Effects of deceptive self-reports of quitting on the results of treatment trials for smoking: A quantitative assessment

Problems with self-report measures for smoking motivate the use of biochemical tests in treatment trials for smoking. These biochemical tests, unfortunately, are not perfect. In this paper, we present an algebraic model of bias in treatment trials for smoking. Bias is expressed in terms of the deception rate among continued smokers in a control group, the relative deception rate among continued smokers in an experimental group, and the sensitivity and specificity of a biochemical test which may be used either to confirm self-reports of,quitting or to replace self-report entirely. For given test specificity and sensitivity, the mode) defines deception rates for which different biochemical testing strategies are preferred. The model is presented in the context of current knowledge on the phenomenon of deception among adult smokers. The paper concludes that better judgements regarding the role of biochemical tests in treatment trials for smoking require more precise information regarding the magnitude and determinants of deception.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28158/1/0000610.pd

Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis

Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy-lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator of autophagy-lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1β levels, leading to reduced atherosclerosis. In order to harness this degradative response therapeutically, we also describe a natural sugar called trehalose as an inducer of macrophage autophagy-lysosomal biogenesis and show trehalose's ability to recapitulate the atheroprotective properties of macrophage TFEB overexpression. Our data support this practical method of enhancing the degradative capacity of macrophages as a therapy for atherosclerotic vascular disease

Carcass Trait Effects from Environment, Growth Rate on Pasture, and Breedtypes

Last updated: 6/12/200

Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating Cytotoxin from Mycoplasma Pneumoniae

Mycoplasma pneumoniae (Mp) infections cause tracheobronchitis and walking pneumonia, and are linked to asthma and other reactive airway diseases. As part of the infectious process, the bacterium expresses a 591-aa virulence factor with both mono-ADP ribosyltransferase (mART) and vacuolating activities known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX binds to human surfactant protein A and annexin A2 on airway epithelial cells and is internalized, leading to a range of pathogenetic events. Here we present the structure of CARDS TX, a triangular molecule in which N-terminal mART and C-terminal tandem beta-trefoil domains associate to form an overall architecture distinct from other well-recognized ADP-ribosylating bacterial toxins. We demonstrate that CARDS TX binds phosphatidylcholine and sphingomyelin specifically over other membrane lipids, and that cell surface binding and internalization activities are housed within the C-terminal beta-trefoil domain. The results enhance our understanding of Mp pathogenicity and suggest a novel avenue for the development of therapies to treat Mp-associated asthma and other acute and chronic airway diseases

Cheops Solar Cell Assemblies Life Test

Life tests are performed to determine the stability of solar cell assemblies under worst case operation conditions for long duration. This test is part of the qualification programme to which solar cell assemblies are submitted according to ECSS standards. This paper presents the test set-up configuration (recently implemented in the European Space Power Laboratory), test conditions and test results obtained of the solar cell assembly life test performed under the ESA CHEOPS satellite programme

Financing of U.S. Biomedical Research and New Drug Approvals across Therapeutic Areas

We estimated U.S. biomedical research funding across therapeutic areas, determined the association with disease burden, and evaluated new drug approvals that resulted from this investment.We calculated funding from 1995 to 2005 and totaled Food and Drug Administration approvals in eight therapeutic areas (cardiovascular, endocrine, gastrointestinal, genitourinary, HIV/AIDS, infectious disease excluding HIV, oncology, and respiratory) primarily using public data. We then calculated correlations between funding, published estimates of disease burden, and drug approvals. Financial support for biomedical research from 1995 to 2005 increased across all therapeutic areas between 43% and 369%. Industry was the principal funder of all areas except HIV/AIDS, infectious disease, and oncology, which were chiefly sponsored by the National Institutes of Health (NIH). Total (rho = 0.70; P = .03) and industry funding (rho = 0.69; P = .04) were correlated with projected disease burden in high income countries while NIH support (rho = 0.80; P = .01) was correlated with projected disease burden globally. From 1995 to 2005 the number of new approvals was flat or declined across therapeutic areas, and over an 8-year lag period, neither total nor industry funding was correlated with future approvals.Across therapeutic areas, biomedical research funding increased substantially, appears aligned with disease burden in high income countries, but is not linked to new drug approvals. The translational gap between funding and new therapies is affecting all of medicine, and remedies must include changes beyond additional financial investment

Speeding Up Microevolution: The Effects of Increasing Temperature on Selection and Genetic Variance in a Wild Bird Population

The authors show that environmental variation may lead to a positive association between the annual strength of selection and expression of genetic variance in a wild bird population, which can speed up microevolution and have important consequences for how fast natural populations adapt to environmental changes