Sade's Itinerary of Transgression

"I would like to address the nature of transgression and its logic or itinerary in Sade's work. If this task is somewhat speculative and incomplete, it perhaps mirrors the foundational incompleteness of the more than sixteen extant volumes of Sade's writings. For a more exhaustive, if not definitive, resolution of the very issue of transgression, the analysis would have to continue the debate between Derrida and Foucault over the validity of Bataille's celebrated account of transgression, which in turn draws upon the earlier work of Roger Caillois." (opening paragraph of the article

Derrida's critique of Husserl and the philosophy of presence

O autor reexamina a crítica de Derrida à fenomenologia de Husserl de forma a mostrar como a sua coerência estrutural emerge não tanto de uma redução a uma doutrina particular mas antes das exigências de uma concepção unitária, especificamente impostas pelas determinações epistemológicas e metafísicas da presenç

The Grand Challenge for Frontiers in Genetics: To Understand Past, Present, and Future

For decades now, scientists have waxed poetically about the excitement of the fields of genetics and genomics, about the bright future ahead, about the exciting times given the advent of new technology and the rapid pace of new discoveries, and about the intense challenges facing us as we think about the ever more enormous quantities of data that stream forth from our machines. Today, things are no different. We face an ever increasing deluge of data and yet it is a welcome deluge and one of our own making. This data deluge is welcome in part because we have worked so hard and long for it, in part because i

Is the US Population Behaving Healthier?

In the past few decades, some measures of population risk have improved, while others have deteriorated. Understanding the health of the population requires integrating these different trends. We compare the risk factor profile of the population in the early 1970s with that of the population in the early 2000s and consider the impact of a continuation of recent trends. Despite substantial increases in obesity in the past three decades, the overall population risk profile is healthier now than it was formerly. For the population aged 25-74, the 10 year probability of death fell from 9.8 percent in 1971-75 to 8.4 percent in 1999-2002. Among the population aged 55-74, the 10 year risk of death fell from 25.7 percent to 21.7 percent. The largest contributors to these changes were the reduction in smoking and better control of blood pressure. Increased obesity increased risk, but not by as large a quantitative amount. In the future, however, increased obesity may play a larger role than continued reductions in smoking. We estimate that a continuation of trends over the past three decades to the next three decades might offset about a third of the behavioral improvements witnessed in recent years.

Characterization of small molecules inhibiting the pro-angiogenic activity of the zinc finger transcription factor Vezf1

Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of anti-angiogenic therapies that treat various diseases, including cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20 μM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases

Role of a plausible nuisance contributor in the declining obesity-mortality risks over time.

CONTEXT: Recent analyses of epidemiological data including the National Health and Nutrition Examination Survey (NHANES) have suggested that the harmful effects of obesity may have decreased over calendar time. The shifting BMI distribution over time coupled with the application of fixed broad BMI categories in these analyses could be a plausible nuisance contributor to this observed change in the obesity-associated mortality over calendar time. OBJECTIVE: To evaluate the extent to which observed temporal changes in the obesity-mortality association may be due to a shifting population distribution for body mass index (BMI), coupled with analyses based on static, broad BMI categories. DESIGN, SETTING, AND PARTICIPANTS: Simulations were conducted using data from NHANES I and III linked with mortality data. Data from NHANES I were used to fit a true model treating BMI as a continuous variable. Coefficients estimated from this model were used to simulate mortality for participants in NHANES III. Hence, the population-level association between BMI and mortality in NHANES III was fixed to be identical to the association estimated in NHANES I. Hazard ratios (HRs) for obesity categories based on BMI for NHANES III with simulated mortality data were compared to the corresponding estimated HRs from NHANES I. MAIN OUTCOME MEASURES: Change in hazard ratios for simulated data in NHANES III compared to observed estimates from NHANES I. RESULTS: On average, hazard ratios for NHANES III based on simulated mortality data were 29.3% lower than the estimates from NHANES I using observed mortality follow-up. This reduction accounted for roughly three-fourths of the apparent decrease in the obesity-mortality association observed in a previous analysis of these data. CONCLUSIONS: Some of the apparent diminution of the association between obesity and mortality may be an artifact of treating BMI as a categorical variable

Association of Allelic Variation in Genes Mediating Aspects of Energy Homeostasis with Weight Gain during Administration of Antipsychotic Drugs (CATIE Study)

Antipsychotic drugs are widely used in treating schizophrenia, bipolar disorder, and other psychiatric disorders. Many of these drugs, despite their therapeutic advantages, substantially increase body weight. We assessed the association of alleles of 31 genes implicated in body weight regulation with weight gain among patients being treated with specific antipsychotic medications in the clinical antipsychotic trials in intervention effectiveness study, we found that rs2237988 in Potassium Channel Inwardly Rectifying Subfamily J Member 11 (KCNJ11), rs13269119 in Solute carrier family 30 member 8 (SLC30A8), and rs9922047 in fat mass and obesity associated (FTO) were associated with percent weight gain. We also observed the significant interaction of rs11643744 by treatment effect on the weight gain

A Proposed Method for Monitoring U.S. Population Health: Linking Symptoms, Impairments, and Health Ratings

We propose a method of quantifying non-fatal health on a 0-1 QALY scale that details the impact of specific symptoms and impairments and is not based on ratings of counterfactual scenarios. Measures of general health status are regressed on health impairments and symptoms in different domains, using ordered probit and ordinary least squares regression. This yields estimates of their effects analogous to disutility weights, and accounts for complex non-additive relationships. Health measures used include self-rated health status on a 5-point scale, EuroQol 5D (EQ-5D) scores, and ratings of current health using a 0-100 rating scale and a time-tradeoff. Data are from the nationally representative Medical Expenditure Panel Survey (MEPS) year 2002 (N=34,615), with validation in an independent sample from MEPS 2000 (N=21,067) and among 1420 adults age 45-89 in the Beaver Dam Health Outcomes Study. Decrement weights for symptoms and impairments are used to derive estimates of overall health-related quality of life, laying the groundwork for a detailed national summary measure of health. To purchase a copy of the earlier version of this paper, please contact the Working Papers department directly at (617) 588 1405.