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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.
Data compilations expand the scope of research; however, data citation practice lags behind advances in data use. It remains uncommon for data users to credit data producers in professionally meaningful ways. In paleontology, databases like the Paleobiology Database (PBDB) enable assessment of patterns and processes spanning millions of years, up to global scale. The status quo for data citation creates an imbalance wherein publications drawing data from the PBDB receive significantly more citations (median: 4.3 ± 3.5 citations/year) than the publications producing the data (1.4 ± 1.3 citations/year). By accounting for data reuse where citations were neglected, the projected citation rate for data-provisioning publications approached parity (4.2 ± 2.2 citations/year) and the impact factor of paleontological journals (n = 55) increased by an average of 13.4% (maximum increase = 57.8%) in 2019. Without rebalancing the distribution of scientific credit, emerging “big data” research in paleontology—and science in general—is at risk of undercutting itself through a systematic devaluation of the work that is foundational to the discipline.
Understanding the distribution and extent of suitable habitats is critical for the conservation of endangered and endemic taxa. Such knowledge is limited for many Central African species, including the rare and globally threatened Grey-necked Picathartes Picathartes oreas, one of only two species in the family Picathartidae endemic to the forests of Central Africa. Despite growing concerns about land-use change resulting in fragmentation and loss of forest cover in the region, neither the extent of suitable habitat nor the potential species’ distribution is well known. We combine 339 (new and historical) occurrence records of Grey-necked Picathartes with environmental variables to model the potential global distribution. We used a Maximum Entropy modelling approach that accounted for sampling bias. Our model suggests that Grey-necked Picathartes distribution is strongly associated with steeper slopes and high levels of forest cover, while bioclimatic, vegetation health, and habitat condition variables were all excluded from the final model. We predicted 17,327 km2 of suitable habitat for the species, of which only 2,490 km2 (14.4%) are within protected areas where conservation designations are strictly enforced. These findings show a smaller global distribution of predicted suitable habitat forthe Grey-necked Picathartes than previously thought. This work provides evidence to inform a revision of the International Union for Conservation of Nature (IUCN) Red List status, and may warrant upgrading the status of the species from “Near Threatened” to “Vulnerable”.
Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, “Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease,” includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework.
Despite an elevated risk of psychopathology stemming from COVID-19-related stress, many essential workers stigmatise and avoid psychiatric care. This randomised controlled trial was designed to compare five versions of a social-contact-based brief video intervention for essential workers, differing by protagonist gender and race/ethnicity.
Aims
We examined intervention efficacy on treatment-related stigma (‘stigma’) and openness to seeking treatment (‘openness’), especially among workers who had not received prior mental healthcare. We assessed effectiveness and whether viewer/protagonist demographic concordance heightened effectiveness.
Method
Essential workers (N = 2734) randomly viewed a control video or brief video of an actor portraying an essential worker describing hardships, COVID-related anxiety and depression, and psychotherapy benefits. Five video versions (Black/Latinx/White and male/female) followed an identical 3 min script. Half the intervention group participants rewatched their video 14 days later. Stigma and openness were assessed at baseline, post-intervention, and at 14- and 30-day follow-ups. Trial registration: NCT04964570.
Results
All video intervention groups reported immediately decreased stigma (P < 0.0001; Cohen's d = 0.10) and increased openness (P < 0.0001; d = 0.23). The initial increase in openness was largely maintained in the repeated-video group at day 14 (P < 0.0001; d = 0.18), particularly among viewers without history of psychiatric treatment (P < 0.0001; d = 0.32). Increases were not sustained at follow-up. Female participants viewing a female protagonist and Black participants viewing a Black protagonist demonstrated greater openness than other demographic pairings.
Conclusions
Brief video-based interventions improved immediate stigma and openness. Greater effects among female and Black individuals viewing demographically matched protagonists emphasise the value of tailored interventions, especially for socially oppressed groups. This easily disseminated intervention may proactively increase care-seeking, encouraging treatment among workers in need. Future studies should examine intervention mechanisms and whether linking referrals to psychiatric services generates treatment-seeking.
Field studies were conducted to determine the effects of synthetic auxin herbicides at simulated exposure rates applied to ‘Covington’ sweetpotato propagation beds on the quality of nonrooted stem cuttings (slips). Treatments included diglycolamine salt of dicamba, 2,4-D choline plus nonionic surfactant (NIS), and 2,4-D choline plus glyphosate at 1/10, 1/33, or 1/66 of a 1X application rate (560 g ae ha−1 dicamba, 1,065 g ae ha−1 2,4-D choline, 1,130 g ae ha−1 glyphosate) applied at 2 or 4 wk after first slip harvest (WASH). Injury to sweetpotato 2 wk after treatment was greatest when herbicides were applied 2 WASH (21%) compared to 4 WASH (16%). More slip injury was caused by 2,4-D choline than by dicamba, and the addition of glyphosate did not increase injury over 2,4-D choline alone. Two weeks after the second application, sweetpotato slips were cut 2 cm above the soil surface and transplanted into production fields. In 2019, sweetpotato ground coverage 8 wk after transplanting was reduced 37% and 26% by the 1/10X rates of dicamba and 2,4-D choline plus NIS, respectively. Though dicamba caused less injury to propagation beds than 2,4-D choline with or without glyphosate, after transplanting, slips treated with 1/10X dicamba did not recover as quickly as those treated with 2,4-D choline. In 2020, sweetpotato ground coverage was 90% or greater for all treatments. Dicamba applied 2 WASH decreased marketable sweetpotato storage root yield by 59% compared to the nontreated check, whereas treatments including 2,4-D choline reduced marketable yield 22% to 29%. All herbicides applied at 4 WASH reduced marketable yield 31% to 36%. The addition of glyphosate to 2,4-D choline did not increase sweetpotato yield. Results indicate that caution should be taken when deciding whether to transplant sweetpotato slips that are suspected to have been exposed to dicamba or 2,4-D choline.
Cross-species evidence suggests that the ability to exert control over a stressor is a key dimension of stress exposure that may sensitize frontostriatal-amygdala circuitry to promote more adaptive responses to subsequent stressors. The present study examined neural correlates of stressor controllability in young adults. Participants (N = 56; Mage = 23.74, range = 18–30 years) completed either the controllable or uncontrollable stress condition of the first of two novel stressor controllability tasks during functional magnetic resonance imaging (fMRI) acquisition. Participants in the uncontrollable stress condition were yoked to age- and sex-matched participants in the controllable stress condition. All participants were subsequently exposed to uncontrollable stress in the second task, which is the focus of fMRI analyses reported here. A whole-brain searchlight classification analysis revealed that patterns of activity in the right dorsal anterior insula (dAI) during subsequent exposure to uncontrollable stress could be used to classify participants' initial exposure to either controllable or uncontrollable stress with a peak of 73% accuracy. Previous experience of exerting control over a stressor may change the computations performed within the right dAI during subsequent stress exposure, shedding further light on the neural underpinnings of stressor controllability.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Many healthcare workers do not seek help, despite their enormous stress and greater risk for anxiety, depression and post-traumatic stress disorder (PTSD).
Aims
This study screened for psychopathology and evaluated the efficacy of a brief, social contact-based video intervention in increasing treatment-seeking intentions among healthcare workers (trial registration: NCT04497415). We anticipated finding high rates of psychopathology and greater treatment-seeking intentions post-intervention.
Method
Healthcare workers (n = 350) were randomised to (a) a brief video-based intervention at day 1, coupled with a booster video at day 14; (b) the video at day 1 only; or (c) a non-intervention control. In the 3 min video, a female nurse described difficulty coping with stress, her anxieties and depression, barriers to care and how therapy helped her. Assessments were conducted pre- and post-intervention and at 14- and 30-day follow-ups.
Results
Of the 350 healthcare workers, 281 (80%) reported probable anxiety, depression and/or PTSD. Participants were principally nurses (n = 237; 68%), physicians (n = 52; 15%) and emergency medical technicians (n = 30; 9%). The brief video-based intervention yielded greater increases in treatment-seeking intentions than the control condition, particularly among participants in the repeat-video group. Exploratory analysis revealed that in both video groups, we found greater effect among nurses than non-nurses.
Conclusions
A brief video-based intervention increased treatment-seeking intention, possibly through identification and emotional engagement with the video protagonist. A booster video magnified that effect. This easily disseminated intervention could increase the likelihood of seeking care and offer employers a proactive approach to encourage employees to search for help if needed.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.
Participants:
The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).
Methods:
Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.
Results:
A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level “harm index” for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.
Conclusions:
We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.
Social cognitive deficits can have many negative consequences, spanning social withdrawal to psychopathology. Prior work has shown that child maltreatment may associate with poorer social cognitive skills in later life. However, no studies have examined this association from early childhood into adolescence. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4,438), we examined the association between maltreatment (caregiver physical or emotional abuse; sexual or physical abuse), assessed repeatedly (every 1–3 years) from birth to age 9, and social cognitive skills at ages 7.5, 10.5, and 14 years. We evaluated the role of both the developmental timing (defined by age at exposure) and accumulation of maltreatment (defined as the number of occasions exposed) using a least angle regression variable selection procedure, followed by structural equation modeling. Among females, accumulation of maltreatment explained the most variation in social cognitive skills. For males, no significant associations were found. These findings underscore the importance of early intervention to minimize the accumulation of maltreatment and showcase the importance of prospective studies to understand the development of social cognition over time.
We implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic coronavirus disease 2019 (COVID-19) was <0.5%, which suggests that early local public health interventions were successful. Although our protocol was resource intensive, it prevented exposures to healthcare team members.
This paper provides an up-to-date review of the problems related to the generation, detection and mitigation of strong electromagnetic pulses created in the interaction of high-power, high-energy laser pulses with different types of solid targets. It includes new experimental data obtained independently at several international laboratories. The mechanisms of electromagnetic field generation are analyzed and considered as a function of the intensity and the spectral range of emissions they produce. The major emphasis is put on the GHz frequency domain, which is the most damaging for electronics and may have important applications. The physics of electromagnetic emissions in other spectral domains, in particular THz and MHz, is also discussed. The theoretical models and numerical simulations are compared with the results of experimental measurements, with special attention to the methodology of measurements and complementary diagnostics. Understanding the underlying physical processes is the basis for developing techniques to mitigate the electromagnetic threat and to harness electromagnetic emissions, which may have promising applications.
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.
After he has been condemned to death, Socrates spends a few minutes talking to the jurors before he is taken away. First, he rebukes those who voted against him for resorting to using the court to kill him when they could have waited and let nature do the same job very soon anyhow, for Socrates is an old man (38C). He next contrasts the evils to which his accusers have resorted to his own unbending resolve never to resort to shameful actions, even though in this case such things might have saved his life (38D-39B; cf. 348-350). Then he prophesies to those jurors that younger men will make their lives far more difficult than ever Socrates did, and thus strips from them any notion they may have had that they gained anything by condemning him.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.