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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
Diagnosis of ventilator-associated pneumonia (VAP) is challenging and relies heavily on respiratory culture results. The results of this survey underscore the potential for a diagnostic stewardship nudge limiting culture reports to “potential colonization or contamination” in those without clinical findings of VAP to decrease unnecessary antibiotic prescribing.
Reading difficulties are prevalent worldwide, including in economically developed countries, and are associated with low academic achievement and unemployment. Longitudinal studies have identified several early childhood predictors of reading ability, but studies frequently lack genotype data that would enable testing of predictors with heritable influences. The National Child Development Study (NCDS) is a UK birth cohort study containing direct reading skill variables at every data collection wave from age 7 years through to adulthood with a subsample (final n = 6431) for whom modern genotype data are available. It is one of the longest running UK cohort studies for which genotyped data are currently available and is a rich dataset with excellent potential for future phenotypic and gene-by-environment interaction studies in reading. Here, we carry out imputation of the genotype data to the Haplotype Reference Panel, an updated reference panel that offers greater imputation quality. Guiding phenotype choice, we report a principal components analysis of nine reading variables, yielding a composite measure of reading ability in the genotyped sample. We include recommendations for use of composite scores and the most reliable variables for use during childhood when conducting longitudinal, genetically sensitive analyses of reading ability.
There is substantial variation in patient symptoms following psychological therapy for depression and anxiety. However, reliance on endpoint outcomes ignores additional interindividual variation during therapy. Knowing a patient's likely symptom trajectories could guide clinical decisions. We aimed to identify latent classes of patients with similar symptom trajectories over the course of psychological therapy and explore associations between baseline variables and trajectory class.
Methods
Patients received high-intensity psychological treatment for common mental health problems at National Health Service Improving Access to Psychological Therapies services in South London (N = 16 258). To identify trajectories, we performed growth mixture modelling of depression and anxiety symptoms over 11 sessions. We then ran multinomial regressions to identify baseline variables associated with trajectory class membership.
Results
Trajectories of depression and anxiety symptoms were highly similar and best modelled by four classes. Three classes started with moderate-severe symptoms and showed (1) no change, (2) gradual improvement, and (3) fast improvement. A final class (4) showed initially mild symptoms and minimal improvement. Within the moderate-severe baseline symptom classes, patients in the two showing improvement as opposed to no change tended not to be prescribed psychotropic medication or report a disability and were in employment. Patients showing fast improvement additionally reported lower baseline functional impairment on average.
Conclusions
Multiple trajectory classes of depression and anxiety symptoms were associated with baseline characteristics. Identifying the most likely trajectory for a patient at the start of treatment could inform decisions about the suitability and continuation of therapy, ultimately improving patient outcomes.
The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.
Method
Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.
Results
Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.
Conclusions
We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
Anxiety and depressive disorders can be chronic and disabling. Although there are effective treatments, only a fraction of those impaired receive treatment. Predictors of treatment-seeking and treatment receipt could be informative for initiatives aiming to tackle the burden of untreated anxiety and depression.
Aims
To investigate sociodemographic characteristics associated with treatment-seeking and treatment receipt.
Method
Two binary retrospective reports of lifetime treatment-seeking (n = 44 810) and treatment receipt (n = 37 346) were regressed on sociodemographic factors (age, gender, UK ethnic minority background, educational attainment, household income, neighbourhood deprivation and social isolation) and alternative coping strategies (self-medication with alcohol/drugs and self-help) in UK Biobank participants with lifetime generalised anxiety or major depressive disorder. Analyses were also stratified by gender.
Results
Treatment access was more likely in those who reported use of self-help strategies, with university-level education and those from less economically advantaged circumstances (household income <£30 000 and greater neighbourhood deprivation). Treatment access was less likely in those who were male, from a UK ethnic minority background and with high household incomes (>£100 000). Men who self-medicated and/or had a vocational qualification were also less likely to seek treatment.
Conclusions
This work on retrospective reports of treatment-seeking and treatment receipt at any time of life replicates known associations with treatment-seeking and treatment receipt during time of treatment need. More work is required to understand whether improving rates of treatment-seeking improves prognostic outcomes for individuals with anxiety or depression.
This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data.
Methods
Individual patient data from all six eligible randomised controlled trials were used to develop (k = 3, n = 1722) and test (k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1–3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3–4 months.
Results
Models 1–7 all outperformed the null model and model 8. Model performance was very similar across models 1–6, meaning that differential weights applied to the baseline sum scores had little impact.
Conclusions
Any of the modelling techniques (models 1–7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.
Chaff lining and chaff tramlining are harvest weed seed control (HWSC) systems that involve the concentration of chaff material containing weed seed into narrow (20 to 30 cm) rows between or on the harvester wheel tracks during harvest. These lines of chaff are left intact in the fields through subsequent cropping seasons in the assumption that the chaff environment is unfavorable for weed seed survival. The chaff row environment effect on weed seed survival was examined in field studies, and chaff response studies determined the influence of increasing amounts of chaff on weed seedling emergence. The objectives of these studies were to determine the influences of (1) chaff lines on the summer–autumn seed survival of selected weed species and (2) chaff type and amount on rigid ryegrass seedling emergence. There was frequently no difference (P > 0.05) in seed survival of four weed species (rigid ryegrass, wild oat, annual sowthistle, and turnip weed) when seeds were placed beneath or beside chaff lines. In one instance, wild oat seed survival was increased (P < 0.05) when seed were placed beneath compared to beside a chaff line. The pot studies determined that increasing amounts of chaff consistently resulted in decreasing numbers of rigid ryegrass seedlings emerging through chaff material. The suppression of emergence broadly followed a linear relationship in which there was approximately a 2.0% reduction in emergence with every 1,000 kg ha–1 increase in chaff material. This relationship was consistent across wheat, barley, canola, and lupin chaff types, indicating that the physical presence of the chaff was more important than chaff type. These studies suggested that chaff lines may not affect the survival over summer–autumn of the contained weed seeds but that the subsequent emergence of weed seedlings will be restricted by high amounts of chaff (>40,000 kg ha–1).
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
Carbonate-rich lacustrine and deltaic deposits, containing thin beds of finely laminated carbonates and thick beds of silt, crop out at several sites in the Taylor Valley and have been encountered in cores obtained by the Dry Valley Drilling Project (DVDP). Fragments of the more indurated carbonate beds have widespread occurrence as part of the desert “lag gravel” which covers much of the valley floor. Analysis of the carbonates suggests that they were deposited as algal limestones from waters derived from the East Antarctic Ice Sheet via the Taylor Glacier at times which correspond to the previous three global interglacial periods, as evidenced by the ice volumes deduced from oxygen-isotopic analysis of oceanic cores. The lacustrine carbonates have been found up to 30 km beyond the present terminus of the Taylor Glacier, and up to 100 m above the level of Lake Bonney, into which the Taylor Glacier at present discharges. It is concluded that the Taylor Glacier has advanced during each of the previous three interglaciations, and it is suggested that this has been caused by a thickening of the East Antarctic Ice Sheet during the interglaciations.
Malaria remains one of the most significant global public health burdens, with nearly half of the world's population at risk of infection. Malaria is not however a monolithic disease – it can be caused by multiple different parasite species of the Plasmodium genus, each of which can induce different symptoms and pathology, and which pose quite different challenges for control. Furthermore, malaria is in no way restricted to humans. There are Plasmodium species that have adapted to infect most warm-blooded vertebrate species, and the genus as a whole is both highly successful and highly diverse. How, where and when human malaria parasites originated from within this diversity has long been a subject of fascination and sometimes also controversy. The past decade has seen the publication of a number of important discoveries about malaria parasite origins, all based on the application of molecular diagnostic tools to new sources of samples. This review summarizes some of those recent discoveries and discusses their implication for our current understanding of the origin and evolution of the Plasmodium genus. The nature of these discoveries and the manner in which they are made are then used to lay out a series of opportunities and challenges for the next wave of parasite hunters.
During spray trials carried out recently for European pine shoot moth control in Ontario, a method was developed to assess dyed, oil-based insecticide spray deposits colorimetrically using a paper sampling surface. The procedure permits intensive sampling without the necessity of handling fragile or bulky sampling kits in the field.
In healthy older subjects, the glycaemic response to carbohydrate-containing meals is dependent on gastric emptying and intestinal absorption; when the latter is slowed, the magnitude of the rise in glucose is attenuated. The oligosaccharide α-cyclodextrin has been reported to diminish the glycaemic response to starch in young adults; this effect has been attributed to the inhibition of pancreatic amylase. We examined the effects of α-cyclodextrin on gastric emptying of, and the glycaemic and insulinaemic responses to, oral sucrose in healthy older subjects; as sucrose is hydrolysed by intestinal disaccharides, any effect(s) of α-cyclodextrin would not be attributable to amylase inhibition. A total of ten subjects (seven males and three females, age 68–76 years) were studied on 2 d. Gastric emptying, blood glucose and serum insulin were measured after ingestion of a 300 ml drink containing 100 g sucrose, labelled with 99mTc-sulphur colloid, with or without 10 g α-cyclodextrin. Gastric emptying was slowed slightly by α-cyclodextrin; this effect was evident between 135 and 195 min and was associated with a slight increase (P < 0·05) in distal stomach retention. After α-cyclodextrin, blood glucose was slightly less (P < 0·05) at 60 min, and serum insulin was less (P < 0·0005) at 90 and 120 min. There was no difference in the incremental areas under the curve (iAUC) for blood glucose, but there was a trend for the iAUC for serum insulin to be lower (P = 0·09) after α-cyclodextrin. We conclude that in a dose of 10 g, α-cyclodextrin has modest effects to slow gastric emptying of, and modify the glycaemic and insulinaemic responses to, oral sucrose, probably due to delayed intestinal carbohydrate absorption.
By
Ian Snape, Contaminants Geochemist Working for the Australian Antarctic Division in Tasmania,
Larry Acomb, Geosphere Inc., 3055 Seawind Drive, Anchorage AK 99516, USA,
David L. Barnes, Dept. of Civil and Environmental Engineering, University of Alaska Fairbanks, PO Box 755900, Fairbanks AK 99775, USA,
Steve Bainbridge, Contaminated Sites Program, Division of Spill Prevention and Response, Department of Environmental Conservation, 610 University Avenue, Fairbanks AK 99709–3643, USA,
Robert Eno, Department of Sustainable Development, Government of Nunavut, PO Box 1000, Stn 1195, Iqaluit NU X0A 0H0, Canada,
Dennis M. Filler, Dept. of Civil and Environmental Engineering, University of Alaska Fairbanks, PO Box 755900, Fairbanks AK 99775, USA,
Natalie Plato, Department of Sustainable Development, Government of Nunavut, PO Box 1000, Stn 1195, Iqaluit NU X0A 0H0, Canada,
John S. Poland, Analytical Services Unit, Queens University, Kingston ON K7L 3N6, Canada,
Tania C. Raymond, Environmental Protection and Change Program, Australian Antarctic Division, Channel Highway, Kingston, Tasmania 7050, Australia,
John L. Rayner, Environmental Protection and Change Program, Australian Antarctic Division, Channel Highway, Kingston, Tasmania 7050, Australia,
Martin J. Riddle, Environmental Protection and Change Program, Australian Antarctic Division, Channel Highway, Kingston, Tasmania 7050, Australia,
Anne G. Rike, Dept. of Environmental Technology, Norwegian Geotechnical Institute, PO Box 3930, Ullevaal Stadion, N-0806 Oslo, Norway,
Allison Rutter, Analytical Services Unit, Queens University, Kingston ON K7L 3N6, Canada,
Alexis N. Schafer, University of Saskatchewan, 51 Campus Drive, Saskatoon, Canada S7N 5A8,
Steven D. Siciliano, University of Saskatchewan, 51 Campus Drive, Saskatoon SK S7N 5A8, Canada,
James L. Walworth, Dept. of Soil Water and Environmental Science, University of Arizona, 429 Shantz Bldg. #38, Tucson AZ 85721, USA
Oil and fuel spills are among the most extensive and environmentally damaging pollution problems in cold regions and are recognized as potential threats to human and ecosystem health. It is generally thought that spills are more damaging in cold regions, and that ecosystem recovery is slower than in warmer climates (AMAP 1998; Det Norske Veritas 2003). Slow natural attenuation rates mean that petroleum concentrations remain high for many years, and site managers are therefore often forced to select among a range of more active remediation options, each of which involves a trade-off between cost and treatment time (Figure 11). The acceptable treatment timeline is usually dictated by financial circumstance, perceived risks, regulatory pressure, or transfer of land ownership.
In situations where remediation and site closure are not urgent, natural attenuation is often considered an option. However, for many cold region sites, contaminants rapidly migrate off-site (Gore et al. 1999; Snape et al. 2006a). In seasonally frozen ground, especially in wetlands, a pulse of contamination is often released with each summer thaw (AMAP 1998; Snape et al. 2002). In these circumstances natural attenuation is likely not a satisfactory option. Simply excavating contaminants and removing them for off-site treatment may not be viable either, because the costs are often prohibitive and the environmental consequences of bulk extraction can equal or exceed the damage caused by the initial spill (Filler et al. 2006; Riser-Roberts 1998).
The lipid composition of natural populations of diatoms in the sea ice at McMurdo Sound was determined during the austral spring bloom of 1985, using and Iatroscan TLC–FID system. The major lipid classes in all samples were polar lipids (including phospholipid, glycolipid and chlorophyll) and triacylglycerol, with lesser proportions of free fatty acids. Total lipid increased through November and early December, reaching a maximum (3300 mg m−2 at Cape Armitage and 1800 mg m−2 at Erebus Ice Tongue) c. one week after the chlorophyll a maxima. This increase was largely attributable to a corresponding increase in triacylglycerol. At the lipid maxima, triacylglycerol/polar lipid ratios in the range 1.0 to 2.5 were observed. The dynamic variations in lipid class abundances indicate that profound changes in the physiology of sea-ice diatoms are occurring throughout the spring bloom. A range of sterols (C26–C30) were detected; 24-methylenecholesterol, brassicasterol and 24-ethylcholesterol were the major sterols at the Cape Armitage and Erebus sites. The similarity of the sterol profiles to those of Antarctic freshwater algal communities strongly indicates diatoms as a more probable source of C29 sterols in the freshwater lakes than cyanobacteria or other algal groups. The hydrocarbons isolated from sea-ice diatoms at all sites were dominated by two unsaturated components, n−C21:6 and a diunsaturated isoprenoid C25 alkene. Until this study, no biological source had been validated for the isoprenoid C25:2 diene, even though it has been detected in many estuarine and coastal sediments.
Plasmodium merozoites are covered by a complex coat of surface proteins. Several of the Merozoite Surface Proteins (MSPs) that make up this coat have been proposed as vaccine candidates although some of the MSPs are known to be highly polymorphic. We present here the first survey and analysis of the polymorphism in the recently characterized P. vivax surface protein PvMSP-3α. Full length or partial sequences were obtained for the Pvmsp-3α gene from isolates originating in Central and South America, Asia and the Pacific. The Pvmsp-3α sequence is remarkably diverse, but this extensive diversity is largely restricted to certain domains of the encoded protein. An acidic C-terminal domain and a smaller hydrophilic N-terminus are relatively conserved, while a central domain containing coiled-coil heptad repeats is highly polymorphic and in some isolates of P. vivax is partially deleted. Unlike other MSPs, there is no evidence of allelic families of PvMSP-3α gene sequences, and no evidence that certain patterns of polymorphism group within isolates of similar geographical origin. The distribution and nature of polymorphism suggest that there are functional restrictions on mutations in this gene, and have implications for inclusion of PvMSP-3α as a candidate in a P. vivax vaccine.
We present the initial results of a medium resolution, 0.8 to 4.2 μm spectroscopic survey of M, L, and T dwarfs. We have identified the most prominent molecular and atomic absorption features found in the spectra of these late-type dwarfs. We have also compared the spectra to a laboratory FeH emission spectrum and identified nearly 100 features common to the FeH spectrum and the dwarf spectra from 0.99 to 1.8 μm.