Priming with recombinant auxotrophic BCG expressing HIV-1 Gag, RT and Gp120 and boosting with recombinant MVA induces a robust T cell response in mice

In previous studies we have shown that a pantothenate auxotroph of Myocbacterium bovis BCG (BCGΔ panCD ) expressing HIV-1 subtype C Gag induced Gag-specific immune responses in mice and Chacma baboons after prime-boost immunization in combination with matched rMVA and VLP vaccines respectively. In this study recombinant BCG (rBCG) expressing HIV-1 subtype C reverse transcriptase and a truncated envelope were constructed using both the wild type BCG Pasteur strain as a vector and the pantothenate auxotroph. Mice were primed with rBCG expressing Gag and RT and boosted with a recombinant MVA, expressing a polyprotein of Gag, RT, Tat and Nef (SAAVI MVA-C). Priming with rBCGΔ panCD expressing Gag or RT rather than the wild type rBCG expressing Gag or RT resulted in higher frequencies of total HIV-specific CD8 + T cells and increased numbers of T cells specific to the subdominant Gag and RT epitopes. Increasing the dose of rBCG from 10 5 cfu to 10 7 cfu also led to an increase in the frequency of responses to subdominant HIV epitopes. A mix of the individual rBCGΔ panCD vaccines expressing either Gag, RT or the truncated Env primed the immune system for a boost with SAAVI MVA-C and generated five-fold higher numbers of HIV-specific IFN-γ-spot forming cells than mice primed with rBCGΔ panCD containing an empty vector control. Priming with the individual rBCGΔ panCD vaccines or the mix and boosting with SAAVI MVA-C also resulted in the generation of HIV-specific CD4 + and CD8 + T cells producing IFN-γ and TNF-α and CD4 + cells producing IL-2. The rBCG vaccines tested in this study were able to prime the immune system for a boost with rMVA expressing matching antigens, inducing robust, HIV-specific T cell responses to both dominant and subdominant epitopes in the individual proteins when used as individual vaccines or in a mix

The genetic history of the Southern Arc: a bridge between West Asia and Europe

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra–West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Effect of a telephone-delivered coronary heart disease secondary prevention program (ProActive Heart) on quality of life and health behaviours: primary outcomes of a randomised controlled trial

Background Participation in coronary heart disease secondary prevention programs is low. Innovative programs to meet this treatment gap are required.Purpose To aim of this study is to describe the effectiveness of a telephone-delivered secondary prevention program for myocardial infarction patients.Methods Four hundred and thirty adult myocardial infarction patients in Brisbane, Australia were randomised to a 6-month secondary prevention program or usual care. Primary outcomes were health-related quality of life (Short Form-36) and physical activity (Active Australia Survey).Results Significant intervention effects were observed for health-related quality of life on the mental component summary score (p = 0.02), and the social functioning (p = 0.04) and role-emotional (p = 0.03) subscales, compared with usual care. Intervention participants were also more likely to meet recommended levels of physical activity (p = 0.02), body mass index (p = 0.05), vegetable intake (p = 0.04) and alcohol consumption (p = 0.05).Conclusions Telephone-delivered secondary prevention programs can significantly improve health outcomes and could meet the treatment gap for myocardial infarction patients

A genetic probe into the ancient and medieval history of Southern Europe and West Asia

Literary and archaeological sources have preserved a rich history of Southern Europe and West Asia since the Bronze Age that can be complemented by genetics. Mycenaean period elites in Greece did not differ from the general population and included both people with some steppe ancestry and others, like the Griffin Warrior, without it. Similarly, people in the central area of the Urartian Kingdom around Lake Van lacked the steppe ancestry characteristic of the kingdom’s northern provinces. Anatolia exhibited extraordinary continuity down to the Roman and Byzantine periods, with its people serving as the demographic core of much of the Roman Empire, including the city of Rome itself. During medieval times, migrations associated with Slavic and Turkic speakers profoundly affected the region

A genetic probe into the ancient and medieval history of Southern Europe and West Asia

Literary and archaeological sources have preserved a rich history of Southern Europe and West Asia since the Bronze Age that can be complemented by genetics. Mycenaean period elites in Greece did not differ from the general population and included both people with some steppe ancestry and others, like the Griffin Warrior, without it. Similarly, people in the central area of the Urartian Kingdom around Lake Van lacked the steppe ancestry characteristic of the kingdom's northern provinces. Anatolia exhibited extraordinary continuity down to the Roman and Byzantine periods, with its people serving as the demographic core of much of the Roman Empire, including the city of Rome itself. During medieval times, migrations associated with Slavic and Turkic speakers profoundly affected the region