Hypofractionated radiotherapy has the potential for second cancer reduction

<p>Abstract</p> <p>Background and Purpose</p> <p>A model for carcinoma and sarcoma induction was used to study the dependence of carcinogenesis after radiotherapy on fractionation.</p> <p>Materials and methods</p> <p>A cancer induction model for radiotherapy doses including fractionation was used to model carcinoma and sarcoma induction after a radiation treatment. For different fractionation schemes the dose response relationships were obtained. Tumor induction was studied as a function of dose per fraction.</p> <p>Results</p> <p>If it is assumed that the tumor is treated up to the same biologically equivalent dose it was found that large dose fractions could decrease second cancer induction. The risk decreases approximately linear with increasing fraction size and is more pronounced for sarcoma induction. Carcinoma induction decreases by around 10% per 1 Gy increase in fraction dose. Sarcoma risk is decreased by about 15% per 1 Gy increase in fractionation. It is also found that tissue which is irradiated using large dose fractions to dose levels lower than 10% of the target dose potentially develop less sarcomas when compared to tissues irradiated to all dose levels. This is not observed for carcinoma induction.</p> <p>Conclusions</p> <p>It was found that carcinoma as well as sarcoma risk decreases with increasing fractionation dose. The reduction of sarcoma risk is even more pronounced than carcinoma risk. Hypofractionation is potentially beneficial with regard to second cancer induction.</p

Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons

BACKGROUND: BCG-vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection. METHODS: We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON(®)-TB-Gold In Tube; QFT-G) during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany. RESULTS: During a 6-month period, 309 contacts (mean age 28.5 ± 10.5 years) from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8%) had received BCG vaccination and 84 (27.2%) had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000). For the TST, the positive response rate was 44.3% (137/309), whilst only 31 (10%) showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (κ = 0.2, with 95% CI 0.14.-0.23), and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7–52.5). In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (κ = 0.58, with 95% CI 0.4–0.68), increasing to 0.68 (95% CI 0.46–0.81), if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany. CONCLUSION: The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection

Mass and Angular Momentum in General Relativity

We present an introduction to mass and angular momentum in General Relativity. After briefly reviewing energy-momentum for matter fields, first in the flat Minkowski case (Special Relativity) and then in curved spacetimes with or without symmetries, we focus on the discussion of energy-momentum for the gravitational field. We illustrate the difficulties rooted in the Equivalence Principle for defining a local energy-momentum density for the gravitational field. This leads to the understanding of gravitational energy-momentum and angular momentum as non-local observables that make sense, at best, for extended domains of spacetime. After introducing Komar quantities associated with spacetime symmetries, it is shown how total energy-momentum can be unambiguously defined for isolated systems, providing fundamental tests for the internal consistency of General Relativity as well as setting the conceptual basis for the understanding of energy loss by gravitational radiation. Finally, several attempts to formulate quasi-local notions of mass and angular momentum associated with extended but finite spacetime domains are presented, together with some illustrations of the relations between total and quasi-local quantities in the particular context of black hole spacetimes. This article is not intended to be a rigorous and exhaustive review of the subject, but rather an invitation to the topic for non-experts. In this sense we follow essentially the expositions in Szabados 2004, Gourgoulhon 2007, Poisson 2004 and Wald 84, and refer the reader interested in further developments to the existing literature, in particular to the excellent and comprehensive review by Szabados (2004).Comment: 41 pages. Notes based on the lecture given at the C.N.R.S. "School on Mass" (June 2008) in Orleans, France. To appear as proceedings in the book "Mass and Motion in General Relativity", eds. L. Blanchet, A. Spallicci and B. Whiting. Some comments and references added

Improving epidemiologic data analyses through multivariate regression modelling

Regression modelling is one of the most widely utilized approaches in epidemiological analyses. It provides a method of identifying statistical associations, from which potential causal associations relevant to disease control may then be investigated. Multivariable regression – a single dependent variable (outcome, usually disease) with multiple independent variables (predictors) – has long been the standard model. Generalizing multivariable regression to multivariate regression – all variables potentially statistically dependent – offers a far richer modelling framework. Through a series of simple illustrative examples we compare and contrast these approaches. The technical methodology used to implement multivariate regression is well established – Bayesian network structure discovery – and while a relative newcomer to the epidemiological literature has a long history in computing science. Applications of multivariate analysis in epidemiological studies can provide a greater understanding of disease processes at the population level, leading to the design of better disease control and prevention programs

Political and social determinants of life expectancy in less developed countries: a longitudinal study

<p>Abstract</p> <p>Background</p> <p>This study aimed to examine the longitudinal contributions of four political and socioeconomic factors to the increase in life expectancy in less developed countries (LDCs) between 1970 and 2004.</p> <p>Methods</p> <p>We collected 35 years of annual data for 119 LDCs on life expectancy at birth and on four key socioeconomic indicators: economy, measured by log10 gross domestic product per capita at purchasing power parity; educational environment, measured by the literacy rate of the adult population aged 15 years and over; nutritional status, measured by the proportion of undernourished people in the population; and political regime, measured by the regime score from the Polity IV database. Using linear mixed models, we analyzed the longitudinal effects of these multiple factors on life expectancy at birth with a lag of 0-10 years, adjusting for both time and regional correlations.</p> <p>Results</p> <p>The LDCs' increases in life expectancy over time were associated with all four factors. Political regime had the least influence on increased life expectancy to begin with, but became significant starting in the 3rd year and continued to increase, while the impact of the other socioeconomic factors began strong but continually decreased over time. The combined effects of these four socioeconomic and political determinants contributed 54.74% - 98.16% of the life expectancy gains throughout the lag periods of 0-10 years.</p> <p>Conclusions</p> <p>Though the effect of democratic politics on increasing life expectancy was relatively small in the short term when compared to the effects of the other socioeconomic factors, the long-term impact of democracy should not be underestimated.</p

Melioidosis Vaccines: A Systematic Review and Appraisal of the Potential to Exploit Biodefense Vaccines for Public Health Purposes

The designation of Burkholderia pseudomallei as a category B select agent has resulted in considerable research funding to develop a protective vaccine. This bacterium also causes a naturally occurring disease (melioidosis), an important cause of death in many countries including Thailand and Australia. In this study, we explored whether a vaccine could be used to provide protection from melioidosis. An economic evaluation based on its use in Thailand indicated that a vaccine could be a cost-effective intervention if used in high-risk populations such as diabetics and those with chronic kidney or lung disease. A literature search of vaccine studies in animal models identified the current candidates, but noted that models failed to take account of the common routes of infection in natural melioidosis and major risk factors for infection, primarily diabetes. This review highlights important areas for future research if biodefence-driven vaccines are to play a role in reducing the global incidence of melioidosis