In the Supreme Court of the United States Barbara Grutter, Petitioner, v. Lee Bollinger, et al., Respondents. On Writ of Certiorari to the United States Court of Appeals for the Sixth Circuit

Brief of the University of Michigan Asian Pacific American Law Students Association, the University of Michigan Black Law Students\u27 Alliance, the University of Michigan Latino Law Students Association, and the University of Michigan Native American Law Students Association as Amici Curiae in Support of Respondent

In the Supreme Court of the United States Barbara Grutter, Petitioner, v. Lee Bollinger, et al., Respondents. On Writ of Certiorari to the United States Court of Appeals for the Sixth Circuit

Brief of the University of Michigan Asian Pacific American Law Students Association, the University of Michigan Black Law Students\u27 Alliance, the University of Michigan Latino Law Students Association, and the University of Michigan Native American Law Students Association as Amici Curiae in Support of Respondent

HIV-associated bladder cancer: a case series evaluating difficulties in diagnosis and management

<p>Abstract</p> <p>Background</p> <p>Chronic human immunodeficiency virus (HIV) infection is associated with an increased incidence of Non-Acquired Immunodeficiency Syndrome (non-AIDS) defining cancers. To date, only a limited number of cases of bladder cancer have been linked with HIV infection. We sought to describe the clinical characteristics of HIV-associated bladder cancer.</p> <p>Methods</p> <p>A retrospective study was performed involving HIV-positive patients with bladder cancer, combining cases from multiple institutions with published case reports. Data regarding patient demographics, HIV status, clinical presentation, pathology, cancer treatment, and outcome were analyzed using descriptive statistics.</p> <p>Results</p> <p>Eleven patients were identified with a median age of 55 years (range, 33 - 67). The median CD4+ count at cancer diagnosis was 280 cells/mm³(range, 106 - 572 cells/mm³). Six patients (55%) had a known risk factor for bladder cancer, and nine (82%) presented with hematuria. Ten patients had transitional cell carcinoma, and most had superficial disease at presentation. Treatment included mainly transurethral resection of bladder tumor followed by a combination of local and systemic therapies. One patient received intravesical bacillus Calmette-Guèrin (BCG) without complication. Several patients (55%) were alive following therapy, although many (64%) suffered from local relapse and metastatic disease.</p> <p>Conclusion</p> <p>Bladder cancer is part of the growing list of cancers that may be encountered in patients living longer with chronic HIV-infection. Our patients presented at a younger age and with only mild immunosuppression, however, they experienced an expected course for their bladder cancer. Hematuria in an HIV-infected patient warrants a complete evaluation.</p

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations

Phenotype Risk Scores: moving beyond ‘cases’ and ‘controls’ to classify psychiatric disease in hospital-based biobanks

AbstractCurrent phenotype classifiers for large biobanks with coupled electronic health records EHR and multi-omic data rely on ICD-10 codes for definition. However, ICD-10 codes are primarily designed for billing purposes, and may be insufficient for research. Nuanced phenotypes composed of a patients’ experience in the EHR will allow us to create precision psychiatry to predict disease risk, severity, and trajectories in EHR and clinical populations. Here, we create a phenotype risk score (PheRS) for major depressive disorder (MDD) using 2,086 cases and 31,000 individuals from Mount Sinai’s biobank BioMe ™. Rather than classifying individuals as ‘cases’ and ‘controls’, PheRS provide a whole-phenome estimate of each individual’s likelihood of having a given complex trait. These quantitative scores substantially increase power in EHR analyses and may identify individuals with likely ‘missing’ diagnoses (for example, those with large numbers of comorbid diagnoses and risk factors, but who lack explicit MDD diagnoses).Our approach applied ten-fold cross validation and elastic net regression to select comorbid ICD-10 codes for inclusion in our PheRS. We identified 158 ICD-10 codes significantly associated with Moderate MDD (F33.1). Phenotype Risk Score were significantly higher among individuals with ICD-10 MDD diagnoses compared to the rest of the population (Kolgorov-Smirnov p&lt;2.2e-16), and were significantly correlated with MDD polygenic risk scores (R2&gt;0.182). Accurate classifiers are imperative for identification of genetic associations with psychiatric disease; therefore, moving forward research should focus on algorithms that can better encompass a patient’s phenome.</jats:p

Urologic complications of HIV and AIDS

The original publication is available at http://www.nature.com/nrurol/journal/v6/n1/full/ncpuro1273.htmlIn recent years the nature of HIV infection has been dramatically transformed from an invariably fatal disease to a chronic disorder with a relatively benign course. Disease progression from HIV to AIDS and HIV-related mortality can be reduced effectively by several years of treatment with highly active antiretroviral therapy (HAART). For patients who do not have access to HAART, HIV infection continues to be a lethal disorder characterized by opportunistic infection with uncommon organisms (e.g. mycobacteria, fungi, parasites and viruses), as well as lethal malignancies such as Kaposi sarcoma, non-Hodgkin lymphoma and squamous cell carcinoma of the penis or cervix. In patients receiving HAART, urologic complications are likely to be caused by adverse effects of antiretroviral medication (e.g. indinavir urolithiasis) or disorders associated with aging, such as benign prostatic hyperplasia and prostate cancer. Prospective clinical trials have shown that adult male circumcision can reduce the rate of female to male HIV transmission by more than 50%; however, the development of preventive or curative modalities with 100% efficacy remains elusive.Publishers' versio

Comorbid-phenome prediction and phenotype risk scores enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder

AbstractUK Biobank (UKB) is a key contributor in mental health genome-wide association studies (GWAS) but only ~31% of participants completed the Mental Health Questionnaire (“MHQ responders”). We predicted generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and major depression symptoms using elastic net regression in the ~69% of UKB participants lacking MHQ data (“MHQ non-responders”; NTraining=50%; NTest=50%), maximizing the informative sample for these traits. MHQ responders were more likely to be female, from higher socioeconomic positions, and less anxious than non-responders. Genetic correlation of GAD and PTSD between MHQ responders and non-responders ranged from 0.636-1.08; both were predicted by polygenic scores generated from independent cohorts. In meta-analyses of GAD (N=489,579) and PTSD (N=497,803), we discovered many novel genomic risk loci (13 for GAD and 40 for PTSD). Transcriptomic analyses converged on altered regulation of prenatal dorsolateral prefrontal cortex in these disorders.</jats:p