Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Use of enoxaparin in end-stage renal disease

Enoxaparin has become the treatment of choice for various thromboembolic diseases. In most patients with end-stage renal disease (ESRD), prophylactic dosage of enoxaparin does not appear to be associated with an increased bleeding risk and can be used without the need for monitoring and adjustment of regimens. Empirical dose adjustment and biological monitoring seem to be necessary along with therapeutic doses. Anti-factor Xa poorly predicts the degree of anticoagulation in ESRD patients given enoxaparin

Autoimmune polyglandular syndrome in a woman of 51 years.

Autoimmune polyglandular syndromes (APS) are constellations of symptoms and signs of multiple glandular insufficiencies. We report a rare case of type III APS in a female patient. A 51-year-old woman was treated with radiotherapy because of thymus hyperplasia when she was two years old; she was diagnosed with celiac disease and autoimmune hypothyroidism at 41 years old and with sicca syndrome and myasthenia gravis seronegative a few years later. Our patient demonstrates a previous constellation of diseases of APS, which may be a random association but may also indicate a common immunological and genetic disturbance. The APS is an expression of a system impairment of immune tolerance to autoreactive clones, and this is necessary because the phenomena can become aggressive and expressed clinically. We suppose that the development of thymic hyperplasia or its radiotherapy in childhood may have compromise the patient's immune system

Savings in times of demographic change: Lessons from the German experience

Pension reforms in many developed countries make individuals shoulder a bigger share of longevity and income risks. The desired response is that individuals accumulate private assets for retirement. Whether this actually takes place, is of paramount relevance for scientists and policy makers. We take Germany as an example: Twenty years of pension reform have transformed the monolithic German pension system into a multi-pillar system. Formerly generous public pension benefits are gradually being reduced, while substantial incentives are granted to occupational and private saving schemes. Has this transition worked out? We survey the reform steps and household’s reactions: How did individuals adjust their labor market behavior? How did private and occupational pension plans take off? How do behavioral adjustments vary in the population?Most Germans adapted to the new situation. Both actual and expected retirement decisions changedand the share of households without supplementary pensions decreased from 73% to 39% in little more than a decade. This is a remarkable success. Nonetheless, households with low education, low income and less financial education did neither adjust their retirement behavior nor pick up supplementary pension plans and are thus likely to face difficulties in bridging the gap arising in future pension income

Savings in times of demographic change: Lessons from the German experience

Pension reforms in many developed countries make individuals shoulder a bigger share of longevity and income risks. The desired response is that individuals accumulate private assets for retirement. Whether this actually takes place, is of paramount relevance for scientists and policy makers. We take Germany as an example: Twenty years of pension reform have transformed the monolithic German pension system into a multi-pillar system. Formerly generous public pension benefits are gradually being reduced, while substantial incentives are granted to occupational and private saving schemes. Has this transition worked out? We survey the reform steps and household’s reactions: How did individuals adjust their labor market behavior? How did private and occupational pension plans take off? How do behavioral adjustments vary in the population?Most Germans adapted to the new situation. Both actual and expected retirement decisions changedand the share of households without supplementary pensions decreased from 73% to 39% in little more than a decade. This is a remarkable success. Nonetheless, households with low education, low income and less financial education did neither adjust their retirement behavior nor pick up supplementary pension plans and are thus likely to face difficulties in bridging the gap arising in future pension income

Savings in times of demographic change: Lessons from the German experience

Pension reforms in many developed countries make individuals shoulder a bigger share of longevity and income risks. The desired response is that individuals accumulate private assets for retirement. Whether this actually takes place, is of paramount relevance for scientists and policy makers. We take Germany as an example: Twenty years of pension reform have transformed the monolithic German pension system into a multi-pillar system. Formerly generous public pension benefits are gradually being reduced, while substantial incentives are granted to occupational and private saving schemes. Has this transition worked out? We survey the reform steps and household’s reactions: How did individuals adjust their labor market behavior? How did private and occupational pension plans take off? How do behavioral adjustments vary in the population?Most Germans adapted to the new situation. Both actual and expected retirement decisions changedand the share of households without supplementary pensions decreased from 73% to 39% in little more than a decade. This is a remarkable success. Nonetheless, households with low education, low income and less financial education did neither adjust their retirement behavior nor pick up supplementary pension plans and are thus likely to face difficulties in bridging the gap arising in future pension income