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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.
Objectives: Research on developmental outcomes of preterm birth has traditionally focused on adverse effects. This study investigated the prevalence and correlates of resilience in 146 extremely preterm/extremely low birth weight (EPT/ELBW) children (gestational age <28 weeks and/or birth weight <1000 g) attending kindergarten and 111 term-born normal birth weight (NBW) controls. Methods: Adaptive competence (i.e., “resilience” in the EPT/ELBW group) was defined by scores within grade expectations on achievement tests and the absence of clinically elevated parent ratings of child behavior problems. The “adaptive” children who met these criteria were compared to the “maladaptive” children who did not on child and family characteristics. Additional analyses were conducted to assess the conjoint effects of group (ELBW vs. NBW) and family factors on adaptive competence. Results: A substantial minority of the EPT/ELBW group (45%) were competent compared to a majority of NBW controls (73%), odds ratio (95% confidence interval)=0.26 (0.15, 0.45), p<.001. Adaptive competence was associated with higher cognitive skills, more favorable ratings of behavior and learning not used to define adaptive competence, and more advantaged family environments in both groups, as well as with a lower rate of earlier neurodevelopmental impairment in the EPT/ELBW group. Higher socioeconomic status and more favorable proximal home environments were associated with competence independent of group, and group differences in competence persisted across the next two school years. Conclusions: The findings document resilience in kindergarten children with extreme prematurity and highlight the role of environmental factors as potential influences on outcome. (JINS, 2019, 25, 362–374)
The physical and mechanical properties of many industrially important polymers are profoundly influenced by their degree of crystallinity; such properties include flex modulus, tensile strength, percent elongation, and impact strength. Commonly used polymers influenced by their crystallinity level include polyethlene, polypropylene, polyesters, and nylons. Many of these materials are above their glass transition temperature at room temperature and would be useless were it not for their crystalline phase which typically has a melting point far above room temperature. The crystalline ‘ regions (domains) in these materials are frequently very small, typically in the nanometer range in diameter. These crystalline domains act as reinforcing fillers (in somewhat the same manner as carbon black In rubber) and give strength to the polymer.
To assess current performance and identify opportunities and reforms necessary for positioning a food standards programme to help protect public health against dietary risk factors.
A case study design in which a food standards programme’s public health protection performance was analysed against an adapted Donabedian model for assessing health-care quality. The criteria were the food standards programme’s structure (governance arrangements and membership of its decision-making committees), process (decision-making tools, public engagement and transparency) and food standards outcomes, which provided the information base on which performance quality was inferred.
The Australia and New Zealand food standards programme.
The structure, process and outcomes of the Programme.
The Programme’s structure and processes produce food standards outcomes that perform well in protecting public health from risks associated with nutrient intake excess or inadequacy. The Programme performs less well in protecting public health from the proliferation and marketing of ‘discretionary’ foods that can exacerbate dietary risks. Opportunities to set food standards to help protect public health against dietary risks are identified.
The structures and decision-making processes used in food standards programmes need to be reformed so they are fit for purpose for helping combat dietary risks caused by dietary excess and imbalances. Priorities include reforming the risk analysis framework, including the nutrient profiling scoring criterion, by extending their nutrition science orientation from a nutrient (reductionist) paradigm to be more inclusive of a food/diet (holistic) paradigm.
The aim of this study was the construction and validation of a novel research instrument to quantify the degree of post-hurricane trauma and distress in an affected population. The Post-Hurricane Distress Scale (PHDS) has quantitative measures of both acute and prolonged distress, attributable to meteorological and hydrological disasters.
A careful evaluation of existing questionnaires, as well as extensive canvasing of the post-Maria population of Puerto Rico, availed the construction of the PHDS. The PHDS consists of 20 items, organized into 4 subscales. The PHDS was pre-validated (n=79), revised, and then distributed to a broad sampling of the post-Hurricane Maria Puerto Rican population (n=597). Validation, including factor analysis, analyses of concurrent validity, discriminant validity, and internal reliability, was performed.
After comparing various scales, factor loading profiles, concurrent validities, and models of fit, we show that the PHDS is best scored as a single 0–6 distress scale. When compared with the Traumatic Exposure Severity Scale, the PHDS shows superior concurrent validity, more accurately predicting scores for the Peritraumatic Distress Inventory, Impact of Event Scale – Revised, and Generalized Anxiety Disorder 7 Scale. The PHDS shows good internal reliability and discriminant validity.
The PHDS represents a novel, useful instrument for disaster first-responders and researchers. The prompt identification of high-risk populations is possible using this instrument. (Disaster Med Public Health Preparedness. 2019;13:82-89)
More than 1 million tons of oil is inadvertently spilled each year. The economic and environmental costs of these spills are enormous and compel further development of environmentally friendly sorbent materials. Here, we demonstrate a vapor-phase modification approach to create a new class of oil sorbents composed of cellulosic materials (cotton) coated with a subnanometer layer of inorganic oxide. This new cellulosic sorbent remains buoyant in water indefinitely and achieves a selective oil sorption capacity (23 g/g or 1.05 g/cm3) that is at least 35 times better than untreated cellulose in aqueous environments. This new sorbent particularly excels under “realistic” conditions such as continuous agitation (e.g., simulated waves) and presoaking in water (e.g., rain or forced immersion). When sorption performance is compared on a per-volume basis—which better captures use conditions than a per-mass basis—this modified natural product becomes comparable to the best sorbents reported in the literature.
Health technology assessments (HTA) for combination drug therapies in oncology are increasingly common. Companies face multiple challenges when determining their economic value due to their complexity and high cost, while payers must balance the need for these vital innovations with sensitivity to rising costs. The study objective was to evaluate the current HTA frameworks in Europe and identify the potential barriers/solutions to reimbursement of brand-on-brand (BoB) combination therapy.
A targeted literature review of HTA agency websites was undertaken to identify any literature/guidance relating to HTA decision-making for combination oncology therapies in France, Germany, Sweden, and the UK.
In France and the UK, BoB HTA decisions reflect clinical- and cost-effectiveness. Combination therapies have been accepted for use in France and the UK, for example, dabrafenib plus trametinib, are assessed through standard HTA processes, exemplifying that positive reimbursement is not unattainable where there is an unmet need and high clinical value. Despite this flexibility, many therapies will fail to prove their cost-effectiveness, resulting in delays or arbitrary pricing decisions. Potential solutions are the use of the ‘efficiency frontier’, as typified by the German HTA system, giving more ‘scope‘ to expensive innovations; or the Swedish HTA approach, which applies variable cost-effectiveness thresholds according to therapeutic area, disease severity, and social criteria. Other possibilities include indication-specific pricing, multiple-criteria decision analysis, and net monetary benefit with willingness-to-trade weights. One likely issue to arise is when different companies are involved, necessitating co-operation. In this scenario, a simplistic solution would be arbitration of the division of the combined price, circumventing the need for HTA agencies to make changes to decision-making criteria.
Constructive debates and collaboration between industry and decision-makers are vital to achieve a harmonized HTA process for high-cost combination therapies which offer advanced benefits and improved safety outcomes, whilst satisfying HTA bodies and providing better access for patients.
For patients with bifascicular block and syncope of unknown origin, different American Heart Association guidelines give Class 2A recommendations for two treatments: the implantable loop recorder (ILR) and empiric pacemaker insertion (PM). Equipoise reflected in guidelines may contribute to uncertainty in management and inefficient resource use. The objective of this analysis is to determine the cost-effectiveness of ILR compared to PM in the management of older adults (age>50 years) with bifascicular block and syncope over two years, from the perspective of a Canadian publicly funded health care system, in the Syncope: Pacing or Recording In ThE Later Years (SPRITELY) trial.
Resource utilization data was collected throughout the trial, and unit costs were assigned (2017 Canadian dollars). Utility was measured at baseline and annually with the EQ-5D-3L. Quality adjusted life years (QALYs) were calculated as area-under-the-curve, and adjusted for baseline imbalances in utility. Confidence intervals for the incremental cost effectiveness ratio were generated with non-parametric bootstrapping.
Mean cost in participants randomized to PM was CAD 9,759 (USD 7,400), compared to CAD 13,453 (USD 10,200) in participants randomized to ILR. The ILR strategy resulted in 0.020 QALYs more than the PM strategy. The incremental cost effectiveness ratio was CAD 186,553 (95% CI: −831,950–1,191,816) (USD 141,900, 95% CI: −632,740–906,440) per additional QALY. In 1,000 bootstrapped replicates, the cost of the ILR strategy was always greater than that of the PM strategy. At the threshold of CAD 50,000 (USD 38,000) per additional QALY, the probability that the ILR strategy is the cost effective option is 0.504.
ILR costs were greater than PM costs, with little difference in QALY outcomes over two-years. Findings are generalizable to patients similar to SPRITELY participants, from the perspective of the Canadian health care system. However, practice pattern variation and payment systems inhibit generalizability to other countries. Future analysis will explore cost and QALY outcomes in countries that participated in the SPRITELY trial.