Higher Education Exchange: 2008

This annual publication serves as a forum for new ideas and dialogue between scholars and the larger public. Essays explore ways that students, administrators, and faculty can initiate and sustain an ongoing conversation about the public life they share.The Higher Education Exchange is founded on a thought articulated by Thomas Jefferson in 1820: "I know no safe depository of the ultimate powers of the society but the people themselves; and if we think them not enlightened enough to exercise their control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion by education."In the tradition of Jefferson, the Higher Education Exchange agrees that a central goal of higher education is to help make democracy possible by preparing citizens for public life. The Higher Education Exchange is part of a movement to strengthen higher education's democratic mission and foster a more democratic culture throughout American society.Working in this tradition, the Higher Education Exchange publishes interviews, case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies

Identity-by-descent analysis of a large Tourette’s syndrome pedigree from Costa Rica implicates genes involved in neuronal development and signal transduction:Molecular psychiatry

Tourette Syndrome (TS) is a heritable, early-onset neuropsychiatric disorder that typically begins in early childhood. Identifying rare genetic variants that make a significant contribution to risk in affected families may provide important insights into the molecular aetiology of this complex and heterogeneous syndrome. Here we present a whole-genome sequencing (WGS) analysis from the 11-generation pedigree (>500 individuals) of a densely affected Costa Rican family which shares ancestry from six founder pairs. By conducting an identity-by-descent (IBD) analysis using WGS data from 19 individuals from the extended pedigree we have identified putative risk haplotypes that were not seen in controls, and can be linked with four of the six founder pairs. Rare coding and non-coding variants present on the haplotypes and only seen in haplotype carriers show an enrichment in pathways such as regulation of locomotion and signal transduction, suggesting common mechanisms by which the haplotype-specific variants may be contributing to TS-risk in this pedigree. In particular we have identified a rare deleterious missense variation in RAPGEF1 on a chromosome 9 haplotype and two ultra-rare deleterious intronic variants in ERBB4 and IKZF2 on the same chromosome 2 haplotype. All three genes play a role in neurodevelopment. This study, using WGS data in a pedigree-based approach, shows the importance of investigating both coding and non-coding variants to identify genes that may contribute to disease risk. Together, the genes and variants identified on the IBD haplotypes represent biologically relevant targets for investigation in other pedigree and population-based TS data

Contextualizing genetic risk score for disease screening and rare variant discovery.

Studies of the genetic basis of complex traits have demonstrated a substantial role for common, small-effect variant polygenic burden (PB) as well as large-effect variants (LEV, primarily rare). We identify sufficient conditions in which GWAS-derived PB may be used for well-powered rare pathogenic variant discovery or as a sample prioritization tool for whole-genome or exome sequencing. Through extensive simulations of genetic architectures and generative models of disease liability with parameters informed by empirical data, we quantify the power to detect, among cases, a lower PB in LEV carriers than in non-carriers. Furthermore, we uncover clinically useful conditions wherein the risk derived from the PB is comparable to the LEV-derived risk. The resulting summary-statistics-based methodology (with publicly available software, PB-LEV-SCAN) makes predictions on PB-based LEV screening for 36 complex traits, which we confirm in several disease datasets with available LEV information in the UK Biobank, with important implications on clinical decision-making

Self-Reported vs. Measured Height, Weight, and BMI in Young Adults

Self-reported height and weight, if accurate, provide a simple and economical method to track changes in body weight over time. Literature suggests adults tend to under-report their own weight and that the gap between self-reported weight and actual weight increases with obesity. This study investigates the extent of discrepancy in self-reported height, weight, and subsequent Body Mass Index (BMI) versus actual measurements in young adults. Physically measured and self-reported height and weight were taken from 1562 students. Male students marginally overestimated height, while females were closer to target. Males, on average, closely self-reported weight. Self-reported anthropometrics remained statistically correlated to actual measures in both sexes. Categorical variables of calculated BMI from both self-reported and actual height and weight resulted in significant agreement for both sexes. Researcher measured BMI (via anthropometric height and weight) and sex were both found to have association with self-reported weight while only sex was related to height difference. Regression examining weight difference and BMI was significant, specifically with a negative slope indicating increased BMI led to increased underestimation of weight in both sexes. This study suggests self-reported anthropometric measurements in young adults can be used to calculate BMI for weight classification purposes. Further investigation is needed to better assess self-reported vs measured height and weight discrepancies across populations

Higher Education Exchange:2004

This annual publication serves as a forum for new ideas and dialogue between scholars and the larger public. Essays explore ways that students, administrators, and faculty can initiate and sustain an ongoing conversation about the public life they share.The Higher Education Exchange is founded on a thought articulated by Thomas Jefferson in 1820: "I know no safe depository of the ultimate powers of the society but the people themselves; and if we think them not enlightened enough to exercise their control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion by education."In the tradition of Jefferson, the Higher Education Exchange agrees that a central goal of higher education is to help make democracy possible by preparing citizens for public life. The Higher Education Exchange is part of a movement to strengthen higher education's democratic mission and foster a more democratic culture throughout American society.Working in this tradition, the Higher Education Exchange publishes interviews, case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies

Development and Validation of the Short Healthy Eating Index Survey with a College Population to Assess Dietary Quality and Intake

Because diet quality (DQ) is associated with risk of chronic disease and is a common construct assessed in health-related research, validated tools to assess DQ are needed that have low respondent and researcher burden. Thus, content experts develop the Short Healthy Eating Index (sHEI) tool and an associated scoring system. The sHEI scoring system was then refined using a classification and regression tree (CRT) algorithm methodology with an iterative feedback process with expert review and input. The sHEI scoring system was then validated using a concurrent criterion validation process that included the sHEI DQ scores (calculated from responses from 50 participants) being compared to the participants’ Healthy Eating Index scores derived from 24 h recalls. The total HEI score from the CRT algorithm highly correlated with the 24 h recall HEI score (0.79). For individual food group items, the correlation between the CRT algorithm scoring and the 24 h recall data scoring ranged from 0.44 for refined grains to 0.64 for whole fruits. The sHEI appears to be a valid tool for estimating overall dietary quality and individual items (with correlations \u3e 0.49) for fruits, vegetables, dairy, added sugar, sugar from sugar-sweetened beverages, and calcium

Doing time and motion diffractively: Academic life everywhere and all the time

This article offers a diffractive methodological intervention into workplace studies of academic life. In its engagement of a playful, performative research and writing practice the article speaks back to technocratic organisational and sociological workplace ‘time and motion’ studies which centre on the human and rational, and presume a linear teleology of cause and effect. As a counterpoint, we deploy posthumanist new materialist research practices which refuse human-centric approaches and aim to give matter its due. As a means to analyse what comes out of our joint workspaces photo project we produce two ‘passes’ through data – two diffractive experiments which destabilise what normally counts as ‘findings’ and their academic presentation. The article deploys the motif of ‘starting somewhere else’ to signal both our intention to keep data animated, alive and interactive, and to utilise visual and written modes of seriality as enabling constraints which produce a more generative focus on the mundane, emergent, unforeseen, and happenstance in studies of daily working life

Lifetime Prevalence, Age of Risk, and Etiology of Comorbid Psychiatric Disorders in Tourette Syndrome

IMPORTANCE: Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (<200), and none has examined the ages of highest risk for each TS-associated comorbidity or their etiologic relationship to TS. OBJECTIVE: To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional structured diagnostic interviews conducted between April 1, 1992, and December 31, 2008, of participants with TS (n = 1374) and TS-unaffected family members (n = 1142). MAIN OUTCOMES AND MEASURES: Lifetime prevalence of comorbid DSM-IV-TR disorders, their heritabilities, ages of maximal risk, and associations with symptom severity, age at onset, and parental psychiatric history. RESULTS: The lifetime prevalence of any psychiatric comorbidity among individuals with TS was 85.7%; 57.7% of the population had 2 or more psychiatric disorders. The mean (SD) number of lifetime comorbid diagnoses was 2.1 (1.6); the mean number was 0.9 (1.3) when obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) were excluded, and 72.1% of the individuals met the criteria for OCD or ADHD. Other disorders, including mood, anxiety, and disruptive behavior, each occurred in approximately 30% of the participants. The age of greatest risk for the onset of most comorbid psychiatric disorders was between 4 and 10 years, with the exception of eating and substance use disorders, which began in adolescence (interquartile range, 15–19 years for both). Tourette syndrome was associated with increased risk of anxiety (odds ratio [OR], 1.4; 95% CI, 1.0–1.9; P = .04) and decreased risk of substance use disorders (OR, 0.6; 95% CI, 0.3–0.9; P = .02) independent from comorbid OCD and ADHD; however, high rates of mood disorders among participants with TS (29.8%) may be accounted for by comorbid OCD (OR, 3.7; 95% CI, 2.9–4.8; P < .001). Parental history of ADHD was associated with a higher burden of non-OCD, non-ADHD comorbid psychiatric disorders (OR, 1.86; 95% CI, 1.32–2.61; P < .001). Genetic correlations between TS and mood (RhoG, 0.47), anxiety (RhoG, 0.35), and disruptive behavior disorders (RhoG, 0.48), may be accounted for by ADHD and, for mood disorders, by OCD. CONCLUSIONS AND RELEVANCE: This study is, to our knowledge, the most comprehensive of its kind. It confirms the belief that psychiatric comorbidities are common among individuals with TS, demonstrates that most comorbidities begin early in life, and indicates that certain comorbidities may be mediated by the presence of comorbid OCD or ADHD. In addition, genetic analyses suggest that some comorbidities may be more biologically related to OCD and/or ADHD rather than to TS

COMT and MAO-A Polymorphisms and Obsessive-Compulsive Disorder: A Family-Based Association Study

ObjectiveObsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. the catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. in an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.MethodsTransmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed.ResultsOCD, broad and narrow phenotypes, were not associated with any of the investigated COMT and MAO-A polymorphisms. in addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.ConclusionsThe findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. the evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.Brazilian governmental agenciesConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundo de Aprimoramento Academico (FUAA-Grant for Academic Improvement)Department of Psychiatry University of São Paulo School of MedicineUniv São Paulo, Fac Med, Dept & Inst Psychiat, São Paulo, SP, BrazilUniv Fed Bahia, Serv Med Univ, Salvador, BA, BrazilUniv Pernambuco, Fac Ciencias Med, Recife, PE, BrazilUniversidade Federal de São Paulo, São Paulo, SP, BrazilBritish Columbia Mental Hlth & Addict Res Inst, Vancouver, BC, CanadaMassachusetts Gen Hosp, PNGU, Boston, MA 02114 USAMassachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USAUniv Calif San Francisco, Dept Psychiat, San Francisco, CA USAHosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, CanadaUniv Michigan, Dept Psychiat, Ann Arbor, MI 48109 USASunnybrook Hlth Sci Ctr, Frederick W Thompson Anxiety Disorders Ctr, Toronto, ON M4N 3M5, CanadaUniv Toronto, Ctr Addict & Mental Hlth, Toronto, ON, CanadaUniv Fed Rio de Janeiro, Inst Psiquiatria, IPUB, Programa Ansiedade & Depressao, Rio de Janeiro, BrazilUniv São Paulo, Inst Math & Stat, Dept Stat, São Paulo, SP, BrazilUniversidade Federal de São Paulo, São Paulo, SP, BrazilCNPq: 573974/2008-0FAPESP: 2005/55628-08FAPESP: 2008/57896-8Web of Scienc

Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial

OBJECTIVES. In the phase III SOLO1 trial (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation who were in response after platinum-based chemotherapy. We analyzed the timing, duration and grade of the most common hematologic and non-hematologic adverse events in SOLO1. METHODS. Eligible patients were randomized to olaparib tablets 300 mg twice daily (N = 260)or placebo (N = 131), with a 2-year treatment cap in most patients. Safety outcomes were analyzed in detail in randomized patients who received at least one dose of study drug (olaparib, n = 260; placebo, n = 130). RESULTS. Median time to first onset of the most common hematologic (anemia, neutropenia, thrombocytopenia) and non-hematologic (nausea, fatigue/asthenia, vomiting) adverse events was <3 months in olaparibtreated patients. The first event of anemia, neutropenia, thrombocytopenia, nausea and vomiting lasted a median of <2 months and the first event of fatigue/asthenia lasted a median of 3.48 months in the olaparib group. These adverse events were manageable with supportive treatment and/or olaparib dose modification in most patients, with few patients requiring discontinuation of olaparib. Of 162 patients still receiving olaparib at month 24, 64.2% were receiving the recommended starting dose of olaparib 300 mg twice daily. CONCLUSIONS. Maintenance olaparib had a predictable and manageable adverse event profile in the newly diagnosed setting with no new safety signals identified. Adverse events usually occurred early, were largely manageable and led to discontinuation in a minority of patients