We investigated whether household to clinic distance was a risk factor for death on tuberculosis (TB) treatment in Malawi. Using enhanced TB surveillance data, we recorded all TB treatment initiations and outcomes between 2015 and 2018. Household locations were geolocated, and distances were measured by a straight line or shortest road network. We constructed Bayesian multi-level logistic regression models to investigate associations between distance and case fatality. A total of 479/4397 (10.9%) TB patients died. Greater distance was associated with higher (odds ratio (OR) 1.07 per kilometre (km) increase, 95% credible interval (CI) 0.99–1.16) odds of death in TB patients registered at the referral hospital, but not among TB patients registered at primary clinics (OR 0.98 per km increase, 95% CI 0.92–1.03). Age (OR 1.02 per year increase, 95% CI 1.01–1.02) and HIV-positive status (OR 2.21, 95% CI 1.73–2.85) were also associated with higher odds of death. Model estimates were similar for both distance measures. Distance was a risk factor for death among patients at the main referral hospital, likely due to delayed diagnosis and suboptimal healthcare access. To reduce mortality, targeted community TB screening interventions for TB disease and HIV, and expansion of novel sensitive diagnostic tests are required.

Our population-based study objectives were to describe characteristics and outcomes of Escherichia coli bloodstream infections (BSIs), and to evaluate factors associated with outcomes. We included incident E. coli BSIs from western interior residents (British Columbia, Canada; 04/2010–03/2020). We obtained data including patient demographics, location of onset, infection focus, Charlson comorbidity index (CCI), antimicrobial resistance, 30-day all-cause mortality and length of hospital stay (LOS). Using multivariable logistic regression models fitted with generalised estimating equations, we estimated factors associated with 30-day mortality and long post-infection LOS (>75th percentile). We identified 1080 incident E. coli BSIs in 1009 patients. The crude incidence and 30-day mortality rates were 59.1 BSIs and 6.8 deaths/100 000 person-years, respectively. The 30-day case fatality risk was 11.5%. Compared to community-acquired E. coli BSIs, either healthcare-associated or nosocomial cases had higher odds of 30-day mortality. Older cases, non-urogenital BSI foci and CCI ⩾ 3 had higher odds of 30-day mortality compared to younger cases, urogenital foci and CCI < 3. In patients that survived to discharge, those with extended-spectrum β-lactamase (ESBL)-producing E. coli BSIs, nosocomial BSIs, and CCI ⩾ 3 had higher odds of long post-infection LOS compared to those with non-ESBL-producing, community-acquired and healthcare-associated, and CCI < 3. There is a substantial disease burden from E. coli BSIs.

Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10−4, R2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10−9, R2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health.

We present a detailed discussion of the implementation strategies for a recently developed w-stacking w-projection hybrid algorithm used to reconstruct wide-field interferometric images. In particular, we discuss the methodology used to deploy the algorithm efficiently on a supercomputer via use of a Message Passing Interface (MPI) k-means clustering technique to achieve efficient construction and application of non-coplanar effects. Additionally, we show that the use of conjugate symmetry can increase the w-stacking efficiency, decrease the time required to construction, and apply w-projection kernels for large data sets. We then demonstrate this implementation by imaging an interferometric observation of Fornax A from the Murchison Widefield Array (MWA). We perform an exact non-coplanar wide-field correction for 126.6 million visibilities using 50 nodes of a computing cluster. The w-projection kernel construction takes only 15 min prior to reconstruction, demonstrating that the implementation is both fast and efficient.

The hippocampal formation, a structure involved in declarative, spatial and contextual memory, undergoes atrophy in depressive illness along with impairment in cognitive function. Animal model studies have shown that the hippocampus is a particularly sensitive and vulnerable brain region that responds to stress and stress hormones. Studies on models of stress and glucocorticoid actions reveal that the hippocampus shows a considerable degree of structural plasticity in the adult brain. Stress suppresses neurogenesis of dentate gyrus granule neurons, and repeated stress causes remodeling of dendrites in the CA3 region, a region that is particularly important in memory processing. Both forms of structural remodeling of the hippocampus are mediated by adrenal steroids working in concert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures, head trauma, and ischemia, and alterations of calcium homeostasis that accompany age-related cognitive impairment. Tianeptine (tianeptine) is an effective antidepressant that prevents and even reverses the actions of stress and glucocorticoids on dendritic remodeling in an animal model of chronic stress. Multiple neurotransmitter systems contribute to dendritic remodeling, including EAA, serotonin, and gamma-aminobutyric acid (GABA), working synergistically with glucocorticoids. This review summarizes findings on neurochemical targets of adrenal steroid actions that may explain their role in the remodeling process. In studying these actions, we hope to better understand the molecular and cellular targets of action of tianeptine in relation to its role in influencing structural plasticity of the hippocampus.

Stress elicits adaptive responses from the brain, but it can also lead to maladaptive consequences. For example, stress can precipitate mental illness, including depression. Prolonged stress also causes damage to neurons in the hippocampus. Antidepressant drugs must be evaluated, not only for their ability to potentiate adaptive responses, but also to inhibit maladaptive consequences of stress. Ongoing research in our laboratory has compared the atypical tricyclic antidepressant, tianeptine, with the typical tricyclics, desipramine and imipramine, with respect to the effects of isolation and repeated restraint stress. Tianeptine and desipramine similarly attenuated isolation stress-induced increases in locus coeruleus and midbrain tyrosine hydroxylase mRNA levels and isolation-stress induced decreases in preproenkephalin mRNA levels in striatum and nucleus accumbens. However, tianeptine and imipramine differed in their effects in the cerebral cortex and hippocampus on 5HT2, and 5HT1A receptor levels but, surprisingly, produced similar effects on levels of the serotonin transporter labelled with [3H] paroxetine. Tianeptine also prevented stress-induced reductions in the length and number of branchpoints of dendrites of CA3 pyramidal neurons in hippocampus; comparison with effects of typical tricyclics are ongoing. Tianeptine also blocked effects of corticosterone treatment to reduce branching and length of CA3 dendrites. These actions of tianeptine may be due to interactions between 5HT and excitatory amino acids in the mossy fiber terminals on CA3 pyramidal neurons. Taken together, these results indicate that tianeptine has unique properties compared to some other antidepressant drugs, but shares in common with those drugs the ability to attenuate stress effects on tyrosine hydroxylase gene expression and on the serotonin transporter. It remains to be seen whether these actions are the basis of a common antidepressant action.

There is a renewed interest in writing about the First Republic among Austrian historians. As always, it is political: how to frame the collapse of the empire, how to address the political divides of the era, whether to attribute “fascism” to the Ständestaat, what constitutes history, and what is mere description. The following essay takes into account five new and large additions to the canon.

Insulin resistance and markers of Allostatic load in depression

Livestock producers are encouraged to reduce the use of antibiotics belonging to classes of medical importance to humans. We conducted a scoping review on non-antibiotic interventions in the form of products or management practices that could potentially reduce the need for antibiotics in beef and veal animals living under intensive production conditions. Our objectives were to systematically describe the research on this broad topic, identify specific topics that could feasibly support systematic reviews, and identify knowledge gaps. Multiple databases were searched. Two reviewers independently screened and charted the data. From the 13,598 articles screened, 722 relevant articles were charted. The number of relevant articles increased steadily from 1990. The Western European research was dominated by veal production studies whereas the North American research was dominated by beef production studies. The interventions and outcomes measured were diverse. The four most frequent interventions included non-antibiotic feed additives, vaccinations, breed type, and feed type. The four most frequent outcomes were indices of immunity, non-specific morbidity, respiratory disease, and mortality. There were seven topic areas evaluated in clinical trials that may share enough commonality to support systemic reviews. There was a dearth of studies in which interventions were compared to antibiotic comparison groups.

In June of 2016, the Collaborative Working Group (CWG) on the Future of Emergency Medicine presented its final report at the Canadian Association of Emergency Physicians (CAEP) annual meeting in Quebec City. The CWG report made a number of recommendations concerning physician Human Health Resource (HHR) shortfalls in emergency medicine, specific changes for both the Royal College of Physicians and Surgeons of Canada (FRCPC) and the College of Family Physicians of Canada (CCFP-EM) training programs, HHR needs in rural and remote hospitals, future collaboration of the CCFP-EM and FRCPC programs, and directions for future research. All recommendations were endorsed by CAEP, the Royal College of Physicians and Surgeons of Canada (RCPSC), and the College of Family Physicians of Canada (CFPC). The CWG report was published in CJEM and has served as a basis for ongoing discussion in the emergency medicine community in Canada. The CWG identified an estimated shortfall of 478 emergency physicians in Canada in 2016, rising to 1071 by 2020 and 1518 by 2025 assuming no expansion of EM residency training capacity. In 2017, the CAEP board struck a new committee, The Future of Emergency Medicine in Canada (FEMC), to advocate with appropriate stakeholders to implement the CWG recommendations and to continue with this important work. FEMC led a workshop at CAEP 2018 in Calgary to develop a regional approach to HHR advocacy, recognizing different realities in each province and region. There was wide representation at this workshop and a rich and passionate discussion among those present. This paper represents the output of the workshop and will guide subsequent deliberations by FEMC. FEMC has set the following three goals as we work toward the overarching purpose to improve timely access to high quality emergency care: (1) to define and describe categories of emergency departments (EDs) in Canada, (2) define the full time equivalents required by category of ED in Canada, and (3) recommend the ideal combination of training and certification for emergency physicians in Canada. A fourth goal supports the other three goals: (4) urge further consideration and implementation of the CWG-EM recommendations related to coordination and optimization of the current two training programs. We believe that goals 1 and 2 can largely be accomplished by the CAEP annual meeting in 2020, and goal 3 by the CAEP annual meeting in 2021. Goal 4 is ongoing with both the RCPSC and the CFPC. We urge the EM community across Canada to engage with our committee to support improved access and EM care for all Canadians.