Improving local health through community health workers in Cambodia: challenges and solutions

Volunteer community health workers (CHWs) are an important link between the public health system and the community. The ‘Community Participation Policy for Health’ in Cambodia identifies CHWs as key to local health promotion and as a critical link between district health centres and the community. However, research on the challenges CHWs face and identifying what is required to optimise their performance is limited in the Cambodian context. This research explores the views of CHWs in rural Cambodia, on the challenges they face when implementing health initiatives

Test accuracy of human papillomavirus in urine for detection of cervical intraepithelial neoplasia

The objective was to assess the diagnostic test accuracy of high-risk human papillomavirus (hrHPV) testing of self-collected urine and cervicovaginal samples for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We recruited a convenience sample of women 25 to 65 years of age who were undergoing clinically indicated colposcopy at two medical centers in North Carolina between November 2016 and January 2019. Women with normal cytology results and positive hrHPV results were also recruited. Urine samples, self-collected cervicovaginal samples, provider-collected cervical samples, and cervical biopsy samples were obtained from all enrolled women. Samples were tested for hrHPV DNA using the Onclarity assay (Becton Dickinson, Sparks, MD). Biopsy samples were histologically graded as CIN2+ or <CIN2. We calculated the sensitivity and specificity for detection of CIN2+ and assessed agreement between sample collection methods. We included 307 women (median age, 36 years) with valid histology results and triplematched urine, self-collected cervicovaginal, and provider-collected cervical hrHPV results; 83 women (27%) had CIN2+. Urine-based hrHPV testing correctly identified 80% of CIN2+ cases (95% confidence interval [CI], 71 to 88%) using the PCR cycle threshold (CT) established for provider-collected cervical samples, but sensitivity remained below the estimates for self-collected cervicovaginal and provider-collected cervical samples (both 94% [95% CI, 89 to 99%]). Using a higher CT cutoff value of ≤40, 90% sensitivity was achieved for urine-based hrHPV testing. Agreement between results for urine samples and self-collected cervicovaginal samples (kappa = 0.58) or provider-collected cervical samples (kappa = 0.54) was moderate. Urinebased hrHPV testing may be a promising approach to improve cervical cancer screening coverage, especially among women with limited access to health care

The Path to Sustainable Nuclear Energy. Basic and Applied Research Opportunities for Advanced Fuel Cycles

The objective of this report is to identify new basic science that will be the foundation for advances in nuclear fuel-cycle technology in the near term, and for changing the nature of fuel cycles and of the nuclear energy industry in the long term. The goals are to enhance the development of nuclear energy, to maximize energy production in nuclear reactor parks, and to minimize radioactive wastes, other environmental impacts, and proliferation risks. The limitations of the once-through fuel cycle can be overcome by adopting a closed fuel cycle, in which the irradiated fuel is reprocessed and its components are separated into streams that are recycled into a reactor or disposed of in appropriate waste forms. The recycled fuel is irradiated in a reactor, where certain constituents are partially transmuted into heavier isotopes via neutron capture or into lighter isotopes via fission. Fast reactors are required to complete the transmutation of long-lived isotopes. Closed fuel cycles are encompassed by the Department of Energy?s Advanced Fuel Cycle Initiative (AFCI), to which basic scientific research can contribute. Two nuclear reactor system architectures can meet the AFCI objectives: a ?single-tier? system or a ?dual-tier? system. Both begin with light water reactors and incorporate fast reactors. The ?dual-tier? systems transmute some plutonium and neptunium in light water reactors and all remaining transuranic elements (TRUs) in a closed-cycle fast reactor. Basic science initiatives are needed in two broad areas: ? Near-term impacts that can enhance the development of either ?single-tier? or ?dual-tier? AFCI systems, primarily within the next 20 years, through basic research. Examples: Dissolution of spent fuel, separations of elements for TRU recycling and transmutation Design, synthesis, and testing of inert matrix nuclear fuels and non-oxide fuels Invention and development of accurate on-line monitoring systems for chemical and nuclear species in the nuclear fuel cycle Development of advanced tools for designing reactors with reduced margins and lower costs ? Long-term nuclear reactor development requires basic science breakthroughs: Understanding of materials behavior under extreme environmental conditions Creation of new, efficient, environmentally benign chemical separations methods Modeling and simulation to improve nuclear reaction cross-section data, design new materials and separation system, and propagate uncertainties within the fuel cycle Improvement of proliferation resistance by strengthening safeguards technologies and decreasing the attractiveness of nuclear materials A series of translational tools is proposed to advance the AFCI objectives and to bring the basic science concepts and processes promptly into the technological sphere. These tools have the potential to revolutionize the approach to nuclear engineering R&D by replacing lengthy experimental campaigns with a rigorous approach based on modeling, key fundamental experiments, and advanced simulations

Modulation of calcification of vascular smooth muscle cells in culture by calcium antagonists, statins, and their combination

Background Vascular calcification is an organized process in which vascular smooth muscle cells (VSMCs) are implicated primarily. The purpose of the present study was to assess the effects of calcium antagonists and statins on VSMC calcification in vitro. Methods VSMC calcification was stimulated by incubation in growth medium supplemented with 10 mmol/l β-glycerophosphate, 8 mmol/l CaCl2, 10 mmol/l sodium pyruvate, 1 μmol/l insulin, 50 μg/ml ascorbic acid, and 100 nmol/l dexamethasone (calcification medium). Calcification, proliferation, and apoptosis of VSMCs were quantified. Results Calcium deposition was stimulated dose-dependently by β-glycerophosphate, CaCl2, and ascorbic acid (all P < 0.01). Addition of amlodipine (0.01–1 μmol/l) to the calcification medium did not affect VSMC calcification. However, atorvastatin (2–50 μmol/l) stimulated calcium deposition dose-dependently. Combining treatments stimulated calcification to a degree similar to that observed with atorvastatin alone. Both atorvastatin and amlodipine inhibited VSMC proliferation at the highest concentration used. Only atorvastatin (50 μmol/l) induced considerable apoptosis of VSMCs. Conclusion In vitro calcification of VSMCs is not affected by amlodipine, but is stimulated by atorvastatin at concentrations ≥10 μmol/l, which could contribute to the plaque-stabilizing effect reported for statins

A median fin derived from the lateral plate mesoderm and the origin of paired fins

The development of paired appendages was a key innovation during evolution and facilitated the aquatic to terrestrial transition of vertebrates. Largely derived from the lateral plate mesoderm (LPM), one hypothesis for the evolution of paired fins invokes derivation from unpaired median fins via a pair of lateral fin folds located between pectoral and pelvic fin territories1. Whilst unpaired and paired fins exhibit similar structural and molecular characteristics, no definitive evidence exists for paired lateral fin folds in larvae or adults of any extant or extinct species. As unpaired fin core components are regarded as exclusively derived from paraxial mesoderm, any transition presumes both co-option of a fin developmental programme to the LPM and bilateral duplication2. Here, we identify that the larval zebrafish unpaired pre-anal fin fold (PAFF) is derived from the LPM and thus may represent a developmental intermediate between median and paired fins. We trace the contribution of LPM to the PAFF in both cyclostomes and gnathostomes, supporting the notion that this is an ancient trait of vertebrates. Finally, we observe that the PAFF can be bifurcated by increasing bone morphogenetic protein signalling, generating LPM-derived paired fin folds. Our work provides evidence that lateral fin folds may have existed as embryonic anlage for elaboration to paired fins

Triglyceride Blisters in Lipid Bilayers: Implications for Lipid Droplet Biogenesis and the Mobile Lipid Signal in Cancer Cell Membranes

Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO) than earlier anticipated, by sequestering triolein molecules to the bilayer center in the form of a disordered, isotropic, mobile neutral lipid aggregate, at least 17 nm in diameter, which forms spontaneously, and remains stable on at least the microsecond time scale. The results give credence to the hotly debated existence of mobile neutral lipid aggregates of unknown function present in malignant cells, and to the early biogenesis of lipid droplets accommodated between the two leaflets of the endoplasmic reticulum membrane. The TO aggregates give the bilayer a blister-like appearance, and will hinder the formation of multi-lamellar phases in model, and possibly living membranes. The blisters will result in anomalous membrane probe partitioning, which should be accounted for in the interpretation of probe-related measurements

The global pendulum swing towards community health workers in low- and middle-income countries: A scoping review of trends, geographical distribution and programmatic orientations, 2005 to 2014

BACKGROUND: There has been a substantial increase in publications and interest in community health workers (CHWs) in low- and middle-income countries (LMIC) over the last years. This paper examines the growth, geographical distribution and programmatic orientations of the indexed literature on CHWs in LMIC over a 10-year period. METHODS: A scoping review of publications on CHWs from 2005 to 2014 was conducted. Using an inclusive list of terms, we searched seven databases (including MEDLINE, CINAHL, Cochrane) for all English-language publications on CHWs in LMIC. Two authors independently screened titles/abstracts, downloading full-text publications meeting inclusion criteria. These were coded in an Excel spreadsheet by year, type of publication (e.g. review, empirical), country, region, programmatic orientation (e.g. maternal-child health, HIV/AIDS, comprehensive) and CHW roles (e.g. prevention, treatment) and further analysed in Stata14. Drawing principally on the subset of review articles, specific roles within programme areas were identified and grouped. FINDINGS: Six hundred seventy-eight publications from 46 countries on CHWs were inventoried over the 10-year period. There was a sevenfold increase in annual number of publications from 23 in 2005 to 156 in 2014. Half the publications were reporting on initiatives in Africa, a third from Asia and 11 % from the Americas (mostly Brazil). The largest single focus and driver of the growth in publications was on CHW roles in meeting the Millennium Development Goals of maternal, child and neonatal survival (35 % of total), followed by HIV/AIDS (16 %), reproductive health (6 %), non-communicable diseases (4 %) and mental health (4 %). Only 17 % of the publications approached CHW roles in an integrated fashion. There were also distinct regional (and sometimes country) profiles, reflecting different histories and programme traditions. CONCLUSIONS: The growth in literature on CHWs provides empirical evidence of ever-increasing expectations for addressing health burdens through community-based action. This literature has a strong disease- or programme-specific orientation, raising important questions for the design and sustainable delivery of integrated national programmes.Scopu

Leadership and governance of community health worker programmes at scale: a cross case analysis of provincial implementation in South Africa

BACKGROUND: National community health worker (CHW) programmes are returning to favour as an integral part of primary health care systems, often on the back of pre-existing community based initiatives. There are significant challenges to the integration and support of such programmes, and they require coordination and stewardship at all levels of the health system. This paper explores the leadership and governance tasks of large-scale CHW programmes at sub-national level, through the case of national reforms to South Africa’s community based sector, referred to as the Ward Based Outreach Team (WBOT) strategy. METHODS: A cross case analysis of leadership and governance roles, drawing on three case studies of adoption and implementation of the WBOTs strategy at provincial level (Western Cape, North West and Gauteng) was conducted. The primary case studies mapped system components and assessed implementation processes and contexts. They involved teams of researchers and over 200 interviews with stakeholders from senior to frontline, document reviews and analyses of routine data. The secondary, cross case analysis specifically focused on the issues and challenges facing, and strategies adopted by provincial and district policy makers and managers, as they engaged with the new national mandate. From this key sub-national leadership and governance roles were formulated. RESULTS: Four key roles are identified and discussed: 1. Negotiating a fit between national mandates and provincial and district histories and strategies of community based services 2. Defining new organisational and accountability relationships between CHWs, local health services, communities and NGOs 3. Revising and developing new aligned and integrated planning, human resource, financing and information systems 4. Leading change by building new collective visions, mobilising political, including budgetary, support and designing implementation strategies. CONCLUSION: This analysis, from real-life systems, adds to understanding of the processes involved in developing CHW programmes at scale, and specifically the negotiated and multilevel nature of leadership and governance in such programmes, spanning analytic, managerial, technical and political roles.IS