Sudden Cardiac Death with Clozapine and Lorazepam Combination

Objective: To report a case of sudden cardiac death in a patient taking a combination of clozapine and lorazepam. Case summary: A 31-year-old white man with schizophrenia was found dead at his apartment. His medication regimen included clozapine 500 mg at bed time, lorazepam 0.5 mg three times daily and levothyroxine 75 mcg once a day. Autopsy studies revealed cardiac hypertrophy, pulmonary congestion and edema. Discussion: Clozapine therapy may cause cardiomyopathy and reduction in heart rate variability (HRV) indices. Benzodiazepines can reduce vagal tone and increase sympathetic activity. This combination can have an enhanced potential for sudden cardiac death. Conclusions: Clozapine induced cardiomyopathy and arrhythmias from clozapine and/or lorazepam use may have contributed to this man\u27s death

Measurements and Analysis of Secondary User Device Effects on Digital Television Receivers

This is the published version. Copyright © 2009 Newman et al.This article presents results from a study of the potential effects of secondary users operating in unoccupied television spectrum. Television spectrum is known within the wireless communications community as being underutilized, making it a prime candidate for dynamic spectrum access. The proposed use of this open spectrum has prompted questions concerning the quantity of available channel space that could be used without negative impact on consumers who view digital television broadcasts and the viability of secondary use of open channels immediately adjacent to a digital television broadcast channel. In this work, we investigate secondary device operation in the channels directly adjacent to a desired television channel, and the effects upon a selection of consumer digital television (DTV) receivers. Our observations strongly suggest that secondary users could operate "White Space Devices" (WSDs) in unoccupied channel bandwidth directly adjacent to a desired digital television (DTV) channel, with no observable adverse impact upon the reception of the desired channel content

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Energy transfer in collisions of small molecules

Ph.D.Tom Mora