"My Children and I Will no Longer Suffer from Malaria": A Qualitative Study of the Acceptance and Rejection of Indoor Residual Spraying to Prevent Malaria in Tanzania.

The objective of this study was to identify attitudes and misconceptions related to acceptance or refusal of indoor residual spraying (IRS) in Tanzania for both the general population and among certain groups (e.g., farmers, fishermen, community leaders, and women). This study was a series of qualitative, semi-structured, in-depth interviews and focus group discussions conducted from October 2010 to March 2011 on Mainland Tanzania and Zanzibar. Three groups of participants were targeted: acceptors of IRS (those who have already had their homes sprayed), refusers (those whose communities have been sprayed, but refused to have their individual home sprayed), and those whose houses were about to be sprayed as part of IRS scale-up. Interviews were also conducted with farmers, fishermen, women, community leaders and members of non-government organizations responsible for community mobilization around IRS. Results showed refusers are a very small percentage of the population. They tend to be more knowledgeable people such as teachers, drivers, extension workers, and other civil servants who do not simply follow the orders of the local government or the sprayers, but are skeptical about the process until they see true results. Refusal took three forms: 1) refusing partially until thorough explanation is provided; 2) accepting spray to be done in a few rooms only; and 3) refusing outright. In most of the refusal interviews, refusers justified why their houses were not sprayed, often without admitting that they had refused. Reasons for refusal included initial ignorance about the reasons for IRS, uncertainty about its effectiveness, increased prevalence of other insects, potential physical side effects, odour, rumours about the chemical affecting fertility, embarrassment about moving poor quality possessions out of the house, and belief that the spray was politically motivated. To increase IRS acceptance, participants recommended more emphasis on providing thorough public education, ensuring the sprayers themselves are more knowledgeable about IRS, and asking that community leaders encourage participation by their constituents rather than threatening punishment for noncompliance. While there are several rumours and misconceptions concerning IRS in Tanzania, acceptance is very high and continues to increase as positive results become apparent

Identification of complex health interventions suitable for evaluation: development and validation of the 8-step scoping framework

Background: There is extensive literature on the methodology of evaluation research and the development and evaluation of complex interventions but little guidance on the formative stages before evaluation and how to work with partner organizations that wish to have their provision evaluated. It is important to be able to identify suitable projects for evaluation from a range of provision and describe the steps required, often with academic institutions working in partnership with external organizations, in order to set up an evaluation. However, research evaluating programs or interventions rarely discusses these stages. Objective: This study aimed to extend work on evaluability assessment and pre-evaluation planning by proposing an 8-Step Scoping Framework to enable the appraisal of multiple programs in order to identify interventions suitable for evaluation. We aimed to add to the literature on evaluability assessment and more recent evaluation guidance by describing the processes involved in working with partner organizations. Methods: This paper documents the steps required to identify multiple complex interventions suitable for process and outcome evaluation. The steps were developed using an iterative approach by working alongside staff in a local government organization, to build an evidence base to demonstrate which interventions improve children’s outcomes. The process of identifying suitable programs for evaluation, thereby establishing the pre-evaluation steps, was tested using all Flying Start provision. Results: The 8-Step Scoping Framework was described using the example of the local government organization Flying Start to illustrate how each step contributes to finding projects suitable for process and outcome evaluation: (1) formulating overarching key questions that encompass all programs offered by an organization, (2) gaining an in-depth understanding of the work and provision of an organization and engaging staff, (3) completing a data template per project/program offered, (4) assessing the robustness/validity of data across all programs, (5) deciding on projects suitable for evaluation and those requiring additional data, (6) negotiating with chosen project leads, both within and outside the organization, (7) developing individual project evaluation protocols, and (8) applying for ethical approval from the university and partner organization. Conclusions: This paper describes the processes involved in identifying suitable projects for evaluation. It adds to the existing literature on the assessment of specific programs suitable for evaluation and guidance for conducting evaluations by establishing the formative steps required to identify suitable programs from a range of provision. This scoping framework particularly relates to academic partners and organizations tasked with delivering evidence-based services designed to meet local needs. The steps identified have been described in the context of early years provision but can be applied to a range of community-based evaluations, or more generally, to cases where an academic partner is working with external stakeholders to identify projects suitable for academic evaluation

A qualitative study of enablers and barriers influencing the incorporation of social accountability values into organisational culture: a perspective from two medical schools

Background: Definitions of social accountability describe the obligation of medical schools to direct education, research and service activities towards addressing the priority health concerns of the population they serve. While such statements give some direction as to how the goal might be reached, it does not identify what factors might facilitate or hinder its achievement. This study set out to identify and explore enablers and barriers influencing the incorporation of social accountability values into medical schools. Methods: Semi structured interviews of fourteen senior staff in Bar Ilan and Leeds medical schools were undertaken following a literature review. Participants were recruited by purposive sampling in order to identify factors perceived to play a part in the workings of each institution. Results: Academic prestige was seen as a key barrier that was dependent on research priorities and student selection. The role of champions was considered to be vital to tackle staff perceptions and facilitate progress. Including practical community experience for students was felt to be a relevant way in which the curriculum could be designed through engagement with local partners. Conclusions: Successful adoption of social accountability values requires addressing concerns around potential negative impacts on academic prestige and standards. Identifying and supporting credible social accountability champions to disseminate the values throughout research and education departments in medical and other faculties is also necessary, including mapping onto existing work streams and research agendas. Demonstrating the contribution the institution can make to local health improvement and regional development by a consideration of its economic footprint may also be valuable

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Acute Chloroform Ingestion Successfully Treated with Intravenously Administered N-acetylcysteine

Chloroform, a halogenated hydrocarbon, causes central nervous system depression, cardiac arrhythmias, and hepatotoxicity. We describe a case of chloroform ingestion with a confirmatory serum level and resultant hepatotoxicity successfully treated with intravenously administered N-acetylcysteine (NAC). A 19-year-old man attempting suicide ingested approximately 75 mL of chloroform. He was unresponsive and intubated upon arrival. Intravenously administered NAC was started after initial stabilization was complete. His vital signs were normal. Admission laboratory values revealed normal serum electrolytes, AST, ALT, PT, BUN, creatinine, and bilirubin. Serum ethanol level was 15 mg/dL, and aspirin and acetaminophen were undetectable. The patient was extubated but developed liver function abnormalities with a peak AST of 224 IU/L, ALT of 583 IU/L, and bilirubin level reaching 16.3 mg/dL. NAC was continued through hospital day 6. Serum chloroform level obtained on admission was 91 μg/mL. The patient was discharged to psychiatry without known sequelae and normal liver function tests. The average serum chloroform level in fatal cases of inhalational chloroform poisoning was 64 μg/mL, significantly lower than our patient. The toxicity is believed to be similar in both inhalation and ingestion routes of exposure, with mortality predominantly resulting from anoxia secondary to central nervous system depression. Hepatocellular toxicity is thought to result from free radical-induced oxidative damage. Previous reports describe survival after treatment with orally administered NAC, we report the first use of intravenously administered NAC for chloroform ingestion. Acute oral ingestion of chloroform is extremely rare. Our case illustrates that with appropriate supportive care, patients can recover from chloroform ingestion, and intravenously administered NAC may be of benefit in such cases

Ready or not? Expectations of faculty and medical students for clinical skills preparation for clerkships

Background: Preclerkship clinical-skills training has received increasing attention as a foundational preparation for clerkships. Expectations among medical students and faculty regarding the clinical skills and level of skill mastery needed for starting clerkships are unknown. Medical students, faculty teaching in the preclinical setting, and clinical clerkship faculty may have differing expectations of students entering clerkships. If students' expectations differ from faculty expectations, students may experience anxiety. Alternately, congruent expectations among students and faculty may facilitate integrated and seamless student transitions to clerkships. Aims: To assess the congruence of expectations among preclerkship faculty, clerkship faculty, and medical students for the clinical skills and appropriate level of clinical-skills preparation needed to begin clerkships. Methods: Investigators surveyed preclinical faculty, clerkship faculty, and medical students early in their basic clerkships at a North American medical school that focuses on preclerkship clinical-skills development. Survey questions assessed expectations for the appropriate level of preparation in basic and advanced clinical skills for students entering clerkships. Results: Preclinical faculty and students had higher expectations than clerkship faculty for degree of preparation in most basic skills. Students had higher expectations than both faculty groups for advanced skills preparation. Conclusions: Preclinical faculty, clerkship faculty, and medical students appear to have different expectations of clinical-skills training needed for clerkships. As American medical schools increasingly introduce clinical-skills training prior to clerkships, more attention to alignment, communication, and integration between preclinical and clerkship faculty will be important to establish common curricular agendas and increase integration of student learning. Clarification of skills expectations may also alleviate student anxiety about clerkships and enhance their learning

Biological Function and Molecular Mapping of M Antigen in Yeast Phase of Histoplasma capsulatum

Histoplasmosis, due to the intracellular fungus Histoplasma capsulatum, can be diagnosed by demonstrating the presence of antibodies specific to the immunodominant M antigen. However, the role of this protein in the pathogenesis of histoplasmosis has not been elucidated. We sought to structurally and immunologically characterize the protein, determine yeast cell surface expression, and confirm catalase activity. A 3D-rendering of the M antigen by homology modeling revealed that the structures and domains closely resemble characterized fungal catalases. We generated monoclonal antibodies (mAbs) to the protein and determined that the M antigen is present on the yeast cell surface and in cell wall/cell membrane preparations. Similarly, we found that the majority of catalase activity was in extracts containing fungal surface antigens and that the M antigen is not significantly secreted by live yeast cells. The mAbs also identified unique epitopes on the M antigen. The localization of the M antigen to the cell surface of H. capsulatum yeast and the characterization of the protein's major epitopes have important implications since it demonstrates that although the protein may participate in protecting the fungus against oxidative stress it is also accessible to host immune cells and antibody

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

<p>Abstract</p> <p>Purpose</p> <p>An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.</p> <p>Patients and methods</p> <p>Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM) (PANVAC-V) and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F). Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis.</p> <p>Results</p> <p>The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%). Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; <it>P </it>= .002).</p> <p>Conclusion</p> <p>Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.</p