Measuring implementation strength: lessons from the evaluation of public health strategies in low- and middle-income settings.

Evaluation of strategies to ensure evidence-based, low-cost interventions reach those in need is critical. One approach is to measure the strength, or intensity, with which packages of interventions are delivered, in order to explore the association between implementation strength and public health gains. A recent systematic review suggested methodological guidance was needed. We described the approaches used in three examples of measures of implementation strength in evaluation. These addressed important public health topics with a substantial disease burden in low-and middle-income countries; they involved large-scale implementation; and featured evaluation designs without comparison areas. Strengths and weaknesses of the approaches were discussed. In the evaluation of Ethiopia's Health Extension Programme, implementation strength scoring for each kebele (ward) was based on aggregated data from interviews with mothers of children aged 12-23 months, reflecting their reports of contact with four elements of the programme. An evaluation of the Avahan HIV prevention programme in India used the cumulative amount of Avahan funding per HIV-infected person spent each year in each district. In these cases, a single measure was developed and the association with hypothesised programme outcomes presented. In the evaluation of the Affordable Medicines Facility-malaria, several implementation strength measures were developed based on the duration of activity of the programme and the level of implementation of supporting interventions. Measuring the strength of programme implementation and assessing its association with outcomes is a promising approach to strengthen pragmatic impact evaluation. Five key aspects of developing an implementation strength measure are to: (a) develop a logic model; (b) identify aspects of implementation to be assessed; (c) design and implement data collection from a range of data sources; (d) decide whether and how to combine data into a single measure; and, (e) plan whether and how to use the measure(s) in outcome analysis

Heat transport in insulators from ab initio Green-Kubo theory

The Green-Kubo theory of thermal transport has long be considered incompatible with modern simulation methods based on electronic-structure theory, because it is based on such concepts as energy density and current, which are ill-defined at the quantum-mechanical level. Besides, experience with classical simulations indicates that the estimate of heat-transport coefficients requires analysing molecular trajectories that are more than one order of magnitude longer than deemed feasible using ab initio molecular dynamics. In this paper we report on recent theoretical advances that are allowing one to overcome these two obstacles. First, a general gauge invariance principle has been established, stating that thermal conductivity is insensitive to many details of the microscopic expression for the energy density and current from which it is derived, thus permitting to establish a rigorous expression for the energy flux from Density-Functional Theory, from which the conductivity can be computed in practice. Second, a novel data analysis method based on the statistical theory of time series has been proposed, which allows one to considerably reduce the simulation time required to achieve a target accuracy on the computed conductivity. These concepts are illustrated in detail, starting from a pedagogical introduction to the Green-Kubo theory of linear response and transport, and demonstrated with a few applications done with both classical and quantum-mechanical simulation methods.Comment: 36 pages, 14 figure

Role of oxidative stress in oxaliplatin-induced enteric neuropathy and colonic dysmotility in mice

BACKGROUND AND PURPOSE: Oxaliplatin is a platinum‐based chemotherapeutic drug used as a first‐line therapy for colorectal cancer. However, its use is associated with severe gastrointestinal side‐effects resulting in dose limitations and/or cessation of treatment. In this study, we tested whether oxidative stress, caused by chronic oxaliplatin treatment, induces enteric neuronal damage and colonic dysmotility. EXPERIMENTAL APPROACH: Oxaliplatin (3 mg·kg(−1) per day) was administered in vivo to Balb/c mice intraperitoneally three times a week. The distal colon was collected at day 14 of treatment. Immunohistochemistry was performed in wholemount preparations of submucosal and myenteric ganglia. Neuromuscular transmission was studied by intracellular electrophysiology. Circular muscle tone was studied by force transducers. Colon propulsive activity studied in organ bath experiments and faeces were collected to measure water content. KEY RESULTS: Chronic in vivo oxaliplatin treatment resulted in increased formation of reactive oxygen species (O(2)ˉ), nitration of proteins, mitochondrial membrane depolarisation resulting in the release of cytochrome c, loss of neurons, increased inducible NOS expression and apoptosis in both the submucosal and myenteric plexuses of the colon. Oxaliplatin treatment enhanced NO‐mediated inhibitory junction potentials and altered the response of circular muscles to the NO donor, sodium nitroprusside. It also reduced the frequency of colonic migrating motor complexes and decreased circular muscle tone, effects reversed by the NO synthase inhibitor, Nω‐Nitro‐L‐arginine. CONCLUSION AND IMPLICATIONS: Our study is the first to provide evidence that oxidative stress is a key player in enteric neuropathy and colonic dysmotility leading to symptoms of chronic constipation observed in oxaliplatin‐treated mice

Gene Function Classification Using Bayesian Models with Hierarchy-Based Priors

We investigate the application of hierarchical classification schemes to the annotation of gene function based on several characteristics of protein sequences including phylogenic descriptors, sequence based attributes, and predicted secondary structure. We discuss three Bayesian models and compare their performance in terms of predictive accuracy. These models are the ordinary multinomial logit (MNL) model, a hierarchical model based on a set of nested MNL models, and a MNL model with a prior that introduces correlations between the parameters for classes that are nearby in the hierarchy. We also provide a new scheme for combining different sources of information. We use these models to predict the functional class of Open Reading Frames (ORFs) from the E. coli genome. The results from all three models show substantial improvement over previous methods, which were based on the C5 algorithm. The MNL model using a prior based on the hierarchy outperforms both the non-hierarchical MNL model and the nested MNL model. In contrast to previous attempts at combining these sources of information, our approach results in a higher accuracy rate when compared to models that use each data source alone. Together, these results show that gene function can be predicted with higher accuracy than previously achieved, using Bayesian models that incorporate suitable prior information

Submillimeter Studies of Prestellar Cores and Protostars: Probing the Initial Conditions for Protostellar Collapse

Improving our understanding of the initial conditions and earliest stages of protostellar collapse is crucial to gain insight into the origin of stellar masses, multiple systems, and protoplanetary disks. Observationally, there are two complementary approaches to this problem: (1) studying the structure and kinematics of prestellar cores observed prior to protostar formation, and (2) studying the structure of young (e.g. Class 0) accreting protostars observed soon after point mass formation. We discuss recent advances made in this area thanks to (sub)millimeter mapping observations with large single-dish telescopes and interferometers. In particular, we argue that the beginning of protostellar collapse is much more violent in cluster-forming clouds than in regions of distributed star formation. Major breakthroughs are expected in this field from future large submillimeter instruments such as Herschel and ALMA.Comment: 12 pages, 9 figures, to appear in the proceedings of the conference "Chemistry as a Diagnostic of Star Formation" (C.L. Curry & M. Fich eds.

Geogenetic patterns in mouse lemurs (genus Microcebus) reveal the ghosts of Madagascar's forests past.

Phylogeographic analysis can be described as the study of the geological and climatological processes that have produced contemporary geographic distributions of populations and species. Here, we attempt to understand how the dynamic process of landscape change on Madagascar has shaped the distribution of a targeted clade of mouse lemurs (genus Microcebus) and, conversely, how phylogenetic and population genetic patterns in these small primates can reciprocally advance our understanding of Madagascar's prehuman environment. The degree to which human activity has impacted the natural plant communities of Madagascar is of critical and enduring interest. Today, the eastern rainforests are separated from the dry deciduous forests of the west by a large expanse of presumed anthropogenic grassland savanna, dominated by the Family Poaceae, that blankets most of the Central Highlands. Although there is firm consensus that anthropogenic activities have transformed the original vegetation through agricultural and pastoral practices, the degree to which closed-canopy forest extended from the east to the west remains debated. Phylogenetic and population genetic patterns in a five-species clade of mouse lemurs suggest that longitudinal dispersal across the island was readily achieved throughout the Pleistocene, apparently ending at ∼55 ka. By examining patterns of both inter- and intraspecific genetic diversity in mouse lemur species found in the eastern, western, and Central Highland zones, we conclude that the natural environment of the Central Highlands would have been mosaic, consisting of a matrix of wooded savanna that formed a transitional zone between the extremes of humid eastern and dry western forest types

Community-based intervention to promote breast cancer awareness and screening: The Korean experience

<p>Abstract</p> <p>Background</p> <p>There are many differences in culture, community identity, community participation, and ownership between communities in Western and Asian countries; thus, it is difficult to adopt the results of community intervention studies from Western countries. In this study, we conducted a multicity, multicomponent community intervention trial to correct breast cancer myths and promote screening mammography for women living in an urban community in Korea.</p> <p>Methods</p> <p>A 6-month, 2-city community intervention trial was conducted. In the intervention city, 480 women were surveyed at baseline and 7 months later to evaluate the effects of the intervention program. Strategies implemented in the intervention city included community outreach and clinic and pharmacy-based in-reach strategies.</p> <p>Results</p> <p>This study showed a 20.4-percentage-point decrease in myths about the link between cancer and breast size, a 19.2-percentage-point decrease in myths concerning mammography costs, and a 14.1-percentage-point increase in intention to undergo screening mammography. We also saw a 23.4-percentage-point increase in the proportion of women at the action stage of the transtheoretical model in the intervention city. In the comparison city, smaller decreases and increases were observed.</p> <p>Conclusions</p> <p>Our study showed the value of an intervention study aimed at reducing belief in breast cancer myths in an urban community in Korea. The invention also made women more likely to undergo mammography in future.</p

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

Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance