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We conducted a preregistered multilaboratory project ( k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result ( d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect ( d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

BackgroundDepression is a heterogeneous disorder with multiple aetiological pathways and multiple therapeutic targets. This study aims to determine whether atypical depression (AD) characterized by reversed neurovegetative symptoms is associated with a more pernicious course and a different sociodemographic, lifestyle, and comorbidity profile than nonatypical depression (nonAD).MethodsAmong 157 366 adults who completed the UK Biobank Mental Health Questionnaire (MHQ), N = 37 434 (24%) met the DSM-5 criteria for probable lifetime major depressive disorder (MDD) based on the Composite International Diagnostic Interview Short Form. Participants reporting both hypersomnia and weight gain were classified as AD cases (N = 2305), and the others as nonAD cases (N = 35 129). Logistic regression analyses were conducted to examine differences between AD and nonAD in depression features, sociodemographic and lifestyle factors, lifetime adversities, psychiatric and physical comorbidities.ResultsPersons with AD experienced an earlier age of depression onset, longer, more severe and recurrent episodes, and higher help-seeking rates than nonAD persons. AD was associated with female gender, unhealthy behaviours (smoking, social isolation, low physical activity), more lifetime deprivation and adversity, higher rates of comorbid psychiatric disorders, obesity, cardiovascular disease (CVD), and metabolic syndrome. Sensitivity analyses comparing AD persons with those having typical neurovegetative symptoms (hyposomnia and weight loss) revealed similar results.ConclusionsThese findings highlight the clinical and public health significance of AD as a chronic form of depression, associated with high comorbidity and lifetime adversity. Our findings have implications for predicting depression course and comorbidities, guiding research on aetiological mechanisms, planning service use and informing therapeutic approaches.

Background As HIV has become a chronic condition, management of the disease and preventing resistance is paramount to improving patient outcomes. Medication errors can lead to suboptimal therapy and potential development of resistance. The purpose of this study was to identify the rate of antiretroviral (ART)-related medication errors in hospitalized people living with HIV (PWLH). Methods This was a multi-center, retrospective cohort study of patients diagnosed with HIV and/or AIDS based on International Classification of Diseases codes. Patients were included if they were at least 18 years old and hospitalized between March 2016 and March 2018. Patients were excluded if they were pregnant and only received intravenous zidovudine during their hospitalization. Of the patients eligible for inclusion, 400 were randomly selected and included in this study. The primary objective was to determine the rate of inpatient ART-related medication errors. Secondary objectives included the type of errors and rate of error resolution prior to discharge. Results A total of 203 ART-related medication errors occurred during the study period (mean 0.9 ± 1.2 errors per patient). Incorrect schedule was the most common type of error followed by incorrect or incomplete regimen. More errors occurred in male patients (P = 0.01), those known to be infected with HIV on admission (P < 0.05), and in patients with an undetectable viral load (P = 0.01). Approximately 30% of ART-related medication errors were resolved prior to discharge, of which pharmacists were responsible for 25%. Incorrect schedule, incorrect or incomplete regimen, and clinically significant drug-drug interaction (DDI) were the most common medication errors that persisted at discharge. Among resolved errors, resolution of clinically significantly DDI or incorrect/incomplete ART were the most common interventions. Conclusion ART-related medication errors continue to occur in hospitalized PLWH and frequently persist at discharge. Interventions should be developed to reduce rates of ART-related medication errors on admission. Antimicrobial stewardship programs serve as an ideal platform to incorporate ART stewardship into routine activities to help minimize errors while inpatient and during transitions of care. Disclosures All authors: No reported disclosures.

OBJECTIVE Peripheral insulin resistance is linked to an increase in reactive oxygen species (ROS), leading in part to the production of reactive lipid aldehydes that modify the side chains of protein amino acids in a reaction termed protein carbonylation. The primary enzymatic method for lipid aldehyde detoxification is via glutathione S-transferase A4 (GSTA4) dependent glutathionylation. The objective of this study was to evaluate the expression of GSTA4 and the role(s) of protein carbonylation in adipocyte function. RESEARCH DESIGN AND METHODS GSTA4-silenced 3T3-L1 adipocytes and GSTA4-null mice were evaluated for metabolic processes, mitochondrial function, and reactive oxygen species production. GSTA4 expression in human obesity was evaluated using microarray analysis. RESULTS GSTA4 expression is selectively downregulated in adipose tissue of obese insulin-resistant C57BL/6J mice and in human obesity-linked insulin resistance. Tumor necrosis factor-α treatment of 3T3-L1 adipocytes decreased GSTA4 expression, and silencing GSTA4 mRNA in cultured adipocytes resulted in increased protein carbonylation, increased mitochondrial ROS, dysfunctional state 3 respiration, and altered glucose transport and lipolysis. Mitochondrial function in adipocytes of lean or obese GSTA4-null mice was significantly compromised compared with wild-type controls and was accompanied by an increase in superoxide anion. CONCLUSIONS These results indicate that downregulation of GSTA4 in adipose tissue leads to increased protein carbonylation, ROS production, and mitochondrial dysfunction and may contribute to the development of insulin resistance and type 2 diabetes.

The nature and frequency of voter fraud figure prominently in many ongoing policy debates about election laws in the United States. Policy makers frequently cite allegations of voter fraud reported in the press during these debates. While recent studies find that voter fraud is a rare event, a substantial segment of the public believes that voter fraud is a rampant problem in the United States. It stands to reason that public beliefs are shaped by news coverage of voter fraud. However, there is very little extant academic research on how the news media, at any level, covers allegations or documented cases of voter fraud. This paper examines local newspaper attention to voter fraud in each of the 50 states during the 2008 and 2012 US elections. The results show that local coverage of voter fraud during the 2012 elections was greatest in presidential swing states and states that passed restrictive voting laws prior to the 2012 election. No evidence that newspaper attention is related to the rate of actual voter fraud cases in each state was found. The findings are consistent with other studies indicating that parties and campaigns sought to place voter fraud on the political agenda in strategically important states to motivate their voting base ahead of the election.

Cytochrome b5 reductases (CYB5R) are required for the elongation and desaturation of fatty acids, cholesterol synthesis and mono-oxygenation of cytochrome P450 enzymes, all of which are associated with protection against metabolic disorders. However, the physiological role of CYB5R in the context of metabolism, healthspan and aging remains ill-defined. We generated CYB5R-overexpressing flies (CYB5R-OE) and created a transgenic mouse line overexpressing CYB5R3 (CYB5R3-Tg) in the C57BL/6J background to investigate the function of this class of enzymes as regulators of metabolism and age-associated pathologies. Gender- and/or stage-specific induction of CYB5R, and pharmacological activation of CYB5R with tetrahydroindenoindole extended fly lifespan. Increased expression of CYB5R3 was associated with significant improvements in several metabolic parameters that resulted in modest lifespan extension in mice. Diethylnitrosamine-induced liver carcinogenesis was reduced in CYB5R3-Tg mice. Accumulation of high levels of long-chain polyunsaturated fatty acids, improvement in mitochondrial function, decrease in oxidative damage and inhibition of chronic pro-inflammatory pathways occurred in the transgenic animals. These results indicate that CYB5R represents a new target in the study of genes that regulate lipid metabolism and healthspan.