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Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments.
We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994–1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences.
Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06–1.33), depression PRS (OR = 1.20, 95% CI = 1.08–1.34), family history (OR = 1.25, 95% CI = 1.11–1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07–1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk.
Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.
Acanthocephalans are parasites with complex lifecycles that are important components of aquatic systems and are often model species for parasite-mediated host manipulation. Genetic characterization has recently resurrected Pomphorhynchus tereticollis as a distinct species from Pomphorhynchus laevis, with potential implications for fisheries management and host manipulation research. Morphological and molecular examinations of parasites from 7 English rivers across 9 fish species revealed that P. tereticollis was the only Pomphorhynchus parasite present in Britain, rather than P. laevis as previously recorded. Molecular analyses included two non-overlapping regions of the mitochondrial gene – cytochrome oxidase and generated 62 sequences for the shorter fragment (295 bp) and 74 for the larger fragment (583 bp). These were combined with 61 and 13 sequences respectively, from Genbank. A phylogenetic analysis using the two genetic regions and all the DNA sequences available for P. tereticollis identified two distinct genetic lineages in Britain. One lineage, possibly associated with cold water tolerant fish, potentially spread to the northern parts of Britain from the Baltic region via a northern route across the estuarine area of what is now the North Sea during the last Glaciation. The other lineage, associated with temperate freshwater fish, may have arrived later via the Rhine/Thames fluvial connection during the last glaciation or early Holocene when sea levels were low. These results raise important questions on this generalist parasite and its variously environmentally adapted hosts, and especially in relation to the consequences for parasite vicariance.
Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described.
Emergency Medical Services (EMS) systems have developed protocols for prehospital activation of the cardiac catheterization laboratory for patients with suspected ST-elevation myocardial infarction (STEMI) to decrease first-medical-contact-to-balloon time (FMC2B). The rate of “false positive” prehospital activations is high. In order to decrease this rate and expedite care for patients with true STEMI, the American Heart Association (AHA; Dallas, Texas USA) developed the Mission Lifeline PreAct STEMI algorithm, which was implemented in Los Angeles County (LAC; California USA) in 2015. The hypothesis of this study was that implementation of the PreAct algorithm would increase the positive predictive value (PPV) of prehospital activation.
This is an observational pre-/post-study of the effect of the implementation of the PreAct algorithm for patients with suspected STEMI transported to one of five STEMI Receiving Centers (SRCs) within the LAC Regional System. The primary outcome was the PPV of cardiac catheterization laboratory activation for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The secondary outcome was FMC2B.
A total of 1,877 patients were analyzed for the primary outcome in the pre-intervention period and 405 patients in the post-intervention period. There was an overall decrease in cardiac catheterization laboratory activations, from 67% in the pre-intervention period to 49% in the post-intervention period (95% CI for the difference, -14% to -22%). The overall rate of cardiac catheterization declined in post-intervention period as compared the pre-intervention period, from 34% to 30% (95% CI, for the difference -7.6% to 0.4%), but actually increased for subjects who had activation (48% versus 58%; 95% CI, 4.6%-15.0%). Implementation of the PreAct algorithm was associated with an increase in the PPV of activation for PCI or CABG from 37.9% to 48.6%. The overall odds ratio (OR) associated with the intervention was 1.4 (95% CI, 1.1-1.8). The effect of the intervention was to decrease variability between medical centers. There was no associated change in average FMC2B.
The implementation of the PreAct algorithm in the LAC EMS system was associated with an overall increase in the PPV of cardiac catheterization laboratory activation.
Attention deficit/hyperactivity disorder (ADHD) often presents as an impairing lifelong condition in adults, yet it is currently under-diagnosed and under-treated in many European countries.
To establish the characteristics of the European (EU) adult ADHD patient relative to adult patients outside the EU (OEU).
To compare the baseline characteristics of patients with ADHD in regions where adult ADHD is relatively well established (e.g., USA), with EU adult ADHD patients.
Baseline data was used from the open-label acute treatment period of a multicenter, randomized, withdrawal trial of atomoxetine in adult patients with ADHD (N = 2017; EU, n = 1217; OEU, n = 800). All enrolled patients were included in the baseline analyses.
The demographics for patients in the EU region and regions OEU were comparable. Patients in the EU region had a somewhat lower percentage of prior exposure to psychostimulants compared to the region OEU (32.7% versus 38.9%, p = .005). Conners’ Adult ADHD Rating Scale-Investigator Rated: Screening Version with adult ADHD prompts (18 item total, inattentive and hyperactive/impulsive subscales, and index) were comparable. The adult ADHD Quality of Life life outlook and life productivity domain scores were different between groups (p ≤ .0004). The EuroQol-5 Dimension UK and US population-based Index score, and health state score were comparable between groups.
There were some subtle differences between study groups; however, overall, the adult ADHD patients were not substantially different between the EU region and regions OEU, suggesting that baseline features of ADHD in adult EU patients manifest comparable to those in patients OEU.
Glyphosate-resistant (GR) canola is a widely grown crop across western Canada and has quickly become a prolific volunteer weed. Glyphosate-resistant soybean is rapidly gaining acreage in western Canada. Thus, there is a need to evaluate herbicide options to manage volunteer GR canola in GR soybean crops. We conducted an experiment to evaluate the efficacy of various PRE and POST herbicides applied sequentially to volunteer GR canola and to evaluate soybean injury caused by these herbicides. Trials were conducted across Saskatchewan and Manitoba in 2014 and 2015. All treatments provided a range of suppression (>70%) to control (>80%) of volunteer canola. All treatments with the exception of the glyphosate-treated control reduced aboveground canola biomass by an average of 96%. As well, canola seed contamination was reduced from 36% to less than 5% when a PRE and POST herbicide were both used. Moreover, all combinations of herbicides used had excellent crop safety (<10%). All PRE and POST herbicide combinations provided better control of volunteer canola compared with the glyphosate-only control, but tribenuron followed by bentazon and tribenuron followed by imazamox plus bentazon provided solutions that were low cost, currently available (registered in western Canada), and had the potential to minimize development of herbicide resistance in other weeds.
Psychotropic prescription rates continue to increase in the United States (USA). Few studies have investigated whether social-structural factors may play a role in psychotropic medication use independent of mental illness. Food insecurity is prevalent among people living with HIV in the USA and has been associated with poor mental health. We investigated whether food insecurity was associated with psychotropic medication use independent of the symptoms of depression and anxiety among women living with HIV in the USA.
We used cross-sectional data from the Women's Interagency HIV Study (WIHS), a nationwide cohort study. Food security (FS) was the primary explanatory variable, measured using the Household Food Security Survey Module. First, we used multivariable linear regressions to test whether FS was associated with symptoms of depression (Center for Epidemiologic Studies Depression [CESD] score), generalised anxiety disorder (GAD-7 score) and mental health-related quality of life (MOS-HIV Mental Health Summary score; MHS). Next, we examined associations of FS with the use of any psychotropic medications, including antidepressants, sedatives and antipsychotics, using multivariable logistic regressions adjusting for age, race/ethnicity, income, education and alcohol and substance use. In separate models, we additionally adjusted for symptoms of depression (CESD score) and anxiety (GAD-7 score).
Of the 905 women in the sample, two-thirds were African-American. Lower FS (i.e. worse food insecurity) was associated with greater symptoms of depression and anxiety in a dose–response relationship. For the psychotropic medication outcomes, marginal and low FS were associated with 2.06 (p < 0.001; 95% confidence interval [CI] = 1.36–3.13) and 1.99 (p < 0.01; 95% CI = 1.26–3.15) times higher odds of any psychotropic medication use, respectively, before adjusting for depression and anxiety. The association of very low FS with any psychotropic medication use was not statistically significant. A similar pattern was found for antidepressant and sedative use. After additionally adjusting for CESD and GAD-7 scores, marginal FS remained associated with 1.93 (p < 0.05; 95% CI = 1.16–3.19) times higher odds of any psychotropic medication use. Very low FS, conversely, was significantly associated with lower odds of antidepressant use (adjusted odds ratio = 0.42; p < 0.05; 95% CI = 0.19–0.96).
Marginal FS was associated with higher odds of using psychotropic medications independent of depression and anxiety, while very low FS was associated with lower odds. These complex findings may indicate that people experiencing very low FS face barriers to accessing mental health services, while those experiencing marginal FS who do access services are more likely to be prescribed psychotropic medications for distress arising from social and structural factors.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
In recent years, soybean acreage has increased significantly in western Canada. One of the challenges associated with growing soybean in western Canada is the control of volunteer glyphosate-resistant (GR) canola, because most soybean cultivars are also glyphosate resistant. The objective of this research was to determine the impact of soybean seeding rate and planting date on competition with volunteer canola. We also attempted to determine how high seeding rate could be raised while still being economically feasible for producers. Soybean was seeded at five different seeding rates (targeted 10, 20, 40, 80, and 160 plants m−2) and three planting dates (targeted mid-May, late May, and early June) at four sites across western Canada in 2014 and 2015. Soybean yield consistently increased with higher seeding rates, whereas volunteer canola biomass decreased. Planting date generally produced variable results across site-years. An economic analysis determined that the optimal rate was 40 to 60 plants m−2, depending on market price, and the optimal planting date range was from May 20 to June 1.
TwinsUK is the largest cohort of community-dwelling adult twins in the UK. The registry comprises over 14,000 volunteer twins (14,838 including mixed, single and triplets); it is predominantly female (82%) and middle-aged (mean age 59). In addition, over 1800 parents and siblings of twins are registered volunteers. During the last 27 years, TwinsUK has collected numerous questionnaire responses, physical/cognitive measures and biological measures on over 8500 subjects. Data were collected alongside four comprehensive phenotyping clinical visits to the Department of Twin Research and Genetic Epidemiology, King’s College London. Such collection methods have resulted in very detailed longitudinal clinical, biochemical, behavioral, dietary and socioeconomic cohort characterization; it provides a multidisciplinary platform for the study of complex disease during the adult life course, including the process of healthy aging. The major strength of TwinsUK is the availability of several ‘omic’ technologies for a range of sample types from participants, which includes genomewide scans of single-nucleotide variants, next-generation sequencing, metabolomic profiles, microbiomics, exome sequencing, epigenetic markers, gene expression arrays, RNA sequencing and telomere length measures. TwinsUK facilitates and actively encourages sharing the ‘TwinsUK’ resource with the scientific community — interested researchers may request data via the TwinsUK website (http://twinsuk.ac.uk/resources-for-researchers/access-our-data/) for their own use or future collaboration with the study team. In addition, further cohort data collection is planned via the Wellcome Open Research gateway (https://wellcomeopenresearch.org/gateways). The current article presents an up-to-date report on the application of technological advances, new study procedures in the cohort and future direction of TwinsUK.
We describe the design and deployment of GREENBURST, a commensal Fast Radio Burst (FRB) search system at the Green Bank Telescope. GREENBURST uses the dedicated L-band receiver tap to search over the 960–1 920 MHz frequency range for pulses with dispersion measures out to
. Due to its unique design, GREENBURST is capable of conducting searches for FRBs when the L-band receiver is not being used for scheduled observing. This makes it a sensitive single pixel detector capable of reaching deeper in the radio sky. While single pulses from Galactic pulsars and rotating radio transients will be detectable in our observations, and will form part of the database we archive, the primary goal is to detect and study FRBs. Based on recent determinations of the all-sky rate, we predict that the system will detect approximately one FRB for every 2–3 months of continuous operation. The high sensitivity of GREENBURST means that it will also be able to probe the slope of the FRB fluence distribution, which is currently uncertain in this observing band.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
The characterization of modern pollen rain assemblages along environmental gradients is an essential prerequisite for reliable interpretations of fossil pollen records. In this study, we identify pollen-vegetation relationships using modern pollen rain assemblages in moss polsters (n = 13) and lake sediment surface samples (n = 11) along a steep temperature gradient of 7°C (3100–4200 m above sea level) on the western Andean Cordillera, Ecuador. The pollen rain is correlated to vascular plant abundance data recorded in vegetation relevées (n = 13). Results show that pollen spectra from both moss polsters and sediment surface samples reflect changes in species composition along the temperature gradient, despite overrepresentation of upper montane forest taxa in the latter. Estimated pollen transport distance for a lake (Laguna Llaviucu) situated in a steep upper montane forest valley is 1–2 km, while a lake (Laguna Pallcacocha) in the páramo captures pollen input from a distance of up to 10–40 km. Weinmannia spp., Podocarpus spp., and Hedyosmum sp. are indicators of local upper montane forest vegetation, while Phlegmariurus spp. and Plantago spp. are indicators for local páramo vegetation.
We present a workflow to track icebergs in proglacial fjords using oblique time-lapse photos and the Lucas-Kanade optical flow algorithm. We employ the workflow at LeConte Bay, Alaska, where we ran five time-lapse cameras between April 2016 and September 2017, capturing more than 400 000 photos at frame rates of 0.5–4.0 min−1. Hourly to daily average velocity fields in map coordinates illustrate dynamic currents in the bay, with dominant downfjord velocities (exceeding 0.5 m s−1 intermittently) and several eddies. Comparisons with simultaneous Acoustic Doppler Current Profiler (ADCP) measurements yield best agreement for the uppermost ADCP levels (~ 12 m and above), in line with prevalent small icebergs that trace near-surface currents. Tracking results from multiple cameras compare favorably, although cameras with lower frame rates (0.5 min−1) tend to underestimate high flow speeds. Tests to determine requisite temporal and spatial image resolution confirm the importance of high image frame rates, while spatial resolution is of secondary importance. Application of our procedure to other fjords will be successful if iceberg concentrations are high enough and if the camera frame rates are sufficiently rapid (at least 1 min−1 for conditions similar to LeConte Bay).
Buprenorphine/samidorphan (BUP/SAM), a combination of BUP (a µ-opioid receptor partial agonist and κ-antagonist) and SAM (a sublingually bioavailable µ-opioid antagonist), is an investigational opioid system modulator for depression. BUP/SAM has shown efficacy versus placebo as an adjunctive treatment for major depressive disorder (MDD) and a consistent safety profile in previously reported, placebo-controlled clinical studies.1,2
1. To characterize the safety profile following long-term treatment with BUP/SAM
2. To explore depression symptoms and remission rates in patients with MDD following long-term treatment with BUP/SAM
FORWARD-2 (Clinicaltrials.gov ID: NCT02141399) enrolled patients who had participated in 1 of 4 controlled studies as well as de novo patients. All patients had a confirmed diagnosis of MDD, had a history of inadequate response to standard antidepressant therapies (ADTs), and had been treated with an adequate dose of an established ADT for ≥8weeks before BUP/SAM initiation. ADT dosage could be titrated, but the ADT could not be changed. During the study, patients received open-label, sublingual BUP/SAM 2mg/2mg as adjunctive treatment for up to 52weeks. Safety (primary objective) was assessed via adverse events (AEs), vital signs, laboratory analytes, and electrocardiography. Suicidal ideation or behavior (SIB) was evaluated by the Columbia Suicide Severity Rating Scale. Abuse potential, dependence, and withdrawal were assessed by AEs and the Clinical Opiate Withdrawal Scale. Exploratory efficacy endpoints included mean Montgomery–Åsberg Depression Rating Scale (MADRS) scores and remission rate (MADRS ≤10).
Of 1454 total patients, 49% completed the 52-week study, 11% discontinued due to an AE, and 40% discontinued because of other reasons as of the interim data cutoff date (April 30, 2017). Most AEs were of mild/moderate severity. Serious AEs were reported in 3.2% of patients. AEs occurring in ≥10% of patients were nausea, headache, constipation, dizziness, and somnolence. There was no evidence of increased risk of SIB with BUP/SAM. Incidence of euphoria-related events was low (1.2%). After abrupt discontinuation of BUP/SAM, there was little evidence of withdrawal. BUP/SAM was not associated with meaningful changes in laboratory or metabolic parameters or in bodyweight. The mean MADRS score decreased from 22.9 (±9.7) at baseline to 9.8 (±8.8) after 52weeks. The remission rate at 52weeks was 52.5%.
Long-term treatment with BUP/SAM did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low. BUP/SAM maintained an antidepressant effect for up to 52weeks of treatment in patients with MDD.
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.