Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages

The RAW264 murine macrophage cell line was used as a model to examine the role of the tat and nef gene products in the transcription regulation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in macrophages. Contrary to claims that the activity of the HIV-1 LTR responds poorly in rodent cells to trans activation by the viral tat gene product, cotransfection of RAW264 cells with a tat expression plasmid in transient transfection assays caused a > 20-fold increase in reporter gene expression that was inhibited by mutations in the TAR region. RAW264 cells stably transfected with the tat plasmid displayed similarly elevated HIV-1 LTR-driven reporter gene activity. By contrast to previous reports indicating a negative role for nef in HIV transcription, cotransfection of RAW264 cells with a nef expression plasmid trans activated the HIV-1 LTR driving either a chloramphenicol acetyltransferase or a luciferase reporter gene. The action of nef was specific to the LTR, as expression of nef had no effect on the activity of the simian virus 40, c-fms, urokinase plasminogen activator, or type 5 acid phosphatase promoter. trans-activating activity was also manifested by a frameshift mutant expressing only the first 35 amino acids of the protein. The effects of nef were multiplicative with those of tat gene product and occurred even in the presence of bacterial lipopolysaccharide, which itself activated LTR-directed transcription. Examination of the effects of selected mutations in the LTR revealed that neither the kappa B sites in the direct repeat enhancer nor the TAR region was required as a cis-acting element in nef action. The action of nef was not species restricted; it was able to trans activate in the human monocyte-like cell line Mono Mac 6. The presence of a nef expression cassette in a neomycin phosphotransferase gene expression plasmid greatly reduced the number of G418-resistant colonies generated in stable transfection of RAW264 cells, and many of the colonies that were formed exhibited very slow growth. The frameshift mutant was also active in reducing colony generation. Given the absence of any effect of the frameshift mutation on nef function, its actions on macrophage growth and HIV transcription are discussed in terms of the role of the N-terminal 30 amino acids and of stable secondary structures in the mRNA

The Makings of an Evidence-Based Local Health Department: Identifying Administrative and Management Practices

There is a gap in knowledge about how to best organize and administer practice in local health departments to implement sustained evidence-based policies, programs, and interventions. This report identifies administrative and management evidence-based practices to inform ongoing initiatives in local public health system quality improvement, accreditation processes, and performance. The article presents administrative elements in workforce development, leadership, organizational climate and culture, relationships and partnerships, and financial processes that local health departments can address at modest cost within a few years or less. Local public health systems can further identify, implement and evaluate evidence-based administrative practices

Developing a Tool to Assess Administrative Evidence-Based Practices in Local Health Departments

There is need for assessing the practices undertaken by local health departments in order to improve the implementation of evidence-based actions. This paper describes the development and testing of a survey instrument for assessing Administrative Evidence-Based Practices (A-EBPs) in Local Health Departments. A-EBPs identified through a review of the literature were used to develop a survey composed of nine sections and tested in a sample of local health department practitioners. The resulting tool showed adequate test-retest reliability and internal consistency. Practitioners and researchers may apply this tool in practice-based and evaluation research

Training needs and supports for evidence-based decision making among the public health workforce in the United States

BACKGROUND: Preparing the public health workforce to practice evidence-based decision making (EBDM) is necessary to effectively impact health outcomes. Few studies report on training needs in EBDM at the national level in the United States. We report competency gaps to practice EBDM based on four U.S. national surveys we conducted with the state and local public health workforce between 2008 and 2013. METHODS: We compared self-reported data from four U.S. national online surveys on EBDM conducted between 2008 and 2013. Participants rated the importance of each EBDM competency then rated how available the competency is to them when needed on a Likert scale. We calculated a gap score by subtracting availability scores from importance scores. We compared mean gaps across surveys and utilized independent samples t tests and Cohen’s d values to compare state level gaps. In addition, participants in the 2013 state health department survey selected and ranked three items that “would most encourage you to utilize EBDM in your work” and items that “would be most useful to you in applying EBDM in your work”. We calculated the percentage of participants who ranked each item among their top three. RESULTS: The largest competency gaps were consistent across all four surveys: economic evaluation, communicating research to policymakers, evaluation designs, and adapting interventions. Participants from the 2013 state level survey reported significantly larger mean importance and availability scores (p <0.001, d =1.00, and p <0.001, d = .78 respectively) and smaller mean gaps (p <0.01, d = .19) compared to the 2008 survey. Participants most often selected “leaders prioritizing EBDM” (67.9%) among top ways to encourage EBDM use. “EBDM training for specific areas” was most commonly ranked as important in applying EBDM (64.3%). CONCLUSION: Perceived importance and availability of EBDM competencies may be increasing as supports for EBDM continue to grow through trends in funding, training, and resources. However, more capacity building is needed overall, with specific attention to the largest competency gaps. More work with public health departments to both situate trainings to boost competency in these areas and continued improvements for organizational practices (leadership prioritization) are possible next steps to sustain EBDM efforts

The global distribution of Bacillus anthracis and associated anthrax risk to humans, livestock and wildlife.

Bacillus anthracis is a spore-forming, Gram-positive bacterium responsible for anthrax, an acute infection that most significantly affects grazing livestock and wild ungulates, but also poses a threat to human health. The geographic extent of B. anthracis is poorly understood, despite multi-decade research on anthrax epizootic and epidemic dynamics; many countries have limited or inadequate surveillance systems, even within known endemic regions. Here, we compile a global occurrence dataset of human, livestock and wildlife anthrax outbreaks. With these records, we use boosted regression trees to produce a map of the global distribution of B. anthracis as a proxy for anthrax risk. We estimate that 1.83 billion people (95% credible interval (CI): 0.59-4.16 billion) live within regions of anthrax risk, but most of that population faces little occupational exposure. More informatively, a global total of 63.8 million poor livestock keepers (95% CI: 17.5-168.6 million) and 1.1 billion livestock (95% CI: 0.4-2.3 billion) live within vulnerable regions. Human and livestock vulnerability are both concentrated in rural rainfed systems throughout arid and temperate land across Eurasia, Africa and North America. We conclude by mapping where anthrax risk could disrupt sensitive conservation efforts for wild ungulates that coincide with anthrax-prone landscapes

Long-term evaluation of a course on evidence-based public health in the U.S. and Europe

The evidence-based public health course equips public health professionals with skills and tools for applying evidence-based frameworks and processes in public health practice. To date, training has included participants from all the 50 U.S. states, 2 U.S. territories, and multiple other countries besides the U.S. This study pooled follow-up efforts (5 surveys, with 723 course participants, 2005-2019) to explore the benefits, application, and barriers to applying the evidence-based public health course content. All analyses were completed in 2020. The most common benefits (reported by \u3e80% of all participants) were identifying ways to apply knowledge in their work, acquiring new knowledge, and becoming a better leader who promotes evidence-based approaches. Participants most frequently applied course content to searching the scientific literature (72.9%) and least frequently to writing grants (42.7%). Lack of funds for continued training (35.3%), not having enough time to implement evidence-based public health approaches (33.8%), and not having coworkers trained in evidence-based public health (33.1%) were common barriers to applying the content from the course. Mean scores were calculated for benefits, application, and barriers to explore subgroup differences. European participants generally reported higher benefits from the course (mean difference=0.12, 95% CI=0.00, 0.23) and higher frequency of application of the course content to their job (mean difference=0.17, 95% CI=0.06, 0.28) than U.S. participants. Participants from later cohorts (2012-2019) reported more overall barriers to applying course content in their work (mean difference=0.15, 95% CI=0.05, 0.24). The evidence-based public health course represents an important strategy for increasing the capacity (individual skills) for evidence-based processes within public health practice. Organization-level methods are also needed to scale up and sustain capacity-building efforts

Evaluating a train-the-trainer approach for improving capacity for evidence-based decision making in public health

BACKGROUND: Evidence-based public health gives public health practitioners the tools they need to make choices based on the best and most current evidence. An evidence-based public health training course developed in 1997 by the Prevention Research Center in St. Louis has been taught by a transdisciplinary team multiple times with positive results. In order to scale up evidence-based practices, a train-the-trainer initiative was launched in 2010. METHODS: This study examines the outcomes achieved among participants of courses led by trained state-level faculty. Participants from trainee-led courses in four states (Indiana, Colorado, Nebraska, and Kansas) over three years were asked to complete an online survey. Attempts were made to contact 317 past participants. One-hundred forty-four (50.9 %) reachable participants were included in analysis. Outcomes measured include frequency of use of materials, resources, and other skills or tools from the course; reasons for not using the materials and resources; and benefits from attending the course. Survey responses were tabulated and compared using Chi-square tests. RESULTS: Among the most commonly reported benefits, 88 % of respondents agreed that they acquired knowledge about a new subject, 85 % saw applications for the knowledge to their work, and 78 % agreed the course also improved abilities to make scientifically informed decisions at work. The most commonly reported reasons for not using course content as much as intended included not having enough time to implement evidence-based approaches (42 %); other staff/peers lack training (34 %); and not enough funding for continued training (34 %). The study findings suggest that utilization of course materials and teachings remains relatively high across practitioner groups, whether they were taught by the original trainers or by state-based trainers. CONCLUSIONS: The findings of this study suggest that train-the-trainer is an effective method for broadly disseminating evidence-based public health principles. Train-the-trainer is less costly than the traditional method and allows for courses to be tailored to local issues, thus making it a viable approach to dissemination and scale up of new public health practices. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12913-015-1224-2) contains supplementary material, which is available to authorized users

Public Scholarship at Indiana University-Purdue University

Community engagement is a defining attribute of the campus, and the current Strategic Plan identifies a number of strategic actions to “Deepen our Commitment to Community Engagement.” In May 2015, A Faculty Learning Community (FLC) on Public Scholarship was established in May, 2015 to address the campus strategic goals to “recognize and reward contributions to community engagement” and “define community engagement work…in Faculty Annual Reports and promotion and tenure guidelines.” At IUPUI, scholarly work occurs in research and creative activity, teaching, and/or service. In terms of promotion and tenure, faculty members must declare an area of excellence in one of these three domains. The FLC on Public Scholarship is a 3-year initiative co-sponsored by Academic Affairs and the Center for Service and Learning (CSL). Seven faculty members from across campus were selected to be part of the 2015-2016 FLC, and two co-chairs worked closely with CSL staff to plan and facilitate the ongoing work. The FLC is charged with defining public scholarship, identifying criteria to evaluate this type of scholarship, assist faculty in documenting their community-engaged work, and working with department Chairs and Deans in adapting criteria into promotion and tenure materials. The intended audiences for this work includes faculty, community-engaged scholars, public scholars, promotion and tenure committees, external reviewers, and department Chairs and Deans. The following provides background to the campus context and a brief summary of work to date, including definition and proposed criteria to evaluate public scholarship.IUPUI Center for Service and Learning; IUPUI Office of Academic Affair

Structure–activity relationship study of EphB3 receptor tyrosine kinase inhibitors

A structure–activity relationship study for a 2-chloroanilide derivative of pyrazolo[1,5-a]pyridine revealed that increased EphB3 kinase inhibitory activity could be accomplished by retaining the 2-chloroanilide and introducing a phenyl or small electron donating substituents to the 5-position of the pyrazolo[1,5-a]pyridine. In addition, replacement of the pyrazolo[1,5-a]pyridine with imidazo[1,2-a]pyridine was well tolerated and resulted in enhanced mouse liver microsome stability. The structure–activity relationship for EphB3 inhibition of both heterocyclic series was similar. Kinase inhibitory activity was also demonstrated for representative analogs in cell culture. An analog (32, LDN-211904) was also profiled for inhibitory activity against a panel of 288 kinases and found to be quite selective for tyrosine kinases. Overall, these studies provide useful molecular probes for examining the in vitro, cellular and potentially in vivo kinase-dependent function of EphB3 receptor

Training the workforce in evidence-based public health: An evaluation of impact among US and international practitioners

INTRODUCTION: The Prevention Research Center in St. Louis developed a course on evidence-based public health in 1997 to train the public health workforce in implementation of evidence-based public health. The objective of this study was to assess use and benefits of the course and identify barriers to using evidence-based public health skills as well as ways to improve the course. METHODS: We used a mixed-method design incorporating on-site pre- and post-evaluations among US and international course participants who attended from 2008 through 2011 and web-based follow-up surveys among course participants who attended from 2005 through 2011 (n = 626). Respondents included managers, specialists, and academics at state health departments, local health departments, universities, and national/regional health departments. RESULTS: We found significant improvement from pre- to post-evaluation for 11 measures of knowledge, skill, and ability. Follow-up survey results showed at least quarterly use of course skills in most categories, majority endorsement of most course benefits, and lack of funding and coworkers who do not have evidence-based public health training as the most significant barriers to implementation of evidence-based public health. Respondents suggested ways to increase evidence-based decision making at their organization, focusing on organizational support and continued access to training. CONCLUSION: Although the evidence-based public health course is effective in improving self-reported measures of knowledge, skill, and ability, barriers remain to the implementation of evidence-based decision making, demonstrating the importance of continuing to offer and expand training in evidence-based public health