios appropriate to two Marine Isotope Stages (MISs), MIS KM5c, and K1. Our results indicate that during MIS KM5c both the Antarctic and Greenland ice sheets contributed to sea level rise relative to present and were relatively stable. Insolation forcing between the hemispheres was out of phase during MIS K1 and led to an asynchronous response of ice volume globally. Therefore, when variations of precession were high, inferring the behavior of ice sheets from benthic isotope or sea level records is complex

    Psychosis and the level of mood incongruence in Bipolar Disorder are related to genetic liability for Schizophrenia

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    Abstract Importance Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms. Objectives To investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and level of mood-incongruent psychotic features. Design Case-control design: using multinomial logistic regression, to estimate differential associations of PRS across categories of cases and controls. Settings & Participants 4399 BDcases, mean [sd] age-at-interview 46[12] years, of which 2966 were woman (67%) from the BD Research Network (BDRN) were included in the final analyses, with data for 4976 schizophrenia cases and 9012 controls from the Type-1 diabetes genetics consortium and Generation Scotland included for comparison. Exposure Standardised PRS, calculated using alleles with an association p-value threshold < 0.05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, adjusted for the first 10 population principal components and genotyping-platform. Main outcome measure Multinomial logit models estimated PRS associations with BD stratified by (1) Research Diagnostic Criteria (RDC) BD subtypes (2) Lifetime occurrence of psychosis.(3) Lifetime mood-incongruent psychotic features and (4) ordinal logistic regression examined PRS associations across levels of mood-incongruence. Ratings were derived from the Schedule for Clinical Assessment in Neuropsychiatry interview (SCAN) and the Bipolar Affective Disorder Dimension Scale (BADDS). Results Across clinical phenotypes, there was an exposure-response gradient with the strongest PRS association for schizophrenia (RR=1.94, (95% C.I. 1.86, 2.01)), then schizoaffective BD (RR=1.37, (95% C.I. 1.22, 1.54)), BD I (RR= 1.30, (95% C.I. 1.24, 1.36)) and BD II (RR=1.04, (95% C.I. 0.97, 1.11)). Within BD cases, there was an effect gradient, indexed by the nature of psychosis, with prominent mood-incongruent psychotic features having the strongest association (RR=1.46, (95% C.I. 1.36, 1.57)), followed by mood-congruent psychosis (RR= 1.24, (95% C.I. 1.17, 1.33)) and lastly, BD cases with no history of psychosis (RR=1.09, (95% C.I. 1.04, 1.15)). Conclusion We show for the first time a polygenic-risk gradient, across schizophrenia and bipolar disorder, indexed by the occurrence and level of mood-incongruent psychotic symptoms

    Predictors of patterns of change in health-related quality of life in older women over 7 years: evidence from a prospective cohort study.

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    BACKGROUND: the evaluation of the determinants of change over time in health-related quality of life (HR-QoL) in older people is limited. This study aims to identify patterns of change in HR-QoL over 7 years and their determinants using data from the British Women's Heart and Health Study, a representative sample of older women (n = 4286). METHODS: longitudinal latent class analysis was used to identify subpopulations of women with similar HR-QoL trajectories from 1999-2000 to 2007. HR-QoL was measured using the EQ-5D. Multivariate multinomial logistic regression was used to model the association of identified trajectories with baseline predictors after multiple imputation of missing data. RESULTS: four distinct EQ-5D trajectories were suggested: high (19% of women), high decline (22%), intermediate (42%) and low decline (16%). Prevalent arthritis (OR = 13.4; 95% CI: 8.8, 20.5), diabetes (OR = 4.6; 95% CI: 1.5, 14.2) and obesity (OR = 3.9; 95% CI: 2.5, 6.0) were the strongest predicting health conditions of adverse changes in HR-QoL and physical activity the strongest predicting lifestyle factor (OR = 2.8; 95% CI: 2.0, 3.9). CONCLUSIONS: findings suggest that older women without obesity or pre-existing health conditions who undertake more physical activity are more likely to experience high HR-QoL, reinforcing the importance of these factors for healthy ageing

    A re-randomisation design for clinical trials

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    Background: Recruitment to clinical trials is often problematic, with many trials failing to recruit to their target sample size. As a result, patient care may be based on suboptimal evidence from underpowered trials or non-randomised studies. Methods: For many conditions patients will require treatment on several occasions, for example, to treat symptoms of an underlying chronic condition (such as migraines, where treatment is required each time a new episode occurs), or until they achieve treatment success (such as fertility, where patients undergo treatment on multiple occasions until they become pregnant). We describe a re-randomisation design for these scenarios, which allows each patient to be independently randomised on multiple occasions. We discuss the circumstances in which this design can be used. Results: The re-randomisation design will give asymptotically unbiased estimates of treatment effect and correct type I error rates under the following conditions: (a) patients are only re-randomised after the follow-up period from their previous randomisation is complete; (b) randomisations for the same patient are performed independently; and (c) the treatment effect is constant across all randomisations. Provided the analysis accounts for correlation between observations from the same patient, this design will typically have higher power than a parallel group trial with an equivalent number of observations. Conclusions: If used appropriately, the re-randomisation design can increase the recruitment rate for clinical trials while still providing an unbiased estimate of treatment effect and correct type I error rates. In many situations, it can increase the power compared to a parallel group design with an equivalent number of observations

    Rating the methodological quality in systematic reviews of studies on measurement properties: a scoring system for the COSMIN checklist

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    Background: The COSMIN checklist is a standardized tool for assessing the methodological quality of studies on measurement properties. It contains 9 boxes, each dealing with one measurement property, with 5-18 items per box about design aspects and statistical methods. Our aim was to develop a scoring system for the COSMIN checklist to calculate quality scores per measurement property when using the checklist in systematic reviews of measurement properties. Methods: The scoring system was developed based on discussions among experts and testing of the scoring system on 46 articles from a systematic review. Four response options were defined for each COSMIN item (excellent, good, fair, and poor). A quality score per measurement property is obtained by taking the lowest rating of any item in a box ("worst score counts"). Results: Specific criteria for excellent, good, fair, and poor quality for each COSMIN item are described. In defining the criteria, the "worst score counts" algorithm was taken into consideration. This means that only fatal flaws were defined as poor quality. The scores of the 46 articles show how the scoring system can be used to provide an overview of the methodological quality of studies included in a systematic review of measurement properties. Conclusions: Based on experience in testing this scoring system on 46 articles, the COSMIN checklist with the proposed scoring system seems to be a useful tool for assessing the methodological quality of studies included in systematic reviews of measurement properties. © The Author(s) 2011

    Parental influences on children's eating behaviour and characteristics of successful parent-focussed interventions

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    Parental reports suggest that difficulties related to child-feeding and children's eating behaviour are extremely common. While 'fussy eating' does not pose an immediate threat to health, over the long-term, consumption of a poor diet can contribute to the development of a range of otherwise preventable diseases. In addition, the stress and anxiety that can surround difficult mealtimes can have a detrimental impact upon both child and parental psychological wellbeing. Since parents have a great influence over what, when, and how much food is offered, feeding difficulties may be preventable by better parental awareness. The aim of this review is to describe how parental factors contribute to the development of common feeding problems, and to discuss the merits of existing interventions aimed at parents/primary caregivers to improve child-feeding and children's eating behaviour. The potential for different technologies to be harnessed in order to deliver interventions in new ways will also be discussed

    The status of the world's land and marine mammals: diversity, threat, and knowledge

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    Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action

    The wide-field, multiplexed, spectroscopic facility WEAVE : survey design, overview, and simulated implementation

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    Funding for the WEAVE facility has been provided by UKRI STFC, the University of Oxford, NOVA, NWO, Instituto de Astrofísica de Canarias (IAC), the Isaac Newton Group partners (STFC, NWO, and Spain, led by the IAC), INAF, CNRS-INSU, the Observatoire de Paris, Région Île-de-France, CONCYT through INAOE, Konkoly Observatory (CSFK), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Lund University, the Leibniz Institute for Astrophysics Potsdam (AIP), the Swedish Research Council, the European Commission, and the University of Pennsylvania.WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959 nm at R ∼ 5000, or two shorter ranges at R ∼ 20,000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∼ 3 million stars and detailed abundances for ∼ 1.5 million brighter field and open-cluster stars; (ii) survey ∼ 0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey  ∼ 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z 1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.PostprintPeer reviewe
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