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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.
Galeaclolusite, [Al6(AsO4)3(OH)9(H2O)4]⋅8H2O, is a new secondary hydrated aluminium arsenate mineral from Cap Garonne, Var, France. It forms crusts and spheroids of white fibres up to 50 μm long by 0.4 μm wide and only 0.1 μm thick. The fibres are elongated along  and flattened on (100). The calculated density is 2.27 g⋅cm–3. Optically, galeaclolusite is biaxial with α = 1.550(5), β not determined, γ = 1.570(5) (white light) and partial orientation: Z = c (fibre axis). Electron microprobe analyses coupled with crystal structure refinement results gives an empirical formula based on 33 O atoms of Al5.72Si0.08As2.88O33H34.12. Galeaclolusite is orthorhombic, Pnma, with a = 19.855(4), b = 17.6933(11), c = 7.7799(5) Å, V = 2733.0(7) Å3 and Z = 4. The crystal structure of galeaclolusite was established from its close relationship to bulachite and refined using synchrotron powder X-ray diffraction data. It is based on heteropolyhedral layers, parallel to (100), of composition Al6(AsO4)3(OH)9(H2O)4 and with H-bonded H2O between the layers. The layers contain  spiral chains of edge-shared octahedra, decorated with corner-connected AsO4 tetrahedra, that are the same as in the mineral liskeardite.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
made over a 288-MHz band centred at 887.5 MHz.
Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Patients with poorly controlled diabetes mellitus may have a sentinel emergency department (ED) visit for a precipitating condition prior to presenting for a hyperglycemic emergency, such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS). This study’s objective was to describe the epidemiology and outcomes of patients with a sentinel ED visit prior to their hyperglycemic emergency visit.
This was a 1-year health records review of patients≥18 years old presenting to one of four tertiary care EDs with a discharge diagnosis of hyperglycemia, DKA, or HHS. Trained research personnel collected data on patient characteristics, management, disposition, and determined whether patients came to the ED within the 14 days prior to their hyperglycemia visit. Descriptive statistics were used to summarize the data.
Of 833 visits for hyperglycemia, 142 (17.0%; 95% CI: 14.5% to 19.6%) had a sentinel ED presentation within the preceding 14 days. Mean (SD) age was 50.5 (19.0) years and 54.4% were male; 104 (73.2%) were discharged from this initial visit, and 98/104 (94.2%) were discharged either without their glucose checked or with an elevated blood glucose (>11.0 mmol/L). Of the sentinel visits, 93 (65.5%) were for hyperglycemia and 22 (15.5%) for infection. Upon returning to the ED, 61/142 (43.0%) were admitted for severe hyperglycemia, DKA, or HHS.
In this unique ED-based study, diabetic patients with a sentinel ED visit often returned and required subsequent admission for hyperglycemia. Clinicians should be vigilant in checking blood glucose and provide clear discharge instructions for follow-up and glucose management to prevent further hyperglycemic emergencies from occurring.
Nurses and respiratory therapists are seldom allowed to use automated external defibrillators (AED) during in-hospital cardiac arrest. This can result in significant time delays before defibrillation occurs and lower survival for cardiac arrest victims. We sought to identify barriers and facilitators to AED use by nurses and respiratory therapists.
We conducted semi-structured qualitative interviews with a purposeful sample of nurses and respiratory therapists. We developed the interview guide based on the constructs of the theory of planned behaviour, which elicits salient attitudes, social influences, and control beliefs potentially influencing the intent to use an AED. Interviews were recorded, transcribed verbatim, and analysed until achieving data saturation. Two independent reviewers performed inductive analyses to identify emerging categories and themes, and ranked them by frequency of the number of participants stating the topic.
Demographics for the 24 interviewees include mean age 40.5, 79.2% female, 87.5% performed cardiopulmonary resuscitation (CPR), 29.2% defibrillated a patient. Identified attitudes pertained to the timeliness of defibrillation, patient survival, simplicity of AED use, accuracy of rhythm recognition, and harm to self or others. Social influences consisted of physician and hospital administration support of AED use. Control beliefs included training on AED use, policy allowing AED use, familiarity with AED, and task burden during resuscitation.
Most nurses and respiratory therapists intended to use an AED if permitted to do so by a medical directive. Successful implementation would require educational initiatives focusing on safety and efficacy of AEDs, support from physicians and hospital administrators, and additional training on AED use.
Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of CVD in otherwise healthy individuals. Low n-3 PUFA intake has been associated with the presence of NAFLD; however, the relationship between a biomarker of n-3 status – the Omega-3 Index – and liver fat is yet to be elucidated. A total of eighty overweight adults (fifty-six men) completed the anthropometric and biochemical measurements, including the Omega-3 Index, and underwent proton magnetic resonance spectroscopy assessment of liver fat. Bivariate correlations and multiple regression analyses were performed with reference to prediction of liver fat percentage. The mean Omega-3 Index was high in both NAFLD (intrahepatic lipid concentration≥5·5 %) and non-NAFLD groups. The Omega-3 Index, BMI, waist circumference, glucose, insulin, TAG, high-sensitive C-reactive protein (hsCRP) and alanine aminotransferase (ALT) were positively correlated, and HDL and erythrocyte n-6:n-3 ratio negatively correlated with liver fat concentration. Regression analysis found that simple anthropometric and demographic variables (waist, age) accounted for 31 % of the variance in liver fat and the addition of traditional cardiometabolic blood markers (TAG, HDL, hsCRP and ALT) increased the predictive power to 43 %. The addition of the novel erythrocyte fatty acid variable (Omega-3 Index) to the model only accounted for a further 3 % of the variance (P=0·049). In conclusion, the Omega-3 Index was associated with liver fat concentration but did not improve the overall capacity of demographic, anthropometric and blood markers to predict NAFLD.
Amphibian populations have been declining worldwide, with multiple potential causes. At La Selva field station in north-eastern Costa Rica, previous work has shown that populations of many amphibians have decreased significantly since the 1970s, especially in primary forest. Starting in 1998, we investigated one of the most common frog species at La Selva, the poison-dart frog Oophaga pumilio (= Dendrobates pumilio). In a survey of 50 plots of 100 m2 in 1998, adult frogs were 4.6 times more abundant in secondary forest than in primary forest. Tadpoles were found only in secondary-forest plots. Almost all (89%) of the tadpoles were found in leaf axils of Dieffenbachia spp., which were much more abundant in secondary-forest than in primary-forest plots. The greater abundance of Dieffenbachia spp. in secondary forest was confirmed in a broad survey of ~11 km of trails within La Selva in 2002. When the same trails were resampled in 2012, Dieffenbachia spp. had been extirpated from 72% of the 50-m segments where plants were present in 2002; abundance was greatly reduced in the few trail segments where any Dieffenbachia spp. remained in 2012. The loss of Dieffenbachia spp., especially in secondary forest, removed the species most often used by O. pumilio for tadpole rearing. Based on counts of calling frogs in 2010, there was no difference in O. pumilio abundance in primary versus secondary forest, in striking contrast to multiple earlier surveys that found much greater frog abundance in secondary forest. We propose that the reason for the rapid decline in Dieffenbachia spp. is herbivory by the collared peccary (Pecari tajacu), which has increased in abundance at La Selva in recent years. A likely consequence is continued reduction in O. pumilio populations.
It is believed that when patients present to the emergency department (ED) with recent-onset atrial fibrillation or flutter (RAFF), controlling the ventricular rate before cardioversion improves the success rate. We evaluated the influence of rate control medication and other variables on the success of cardioversion.
This secondary analysis of a medical records review comprised 1,068 patients with RAFF who presented to eight Canadian EDs over 12 months. Univariate analysis was performed to find associations between predictors of conversion to sinus rhythm including use of rate control, rhythm control, and other variables. Predictive variables were incorporated into the multivariate model to calculate adjusted odds ratios (ORs) associated with successful cardioversion.
A total of 634 patients underwent attempted cardioversion: 428 electrical, 354 chemical, and 148 both. Adjusted ORs for factors associated with successful electrical cardioversion were use of rate control medication, 0.39 (95% confidence interval [CI] 0.21-0.74); rhythm control medication, 0.28 (95% CI 0.15-0.53); and CHADS2 score > 0, 0.43 (95% CI 0.15-0.83). ORs for factors associated with successful chemical cardioversion were use of rate control medication, 1.29 (95% CI 0.82-2.03); female sex, 2.37 (95% CI 1.50-3.72); and use of procainamide, 2.32 (95% CI 1.43-3.74).
We demonstrated reduced successful electrical cardioversion of RAFF when patients were pretreated with either rate or rhythm control medication. Although rate control medication was not associated with increased success of chemical cardioversion, use of procainamide was. Slowing the ventricular rate prior to cardioversion should be avoided.