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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.
Apex predators play a critical role in maintaining the health of ecosystems but are highly susceptible to habitat degradation and loss caused by land-use changes, and to anthropogenic mortality. The leopard Panthera pardus is the last free-roaming large carnivore in the Western Cape province, South Africa. During 2011–2015, we carried out a camera-trap survey across three regions covering c. 30,000 km2 of the Western Cape. Our survey comprised 151 camera sites sampling nearly 14,000 camera-trap nights, resulting in the identification of 71 individuals. We used two spatially explicit capture–recapture methods (R programmes secr and SPACECAP) to provide a comprehensive density analysis capable of incorporating environmental and anthropogenic factors. Leopard density was estimated to be 0.35 and 1.18 leopards/100 km2, using secr and SPACECAP, respectively. Leopard population size was predicted to be 102–345 individuals for our three study regions. With these estimates and the predicted available leopard habitat for the province, we extrapolated that the Western Cape supports an estimated 175–588 individuals. Providing a comprehensive baseline population density estimate is critical to understanding population dynamics across a mixed landscape and helping to determine the most appropriate conservation actions. Spatially explicit capture–recapture methods are unbiased by edge effects and superior to traditional capture–mark–recapture methods when estimating animal densities. We therefore recommend further utilization of robust spatial methods as they continue to be advanced.
Evidence regarding the seasonality of urinary tract infection (UTI) consultations in primary care is conflicting and methodologically poor. To our knowledge, this is the first study to determine whether this seasonality exists in the UK, identify the peak months and describe seasonality by age. The monthly number of UTI consultations (N = 992 803) and nitrofurantoin and trimethoprim prescriptions (N = 1 719 416) during 2008–2015 was extracted from The Health Improvement Network (THIN), a large nationally representative UK dataset of electronic patient records. Negative binomial regression models were fitted to these data to investigate seasonal fluctuations by age group (14–17, 18–24, 25–45, 46–69, 70–84, 85+) and by sex, accounting for a change in the rate of UTI over the study period. A September to November peak in UTI consultation incidence was observed for ages 14–69. This seasonality progressively faded in older age groups and no seasonality was found in individuals aged 85+, in whom UTIs were most common. UTIs were rare in males but followed a similar seasonal pattern than in females. We show strong evidence of an autumnal seasonality for UTIs in individuals under 70 years of age and a lack of seasonality in the very old. These findings should provide helpful information when interpreting surveillance reports and the results of interventions against UTI.
Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear.
We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments.
Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72–0.82] and positive predictive value of 0.76 (95% CI 0.70–0.80), the specificity of 0.29 (95% CI 0.20–0.38) and negative predictive value of 0.36 (95% CI 0.22–0.40) were low. Thus, 64% of those who scored below the AQ cut-off were ‘false negatives’ who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may ‘mimic’ ASD and inflate AQ scores, leading to false positives.
The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.
The ultimate goal of upper-limb rehabilitation after stroke is to promote real-world use, that is, use of the paretic upper-limb in everyday activities outside the clinic or laboratory. Although real-world use can be collected through self-report questionnaires, an objective indicator is preferred. Accelerometers are a promising tool. The current paper aims to explore the feasibility of accelerometers to measure upper-limb use after stroke and discuss the translation of this measurement tool into clinical practice. Accelerometers are non-invasive, wearable sensors that measure movement in arbitrary units called activity counts. Research to date indicates that activity counts are a reliable and valid index of upper-limb use. While most accelerometers are unable to distinguish between the type and quality of movements performed, recent advancements have used accelerometry data to produce clinically meaningful information for clinicians, patients, family and care givers. Despite this, widespread uptake in research and clinical environments remains limited. If uptake was enhanced, we could build a deeper understanding of how people with stroke use their arm in real-world environments. In order to facilitate greater uptake, however, there is a need for greater consistency in protocol development, accelerometer application and data interpretation.
Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.
Aim: To evaluate factors that may contribute to the decision of the consultant medical officer (CMO) to: (1) admit a person with stroke to inpatient rehabilitation from acute hospitalisation; and (2) continue or cease inpatient rehabilitation.
Methods: A web-based survey of CMOs practising in Queensland Australia, who were members of the Australian and New Zealand Society of Geriatric Medicine (n ~ 90) or the Queensland Stroke Clinical Network (n ~ 30) was completed. The survey contained two sections to explore factors that could: (1) favour or disfavour admission to inpatient rehabilitation from acute hospitalisation; and (2) favour continuation or cessation of inpatient rehabilitation. Open and closed questions were used.
Results: Twenty-one CMOs (13–20% response rate, 43% geriatrician) completed the survey. Factors related to physical function, along with the presence of social supports favoured admission, while the presence of behavioural and cognitive impairments and a lack of staff capacity disfavoured admission. Improvements in function favoured continuation of inpatient rehabilitation, while a lack of improvement favoured cessation.
Conclusion: Factors related to the patient, their social support network and the organisation were found to influence the decision of the CMO to admit a person with stroke to inpatient rehabilitation from acute hospitalisation. Once in rehabilitation, demonstration of benefit was consistently reported to indicate continued service need.
Background: To retrain upper limb function after stroke, a high dose of activity-related therapy is recommended. However, observational studies indicate that the dose undertaken is minimal. While it is speculated that those with severe disability will perform less therapy, this remains to be explored.
Objective: Quantify the dose and content of upper limb therapy performed by stroke survivors with severe upper limb disability during routine inpatient rehabilitation.
Methods: Therapy provided by physiotherapists and occupational therapists to 32 stroke survivors receiving inpatient rehabilitation over 20 weekdays was recorded. Dose of individual and group therapy was analysed by discipline and severity of upper and lower limb disability. Dose and content of individual therapy was also analysed by functional domain.
Results: On average, 46 minutes of individual and 11 minutes of group upper limb therapy were provided per participant, per day. Occupational therapists provided a higher dose of both individual and group therapy compared to physiotherapists (p < 0.0005). Findings suggest that greater residual upper and lower limb movement can lead to provision of a higher dose of activity-related therapy. Within individual therapy, a higher dose (29 versus 17 minutes, p < 0.002) and greater number (1218 versus 549) of impairment- than activity-related interventions were administered.
Conclusions: The dose of activity-related upper limb therapy provided to stroke survivors with severe disability was limited. There is a need to identify interventions and models of service delivery that can increase the intensity and appropriateness of therapy that stroke survivors with severe disability undertake during inpatient rehabilitation.
Attention deficit hyperactivity disorder (ADHD) often, but not always, persists into adulthood. Investigations of the associations between clinical and biological markers of persistence can shed light on causal pathways. It has been proposed that compensatory improvements in executive neuropsychological functioning are associated with clinical improvements. This is the first study to test this hypothesis prospectively.
The clinical and neuropsychological functioning of 17 boys with ADHD (mean age 10.45 years at time 1; 14.65 years at time 2) and 17 typically developing (TYP) boys (mean age 10.39 years at time 1; 14.47 years at time 2) was tested on two occasions, 4 years apart. This was done using a battery of standardized neuropsychological tests that included tasks with high and low executive demands.
Clinical improvements were observed over time. Neuropsychological performance improvements were also evident, with ADHD boys developing with a similar pattern to TYP boys, but with a developmental lag. Whilst there was an association between reduced symptoms and superior performance at retest for one task with a high executive demand (spatial working memory), this was not seen with two further high executive demand tasks [Stockings of Cambridge and intra-dimensional extra-dimensional (ID/ED) set shifting]. Also, there was no association between change in executive functioning and change in symptoms. Baseline performance on the ID/ED set-shifting task predicted better clinical outcome. Only change in performance on the low executive demand delayed matching-to-sample task predicted better clinical outcome.
These data highlight the importance of longitudinal measurements of cognition, symptoms and treatment response over time in children and adolescents with ADHD.
We present a general method for investigating the energetics of small impurity-vacancy clusters in crystalline materials. We use a combination of molecular dynamics and Monte Carlo methods to locate low energy configurations of the bubbles, from which the binding energies of various point defects can be determined. This method is applied to case of hydrogen bubbles in alpha-iron. Clusters with ratios of up to 10 hydrogen atoms to a vacancy are studied. We find that hydrogen does help to stabilize voids in alpha-iron, but that hydrogen is quite weakly bound to these voids. Ratios of up to approximately 4 can be supported at low temperatures.
Mental capacity is an emerging ethical legal concept in psychiatric settings but its relation to clinical parameters remains uncertain. We sought to investigate the associations of regaining capacity to make treatment decisions following approximately 1 month of in-patient psychiatric treatment.
We followed up 115 consecutive patients admitted to a psychiatric hospital who were judged to lack capacity to make treatment decisions at the point of hospitalization. We were primarily interested in whether the diagnosis of schizophrenia and schizoaffective disorder associated with reduced chances of regaining capacity compared with other diagnoses and whether affective symptoms on admission associated with increased chances of regaining capacity. In addition, we examined how change in insight was associated with regaining capacity in schizophrenia, bipolar affective disorder (BPAD)-mania, and depression.
We found evidence that the category of ‘schizophrenia or schizoaffective disorder’ associated with not regaining capacity at 1 month compared with BPAD-mania [odds ratio (OR) 3.62, 95% confidence intervals (CI) 1.13–11.6] and depression (OR 5.35, 95% CI 1.47–9.55) and that affective symptoms on admission associated with regaining capacity (OR 1.23, 95% CI 1.02–1.48). In addition, using an interaction model, we found some evidence that gain in insight may not be a good indicator of regaining capacity in patients with depression compared with patients with schizophrenia and BPAD-mania.
We suggest that clinico-ethical studies using mental capacity provide a way of assessing the validity of nosological and other clinical concepts in psychiatry.
An individual's right to self-determination in treatment decisions is a central principle of modern medical ethics and law, and is upheld except under conditions of mental incapacity. When doctors, particularly psychiatrists, override the treatment wishes of individuals, they risk conflicting with this principle. Few data are available on the views of people regaining capacity who had their treatment wishes overridden.
To investigate individuals' views on treatment decisions after they had regained capacity.
One hundred and fifteen people who lacked capacity to make treatment decisions were recruited from a sample of consecutively admitted patients to a large psychiatric hospital. After 1 month of treatment we asked the individuals for their views on the surrogate treatment decisions they received.
Eighty-three per cent (95% CI 66–93) of people who regained capacity gave retrospective approval. Approval was no different between those admitted informally or involuntarily using Mental Health Act powers (χ2 = 1.52, P = 0.47). Individuals were more likely to give retrospective approval if they regained capacity (χ2 = 14.2, P = 0.001).
Most people who regain capacity following psychiatric treatment indicate retrospective approval. This is the case even if initial treatment wishes are overridden. These findings moderate concerns both about surrogate decision-making by psychiatrists and advance decision-making by people with mental illness.
In England and Wales mental health services need to take account of the
Mental Capacity Act 2005 and the Mental Health Act 1983. The overlap
between these two causes dilemmas for clinicians.
To describe the frequency and characteristics of patients who fall into
two potentially anomalous groups: those who are not detained but lack
mental capacity; and those who are detained but have mental capacity.
Cross-sectional study of 200 patients admitted to psychiatric wards. We
assessed mental capacity using a semi-structured interview, the MacArthur
Competence Assessment Tool for Treatment (MacCAT–T).
Of the in-patient sample, 24% were informal but lacked capacity: these
patients felt more coerced and had greater levels of treatment refusal
than informal participants with capacity. People detained under the
Mental Health Act with capacity comprised a small group (6%) that was
hard to characterise.
Our data suggest that psychiatrists in England and Wales need to take
account of the Mental Capacity Act, and in particular best interests
judgments and deprivation of liberty safeguards, more explicitly than is
perhaps currently the case.
The essays in this volume stem from a very productive and rewarding public seminar held at Birkbeck College, University of London, in 2004. The seminar, entitled St Edmund: Royalty, Martyrdom, Masculinity, was sponsored by Birkbeck's School of English and Humanities but was not just focused on literary texts. The seminar brought together an exciting and diverse range of disciplines: Old and Middle English studies, Scandinavian studies, music, art history, histories of gender and sexuality, book history, theology, political history. The audience, comprising scholars, students and members of the public, likewise attested to the appeal and relevance of the saint and to the ongoing blossoming of ‘medieval studies’, broadly conceived. The essays assembled here contribute a range of readings of St Edmund's cult, from different disciplines, and also offer a kind of history of St Edmund's cult in its many different facets, from the ninth century to the early modern period.
The time-frame of this collection covers the chronological span of Edmund's medieval cult, from the murky circumstances of the saint's death and his first vita, written between 985 and 987 by Abbo of Fleury, to a life of the saint written in newly Protestant sixteenth-century England. This collection is not, however, intended to provide an exhaustive account of the cult of St Edmund; given the enormous range and reach of the cult, such would be an over-ambitious undertaking. Rather, the guiding principle to these essays is the rewritings, continuities and reconceptualisations of sanctity represented in Edmund's changing saintly image. In this way, the intention of the volume is to show the openness and dynamism of a medieval saint's cult, to demonstrate how the saint's image could be used in many and changing contexts. Edmund's image was bent to various political and propagandistic ends, negotiating identity, politics and belief. While Edmund's iconographic attributes generally remain constant – crowned or shot through with arrows – this stability belies a variety of rewritings of his life and a steady accretion of traditions and apocrypha. When we think of medieval people being devoted to a saint, we need to prompt ourselves to ask what it is that people were devoted to; the substance of devotion is not necessarily fixed or stable, and it is not easily retrievable.