Forty Years of Inferential Methods in the Journals of the Society for Molecular Biology and Evolution.

We are launching a series to celebrate the 40th anniversary of the first issue of Molecular Biology and Evolution. In 2024, we will publish virtual issues containing selected papers published in the Society for Molecular Biology and Evolution journals, Molecular Biology and Evolution and Genome Biology and Evolution. Each virtual issue will be accompanied by a perspective that highlights the historic and contemporary contributions of our journals to a specific topic in molecular evolution. This perspective, the first in the series, presents an account of the broad array of methods that have been published in the Society for Molecular Biology and Evolution journals, including methods to infer phylogenies, to test hypotheses in a phylogenetic framework, and to infer population genetic processes. We also mention many of the software implementations that make methods tractable for empiricists. In short, the Society for Molecular Biology and Evolution community has much to celebrate after four decades of publishing high-quality science including numerous important inferential methods.

Spexwavepy: an open-source Python package for X-ray wavefront sensing using speckle-based techniques.

In situ wavefront sensing plays a critical role in the delivery of high-quality beams for X-ray experiments. X-ray speckle-based techniques stand out among other in situ techniques for their easy experimental setup and various data acquisition modes. Although X-ray speckle-based techniques have been under development for more than a decade, there are still no user-friendly software packages for new researchers to begin with. Here, we present an open-source Python package, spexwavepy, for X-ray wavefront sensing using speckle-based techniques. This Python package covers a variety of X-ray speckle-based techniques, provides plenty of examples with real experimental data and offers detailed online documentation for users. We hope it can help new researchers learn and apply the speckle-based techniques for X-ray wavefront sensing to synchrotron radiation and X-ray free-electron laser beamlines.

Bayesian survival analysis with INLA.

This tutorial shows how various Bayesian survival models can be fitted using the integrated nested Laplace approximation in a clear, legible, and comprehensible manner using the INLA and INLAjoint R-packages. Such models include accelerated failure time, proportional hazards, mixture cure, competing risks, multi-state, frailty, and joint models of longitudinal and survival data, originally presented in the article "Bayesian survival analysis with BUGS." In addition, we illustrate the implementation of a new joint model for a longitudinal semicontinuous marker, recurrent events, and a terminal event. Our proposal aims to provide the reader with syntax examples for implementing survival models using a fast and accurate approximate Bayesian inferential approach.

Effects of health educational and participatory consumer group interventions in improving food handling practices in regional director of health services area Kalutara, Sri Lanka: non-randomized controlled community trial.

INTRODUCTION: Safe and nutritious food is the key to sustaining life and promoting good health. Unsafe food creates a vicious cycle of disease and malnutrition, particularly affecting infants, young children, the elderly, and the sick. METHODS: The study consisted of two phases, a descriptive cross-sectional study, and an intervention study. Both studies were conducted in the Regional Director of Health Services area, Kalutara, Sri Lanka. The descriptive cross-sectional study [food handlers (n = 904), food establishments (n = 421)] was conducted with the objective of determining factors associated with food handling practices among food handlers and in food establishments. The interventional study was a three-arm non-randomized controlled community trial (n = 50 per arm) with interventions of a participatory consumer group, educational package group, and control group. RESULTS: The food establishments assessment tool (FEAT) contained 11 domains including 75 items with more than a hundred assessment points with a guide to conduct an assessment of food handling. The descriptive cross-sectional study found that food handlers' knowledge of food handling practices of storing milk, fish, and meat and fast-food items containing fish and meat was very poor (96.6%). Visibility of the last place of processing inside the food establishments to consumers was inadequate (19.2%) and the absence of the above-mentioned factor was significantly associated with an unsatisfactory level of food handling score in food establishments (p = 0.03). The unsatisfactory level of food handling was significantly higher among food establishments with non-personal ownership (p = 0.005), a low number of notices issued by legal authorities (p = 0.02), dereliction of duty by owners/managers on supervising (p < 0.001) and lack of medical certification to food handlers (p < 0.0001). Participatory consumer group intervention and educational package interventions were effective in improving food handling practices in food establishments and among food handlers (p < 0.0001). Two independent sample analysis using the Mann-Whitney U test showed, the best improvement in food handling practices was by participatory consumer group intervention (p < 0.0001) and the second was educational package intervention (p < 0.0001). CONCLUSIONS: Knowledge and practices of food handling among participants were poor. A participatory consumer group is more effective than an educational package on improving food handling practices both among food handlers and in food establishments.

Identification of Differentially Expressed Genes in Human Colorectal Cancer Using RNASeq Data Validated on the Molecular Level with Real-Time PCR.

Colorectal cancer (CRC) is a prevalent cancer with high morbidity and mortality rates worldwide. Late diagnosis is a significant contributor to low survival rates in a minority of cases. The study aimed to perform a robust pipeline using integrated bioinformatics tools that will enable us to identify potential diagnostic and prognostic biomarkers for early detection of CRC by exploring differentially expressed genes (DEGs). In addition to, testing the capability of replacing chemotherapy with plant extract in CRC treatment by validating it using real-time PCR. RNA-seq data from cancerous and adjacent normal tissues were pre-processed and analyzed using various tools such as FastQC, Kallisto, DESeq@ R package, g:Profiler, GNEMANIA-CytoScape and CytoHubba, resulting in the identification of 1641 DEGs enriched in various signaling routes. MMP7, TCF21, and VEGFD were found to be promising diagnostic biomarkers for CRC. An in vitro experiment was conducted to examine the potential anticancer properties of 5-fluorouracile, Withania somnifera extract, and their combination. The extract was found to exhibit a positive trend in gene expression and potential therapeutic value by targeting the three genes; however, further trials are required to regulate the methylation promoter. Molecular docking tests supported the findings by revealing a stable ligand-receptor complex. In conclusion, the study's analysis workflow is precise and robust in identifying DEGs in CRC that may serve as biomarkers for diagnosis and treatment. Additionally, the identified DEGs can be used in future research with larger sample sizes to analyze CRC survival.

Simultaneous Inference Using Multiple Marginal Models.

This tutorial describes single-step low-dimensional simultaneous inference with a focus on the availability of adjusted p values and compatible confidence intervals for more than just the usual mean value comparisons. The basic idea is, first, to use the influence of correlation on the quantile of the multivariate t-distribution: the higher the less conservative. In addition, second, the estimability of the correlation matrix using the multiple marginal models approach (mmm) using multiple models in the class of linear up to generalized linear mixed models. The underlying maxT-test using mmm is discussed by means of several real data scenarios using selected R packages. Surprisingly, different features are highlighted, among them: (i) analyzing different-scaled, correlated, multiple endpoints, (ii) analyzing multiple correlated binary endpoints, (iii) modeling dose as qualitative factor and/or quantitative covariate, (iv) joint consideration of several tuning parameters within the poly-k trend test, (v) joint testing of dose and time, (vi) considering several effect sizes, (vii) joint testing of subgroups and overall population in multiarm randomized clinical trials with correlated primary endpoints, (viii) multiple linear mixed effect models, (ix) generalized estimating equations, and (x) nonlinear regression models.

Mechanochemical recycling of cellulose multilayer carton packages to produce micro and nanocellulose from the perspective of techno-economic and environmental analysis.

Despite being composed of recyclable materials, the main technological challenge of multilayer carton packs involves the efficient decompatibilization of the cellulosic, polymeric, and metallic phases. Here, a simple two-step mechanochemical process is described that uses only aqueous media and mechanical force to promote phase separation in order to fully recycle multi-layer carton packaging. The first step produces value-added micro- and nanocellulose, while in the second step, aluminum is extracted, forming precipitated aluminum and aluminum oxyhydroxides. Solid polyethylene (PE) remains with a degree of purity defined by the process efficiency. The results show that cellulose is efficiently extracted and converted into micro- and nanocellulose after 15 min of milling. In the second stage, approximately 90% of the aluminum is extracted from the PE after 15 min of milling. Due to the separation and drying medium conditions, the finely divided particles of extracted aluminum also have oxyhydroxides in their composition. It is believed that a passivation layer forms on the metallic aluminum particle. The techno-economic analysis revealed a positive net present value (NPV) of $17.5 million, with a minimum selling price of 1.62 USD/kg of cellulose. The environmental analysis concluded that most of the environmental impact of the process is associated with the entry of carton packages into the system, incorporating a small environmental load related to the industrial process. The results indicate a promising option toward a circular economy and carbon neutrality.

Traceability of Microplastic Fragments from Waste Plastic Express Packages Using Near-Infrared Spectroscopy Combined with Chemometrics.

The pollution from waste plastic express packages (WPEPs), especially microplastic (MP) fragments, caused by the blowout development of the express delivery industry has attracted widespread attention. On account of the variety of additives, strong complexity, and high diversity of plastic express packages (PEPs), the multi-class classification of WPEPs is a typical large-class-number classification (LCNC). The traceability and identification of microplastic fragments from WPEPs is very challenging. An effective chemometric method for large-class-number classification would be very beneficial for the comprehensive treatment of WPEP pollution through the recycling and reuse of waste plastic express packages, including microplastic fragments and plastic debris. Rather than using the traditional one-against-one (OAO) and one-against-all (OAA) dichotomies, an exhaustive and parallel half-against-half (EPHAH) decomposition, which overcomes the defects of the OAO's classifier learning limitations and the OAA's data proportion imbalance, is proposed for feature selection. EPHAH analysis, combined with partial least squares discriminant analysis (PLS-DA) for large-class-number classification, was performed on 750 microplastic fragments of polyethylene WPEPs from 10 major courier companies using near-infrared (NIR) spectroscopy. After the removal of abnormal samples through robust principal component analysis (RPCA), the root mean square error of cross-validation (RMSECV) value for the model was reduced to 0.01, which was 21.5% lower than that including the abnormal samples. The best models of PLS-DA were obtained using SNV combined with SG-17 smoothing and 2D (SNV+SG-17+2D); the latent variables (LVs), the error rates of Monte Carlo cross-validation (ERMCCVs), and the final classification accuracies were 6.35, 0.155, and 88.67% for OAO-PLSDA; 5.37, 0.103, and 87.33% for OAA-PLSDA; and 3.12, 0.054, and 96.00% for EPHAH-PLSDA. The results showed that the EPHAH strategy can completely learn the complex LCNC decision boundaries for 10 classes, effectively break the tie problem, and greatly improve the voting resolution, thereby demonstrating significant superiority to both the OAO and OAA strategies in terms of classification accuracy. Meanwhile, PLS-DA further maximized the covariance and data interpretation abilities between the potential variables and categories of microplastic debris, thereby establishing an ideal performance identification model with a recognition rate of 96.00%.

Flexible All-Solid-State Direct Methanol Fuel Cells with High Specific Power Density.

It is vital to create flexible batteries as power sources to suit the needs of flexible electronic devices because they are widely employed in wearable and portable electronics. The direct methanol fuel cell (DMFC) is a desirable alternative portable energy source since it is a clean, safe, and high energy density cell. The traditional DMFC in mechanical assembly and its unbending property, however, prevent it from being employed in flexible electrical devices. In this study, the flexible membrane electrode assembly (MEA) with superior electrical conductivity and nanoscale TiC-modified carbon cloth (TiC/CC) is used as supporting layer. Additionally, solid methanol fuels used in the manufacturing of flexible all-solid-state DMFC have the advantages of being tiny, light, and having high energy density. Furthermore, the DMFC's placement and bending angle have little effect on its performance, suggesting that DMFC is appropriate for flexible portable energy. The flexible all-solid-state DMFC's power density can reach 14.06 mW cm-2 , and after 50 bends at 60°, its voltage loss can be disregarded. The flexible all-solid DMFC has an energy density that is 777.78 Wh Kg-1 higher than flexible lithium-ion batteries, which is advantageous for the commercialization of flexible electronic products.

Translating the Value of the Academic Surgeon Into Salary, Time, and Resources.

Academic surgeons provide tremendous value to institutions including notoriety, publicity, cutting-edge clinical advances, extramural funding, and academic growth and development. In turn, these attributes may result in improved reputation scores and hospital or medical center rankings. While many hospital systems, schools of medicine, and departments of surgery claim to have a major commitment to academic surgery and research, academic surgeons are often undercompensated compared to clinically focused counterparts. Existing salary benchmarks (e.g., the Medical Group Management Association (MGMA) or the Association of American Medical Colleges (AAMC)) are often used but are imperfect. Thus, the value proposition for academic surgeons goes beyond compensation and often includes protected time for academic pursuit, nonsalary financial support, and other intangible benefits to being associated with a major academic center (e.g., abundance of scientific collaborators, infrastructure for grant management). As a result, institution-specific practices have developed and academic surgeons are left to negotiate salary support including bonus structures, protected time, and recruitment packages on a case-by-case basis without a clear roadmap. A diverse panel representing a range of academic surgical experiences was convened at the 2022 Academic Surgical Congress to illuminate this complex, often stress-inducing, aspect of an academic surgeon's professional career.

The use of cost-effectiveness analysis for health benefit package design - should countries follow a sectoral, incremental or hybrid approach?

BACKGROUND: Countries around the world are increasingly rethinking the design of their health benefit package to achieve universal health coverage. Countries can periodically revise their packages on the basis of sectoral cost-effectiveness analyses, i.e. by evaluating a broad set of services against a 'doing nothing' scenario using a budget constraint. Alternatively, they can use incremental cost-effectiveness analyses, i.e. to evaluate specific services against current practice using a threshold. In addition, countries may employ hybrid approaches which combines elements of sectoral and incremental cost-effectiveness analysis - a country may e.g. not evaluate the comprehensive set of all services but rather relatively small sets of services targeting a certain condition. However, there is little practical guidance for countries as to which kind of approach they should follow. METHODS: The present study was based on expert consultation. We refined the typology of approaches of cost-effectiveness analysis for benefit package design, identified factors that should be considered in the choice of approach, and developed recommendations. We reached consensus among experts over the course of several review rounds. RESULTS: Sectoral cost-effectiveness analysis is especially suited in contexts with large allocative inefficiencies in current service provision and can, in theory, realize large efficiency gains. However, it may be challenging to implement a comprehensive redesign of the package in practice. Incremental cost-effectiveness analysis is especially relevant in contexts where specific new services may impact the sustainability of the health system. It may potentially support efficiency improvement, but its focus has typically been on new services while existing inefficiencies remain unchallenged. The use of hybrid approach may be a way forward to address the strengths and weaknesses of sectoral and incremental analysis areas. Such analysis may be especially useful to target disease areas with suspected high inefficiencies in service provision, and would then make good use of the available research capacity and be politically rewarding. However, disease-specific analyses bear the risk of not addressing resource allocation inefficiencies across disease areas. CONCLUSIONS: Countries should carefully select their approach of cost-effectiveness analyses for benefit package design, based on their decision-making context.

Electronic common technical document submission with analysis using R.

BACKGROUND: In clinical trial development, it is a critical step to submit applications, amendments, supplements, and reports on medicinal products to regulatory agencies. The electronic common technical document is the standard format to enable worldwide regulatory submission. There is a growing trend of using R for clinical trial analysis and reporting as part of regulatory submissions, where R functions, analysis scripts, analysis results, and all proprietary code dependencies are required to be included. One unmet and significant gap is the lack of tools, guidance, and publicly available examples to prepare submission R programs following the electronic common technical document specification. METHODS: We introduce a simple and sufficient R package, pkglite, to convert analysis scripts and associated proprietary dependency R packages into a compact, text-based file, which makes the submission document self-contained, easy to restore, transfer, review, and submit following the electronic common technical document specification and regulatory guidelines (e.g. the study data technical conformance guide from the US Food and Drug Administration). The pkglite R package is published on Comprehensive R Archive Network and developed on GitHub. RESULTS: As a tool, pkglite can pack and unpack multiple R packages with their dependencies to facilitate the reproduction and make it an off-the-shelf tool for both sponsors and reviewers. As a grammar, pkglite provides an explicit trace of the packing scope using the concept of file specifications. As a standard, pkglite offers an open file format to represent and exchange R packages as a text file. We use a mock-up example to demonstrate the workflow of using pkglite to prepare submission programs following the electronic common technical document specification. CONCLUSION: pkglite and the proposed workflow enable the sponsor to submit well-organized R scripts following the electronic common technical document specification. The workflow has been used in the first publicly available R-based submission to the US Food and Drug Administration by the R Consortium R submission working group (https://www.r-consortium.org/blog/2022/03/16/update-successful-r-based-test-package-submitted-to-fda).

Early introduction of complementary foods/drinks and milk feeding type in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC).

Infants younger than 4 months are not ready for complementary foods/drinks (any solid or liquid other than breast milk or infant formula). Almost half of US infants participate in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC), which provides nutrition education and support to low-income families. We describe the prevalence of early introduction (<4 months) of complementary foods/drinks and examine the association of milk feeding type (fully breastfed, partially breastfed or fully formula fed) with early introduction of complementary foods/drinks. We used data from 3310 families in the longitudinal WIC Infant and Toddler Feeding Practices Study-2. We described the prevalence of early introduction of complementary foods/drinks and modeled the association of milk feeding type at Month 1 with early introduction of complementary foods/drinks using multi-variable logistic regression. Thirty-eight percent of infants were introduced early to complementary foods/drinks (<4 months). In adjusted models, infants who were fully formula fed or partially breastfed at Month 1 were 75% and 57%, respectively, more likely to be introduced early to complementary foods/drinks compared with fully breastfed infants. Almost two in five infants were given complementary foods/drinks early. Formula feeding at Month 1 was associated with higher odds of early introduction of complementary foods/drinks. There are opportunities to support families participating in WIC to prevent early introduction of complementary foods/drinks and promote child health.

A mini-review on the use of waste in the production of sustainable Portland cement composites.

With an increase in climate and environmental issues awareness, the use of waste of various types has gained increased visibility, acknowledging that wastes are any and all kinds of unused materials from the production process or after using the final product for its intended purpose. The use of wastes to produce alternative cement materials is an alternative to reduce the use of natural resources. Forestry residues, ash, plastic residues, LDPE/Al composites, and geopolymer materials are some of the possible residues used for the partial replacement of cement materials. The objective of this research is to establish how these materials relate to each other, based on a topic review and how they can contribute towards sustainability. The study was performed on several scientific article search engines, in which the keywords 'Carton Packages', 'Wood Waste' and 'Geopolymers' were inserted, and then a refinement was carried out using the term 'Cement Materials'. Such analysis allowed the generation of information related to publication numbers, countries, research areas, as well as publication types. Co-authorship networks of organization, co-citation of references, co-occurrence of keywords, among others, were also plotted. Through this bibliometric analysis, it was possible to reveal the structure of the research, analyse the developments and predict the future directions for the research regarding the use of residues in the production of sustainable Portland cement composites.

tReasure: R-based GUI package analyzing tRNA expression profiles from small RNA sequencing data.

BACKGROUND: Recent deep sequencing technologies have proven to be valuable resources to gain insights into the expression profiles of diverse tRNAs. However, despite these technologies, the association of tRNAs with diverse diseases has not been explored in depth because analytical tools are lacking. RESULTS: We developed a user-friendly tool, tRNA Expression Analysis Software Utilizing R for Easy use (tReasure), to analyze differentially expressed tRNAs (DEtRNAs) from deep sequencing data of small RNAs using R packages. tReasure can quantify individual mature tRNAs, isodecoders, and isoacceptors. By adopting stringent mapping strategies, tReasure supports the precise measurement of mature tRNA read counts. The whole analysis workflow for determining DEtRNAs (uploading FASTQ files, removing adapter sequences and poor-quality reads, mapping and quantifying tRNAs, filtering out low count tRNAs, determining DEtRNAs, and visualizing statistical analysis) can be performed with the tReasure package. CONCLUSIONS: tReasure is an open-source software available for download at https://treasure.pmrc.re.kr and will be indispensable for users who have little experience with command-line software to explore the biological implication of tRNA expression.

The political economy of priority-setting for health in South Sudan: a case study of the health pooled fund.

BACKGROUND: In fragile and conflict affected settings (FCAS) such as South Sudan, where health needs are immense, resources are scarce, health infrastructure is rudimentary or damaged, and government stewardship is weak, adequate health intervention priority-setting is especially important. There is a scarcity of research examining priority-setting in FCAS and the related political economy. Yet, capturing these dynamics is important to develop context-specific guidance for priority-setting. The objective of this study is to analyze the priority-setting practices in the Health Pooled Fund (HPF), a multi-donor fund that supports service delivery in South Sudan, using a political economy perspective. METHODS: A multi-method study was conducted combining document review, 30 stakeholder interviews, and an examination of service delivery. An adapted version of the Walt and Gilson policy analysis triangle guided the study's design and analysis. RESULTS: Priority-setting in HPF occurs in a context of immense fragility where health needs are vast, service delivery remains weak, and external funding is essential. HPF's service package gives priority to the health of mothers and children, gender-sensitive programming, immunization services, and a community health initiative. HPF is structured by a web of actors at national and local levels with pronounced power asymmetries and differing vested interests and ideas about HPF's role. Priority-setting takes place throughout program design, implementing partner (IP) contract negotiation, and implementation of the service package. In practice the BPHNS does not provide adequate guidance for priority-setting because it is too expansive and unrealistic given financial and health system constraints. At the local level, IPs must manage the competing interests of the HPF program and local health authorities as well as challenging contextual factors, including conflict and shortages of qualified health workers, which affect service provision. The resulting priority-setting process remains implicit, scarcely documented, and primarily driven by donors' interests. CONCLUSION: This study highlights power asymmetries between donors and national health authorities within a FCAS context, which drive a priority-setting process that is dominated by donor agendas and leave little room for government ownership. These findings emphasize the importance of paying attention to the influence of stakeholders and their interests on the priority-setting process in FCAS.

Screening is not always healthy: an ethical analysis of health screening packages in Singapore.

BACKGROUND: Health screening is undertaken to identify individuals who are deemed at higher risk of disease for further diagnostic testing so that they may possibly benefit from interventions to modify the natural course of disease. In Singapore, screening tests are widely available in the form of a package, which bundles multiple tests in one session and commonly includes non-recommended tests. There are various ethical issues associated with such testing as they may not be clinically appropriate and can result in more harm than benefit. This article describes the practice of health screening packages, identifies the ethical issues arising from such packages and discusses the implications of these ethical issues on policy and practice of screening in Singapore. METHODS: A content analysis of the websites of providers offering general health screening packages to individuals was conducted. A total of 14 health screening package providers were analysed for how packages were conducted and promoted, how clinically appropriate screening tests were, and the price range and composition of screening packages. A normative ethical analysis based on the four principles approach of beneficence, non-maleficence, autonomy and justice in biomedical ethics was used. RESULTS: Twelve of the 14 providers included non-recommended tests such as tumour markers, treadmill stress tests and MRI scans in their general health screening packages. Package prices ranged from S$26 to S$10,561, with providers charging higher when more tests were included. Health screening packages were broadly conducted in three stages: (1) the offer and selection of a health screening package; (2) medical assessment and performance of screening tests; (3) a post-screening review. While material provided by all providers was factual, there was no information on the potential risks or harms of screening. CONCLUSION: Several ethical issues were identified that should be addressed with regard to health screening packages in Singapore. A key issue was the information gap between providers and patients, which may result in patients undergoing inappropriate testing that may be more harmful than beneficial. Health screening packages can stimulate unnecessary demand for healthcare and contribute to an inequitable distribution of healthcare resources.

Bayesian survival analysis with BUGS.

Survival analysis is one of the most important fields of statistics in medicine and biological sciences. In addition, the computational advances in the last decades have favored the use of Bayesian methods in this context, providing a flexible and powerful alternative to the traditional frequentist approach. The objective of this article is to summarize some of the most popular Bayesian survival models, such as accelerated failure time, proportional hazards, mixture cure, competing risks, multi-state, frailty, and joint models of longitudinal and survival data. Moreover, an implementation of each presented model is provided using a BUGS syntax that can be run with JAGS from the R programming language. Reference to other Bayesian R-packages is also discussed.

Costing of Essential Health Service Packages: A Systematic Review of Methods From Developing Economies.

OBJECTIVES: Although an increasing number of countries are adopting essential health service packages (EHSPs) and undertaking their cost assessment, standardization of the costing methods and their reporting are imperative to instill confidence in the use of findings of EHSPs as evidence for decision making and resource allocation. This review was conducted to synthesize the EHSP costing reports, focusing on the key costing methods and their reporting standards. METHODS: A systematic review of English language literature (peer-reviewed as well as gray) was conducted. PubMed, Embase, Scopus, NHS Economic Evaluation Database, Google Scholar, and websites of key institutions were reviewed (2000-2020). Publication characteristics, costing methods, valuation sources, quality, transparency, and reporting standards were assessed and synthesized. RESULTS: A total of 29 studies from 19 countries were included. Most studies were government reports (69%) and reported the use of "bottom-up" approach (76%), OneHealth tool (38%), had international funding (79%), and reported both normative and empirical cost estimates (41%). Six studies (21%) scored "excellent" in conduct and reporting. Stand-alone costing of EHSP had higher mean quality score (80). The projected increase in government budget to implement EHSP ranged from 17% to 117%. Limited availability of reliable data on resources, prices, and coverage of interventions were identified as major limitations for costing of EHSPs. CONCLUSIONS: Substantial differences in the costing methods and reporting standards of EHSPs made comparisons across countries difficult. Existing costing guidelines and checklists should be adapted for EHSPs with more specific methodological guidance to allow harmonization of methods and reporting.

Trading off health and financial protection benefits with multiobjective optimization.

Countries which are introducing a system of Universal health coverage have to make a number of key tradeoffs, of which one is the tradeoff between the level of coverage and the degree to which patients are exposed to potentially catastrophic financial risk. In this study, we first present a way in which decision makers might be supported to focus on in a particular part of the tradeoff curve and ultimately choose an efficient solution. We then introduce some multiobjective optimization models for generating the tradeoff curves given data about potential treatment numbers, costs, and benefits. Using a dataset from Malawi, we demonstrate the approach and suggest a core index metric to make specific observations on the individual treatments. Moreover, as there has been some debate about the best way to measure financial exposure, we also investigate the extent to sensitivity of our results to the precise technical choice of financial exposure metric. Specifically, we consider two metrics, which are the total number of cases protected from catastrophic expenditure and a convex penalty function that penalizes out-of-pocket expenditures in an increasingly growing way, respectively.