DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

Clinical and patient-reported trajectories at end-of-life in older patients with advanced CKD

Background We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with advanced chronic kidney disease (CKD). Methods The EQUAL study is a European observational prospective cohort study with an incident eGFR Results We included 661 decedents with a median time to death of 2.0 years (IQR 0.9-3.2). During the years preceding death, eGFR, Subjective Global Assessment score, and blood pressure declined, with accelerations seen at 6 months preceding death. Serum hemoglobin, hematocrit, cholesterol, calcium, albumin, and sodium values declined slowly during follow-up, with accelerations observed between 6 and 12 months preceding death. Physical and mental quality of life declined linearly throughout follow-up. The number of reported symptoms was stable up to 2 years prior to death, with an acceleration observed at 1 year prior to death. The rate of hospitalization was stable at around one hospitalization per person year, increasing exponentially at 6 months preceding death. Conclusions We identified clinically relevant physiological accelerations in patient trajectories that began similar to 6 to 12 months prior to death, which are likely multifactorial in nature, but correlate with a surge in hospitalizations. Further research should focus on how to effectively use this knowledge to inform patient and family expectations, to benefit the planning of (end-of-life) care, and to establish clinical alert systems.Clinical epidemiolog

Modeling and Simulation of Void Closure during Steckel Mill Rolling for Steel Plate

Internal void defects as shrinkage porosity, gas bubble, and thermo-mechanical cracks are usually formed during steel casting processes. These defects have critical impact on the quality and service life of hot-rolled products. Study of the possibility of self-healing of existing internal defects during hot-rolling process has been of interest to industry and researchers. Prediction of void closure is extremely useful in relation to better product design and manufacturing process optimization. Herein, a 3D finite element model of the slab hot-rolling process is developed to simulate and analyze the healing of internal voids in hot-rolled steel plate. The material model for the steel plate is developed based on Johnson–Cook constitutive relation to accurately represent its viscoplastic behavior at high temperatures as well as account for strain rate sensitivity. The study evaluates the thermal and mechanical response of low-carbon steel slabs having pre-existing voids during multi-pass strands reverse hot-rolling process. Through thickness plastic strains within the slab are found to influence void closure. Results show that variation in void size and locations also affect the healing possibilities. Finally, the effect of thermal history and thermo-mechanical stresses on void closure is studied