Evidence-informed health policy 3 – Interviews with the directors of organizations that support the use of research evidence

Background: Previous surveys of organizations that support the development of evidence-informed health policies have focused on organizations that produce clinical practice guidelines (CPGs) or undertake health technology assessments (HTAs). Only rarely have surveys focused at least in part on units that directly support the use of research evidence in developing health policy on an international, national, and state or provincial level (i.e., government support units, or GSUs) that are in some way successful or innovative or that support the use of research evidence in low- and middle-income countries (LMICs). Methods: We drew on many people and organizations around the world, including our project reference group, to generate a list of organizations to survey. We modified a questionnaire that had been developed originally by the Appraisal of Guidelines, Research and Evaluation in Europe (AGREE) collaboration and adapted one version of the questionnaire for organizations producing CPGs and HTAs, and another for GSUs. We sent the questionnaire by email to 176 organizations and followed up periodically with non-responders by email and telephone. Results: We received completed questionnaires from 152 (86%) organizations. More than one-half of the organizations (and particularly HTA agencies) reported that examples from other countries were helpful in establishing their organization. A higher proportion of GSUs than CPG-or HTA-producing organizations involved target users in the selection of topics or the services undertaken. Most organizations have few (five or fewer) full-time equivalent (FTE) staff. More than four-fifths of organizations reported providing panels with or using systematic reviews. GSUs tended to use a wide variety of explicit valuation processes for the research evidence, but none with the frequency that organizations producing CPGs, HTAs, or both prioritized evidence by its quality. Between one-half and two-thirds of organizations do not collect data systematically about uptake, and roughly the same proportions do not systematically evaluate their usefulness or impact in other ways. Conclusion: The findings from our survey, the most broadly based of its kind, both extend or clarify the applicability of the messages arising from previous surveys and related documentary analyses, such as how the 'principles of evidence-based medicine dominate current guideline programs' and the importance of collaborating with other organizations. The survey also provides a description of the history, structure, processes, outputs, and perceived strengths and weaknesses of existing organizations from which those establishing or leading similar organizations can draw

Root phenotyping pipeline for cereal plants

The proposed system for the phenotypic analysis of root traits that is presented here enables the precise description of the root growth kinetics of cereal plants. The designed pipeline is composed of a drip irrigation system to supplement plants with a medium, a high-resolution root system scanning facility and a method for comprehensive image analysis. The system enables low-effort, accurate and highly repeatable analysis of features of the root system of cereal seedlings and young plants until the early tillering stage. This system employs an automatic drip irrigation line, which is controlled remotely by a programmable logic controller (PLC). The PLC adapter used facilitates the automated control of all system modules, thus allowing the rate of the medium flow to be adjusted for the supplementation of plants. The system employs measuring sensors for the continuous monitoring of the parameters of the culture medium. This continuous sensing of medium parameters can be applicable for mineral nutrition studies and abiotic stress response testing. The installed drip lines are injected into transparent acrylic tubes (500 mm high, 32/30 mm in outer and inner diameter, with a circular opening in the bottom of 3 mm in diameter) that are filled with glass beads. The acrylic tubes are placed in opaque cover tubes that permit the non-destructive observation of the growth of the root system. Enhanced imaging quality contributes to an increase in the precision of the results that are obtained in the course of the analysis of root parameters using specialised root scanners coupled with the WinRHIZO system. This novel phenotyping pipeline permits noninvasive observation of root system growth adjusted for the subsequent root image acquisition with a reduced background noise. The method combines automated control of plant growth conditions with good imaging quality and high replicability of growth parameters

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

General Analysis of Antideuteron Searches for Dark Matter

Low energy cosmic ray antideuterons provide a unique low background channel for indirect detection of dark matter. We compute the cosmic ray flux of antideuterons from hadronic annihilations of dark matter for various Standard Model final states and determine the mass reach of two future experiments (AMS-02 and GAPS) designed to greatly increase the sensitivity of antideuteron detection over current bounds. We consider generic models of scalar, fermion, and massive vector bosons as thermal dark matter, describe their basic features relevant to direct and indirect detection, and discuss the implications of direct detection bounds on models of dark matter as a thermal relic. We also consider specific dark matter candidates and assess their potential for detection via antideuterons from their hadronic annihilation channels. Since the dark matter mass reach of the GAPS experiment can be well above 100 GeV, we find that antideuterons can be a good indirect detection channel for a variety of thermal relic electroweak scale dark matter candidates, even when the rate for direct detection is highly suppressed.Comment: 44 pages, 15 Figure

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Knowledge mobilization in the context of health technology assessment: an exploratory case study

<p>Abstract</p> <p>Background</p> <p>Finding measures to enhance the dissemination and implementation of their recommendations has become part of most health technology assessment (HTA) bodies' preoccupations. The Quebec government HTA organization in Canada observed that some of its projects relied on innovative practices in knowledge production and dissemination. A research was commissioned in order to identify what characterized these practices and to establish whether they could be systematized.</p> <p>Methods</p> <p>An exploratory case study was conducted during summer and fall 2010 in the HTA agency in order to determine what made the specificity of its context, and to conceptualize an approach to knowledge production and dissemination that was adapted to the mandate and nature of this form of HTA organization. Six projects were selected. For each, the HTA report and complementary documents were analyzed, and semi-structured interviews were carried out. A narrative literature review of the most recent literature reviews of the principal knowledge into practice frameworks (2005-2010) and of articles describing such frameworks (2000-2010) was undertaken.</p> <p>Results and discussion</p> <p>Our observations highlighted an inherent difficulty as regards applying the dominant knowledge translation models to HTA and clinical guidance practices. For the latter, the whole process starts with an evaluation question asked in a problematic situation for which an actionable answer is expected. The objective is to produce the evidence necessary to respond to the decision-maker's request. The practices we have analyzed revealed an approach to knowledge production and dissemination, which was multidimensional, organic, multidirectional, dynamic, and dependent on interactions with stakeholders. Thus, HTA could be considered as a knowledge mobilization process per se.</p> <p>Conclusions</p> <p>HTA's purpose is to solve a problem by mobilizing the types of evidence required and the concerned actors, in order to support political, organizational or clinical decision-making. HTA relies on the mediation between contextual, colloquial and scientific evidence, as well as on interactions with stakeholders for recommendation making. Defining HTA as a knowledge mobilization process might contribute to consider the different orders of knowledge, the social, political and ethical dimensions, and the interactions with stakeholders, among the essential components required to respond to the preoccupations, needs and contexts of all actors concerned with the evaluation question's issues.</p

Signatures of large composite Dark Matter states

We investigate the interactions of large composite dark matter (DM) states with the Standard Model (SM) sector. Elastic scattering with SM nuclei can be coherently enhanced by factors as large as A^2, where A is the number of constituents in the composite state (there exist models in which DM states of very large A > 10^8 may be realised). This enhancement, for a given direct detection event rate, weakens the expected signals at colliders by up to 1/A. Moreover, the spatially extended nature of the DM states leads to an additional, characteristic, form factor modifying the momentum dependence of scattering processes, altering the recoil energy spectra in direct detection experiments. In particular, energy recoil spectra with peaks and troughs are possible, and such features could be confirmed with only O(50) events, independently of the assumed halo velocity distribution. Large composite states also generically give rise to low-energy collective excitations potentially relevant to direct detection and indirect detection phenomenology. We compute the form factor for a generic class of such excitations - quantised surface modes - finding that they can lead to coherently-enhanced, but generally sub-dominant, inelastic scattering in direct detection experiments. Finally, we study the modifications to capture rates in astrophysical objects that follow from the elastic form factor, as well as the effects of inelastic interactions between DM states once captured. We argue that inelastic interactions may lead to the DM collapsing to a dense configuration at the centre of the object.Comment: 30 pages, 5 figures, v2; references and minor additional comments adde

Thirty years after Alma-Ata: a systematic review of the impact of community health workers delivering curative interventions against malaria, pneumonia and diarrhoea on child mortality and morbidity in sub-Saharan Africa

BACKGROUND: Over thirty years have passed since the Alma-Ata Declaration on primary health care in 1978. Many governments in the first decade following the declaration responded by developing national programmes of community health workers (CHWs), but evaluations of these often demonstrated poor outcomes. As many CHW programmes have responded to the HIV/AIDS pandemic, international interest in them has returned and their role in the response to other diseases should be examined carefully so that lessons can be applied to their new roles. Over half of the deaths in African children under five years of age are due to malaria, diarrhoea and pneumonia - a situation which could be addressed through the use of cheap and effective interventions delivered by CHWs. However, to date there is very little evidence from randomised controlled trials of the impacts of CHW programmes on child mortality in Africa. Evidence from non-randomised controlled studies has not previously been reviewed systematically. METHODS: We searched databases of published and unpublished studies for RCTs and non-randomised studies evaluating CHW programmes delivering curative treatments, with or without preventive components, for malaria, diarrhoea or pneumonia, in children in sub-Saharan Africa from 1987 to 2007. The impact of these programmes on morbidity or mortality in children under six years of age was reviewed. A descriptive analysis of interventional and contextual factors associated with these impacts was attempted. RESULTS: The review identified seven studies evaluating CHWs, delivering a range of interventions. Limited descriptive data on programmes, contexts or process outcomes for these CHW programmes were available. CHWs in national programmes achieved large mortality reductions of 63% and 36% respectively, when insecticide-treated nets and anti-malarial chemoprophylaxis were delivered, in addition to curative interventions. CONCLUSIONS: CHW programmes could potentially achieve large gains in child survival in sub-Saharan Africa if these programmes were implemented at scale. Large-scale rigorous studies, including RCTs, are urgently needed to provide policymakers with more evidence on the effects of CHWs delivering these interventions