Considerations for preparing a randomized population health intervention trial: lessons from a South African–Canadian partnership to improve the health of health workers

Background: Community-based cluster-randomized controlled trials (RCTs) are increasingly being conducted to address pressing global health concerns. Preparations for clinical trials are well-described, as are the steps for multi-component health service trials. However, guidance is lacking for addressing the ethical and logistic challenges in (cluster) RCTs of population health interventions in low- and middle-income countries. Objective: We aimed to identify the factors that population health researchers must explicitly consider when planning RCTs within North–South partnerships. Design: We reviewed our experiences and identified key ethical and logistic issues encountered during the pre-trial phase of a recently implemented RCT. This trial aimed to improve tuberculosis (TB) and Human Immunodeficiency Virus (HIV) prevention and care for health workers by enhancing workplace assessment capability, addressing concerns about confidentiality and stigma, and providing onsite counseling, testing, and treatment. An iterative framework was used to synthesize this analysis with lessons taken from other studies. Results: The checklist of critical factors was grouped into eight categories: 1) Building trust and shared ownership; 2) Conducting feasibility studies throughout the process; 3) Building capacity; 4) Creating an appropriate information system; 5) Conducting pilot studies; 6) Securing stakeholder support, with a view to scale-up; 7) Continuously refining methodological rigor; and 8) Explicitly addressing all ethical issues both at the start and continuously as they arise. Conclusion: Researchers should allow for the significant investment of time and resources required for successful implementation of population health RCTs within North–South collaborations, recognize the iterative nature of the process, and be prepared to revise protocols as challenges emerge

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

Frontal Bone Remodeling for Gender Reassignment of the Male Forehead: A Gender-Reassignment Surgery

Gender-reassignment therapy, especially for reshaping of the forehead, can be an effective treatment to improve self-esteem. Contouring of the cranial vault, especially of the forehead, still is a rarely performed surgical procedure for gender reassignment. In addition to surgical bone remodeling, several materials have been used for remodeling and refinement of the frontal bone. But due to shortcomings of autogenous bone material and the disadvantages of polyethylene or methylmethacrylate, hydroxyapatite cement (HAC) composed of tetracalcium phosphate and dicalcium phosphate seems to be an alternative. This study aimed to analyze the clinical outcome after frontal bone remodeling with HAC for gender male-to-female reassignment. The 21 patients in the study were treated for gender reassignment of the male frontal bone using HAC. The average age of these patients was 33.4 years (range, 21–42 years). The average volume of HAC used per patient was 3.83 g. The authors’ clinical series demonstrated a satisfactory result. The surgery was easy to perform, and HAC was easy to apply and shape to suit individual needs. Overall satisfaction was very high. Therefore, HAC is a welcome alternative to the traditional use of autogenous bone graft for correction of cranial vault irregularities

Sphingosine-1-phosphate attenuates proteoglycan aggrecan expression via production of prostaglandin E(2 )from human articular chondrocytes

BACKGROUND: Sphingosine-1-phosphate (S1P), a downstream metabolite of ceramide, induces various bioactivities via two distinct pathways: as an intracellular second messenger or through receptor activation. The receptor for S1P (S1PR) is the family of Endothelial differentiation, sphingolipid G-protein-coupled receptor (EDG). We have here attempted to reveal the expression of EDG/S1PR in human articular chondrocytes (HAC), exploring the implications of S1P in cartilage degradation. METHODS: Articular cartilage specimens were obtained from patients with rheumatoid arthritis (RA), osteoarthritis (OA) or traumatic fracture (representing normal chondrocytes) who underwent joint surgery. Isolated HAC were cultured in vitro by monolayer and stimulated with S1P in the presence or absence of inhibitors of signaling molecules. Stimulated cells and culture supernatants were collected and subjected to analyses using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). RESULTS: All of the tested HAC samples showed positive results in terms of EDG/S1PR expression in basal condition. When HAC was stimulated with S1P, a significant increase in prostaglandin (PG) E(2 )production was observed together with enhanced expression of cyclooxygenase (COX)-2. S1P stimulated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) in HAC, and the PGE(2 )induction was abrogated by PD98059 and SB203580. Pertussis toxin inhibited the PGE(2 )induction from HAC by S1P, suggesting an essential role for Gi protein. S1P also attenuated the expression of proteoglycan aggrecan, a component of cartilage matrix, in HAC at transcriptional level. CONCLUSION: It was suggested that the S1P-induced PGE(2 )was at least in part involved in the aggrecan-suppressing effect of S1P, seeing as COX inhibitors attenuated the effect. Accordingly, S1P might play an important role in cartilage degradation in arthritides

Characteristics and risk factors for typhoid fever after the tsunami, earthquake and under normal conditions in Indonesia

<p>Abstract</p> <p>Background</p> <p>Although typhoid transmitted by food and water is a common problem in daily life, its characteristics and risk factors may differ in disaster-affected areas, which reinforces the need for rapid public health intervention. Surveys were carried out post-tsunami in Banda Aceh, post-earthquake in Yogyakarta, and under normal conditions in Bandung, Indonesia. Logistic regression analysis was used to assess the risk factors with the dependent variable of typhoid fever, with or without complications.</p> <p>Findings</p> <p>Characteristic typhoid fever with complications was found in 5 patients (11.9%) affected by the tsunami in Aceh, 8 (20.5%) after the earthquake in Yogyakarta, and 13 (18.6%) in Bandung. After the tsunami in Aceh, clean water (OR = 0.05; 95%CI: 0.01-0.47) and drug availability (OR = 0.23; 95%CI: 0.02-2.43) are significant independent risk factors, while for the earthquake in Yogyakarta, contact with other typhoid patients (OR = 20.30; 95%CI: 1.93-213.02) and education (OR = 0.08; 95%CI: 0.01-0.98) were significant risk factors. Under normal conditions in Bandung, hand washing (OR = 0.07; 95%CI: 0.01-0.50) and education (OR = 0.08; 95%CI: 0.01-0.64) emerged as significant risk factors.</p> <p>Conclusion</p> <p>The change in risk factors for typhoid complication after the tsunami in Aceh and the earthquake in Yogyakarta emphasizes the need for rapid public health intervention in natural disasters in Indonesia.</p

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Association of dialysis facility-level hemoglobin measurement and erythropoiesis-stimulating agent dose adjustment frequencies with dialysis facility-level hemoglobin variation: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>A key goal of anemia management in dialysis patients is to maintain patients' hemoglobin (Hb) levels consistently within a target range. Our aim in this study was to assess the association of facility-level practice patterns representing Hb measurement and erythropoiesis-stimulating agent (ESA) dose adjustment frequencies with facility-level Hb variation.</p> <p>Methods</p> <p>This was a retrospective observational database analysis of patients in dialysis facilities affiliated with large dialysis organizations as of July 01, 2006, covering a follow-up period from July 01, 2006 to June 30, 2009. A total of 2,763 facilities representing 436,442 unique patients were included. The predictors evaluated were facility-level Hb measurement and ESA dose adjustment frequencies, and the outcome measured was facility-level Hb variation.</p> <p>Results</p> <p>First to 99th percentile ranges for facility-level Hb measurement and ESA dose adjustment frequencies were approximately once per month to once per week and approximately once per 3 months to once per 3 weeks, respectively. Facility-level Hb measurement and ESA dose adjustment frequencies were inversely associated with Hb variation. Modeling results suggested that a more frequent Hb measurement (once per week rather than once per month) was associated with approximately 7% to 9% and 6% to 8% gains in the proportion of patients with Hb levels within a ±1 and ±2 g/dL range around the mean, respectively. Similarly, more frequent ESA dose adjustment (once per 2 weeks rather than once per 3 months) was associated with approximately 6% to 9% and 5% to 7% gains in the proportion of patients in these respective Hb ranges.</p> <p>Conclusions</p> <p>Frequent Hb measurements and timely ESA dose adjustments in dialysis patients are associated with lower facility-level Hb variation and an increase in proportion of patients within ±1 and ±2 g/dL ranges around the facility-level Hb mean.</p

Communicating Phylogeny: Evolutionary Tree Diagrams in Museums

Tree of life diagrams are graphic representations of phylogeny—the evolutionary history and relationships of lineages—and as such these graphics have the potential to convey key evolutionary ideas and principles to a variety of audiences. Museums play a significant role in teaching about evolution to the public, and tree graphics form a common element in many exhibits even though little is known about their impact on visitor understanding. How phylogenies are depicted and used in informal science settings impacts their accessibility and effectiveness in communicating about evolution to visitors. In this paper, we summarize the analysis of 185 tree of life graphics collected from museum exhibits at 52 institutions and highlight some potential implications of how trees are presented that may support or hinder visitors’ understanding about evolution. While further work is needed, existing learning research suggests that common elements among the diversity of museum trees such as the inclusion of anagenesis and absence of time and shared characters might represent potential barriers to visitor understanding

Albumin-Like Protein is the Major Protein Constituent of Luminal Fluid in the Human Endolymphatic Sac

The endolymphatic sac (ES) is an inner ear organ that is connected to the cochleo-vestibular system through the endolymphatic duct. The luminal fluid of the ES contains a much higher concentration of proteins than any other compartment of the inner ear. This high protein concentration likely contributes to inner ear fluid volume regulation by creating an osmotic gradient between the ES lumen and the interstitial fluid. We characterized the protein profile of the ES luminal fluid of patients (n = 11) with enlarged vestibular aqueducts (EVA) by proteomics. In addition, we investigated differences in the protein profiles between patients with recent hearing deterioration and patients without hearing deterioration. The mean total protein concentration of the luminal fluid was 554.7±94.6 mg/dl. A total of 58 out of 517 spots detected by 2-DE were analyzed by MALDI-TOF MS. The protein profile of the luminal fluid was different from the profile of plasma. Proteins identified from 29 of the spots were also present in the MARC-filtered human plasma; however, the proteins identified from the other 25 spots were not detected in the MARC-filtered human plasma. The most abundant protein in the luminal fluid was albumin-like proteins, but most of them were not detected in MARC-filtered human plasma. The concentration of albumin-like proteins was higher in samples from patients without recent hearing deterioration than in patients with recent hearing deterioration. Consequently, the protein of ES luminal fluid is likely to be originated from both the plasma and the inner ear and considering that inner ear fluid volumes increase abnormally in patients with EVA following recent hearing deterioration, it is tempting to speculate that albumin-like proteins may be involved in the regulation of inner ear fluid volume through creation of an osmotic gradient during pathological conditions such as endolymphatic hydrops

Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron

We report a measurement of the diffractive structure function $F_{jj}^D$ of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in $\bar pp$ collisions at $\sqrt s=630$ GeV at the Fermilab Tevatron. The ratio of $F_{jj}^D$ at $\sqrt s=630$ GeV to $F_{jj}^D$ obtained from a similar measurement at $\sqrt s=1800$ GeV is compared with expectations from QCD factorization and with theoretical predictions. We also report a measurement of the $\xi$ ($x$-Pomeron) and $\beta$ ($x$ of parton in Pomeron) dependence of $F_{jj}^D$ at $\sqrt s=1800$ GeV. In the region $0.035<\xi<0.095$, $|t|<1$ GeV$^2$ and $\beta<0.5$, $F_{jj}^D(\beta,\xi)$ is found to be of the form $\beta^{-1.0\pm 0.1} \xi^{-0.9\pm 0.1}$, which obeys $\beta$-$\xi$ factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter