Economic evaluations of onchocerciasis interventions: a systematic review and research needs

Objective To provide a systematic review of economic evaluations that has been conducted for onchocerciasis interventions, to summarise current key knowledge and to identify research gaps. Method A systematic review of the literature was conducted on the 8th of August 2018 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. No date or language stipulations were applied to the searches. Results We identified 14 primary studies reporting the results of economic evaluations of onchocerciasis interventions, seven of which were cost‐effectiveness analyses. The studies identified used a variety of different approaches to estimate the costs of the investigated interventions/programmes. Originally, the studies only quantified the benefits associated with preventing blindness. Gradually, methods improved and also captured onchocerciasis‐associated skin disease. Studies found that eliminating onchocerciasis would generate billions in economic benefits. The majority of the cost‐effectiveness analyses evaluated annual mass drug administration (MDA). The estimated cost per disability‐adjusted life year (DALY) averted of annual MDA varies between US$3 and US$30 (cost year variable). Conclusions The cost benefit and cost effectiveness of onchocerciasis interventions have consistently been found to be very favourable. This finding provides strong evidential support for the ongoing efforts to eliminate onchocerciasis from endemic areas. Although these results are very promising, there are several important research gaps that need to be addressed as we move towards the 2020 milestones and beyond

Improving educational achievement and anaemia of school children: design of a cluster randomised trial of school-based malaria prevention and enhanced literacy instruction in Kenya

BACKGROUND: Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence on the benefits of school-based malaria prevention or how health interventions interact with other efforts to improve education quality. This study aims to evaluate the impact of school-based malaria prevention and enhanced literacy instruction on the health and educational achievement of school children in Kenya. DESIGN: A factorial, cluster randomised trial is being implemented in 101 government primary schools on the coast of Kenya. The interventions are (i) intermittent screening and treatment of malaria in schools by public health workers and (ii) training workshops and support for teachers to promote explicit and systematic literacy instruction. Schools are randomised to one of four groups: receiving either (i) the malaria intervention alone; (ii) the literacy intervention alone; (iii) both interventions combined; or (iv) control group where neither intervention is implemented. Children from classes 1 and 5 are randomly selected and followed up for 24 months. The primary outcomes are educational achievement and anaemia, the hypothesised mediating variables through which education is affected. Secondary outcomes include malaria parasitaemia, school attendance and school performance. A nested process evaluation, using semi-structured interviews, focus group discussion and a stakeholder analysis will investigate the community acceptability, feasibility and cost-effectiveness of the interventions. DISCUSSION: Across Africa, governments are committed to improve health and education of school-aged children, but seek clear policy and technical guidance as to the optimal approach to address malaria and improved literacy. This evaluation will be one of the first to simultaneously evaluate the impact of health and education interventions in the improvement of educational achievement. Reflection is made on the practical issues encountered in conducting research in schools in Africa. TRIAL REGISTRATION: National Institutes of Health NCT00878007

Prediction of Promiscuous P-Glycoprotein Inhibition Using a Novel Machine Learning Scheme

BACKGROUND: P-glycoprotein (P-gp) is an ATP-dependent membrane transporter that plays a pivotal role in eliminating xenobiotics by active extrusion of xenobiotics from the cell. Multidrug resistance (MDR) is highly associated with the over-expression of P-gp by cells, resulting in increased efflux of chemotherapeutical agents and reduction of intracellular drug accumulation. It is of clinical importance to develop a P-gp inhibition predictive model in the process of drug discovery and development. METHODOLOGY/PRINCIPAL FINDINGS: An in silico model was derived to predict the inhibition of P-gp using the newly invented pharmacophore ensemble/support vector machine (PhE/SVM) scheme based on the data compiled from the literature. The predictions by the PhE/SVM model were found to be in good agreement with the observed values for those structurally diverse molecules in the training set (n = 31, r(2) = 0.89, q(2) = 0.86, RMSE = 0.40, s = 0.28), the test set (n = 88, r(2) = 0.87, RMSE = 0.39, s = 0.25) and the outlier set (n = 11, r(2) = 0.96, RMSE = 0.10, s = 0.05). The generated PhE/SVM model also showed high accuracy when subjected to those validation criteria generally adopted to gauge the predictivity of a theoretical model. CONCLUSIONS/SIGNIFICANCE: This accurate, fast and robust PhE/SVM model that can take into account the promiscuous nature of P-gp can be applied to predict the P-gp inhibition of structurally diverse compounds that otherwise cannot be done by any other methods in a high-throughput fashion to facilitate drug discovery and development by designing drug candidates with better metabolism profile

Mapping of schistosomiasis and soil-transmitted helminths in Namibia: The first large-scale protocol to formally include rapid diagnostic tests

Background: Namibia is now ready to begin mass drug administration of praziquantel and albendazole against schistosomiasis and soil-transmitted helminths, respectively. Although historical data identifies areas of transmission of these neglected tropical diseases (NTDs), there is a need to update epidemiological data. For this reason, Namibia adopted a new protocol for mapping of schistosomiasis and geohelminths, formally integrating rapid diagnostic tests (RDTs) for infections and morbidity. In this article, we explain the protocol in detail, and introduce the concept of 'mapping resolution', as well as present results and treatment recommendations for northern Namibia.Methods/Findings/Interpretation: This new protocol allowed a large sample to be surveyed (N = 17 896 children from 299 schools) at relatively low cost (7 USD per person mapped) and very quickly (28 working days). All children were analysed by RDTs, but only a sub-sample was also diagnosed by light microscopy. Overall prevalence of schistosomiasis in the surveyed areas was 9.0%, highly associated with poorer access to potable water (OR = 1.5, P<0.001) and defective (OR = 1.2, P<0.001) or absent sanitation infrastructure (OR = 2.0, P<0.001). Overall prevalence of geohelminths, more particularly hookworm infection, was 12.2%, highly associated with presence of faecal occult blood (OR = 1.9, P<0.001). Prevalence maps were produced and hot spots identified to better guide the national programme in drug administration, as well as targeted improvements in water, sanitation and hygiene. The RDTs employed (circulating cathodic antigen and microhaematuria for Schistosoma mansoni and S. haematobium, respectively) performed well, with sensitivities above 80% and specificities above 95%.Conclusion/Significance: This protocol is cost-effective and sensitive to budget limitations and the potential economic and logistical strains placed on the national Ministries of Health. Here we present a high resolution map of disease prevalence levels, and treatment regimens are recommended.Peer reviewedEntomology and Plant Patholog

Search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks in proton-proton collisions at root s=13TeV

A search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks is performed in proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. The analyzed data sample corresponds to an integrated luminosity of 35.9 fb(-1). The signal is characterized by a large missing transverse momentum recoiling against a bottom quark-antiquark system that has a large Lorentz boost. The number of events observed in the data is consistent with the standard model background prediction. Results are interpreted in terms of limits both on parameters of the type-2 two-Higgs doublet model extended by an additional light pseudoscalar boson a (2HDM+a) and on parameters of a baryonic Z simplified model. The 2HDM+a model is tested experimentally for the first time. For the baryonic Z model, the presented results constitute the most stringent constraints to date.Peer reviewe

Search for low-mass dilepton resonances in Higgs boson decays to four-lepton final states in proton–proton collisions at √s=13TeV

Data Availability: This manuscript has no associated data or the data will not be deposited. [Authors’ comment: For CMS Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy” (https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1.2.pdf&version=2).]Copyright © CERN for the benefit of the CMS collaboration 2022. A search for low-mass dilepton resonances in Higgs boson decays is conducted in the four-lepton final state. The decay is assumed to proceed via a pair of beyond the standard model particles, or one such particle and a Z boson. The search uses proton–proton collision data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 137fb−1, at a center-of-mass energy s√=13TeV. No significant deviation from the standard model expectation is observed. Upper limits at 95% confidence level are set on model-independent Higgs boson decay branching fractions. Additionally, limits on dark photon and axion-like particle production, based on two specific models, are reported.SCOAP3

A portrait of the Higgs boson by the CMS experiment ten years after the discovery

A Correction to this paper has been published (18 October 2023) : https://doi.org/10.1038/s41586-023-06164-8.Data availability: Tabulated results are provided in the HEPData record for this analysis. Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS data preservation, re-use and open acess policy.Code availability: The CMS core software is publicly available on GitHub (https://github.com/cms-sw/cmssw).In July 2012, the ATLAS and CMS collaborations at the CERN Large Hadron Collider announced the observation of a Higgs boson at a mass of around 125 gigaelectronvolts. Ten years later, and with the data corresponding to the production of a 30-times larger number of Higgs bosons, we have learnt much more about the properties of the Higgs boson. The CMS experiment has observed the Higgs boson in numerous fermionic and bosonic decay channels, established its spin–parity quantum numbers, determined its mass and measured its production cross-sections in various modes. Here the CMS Collaboration reports the most up-to-date combination of results on the properties of the Higgs boson, including the most stringent limit on the cross-section for the production of a pair of Higgs bosons, on the basis of data from proton–proton collisions at a centre-of-mass energy of 13 teraelectronvolts. Within the uncertainties, all these observations are compatible with the predictions of the standard model of elementary particle physics. Much evidence points to the fact that the standard model is a low-energy approximation of a more comprehensive theory. Several of the standard model issues originate in the sector of Higgs boson physics. An order of magnitude larger number of Higgs bosons, expected to be examined over the next 15 years, will help deepen our understanding of this crucial sector.BMBWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, FAPERGS, and FAPESP (Brazil); MES and BNSF (Bulgaria); CERN; CAS, MoST, and NSFC (China); MINCIENCIAS (Colombia); MSES and CSF (Croatia); RIF (Cyprus); SENESCYT (Ecuador); MoER, ERC PUT and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRI (Greece); NKFIH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); MES (Latvia); LAS (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MOS (Montenegro); MBIE (New Zealand); PAEC (Pakistan); MES and NSC (Poland); FCT (Portugal); MESTD (Serbia); MCIN/AEI and PCTI (Spain); MOSTR (Sri Lanka); Swiss Funding Agencies (Switzerland); MST (Taipei); MHESI and NSTDA (Thailand); TUBITAK and TENMAK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie programme and the European Research Council and Horizon 2020 Grant, contract Nos. 675440, 724704, 752730, 758316, 765710, 824093, 884104, and COST Action CA16108 (European Union); the Leventis Foundation; the Alfred P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the F.R.S.-FNRS and FWO (Belgium) under the “Excellence of Science – EOS” – be.h project n. 30820817; the Beijing Municipal Science & Technology Commission, No. Z191100007219010; the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Stavros Niarchos Foundation (Greece); the Deutsche Forschungsgemeinschaft (DFG), under Germany’s Excellence Strategy – EXC 2121 “Quantum Universe” – 390833306, and under project number 400140256 - GRK2497; the Hungarian Academy of Sciences, the New National Excellence Program - ÚNKP, the NKFIH research grants K 124845, K 124850, K 128713, K 128786, K 129058, K 131991, K 133046, K 138136, K 143460, K 143477, 2020-2.2.1-ED-2021-00181, and TKP2021-NKTA-64 (Hungary); the Council of Science and Industrial Research, India; the Latvian Council of Science; the Ministry of Education and Science, project no. 2022/WK/14, and the National Science Center, contracts Opus 2021/41/B/ST2/01369 and 2021/43/B/ST2/01552 (Poland); the Fundação para a Ciência e a Tecnologia, grant CEECIND/01334/2018 (Portugal); the National Priorities Research Program by Qatar National Research Fund; MCIN/AEI/10.13039/501100011033, ERDF “a way of making Europe”, and the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2017-0765 and Programa Severo Ochoa del Principado de Asturias (Spain); the Chulalongkorn Academic into Its 2nd Century Project Advancement Project, and the National Science, Research and Innovation Fund via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation, grant B05F650021 (Thailand); the Kavli Foundation; the Nvidia Corporation; the SuperMicro Corporation; the Welch Foundation, contract C-1845; and the Weston Havens Foundation (USA)

Precision measurement of the W boson decay branching fractions in proton-proton collisions at √s=13 TeV

The leptonic and inclusive hadronic decay branching fractions of the W boson are measured using proton-proton collision data collected at ffiffi s p ¼ 13 TeV by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of 35.9 fb−1. Events characterized by the production of one or two W bosons are selected and categorized based on the multiplicity and flavor of reconstructed leptons, the number of jets, and the number of jets identified as originating from the hadronization of b quarks. A binned maximum likelihood estimate of the W boson branching fractions is performed simultaneously in each event category. The measured branching fractions of the W boson decaying into electron, muon, and tau lepton final states are ð10.83 0.10Þ%, ð10.94 0.08Þ%, and ð10.77 0.21Þ%, respectively, consistent with lepton flavor universality for the weak interaction. The average leptonic and inclusive hadronic decay branching fractions are estimated to be ð10.89 0.08Þ% and ð67.32 0.23Þ%, respec tively. Based on the hadronic branching fraction, three standard model quantities are subsequently derived: the sum of squared elements in the first two rows of the Cabibbo–Kobayashi–Maskawa (CKM) matrix P ij jVijj 2 ¼ 1.984 0.021, the CKM element jVcsj ¼ 0.967 0.011, and the strong coupling constant at the W boson mass scale, αSðm2 WÞ ¼ 0.095 0.033