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Understanding the mechanisms of major depressive disorder (MDD) improvement is a key challenge to determining effective personalized treatments.
Methods
To identify a data-driven pattern of clinical improvement in MDD and to quantify neural-to-symptom relationships according to antidepressant treatment, we performed a secondary analysis of the publicly available dataset EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care). In EMBARC, participants with MDD were treated either by sertraline or placebo for 8 weeks (Stage 1), and then switched to bupropion according to clinical response (Stage 2). We computed a univariate measure of clinical improvement through a principal component (PC) analysis on the variations of individual items of four clinical scales measuring depression, anxiety, suicidal ideas, and manic-like symptoms. We then investigated how initial clinical and neural factors predicted this measure during Stage 1 by running a linear model for each brain parcel’s resting-state global brain connectivity (GBC) with individual improvement scores during Stage 1.
Results
The first PC (PC1) was similar across treatment groups at stages 1 and 2, suggesting a shared pattern of symptom improvement. PC1 patients’ scores significantly differed according to treatment, whereas no difference in response was evidenced between groups with the Clinical Global Impressions Scale. Baseline GBC correlated with Stage 1 PC1 scores in the sertraline but not in the placebo group.
Using data-driven reduction of symptom scales, we identified a common profile of symptom improvement with distinct intensity between sertraline and placebo.
Conclusions
Mapping from data-driven symptom improvement onto neural circuits revealed treatment-responsive neural profiles that may aid in optimal patient selection for future trials.
The antibiotic spectrum index (ASI) outcome quantifies antibiotic exposure based on spectrum of activity. Our objective was to examine ASI as an exploratory outcome in the context of a recent stewardship-focused, clinical trial in childhood pneumonia that originally used a binary guideline-concordant outcome.
Design:
Secondary analysis of a randomized clinical trial.
Setting:
Two tertiary pediatric hospitals.
Methods:
Encounters were randomly assigned to clinical decision support (CDS) or usual care treatment arm. The ASI was calculated by summing daily ASI scores for each unique antibiotic administered. It was evaluated as a continuous and ordinal measure: No Antibiotics (ASI = 0), Narrow (1-2), Intermediate (3-4), Broad (5-7), and Very Broad (≥8). Proportional odds regression modeled the ordinal ASI outcome in the first 24 hours by treatment arm and compared to the guideline-concordance outcome. Results were stratified by emergency department (ED) disposition. We also conducted a longitudinal, descriptive analysis of day-to-day ASI for those with in-hospital dispositions.
Results:
We included 1027 encounters, 549 (53%) were randomized to CDS and 478 (47%) usual care respectively. ASI Category did not differ by treatment arm overall (Odds Ratio: 0.88[95% Confidence Interval: 0.70,1.09]), which mirrored binary guideline-concordance. Mean ASI was lower for concordant encounters (2.1 vs 8.4, P < 0.001) and across all ED dispositions. In the longitudinal analysis, there were 1137 day-to-day ASI comparisons, with only 7% representing spectrum escalations.
Conclusions:
The ASI outcome yielded similar results to a dichotomous concordance outcome. However, ASI provided more granular insights into antibiotic prescribing, suggesting ASI may be a useful outcome measure in future stewardship-focused trials.
Functional cognitive disorder is an increasingly recognised subtype of functional neurological disorder for which treatment options are currently limited. We have developed a brief online group acceptance and commitment therapy (ACT)-based intervention.
Aims
To assess the feasibility of conducting a randomised controlled trial of this intervention versus treatment as usual (TAU).
Method
The study was a parallel-group, single-blind randomised controlled trial, with participants recruited from cognitive neurology, neuropsychiatry and memory clinics in London. Participants were randomised into two groups: ACT + TAU or TAU alone. Feasibility was assessed on the basis of recruitment and retention rates, the acceptability of the intervention, and signal of efficacy on the primary outcome measure (Acceptance and Action Questionnaire II (AAQ-II)) score, although the study was not powered to demonstrate this statistically. Outcome measures were collected at baseline and at 2, 4 and 6 months post-intervention, including assessments of quality of life, memory, anxiety, depression and healthcare use.
Results
We randomised 44 participants, with a participation rate of 51.1% (95% CI 40.8–61.5%); 36% of referred participants declined involvement, but retention was high, with 81.8% of ACT participants attending at least four sessions, and 64.3% of ACT participants reported being ‘satisfied’ or ‘very satisfied’ compared with 0% in the TAU group. Psychological flexibility as measured using the AAQ-II showed a trend towards modest improvement in the ACT group at 6 months. Other measures (quality of life, mood, memory satisfaction) also demonstrated small to modest positive trends.
Conclusions
It has proven feasible to conduct a randomised controlled trial of ACT versus TAU.
In laboratory testing, a novel hydrogen peroxide gas plasma endoscope sterilizer consistently reduced vegetative organisms, but not bacterial spores, to undetectable levels in the presence of high organism load (≥6.5 log10) and organic material and salts. These findings highlight the importance of meticulous cleaning of endoscopes prior to sterilization.
The opportunity to increase soybean yield has prompted Illinois farmers to plant soybean earlier than historical norms. Extending the growing season with an earlier planting date might alter the relationship between soybean growth and weed emergence timings, potentially altering the optimal herbicide application timings to minimize crop yield loss due to weed interference and ensure minimal weed seed production. The objective of this research was to examine various herbicide treatments applied at different timings and rates to assess the effect on weed control and yield in early-planted soybean. Field experiments were conducted in 2021 at three locations across central Illinois to determine effective chemical strategies for weed management in early-planted soybean. PRE treatments consisted of a S-metolachlor + metribuzin premix applied at planting or just prior to soybean emergence at 0.5X (883 + 210 g ai ha−1) or 1X (1,766 + 420 g ai ha−1) label-recommended rates. POST treatments were applied when weeds reached 10 cm tall and consisted of 1X rates of glufosinate (655 g ai ha−1) + glyphosate (1,260 g ae ha−1) + ammonium sulfate, without or with pyroxasulfone at a 0.5X (63 g ai ha−1) or 1X (126 g ai ha−1) rate. Treatments comprising both a full rate of PRE followed by a POST resulted in the greatest and most consistent weed control at the final evaluation timing. The addition of pyroxasulfone to POST treatments did not consistently reduce late-season weed emergence. The lack of a consistent effect by pyroxasulfone could be attributed to suppression of weeds by soybean canopy closure due to earlier soybean development. The full rate of PRE extended the timing of POST application 2 to 3 wk for all treatments at all locations except Urbana. Full-rate PRE treatments also reduced the time between the POST application and soybean canopy closure. Overall, a full-rate PRE reduced early-season weed interference and minimized soybean yield loss due to weed interference.
Foliar-applied postemergence applications of glufosinate are often applied to glufosinate-resistant crops to provide nonselective weed control without significant crop injury. Rainfall, air temperature, solar radiation, and relative humidity near the time of application have been reported to affect glufosinate efficacy. However, previous research may have not captured the full range of weather variability to which glufosinate may be exposed before or following application. Additionally, climate models suggest more extreme weather will become the norm, further expanding the weather range to which glufosinate can be exposed. The objective of this research was to quantify the probability of successful weed control (efficacy ≥85%) with glufosinate applied to some key weed species across a broad range of weather conditions. A database of >10,000 North American herbicide evaluation trials was used in this study. The database was filtered to include treatments with a single postemergence application of glufosinate applied to waterhemp [Amaranthus tuberculatus (Moq.) Sauer], morningglory species (Ipomoea spp.), and/or giant foxtail (Setaria faberi Herrm.) <15 cm in height. These species were chosen because they are well represented in the database and listed as common and troublesome weed species in both corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] (Van Wychen 2020, 2022). Individual random forest models were created. Low rainfall (≤20 mm) over the 5 d before glufosinate application was detrimental to the probability of successful control of A. tuberculatus and S. faberi. Lower relative humidity (≤70%) and solar radiation (≤23 MJ m−1 d−1) on the day of application reduced the probability of successful weed control in most cases. Additionally, the probability of successful control decreased for all species when average air temperature over the first 5 d after application was ≤25 C. As climate continues to change and become more variable, the risk of unacceptable control of several common species with glufosinate is likely to increase.
We present a re-discovery of G278.94+1.35a as possibly one of the largest known Galactic supernova remnants (SNRs) – that we name Diprotodon. While previously established as a Galactic SNR, Diprotodon is visible in our new Evolutionary Map of the Universe (EMU) and GaLactic and Extragalactic All-sky MWA (GLEAM) radio continuum images at an angular size of $3{{{{.\!^\circ}}}}33\times3{{{{.\!^\circ}}}}23$, much larger than previously measured. At the previously suggested distance of 2.7 kpc, this implies a diameter of 157$\times$152 pc. This size would qualify Diprotodon as the largest known SNR and pushes our estimates of SNR sizes to the upper limits. We investigate the environment in which the SNR is located and examine various scenarios that might explain such a large and relatively bright SNR appearance. We find that Diprotodon is most likely at a much closer distance of $\sim$1 kpc, implying its diameter is 58$\times$56 pc and it is in the radiative evolutionary phase. We also present a new Fermi-LAT data analysis that confirms the angular extent of the SNR in gamma rays. The origin of the high-energy emission remains somewhat puzzling, and the scenarios we explore reveal new puzzles, given this unexpected and unique observation of a seemingly evolved SNR having a hard GeV spectrum with no breaks. We explore both leptonic and hadronic scenarios, as well as the possibility that the high-energy emission arises from the leftover particle population of a historic pulsar wind nebula.
Preschool anxiety is highly prevalent and well known to predict risk for future psychopathology. The present study explores whether a diagnosis of an anxiety disorder in preschool interacts with (a) social skills and (b) cognitive ability to longitudinally predict psychopathology, two well-known protective factors, among a sample of 207 children measured at preschool (Mage = 4.34 years) and early childhood (Mage = 6.61 years). To assess social skills and cognitive ability, we utilized the Social Skills Rating Scale and the Differential Abilities Scale, respectively. To assess psychopathology, we utilized the parent report of the Preschool Age Psychiatric Assessment. Hierarchical linear regression models revealed significant interactions between both social skills and cognitive ability with preschool anxiety. We observed that social skills protected against emergent psychopathology for both children with and without anxiety, although this association was stronger for children with preschool anxiety. Contrastingly, cognitive ability served as a protective factor against future psychopathology primarily among children without preschool anxiety. Results from this study identify targets for future intervention and inform our understanding of how preschool anxiety, a common disorder among young children, shapes future psychopathology risk in childhood.
Foliar-applied postemergence herbicides are a critical component of corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] weed management programs in North America. Rainfall and air temperature around the time of application may affect the efficacy of herbicides applied postemergence in corn or soybean production fields. However, previous research utilized a limited number of site-years and may not capture the range of rainfall and air temperatures that these herbicides are exposed to throughout North America. The objective of this research was to model the probability of achieving successful weed control (≥85%) with commonly applied postemergence herbicides across a broad range of environments. A large database of more than 10,000 individual herbicide evaluation field trials conducted throughout North America was used in this study. The database was filtered to include only trials with a single postemergence application of fomesafen, glyphosate, mesotrione, or fomesafen + glyphosate. Waterhemp [Amaranthus tuberculatus (Moq.) Sauer], morningglory species (Ipomoea spp.), and giant foxtail (Setaria faberi Herrm.) were the weeds of focus. Separate random forest models were created for each weed species by herbicide combination. The probability of successful weed control deteriorated when the average air temperature within the first 10 d after application was <19 or >25 C for most of the herbicide by weed species models. Additionally, drier conditions before postemergence herbicide application reduced the probability of successful control for several of the herbicide by weed species models. As air temperatures increase and rainfall becomes more variable, weed control with many of the commonly used postemergence herbicides is likely to become less reliable.
Weeds are one of the greatest challenges to snap bean (Phaseolus vulgaris L.) production. Anecdotal observation posits certain species frequently escape the weed management system by the time of crop harvest, hereafter called residual weeds. The objectives of this work were to (1) quantify the residual weed community in snap bean grown for processing across the major growing regions in the United States and (2) investigate linkages between the density of residual weeds and their contributions to weed canopy cover. In surveys of 358 fields across the Northwest (NW), Midwest (MW), and Northeast (NE), residual weeds were observed in 95% of the fields. While a total of 109 species or species-groups were identified, one to three species dominated the residual weed community of individual fields in most cases. It was not uncommon to have >10 weeds m−2 with a weed canopy covering >5% of the field’s surface area. Some of the most abundant and problematic species or species-groups escaping control included amaranth species such as smooth pigweed (Amaranthus hybridus L.), Palmer amaranth (Amaranthus palmeri S. Watson), redroot pigweed (Amaranthus retroflexus L.), and waterhemp [Amaranthus tuberculatus (Moq.) Sauer]; common lambsquarters (Chenopodium album L.); large crabgrass [Digitaria sanguinalis (L.) Scop.]; and ivyleaf morningglory (Ipomoea hederacea Jacq.). Emerging threats include hophornbeam copperleaf (Acalypha ostryifolia Riddell) in the MW and sharppoint fluvellin [Kickxia elatine (L.) Dumort.] in the NW. Beyond crop losses due to weed interference, the weed canopy at harvest poses a risk to contaminating snap bean products with foreign material. Random forest modeling predicts the residual weed canopy is dominated by C. album, D. sanguinalis, carpetweed (Mollugo verticillata L.), I. hederacea, amaranth species, and A. ostryifolia. This is the first quantitative report on the weed community escaping control in U.S. snap bean production.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
While clinical research intends to improve health outcomes for all, access to research participation is often limited and inequitable. Geographic proximity is a recognized barrier, thus, systemic infrastructure solutions through federal programs including General Clinical Research Centers and Clinical and Translational Science Awards have sought to improve accessibility. Even with such support, academic medical centers often have limited clinical research-dedicated space apart from shared exam rooms in difficult-to-navigate hospitals or clinics. In 2019, the Duke University School of Medicine looked beyond its medical center campus to identify free-standing sites within Durham communities for participant study visits. Catalyzed by the COVID-19 pandemic, Duke Research at Pickett, a 22 000-square-foot building with a laboratory, 30 exam rooms, and on-site parking, opened in October 2020 to support vaccine and treatment trials. Upon the lifting of many COVID-19 restrictions, and in partnership with the Research Equity and Diversity Initiative (READI) Community Advisory Council, the building was transformed to encourage community gatherings, education, and training programs. To date, Duke Research at Pickett has hosted 2692 participants in 78 research trials and 14 community-engaged activities.
From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants’ preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.
Amaranthus species are problematic weeds in snap bean production systems. They reduce crop yields, and their stem fragments contaminate harvested pods. Knowledge of snap bean tolerance to different preemergence herbicides is limited; however, knowing this tolerance is essential for planning a reliable weed management system, breeding herbicide-tolerant cultivars, and registering herbicides for use on minor crops such as snap bean. Field trials were conducted in 2021 and 2022 to determine the tolerance of eight snap bean cultivars to preemergence herbicides with activity on Amaranthus species, including dimethenamid-P, flumioxazin, lactofen, metribuzin, saflufenacil, and sulfentrazone. Snap bean plant density (number of plants per square meter), plant biomass (grams per plant), and canopy biomass (grams per square meter) 21 d after treatment were used to assess crop tolerance to a range of herbicide rates. Linear mixed-effects regression models were fitted to quantify the relationships between preemergence herbicide rate and snap bean cultivar tolerance. Results indicated a high margin of crop safety with dimethenamid-P and lactofen for weed control in snap bean, and a low margin of crop safety with metribuzin and saflufenacil. Results indicated differential cultivar tolerance to flumioxazin and sulfentrazone, which could be driven by genetic variability among cultivars.
The time-evolution of glacier basal motion remains poorly constrained, despite its importance in understanding the response of glaciers to climate warming. Athabasca Glacier provides an ideal site for observing changes in basal motion over long timescales. Studies from the 1960s provide an in situ baseline dataset constraining ice deformation and basal motion. We use two complementary numerical flow models to investigate changes along a well-studied transverse profile and throughout a larger study area. A cross-sectional flow model allows us to calculate transverse englacial velocity fields to simulate modern and historical conditions. We subsequently use a 3-D numerical ice flow model, Icepack, to estimate changes in basal friction by inverting known surface velocities. Our results reproduce observed velocities well using standard values for flow parameters. They show that basal motion declined significantly (30–40%) and this constitutes the majority (50–80%) of the observed decrease in surface velocities. At the same time, basal resistive stress has remained nearly constant and now balances a much larger fraction of the driving stress. The decline in basal motion over multiple decades of climate warming could serve as a stabilizing feedback mechanism, slowing ice transport to lower elevations, and therefore moderating future mass loss rates.
Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations.
Methods
This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples.
Results
We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18–0.34, p = 8.5 × 10−6). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI −0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06–0.08), female sex (beta = 0.160, 95% CI 0.15–0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03–0.07), while neither the depression PGS (beta = 0.004, 95% CI −0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI −0.01 to 0.03) were strongly associated with MDD.
Conclusions
Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.
Sex differences in the prevalence of ADHD are well reported in the literature, with childhood ADHD being diagnosed 7–8 times more frequently in males than females, despite a population sex ratio of 3–4:1. A recent consensus statement argued that ADHD is under-identified and under-diagnosed in the UK, and this is especially concerning with regards to females. This systematic review aims to investigate specific symptoms characterising the manifestation of ADHD in females compared with both males with ADHD and females without ADHD.
Methods
A systematic search of eligible studies was conducted using predefined search criteria across six databases (Ovid MEDLINE, Ovid EMBASE, Ovid APA PsycINFO, ProQuest, EBSCO ERIC and EBSCO British Education Index), in line with a registration protocol on PROSPERO. Eligible studies included those with statistical analysis comparing ADHD, impact or co-occurring mental health difficulties at the item level, which compared ADHD symptoms in both sexes, or contrasted females with and without ADHD. Studies that exclusively reported total scores without item-level statistical results were excluded. A total of 5,378 articles were identified in the search and 13 studies met the criteria for inclusion.
Results
Outcomes from 13 studies were analysed thematically. 7 studies looked at ADHD at an item level, while 7 studies explored disparities in impairment or other items. Of the eligible studies, 12 compared males and females with ADHD and 4 compared females with and without ADHD. 7 studies focussed on children with ADHD and 6 on adults. Preliminary results from 3 studies of ADHD symptoms in children indicated sex differences in hyperactive and impulsive symptoms: males were more likely to exhibit symptoms such as fidgeting and difficulty remain seated, while females exhibited higher rates of excessive talking and interrupting. Sex differences in impairment showed mixed results. Females with ADHD endorsed self-reported items related to mind-wandering and parent-reported impairment, including friendship difficulties, more than females without ADHD. Overall, the analysis of the results suggested that most studies do show some sex differences in ADHD and impairment items.
Conclusion
While current studies of individuals diagnosed with ADHD highlight important sex differences, the limited number of direct investigations and predominant focus on total symptoms underscore the need for further research. Item-level analysis of symptoms and their impact is essential in exploring how sex influences the associations between ADHD, risk factors and functional outcomes. Recognising potential sex differences is essential for improving ADHD assessment in females and later life outcomes.
The Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) is a landmark prospective, longitudinal study of human development focused on a sample of mothers experiencing poverty and their firstborn children. Although the MLSRA pioneered a number of important topics in the area of social and emotional development, it began with the more specific goal of examining the antecedents of child maltreatment. From that foundation and for more than 40 years, the study has produced a significant body of research on the origins, sequelae, and measurement of childhood abuse and neglect. The principal objectives of this report are to document the early history of the MLSRA and its contributions to the study of child maltreatment and to review and summarize results from the recently updated childhood abuse and neglect coding of the cohort, with particular emphasis on findings related to adult adjustment. While doing so, we highlight key themes and contributions from Dr Dante Cicchetti’s body of research and developmental psychopathology perspective to the MLSRA, a project launched during his tenure as a graduate student at the University of Minnesota.