Characterisation of age and polarity at onset in bipolar disorder

Background 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

The cost of firearm violent crime in British Columbia, Canada

This study aimed to quantify the total cost of violent firearm-related offenses in British Columbia in 2016 Canadian dollars over a five-year period, 2012 to 2016. The purposes of this study were to estimate the direct costs to the health care system and indirect costs to society for violent firearm injuries and deaths; and to estimate criminal justice system costs pertaining to firearm incidents. This study clearly demonstrates the significant cost of violent firearm injury in British Columbia and the impacts on the health care system, criminal justice system, and to society at large, particularly within the criminal justice system where the costs were significantly higher than health care.Medicine, Faculty ofPediatrics, Department ofNon UBCReviewedFacultyResearche

Alternative nuclear certified reference materials for safeguards and industry

Large Scale Dried (LSD) spikes are Certified Reference Materials (CRMs) used in nuclear safeguards for an accurate determination and verification of nuclear material inventories by Isotope Dilution Mass Spectrometric (IDMS). They are a metrological quality tool for nuclear plant operators and safeguards laboratories to meet the existing requirements for reliable accountancy and verification measurements (IAEA STR-368). LSD spikes are produced by dispensing and drying down accurately-weighed quantities of Uranium and Plutonium nuclear reference solutions into vials. The dried deposits are not stable over time. To keep the integrity of the spike and to prevent unintended losses of material, the CRMs need to be protected with a matrix or coating material. This material is a critical component for the quality and long-term stability of these CRMs. IDMS relies on the mechanical integrity of the spikes; they need to be robust during transport and storage for their guaranteed life-time. The main requirements for the matrix/coating are good adherence to glass, mechanical stability, resistance to radiation and long term stability. Besides, the material should readily dissolve in nitric acid and should not interfere with chromatographic separation and subsequent mass spectrometric measurements. Under the project "Innovative nuclear CRMs for EURATOM safeguards and industry" (INS-CRM), the JRC Directorate G (Geel and Karlsruhe) is doing research on alternative substances to be used as matrix and/or coating in the spikes. The main candidate is the CarboxyMethyl Cellulose (CMC) which seems to meet the requirements above mentioned. The main goal of the project is to find the right methodology and composition for the preparation of the coatings. Furthermore, the mechanical integrity needs to be proved under simulated transport and radiation conditions. Finally, the self-life of the spikes will be determined. It is also planned to introduce and to test several U/Pu ratios for CRMs suitable for different sample types.JRC.G.II.6-Nuclear Safeguards and Forensic

Alternative nuclear certified reference materials for safeguards and industry

Large-Sized Dried (LSD) spikes are Certified Reference Materials (CRMs) used in nuclear safeguards for accurate determination of nuclear material inventories by Isotope Dilution Mass Spectrometry (IDMS). They are a metrological quality tool to meet the existing requirements for reliable accountancy and verification measurements (IAEA STR-368). LSD spikes are produced by drying down accurately weighed quantities of uranium and plutonium nuclear reference solutions into vials. The dried deposits are not stable over time. To keep the spikes integrity and to prevent unintended losses of material, the CRMs need to be protected with a matrix or coating material. This substance is a critical component for the quality and long-term stability of these CRMs. IDMS relies on the mechanical integrity of the spikes; they need to be robust during transport and storage for their guaranteed life-time. The main requirements for coating materials are good adherence to glass, mechanical stability, resistance to radiation and long term stability. The material should furthermore, not interfere with the preparation and mass spectrometric measurements. Under the project "Innovative nuclear CRMs for EURATOM safeguards and industry" (INS-CRM), the JRC Directorate G for Nuclear Safety and Security examines alternative substances for coating spikes. The main candidate is CarboxyMethyl Cellulose (CMC) which seems to meet the requirements mentioned above. The goal of the project is to find the right methodology and composition for the preparation of the coatings. Additionally, the mechanical integrity needs to be proven under simulated transport and radiation conditions, and finally the spikes shelf life will be determined. Furthermore, to understand better the interaction between the matrix and the actinides, the structure and chemical properties have to be investigated using different analytical techniques. It is also planned to test several U/Pu ratios for CRMs suitable for different sample types. This paper reports on the current status of the project.JRC.G.II.6-Nuclear Safeguards and Forensic

Management of people with a Fontan circulation: a Cardiac Society of Australia and New Zealand position statement

The Fontan circulation describes the circulatory state resulting from an operation in congenital heart disease where systemic venous return is directed to the lungs without an intervening active pumping chamber. As survival increases, so too does recognition of the potential health challenges. This document aims to allow clinicians, people with a Fontan circulation, and their families to benefit from consensus agreement about management of the person with a Fontan circulation. The document was crafted with input from a multidisciplinary group of health care providers as well as individuals with a Fontan circulation and families. It is hoped that the shared common vision of long-term wellbeing will continue to drive improvements in care and quality of life in this patient population and eventually translate into improved survival. Keypoints: • Lifelong quality medical care with access to multidisciplinary services, is of prime importance. Care includes regular tests for surveillance of health status. • Transition from paediatric to adult care is an active process that should commence during early adolescence and continue until successful engagement with adult congenital cardiology care. • Children and adults with a Fontan circulation often have reduced peak exercise capacity (on average, 60–65% of predicted values). Increasingly, evidence suggests exercise training may improve exercise capacity and cardiovascular function. • People with a Fontan circulation have higher rates of anxiety and behavioural disorders, and there needs to be a low threshold for the provision of mental health care. • Pregnancy has increased maternal and fetal risks, and pre-conception multidisciplinary assessment and counselling is essential. • Atrial arrhythmias are common, often late after Fontan surgical repair and due to intra-atrial re-entry or “flutter” mediated by atrial stretch and scarring. Some anti-arrhythmic agents, most classically the type IC drugs, may allow haemodynamically unstable, life-threatening 1:1 AV conduction. • Anticoagulation with warfarin is routine care in patients with atrial arrhythmias. • In patients with recurrent atrial arrhythmias, catheter ablation or surgical conversion may be considered. • The Fontan circulation is an ideal substrate for thrombus formation and may result in intracardiac or intravascular thrombosis, ischaemic stroke, or other embolic phenomena. Antiplatelet and anticoagulant agents are commonly prescribed for thromboprophylaxis in patients with a Fontan circulation. Evidence suggests that treatment with one of these agents is advantageous, but there is no consensus on which is optimal. Despite treatment, symptomatic thromboembolic events are associated with significant mortality. • Heart failure is the leading cause of morbidity and mortality. Diuretics provide symptomatic relief, however standard heart failure medical therapy is not of proven benefit. • Though not well understood, there is increasing concern regarding progressive liver disease with a long-term risk of hepatocellular carcinoma. • Despite early higher mortality post heart transplant, these individuals have better long-term survival outcomes compared with many other heart transplant recipients

Characterisation of age and polarity at onset in bipolar disorder.

BackgroundStudying 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.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-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.ResultsEarlier 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.ConclusionsAAO 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