Health worker performance in the management of paediatric fevers following in-service training and exposure to job aids in Kenya

BACKGROUND: Improving the way artemether-lumefantrine (AL) is provided to patients attending clinics is critical to maximize the benefit of this new medicine. In 2007, a new initiative was launched in one part of Kenya to improve malaria case-management through enhanced in-service training and provision of job aids. METHODS: An evaluation of the intervention using pre- and post-intervention cross sectional health facility surveys was conducted in Bondo district. The surveys included: audit of government health facilities, health worker structured interviews and exit interviews with caretakers of sick children below five years of age. The outcome indicators were the proportions of febrile children who had AL prescribed, AL dispensed, and four different dispensing and counseling tasks performed. RESULTS: At baseline 33 government health facilities, 48 health workers and 386 febrile child consultations were evaluated. At follow-up the same health facilities were surveyed and 36 health workers and 390 febrile child consultations evaluated. The findings show: 1) no health facility or health worker was exposed to all components of the intervention; 2) the proportion of health workers who received the enhanced in-service training was 67%; 3) the proportion of febrile children with uncomplicated malaria treated with the first-line anti-malarial drug, artemether-lumefantrine (AL), at health facilities where AL was in stock increased from 76.9% (95%CI: 69.4, 83.1) to 87.6% (95% CI: 82.5, 91.5); 4) there were modest but non-significant improvements in dispensing and counseling practices; and 5) when the analyses were restricted to health workers who received the enhanced in-service training and/or had received new guidelines and job aids, no significant improvements in reported case-management tasks were observed compared to baseline. CONCLUSION: In-service training and provision of job aids alone may not be adequate to improve the prescribing, dispensing and counseling tasks necessary to change malaria case-management practices and the inclusion of supervision and post-training follow-up should be considered in future clinical practice change initiatives

“Even if You Know Everything You Can Forget”: Health Worker Perceptions of Mobile Phone Text-Messaging to Improve Malaria Case-Management in Kenya

This paper presents the results of a qualitative study to investigate the perceptions and experiences of health workers involved in a a cluster-randomized controlled trial of a novel intervention to improve health worker malaria case-management in 107 government health facilities in Kenya. The intervention involved sending text-messages about paediatric outpatient malaria case-management accompanied by “motivating” quotes to health workers’ mobile phones. Ten malaria messages were developed reflecting recommendations from the Kenyan national guidelines. Two messages were delivered per day for 5 working days and the process was repeated for 26 weeks (May to October 2009). The accompanying quotes were unique to each message. The intervention was delivered to 119 health workers and there were significant improvements in correct artemether-lumefantrine (AL) management both immediately after the intervention (November 2009) and 6 months later (May 2010). In-depth interviews with 24 health workers were undertaken to investigate the possible drivers of this change. The results suggest high acceptance of all components of the intervention, with the active delivery of information in an on the job setting, the ready availability of new and stored text messages and the perception of being kept ‘up to date’ as important factors influencing practice. Applying the construct of stages of change we infer that in this intervention the SMS messages were operating primarily at the action and maintenance stages of behaviour change achieving their effect by creating an enabling environment and providing a prompt to action for the implementation of case management practices that had already been accepted as the clinical norm by the health workers. Future trials testing the effectiveness of SMS reminders in creating an enabling environment for the establishment of new norms in clinical practice as well as in providing a prompt to action for the implementation of the new case-management guidelines are justified

Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle

Can on-site management mitigate nitrogen deposition impacts in non-wooded habitats?

Nitrogen (N) deposition is a major cause of plant biodiversity loss, with serious implications for appropriate management of protected sites. Reducing N emissions is the only long-term solution. However, on-site management has the potential to mitigate some of the adverse effects of N deposition. In this paper we review how management activities such as grazing, cutting, burning, hydrological management and soil disturbance measures can mitigate the negative impacts of N across a range of temperate habitats (acid, calcareous and neutral grasslands, sand dunes and other coastal habitats, heathlands, bogs and fens). The review focuses mainly on European habitats, which have a long history of N deposition, and it excludes forested systems. For each management type we distinguish between actions that improve habitat suitability for plant species of conservation importance, and actions that immobilize N or remove it from the system. For grasslands and heathlands we collate data on the quantity of N removal by each management type. Our findings show that while most activities improve habitat suitability, the majority do little to slow or to reduce the amount of N accumulating in soil pools at current deposition rates. Only heavy cutting/mowing with removal in grasslands, high intensity burns in heathlands and sod cutting remove more N than comes in from deposition under typical management cycles. We conclude by discussing some of the unintended consequences of managing specifically for N impacts, which can include damage to non-target species, alteration of soil processes, loss of the seedbank and loss of soil carbon

Retrospective analysis of Schlafen11 (SLFN11) to predict the outcomes to therapies affecting the DNA damage response

BACKGROUND: The absence of the putative DNA/RNA helicase Schlafen11 (SLFN11) is thought to cause resistance to DNAdamaging agents (DDAs) and PARP inhibitors. METHODS: We developed and validated a clinically applicable SLFN11 immunohistochemistry assay and retrospectively correlated SLFN11 tumour levels to patient outcome to the standard of care therapies and olaparib maintenance. RESULTS: High SLFN11 associated with improved prognosis to the first-line treatment with DDAs platinum-plus-etoposide in SCLC patients, but was not strongly linked to paclitaxel–platinum response in ovarian cancer patients. Multivariate analysis of patients with relapsed platinum-sensitive ovarian cancer from the randomised, placebo-controlled Phase II olaparib maintenance Study19 showed SLFN11 tumour levels associated with sensitivity to olaparib. Study19 patients with high SLFN11 had a lower progression-free survival (PFS) hazard ratio compared to patients with low SLFN11, although both groups had the benefit of olaparib over placebo. Whilst caveated by small sample size, this trend was maintained for PFS, but not overall survival, when adjusting for BRCA status across the olaparib and placebo treatment groups, a key driver of PARP inhibitor sensitivity. CONCLUSION: We provide clinical evidence supporting the role of SLFN11 as a DDA therapy selection biomarker in SCLC and highlight the need for further clinical investigation into SLFN11 as a PARP inhibitor predictive biomarker

Reviewing research evidence and the case of participation in sport and physical recreation by black and minority ethnic communities

The paper addresses the implications of using the process of systematic review in the many areas of leisure where there is a dearth of material that would be admitted into conventional Cochrane Reviews. This raises important questions about what constitutes legitimate knowledge, questions that are of critical import not just to leisure scholars, but to the formulation of policy. The search for certainty in an area that lacks conceptual consensus results in an epistemological imperialism that takes a geocentric form. While clearly, there is a need for good research design whatever the style of research, we contend that the wholesale rejection of insightful research is profligate and foolhardy. A mechanism has to be found to capitalise on good quality research of whatever form. In that search, we draw upon our experience of conducting a review of the material available on participation in sport and physical recreation by people from Black and minority ethnic groups. The paper concludes with a proposal for a more productive review process that makes better use of the full panoply of good quality research available. © 2012 © 2012 Taylor & Francis

Presence of Epstein-Barr virus latency type III at the single cell level in post- transplantation lymphoproliferative disorders and AIDS related lymphomas

AIMS: To investigate the expression pattern of Epstein-Barr virus (EBV) latent genes at the single cell level in post-transplantation lymphoproliferative disorders and acquired immunodefiency syndrome (AIDS) related lymphomas, in relation to cellular morphology. METHODS: Nine post-transplantation lymphoproliferative disorders and three AIDS related lymphomas were subjected to immunohistochemistry using monoclonal antibodies specific for EBV nuclear antigen 1 (EBNA1) (2H4), EBNA2 (PE2 and the new rat anti-EBNA2 monoclonal antibodies 1E6, R3, and 3E9), and LMP1 (CS1-4 and S12). Double staining was performed combining R3 or 3E9 with S12. RESULTS: R3 and 3E9 anti-EBNA2 monoclonal antibodies were more sensitive than PE2, enabling the detection of more EBNA2 positive lymphoma cells. Both in post-transplantation lymphoproliferative disorders and AIDS related lymphomas, different expression patterns were detected at the single cell level. Smaller neoplastic cells were positive for EBNA2 but negative for LMP1. Larger and more blastic neoplastic cells, sometimes resembling Reed-Sternberg cells, were LMP1 positive but EBNA2 negative (EBV latency type II). Morphologically intermediate neoplastic cells coexpressing EBNA2 and LMP1 (EBV latency type III), were detected using R3 and 3E9, and formed a considerable part of the neoplastic population in four of nine post-transplantation lymphoproliferative disorders and two of three AIDS related lymphomas. All samples contained a subpopulation of small tumour cells positive exclusively for Epstein-Barr early RNA and EBNA1. The relation between cellular morphology and EBV expression patterns in this study was less pronounced in AIDS related lymphomas than in post-transplantation lymphoproliferative disorders, because the AIDS related lymphomas were less polymorphic than the post-transplantation lymphoproliferative disorders. CONCLUSIONS: In post-transplantation lymphoproliferative disorders and AIDS related lymphomas, EBV latency type III can be detected by immunohistochemistry in a subpopulation of tumour cells using sensitive monoclonal antibodies R3 and 3E9. Our data suggest that EBV infected tumour cells in these lymphomas undergo gradual changes in the expression of EBV latent genes, and that these changes are associated with changes in cellular morphology

Mental Health of Parents and Life Satisfaction of Children: A Within-Family Analysis of Intergenerational Transmission of Well-Being

This paper addresses the extent to which there is an intergenerational transmission of mental health and subjective well-being within families. Specifically it asks whether parents’ own mental distress influences their child’s life satisfaction, and vice versa. Whilst the evidence on daily contagion of stress and strain between members of the same family is substantial, the evidence on the transmission between parental distress and children’s well-being over a longer period of time is sparse. We tested this idea by examining the within-family transmission of mental distress from parent to child’s life satisfaction, and vice versa, using rich longitudinal data on 1,175 British youths. Results show that parental distress at year t-1 is an important determinant of child’s life satisfaction in the current year. This is true for boys and girls, although boys do not appear to be affected by maternal distress levels. The results also indicated that the child’s own life satisfaction is related with their father’s distress levels in the following year, regardless of the gender of the child. Finally, we examined whether the underlying transmission correlation is due to shared social environment, empathic reactions, or transmission via parent-child interaction

Relationship Difficulties Among U.K. Military Personnel: Impact of Sociodemographic, Military, and Deployment-Related Factors

© 2015, Taylor & Francis Group, LLC. Military work, especially operational deployments, may impact the romantic relationships of military personnel. Using a subsample of 7,581 participants from a cohort study of U.K. military personnel (data collected between 2007 and 2009), the prevalence of relationship difficulties and associations with sociodemographic, military-, and deployment-related characteristics was examined. Most participants did not report experiencing relationship difficulties. Adjusted regression analyses indicate that childhood adversity, limited support for and from partners, being in unmarried relationships, financial problems, deploying for more than 13 months in 3 years, and work being above trade, ability, and experience were key factors associated with relationship difficulties. The likelihood of U.K. military personnel experiencing relationship difficulties is increased because of personal vulnerabilities that may be exacerbated in the military context