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Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
We first published on the subject of pregnancy management via fetal reduction (FR) 30 years ago . Dramatic changes have occurred in medical technology, outcomes, and patient choices – large demographic and cultural shifts that have driven the pace and direction of progress and research [2, 3].
Three new Llandovery (early Silurian) crinoids from Estonia provide an improved understanding of the paleogeographic aspects of the crinoid diversification following the end-Ordovician extinctions. The new taxa are Euspirocrinus hintsae new species (Rhuddanian eucladid), Oepikicrinus perensae new genus new species (Aeronian camerate), and Rozhnovicrinus isakarae new genus new species (Aeronian eucladid). This brings the total of described Llandovery crinoids in Estonia to eight nominal species and a further three taxa in open nomenclature. The Rhuddanian radiation in Baltica mirrored that on Laurentia and Avalonia and was dominated by Ordovician clades that continued to diversify during the Silurian. Known Aeronian crinoids from Estonia continue these clades, whereas new clades diversified on Laurentia and Avalonia. However, by the Wenlock, a largely cosmopolitan fauna existed on Laurentia, Avalonia, and Baltica.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
The Kalana Lagerstätte of early Aeronian (Llandovery, Silurian) age in central Estonia preserves a diverse shallow marine biota dominated by non-calcified algae. This soft-tissue flora and decalcified and calcified crinoids are preserved in situ, in a lens of microlaminated, dolomitized micrite interbedded in a sequence of dolomitized packstones and wackestones. Although the Lagerstätte is dominated by non-calcified algae, crinoids (together with brachiopods and gastropods) are among the most common organisms that were originally comprised of a carbonate skeleton. Two new crinoids are described from this unit, Kalanacrinus mastikae n. gen. n. sp. (large camerate) and Tartucrinus kalanaensis n. gen. n. sp. (small disparid). Interestingly, these two crinoids display contrasting preservation, with the more common large camerate preserved primarily as a decalcified organic residue, whereas the smaller disparid is preserved primarily in calcite. Preservation was assessed using elemental mapping of C, Ca, S, and Si. Columns have the highest portion of Ca, once living soft tissue is indicated by C, S was dispersed as pyrite or associated with organics, and Si is probably associated with clay minerals in the matrix. This new fauna increases our understanding of the crinoid radiation on Baltica following Late Ordovician extinctions.
Compulsory admission is commonly regarded as necessary and justified for patients whose psychiatric condition represents a severe danger to themselves and others. However, while studies on compulsory admissions have reported on various clinical and social outcomes, little research has focused specifically on dangerousness, which in many countries is the core reason for compulsory admission.
To study changes in dangerousness over time in adult psychiatric patients admitted by compulsory court order, and to relate these changes to these patients' demographic and clinical characteristics.
In this explorative prospective observational cohort study of adult psychiatric patients admitted by compulsory court order, demographic and clinical data were collected at baseline. At baseline and at 6 and 12 month follow-up, dangerousness was assessed using the Dangerousness Inventory, an instrument based on the eight types of dangerousness towards self or others specified in Dutch legislation on compulsory admissions. We used descriptive statistics and logistic regression to analyse the data.
We included 174 participants with a court-ordered compulsory admission. At baseline, the most common dangerousness criterion was inability to cope in society. Any type of severe or very severe dangerousness decreased from 86.2% at baseline to 36.2% at 6 months and to 28.7% at 12 months. Being homeless at baseline was the only variable which was significantly associated with persistently high levels of dangerousness.
Dangerousness decreased in about two-thirds of the patients after court-ordered compulsory admission. It persisted, however, in a substantial minority (approximately one-third).
Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
Background: Two ‘sibling’ disorders have been proposed for the fourthcoming 11th version of the International Classification of Diseases (ICD-11): post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD). Examining psychological factors that may be associated with CPTSD, such as self-compassion, is an important first step in its treatment that can inform consideration of which problems are most salient and what interventions are most relevant. Aims: We set out to investigate the association between self-compassion and the two factors of CPTSD: the PTSD factor (re-experiencing, avoidance, sense of threat) and the Disturbances in Self-Organization (DSO) factor (affect dysregulation, negative self-concept and disturbances in relationships). We hypothesized that self-compassion subscales would be negatively associated with both PTSD and DSO symptom clusters. Method: A predominantly female, clinical sample (n = 106) completed self-report scales to measure traumatic life events, ICD-11 CPTSD and self-compassion. Results: Significant negative associations were found between the CPTSD DSO clusters of symptoms and self-compassion subscales, but not for the PTSD ones. Specifically it was also found that self-judgement and common humanity significantly predicted hypoactive affect dysregulation whereas self-judgement and isolation significantly predicted negative self-concept. Conclusions: Our results indicate that self-compassion may be a useful treatment target for ICD-11 CPTSD, particularly for symptoms of negative self-concept and affect dysregulation. Future research is required to investigate the efficacy and acceptability of interventions that have implicit foundations on compassion.
Before wastewaters can be released into the environment, they must be treated to reduce the concentration of organic pollutants in the effluent stream. There is a growing concern as to whether wastewater treatment plants are able to effectively reduce the concentration of micropollutants that are also contained in their influent streams. We investigate the removal of micropollutants in treatment plants by analysing a model that includes biodegradation and sorption as the main mechanisms of micropollutant removal. For the latter a linear adsorption model is used in which adsorption only occurs onto particulates.
The steady-state solutions of the model are found and their stability is determined as a function of the residence time. In the limit of infinite residence time, we show that the removal of biodegradable micropollutants is independent of the processes of adsorption and desorption. The limiting concentration can be decreased by increasing the concentration of growth-related macropollutants. Although, in principle, it is possible that the concentration of micropollutants is minimized at a finite value of the residence time, this was found not to be the case for the particular biodegradable micropollutants considered.
For nonbiodegradable pollutants, we show that their removal is always optimized at a finite value of the residence time. For finite values of the residence time, we obtain a simple condition which identifies whether biodegradation is more or less efficient than adsorption as a removal mechanism. Surprisingly, we find that, for the micropollutants considered, adsorption is always more important than biodegradation, even when the micropollutant is classified as being highly biodegradable with low adsorption.
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.
Over a century ago microfaunal diversity was first recorded by James Murray in lakes at Cape Royds, Ross Island, Antarctica. The report stands as the seminal study for today’s biodiversity investigations, and as a baseline to evaluate changes in faunal communities and introductions. In the present study, Cape Royds lakes were revisited and the mitochondrial c oxidase subunit I (COI) gene and morphology were used to compare diversity of Rotifera, Tardigrada and Nematoda with the records Murray published in the early 1900s. Cyanobacterial mats and the water column were sampled for microfauna from the five largest lakes using methods described by Murray. Across all five lakes similar patterns were observed for species distribution of all three phyla reported by Murray over 100 years ago. Some changes in species assemblages were identified within and between lakes, but there were no new introductions of named species for the Cape Royds region. Some of the species included by Murray in his monograph have been recently redescribed as Antarctic endemics, but others still retain their original name from the Northern Hemisphere holotypes and are also in need of revision to adequately determine the true endemism for these faunal groups.
The decrease in quality of Australian iron ore, coupled with the demand for more efficient energy use, means that closer monitoring and optimisation of process conditions for iron ore sinter production is required. Here, the suitability of using partial least-squares regression analysis of powder X-ray diffraction data, collected for iron ore sinter samples, for the prediction of iron ore sinter strength has been further assessed. In addition, a preliminary assessment of the effect of 2θ range on the quality of prediction has been made. For the purposes of process control, the level of correlation between predicted strength and actual sinter strength would inform an operator whether or not the process was operating within the acceptable limits, or whether there was a potential problem requiring further investigation or rapid intervention. Reducing the 2θ range was found to reduce the level of correlation between predicted and actual strength, to a point where the particular analysis may no longer be suitable for process control.
During the years 1814–1819, William Higgins, an Irish chemist who worked at the Dublin Society, claimed he had anticipated John Dalton in developing the atomic theory and insinuated that Dalton was a plagiarist. This essay focuses not on William Higgins, but on his uncle Bryan Higgins, a well-known chemist of his day, who had developed his own theories of caloric and chemical combination, similar in many respects to that of Dalton. New evidence is first introduced addressing Bryan's disappearance from the scientific community after 1803. In his later years, Bryan apparently suffered from a condition resulting in a decline in his mental health, which explains why he never lodged any priority claims of his own against Dalton, or defended those of his nephew. Dalton's mention of Bryan's name in Part II of A New System of Chemical Philosophy, his laboratory notebook entries, and a fresh look at his correspondence with chemist Thomas Charles Hope indicate that Dalton adopted a Higgins-like caloric model in 1803. Together these factors provide evidence to support the argument that Dalton learned of Bryan's theories via a meeting he had with William Allen on 10 July 1803. Existing evidence related to the origin of the atomic theory is worthy of re-examination in light of Dalton's possible prior knowledge of Bryan's work.
The thermal decomposition of mill scale, and the effect of mill scale addition on the formation and decomposition of Silico-Ferrite of Calcium and Aluminium (SFCA) and SFCA-I iron ore sinter bonding phases, has been investigated using in situ X-ray diffraction. Application of the external standard method of quantitative phase analysis of the in situ data collected during decomposition of the mill scale highlighted the applicability of this method for the determination of the nature and abundance of amorphous material in a mineral sample. Increasing mill scale addition from 2.6 to 10.6 and to 21.2 wt% in an otherwise synthetic sinter mixture composition designed to form SFCA did not significantly affect the thermal stability ranges of SFCA-I or SFCA, nor did it significantly affect the amount of each of SFCA or SFCA-I, which formed. This was attributed to the low impurity (i.e. Mn, Mg) concentration in the mill scale, and also the transformation to hematite during heating of the wüstite and magnetite present in the mill scale, with the hematite available for reaction to form SFCA and SFCA-I.
Water samples taken from extracorporeal membrane oxygenator (ECMO) devices used at University Hospitals Birmingham yielded high total viable counts (TVCs) containing a variety of microorganisms, including M. chimaera. Disinfection resulted in the reduction of TVCs and eradication of Mycobacterium chimaera. Weekly disinfection and water sampling are required to manage the water quality in these devices.