Comparing the health and social protection effects of measles vaccination strategies in Ethiopia: An extended cost-effectiveness analysis

AbstractVaccination coverage rates often mask wide variation in access, uptake, and cost of providing vaccination. Financial incentives have been effective at creating demand for social services in a variety of settings. Using methods of extended cost-effectiveness analysis, we compare the health and economic implications of three different vaccine delivery strategies for measles vaccination in Ethiopia: i) routine immunization, ii) routine immunization with financial incentives, and iii) mass campaigns, known as supplemental immunization activities (SIAs). We examine annual birth cohorts of almost 3,000,000 births over a ten year period, exploring variation in these outcomes based on economic status to understand how various options may improve equity. SIAs naturally achieve higher levels of vaccine coverage, but at higher costs. Routine immunization combined with financial incentives bolsters demand among more economically vulnerable households. The relative appeal of routine immunization with financial incentives and SIAs will depend on the policy environment, including short-term financial limitations, time horizons, and the types of outcomes that are desired. While the impact of financial incentives has been more thoroughly studied in other policy arenas, such as education, consideration of this approach alongside standard vaccination models such as SIAs is timely given the dialog around measles eradication

Magnetically-controlled velocity selection in a cold atom sample using stimulated Raman transitions

We observe velocity-selective two-photon resonances in a cold atom cloud in the presence of a magnetic field. We use these resonances to demonstrate a simple magnetometer with sub-mG resolution. The technique is particularly useful for zeroing the magnetic field and does not require any additional laser frequencies than are already used for standard magneto-optical traps. We verify the effects using Faraday rotation spectroscopy.Comment: 5 pages, 6 figure

Annual rates of decline in child, maternal, HIV, and tuberculosis mortality across 109 countries of low and middle income from 1990 to 2013: an assessment of the feasibility of post-2015 goals

Background Measuring a country’s health performance has focused mostly on estimating levels of mortality. An alternative is to measure rates of decline in mortality, which are more sensitive to changes in health policy than are mortality levels. Historical rates of decline in mortality can also help test the feasibility of future health goals (eg, post-2015). We aimed to assess the annual rates of decline in under-5, maternal, tuberculosis, and HIV mortality over the past two decades for 109 low-income and middle-income countries. Methods For the period 1990–2013, we estimated annual rates of decline in under-5 mortality (deaths per 1000 livebirths), the maternal mortality ratio (deaths per 100 000 livebirths), and tuberculosis and HIV mortality (deaths per 100 000 population per year) using published data from UNICEF and WHO. For every 5-year interval (eg, 1990–95), we defi ned performance as the size of the annual rate of decline for every mortality indicator. Subsequently, we tested the feasibility of post-2015 goals by estimating the year by which countries would achieve 2030 targets proposed by The Lancet’s Commission on Investing in Health (ie, 20 deaths per 1000 for under-5 mortality, 94 deaths per 100 000 for maternal mortality, four deaths per 100 000 for tuberculosis mortality, and eight deaths per 100 000 for HIV mortality) at observed country and aspirational best-performer (90th percentile) rates. Findings From 2005 to 2013, the mean annual rate of decline in under-5 mortality was 4·3% (95% uncertainty interval [UI] 3·9–4·6), for maternal mortality it was 3·3% (2·5–4·1), for tuberculosis mortality 4·1% (2·8–5·4), and for HIV mortality 2·2% (0·1–4·3); aspirational best-performer rates per year were 7·1% (6·8–7·5), 6·3% (5·5–7·1), 12·8% (11·5–14·1), and 15·3% (13·2–17·4), respectively. The top two country performers were Macedonia and South Africa for under-5 mortality, Belarus and Bulgaria for maternal mortality, Uzbekistan and Macedonia for tuberculosis mortality, and Namibia and Rwanda for HIV mortality. At aspirational rates of decline, The Lancet’s Commission on Investing in Health target for under-5 mortality would be achieved by 50–64% of countries, 35–41% of countries would achieve the 2030 target for maternal mortality, 74–90% of countries would meet the goal for tuberculosis mortality, and 66–82% of countries would achieve the target for HIV mortality. Interpretation Historical rates of decline can help defi ne realistic targets for Sustainable Development Goals. The gap between targets and projected achievement based on recent trends suggests that countries and the international community must seek further acceleration of progress in mortality

Health gains and fi nancial risk protection aff orded by public fi nancing of selected interventions in Ethiopia: an extended cost-eff ectiveness analysis

Background The way in which a government chooses to fi nance a health intervention can aff ect the uptake of health interventions and consequently the extent of health gains. In addition to health gains, some policies such as public fi nance can insure against catastrophic health expenditures. We aimed to evaluate the health and fi nancial risk protection benefi ts of selected interventions that could be publicly fi nanced by the government of Ethiopia. Methods We used extended cost-eff ectiveness analysis to assess the health gains (deaths averted) and fi nancial risk protection aff orded (cases of poverty averted) by a bundle of nine (among many other) interventions that the Government of Ethiopia aims to make universally available. These nine interventions were measles vaccination, rotavirus vaccination, pneumococcal conjugate vaccination, diarrhoea treatment, malaria treatment, pneumonia treatment, caesarean section surgery, hypertension treatment, and tuberculosis treatment. Findings Our analysis shows that, per dollar spent by the Ethiopian Government, the interventions that avert the most deaths are measles vaccination (367 deaths averted per $100 000 spent), pneumococcal conjugate vaccination (170 deaths averted per$100 000 spent), and caesarean section surgery (141 deaths averted per $100 000 spent). The interventions that avert the most cases of poverty are caesarean section surgery (98 cases averted per$100 000 spent), tuberculosis treatment (96 cases averted per $100 000 spent), and hypertension treatment (84 cases averted per$100 000 spent). Interpretation Our approach incorporates fi nancial risk protection into the economic evaluation of health interventions and therefore provides information about the effi ciency of attainment of both major objectives of a health system: improved health and fi nancial risk protection. One intervention might rank higher on one or both metrics than another, which shows how intervention choice—the selection of a pathway to universal health coverage—might involve weighing up of sometimes competing objectives. This understanding can help policy makers to select interventions to target specifi c policy goals (ie, improved health or fi nancial risk protection). It is especially relevant for the design and sequencing of universal health coverage to meet the needs of poor populations

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.

INTRODUCTION: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. METHODS: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. RESULTS: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. CONCLUSIONS: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are