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

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

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.

Value of Medical Innovation in the United States: 1960-2000

Background: The increased use of medical therapies has led to increased medical costs. To provide insight into the value of this increased spending, we compared gains in life expectancy with the increased costs of care from 1960 through 2000. Methods: We estimated life expectancy in 1960, 1970, 1980, 1990, and 2000 for four age groups. To control for the influence of nonmedical factors on survival, we assumed in our base-case analysis that 50 percent of the gains were due to medical care. We compared the adjusted increases in life expectancy with the lifetime cost of medical care in the same years. Results: From 1960 through 2000, the life expectancy for newborns increased by 6.97 years, lifetime medical spending adjusted for inflation increased by approximately $69,000, and the cost per year of life gained was$19,900. The cost increased from $7,400 per year of life gained in the 1970s to$36,300 in the 1990s. The average cost per year of life gained in 1960–2000 was approximately $31,600 at 15 years of age,$53,700 at 45 years of age, and $84,700 at 65 years of age. At 65 years of age, costs rose more rapidly than did life expectancy: the cost per year of life gained was$121,000 between 1980 and 1990 and $145,000 between 1990 and 2000. Conclusions: On average, the increases in medical spending since 1960 have provided reasonable value. However, the spending increases in medical care for the elderly since 1980 are associated with a high cost per year of life gained. The national focus on the rise in medical spending should be balanced by attention to the health benefits of this increased spending.Economic

Forecasting the Effects of Obesity and Smoking on U.S. Life Expectancy

Background: While increases in obesity over the past 30 years have adversely affected population health, there have been concomitant improvements due to reductions in smoking. Better understanding of the joint effects of these trends on longevity and quality of life will help policymakers target resources more efficiently. Methods: For each year from 2005 to 2020, we forecast life expectancy and qualityadjusted life expectancy for a representative 18 year old, assuming a continuation of past trends in smoking from the National Health Interview Survey (1978-79, 1990-91 and 2004-06), and past trends in body-mass index (BMI) from the National Health and Nutrition Examination Survey (1971-75, 1998-1994, and 2003-06). The 2003 Medical Expenditure Panel Survey was used to examine the effects of smoking and BMI on health-related quality of life. Results: The negative effects of increasing BMI overwhelmed the positive effects of declines in smoking in multiple scenarios. In the base case, increases in the remaining life expectancy of a typical 18 year old are held back by 0.71 years or 0.91 quality-adjusted years between 2005 and 2020. If all U.S. adults became normal weight non-smokers by 2020, LE is forecast to increase by 3.76 life years or 5.16 quality-adjusted years. Conclusions: If past obesity trends continue unchecked, the negative impact on U.S. population health is forecast to overtake the positive effect from declining smoking rates, which could erode the pattern of steady gains in health experienced since early in the 20th century.Economic