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Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD.
Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457–14,836, age 45–81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use.
Lifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7 × 10−5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5 × 10−5).
Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.
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 Atlantic Sea Scallop fishery has grown tremendously over the past twenty years. The location and magnitude of harvestable biomass fluctuates dramatically due to both natural variation and the explicitly spatial management system designed to allow small individuals to grow larger and more valuable. These fluctuations in natural advantages can have profound effects on fishing ports. We use methods from economic growth literature to show that ports with lower initial scallop landings have grown the fastest. Furthermore, good access to biomass influences long-run changes in landings, although this effect exhibits considerable variability across ports. We also find evidence of returns to scope, suggesting that ports with other fishing activities could be well positioned to attract new scalloping activity when stock conditions are favorable. Further investigation of the largest ports using time-series methods also shows a high degree of variability; there are long-run relationships between scallop fishing and harvestable scallop stock in some ports, short-run relationships in some ports, and no relationship between the two in others. We interpret this as evidence that heterogeneity in the natural productivity of the ocean combined with explicitly spatial fisheries management has induced a spatial component to the port-level response to changes in biomass availability.
Recent progress in semiconductor materials with minor nonradiative recombination has stimulated investigations of novel photovoltaic (PV) converters with optical control of radiative emission. Angle restricted emission was experimentally demonstrated in PV devices with external photon recycling due to specific photonic crystals or mirrors. In this work we investigate the power beam conversion by the cell with front “greenhouse” filter, which transmits the laser light, but recycles the low energy bandgap quanta emitted by the semiconductor cell. We calculate the limiting characteristics of the greenhouse PV converters and optimize design of the converter taking into account the nonradiative recombination processes. In optimized devices addition of the greenhouse filter can increase power beam conversion efficiency by several percent.
We leverage innovative spatial modeling techniques and data on the
precise geo-locations of more than 32,000 Constituency Development
Fund (CDF) projects in Kenya to test whether Members of Parliament
(MPs) reward their supporters. We find only weak evidence that MPs
channel projects disproportionately to areas inhabited by their
political allies, once we control for other factors that affect
where projects are placed, such as population density, poverty
rates, ethnic demographics, and distance to paved roads.
Notwithstanding this result, we find evidence for cross-constituency
variation in political targeting, driven in large part by the
spatial segregation of the MP’s supporters and opponents. Our
findings challenge the conventional wisdom about the centrality of
clientelistic transfers in Africa and underscore how local
conditions generate particular incentives and opportunities for the
strategic allocation of political goods. We also highlight the
benefits and challenges of analyzing allocations at the project
level rather than aggregated to the administrative unit.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
During the last 30 years, economic and social historians have collected and analyzed large amounts of anthropometric data to explore key aspects of the human past. Attention has also been devoted to the examination of factors that can exert an influence on stature. This article outlines the different ways in which climate might influence stature, either directly or indirectly. It then uses geographical information system software to explore the relationship between variations in temperature and precipitation and the average heights of men in France, India, Mexico, Spain, and the United States over the last two centuries. It is possible to observe an influence of climate on stature in some countries, especially during the nineteenth century, but the relationship weakens across time and largely disappears in recent decades. The attenuation of this relationship is attributed to a process of “technophysio evolution” as countries modernized and developed economically.
The Canadian Stroke Best Practice Recommendations suggests that patients suspected of transient ischemic attack (TIA)/minor stroke receive urgent brain imaging, preferably computed tomography angiography (CTA). Yet, high requisition rates for non-cerebrovascular patients overburden limited radiological resources, putting patients at risk. We hypothesize that our clinical decision support tool (CDST) developed for risk stratification of TIA in the emergency department (ED), and which incorporates Canadian guidelines, could improve CTA utilization.
Retrospective study design with clinical information gathered from ED patient referrals to an outpatient TIA unit in Victoria, BC, from 2015-2016. Actual CTA orders by ED and TIA unit staff were compared to hypothetical CTA ordering if our CDST had been used in the ED upon patient arrival.
For 1,679 referrals, clinicians ordered 954 CTAs. Our CDST would have ordered a total of 977 CTAs for these patients. Overall, this would have increased the number of imaged-TIA patients by 89 (10.1%) while imaging 98 (16.1%) fewer non-cerebrovascular patients over the 2-year period. Our CDST would have ordered CTA for 18 (78.3%) of the recurrent stroke patients in the sample.
Our CDST could enhance CTA utilization in the ED for suspected TIA patients, and facilitate guideline-based stroke care. Use of our CDST would increase the number of TIA patients receiving CTA before ED discharge (rather than later at TIA units) and reduce the burden of imaging stroke mimics in radiological departments.
One year of antipsychotic treatment from symptom remission is recommended following a first episode of psychosis (FEP).
To investigate the effectiveness of commonly used antipsychotic medications in FEP.
A retrospective cohort study of naturalistic treatment of patients (N = 460) accepted by FEP services across seven UK sites. Treatment initiation to all-cause discontinuation determined from case files.
Risk of treatment discontinuation is greatest within 3 months of treatment initiation. Risperidone had longest median survival time. No significant differences were observed in time to discontinuation between commonly used antipsychotics on multivariable Cox regression analysis. Poor adherence and efficacy failure were the most common reasons for discontinuation.
Effectiveness differences appear not to be a current reason for antipsychotic choice in FEP. Adherence strategies and weighing up likely adverse effects should be the clinical focus.
It is established that the current cost effectiveness health technology assessment (HTA) paradigm does not appropriately value rare disease technologies. Social willingness-to-pay (SWTP) has been suggested to be higher for rare disease technologies, it's inclusion into existing HTA framework could better reflect social preferences (SP) and enable a more equitable evaluation of rare disease technologies. Our study aims to estimate SP and SWTP for a rare disorder, CLN2 disease.
Relevant attributes for CLN2 disease were developed and validated by literature review and focus groups with patient's primary caregivers. An elicitation survey (discrete choice experiment (DCE) WTP and relative social willingness to pay (RS-WTP)) was developed using the selected attributes and levels of each attribute. The survey instruments and attributes/levels were tested and validated in a pre-pilot survey (n = 103) and a subsequent pilot survey (n = 286) of the United Kingdom (UK) general population. Information about CLN2 disease was provided to respondents and their understanding of the disease was tested including assessment of framing effects. The main survey with the general UK population (n = 4,009) is now complete.
Eight hundred and twenty-six people were contacted, of which 286 completed the DCE, 113 abandoned the survey before the DCE and 92 abandoned after the DCE. There were no significant differences in characteristics of respondents completing the DCE and those starting but not completing the DCE. Median survey completion time was 20 minutes with 90 percent of participants completing in a single sitting. Median score for the understanding test was 3 (Min = 0 and Max = 4). Incoherencies in WTP estimates were analyzed enabling us introduce relevant modifications and select the most appropriate attribute levels.
DCE and RS-WTP potentially are appropriate methods for assessment of social preferences. The selected attributes/levels for the experiment in CLN2 disease have been validated in this pilot.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
Questions about racial or ethnic group identity feature centrally in many social science theories, but detailed data on ethnic composition are often difficult to obtain, out of date, or otherwise unavailable. The proliferation of publicly available geocoded person names provides one potential source of such data'if researchers can effectively link names and group identity. This article examines that linkage and presents a methodology for estimating local ethnic or racial composition using the relationship between group membership and person names. Common approaches for linking names and identity groups perform poorly when estimating group proportions. I have developed a new method for estimating racial or ethnic composition from names which requires no classification of individual names. This method provides more accurate estimates than the standard approach and works in any context where person names contain information about group membership. Illustrations from two very different contexts are provided: the United States and the Republic of Kenya.
The oxidation of nickel powder under a controlled gas and temperature environment was studied using synchrotron-based full-field transmission X-ray microscopy. The use of this technique allowed for the reaction to be imaged in situ at 55 nm resolution. The setup was designed to fit in the limited working distance of the microscope and to provide the gas and temperature environments analogous to solid oxide fuel cell operating conditions. Chemical conversion from nickel to nickel oxide was confirmed using X-ray absorption near-edge structure. Using an unreacted core model, the reaction rate as a function of temperature and activation energy were calculated. This method can be applied to study many other chemical reactions requiring similar environmental conditions.
During the last two decades, historians and social scientists have paid increasing attention to the history of friendly societies and other forms of mutual support. In Britain, authors such as Eric Hopkins, David Neave, Martin Gorsky, Simon Cordery and Daniel Weinbren have examined the role played by friendly societies both as cultural organizations and as sources of welfare support, and Weinbren has also explored the relationship between friendly societies and philanthropy. Nor has interest been confined to purely historical circles. In recent years, commentators on both left and right have attempted to invoke the vibrancy of Britain's mutualist tradition as an alternative to the ‘top-down’ welfare state.
One of the most important issues raised by these debates has been the relationship between mutualism in general, and the friendly societies in particular, and the growth of state welfare in the early years of the twentieth century. The friendly societies played a central role in the process because of their own responsibility for the provision of both sickness insurance and pension benefits. This chapter begins by looking at the societies’ own attempts to estimate welfare needs by examining their efforts to measure the sickness experience of their members. It then goes to review the role played by the societies in the introduction of both old age pensions and national health insurance.
During the eighteenth and nineteenth centuries, friendly societies played a key role in protecting the working-class population from the economic risks associated with sickness, old age and death.