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Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder characterized by recurrent intrusive thoughts and ritualized behaviors, often aimed at reducing distress. OCD is heterogeneous in its presentation and many patients with OCD experience a variety of different symptoms throughout their course of illness. Efforts to understand symptom domains in OCD have typically identified three to five symptom domains, such as the domains of doubt/checking, contamination, superstitions/rituals, symmetry/hoarding, and taboo thoughts. Recent studies in the genetics of OCD have suggested a common OCD dimension may provide additional information above and beyond the previously identified symptom domains. Thus, we sought to test a hierarchical model of lifetime OCD symptoms and evaluate the utility of the inclusion of a common OCD dimension.
Methods
Participants included 999 individuals participating in the OCD Collaborative Genetics Study (OCGS) and an additional 2363 individuals participating in the OCD Genetic Association Study (OCGAS). We evaluated unidimensional, 5-factor, and hierarchical models of lifetime OCD symptom presentation using confirmatory factor analysis.
Results
Results suggested that the hierarchical model best fit the data. Further evaluation of these models using a Bayesian testlet response model showed that lifetime presence of specific OCD symptoms was differentially associated with lifetime OCD severity. Moreover, symptoms associated with greater lifetime severity were generally reported less frequently than symptoms present at lower levels of lifetime severity. Implications of these findings and future directions are discussed.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Develop and implement a system in the Veterans Health Administration (VA) to alert local medical center personnel in real time when an acute- or long-term care patient/resident is admitted to their facility with a history of colonization or infection with a multidrug-resistant organism (MDRO) previously identified at any VA facility across the nation.
Methods:
An algorithm was developed to extract clinical microbiology and local facility census data from the VA Corporate Data Warehouse initially targeting carbapenem-resistant Enterobacterales (CRE) and methicillin-resistant Staphylococcus aureus (MRSA). The algorithm was validated with chart review of CRE cases from 2010-2018, trialed and refined in 24 VA healthcare systems over two years, expanded to other MDROs and implemented nationwide on 4/2022 as “VA Bug Alert” (VABA). Use through 8/2023 was assessed.
Results:
VABA performed well for CRE with recall of 96.3%, precision of 99.8%, and F1 score of 98.0%. At the 24 trial sites, feedback was recorded for 1,011 admissions with a history of CRE (130), MRSA (814), or both (67). Among Infection Preventionists and MDRO Prevention Coordinators, 338 (33%) reported being previously unaware of the information, and of these, 271 (80%) reported they would not have otherwise known this information. By fourteen months after nationwide implementation, 113/130 (87%) VA healthcare systems had at least one VABA subscriber.
Conclusions:
A national system for alerting facilities in real-time of patients admitted with an MDRO history was successfully developed and implemented in VA. Next steps include understanding facilitators and barriers to use and coordination with non-VA facilities nationwide.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Background: There is presently no cure for locomotor deficits after spinal cord injury (SCI). Very few therapies effectively target the brain due to poor understanding of the brain’s role post-SCI. Newly developed tissue clearing techniques have permitted unbiased three-dimensional circuit analysis, opening new opportunities for SCI-related brain interrogation. Methods: We established a novel brain interrogation pipeline by optimizing mouse brain clearing, imaging, and atlas registration. We leveraged a spontaneous recovery lateral hemisection model to analyze whole brain cell activity and connectivity with the lumbar cord using cFos immunolabelling and virus-mediated projection tracing. We identified a functionally and anatomically dynamic region correlating with recovery and interrogated its locomotor role with optogenetics. We assessed deep brain electrical stimulation (DBS) of this region in a more clinically relevant rat contusion SCI using an established bipedal robotic interface. Results: We unexpectedly uncovered the lateral hypothalamus (LH) to functionally and anatomically correlate with recovery. LHVglut2 optogenetic stimulation significantly augmented locomotor function. LH DBS in rats acutely robustly augmented bipedal locomotion post-SCI. Conclusions: This is the first demonstration of the LH’s role in locomotion post-SCI and is a novel DBS target that robustly augmented locomotor function, dependent on LH glutamatergic cells. LH DBS may be a promising intervention in humans.
We describe the scientific goals and survey design of the First Large Absorption Survey in H i (FLASH), a wide field survey for 21-cm line absorption in neutral atomic hydrogen (H i) at intermediate cosmological redshifts. FLASH will be carried out with the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope and is planned to cover the sky south of $\delta \approx +40\,\deg$ at frequencies between 711.5 and 999.5 MHz. At redshifts between $z = 0.4$ and $1.0$ (look-back times of 4 – 8 Gyr), the H i content of the Universe has been poorly explored due to the difficulty of carrying out radio surveys for faint 21-cm line emission and, at ultra-violet wavelengths, space-borne searches for Damped Lyman-$\alpha$ absorption in quasar spectra. The ASKAP wide field of view and large spectral bandwidth, in combination with a radio-quiet site, will enable a search for absorption lines in the radio spectra of bright continuum sources over 80% of the sky. This survey is expected to detect at least several hundred intervening 21-cm absorbers and will produce an H i-absorption-selected catalogue of galaxies rich in cool, star-forming gas, some of which may be concealed from optical surveys. Likewise, at least several hundred associated 21-cm absorbers are expected to be detected within the host galaxies of radio sources at $0.4 < z < 1.0$, providing valuable kinematical information for models of gas accretion and jet-driven feedback in radio-loud active galactic nuclei. FLASH will also detect OH 18-cm absorbers in diffuse molecular gas, megamaser OH emission, radio recombination lines, and stacked H i emission.
To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection.
Design:
Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020.
Setting:
Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia.
Participants:
HCP, including those with and without direct patient-care activities, working during the coronavirus disease 2019 (COVID-19) pandemic.
Methods:
Incident SARS-CoV-2 infections were determined through serologic testing for SARS-CoV-2 IgG at enrollment, at 3 months, and at 6 months. HCP completed monthly surveys regarding occupational activities. Multivariable logistic regression was used to identify occupational factors that increased the risk of SARS-CoV-2 infection.
Results:
Of the 304 evaluable HCP that were seronegative at enrollment, 26 (9%) seroconverted for SARS-CoV-2 IgG by 6 months. Overall, 219 participants (73%) self-identified as White race, 119 (40%) were nurses, and 121 (40%) worked on inpatient medical-surgical floors. In a multivariable analysis, HCP who identified as Black race were more likely to seroconvert than HCP who identified as White (odds ratio, 4.5; 95% confidence interval, 1.3–14.2). Increased risk for SARS-CoV-2 infection was not identified for any occupational activity, including spending >50% of a typical shift at a patient’s bedside, working in a COVID-19 unit, or performing or being present for aerosol-generating procedures (AGPs).
Conclusions:
In our study cohort of HCP working in an academic healthcare system, <10% had evidence of SARS-CoV-2 infection over 6 months. No specific occupational activities were identified as increasing risk for SARS-CoV-2 infection.
Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May–June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.4; 95% CI, 1.2–10.5) and black race (OR, 8.4; 95% CI, 2.7–27.4) were associated with SARS-CoV-2 seropositivity.
Nutrition during the periconceptional period influences postnatal cardiovascular health. We determined whether in vitro embryo culture and transfer, which are manipulations of the nutritional environment during the periconceptional period, dysregulate postnatal blood pressure and blood pressure regulatory mechanisms. Embryos were either transferred to an intermediate recipient ewe (ET) or cultured in vitro in the absence (IVC) or presence of human serum (IVCHS) and a methyl donor (IVCHS+M) for 6 days. Basal blood pressure was recorded at 19–20 weeks after birth. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after varying doses of phenylephrine (PE). mRNA expression of signaling molecules involved in blood pressure regulation was measured in the renal artery. Basal MAP did not differ between groups. Baroreflex sensitivity, set point, and upper plateau were also maintained in all groups after PE stimulation. Adrenergic receptors alpha-1A (αAR1A), alpha-1B (αAR1B), and angiotensin II receptor type 1 (AT1R) mRNA expression were not different from controls in the renal artery. These results suggest there is no programmed effect of ET or IVC on basal blood pressure or the baroreflex control mechanisms in adolescence, but future studies are required to determine the impact of ET and IVC on these mechanisms later in the life course when developmental programming effects may be unmasked by age.
Commercialization of 2,4-D–tolerant crops is a major concern for sweetpotato producers because of potential 2,4-D drift that can cause severe crop injury and yield reduction. A field study was initiated in 2014 and repeated in 2015 to assess impacts of reduced rates of 2,4-D, glyphosate, or a combination of 2,4-D with glyphosate on sweetpotato. In one study, 2,4-D and glyphosate were applied alone and in combination at 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of anticipated field use rates (1.05 kg ha−1 for 2,4-D and 1.12 kg ha−1 for glyphosate) to ‘Beauregard’ sweetpotato at storage root formation (10 days after transplanting [DAP]). In a separate study, all these treatments were applied to ‘Beauregard’ sweetpotato at storage root development (30 DAP). Injury with 2,4-D alone or in combination with glyphosate was generally equal or greater than with glyphosate applied alone at equivalent herbicide rates, indicating that injury is attributable mostly to 2,4-D in the combination. There was a quadratic increase in crop injury and quadratic decrease in crop yield (with respect to most yield grades) with increased rate of 2,4-D applied alone or in combination with glyphosate applied at storage root development. However, neither the results of this relationship nor of the significance of herbicide rate were observed on crop injury or sweetpotato yield when herbicide application occurred at storage root formation, with a few exceptions. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of 2,4-D applied alone or in combination with glyphosate, although injury observed at lower rates was also a concern after initial observation by sweetpotato producers. However, in some cases, yield reduction of U.S. no.1 and marketable grades was also observed after application of 1/250×, 1/100×, or 1/10× rates of 2,4-D alone or with glyphosate when applied at storage root development.
A major concern of sweetpotato producers is the potential negative effects from herbicide drift or sprayer contamination events when dicamba is applied to nearby dicamba-resistant crops. A field study was initiated in 2014 and repeated in 2015 to assess the effects of reduced rates of N,N-Bis-(3-aminopropyl)methylamine (BAPMA) or diglycloamine (DGA) salt of dicamba, glyphosate, or a combination of these individually in separate trials with glyphosate on sweetpotato. Reduced rates of 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of the 1× use rate of each dicamba formulation at 0.56 kg ha−1, glyphosate at 1.12 kg ha−1, and a combination of the two at aforementioned rates were applied to ‘Beauregard’ sweetpotato at storage root formation (10 d after transplanting) in one trial and storage root development (30 d after transplanting) in a separate trial. Injury with each salt of dicamba (BAPMA or DGA) applied alone or with glyphosate was generally equal to or greater than glyphosate applied alone at equivalent rates, indicating that injury is most attributable to the dicamba in the combination. There was a quadratic increase in crop injury and a quadratic decrease in crop yield (with respect to most yield grades) observed with an increased herbicide rate of dicamba applied alone or in combination with glyphosate applied at storage root development. However, with a few exceptions, neither this relationship nor the significance of herbicide rate was observed on crop injury or sweetpotato yield when herbicide application occurred at the storage root formation stage. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of either salt of dicamba applied alone or in combination with glyphosate, although injury observed at lower rates would be cause for concern after initial observation by sweetpotato producers. However, in some cases yield reduction of No.1 and marketable grades was observed following 1/250×, 1/100×, or 1/10× application rates of dicamba alone or with glyphosate when applied at storage root development.
Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
Method
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
Results
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Conclusions
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.
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 $60+$ 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.
The National Institute of Health has mandated good clinical practice (GCP) training for all clinical research investigators and professionals. We developed a GCP game using the Kaizen-Education platform. The GCP Kaizen game was designed to help clinical research professionals immerse themselves into applying International Conference on Harmonization GCP (R2) guidelines in the clinical research setting through case-based questions.
Methods:
Students were invited to participate in the GCP Kaizen game as part of their 100% online academic Masters during the Spring 2019 semester. The structure of the game consisted of 75 original multiple choice and 25 repeated questions stemming from fictitious vignettes that were distributed across 10 weeks. Each question presented a teachable rationale after the answers were submitted. At the end of the game, a satisfaction survey was issued to collect player satisfaction data on the game platform, content, experience as well as perceptions of GCP learning and future GCP concept application.
Results:
There were 71 total players who participated and answered at least one question. Of those, 53 (75%) answered all 100 questions. The game had a high Cronbach’s alpha, and item analyses provided information on question quality, thus assisting us in future quality edits before re-testing and wider dissemination.
Conclusions:
The GCP Kaizen game provides an alternative method for mandated GCP training using principles of gamification. It proved to be a reliable and an effective educational method with high player satisfaction.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Jaswal & Akhtar provide several quotes ostensibly from people with autism but obtained via the discredited techniques of Facilitated Communication and the Rapid Prompting Method, and they do not acknowledge the use of these techniques. As a result, their argument is substantially less convincing than they assert, and the article lacks transparency.
We studied neuroinflammation in individuals with late-life, depression, as arisk factor for dementia, using [11C]PK11195 positron emissiontomography (PET). Five older participants with major depression and 13controls underwent PET and multimodal 3T magnetic resonance imaging (MRI),with blood taken to measure C-reactive protein (CRP). We found significantlyhigher CRP levels in those with late-life depression and raised [11C]PK11195 binding compared with controls in brain regionsassociated with depression, including subgenual anterior cingulate cortex,and significant hippocampal subfield atrophy in cornu ammonis 1 andsubiculum. Our findings suggest neuroinflammation requires furtherinvestigation in late-life depression, both as a possible aetiologicalfactor and a potential therapeutic target.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.