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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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.
To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.
Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.
Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).
Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.
An open-label extension study (NCT02873208) evaluated the long-term tolerability, safety, and efficacy of combination olanzapine/samidorphan (OLZ/SAM) treatment in patients with schizophrenia. This qualitative sub study explored perceptions of benefit, burden, and satisfaction with previous medications and OLZ/SAM.
Semi-structured interviews (60 minutes; audio-recorded) were conducted. Interviewer sensitivity training, senior interviewer oversight, and a list of common medications to aid recall supported data collection. Interview transcripts were content coded and analyzed (NVivo v11.0).
All 41 patients reported a lifetime burden with schizophrenia adversely impacting employment, relationships, emotional health, social activities, and daily tasks. Hospitalization for schizophrenia management was another reported aspect of disease burden. Although most (n=32) patients reported previous medication benefits, side effects affecting physical, emotional/behavioral, and cognitive functioning were reported by all (n=41). Following OLZ/SAM treatment, 39/41 patients (95%) reported improvements in symptoms including hallucinations, paranoia, depression, sleep, and concentration. Furthermore, patients described improvements in self-esteem, social activities, relationships, and daily activities. Twenty-three patients (56%) reported side effects attributed to OLZ/SAM; lack of energy (n=12 [29%]) and dry mouth (n= 5 [12%]) were most common. Twenty-four (59%) patients were “very satisfied” with OLZ/SAM; most (n=35 [85%]) preferred to continue OLZ/SAM vs switching to another medication. As most substudy patients (n=40; 98%) completed the extension study, satisfied patients may be overrepresented in this analysis.
This qualitative interview approach provided valuable insight into patients’ experiences with previous medications and OLZ/SAM. Overall, most patients reported treatment satisfaction and improvements in symptoms, function, and health-related quality of life with OLZ/SAM.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
This study examined longitudinal associations between performance on the Rey–Osterrieth Complex Figure–Developmental Scoring System (ROCF-DSS) at 8 years of age and academic outcomes at 16 years of age in 133 children with dextro-transposition of the great arteries (d-TGA).
The ROCF-DSS was administered at the age of 8 and the Wechsler Individual Achievement Test, First and Second Edition (WIAT/WIAT-II) at the ages of 8 and 16, respectively. ROCF-DSS protocols were classified by Organization (Organized/Disorganized) and Style (Part-oriented/Holistic). Two-way univariate (ROCF-DSS Organization × Style) ANCOVAs were computed with 16-year academic outcomes as the dependent variables and socioeconomic status (SES) as the covariate.
The Organization × Style interaction was not statistically significant. However, ROCF-DSS Organization at 8 years was significantly associated with Reading, Math, Associative, and Assembled academic skills at 16 years, with better organization predicting better academic performance.
Performance on the ROCF-DSS, a complex visual-spatial problem-solving task, in children with d-TGA can forecast academic performance in both reading and mathematics nearly a decade later. These findings may have implications for identifying risk in children with other medical and neurodevelopmental disorders affecting brain development.
Goosegrass control options in bermudagrass are limited. Topramezone is one option that offers excellent control of mature goosegrass, but application to bermudagrass results in unacceptable symptoms of bleaching and necrosis typical of hydroxyphenylpyruvate dioxygenase inhibitors. Previous research has shown that adding chelated iron reduced the phytotoxicity of topramezone without reducing the efficacy of the herbicide, resulting in safening when applied to bermudagrass. Our objective was to examine additional iron sources to determine whether similar safening effects occur with other sources. Field trials were conducted in the summers of 2016 to 2018 (Auburn University). Mixtures of topramezone and methylated seed oil were combined with six different commercial iron sources, including sodium ferric ethylenediamine di-o-hydroxyphenyl-acetate (FeEDDHA), ferrous diethylenetriamine pentaacetic acid (FeDTPA), iron citrate, FeSO4, and a combination of iron oxide/sucrate/sulfate, some of which contained nitrogen. Bermudagrass necrosis and bleaching symptoms were visually rated on a 0% to 100% scale. Reflectance (normalized difference vegetation index) and clipping yield measurements were also collected. Application of FeDTPA and FeSO4 reduced symptoms of bleaching and necrosis when applied with topramezone. Other treatments that contained nitrogen did not reduce injury but did reduce bermudagrass recovery time following the appearance of necrosis. Inclusion of small amounts of nitrogen often negated the safening effects of FeSO4. The iron oxide/sucrate/sulfate product had no effect on bleaching or necrosis. Data suggest that the iron source had a differential effect on bleaching and necrosis reduction when applied in combination with topramezone to bermudagrass. Overall, FeSO4 and FeDTPA safened topramezone the most on bermudagrass.
POST goosegrass and other grassy weed control in bermudagrass is problematic. Fewer herbicides that can control goosegrass are available due to regulatory pressure and herbicide resistance. Alternative herbicide options that offer effective control are needed. Previous research demonstrates that topramezone controls goosegrass, crabgrass, and other weed species; however, injury to bermudagrass may be unacceptable. The objective of this research was to evaluate the safening potential of topramezone combinations with different additives on bermudagrass. Field trials were conducted at Auburn University during summer and fall from 2015 to 2018 and 2017 to 2018, respectively. Treatments included topramezone mixtures and methylated seed oil applied in combination with five different additives: triclopyr, green turf pigment, green turf paint, ammonium sulfate, and chelated iron. Bermudagrass bleaching and necrosis symptoms were visually rated. Normalized-difference vegetative index measurements and clipping yield data were also collected. Topramezone plus chelated iron, as well as topramezone plus triclopyr, reduced bleaching potential the best; however, the combination of topramezone plus triclopyr resulted in necrosis that outweighed reductions in bleaching. Masking agents such as green turf paint and green turf pigment were ineffective in reducing injury when applied with topramezone. The combination of topramezone plus ammonium sulfate should be avoided because of the high level of necrosis. Topramezone-associated bleaching symptoms were transient and lasted 7 to 14 d on average. Findings from this research suggest that chelated iron added to topramezone and methylated seed oil mixtures acted as a safener on bermudagrass.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
Improved plasticity models require simultaneous experimental local strain and microstructural evolution data. Microscopy tools, such as electron backscatter diffraction (EBSD), that can monitor transformation at the relevant length-scale, are often incompatible with digital image correlation (DIC) techniques required to determine local deformation. In this paper, the viability of forescatter detector (FSD) images as the basis for the DIC study is investigated. Standard FSD and an integrated EBSD/FSD approach (Pattern Region of Interest Analysis System: PRIAS™) are analyzed. Simultaneous strain and microstructure maps are obtained for tensile deformation of Q&P 1180 steel up to ~14% strain. Tests on an undeformed sample that is simply shifted indicate a standard deviation of error in strain of around 0.4% without additional complications from a deformed surface. The method resolves strain bands at ~2 μm spacing but does not provide significant sub-grain strain resolution. Similar resolution was obtained for mechanically polished and electropolished samples, despite electropolished surfaces presenting a smoother, simpler topography. While the resolution of the PRIAS approach depends upon the EBSD step size, the 80 nm step size used provides seemingly similar resolution as 8,000× (22.7 nm) FSD images. Surface feature evolution prevents DIC analysis across large strain steps (>6% strain), but restarting DIC, using an FSD reference image from an interim strain step, allows reasonable DIC across the stress–strain curve. Furthermore, the data are obtained easily and provide complementary information for EBSD analysis.
To determine the Final ICU Need in the 24 hours prior to ICU discharge for children with cardiac disease by utilising a single-centre survey.
A cross-sectional survey was utilised to determine Final ICU Need, which was categorised as “Cardiovascular”, “Respiratory”, “Feeding”, “Sedation”, “Systems Issue”, or “Other” for each encounter. Survey responses were obtained from attending physicians who discharged children (≤18 years of age with ICU length of stay >24 hours) from the Cardiac ICU between April 2016 and July 2018.
Measurements and results:
Survey response rate was 99% (n = 1073), with 667 encounters eligible for analysis. “Cardiovascular” (61%) and “Respiratory” (26%) were the most frequently chosen Final ICU Needs. From a multivariable mixed effects logistic regression model fitted to “Cardiovascular” and “Respiratory”, operations with significantly reduced odds of having “Cardiovascular” Final ICU Need included Glenn palliation (p = 0.003), total anomalous pulmonary venous connection repair (p = 0.024), truncus arteriosus repair (p = 0.044), and vascular ring repair (p < 0.001). Short lengths of stay (<7.9 days) had significantly higher odds of “Cardiovascular” Final ICU Need (p < 0.001). “Cardiovascular” and “Respiratory” Final ICU Needs were also associated with provider and ICU discharge season.
Final ICU Need is a novel metric to identify variations in Cardiac ICU utilisation and clinical trajectories. Final ICU Need was significantly influenced by benchmark operation, length of stay, provider, and season. Future applications of Final ICU Need include targeting quality and research initiatives, calibrating provider and family expectations, and identifying provider-level variability in care processes and mental models.
Childhood maltreatment is associated with increased risk for most forms of psychopathology. We examine emotion dysregulation as a transdiagnostic mechanism linking maltreatment with general psychopathology. A sample of 262 children and adolescents participated; 162 (61.8%) experienced abuse or exposure to domestic violence. We assessed four emotion regulation processes (cognitive reappraisal, attention bias to threat, expressive suppression, and rumination) and emotional reactivity. Psychopathology symptoms were assessed concurrently and at a 2-year longitudinal follow-up. A general psychopathology factor (p factor), representing co-occurrence of psychopathology symptoms across multiple internalizing and externalizing domains, was estimated using confirmatory factor analysis. Maltreatment was associated with heightened emotional reactivity and greater use of expressive suppression and rumination. The association of maltreatment with attention bias varied across development, with maltreated children exhibiting a bias toward threat and adolescents a bias away from threat. Greater emotional reactivity and engagement in rumination mediated the longitudinal association between maltreatment and increased general psychopathology over time. Emotion dysregulation following childhood maltreatment occurs at multiple stages of the emotion generation process, in some cases varies across development, and serves as a transdiagnostic mechanism linking child maltreatment with general psychopathology.
The Pueblo population of Chaco Canyon during the Bonito Phase (AD 800–1130) employed agricultural strategies and water-management systems to enhance food cultivation in this unpredictable environment. Scepticism concerning the timing and effectiveness of this system, however, remains common. Using optically stimulated luminescence dating of sediments and LiDAR imaging, the authors located Bonito Phase canal features at the far west end of the canyon. Additional ED-XRF and strontium isotope (87Sr/86Sr) analyses confirm the diversion of waters from multiple sources during Chaco’s occupation. The extent of this water-management system raises new questions about social organisation and the role of ritual in facilitating responses to environmental unpredictability.
Rapid or explosive heating of electrically conductive films has several applications, and the use of reactive laminates to increase output energy is an intriguing concept. Past studies have shown electrically heated aluminum/nickel (Al/Ni) nano-laminate films to augment this energy by an amount approximately equivalent to the expected heat of mixing between the two elements, which for most intermetallics is a significant fraction of the total heat of reaction (86% for Al/Ni). In this study, we investigate the use of sputtered aluminum/boron (Al/B) laminates to determine whether a similar increase, as measured by the velocity of an ejected flyer layer, occurs. However, observed velocities in any samples containing boron were 38% to 45% lower than samples without boron, despite much higher heats of reaction reported in the literature for Al/B. We attributed this reduction to the vaporization temperature of boron being much higher than that of Al, and because Al electrical resistivity at elevated temperatures was still much lower than boron, boron heating was less efficient as vaporized Al expanded and drove the ejected flyer. These results and analysis give insight into other reactive material combinations in which one of the constituents is an electrical insulator.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
The Behavioral Health Laboratory (BHL), a telephone-based mental health assessment, is a cost-effective approach that can improve mental illness identification and management. The individual BHL instruments, which were originally designed to be administered in-person, have not yet been validated with an in-person BHL assessment. This study therefore aims to characterize the concordance between the BHL data gathered by telephone and in-person interviews.
A cross-sectional study was conducted with English-speaking aging services network (ASN) clients aged 60 years and older in Monroe County, NY who were randomized to a BHL interview either in-person (n = 55) or by telephone (n = 53).
There was strong evidence of equivalence between telephone and in-person interviews for depressive disorders, generalized anxiety, panic disorder, drug misuse, psychosis, PTSD, mental illness symptom severity, and five of the six questions assessing suicidality. There was marginal equivalence in PHQ-9 total scores and one of the six questions assessing suicidal ideation, and no evidence of equivalence between interview modalities for assessing cognitive impairment.
With a few exceptions, the BHL gathered nearly equivalent information via telephone as compared to in-person interviews. This suggests that the BHL may be a cost-effective approach appropriate for dissemination in a wide variety of settings including the ASN. Dissemination of the BHL has the potential to strengthen the linkages between primary care, mental healthcare, and social service providers and improve identification and management of those with late-life mental illness.
The Galactic Center contains large amounts of molecular and ionized gas as well as a plethora of energetic objects. Water masers are an extinction-insensitive probe for star formation and thus ideal for studies of star formation stages in this highly obscured region. With the Australia Telescope Compact Array, we observed 22 GHz water masers in the entire Central Molecular Zone with sub-parsec resolution as part of the large SWAG survey: “Survey of Water and Ammonia in the Galactic Center”. We detect of order 600 22 GHz masers with isotropic luminosities down to ~10−7 L⊙. Masers with luminosities of ≳10−6 L⊙ are likely associated with young stellar objects. They appear to be close to molecular gas streamers and may be due to star formation events that are triggered at pericenter passages near Sgr A*. Weaker masers are more widely distributed and frequently show double line features, a tell-tale sign for an origin in evolved star envelopes.
We identify characteristics of local health departments, which enhance collaborations with community- and faith-based organizations (CFBOs) for emergency preparedness and response.
Online survey data were collected from a sample of 273 disaster preparedness coordinators working at local health departments across the United States between August and December 2011.
Using multiple linear regression models, we found that perceptions of CFBO trust were associated with more successful partnership planning (β=0.63; P=0.02) and capacity building (β=0.61; P=0.01). Employee layoffs in the past 3 years (β=0.41; P=0.001) and urban location (β=0.41; P=0.005) were positively associated with higher ratings of resource sharing between health agencies and CFBOs. Having 1-3 full-time employees increased the ratings of success in communication and outreach activities compared with health departments having less than 1 full-time employee (β=0.33; P=0.05). Positive attitudes toward CFBOs also enhanced communication and outreach (β=0.16; P=0.03).
Staff-capacity factors are important for quick dissemination of information and resources needed to address emerging threats. Building the trust of CFBOs can help address large-scale disasters by improving the success of more involved activities that integrate the CFBO into emergency plans and operations of the health department and that better align with federal-funding performance measures. (Disaster Med Public Health Preparedness. 2018;12:57–66)