Using formative evaluation in an implementation project to increase vaccination rates in high-risk veterans: QUERI Series

<p>Abstract</p> <p>Background</p> <p>Implementation of research into practice in health care systems is a challenging and often unsuccessful endeavor. The United States Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) research teams include formative evaluations (FE) in their action-oriented VA implementation projects to identify critical information about the processes of implementation that can guide adjustments to project activities, in order to better meet project goals. This article describes the development and use of FE in an action-oriented implementation research project.</p> <p>Methods</p> <p>This two-year action-oriented implementation research project was conducted at 23 VA Spinal Cord Injury (SCI) Centers, and targeted patients, staff and the system of care, such as administration and information technology. Data for FE were collected by electronic and paper surveys, semi-structured and open-ended interviews, notes during conference calls, and exchange of e-mail messages. Specific questions were developed for each intervention (designed to improve vaccination rates for influenza in veterans with spinal cord injury and disorder); informants were selected for their knowledge of interventions and their use in SCI Centers.</p> <p>Results</p> <p>Data from FE were compiled separately for each intervention to describe barriers to progress and guide adjustments to implementation activities. These data addressed the processes of implementing the interventions, problem-solving activities and the status of interventions at SCI Centers.</p> <p>Conclusion</p> <p>Formative evaluations provided the project team with a broad view of the processes of implementing multi-targeted interventions as well as the evolving status of the related best practice. Using FE was useful, although the challenges of conducting FE for non-field researchers should be addressed. Work is needed to develop methods for conducting FE across multiple sites, as well as acknowledging variations in local contexts that affect implementation of interventions.</p

Genetic and Anatomic Determinants of Enzootic Venezuelan Equine Encephalitis Virus Infection of Culex (Melanoconion) taeniopus

Venezuelan equine encephalitis (VEE) is a re-emerging, mosquito-borne viral disease with the potential to cause fatal encephalitis in both humans and equids. Recently, detection of endemic VEE caused by enzootic strains has escalated in Mexico, Peru, Bolivia, Colombia and Ecuador, emphasizing the importance of understanding the enzootic transmission cycle of the etiologic agent, VEE virus (VEEV). The majority of work examining the viral determinants of vector infection has been performed in the epizootic mosquito vector, Aedes (Ochlerotatus) taeniorhynchus. Based on the fundamental differences between the epizootic and enzootic cycles, we hypothesized that the virus-vector interaction of the enzootic cycle is fundamentally different from that of the epizootic model. We therefore examined the determinants for VEEV IE infection in the enzootic vector, Culex (Melanoconion) taeniopus, and determined the number and susceptibility of midgut epithelial cells initially infected and their distribution compared to the epizootic virus-vector interaction. Using chimeric viruses, we demonstrated that the determinants of infection for the enzootic vector are different than those observed for the epizootic vector. Similarly, we showed that, unlike A. taeniorhynchus infection with subtype IC VEEV, C. taeniopus does not have a limited subpopulation of midgut cells susceptible to subtype IE VEEV. These findings support the hypothesis that the enzootic VEEV relationship with C. taeniopus differs from the epizootic virus-vector interaction in that the determinants appear to be found in both the nonstructural and structural regions, and initial midgut infection is not limited to a small population of susceptible cells

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Normative perspectives on journalism studies: Stock-taking and future directions

Journalism has advanced greatly as a field in its own right in recent decades. As well as a cause for celebration, however, this may give rise to concerns – in particular that scholars may pay increasing attention to the inner workings of journalistic institutions at the expense of their external ties, impact and significance, including their normative ones. It is true that important normative analyses have appeared in the literature, six of which the article defines and exemplifies. So far, however, these ideas have had relatively little influence on the thought or practice of journalists. The article concludes by suggesting a way in which a closer and more constructive dialogue could be achieved between journalism scholars and practitioners, centring on the normative challenges faced by both sides

Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas.

Venezuelan equine encephalitis (VEE) complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections. We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins. Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular clock dating of ancestors. Times to most recent common ancestors (tMRCAs) could be robustly estimated only for the more recently diverged subtypes; the tMRCA of the ID/IAB/IC/II and IE clades of VEE virus (VEEV) were estimated at ca. 149–973 years ago. Evolution of the IE subtype has been characterized by a significant evolutionary shift from the rest of the VEEV complex, with an increase in structural protein substitutions that are unique to this group, possibly reflecting adaptation to its unique enzootic mosquito vector Culex (Melanoconion) taeniopus. Our inferred tree topologies suggest that VEEV is maintained primarily in situ, with only occasional spread to neighboring countries, probably reflecting the limited mobility of rodent hosts and mosquito vectors

A model of professional self-identity formation in student doctors and dentists: a mixed method study.

BACKGROUND: Professional self-identity [PSI] can be defined as the degree to which an individual identifies with his or her professional group. Several authors have called for a better understanding of the processes by which healthcare students develop their professional identities, and suggested helpful theoretical frameworks borrowed from the social science and psychology literature. However to our knowledge, there has been little empirical work examining these processes in actual healthcare students, and we are aware of no data driven description of PSI development in healthcare students. Here, we report a data driven model of PSI formation in healthcare students. METHODS: We interviewed 17 student doctors and dentists who had indicated, on a tracking questionnaire, the most substantial changes in their PSI. We analysed their perceptions of the experiences that had influenced their PSI, to develop a descriptive model. Both the primary coder and the secondary coder considered the data without reference to the existing literature; i.e. we used a bottom up approach rather than a top down approach. RESULTS: The results indicate that two overlapping frames of reference affect PSI formation: the students' self-perception and their perception of the professional role. They are 'learning' both; neither is static. Underpinning those two learning processes, the following key mechanisms operated: [1] When students are allowed to participate in the professional role they learn by trying out their knowledge and skill in the real world and finding out to what extent they work, and by trying to visualise themselves in the role. [2] When others acknowledge students as quasi-professionals they experience transference and may respond with counter-transference by changing to meet expectations or fulfil a prototype. [3] Students may also dry-run their professional role (i.e., independent practice of professional activities) in a safe setting when invited. CONCLUSIONS: Students' experiences, and their perceptions of those experiences, can be evaluated through a simple model that describes and organises the influences and mechanisms affecting PSI. This empirical model is discussed in the light of prevalent frameworks from the social science and psychology literature

Small molecules targeted to the microtubule–Hec1 interaction inhibit cancer cell growth through microtubule stabilization

Highly expressed in cancer protein 1 (Hec1) is a subunit of the kinetochore (KT)-associated Ndc80 complex, which ensures proper segregation of sister chromatids at mitosis by mediating the interaction between KTs and microtubules (MTs). HEC1 mRNA and protein are highly expressed in many malignancies as part of a signature of chromosome instability. These properties render Hec1 a promising molecular target for developing therapeutic drugs that exert their anticancer activities by producing massive chromosome aneuploidy. A virtual screening study aimed at identifying small molecules able to bind at the Hec1–MT interaction domain identified one positive hit compound and two analogs of the hit with high cytotoxic, pro-apoptotic and anti-mitotic activities. The most cytotoxic analog (SM15) was shown to produce chromosome segregation defects in cancer cells by inhibiting the correction of erroneous KT–MT interactions. Live cell imaging of treated cells demonstrated that mitotic arrest and segregation abnormalities lead to cell death through mitotic catastrophe and that cell death occurred also from interphase. Importantly, SM15 was shown to be more effective in inducing apoptotic cell death in cancer cells as compared to normal ones and effectively reduced tumor growth in a mouse xenograft model. Mechanistically, cold-induced MT depolymerization experiments demonstrated a hyper-stabilization of both mitotic and interphase MTs. Molecular dynamics simulations corroborate this finding by showing that SM15 can bind the MT surface independently from Hec1 and acts as a stabilizer of both MTs and KT–MT interactions. Overall, our studies represent a clear proof of principle that MT-Hec1-interacting compounds may represent novel powerful anticancer agents

Drivers and Socioeconomic Impacts of Tourism Participation in Protected Areas

Nature-based tourism has the potential to enhance global biodiversity conservation by providing alternative livelihood strategies for local people, which may alleviate poverty in and around protected areas. Despite the popularity of the concept of nature-based tourism as an integrated conservation and development tool, empirical research on its actual socioeconomic benefits, on the distributional pattern of these benefits, and on its direct driving factors is lacking, because relevant long-term data are rarely available. In a multi-year study in Wolong Nature Reserve, China, we followed a representative sample of 220 local households from 1999 to 2007 to investigate the diverse benefits that these households received from recent development of nature-based tourism in the area. Within eight years, the number of households directly participating in tourism activities increased from nine to sixty. In addition, about two-thirds of the other households received indirect financial benefits from tourism. We constructed an empirical household economic model to identify the factors that led to household-level participation in tourism. The results reveal the effects of local households' livelihood assets (i.e., financial, human, natural, physical, and social capitals) on the likelihood to participate directly in tourism. In general, households with greater financial (e.g., income), physical (e.g., access to key tourism sites), human (e.g., education), and social (e.g., kinship with local government officials) capitals and less natural capital (e.g., cropland) were more likely to participate in tourism activities. We found that residents in households participating in tourism tended to perceive more non-financial benefits in addition to more negative environmental impacts of tourism compared with households not participating in tourism. These findings suggest that socioeconomic impact analysis and change monitoring should be included in nature-based tourism management systems for long-term sustainability of protected areas

Venezuelan Equine Encephalitis Virus in Iquitos, Peru: Urban Transmission of a Sylvatic Strain

Enzootic strains of Venezuelan equine encephalitis virus (VEEV) have been isolated from febrile patients in the Peruvian Amazon Basin at low but consistent levels since the early 1990s. Through a clinic-based febrile surveillance program, we detected an outbreak of VEEV infections in Iquitos, Peru, in the first half of 2006. The majority of these patients resided within urban areas of Iquitos, with no report of recent travel outside the city. To characterize the risk factors for VEEV infection within the city, an antibody prevalence study was carried out in a geographically stratified sample of urban areas of Iquitos. Additionally, entomological surveys were conducted to determine if previously incriminated vectors of enzootic VEEV were present within the city. We found that greater than 23% of Iquitos residents carried neutralizing antibodies against VEEV, with significant associations between increased antibody prevalence and age, occupation, mosquito net use, and overnight travel. Furthermore, potential vector mosquitoes were widely distributed across the city. Our results suggest that while VEEV infection is more common in rural areas, transmission also occurs within urban areas of Iquitos, and that further studies are warranted to identify the precise vectors and reservoirs involved in urban VEEV transmission

Prodigious submarine landslides during the inception and early growth of volcanic islands

Volcanic island inception applies large stresses as the ocean crust domes in response to magma ascension and is loaded by eruption of lavas. There is currently limited information on when volcanic islands are initiated on the seafloor, and no information regarding the seafloor instabilities island inception may cause. The deep sea Madeira Abyssal Plain contains a 43 million year history of turbidites among which many originate from mass movements in the Canary Islands. Here, we investigate the composition and timing of a distinctive group of turbidites that we suggest represent a new unique record of large-volume submarine landslides triggered during the inception, submarine shield growth, and final subaerial emergence of the Canary Islands. These slides are predominantly multi-stage and yet represent among the largest mass movements on the Earth’s surface up to three or more-times larger than subaerial Canary Islands flank collapses. Thus whilst these deposits provide invaluable information on ocean island geodynamics they also represent a significant, and as yet unaccounted, marine geohazard