The PD-1/PD-L1 (B7-H1) Pathway in Chronic Infection-Induced Cytotoxic T Lymphocyte Exhaustion

Cytotoxic CD8 T lymphocytes (CTLs) play a pivotal role in the control of infection. Activated CTLs, however, often lose effector function during chronic infection. PD-1 receptor and its ligand PD-L1 of the B7/CD28 family function as a T cell coinhibitory pathway and are emerging as major regulators converting effector CTLs into exhausted CTLs during chronic infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and other pathogens capable of establishing chronic infections. Importantly, blockade of the PD-1/PD-L1 pathway is able to restore functional capabilities to exhausted CTLs and early clinical trials have shown promise. Further research will reveal how chronic infection induces upregulation of PD-1 on CTLs and PD-L1 on antigen-presenting cells and other tissue cells and how the PD-1/PD-L1 interaction promotes CTLs exhaustion, which is crucial for developing effective prophylactic and therapeutic vaccination against chronic infections

Hiding In Plain Sight: Building Community Social Capital In Distance Education Graduate Programs

There is an increasing global demand for a broad range of academic programs to be offered by distance education. The development of flexible online technology has made studying for a degree ‘anywhere and anytime’ possible and this option has significant appeal for many people. However, there is limited knowledge available to guide faculty in the strategic development of supportive learning environments for distance education students that fosters connectedness for academic success. The purpose of this three-phase study was to introduce the concept of community social capital to a cohort of graduate nursing students (N=97) and then track implementation and impact in their on-line academic learning environment. Understanding social capital at the onset of graduate school can lead to an improved sense of how students can utilize and grow social capital, enhance bonding, and increase their academic advantage. The findings inform future education curricula, innovative strategies, and educational research agendas by suggesting that social capital awareness is beneficial to students enrolled in distance education

Making Things Right: Nurses' Experiences with Workplace Bullying—A Grounded Theory

While bullying in the healthcare workplace has been recognized internationally, there is still a culture of silence in many institutions in the United States, perpetuating underreporting and insufficient and unproven interventions. The deliberate, repetitive, and aggressive behaviors of bullying can cause psychological and/or physical harm among professionals, disrupt nursing care, and threaten patient safety and quality outcomes. Much of the literature focuses on categories of bullying behaviors and nurse responses. This qualitative study reports on the experiences of nurses confronting workplace bullying. We collected data from the narratives of 99 nurses who completed an open-ended question embedded in an online survey in 2007. A constructivist grounded theory approach was used to analyze the data and shape a theory of how nurses make things right when confronted with bullying. In a four-step process, nurses place bullying in context, assess the situation, take action, and judge the outcomes of their actions. While many nurses do engage in a number of effective yet untested strategies, two additional concerns remain: inadequate support among nursing colleagues and silence and inaction by nurse administrators. Qualitative inquiry has the potential to guide researchers to a greater understanding of the complexities of bullying in the workplace

Building social capital through breastfeeding peer support: Insights from an evaluation of a voluntary breastfeeding peer support service in North-West England

Background: Peer support is reported to be a key method to help build social capital in communities. To date there are no studies that describe how this can be achieved through a breastfeeding peer support service. In this paper we present findings from an evaluation of a voluntary model of breastfeeding peer support in North-West England to describe how the service was operationalized and embedded into the community. This study was undertaken from May, 2012 to May, 2013. Methods: Interviews (group or individual) were held with 87 participants: 24 breastfeeding women, 13 peer supporters and 50 health and community professionals. The data contained within 23 monthly monitoring reports (January, 2011 to February 2013) compiled by the voluntary peer support service were also extracted and analysed. Results: Thematic analysis was undertaken using social capital concepts as a theoretical lens. Key findings were identified to resonate with ’bonding’, ‘bridging’ and ‘linking’ forms of social capital. These insights illuminate how the peer support service facilitates ‘bonds’ with its members, and within and between women who access the service; how the service ‘bridges’ with individuals from different interests and backgrounds, and how ‘links’ were forged with those in authority to gain access and reach to women and to promote a breastfeeding culture. Some of the tensions highlighted within the social capital literature were also identified. Conclusions: Horizontal and vertical relationships forged between the peer support service and community members enabled peer support to be embedded into care pathways, helped to promote positive attitudes to breastfeeding and to disseminate knowledge and maximise reach for breastfeeding support across the community. Further effort to engage with those of different ethnic backgrounds and to resolve tensions between peer supporters and health professionals is warranted

Statistical evaluation of a new resistance model for cold-formed stainless steel cross-sections subjected to web crippling

This paper presents a statistical evaluation according to Annex D of EN 1990 (2002) of a new resistance function for web crippling design of cold-formed stainless steel cross-sections. This resistance function was derived by Bock et al. (2013) through the use of carefully validated numerical models with the aim to propose a design expression for stainless steel sections, which are currently designed following the provisions for cold-formed carbon steel sections given in EN 1993-1-3 (2006). Although it was shown that the proposed design equation is appropriate for application to various stainless steels, the statistical uncertainties in material properties that the different types of stainless steels exhibit require an assessment of various partial safety factors. The statistical assessment showed that the proposed resistance function by Bock et al. (2013) requires adjustment to satisfy the safety level set out in EN 1993-1-4 (2006); A recalibration is performed herein. The web crippling design provisions given in EN 1993-1-3 (2006) and SEI/ASCE 8-02 (2002) American standard for application to stainless steel are also statistically evaluated herein. Comparison with test and numerical data showed that the predictions of the recalibrated resistance function are better suited and consistent than existing design provisionsResearch Fund for Coal and Stee

Study protocol: a double blind placebo controlled trial examining the effect of domperidone on the composition of breast milk [NCT00308334]

BACKGROUND: Domperidone, a drug that enhances upper gastric motility, is an anti-dopaminergic medication that also elevates prolactin levels. It has been shown to safely increase the milk supply of lactating women. To date, researchers have analyzed the effects of domperidone on lactating woman with respect to the quantity of their milk production, adverse effects, and drug levels in the breast milk. However, the effect of domperidone on the macronutrient composition of breast milk has not been studied and current guidelines for fortification of human milk for premature infants do not distinguish between those women using or those not using domperidone. The purpose of this study is to evaluate the effect of domperidone (given to lactating mothers of very preterm infants) on the macronutrient composition of breast milk. METHODS/DESIGN: Mothers of infants delivered at less than 31 weeks gestation, who are at least 3 weeks postpartum, and experiencing lactational failure despite non-pharmacological interventions, will be randomized to receive domperidone (10 mg three times daily) or placebo for a 14-day period. Breast milk samples will be obtained the day prior to beginning treatment and on days 4, 7 and 14. The macronutrient (protein, fat, carbohydrate and energy) and macromineral content (calcium, phosphorus and sodium) will be analyzed and compared between the two groups. Additional outcome measures will include milk volumes, serum prolactin levels (measured on days 0, 4, and 10), daily infant weights and breastfeeding rates at 2 weeks post study completion and at discharge. Forty-four participants will be recruited into the study. Analysis will be carried out using the intention to treat approach. DISCUSSION: If domperidone causes significant changes to the nutrient content of breast milk, an alteration in feeding practices for preterm infants may need to be made in order to optimize growth, nutrition and neurodevelopment outcomes

Networks and social capital: a relational approach to primary healthcare reform

Collaboration among health care providers and across systems is proposed as a strategy to improve health care delivery the world over. Over the past two decades, health care providers have been encouraged to work in partnership and build interdisciplinary teams. More recently, the notion of networks has entered this discourse but the lack of consensus and understanding about what is meant by adopting a network approach in health services limits its use. Also crucial to this discussion is the work of distinguishing the nature and extent of the impact of social relationships – generally referred to as social capital. In this paper, we review the rationale for collaboration in health care systems; provide an overview and synthesis of key concepts; dispel some common misconceptions of networks; and apply the theory to an example of primary healthcare network reform in Alberta (Canada). Our central thesis is that a relational approach to systems change, one based on a synthesis of network theory and social capital can provide the fodation for a multi-focal approach to primary healthcare reform. Action strategies are recommended to move from an awareness of 'networks' to fully translating knowledge from existing theory to guide planning and practice innovations. Decision-makers are encouraged to consider a multi-focal approach that effectively incorporates a network and social capital approach in planning and evaluating primary healthcare reform

A protocol for a systematic review of knowledge translation strategies in the allied health professions

<p>Abstract</p> <p>Background</p> <p>Knowledge translation (KT) aims to close the gap between knowledge and practice in order to realize the benefits of research through (a) improved health outcomes, (b) more effective health services and products, and (c) strengthened healthcare systems. While there is some understanding of strategies to put research findings into practice within nursing and medicine, we have limited knowledge of KT strategies in allied health professions. Given the interprofessional nature of healthcare, a lack of guidance for supporting KT strategies in the allied health professions is concerning. Our objective in this study is to systematically review published research on KT strategies in five allied health disciplines.</p> <p>Methods</p> <p>A medical research librarian will develop and implement search strategies designed to identify evidence that is relevant to each question of the review. Two reviewers will perform study selection and quality assessment using standard forms. For study selection, data will be extracted by two reviewers. For quality assessment, data will be extracted by one reviewer and verified by a second. Disagreements will be resolved through discussion or third party adjudication. Within each profession, data will be grouped and analyzed by research design and KT strategies using the Effective Practice and Organisation of Care Review Group classification scheme. An overall synthesis across professions will be conducted.</p> <p>Significance</p> <p>A uniprofessional approach to KT does not represent the interprofessional context it targets. Our findings will provide the first systematic overview of KT strategies used in allied health professionals' clinical practice, as well as a foundation to inform future KT interventions in allied healthcare settings.</p