Reproductive characteristics of high body condition mares with high versus low leptin concentrations

Two experiments were performed to discover what, if any, reproductive differences exist in high body condition (BCS) mares with varying concentrations of leptin. Previous research showed that mares with high body condition scores can have a range of leptin levels, from very low (\u3c5 ng/mL) to very high (\u3e10 ng/mL). Earlier results indicated that most mares with high body condition scores maintain estrous cycles or show significant follicular activity during the winter. Among these high BCS mares, about 30% of them exhibit hyperleptinemia and hyperinsulinemia. The first experiment was designed to compare the reproductive characteristics of high BCS mares with high versus low leptin levels during vernal transition and the first estrous cycle. Also, an IVGTT, insulin challenge, and two sulpiride challenges were performed to characterize endocrine profiles of these mares. Results of these challenges were similar to previous work, in that hyperleptinemic mares had greater insulin responses to glucose and greater clearance rates of infused glucose compared to low leptin mares. These mares also showed a slightly greater prolactin response to sulpiride than their low leptin counterparts. When analyzing the reproductive traits of these mares, no differences between groups existed for follicular sizes or distributions, gonadotropin levels, or date of first ovulation. The second experiment was designed to assess what differences may exist between high BCS mares with high versus low leptin levels with regard to their gonadotropin and ovarian responses to several analogs of gonadotropin releasing hormone (GnRH). Histrelin and deslorelin appeared to be the most potent of the analogs, followed by buserelin and then GnRH. Leptin status did not appear to affect the gonadotropin response or time to ovulation for any of the analogs used in this trial. In conclusion, although hyperleptinemic mares showed altered insulin and glucose characteristics, no significant reproductive differences were observed between these mares and their normal counterparts in terms of ovarian function or the hypothalamic- pituitary axis during vernal transition or the estrous cycle

Mechanisms for inspiring action in South African youth

Many young people in South Africa are in the process of transforming their country. To positively contribute to the development agenda, young people need the skills and capacity to bring about change and set themselves apart as leaders. This retrospective, mixed-method evaluation study provides insight into the multi-level mechanisms that allow young South Africans opportunities to grow personally and to take action on issues of significance.  Results show that development of three non-cognitive competencies (grit, growth mindset, and self-efficacy) was integral to starting (and finishing) a social action project. Social support, social capital and teamwork were also critical mechanisms – while school location, socioeconomic status and gender were not. Non-cognitive competency development is integral to this research as there is evidence that building these skills promotes leadership which creates a bias to action.  This article reflects on the implications for effective youth development program design and the youth leadership sector more generally

"It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The State of Research and Platforms for Access: Cara Caddoo

Click on the first URL link below in the "External Files" section to play the authoritative published version of the streaming video accompanying this transcript.The second URL link provided below in the "External Files" section forwards to a second version of the streaming video file associated with this transcript. This streaming video, hosted on Indiana University's Avalon Media System, represents the efforts of the Black Film Center/Archive to ensure the long-term preservation of the digital file associated with this transcript

Sustainability in health care by allocating resources effectively (SHARE) 3: examining how resource allocation decisions are made, implemented and evaluated in a local healthcare setting

Abstract Background This is the third in a series of papers reporting a program of Sustainability in Health care by Allocating Resources Effectively (SHARE) in a local healthcare setting. Leaders in a large Australian health service planned to establish an organisation-wide, systematic, integrated, evidence-based approach to disinvestment. In order to introduce new systems and processes for disinvestment into existing decision-making infrastructure, we aimed to understand where, how and by whom resource allocation decisions were made, implemented and evaluated. We also sought the knowledge and experience of staff regarding previous disinvestment activities. Methods Structured interviews, workshops and document analysis were used to collect information from multiple sources in an environmental scan of decision-making systems and processes. Findings were synthesised using a theoretical framework. Results Sixty-eight respondents participated in interviews and workshops. Eight components in the process of resource allocation were identified: Governance, Administration, Stakeholder engagement, Resources, Decision-making, Implementation, Evaluation and, where appropriate, Reinvestment of savings. Elements of structure and practice for each component are described and a new framework was developed to capture the relationships between them. A range of decision-makers, decision-making settings, type and scope of decisions, criteria used, and strengths, weaknesses, barriers and enablers are outlined. The term ‘disinvestment’ was not used in health service decision-making. Previous projects that involved removal, reduction or restriction of current practices were driven by quality and safety issues, evidence-based practice or a need to find resource savings and not by initiatives where the primary aim was to disinvest. Measuring resource savings is difficult, in some situations impossible. Savings are often only theoretical as resources released may be utilised immediately by patients waiting for beds, clinic appointments or surgery. Decision-making systems and processes for resource allocation are more complex than assumed in previous studies. Conclusion There is a wide range of decision-makers, settings, scope and type of decisions, and criteria used for allocating resources within a single institution. To our knowledge, this is the first paper to report this level of detail and to introduce eight components of the resource allocation process identified within a local health service

Health technology disinvestment: tests, drugs and clinical practice: part 1 Report

Most new health technologies and clinical practices are assessed for safety, effectiveness and cost effectiveness before they are introduced. However most of our current practices are not subjected to these rigorous assessments and recent research shows that many are not effective and are sometimes even harmful. Cessation or restriction of potentially harmful, ineffective or inefficient practices has the dual advantage of improving patient care and allowing for a more efficient use of scarce resources. This approach, also known as 'disinvestment', has the potential to increase total health benefits without increasing spending.<p>A national workshop was held to explore issues related to disinvestment of health technologies and clinical practices. This was approached from three perspectives: health policy researchers, health economists and health service decision-makers.</p><p>Seventy two participants attended and included representation from national and state government departments, health services, academic and research groups, professional associations and consumers.</p><p>While disinvestment is a relatively new concept, this workshop identified that there is already considerable knowledge and experience in Australia. Although significant work is being undertaken, it is usually in isolation. There are no standard methods, agreed approaches or shared understanding of what disinvestment is and what it means in various settings and contexts. There is no systematic sharing of information, little collaboration on projects and no community of practice.</p><p>A range of strong, consistent messages emerged and are reported</p

Additional file 1: of Sustainability in health care by allocating resources effectively (SHARE) 3: examining how resource allocation decisions are made, implemented and evaluated in a local healthcare setting

Methods. (PDF 328 kb

Sustainability in Health care by Allocating Resources Effectively (SHARE) 8: developing, implementing and evaluating an evidence dissemination service in a local healthcare setting

Abstract Background This is the eighth in a series of papers reporting Sustainability in Health care by Allocating Resources Effectively (SHARE) in a local healthcare setting. The SHARE Program was a systematic, integrated, evidence-based program for disinvestment within a large Australian health service. One of the aims was to explore methods to deliver existing high quality synthesised evidence directly to decision-makers to drive decision-making proactively. An Evidence Dissemination Service (EDS) was proposed. While this was conceived as a method to identify disinvestment opportunities, it became clear that it could also be a way to review all practices for consistency with current evidence. This paper reports the development, implementation and evaluation of two models of an in-house EDS. Methods Frameworks for development of complex interventions, implementation of evidence-based change, and evaluation and explication of processes and outcomes were adapted and/or applied. Mixed methods including a literature review, surveys, interviews, workshops, audits, document analysis and action research were used to capture barriers, enablers and local needs; identify effective strategies; develop and refine proposals; ascertain feedback and measure outcomes. Results Methods to identify, capture, classify, store, repackage, disseminate and facilitate use of synthesised research evidence were investigated. In Model 1, emails containing links to multiple publications were sent to all self-selected participants who were asked to determine whether they were the relevant decision-maker for any of the topics presented, whether change was required, and to take the relevant action. This voluntary framework did not achieve the aim of ensuring practice was consistent with current evidence. In Model 2, the need for change was established prior to dissemination, then a summary of the evidence was sent to the decision-maker responsible for practice in the relevant area who was required to take appropriate action and report the outcome. This mandatory governance framework was successful. The factors influencing decisions, processes and outcomes were identified. Conclusion An in-house EDS holds promise as a method of identifying disinvestment opportunities and/or reviewing local practice for consistency with current evidence. The resource-intensive nature of delivery of the EDS is a potential barrier. The findings from this study will inform further exploration