The TD50: a proposed general convention for the numerical description of the carcinogenic potency of chemicals in chronic-exposure animal experiments.

A generally accepted format for the numerical description of the carcinogenic potency of a particular chemical in a particular strain of animals is desirable so that statements from different sources about potency and attempts by different authors to correlate potency with particular laboratory measurements will be comparable. The choice of an appropriate standard format is to a certain extent arbitrary. In this paper we recommend that the TD50 (tumorigenic dose rate 50) be used. TD50 can be calculated for a single target site or combination of sites. The TD50, in analogy with the LD50, is defined as that chronic dose rate (in mg/kg body weight/day) which would halve the actuarially adjusted percentage of tumor-free animals at the end of a standard experiment time--the "standard lifespan" for the species. This paper consists of a brief discussion of the TD50, sufficient to make the general reader familiar with the properties of such an index, an appendix discussing methods for its estimation and certain conventions we have adopted for use in analyzing "nonstandard" experiments. A major problem in calculating any index of carcinogenic potency is that much published material gives only the final crude percentage of tumor-bearing animals at each dose, instead of percentages adjusted for the effects of intercurrent mortality or data from which these adjusted percentages can be derived. If the dose level administered to the animals is toxic, then premature death from nonneoplastic causes may prevent some dosed animals that would have developed tumors from actually doing so. This will particularly affect the high-dose group.(ABSTRACT TRUNCATED AT 250 WORDS

The crossroads of evidence-based medicine and health policy: implications for urology

As healthcare spending in the United States continues to rise at an unsustainable rate, recent policy decisions introduced at the national level will rely on precepts of evidence-based medicine to promote the determination, dissemination, and delivery of “best practices” or quality care while simultaneously reducing cost. We discuss the influence of evidence-based medicine on policy and, in turn, the impact of policy on the developing clinical evidence base with an eye to the potential effects of these relationships on the practice and provision of urologic care

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

The relationship of punishment- and victim-based moral orientation to prosocial, externalizing, and norm trespassing behaviour in delinquent and non-delinquent adolescents:a validation study of the Moral Orientation Measure

This study examined the reliability and validity of the Moral Orientation Measure (MOM), which was administered to 75 juvenile delinquents and 579 non-delinquent adolescents from lower socio-economic and educational backgrounds. Confirmatory factor analysis of a two-factor model, with punishment- and victim-based moral orientation as factors, showed an adequate fit to the data, indicating construct validity of the MOM. Moderate associations between moral orientation and sociomoral reasoning, as well as empathy, were also considered indicative of construct validity. Additional evidence for construct validity was found in only small associations between moral orientation and social desirability and verbal intelligence. Stronger victim-based orientation proved to be associated with less norm trespassing behaviour in non-delinquent adolescents and more prosocial behaviour in juvenile delinquents, which was considered indicative of concurrent validity. The results of this study strengthen the case for the MOM as a reliable and valid instrument to assess moral development in adolescents at risk of behavioural maladjustment, showing that moral orientation is differently associated with morally relevant behaviour in delinquent and non-delinquent adolescents

Alcohol Exposure Decreases CREB Binding Protein Expression and Histone Acetylation in the Developing Cerebellum

Fetal alcohol exposure affects 1 in 100 children making it the leading cause of mental retardation in the US. It has long been known that alcohol affects cerebellum development and function. However, the underlying molecular mechanism is unclear.We demonstrate that CREB binding protein (CBP) is widely expressed in granule and Purkinje neurons of the developing cerebellar cortex of naïve rats. We also show that exposure to ethanol during the 3(rd) trimester-equivalent of human pregnancy reduces CBP levels. CBP is a histone acetyltransferase, a component of the epigenetic mechanism controlling neuronal gene expression. We further demonstrate that the acetylation of both histone H3 and H4 is reduced in the cerebellum of ethanol-treated rats.These findings indicate that ethanol exposure decreases the expression and function of CBP in the developing cerebellum. This effect of ethanol may be responsible for the motor coordination deficits that characterize fetal alcohol spectrum disorders

Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop

<p>Abstract</p> <p>Background</p> <p>Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists.</p> <p>Methods</p> <p>A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm.</p> <p>Results</p> <p>A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy.</p> <p>Conclusions</p> <p>Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.</p