Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers.

Benzene exposure causes acute myeloid leukemia and hematotoxicity, shown as suppression of mature blood and myeloid progenitor cell numbers. As the leukemia-related aneuploidies monosomy 7 and trisomy 8 previously had been detected in the mature peripheral blood cells of exposed workers, we hypothesized that benzene could cause leukemia through the induction of these aneuploidies in hematopoietic stem and progenitor cells. We measured loss and gain of chromosomes 7 and 8 by fluorescence in situ hybridization in interphase colony-forming unit-granulocyte-macrophage (CFU-GM) cells cultured from otherwise healthy benzene-exposed (n=28) and unexposed (n=14) workers. CFU-GM monosomy 7 and 8 levels (but not trisomy) were significantly increased in subjects exposed to benzene overall, compared with levels in the control subjects (P=0.0055 and P=0.0034, respectively). Levels of monosomy 7 and 8 were significantly increased in subjects exposed to <10 p.p.m. (20%, P=0.0419 and 28%, P=0.0056, respectively) and ≥ 10 p.p.m. (48%, P=0.0045 and 32%, 0.0354) benzene, compared with controls, and significant exposure-response trends were detected (P(trend)=0.0033 and 0.0057). These data show that monosomies 7 and 8 are produced in a dose-dependent manner in the blood progenitor cells of workers exposed to benzene, and may be mechanistically relevant biomarkers of early effect for benzene and other leukemogens

Ensuring Best Practice in Genomic Education and Evaluation: A Program Logic Approach

© Copyright © 2019 Nisselle, Martyn, Jordan, Kaunein, McEwen, Patel, Terrill, Bishop, Metcalfe and Gaff. Targeted genomic education and training of professionals have been identified as core components of strategies and implementation plans for the use of genomics in health care systems. Education needs to be effective and support the sustained and appropriate use of genomics in health care. Evaluation of education programs to identify effectiveness is challenging. Furthermore, those responsible for development and delivery are not necessarily trained in education and/or evaluation. Program logic models have been used to support the development and evaluation of education programs by articulating a logical explanation as to how a program intends to produce the desired outcomes. These are highly relevant to genomic education programs, but do not appear to have been widely used to date. To assist those developing and evaluating genomic education programs, and as a first step towards enabling identification of effective genomic education approaches, we developed a consensus program logic model for genomic education. We drew on existing literature and a co-design process with 24 international genomic education and evaluation experts to develop the model. The general applicability of the model to the development of programs was tested by program convenors across four diverse settings. Conveners reported on the utility and relevance of the logic model across development, delivery and evaluation. As a whole, their feedback suggests that the model is flexible and adaptive across university award programs, competency development and continuing professional development activities. We discuss this program logic model as a potential best practice mechanism for developing genomic education, and to support development of an evaluation framework and consistent standards to evaluate and report genomic education program outcomes and impacts

Neighborhood Factors Relevant for Walking in Older, Urban, African American Adults

Focus-group and photo-voice methodology were used to identify the salient factors of the neighborhood environment that encourage or discourage walking in older, urban African Americans. Twenty-one male (n = 2) and female (n = 19) African Americans age 60 years and older (M = 70 ± 8.7, range = 61–85) were recruited from a large urban senior center. Photographs taken by the participants were used to facilitate focus-group discussions. The most salient factors that emerged included the presence of other people, neighborhood surroundings, and safety from crime, followed by sidewalk and traffic conditions, animals, public walking tracks and trails, and weather. Future walking interventions for older African Americans should include factors that encourage walking, such as the presence of other friendly or active people, attractive or peaceful surroundings, and a sense of safety from crime

Stress in nurses : stress-related affect and its determinants examined over the nursing day

Peer reviewedPostprin

A transformative translational change programme to introduce genomics into healthcare: a complexity and implementation science study protocol

INTRODUCTION: Translating scientific advances in genomic medicine into evidence-based clinical practice is challenging. Studying the natural translation of genomics into 'early-adopting' health system sectors is essential. We will (a) examine 29 health systems (Australian and Melbourne Genomics Health Alliance flagships) integrating genomics into practice and (b) combine this learning to co-design and test an evidence-based generalisable toolkit for translating genomics into healthcare. METHODS AND ANALYSIS: Twenty-nine flagships integrating genomics into clinical settings are studied as complex adaptive systems to understand emergent and self-organising behaviours among inter-related actors and processes. The Effectiveness-Implementation Hybrid approach is applied to gather information on the delivery and potential for real-world implementation. Stages '1' and '2a' (representing hybrid model 1) are the focus of this protocol. The Translation Science to Population Impact (TSci Impact) framework is used to study policy decisions and service provision, and the Theoretical Domains Framework (TDF) is used to understand individual level behavioural change; both frameworks are applied across stages 1 and 2a. Stage 1 synthesises interview data from 32 participants involved in developing the genomics clinical practice systems and approaches across five 'demonstration-phase' (early adopter) flagships. In stage 2a, stakeholders are providing quantitative and qualitative data on process mapping, clinical audits, uptake and sustainability (TSci Impact), and psychosocial and environmental determinants of change (TDF). Findings will be synthesised before codesigning an intervention toolkit to facilitate implementation of genomic testing. Study methods to simultaneously test the comparative effectiveness of genomic testing and the implementation toolkit (stage 2b), and the refined implementation toolkit while simply observing the genomics intervention (stage 3) are summarised. ETHICS AND DISSEMINATION: Ethical approval has been granted. The results will be disseminated in academic forums and used to refine interventions to translate genomics evidence into healthcare. Non-traditional academic dissemination methods (eg, change in guidelines or government policy) will also be employed

Searches at HERA for Squarks in R-Parity Violating Supersymmetry

A search for squarks in R-parity violating supersymmetry is performed in e^+p collisions at HERA at a centre of mass energy of 300 GeV, using H1 data corresponding to an integrated luminosity of 37 pb^(-1). The direct production of single squarks of any generation in positron-quark fusion via a Yukawa coupling lambda' is considered, taking into account R-parity violating and conserving decays of the squarks. No significant deviation from the Standard Model expectation is found. The results are interpreted in terms of constraints within the Minimal Supersymmetric Standard Model (MSSM), the constrained MSSM and the minimal Supergravity model, and their sensitivity to the model parameters is studied in detail. For a Yukawa coupling of electromagnetic strength, squark masses below 260 GeV are excluded at 95% confidence level in a large part of the parameter space. For a 100 times smaller coupling strength masses up to 182 GeV are excluded.Comment: 32 pages, 14 figures, 3 table

Complementarity of the CERN Large Hadron Collider and the e+e−e^+e^- International Linear Collider

The next-generation high-energy facilities, the CERN Large Hadron Collider (LHC) and the prospective $e^+e^-$ International Linear Collider (ILC), are expected to unravel new structures of matter and forces from the electroweak scale to the TeV scale. In this report we review the complementary role of LHC and ILC in drawing a comprehensive and high-precision picture of the mechanism breaking the electroweak symmetries and generating mass, and the unification of forces in the frame of supersymmetry.Comment: 14 pages, 17 figures, to be published in "Supersymmetry on the Eve of the LHC", a special volume of European Physical Journal C, Particles and Fields (EPJC) in memory of Julius Wes