Does Income Mobility Equalize Longer-term Incomes? New Measures of an Old Concept

This paper develops a new class of measures of mobility as an equalizer of longer-term incomes – a concept different from other notions such as mobility as time-independence, positional movement, share movement, income flux, and directional income movement. A number of properties are specified leading to a class of indices, one easily-implementable member of which is applied to data for the United States and France. Using this index, income mobility is found to have equalized longer-term earnings among U.S. men in the 1970s but not in the 1980s or 1990s. In France, though, income mobility was equalizing throughout, and it has attained its maximum in the most recent period

How important is the context of an adolescent's first alcoholic drink? Evidence that parental provision may reduce later heavy episodic drinking

Objective: This study examined the extent to which a retrospective measure of parental provision of the first alcoholic beverage was related to current heavy episodic drinking and current responsible drinking practices. Sample: 608 14- to 17-year-olds from the 2007 Australian National Drug Strategy Household Survey. Measures: Source of first alcoholic beverage (friends/parents/others), source of current alcohol, age of onset of alcohol use, current responsible drinking practices, and proportion of current friends who drink. Results: Binary logistic and multiple regression procedures revealed that parental provision of an adolescent's first alcoholic beverage predicted lower current heavy episodic drinking, and responsible drinking mediated this association. Discussion: The results suggested that for adolescents who become alcohol users, parental provision of the first drink may reduce subsequent alcohol-related risks compared to introduction to alcohol by friends and other sources. Alcohol-related risks remain significant for adolescents who consume alcohol, independent of who is the provider. Copyright (C) 2012 S. Karger AG, Base

Infant mortality rates regressed against number of vaccine doses routinely given: Is there a biochemical or synergistic toxicity?

The infant mortality rate (IMR) is one of the most important indicators of the socio-economic well-being and public health conditions of a country. The US childhood immunization schedule specifies 26 vaccine doses for infants aged less than 1 year—the most in the world—yet 33 nations have lower IMRs. Using linear regression, the immunization schedules of these 34 nations were examined and a correlation coefficient of r = 0.70 (p < 0.0001) was found between IMRs and the number of vaccine doses routinely given to infants. Nations were also grouped into five different vaccine dose ranges: 12–14, 15–17, 18–20, 21–23, and 24–26. The mean IMRs of all nations within each group were then calculated. Linear regression analysis of unweighted mean IMRs showed a high statistically significant correlation between increasing number of vaccine doses and increasing infant mortality rates, with r = 0.992 (p = 0.0009). Using the Tukey-Kramer test, statistically significant differences in mean IMRs were found between nations giving 12–14 vaccine doses and those giving 21–23, and 24–26 doses. A closer inspection of correlations between vaccine doses, biochemical or synergistic toxicity, and IMRs is essential

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Preferentially Quantized Linker DNA Lengths in Saccharomyces cerevisiae

The exact lengths of linker DNAs connecting adjacent nucleosomes specify the intrinsic three-dimensional structures of eukaryotic chromatin fibers. Some studies suggest that linker DNA lengths preferentially occur at certain quantized values, differing one from another by integral multiples of the DNA helical repeat, ∼10 bp; however, studies in the literature are inconsistent. Here, we investigate linker DNA length distributions in the yeast Saccharomyces cerevisiae genome, using two novel methods: a Fourier analysis of genomic dinucleotide periodicities adjacent to experimentally mapped nucleosomes and a duration hidden Markov model applied to experimentally defined dinucleosomes. Both methods reveal that linker DNA lengths in yeast are preferentially periodic at the DNA helical repeat (∼10 bp), obeying the forms 10n+5 bp (integer n). This 10 bp periodicity implies an ordered superhelical intrinsic structure for the average chromatin fiber in yeast

Supported self-management for adults with type 2 diabetes and a learning disability (OK-Diabetes): study protocol for a randomised controlled feasibility trial

Background: Individuals with a learning disability (LD) are at higher risk of developing type 2 diabetes, but LD is not straightforward to define or identify, especially at the milder end of the spectrum, which makes case finding difficult. While supported self-management of health problems is now established, current material is largely educational and didactic with little that facilitates behavioural change. The interaction between the person with diabetes and others supporting their care is also largely unknown. For these reasons, there is considerable work needed to prepare for a definitive trial. The aim of this paper is to publish the abridged protocol of this preparatory work. Methods/Design: Phase I is a prospective case-finding study (target n = 120 to 350) to identify and characterise potential participants, while developing a standardised supported self-management intervention. Phase II is a randomised feasibility trial (target n = 80) with blinded outcome assessment. Patients identified in Phase I will be interviewed and consented prior to being randomised to (1) standard treatment, or (2) supported self-management. Both arms will also be provided with an ‘easy read’ accessible information resource on managing type 2 diabetes. The intervention will be standardised but delivered flexibly depending on patient need, including components for the participant, a supporter, and shared activities. Outcomes will be (i) robust estimates of eligibility, consent and recruitment rates with refined recruitment procedures; (ii) characterisation of the eligible population; (iii) a standardised intervention with associated written materials, (iv) adherence and negative outcomes measures; (v) preliminary estimates of adherence, acceptability, follow-up and missing data rates, along with refined procedures; and (vi) description of standard treatment. Discussion: Our study will provide important information on the nature of type 2 diabetes in adults with LD living in the community, on the challenges of identifying those with milder LD, and on the possibilities of evaluating a standardised intervention to improve self-management in this population. Trial registration: Current Controlled Trials ISRCTN41897033 (registered 21 January 2013)

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Corporate philanthropy, political influence, and health policy

Background The Framework Convention of Tobacco Control (FCTC) provides a basis for nation states to limit the political effects of tobacco industry philanthropy, yet progress in this area is limited. This paper aims to integrate the findings of previous studies on tobacco industry philanthropy with a new analysis of British American Tobacco's (BAT) record of charitable giving to develop a general model of corporate political philanthropy that can be used to facilitate implementation of the FCTC. Method Analysis of previously confidential industry documents, BAT social and stakeholder dialogue reports, and existing tobacco industry document studies on philanthropy. Results The analysis identified six broad ways in which tobacco companies have used philanthropy politically: developing constituencies to build support for policy positions and generate third party advocacy; weakening opposing political constituencies; facilitating access and building relationships with policymakers; creating direct leverage with policymakers by providing financial subsidies to specific projects; enhancing the donor's status as a source of credible information; and shaping the tobacco control agenda by shifting thinking on the importance of regulating the market environment for tobacco and the relative risks of smoking for population health. Contemporary BAT social and stakeholder reports contain numerous examples of charitable donations that are likely to be designed to shape the tobacco control agenda, secure access and build constituencies. Conclusions and Recommendations Tobacco companies' political use of charitable donations underlines the need for tobacco industry philanthropy to be restricted via full implementation of Articles 5.3 and 13 of the FCTC. The model of tobacco industry philanthropy developed in this study can be used by public health advocates to press for implementation of the FCTC and provides a basis for analysing the political effects of charitable giving in other industry sectors which have an impact on public health such as alcohol and food

Evaluation of Two Models for Human Topoisomerase I Interaction with dsDNA and Camptothecin Derivatives

Human topoisomerase I (Top1) relaxes supercoiled DNA during cell division. Camptothecin stabilizes Top1/dsDNA covalent complexes which ultimately results in cell death, and this makes Top1 an anti-cancer target. There are two current models for how camptothecin and derivatives bind to Top1/dsDNA covalent complexes (Staker, et al., 2002, Proc Natl Acad Sci USA 99: 15387–15392; and Laco, et al., 2004, Bioorg Med Chem 12: 5225–5235). The interaction energies between bound camptothecin, and derivatives, and Top1/dsDNA in the two models were calculated. The published structure-activity-relationships for camptothecin and derivatives correlated with the interaction energies for camptothecin and derivatives in the Laco et al. model, however, this was not the case for several camptothecin derivatives in the Stacker et al. model. By defining the binding orientation of camptothecin and derivatives in the Top1/dsDNA active-site these results allow for the rational design of potentially more efficacious camptothecin derivatives

Study of CP violation in Dalitz-plot analyses of B0 --> K+K-KS, B+ --> K+K-K+, and B+ --> KSKSK+

We perform amplitude analyses of the decays $B^0 \to K^+K^-K^0_S$, $B^+ \rightarrow K^+K^-K^+$, and $B^+ \to K^0_S K^0_S K^+$, and measure CP-violating parameters and partial branching fractions. The results are based on a data sample of approximately $470\times 10^6$ $B\bar{B}$ decays, collected with the BABAR detector at the PEP-II asymmetric-energy $B$ factory at the SLAC National Accelerator Laboratory. For $B^+ \to K^+K^-K^+$, we find a direct CP asymmetry in $B^+ \to \phi(1020)K^+$ of $A_{CP}= (12.8\pm 4.4 \pm 1.3)$, which differs from zero by $2.8 \sigma$. For $B^0 \to K^+K^-K^0_S$, we measure the CP-violating phase $\beta_{\rm eff} (\phi(1020)K^0_S) = (21\pm 6 \pm 2)^\circ$. For $B^+ \to K^0_S K^0_S K^+$, we measure an overall direct CP asymmetry of $A_{CP} = (4 ^{+4}_{-5} \pm 2)$. We also perform an angular-moment analysis of the three channels, and determine that the $f_X(1500)$ state can be described well by the sum of the resonances $f_0(1500)$, $f_2^{\prime}(1525)$, and $f_0(1710)$.Comment: 35 pages, 68 postscript figures. v3 - minor modifications to agree with published versio