Intraindividual Stepping Reaction Time Variability Predicts Falls in Older Adults With Mild Cognitive Impairment

Background: Reaction time measures have considerable potential to aid neuropsychological assessment in a variety of health care settings. One such measure, the intraindividual reaction time variability (IIV), is of particular interest as it is thought to reflect neurobiological disturbance. IIV is associated with a variety of age-related neurological disorders, as well as gait impairment and future falls in older adults. However, although persons diagnosed with Mild Cognitive Impairment (MCI) are at high risk of falling, the association between IIV and prospective falls is unknown. Methods: We conducted a longitudinal cohort study in cognitively intact (n = 271) and MCI (n = 154) community-dwelling adults aged 70–90 years. IIV was assessed through a variety of measures including simple and choice hand reaction time and choice stepping reaction time tasks (CSRT), the latter administered as a single task and also with a secondary working memory task. Results: Logistic regression did not show an association between IIV on the hand-held tasks and falls. Greater IIV in both CSRT tasks, however, did significantly increase the risk of future falls. This effect was specific to the MCI group, with a stronger effect in persons exhibiting gait, posture, or physiological impairment. Conclusions: The findings suggest that increased stepping IIV may indicate compromised neural circuitry involved in executive function, gait, and posture in persons with MCI increasing their risk of falling. IIV measures have potential to assess neurobiological disturbance underlying physical and cognitive dysfunction in old age, and aid fall risk assessment and routine care in community and health care settings

Classic and spatial shift-share analysis of state-level employment change in Brazil

This paper combines classic and spatial shift-share decompositions of 1981 to 2006 employment change across the 27 states of Brazil. The classic shift-share method shows higher employment growth rates for underdeveloped regions that are due to an advantageous industry-mix and also due to additional job creation, commonly referred to as the competitive effect. Alternative decompositions proposed in the literature do not change this broad conclusion. Further examination employing exploratory spatial data analysis (ESDA) shows spatial correlation of both the industry-mix and the competitive effects. Considering that until the 1960s economic activities were more concentrated in southern regions of Brazil than they are nowadays, these results support beta convergence theories but also find evidence of agglomeration effects. Additionally, a very simple spatial decomposition is proposed that accounts for the spatially-weighted growth of surrounding states. Favourable growth in northern and centre-western states is basically associated with those states’ strengths in potential spatial spillover effect and in spatial competitive effect

Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al

Policymakers\u27 experience of a capacity-building intervention designed to increase their use of research: A realist process evaluation

Background: An intervention’s success depends on how participants interact with it in local settings. Process evaluation examines these interactions, indicating why an intervention was or was not effective, and how it (and similar interventions) can be improved for better contextual fit. This is particularly important for innovative trials like Supporting Policy In health with Research: an Intervention Trial (SPIRIT), where causal mechanisms are poorly understood. SPIRIT was testing a multi-component intervention designed to increase the capacity of health policymakers to use research. Methods: Our mixed-methods process evaluation sought to explain variation in observed process effects across the six agencies that participated in SPIRIT. Data collection included observations of intervention workshops (n = 59), purposively sampled interviews (n = 76) and participant feedback forms (n = 553). Using a realist approach, data was coded for context-mechanism-process effect configurations (retroductive analysis) by two authors. Results: Intervention workshops were very well received. There was greater variation of views regarding other aspects of SPIRIT such as data collection, communication and the intervention’s overall value. We identified nine inter-related mechanisms that were crucial for engaging participants in these policy settings: (1) Accepting the premise (agreeing with the study’s assumptions); (2) Self-determination (participative choice); (3) The Value Proposition (seeing potential gain); (4) ‘Getting good stuff’ (identifying useful ideas, resources or connections); (5) Self-efficacy (believing ‘we can do this!’); (6) Respect (feeling that SPIRIT understands and values one’s work); (7) Confidence (believing in the study’s integrity and validity); (8) Persuasive leadership (authentic and compelling advocacy from leaders); and (9) Strategic insider facilitation (local translation and mediation). These findings were used to develop tentative explanatory propositions and to revise the programme theory. Conclusion: This paper describes how SPIRIT functioned in six policy agencies, including why strategies that worked well in one site were less effective in others. Findings indicate a complex interaction between participants’ perception of the intervention, shifting contextual factors, and the form that the intervention took in each site. Our propositions provide transferable lessons about contextualised areas of strength and weakness that may be useful in the development and implementation of similar studies

Drug information resources used by nurse practitioners and collaborating physicians at the point of care in Nova Scotia, Canada: a survey and review of the literature

BACKGROUND: Keeping current with drug therapy information is challenging for health care practitioners. Technologies are often implemented to facilitate access to current and credible drug information sources. In the Canadian province of Nova Scotia, legislation was passed in 2002 to allow nurse practitioners (NPs) to practice collaboratively with physician partners. The purpose of this study was to determine the current utilization patterns of information technologies by these groups of practitioners. METHODS: Nurse practitioners and their collaborating physician partners in Nova Scotia were sent a survey in February 2005 to determine the frequency of use, usefulness, accessibility, credibility, and current/timeliness of personal digital assistant (PDA), computer, and print drug information resources. Two surveys were developed (one for PDA users and one for computer users) and revised based on a literature search, stakeholder consultation, and pilot-testing results. A second distribution to nonresponders occurred two weeks following the first. Data were entered and analysed with SPSS. RESULTS: Twenty-seven (14 NPs and 13 physicians) of 36 (75%) recipients responded. 22% (6) returned personal digital assistant (PDA) surveys. Respondents reported print, health professionals, and online/electronic resources as the most to least preferred means to access drug information, respectively. 37% and 35% of respondents reported using "both print and electronic but print more than electronic" and "print only", respectively, to search monograph-related drug information queries whereas 4% reported using "PDA only". Analysis of respondent ratings for all resources in the categories print, health professionals and other, and online/electronic resources, indicated that the Compendium of Pharmaceuticals and Specialties and pharmacists ranked highly for frequency of use, usefulness, accessibility, credibility, and current/timeliness by both groups of practitioners. Respondents' preferences and resource ratings were consistent with self-reported methods for conducting drug information queries. Few differences existed between NP and physician rankings of resources. CONCLUSION: The use of computers and PDAs remains limited, which is also consistent with preferred and frequent use of print resources. Education for these practitioners regarding available electronic drug information resources may facilitate future computer and PDA use. Further research is needed to determine methods to increase computer and PDA use and whether these technologies affect prescribing and patient outcomes

A systematic review of frameworks for the interrelationships of mental health evidence and policy in low- and middle-income countries

Background: The interrelationships between research evidence and policy-making are complex. Different theoretical frameworks exist to explain general evidence–policy interactions. One largely unexplored element of these interrelationships is how evidence interrelates with, and influences, policy/political agenda-setting. This review aims to identify the elements and processes of theories, frameworks and models on interrelationships of research evidence and health policy-making, with a focus on actionability and agenda-setting in the context of mental health in low- and middle-income countries (LMICs). Methods: A systematic review of theories was conducted based on the BeHeMOTh search method, using a tested and refined search strategy. Nine electronic databases and other relevant sources were searched for peer-reviewed and grey literature. Two reviewers screened the abstracts, reviewed full-text articles, extracted data and performed quality assessments. Analysis was based on a thematic analysis. The included papers had to present an actionable theoretical framework/model on evidence and policy interrelationships, such as knowledge translation or evidence-based policy, specifically target the agenda-setting process, focus on mental health, be from LMICs and published in English. Results: From 236 publications included in the full text analysis, no studies fully complied with our inclusion criteria. Widening the focus by leaving out ‘agenda-setting’, we included ten studies, four of which had unique conceptual frameworks focusing on mental health and LMICs but not agenda-setting. The four analysed frameworks confirmed research gaps from LMICs and mental health, and a lack of focus on agenda-setting. Frameworks and models from other health and policy areas provide interesting conceptual approaches and lessons with regards to agenda-setting. Conclusion: Our systematic review identified frameworks on evidence and policy interrelations that differ in their elements and processes. No framework fulfilled all inclusion criteria. Four actionable frameworks are applicable to mental health and LMICs, but none specifically target agenda-setting. We have identified agenda-setting as a research theory gap in the context of mental health knowledge translation in LMICs. Frameworks from other health/policy areas could offer lessons on agenda-setting and new approaches for creating policy impact for mental health and to tackle the translational gap in LMICs

Comparison between the HCV IRES domain IV RNA structure and the Iron Responsive Element

Background: Serum ferritin and hepatic iron concentrations are frequently elevated in patients who are chronically infected with the hepatitis C virus (HCV), and hepatic iron concentration has been used to predict response to interferon therapy, but these correlations are not well understood. The HCV genome contains an RNA structure resembling an iron responsive element (IRE) in its internal ribosome entry site (IRES) structural domain IV (dIV). An IRE is a stem loop structure used to control the expression of eukaryotic proteins involved in iron homeostasis by either inhibiting ribosomal binding or protecting the mRNA from nuclease degradation. The HCV structure, located within the binding site of the 40S ribosomal subunit, might function as an authentic IRE or by an IRE-like mechanism.----- Results: Electrophoretic mobility shift assays showed that the HCV IRES domain IV structure does not interact with the iron regulatory protein 1 (IRP1) in vitro. Systematic HCV IRES RNA mutagenesis suggested that IRP1 cannot accommodate the shape of the wild type HCV IRES dIV RNA structure.----- Conclusion The HCV IRES dIV RNA structure is not an authentic IRE. The possibility that this RNA structure is responsible for the observed correlations between intracellular iron concentration and HCV infection parameters through an IRE-like mechanism in response to some other cellular signal remains to be tested