Cluster randomized test-negative design (CR-TND) trials: a novel and efficient method to assess the efficacy of community level dengue interventions

Cluster randomized trials are the gold standard for assessing efficacy of community-level interventions, such as vector control strategies against dengue. We describe a novel cluster randomized trial methodology with a test-negative design, which offers advantages over traditional approaches. It utilizes outcome-based sampling of patients presenting with a syndrome consistent with the disease of interest, who are subsequently classified as test-positive cases or test-negative controls on the basis of diagnostic testing. We use simulations of a cluster trial to demonstrate validity of efficacy estimates under the test-negative approach. This demonstrates that, provided study arms are balanced for both test-negative and test-positive illness at baseline and that other test-negative design assumptions are met, the efficacy estimates closely match true efficacy. We also briefly discuss analytical considerations for an odds ratio-based effect estimate arising from clustered data, and outline potential approaches to analysis. We conclude that application of the test-negative design to certain cluster randomized trials could increase their efficiency and ease of implementation

The Resident Assessment Instrument-Minimum Data Set 2.0 quality indicators: a systematic review

BackgroundThe Resident Assessment Instrument-Minimum Data Set (RAI-MDS) 2.0 is designed to collect the minimum amount of data to guide care planning and monitoring for residents in long-term care settings. These data have been used to compute indicators of care quality. Use of the quality indicators to inform quality improvement initiatives is contingent upon the validity and reliability of the indicators. The purpose of this review was to systematically examine published and grey research reports in order to assess the state of the science regarding the validity and reliability of the RAI-MDS 2.0 Quality Indicators (QIs).MethodsWe systematically reviewed the evidence for the validity and reliability of the RAI-MDS 2.0 QIs. A comprehensive literature search identified relevant original research published, in English, prior to December 2008. Fourteen articles and one report examining the validity and/or reliability of the RAI-MDS 2.0 QIs were included.ResultsThe studies fell into two broad categories, those that examined individual quality indicators and those that examined multiple indicators. All studies were conducted in the United States and included from one to a total of 209 facilities. The number of residents included in the studies ranged from 109 to 5758. One study conducted under research conditions examined 38 chronic care QIs, of which strong evidence for the validity of 12 of the QIs was found. In response to these findings, the 12 QIs were recommended for public reporting purposes. However, a number of observational studies (n=13), conducted in &quot;real world&quot; conditions, have tested the validity and/or reliability of individual QIs, with mixed results. Ten QIs have been studied in this manner, including falls, depression, depression without treatment, urinary incontinence, urinary tract infections, weight loss, bedfast, restraint, pressure ulcer, and pain. These studies have revealed the potential for systematic bias in reporting, with under-reporting of some indicators and over-reporting of others.ConclusionEvidence for the reliability and validity of the RAI-MDS QIs remains inconclusive. The QIs provide a useful tool for quality monitoring and to inform quality improvement programs and initiatives. However, caution should be exercised when interpreting the QI results and other sources of evidence of the quality of care processes should be considered in conjunction with QI results.<br /

A controlled trial of the effectiveness of a diabetes education programme in a multi-ethnic community in Glasgow [ISRCT28317455]

BACKGROUND: Epidemiologic data have shown that the prevalence of Type 2 diabetes varies with ethnic origin. Type 2 diabetes is up to four times more common in British South Asians than in the indigenous white population. The aim of this study was to develop a culturally appropriate educational intervention programme for South Asians with Type 2 diabetes. We then investigated whether this intervention could produce an improvement, and finally whether any improvement was greater than background changes in knowledge in comparison groups. METHODS: A multi-site prospective, randomised controlled study was conducted in all day care centres and three general practice registers with high proportion patients from different ethnic minority groups in Glasgow, Scotland. The intervention consisted of 18 educational sessions in 6 separate programmes. A modified questionnaire was used to measure the knowledge, attitudes, and practice of diabetes before and after intervention. RESULTS: Baseline assessment showed that Indian and Pakistani subjects had less knowledge about diabetes, regarded the disease less seriously, and had a lesser understanding of the relationship between control and complications than the white population. No differences in initial responses were found between those who completed the second assessment and those who did not. The intervention group showed significant improvements in scores for Knowledge (+12.5%); Attitudes toward seriousness (+13.5%), complications (+8.1%), Practice (+20.0%). However there were also changes in the ethnic control group scores; respectively +5.0%, +16.3% (significant P < 0.001), +1.5%, +1.7%. The single white control group also showed some improvements; respectively +12.2%, +12.4% (P = 0.04), +6.0%, +25.0% (P = 0.007), but the differences in improvement between these two control groups were not significant. Overall, the improvement seen was similar in both intervention and ethnic control groups and there was no significant difference in the amount of change (P = 0.36 CI -0.9 to +2.6). CONCLUSION: This study has shown that conducting a culturally-competent educational intervention in patients with Type 2 diabetes from ethnic minority groups is feasible and can improve their knowledge and attitudes and practice. However there was no net benefit compared with the control group

Genomic Expansion of Magnetotactic Bacteria Reveals an Early Common Origin of Magnetotaxis with Lineage-specific Evolution

The origin and evolution of magnetoreception, which in diverse prokaryotes and protozoa is known as magnetotaxis and enables these microorganisms to detect Earth’s magnetic field for orientation and navigation, is not well understood in evolutionary biology. The only known prokaryotes capable of sensing the geomagnetic field are magnetotactic bacteria (MTB), motile microorganisms that biomineralize intracellular, membrane-bounded magnetic single-domain crystals of either magnetite (Fe3O4) or greigite (Fe3S4) called magnetosomes. Magnetosomes are responsible for magnetotaxis in MTB. Here we report the first large-scale metagenomic survey of MTB from both northern and southern hemispheres combined with 28 genomes from uncultivated MTB. These genomes expand greatly the coverage of MTB in the Proteobacteria, Nitrospirae, and Omnitrophica phyla, and provide the first genomic evidence of MTB belonging to the Zetaproteobacteria and “Candidatus Lambdaproteobacteria” classes. The gene content and organization of magnetosome gene clusters, which are physically grouped genes that encode proteins for magnetosome biosynthesis and organization, are more conserved within phylogenetically similar groups than between different taxonomic lineages. Moreover, the phylogenies of core magnetosome proteins form monophyletic clades. Together, these results suggest a common ancient origin of iron-based (Fe3O4 and Fe3S4) magnetotaxis in the domain Bacteria that underwent lineage-specific evolution, shedding new light on the origin and evolution of biomineralization and magnetotaxis, and expanding significantly the phylogenomic representation of MTB

Nonlinear Sigma Model for Disordered Media: Replica Trick for Non-Perturbative Results and Interactions

In these lectures, given at the NATO ASI at Windsor (2001), applications of the replicas nonlinear sigma model to disordered systems are reviewed. A particular attention is given to two sets of issues. First, obtaining non-perturbative results in the replica limit is discussed, using as examples (i) an oscillatory behaviour of the two-level correlation function and (ii) long-tail asymptotes of different mesoscopic distributions. Second, a new variant of the sigma model for interacting electrons in disordered normal and superconducting systems is presented, with demonstrating how to reduce it, under certain controlled approximations, to known ``phase-only'' actions, including that of the ``dirty bosons'' model.Comment: 25 pages, Proceedings of the NATO ASI "Field Theory of Strongly Correlated Fermions and Bosons in Low - Dimensional Disordered Systems", Windsor, August, 2001; to be published by Kluwe

PECAM-Independent Thioglycollate Peritonitis Is Associated With a Locus on Murine Chromosome 2

Background: Previous studies have demonstrated that knockout or inhibition of Platelet/Endothelial Cell Adhesion Molecule (PECAM, CD31) in a number of murine strains results in impaired inflammatory responses, but that no such phenotype is seen in the C57BL/6 (B6) murine background. Methodology/Principal Findings: We have undertaken a quantitative trait locus (QTL) mapping effort between FVB/n (FVB) and B6 mice deficient for PECAM to identify the gene or genes responsible for this unique feature of B6 mice. We have identified a locus on murine chromosome 2 at approximately 35.8 Mb that is strongly associated (LOD score = 9.0) with inflammatory responses in the absence of PECAM. Conclusions/Significance: These data potentiate further study of the diapedesis machinery, as well as potential identification of new components of this machinery. As such, this study is an important step to better understanding the processes of inflammation

Seeking legitimacy through CSR: Institutional Pressures and Corporate Responses of Multinationals in Sri Lanka

Arguably, the corporate social responsibility (CSR) practices of multinational enterprises (MNEs) are influenced by a wide range of both internal and external factors. Perhaps most critical among the exogenous forces operating on MNEs are those exerted by state and other key institutional actors in host countries. Crucially, academic research conducted to date offers little data about how MNEs use their CSR activities to strategically manage their relationship with those actors in order to gain legitimisation advantages in host countries. This paper addresses that gap by exploring interactions between external institutional pressures and firm-level CSR activities, which take the form of community initiatives, to examine how MNEs develop their legitimacy-seeking policies and practices. In focusing on a developing country, Sri Lanka, this paper provides valuable insights into how MNEs instrumentally utilise community initiatives in a country where relationship-building with governmental and other powerful non-governmental actors can be vitally important for the long-term viability of the business. Drawing on neo-institutional theory and CSR literature, this paper examines and contributes to the embryonic but emerging debate about the instrumental and political implications of CSR. The evidence presented and discussed here reveals the extent to which, and the reasons why, MNEs engage in complex legitimacy-seeking relationships with Sri Lankan institutions

Quantum Computing

Quantum mechanics---the theory describing the fundamental workings of nature---is famously counterintuitive: it predicts that a particle can be in two places at the same time, and that two remote particles can be inextricably and instantaneously linked. These predictions have been the topic of intense metaphysical debate ever since the theory's inception early last century. However, supreme predictive power combined with direct experimental observation of some of these unusual phenomena leave little doubt as to its fundamental correctness. In fact, without quantum mechanics we could not explain the workings of a laser, nor indeed how a fridge magnet operates. Over the last several decades quantum information science has emerged to seek answers to the question: can we gain some advantage by storing, transmitting and processing information encoded in systems that exhibit these unique quantum properties? Today it is understood that the answer is yes. Many research groups around the world are working towards one of the most ambitious goals humankind has ever embarked upon: a quantum computer that promises to exponentially improve computational power for particular tasks. A number of physical systems, spanning much of modern physics, are being developed for this task---ranging from single particles of light to superconducting circuits---and it is not yet clear which, if any, will ultimately prove successful. Here we describe the latest developments for each of the leading approaches and explain what the major challenges are for the future.Comment: 26 pages, 7 figures, 291 references. Early draft of Nature 464, 45-53 (4 March 2010). Published version is more up-to-date and has several corrections, but is half the length with far fewer reference

Giant Electroresistance in Edge Metal-Insulator-Metal Tunnel Junctions Induced by Ferroelectric Fringe Fields

An enormous amount of research activities has been devoted to developing new types of non-volatile memory devices as the potential replacements of current flash memory devices. Theoretical device modeling was performed to demonstrate that a huge change of tunnel resistance in an Edge Metal-Insulator-Metal (EMIM) junction of metal crossbar structure can be induced by the modulation of electric fringe field, associated with the polarization reversal of an underlying ferroelectric layer. It is demonstrated that single three-terminal EMIM/Ferroelectric structure could form an active memory cell without any additional selection devices. This new structure can open up a way of fabricating all-thin-film-based, high-density, high-speed, and low-power non-volatile memory devices that are stackable to realize 3D memory architectureope