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The UK Biobank contains data with varying degrees of reliability and completeness for assessing depression. A third of participants completed a Mental Health Questionnaire (MHQ) containing the gold-standard Composite International Diagnostic Interview (CIDI) criteria for assessing mental health disorders.
To investigate whether multiple observations of depression from sources other than the MHQ can enhance the validity of major depressive disorder (MDD).
In participants who did not complete the MHQ, we calculated the number of other depression measures endorsed, for example from hospital episode statistics and interview data. We compared cases defined this way with CIDI-defined cases for several estimates: the variance explained by polygenic risk scores (PRS), area under the curve attributable to PRS, single nucleotide polymorphisms (SNPs)-based heritability and genetic correlations with summary statistics from the Psychiatric Genomics Consortium MDD genome-wide association study.
The strength of the genetic contribution increased with the number of measures endorsed. For example, SNP-based heritability increased from 7% in participants who endorsed only one measure of depression, to 21% in those who endorsed four or five measures of depression. The strength of the genetic contribution to cases defined by at least two measures approximated that for CIDI-defined cases. Most genetic correlations between UK Biobank and the Psychiatric Genomics Consortium MDD study exceeded 0.7, but there was variability between pairwise comparisons.
Multiple measures of depression can serve as a reliable approximation for case status where the CIDI measure is not available, indicating sample size can be optimised using the entire suite of UK Biobank data.
From foraging patterns in a single tree to social interactions across a home range, how primates use space is a key question in the field of primate behavioral ecology. Drawing on the latest advances in spatial analysis tools, this book offers practical guidance on applying geographic information systems (GIS) to central questions in primatology. An initial methodological section discusses niche modelling, home range analysis and agent-based modelling, with a focus on remote data collection. Research-based chapters demonstrate how ecologists apply this technology to a suite of topics including: calculating the intensity of use of both range and travel routes, assessing the impacts of logging, mining and hunting, and informing conservation strategies.
AU in days of therapy per 1,000 patient days and microbiologic data from 2015 and 2016 were collected from 26 hospitals. The prevalences of Pseudomonas aeruginosa, extended-spectrum β-lactamase (ESBL)–producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were calculated and compared to the average prevalence of all hospitals in the network. This proportion was used to calculate the adjusted AU (a-AU) for various categories of antimicrobials. For example, a-AU of antipseudomonal β-lactams (APBL) was the AU of APBL divided by (prevalence of P. aeruginosa at that hospital divided by the average prevalence of P. aeruginosa). Hospitals were categorized by bed size and ranked by AU and a-AU, and the rankings were compared.
Most hospitals in 2015 and 2016, respectively, moved ≥2 positions in the ranking using a-AU of APBL (15 of 24, 63%; 22 of 26, 85%), carbapenems (14 of 23, 61%; 22 of 25; 88%), anti-MRSA agents (13 of 23, 57%; 18 of 26, 69%), and anti-VRE agents (18 of 24, 75%; 15 of 26, 58%). Use of a-AU resulted in a shift in quartile of hospital ranking for 50% of APBL agents, 57% of carbapenems, 35% of anti-MRSA agents, and 75% of anti-VRE agents in 2015 and 50% of APBL agents, 28% of carbapenems, 50% of anti-MRSA agents, and 58% of anti-VRE agents in 2016.
The a-AU considerably changes how hospitals compare among each other within a network. Adjusting AU by microbiological burden allows for a more balanced comparison among hospitals with variable baseline rates of resistant bacteria.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to COVID-19 with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplemental materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
South African lovegrass (Eragrostis plana Nees) is the most important weed of native pastures in southern Brazil. Management options are limited under water-stress conditions, and glyphosate has been the main tool for control. This study compared four salts of glyphosate applied at three growth stages and determined the glyphosate tolerance level. In addition, the performance of ammonium sulfate (AMS) under two soil moisture conditions (50% and 100% of water-holding capacity) and the effect of AMS on absorption and translocation of radiolabeled [14C]glyphosate were evaluated. The potassium salt of glyphosate had the fastest activity across growth stages of E. plana, which is more vulnerable to glyphosate at the panicle initiation stage. Isopropylamine salt was the slowest-acting glyphosate formulation. Younger plants were typically more easily controlled than older plants at the full tillering stage. The addition of AMS increased the level of control of drought-stressed E. plana compared with glyphosate alone by increasing translocation out of the treated leaf and consequently increasing the concentration of glyphosate in the primary culm. These data can be used to plan an effective management program for E. plana that takes into account the developmental stage of desired pasture grass species.
Kernza® intermediate wheatgrass [Thinopyrum intermedium (Host) Barkworth & Dewey], the first perennial grain crop to come to market in North America, can provide a number of ecosystem services when integrated into cropping systems that are dominated by annual grain crops. However, grain yield from Kernza is lower than comparable annual cereal crops such as wheat and oats. Also, although Kernza is a long-lived perennial that can persist for decades, grain yield tends to decline over time as Kernza stands age leading most farmers to replant or rotate to a different crop after 3–5 yrs. Increased intraspecific competition as stand density increases with age has been reported to cause grain yield declines. We investigated the effect of strip-tillage applied at two different timings, between the third and fourth grain harvests, from a Kernza stand in upstate New York. Strip-tillage applied in late fall as plants were entering dormancy increased grain yield by 61% when compared to the control treatment without strip-tillage. However, total crop biomass was not reduced resulting in a greater harvest index for the fall strip-tillage treatment. Strip-tillage applied before stem elongation the following spring reduced overall tiller density and total crop biomass but did not impact tiller fertility or grain yield compared to the control treatment without strip-tillage. Increased grain yield in the fall strip-tillage treatment was due to an increase in the percentage of tillers that produced mature seedheads. This suggests that grain yield decline over time is at least partially caused by competition between tillers in dense stands. Results support further research and development of strip-tillage and other forms of managed disturbance as tools for maintaining Kernza grain yield over time.
PUFA modulate immune function and have been associated with the risk of childhood atopy and asthma. We investigated the effect of maternal fat intake in mice on PUFA status, elongase and desaturase gene expression, inflammatory markers and lung function in the offspring. C57BL/6J mice (n 32) were fed either standard chow (C, 20·4 % energy as fat) or a high-fat diet (HFD, 39·9 % energy as fat) for 4 weeks prior to conception and during gestation and lactation. At 21 d of age, offspring were weaned onto either the HFD or C, generating four experimental groups: C/C, C/HF, HF/C and HF/HF. Plasma and liver fatty acid composition were measured by GC and gene expression by quantitative PCR. Lung resistance to methacholine was assessed. Arachidonic acid concentrations in offspring plasma and liver phospholipids were increased by HFD; this effect was greater in the post-natal HFD group. DHA concentration in offspring liver phospholipids was increased in response to HFD and was higher in the post-natal HFD group. Post-natal HFD increased hepatic fatty acid desaturase (FADS) 2 and elongation of very long-chain fatty acid 5 expression in male offspring, whereas maternal HFD elevated expression of FADS1 and FADS2 in female offspring compared with males. Post-natal HFD increased expression of IL-6 and C-C motif chemokine ligand 2 (CCL2) in perivascular adipose tissue. The HFD lowered lung resistance to methacholine. Excessive maternal fat intake during development modifies hepatic PUFA status in offspring through regulation of gene expression of enzymes that are involved in PUFA biosynthesis and modifies the development of the offspring lungs leading to respiratory dysfunction.
An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown.
Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA).
BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). The change in KynA/QA was nominally associated with the magnitude of change in PROMIS-D scores (p = 0.074, Cohen's f2 = 0.054). Baseline KynA/QA did not predict response to BA therapy.
The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.
Infants with moderate-to-severe CHD frequently undergo cardiopulmonary bypass surgery in childhood. Morbidity and mortality are highest in those who develop post-operative low cardiac output syndrome. Vasoactive and inotropic medications are mainstays of treatment for these children, despite limited evidence supporting their use.
To help inform clinical practice, as well as the conduct of future trials, we performed a systematic review of existing literature on inotropes and vasoactives in children after cardiac surgery using the PubMed and EMBASE databases. We included studies from 2000 to 2020, and the patient population was defined as birth – 18 years of age. Two reviewers independently reviewed studies to determine final eligibility.
The final analysis included 37 papers. Collectively, selected studies reported on 12 different vasoactive and inotropic medications in 2856 children. Overall evidence supporting the use of these drugs in children after cardiopulmonary bypass was limited. The majority of studies were small with 30/37 (81%) enrolling less than 100 patients, 29/37 (78%) were not randomised, and safety and efficacy endpoints differed widely, limiting the ability to combine data for meta-analyses.
Vasoactive and inotropic support remain critical parts of post-operative care for children after cardiopulmonary bypass surgery. There is a paucity of data for the selection and dosing of vasoactives and inotropes for these patients. Despite the knowledge gaps that remain, numerous recent innovations create opportunities to rethink the conduct of clinical trials in this high-risk population.
The archaeological assemblage recovered from the Middle Stone Age (MSA) levels in Blombos Cave, South Africa, is central to our understanding of the development of early modern humans. Here, we demonstrate that the cultural and technological innovations inferred from the Blombos Cave MSA record also correlate with significant shifts in site use and occupational intensity. Through a comprehensive geoarchaeological investigation of three MSA occupation phases, we identified distinct diachronic trends in the frequency of visits and the modes of occupation. During the earliest phases (ca. 88–82 ka), humans inhabited the cave for more extended periods, but cave visits were not frequent. During the later phases (ca. 77–72 ka), the cave was more regularly visited but for shorter periods each time. We argue that these changes in local occupational intensity, which also coincide with shifts in vegetation, sea levels, and subsistence, can best be explained by broader changes in hunter-gatherer mobility strategies and occupation patterns. Fundamental changes in regional settlement dynamics during Marine Oxygen Isotope Stages 5b-4 would have significantly affected the nature and frequency of social interaction within and between prehistoric populations living in the southern Cape, a scenario that ultimately may explain some of the social and technological advances that occurred there during this time frame.
This article studies the inscription IG IV2 1.687 (FGrH 95), the only evidence for the historian Philip of Pergamon. The subjects considered include the text itself, the appearance of the stone and the layout in imitation of papyrus, the date as evidenced by the lettering, the use of the Ionic dialect and the references to ‘suffering and continuous mutual slaughter’. Finally, it is proposed that Philip may be ‘the historian Philip’ mentioned in a dialogue of Plutarch.