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Mood and anxiety disorders co-occur and share symptoms, treatments and genetic risk, but it is unclear whether combining them into a single phenotype would better capture genetic variation. The contribution of common genetic variation to these disorders has been investigated using a range of measures; however, the differences in their ability to capture variation remain unclear, while the impact of rare variation is mostly unexplored.
Aims
We aimed to explore the contributions of common genetic variation and copy number variations associated with risk of psychiatric morbidity (P-CNVs) to different measures of internalising disorders.
Method
We investigated eight definitions of mood and anxiety disorder, and a combined internalising disorder, derived from self-report questionnaires, diagnostic assessments and electronic healthcare records (EHRs). Association of these definitions with polygenic risk scores (PRSs) of major depressive disorder and anxiety disorder, as well as presence of a P-CNV, was assessed.
Results
The effect sizes of both PRSs and P-CNVs were similar for mood and anxiety disorder. Compared to mood and anxiety disorder, internalising disorder resulted in higher prediction accuracy for PRSs, and increased significance of associations with P-CNVs for most definitions. Comparison across the eight definitions showed that PRSs had higher prediction accuracy and effect sizes for stricter definitions, whereas P-CNVs were more strongly associated with EHR- and self-report-based definitions.
Conclusions
Future studies may benefit from using a combined internalising disorder phenotype, and may need to consider that different phenotype definitions may be more informative depending on whether common or rare variation is studied.
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.
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.
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.
The accelerated rate of product development and design complexities offered by Additive Manufacturing (AM) has allowed for innovation in the space industry. However, the surface roughness of parts poses a challenge, as it impacts performance and is tied to design choices. Design tools for traditional manufacturing methods fall short in AM contexts, prompting the need for alternative design processes. This work proposes an experimental approach to design for AM investigation using design artefacts to explore a process-structure-property-performance relationship.
Prenatal stress has a significant, but small, negative effect on children’s executive function (EF) in middle and high socioeconomic status (SES) households. Importantly, rates and severity of prenatal stress are higher and protective factors are reduced in lower SES households, suggesting prenatal stress may be particularly detrimental for children’s EF in this population. This study examined whether prenatal stress was linked to 5-year-old’s EF in a predominantly low SES sample and child sex moderated this association, as males may be more vulnerable to adverse prenatal experiences. Participants were 132 mother-child dyads drawn from a prospective prenatal cohort. Mothers reported on their depression symptoms, trait anxiety, perceived stress, everyday discrimination, and sleep quality at enrollment and once each trimester, to form a composite prenatal stress measure. Children’s EF was assessed at age 5 years using the parent-report Behavior Rating Inventory of Executive Function - Preschool (BRIEF-P) Global Executive Composite subscale and neuropsychological tasks completed by the children. Mixed models revealed higher prenatal stress was associated with lower BRIEF-P scores, indicating better EF, for females only. Higher prenatal stress was associated with lower performance on neuropsychological EF measures for both males and females. Results add to the limited evidence about prenatal stress effects on children’s EF in low SES households.
OBJECTIVES/GOALS: Patients frequently need or desire fat grafting to improve common issues such as implant visibility and contour deformity, often done as a second, staged procedure following immediate reconstruction. This study aimed to identify which patient factors and reconstructive techniques predict the need for revision with AFG after IBBR METHODS/STUDY POPULATION: Patients who underwent IBBR with either tissue expanders or implants following mastectomy from 2017 to 2021 were identified. Demographics, comorbidities, and the postoperative course were reviewed. The primary outcome variable was AFG after the initial reconstruction. Univariate and regression analyses were performed to identify factors predictive of AFG. RESULTS/ANTICIPATED RESULTS: Five-hundred twenty-nine patients were included in our analysis, with 43% having AFG. Univariate regression displayed single-stage reconstruction (OR=0.53, 95% 0.37-0.75) and previous radiation (OR 0.59, 95% 0.35-0.99) negatively predicted the need for AFG, while bilateral breast reconstruction (BBR) was a predictor (OR 2.32, 95% 1.58-3.4). On multivariate analysis, decreasing age and BBR remained predictive of AFG. The odds of AFG decreased by 3% for every one-unit increase in age (95% CI [0.96, 0.99]). Interestingly, neither pre-pectoral breast reconstruction nor specimen weight:implant ratio was associated with increased need for AFG on univariate/multivariate analysis. DISCUSSION/SIGNIFICANCE: Patients requiring AFG were likely younger and had undergone BBR with tissue expanders. Plane of implant did not appear to affect need for AFG. Knowledge of these predictive factors may help plastic surgeons in preoperative counseling before implant-based breast reconstruction.
There is limited data on the organisation of paediatric echocardiography laboratories in Europe.
Methods:
A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs.
Results:
Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1–12), and echocardiography machines was four (range 1–12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20–60) minutes, and for repeat examination was 20 (5–30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%).
Conclusion:
Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.
Symptoms and cognition are both utilized as indicators of recovery following pediatric concussion, yet their interrelationship is not well understood. This study aimed to investigate: 1) the association of post-concussion symptom burden and cognitive outcomes (processing speed and executive functioning [EF]) at 4 and 12 weeks after pediatric concussion, and 2) the moderating effect of sex on this association.
Methods:
This prospective, multicenter cohort study included participants aged 5.00–17.99 years with acute concussion presenting to four Emergency Departments of the Pediatric Emergency Research Canada network. Five processing speed and EF tasks and the Post-Concussion Symptom Inventory (PCSI; symptom burden, defined as the difference between post-injury and retrospective [pre-injury] scores) were administered at 4 and 12 weeks post-concussion. Generalized least squares models were conducted with task performances as dependent variables and PCSI and PCSI*sex interaction as the main predictors, with important pre-injury demographic and injury characteristics as covariates.
Results:
311 children (65.0% males; median age = 11.92 [IQR = 9.14–14.21 years]) were included in the analysis. After adjusting for covariates, higher symptom burden was associated with lower Backward Digit Span (χ2 = 9.85, p = .043) and Verbal Fluency scores (χ2 = 10.48, p = .033) across time points; these associations were not moderated by sex, ps ≥ .20. Symptom burden was not associated with performance on the Coding, Continuous Performance Test, and Color-Word Interference scores, ps ≥ .17.
Conclusions:
Higher symptom burden is associated with lower working memory and cognitive flexibility following pediatric concussion, yet these associations were not moderated by sex. Findings may inform concussion management by emphasizing the importance of multifaceted assessments of EF.
Wortupaite (IMA2022–107) is a new hydrated magnesium nickel tellurite mineral with a zemannite-like structure, described from the Wortupa gold mine, South Australia, Australia. Wortupaite forms needles up to 25 μm in length, generally clustered and sometimes in blocky masses of shorter (10‒15 μm) crystals. Wortupaite is found growing on melonite, from which the component nickel and tellurium are derived, and is associated with calcite. The strongest powder diffraction lines are [dobsÅ(Iobs)(hkl)]: 8.059 (93) (100), 4.034 (92) (200), 2.832 (43) (211 and 121), 2.769 (100) (202) and 1.920 (45) (213 and 123). The empirical formula of wortupaite as determined by electron probe microanalysis is (Mg0.57Ni0.39Mn0.04)Σ1(Ni2+1.87Fe3+0.13)Σ2(Te4+O3)3⋅3H2O, simplified to the ideal formula of MgNi2+2(Te4+O3)3⋅3H2O with H2O content calculated from the crystal structure. The average crystal structure of wortupaite was determined by single-crystal X-ray diffraction with synchrotron radiation (R1 = 0.0558 for 100 independent reflections). Wortupaite is hexagonal, crystallising in the space group P63/m, with a = 9.2215(13) Å, c = 7.5150(15) Å, V = 553.43(19) Å3 and Z = 2. Wortupaite has a microporous structure, with the negatively charged zemannite-like framework formed by Te4+O3 trigonal pyramids and Ni2+O6 octahedra. For charge balance, Mg2+ and Ni2+ dominant sites are assumed to be located on central sites in the channels, coordinated by 6 H2O groups. An OW site was refined around the Mg2+ dominant site, but OW position(s) were not locatable around the Ni2+ dominant site. A discussion of the different models for crystallographic arrangement of channel species is provided, taking into account possible Fourier truncation effects. Unlike the other four minerals with zemannite-like structures which have a near 50% split of divalent and trivalent framework cations, wortupaite is the first natural phase to have only divalent cations in the framework sites.