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

A Hausdorff-measure boundary element method for acoustic scattering by fractal screens

Sound-soft fractal screens can scatter acoustic waves even when they have zero surface measure. To solve such scattering problems we make what appears to be the first application of the boundary element method (BEM) where each BEM basis function is supported in a fractal set, and the integration involved in the formation of the BEM matrix is with respect to a non-integer order Hausdorff measure rather than the usual (Lebesgue) surface measure. Using recent results on function spaces on fractals, we prove convergence of the Galerkin formulation of this “Hausdorff BEM” for acoustic scattering in Rn+1 (n=1,2) when the scatterer, assumed to be a compact subset of Rn×{0}, is a d-set for some d∈(n-1,n], so that, in particular, the scatterer has Hausdorff dimension d. For a class of fractals that are attractors of iterated function systems, we prove convergence rates for the Hausdorff BEM and superconvergence for smooth antilinear functionals, under certain natural regularity assumptions on the solution of the underlying boundary integral equation. We also propose numerical quadrature routines for the implementation of our Hausdorff BEM, along with a fully discrete convergence analysis, via numerical (Hausdorff measure) integration estimates and inverse estimates on fractals, estimating the discrete condition numbers. Finally, we show numerical experiments that support the sharpness of our theoretical results, and our solution regularity assumptions, including results for scattering in R2 by Cantor sets, and in R3 by Cantor dusts

Uncertainties in steric sea level change estimation during the satellite altimeter era: concepts and practices

This article presents a review of current practice in estimating steric sea level change, focussed on the treatment of uncertainty. Steric sea level change is the contribution to the change in sea level arising from the dependence of density on temperature and salinity. It is a significant component of sea level rise and a reflection of changing ocean heat content. However tracking these steric changes remains still a significant challenge for the scientific community. We review the importance of understanding the uncertainty in estimates of steric sea level change. Relevant concepts of uncertainty are discussed and illustrated with the example of observational uncertainty propagation from a single profile of temperature and salinity measurements to steric height. We summarise and discuss the recent literature on methodologies and techniques used to estimate steric sea level in the context of the treatment of uncertainty. Our conclusions are that progress in quantifying steric sea level uncertainty will benefit from: greater clarity and transparency in published discussions of uncertainty, including exploitation of international standards for quantifying and expressing uncertainty in measurement; and the development of community ‘recipes’ for quantifying the error covariances in observations and from sparse sampling, and for estimating and propagating uncertainty across spatio-temporal scales

Towards a conceptual framework demonstrating the effectiveness of audiovisual patient descriptions (patient video cases): a review of the current literature

Background: Technological advances have enabled the widespread use of video cases via web-streaming and online download as an educational medium. The use of real subjects to demonstrate acute pathology should aid the education of health care professionals. However, the methodology by which this effect may be tested is not clear. Methods: We undertook a literature review of major databases, found relevant articles relevant to using patient video cases as educational interventions, extracted the methodologies used and assessed these methods for internal and construct validity. Results: A review of 2532 abstracts revealed 23 studies meeting the inclusion criteria and a final review of 18 of relevance. Medical students were the most commonly studied group (10 articles) with a spread of learner satisfaction, knowledge and behaviour tested. Only two of the studies fulfilled defined criteria on achieving internal and construct validity. The heterogeneity of articles meant it was not possible to perform any meta-analysis. Conclusions: Previous studies have not well classified which facet of training or educational outcome the study is aiming to explore and had poor internal and construct validity. Future research should aim to validate a particular outcome measure, preferably by reproducing previous work rather than adopting new methods. In particular cognitive processing enhancement, demonstrated in a number of the medical student studies, should be tested at a postgraduate level

Engineering of a polydisperse small heat-shock protein reveals conserved motifs of oligomer plasticity

Small heat-shock proteins (sHSPs) are molecular chaperones that bind partially and globally unfolded states of their client proteins. Previously, we discovered that the archaeal Hsp16.5, which forms ordered and symmetric 24-subunit oligomers, can be engineered to transition to an ordered and symmetric 48-subunit oligomer by insertion of a peptide from human HspB1 (Hsp27). Here, we uncovered the existence of an array of oligomeric states (30–38 subunits) that can be populated as a consequence of altering the sequence and length of the inserted peptide. Polydisperse Hsp16.5 oligomers displayed higher affinity to a model client protein consistent with a general mechanism for recognition and binding that involves increased access of the hydrophobic N-terminal region. Our findings, which integrate structural and functional analyses from evolutionarily distant sHSPs, support a model wherein the modular architecture of these proteins encodes motifs of oligomer polydispersity, dissociation, and expansion to achieve functional diversity and regulation. Through manipulation of the sequence of an inserted peptide, Mishra et al. generated variants of the monodisperse archaeal Hsp16.5 that assemble into oligomers of different sizes and structures. Measurements of the affinity of these variants toward a client protein reinforces the relationship between oligomer size, polydispersity and chaperone efficiency

Transcriptional Interference Regulates the Evolutionary Development of Speech

The human capacity to speak is fundamental to our advanced intellectual, technological and social development. Yet so very little is known regarding the evolutionary genetics of speech or its relationship with the broader aspects of evolutionary development in primates. In this study, we describe a large family with evolutionary retrograde development of the larynx and wrist. The family presented with severe speech impairment and incremental retrograde elongations of the pisiform in the wrist that limited wrist rotation from 180◦ to 90◦ as in primitive primates. To our surprise, we found that a previously unknown primate-specific gene TOSPEAK had been disrupted in the family. TOSPEAK emerged de novo in an ancestor of extant primates across a 540 kb region of the genome with a pre-existing highly conserved long-range laryngeal enhancer for a neighbouring bone morphogenetic protein gene GDF6. We used transgenic mouse modelling to identify two additional GDF6 long-range enhancers within TOSPEAK that regulate GDF6 expression in the wrist. Disruption of TOSPEAK in the affected family blocked the transcription of TOSPEAK across the 3 GDF6 enhancers in association with a reduction in GDF6 expression and retrograde development of the larynx and wrist. Furthermore, we describe how TOSPEAK developed a human-specific promoter through the expansion of a penta-nucleotide direct repeat that first emerged de novo in the promoter of TOSPEAK in gibbon. This repeat subsequently expanded incrementally in higher hominids to form an overlapping series of Sp1/KLF transcription factor consensus binding sites in human that correlated with incremental increases in the promoter strength of TOSPEAK with human having the strongest promoter. Our research indicates a dual evolutionary role for the incremental increases in TOSPEAK transcriptional interference of GDF6 enhancers in the incremental evolutionary development of the wrist and larynx in hominids and the human capacity to speak and their retrogression with the reduction of TOSPEAK transcription in the affected family

A high frequency boundary element method for scattering by a class of nonconvex obstacles

This is a post-peer-review, pre-copyedit version of an article published in Numerische Mathematik. The final authenticated version is available online at: https://doi.org/10.1007/s00211-014-0648-7EPSR

Multiplexed identification, quantification and genotyping of infectious agents using a semiconductor biochip

The emergence of pathogens resistant to existing antimicrobial drugs is a growing worldwide health crisis that threatens a return to the pre-antibiotic era. To decrease the overuse of antibiotics, molecular diagnostics systems are needed that can rapidly identify pathogens in a clinical sample and determine the presence of mutations that confer drug resistance at the point of care. We developed a fully integrated, miniaturized semiconductor biochip and closed-tube detection chemistry that performs multiplex nucleic acid amplification and sequence analysis. The approach had a high dynamic range of quantification of microbial load and was able to perform comprehensive mutation analysis on up to 1,000 sequences or strands simultaneously in <2 h. We detected and quantified multiple DNA and RNA respiratory viruses in clinical samples with complete concordance to a commercially available test. We also identified 54 drug-resistance-associated mutations that were present in six genes of Mycobacterium tuberculosis, all of which were confirmed by next-generation sequencing

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Over the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is likely to become an option for routine care of a subset of severe inherited genetic/metabolic liver diseases in the relatively near term. In this review, we aim to summarise the milestones in the development of gene therapy, present the different vector tools and their clinical applications for liver-directed gene therapy. AAV-derived vectors are emerging as the leading candidates for clinical translation of gene delivery to the liver. Therefore, we focus on clinical applications of AAV vectors in providing the most recent update on clinical outcomes of completed and ongoing gene therapy trials and comment on the current challenges that the field is facing for large-scale clinical translation. There is clearly an urgent need for more efficient therapies in many severe monogenic liver disorders, which will require careful risk-benefit analysis for each indication, especially in paediatrics

Language in international business: a review and agenda for future research

A fast growing number of studies demonstrates that language diversity influences almost all management decisions in modern multinational corporations. Whereas no doubt remains about the practical importance of language, the empirical investigation and theoretical conceptualization of its complex and multifaceted effects still presents a substantial challenge. To summarize and evaluate the current state of the literature in a coherent picture informing future research, we systematically review 264 articles on language in international business. We scrutinize the geographic distributions of data, evaluate the field’s achievements to date in terms of theories and methodologies, and summarize core findings by individual, group, firm, and country levels of analysis. For each of these dimensions, we then put forward a future research agenda. We encourage scholars to transcend disciplinary boundaries and to draw on, integrate, and test a variety of theories from disciplines such as psychology, linguistics, and neuroscience to gain a more profound understanding of language in international business. We advocate more multi-level studies and cross-national research collaborations and suggest greater attention to potential new data sources and means of analysis