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UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
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.
An abstract system of congruences describes a way of partitioning a space into finitely many pieces satisfying certain congruence relations. Examples of abstract systems of congruences include paradoxical decompositions and
-divisibility of actions. We consider the general question of when there are realizations of abstract systems of congruences satisfying various measurability constraints. We completely characterize which abstract systems of congruences can be realized by nonmeager Baire measurable pieces of the sphere under the action of rotations on the
-sphere. This answers a question by Wagon. We also construct Borel realizations of abstract systems of congruences for the action of
. The combinatorial underpinnings of our proof are certain types of decomposition of Borel graphs into paths. We also use these decompositions to obtain some results about measurable unfriendly colorings.
Background: Adults are at risk of being exposed to influenza from many sources. Healthcare personnel (HCP) have the additional risk of being exposed to ill patients.
To determine whether HCP were at higher risk than adults working in nonhealthcare roles (non-HCP).
Prospective cohort study.
Acute-care hospitals and other businesses in Toronto, Ontario, Canada.
Adults aged 18–69 years were enrolled for 1 or more of the 2010/2011, 2011/2012, and 2012/2013 influenza seasons. Swabs collected during acute respiratory illnesses were tested for influenza and pre- and postseason blood samples were tested for influenza-specific immune response.
The adjusted odds of influenza were similar for HCP and non-HCP (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.63–2.63). Older adults and those vaccinated against influenza had lower odds, and those who shared their workspace and who used corrective eyewear had higher odds of influenza.
HCP and other working adults are at similar risk of influenza infection.
Parasitism can affect every aspect of wildlife ecology, from predator avoidance and competition for food to migrations and reproduction. In the wild, these ecological effects can have implications for host fitness and parasite dynamics. In contrast, domestic environments are typically characterised by high host densities, low host diversity, and veterinary interventions, and are not subject to processes like predation, competition, and migration. When wild and domesticated hosts interact via shared parasite populations, understanding and predicting the outcomes of parasite ecology and evolution for wildlife conservation and sustainable farming can be a challenge. We describe the ecology and evolution of ectoparasitic sea lice that are shared by farmed and wild salmon and the insights that experiments, fieldwork, and mathematical modelling have generated for theory and applied problems of host–parasite interactions over the course of a long-term study in Pacific Canada. The salmon–sea lice host–parasite system provides a rich case study to examine the ecological context of host–parasite interactions and to shed light on the principal challenges of parasite management for wildlife health and conservation.
Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.
Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman’s test.
Median age at echocardiogram was 4.6 (range 2.5–7.4) months. Median ventricular end-diastolic pressure was 7 (range 3–19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range −35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = −0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure.
In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.
Use of the herbicide atrazine (ATR) is banned in the European Union; yet, it is still widely used in the USA and Australia. ATR is known to alter testosterone and oestrogen production and thus reproductive characteristics in numerous species. In this proof of concept study, we examined the effect of ATR exposure, at a supra-environmental dose (5 mg/kg bw/day), beginning on E9.5 in utero, prior to sexual differentiation of the reproductive tissues, until 26 weeks of age, on the development of the mouse penis. Notably, this is the first study to specifically investigate whether ATR can affect penis characteristics. We show that ATR exposure, beginning in utero, causes a shortening (demasculinisation) of penis structures and increases the incidence of hypospadias in mice. These data indicate the need for further studies of ATR on human reproductive development and fertility, especially considering its continued and widespread use.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
The purpose of this study was to examine whether vehicle type based on size (car vs. other = truck/van/SUV) had an impact on the speeding, acceleration, and braking patterns of older male and female drivers (70 years and older) from a Canadian longitudinal study. The primary hypothesis was that older adults driving larger vehicles (e.g., trucks, SUVs, or vans) would be more likely to speed than those driving cars. Participants (n = 493) had a device installed in their vehicles that recorded their everyday driving. The findings suggest that the type of vehicle driven had little or no impact on per cent of time speeding or on the braking and accelerating patterns of older drivers. Given that the propensity for exceeding the speed limit was high among these older drivers, regardless of vehicle type, future research should examine what effect this behaviour has on older-driver road safety.
Healthcare workers (HCWs) are at risk of acquiring and transmitting respiratory viruses while working in healthcare settings.
To investigate the incidence of and factors associated with HCWs working during an acute respiratory illness (ARI).
HCWs from 9 Canadian hospitals were prospectively enrolled in active surveillance for ARI during the 2010–2011 to 2013–2014 influenza seasons. Daily illness diaries during ARI episodes collected information on symptoms and work attendance.
At least 1 ARI episode was reported by 50.4% of participants each study season. Overall, 94.6% of ill individuals reported working at least 1 day while symptomatic, resulting in an estimated 1.9 days of working while symptomatic and 0.5 days of absence during an ARI per participant season. In multivariable analysis, the adjusted relative risk of working while symptomatic was higher for physicians and lower for nurses relative to other HCWs. Participants were more likely to work if symptoms were less severe and on the illness onset date compared to subsequent days. The most cited reason for working while symptomatic was that symptoms were mild and the HCW felt well enough to work (67%). Participants were more likely to state that they could not afford to stay home if they did not have paid sick leave and were younger.
HCWs worked during most episodes of ARI, most often because their symptoms were mild. Further data are needed to understand how best to balance the costs and risks of absenteeism versus those associated with working while ill.
While rhenium has proven to be an ideal material in fast-cycling high-temperature applications such as rocket nozzles, its prohibitive cost limits its continued use and motivates a search for viable cost-effective substitutes. We show that a simple design principle that trades off average valence electron count and cost considerations proves helpful in identifying a promising pool of candidate substitute alloys: The Mo–Ru–Ta–W quaternary system. We demonstrate how this picture can be combined with a computational thermodynamic model of phase stability, based on high-throughput ab initio calculations, to further narrow down the search and deliver alloys that maintain rhenium’s desirable hcp crystal structure. This thermodynamic model is validated with comparisons to known binary phase diagram sections and corroborated by experimental synthesis and structural characterization demonstrating multiprinciple-element hcp solid-solution samples selected from a promising composition range.
In 1918 Charles Gore, the bishop of Oxford, issued queries preparatory to an episcopal visitation, including a series of questions about the future of church schools and religious education more generally. Coming some sixteen years after the restructuring of the dual system of state- and church-supported education by the Balfour Education Act of 1902, this material yields valuable insights into the views of approximately six hundred clergy regarding the successes and dysfunctions of the system at parish level. Set within the context of recent historiography on the trajectory of English Christianity in the1920s, this article uses this material to discuss the clergy's views on the value and purposes of school-based religious education, the prospects for sustaining these after almost four years of war and the compromises that might be required in order to preserve them.
This article discusses the impact of the educational method pioneered in the English public schools on the development of education in Anglican schools in the British empire, with a particular focus on the Indian subcontinent from the turn of the twentieth century until the outbreak of the First World War. It discusses how the focus of missionary activity changed from a desire for overt evangelism into a sense of the transmission of moral and ethical values though a system of education in the Christian virtues. An educational understanding of salvation began to supplant the doctrinal. This is connected with the thinking on ‘higher’ and ‘lower’ civilizations of the period. A central focus is on the preparatory work for, and discussions around, the Pan-Anglican Congress of 1908 and the role played by Bishop H. H. Montgomery.
To identify, in caregivers of patients with Alzheimer’s disease (AD) dementia, factors associated with subjective (personal, physical, emotional, and social) and objective (informal caregiver time and costs) caregiver burden.
Prospective longitudinal European observational study: post-hoc analysis.
Community-dwelling patients in France and Germany aged ≥ 55 years (n = 969) with probable AD and their informal caregivers.
Mini-Mental State Examination (MMSE), Alzheimer’s Disease Cooperative Study—Activities of Daily Living (ADCS-ADL), 12-item Neuropsychiatric Inventory (NPI-12), Zarit Burden Interview (ZBI), informal caregiver basic and instrumental ADL hours (Resource Utilization in Dementia instrument), and informal caregiver costs. Mixed-effect models of repeated measures (MMRM) were run, including baseline and time-dependent covariates (change from baseline [CFB] to 18 months in MMSE, ADCS-ADL, and NPI-12 scores) associated with CFB in ZBI score/informal caregiver time over 36 months (analyzed using linear regression models) and informal caregiver costs over 36 months (analyzed using generalized linear models).
Greater decline in patient function (ADCS-ADL) over 18 months was associated with increased subjective caregiver burden (ZBI), hours, and costs over 36 months. Increased behavioral problems (NPI-12) over 18 months also negatively impacted ZBI. Cognitive decline (MMSE) over 18 months did not affect change in caregiver burden.
Long-term informal caregiver burden was driven by worsening functional abilities and behavioral symptoms but not cognitive decline, over 18 months in community-dwelling patients with AD dementia. Identifying the drivers of caregiver burden could highlight areas in which interventions may benefit both caregivers and patients.
Process mining, a branch of data science, aims at deriving an understanding of process behaviors from data collected during executions of the process. In this study, we apply process mining techniques to examine retrieval and transport of road trauma patients in Queensland. Specifically, we use multiple datasets collected from ground and air ambulance, emergency department, and hospital admissions to investigate the various patient pathways and transport modalities from accident to definitive care.
The project aims to answer the question, “Are we providing the right level of care to patients?” We focus on (i) automatically discovering, from historical records, the different care and transport processes, and (ii) identifying and quantifying factors influencing deviance from standard processes, e.g. mechanisms of injury and geospatial (crash and trauma facility) considerations.
We adapted the Cross-Industry Standard Process for Data Mining methodology to Queensland Ambulance Service, Retrieval Services Queensland (aero-medical), and Queensland Health (emergency department and hospital admissions) data. Data linkage and “case” definition emerged as particular challenges. We developed detailed data models, conduct a data quality assessment, and preliminary process mining analyses.
Preliminary results only with full results are presented at the conference. A collection of process models, which revealed multiple transport pathways, were automatically discovered from pilot data. Conformance checking showed some variations from expected processing. Systematic analysis of data quality allowed us to distinguish between systemic and occasional quality issues, and anticipate and explain certain observable features in process mining analyses. Results will be validated with domain experts to ensure insights are accurate and actionable.
Preliminary analysis unearthed challenging data quality issues that impact the use of historical retrieval data for secondary analysis. The automatically discovered process models will facilitate comparison of actual behavior with existing guidelines.