Last data update: May 13, 2024. (Total: 46773 publications since 2009)
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Query Trace: MacArthur J[original query] |
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Tropical data: Approach and methodology as applied to trachoma prevalence surveys
Harding-Esch EM , Burgert-Brucker CR , Jimenez C , Bakhtiari A , Willis R , Bejiga MD , Mpyet C , Ngondi J , Boyd S , Abdala M , Abdou A , Adamu Y , Alemayehu A , Alemayehu W , Al-Khatib T , Apadinuwe SC , Awaca N , Awoussi MS , Baayendag G , Badiane MD , Bailey RL , Batcho W , Bay Z , Bella A , Beido N , Bol YY , Bougouma C , Brady CJ , Bucumi V , Butcher R , Cakacaka R , Cama A , Camara M , Cassama E , Chaora SG , Chebbi AC , Chisambi AB , Chu B , Conteh A , Coulibaly SM , Courtright P , Dalmar A , Dat TM , Davids T , Djaker MEA , de Fátima Costa Lopes M , Dézoumbé D , Dodson S , Downs P , Eckman S , Elshafie BE , Elmezoghi M , Elvis AA , Emerson P , Epée EE , Faktaufon D , Fall M , Fassinou A , Fleming F , Flueckiger R , Gamael KK , Garae M , Garap J , Gass K , Gebru G , Gichangi MM , Giorgi E , Goépogui A , Gómez DVF , Gómez Forero DP , Gower EW , Harte A , Henry R , Honorio-Morales HA , Ilako DR , Issifou AAB , Jones E , Kabona G , Kabore M , Kadri B , Kalua K , Kanyi SK , Kebede S , Kebede F , Keenan JD , Kello AB , Khan AA , Khelifi H , Kilangalanga J , Kim SH , Ko R , Lewallen S , Lietman T , Logora MSY , Lopez YA , MacArthur C , Macleod C , Makangila F , Mariko B , Martin DL , Masika M , Massae P , Massangaie M , Matendechero HS , Mathewos T , McCullagh S , Meite A , Mendes EP , Abdi HM , Miller H , Minnih A , Mishra SK , Molefi T , Mosher A , M'Po N , Mugume F , Mukwiza R , Mwale C , Mwatha S , Mwingira U , Nash SD , Nassa C , Negussu N , Nieba C , Noah Noah JC , Nwosu CO , Olobio N , Opon R , Pavluck A , Phiri I , Rainima-Qaniuci M , Renneker KK , Saboyá-Díaz MI , Sakho F , Sanha S , Sarah V , Sarr B , Szwarcwald CL , Shah Salam A , Sharma S , Seife F , Serrano Chavez GM , Sissoko M , Sitoe HM , Sokana O , Tadesse F , Taleo F , Talero SL , Tarfani Y , Tefera A , Tekeraoi R , Tesfazion A , Traina A , Traoré L , Trujillo-Trujillo J , Tukahebwa EM , Vashist P , Wanyama EB , Warusavithana SDP , Watitu TK , West S , Win Y , Woods G , Yajima A , Yaya G , Zecarias A , Zewengiel S , Zoumanigui A , Hooper PJ , Millar T , Rotondo L , Solomon AW . Ophthalmic Epidemiol 2023 30 (6) 544-560 PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29(th) February 2016 and 24(th) April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets. |
Improving reporting standards for polygenic scores in risk prediction studies (preprint)
Wand H , Lambert SA , Tamburro C , Iacocca MA , O'Sullivan JW , Sillari C , Kullo IJ , Rowley R , Dron JS , Brockman D , Venner E , McCarthy MI , Antoniou AC , Easton DF , Hegele RA , Khera AV , Chatterjee N , Kooperberg C , Edwards K , Vlessis K , Kinnear K , Danesh JN , Parkinson H , Ramos EM , Roberts MC , Ormond KE , Khoury MJ , Janssens Acjw , Goddard KAB , Kraft P , MacArthur JAL , Inouye M , Wojcik GL . medRxiv 2020 2020.04.23.20077099 Polygenic risk scores (PRS), often aggregating the results from genome-wide association studies, can bridge the gap between the initial discovery efforts and clinical applications for disease risk estimation. However, there is remarkable heterogeneity in the reporting of these risk scores. This lack of adherence to reporting standards hinders the translation of PRS into clinical care. The ClinGen Complex Disease Working Group, in a collaboration with the Polygenic Score (PGS) Catalog, have updated the Genetic Risk Prediction (GRIPS) Reporting Statement to the current state of the field and to enable downstream utility. Drawing upon experts in epidemiology, statistics, disease-specific applications, implementation, and policy, this 22-item reporting framework defines the minimal information needed to interpret and evaluate a PRS, especially with respect to any downstream clinical applications. Items span detailed descriptions of the study population (recruitment method, key demographic and clinical characteristics, inclusion/exclusion criteria, and outcome definition), statistical methods for both PRS development and validation, and considerations for potential limitations of the published risk score and downstream clinical utility. Additionally, emphasis has been placed on data availability and transparency to facilitate reproducibility and benchmarking against other PRS, such as deposition in the publicly available PGS Catalog. By providing these criteria in a structured format that builds upon existing standards and ontologies, the use of this framework in publishing PRS will facilitate translation of PRS into clinical care and progress towards defining best practices.Summary In recent years, polygenic risk scores (PRS) have increasingly been used to capture the genome-wide liability underlying many human traits and diseases, hoping to better inform an individual’s genetic risk. However, a lack of adherence to existing reporting standards has hindered the translation of this important tool into clinical and public health practice; in particular, details necessary for benchmarking and reproducibility are underreported. To address this gap, the ClinGen Complex Disease Working Group and Polygenic Score (PGS) Catalog have updated the Genetic Risk Prediction (GRIPS) Reporting Statement into the 22-item Polygenic Risk Score Reporting Statement (PRS-RS). This framework provides the minimal information expected of authors to promote the validity, transparency, and reproducibility of PRS by encouraging authors to detail the study population, statistical methods, and potential clinical utility of a published score. The widespread adoption of this framework will encourage rigorous methodological consideration and facilitate benchmarking to ensure high quality scores are translated into the clinic.Competing Interest StatementMIM is on the advisory panels Pfizer, Novo Nordisk, and Zoe Global; Honoraria: Merck, Pfizer, Novo Nordisk, and Eli Lilly; Research funding: Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Pfizer, Roche, Sanofi Aventis, Servier & Takeda. As of June 2019, he is an employee of Genentech with stock and stock options in Roche. No other authors have competing interests to declare.Funding StatementClinGen is primarily funded by the National Human Genome Research Institute (NHGRI), through the following three grants: U41HG006834, U41HG009649, U41HG009650. ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the following three grants: U24HD093483, U24HD093486, U24HD093487. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additionally, the views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Research reported in this publication was supported by the National Human Genome Research Institute of the National Institutes of Health under Award Number U41HG007823 (EBI-NHGRI GWAS Catalog, PGS Catalog). In addition, we acknowledge funding from the European Molecular Biology Laboratory. Individuals were funded from the following sources: MIM was a Wellcome Investigator and an NIHR Senior Investigator with funding from NIDDK (U01-DK105535); Wellcome (090532, 098381, 106130, 203141, 212259). MI, SAL, and JD were supported by core funding from: the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). SAL is supported by a Canadian Institutes of Health Research postdoctoral fellowship (MFE-171279). JD holds a British Heart Foundation Personal Chair and a National Institute for Health Research Senior Investigator Award. This work was also supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:N/AAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesN/A |
Public health emergency operations center operations and coordination among Thailand, Cambodia, Lao PDR, and Malaysia during the COVID-19 pandemic
Tsukayama R , Wodniak N , Hinjoy S , Bunthi C , Akarasewi P , Jiaranairungroj W , Pueyo W , Masunglong W , Kleblumjeak P , MacArthur JR , Bloss E . Glob Secur 2023 8 (1) 1-14 Public Health Emergency Operations Centers (PHEOCs) are the critical units to lead communications, information sharing, and resource mobilisation during national and international health emergencies, and are key components for maintaining global health security. This assessment sought to examine the coordination mechanisms between national and sub-national PHEOCs in Thailand, Cambodia, Lao People’s Democratic Republic, and Malaysia (TCLM countries) during the COVID-19 pandemic. Information was collected on PHEOC structures, functions, and cross-border communications in three stages: a literature review of national PHEOC and emergency preparedness capacities; questionnaire responses from stakeholders to describe PHEOC activity at the national level; and meetings with emergency response staff in five border provinces of Thailand to assess communications between sub-national PHEOCs across country borders. The findings showed that each of the countries has demonstrated a commitment to strengthening their national PHEOCs and improving cross-border communication in the face of the COVID-19 pandemic. Strong existing relationships between TCLM countries assisted in activating a coordinated pandemic response, but gaps remain in efficient data sharing, workforce capacity, and the utilisation of consistent communication platforms among countries. Lessons learned from the pandemic can be used to further strengthen countries’ preparedness for future health emergencies, in line with International Health Regulations (2005) and regional plans to build health security in the Southeast Asia region. This assessment provides TCLM countries with the opportunity to address weaknesses in national and international PHEOC capacities. It may be used alongside existing guidelines to prepare the region for a stronger response to future global and regional health emergencies. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. |
Towards comprehensive understanding of bacterial genetic diversity: large-scale amplifications in Bordetella pertussis and Mycobacterium tuberculosis.
Abrahams JS , Weigand MR , Ring N , MacArthur I , Etty J , Peng S , Williams MM , Bready B , Catalano AP , Davis JR , Kaiser MD , Oliver JS , Sage JM , Bagby S , Tondella ML , Gorringe AR , Preston A . Microb Genom 2022 8 (2) Bacterial genetic diversity is often described solely using base-pair changes despite a wide variety of other mutation types likely being major contributors. Tandem duplication/amplifications are thought to be widespread among bacteria but due to their often-intractable size and instability, comprehensive studies of these mutations are rare. We define a methodology to investigate amplifications in bacterial genomes based on read depth of genome sequence data as a proxy for copy number. We demonstrate the approach with Bordetella pertussis, whose insertion sequence element-rich genome provides extensive scope for amplifications to occur. Analysis of data for 2430 B. pertussis isolates identified 272 putative amplifications, of which 94 % were located at 11 hotspot loci. We demonstrate limited phylogenetic connection for the occurrence of amplifications, suggesting unstable and sporadic characteristics. Genome instability was further described in vitro using long-read sequencing via the Nanopore platform, which revealed that clonally derived laboratory cultures produced heterogenous populations rapidly. We extended this research to analyse a population of 1000 isolates of another important pathogen, Mycobacterium tuberculosis. We found 590 amplifications in M. tuberculosis, and like B. pertussis, these occurred primarily at hotspots. Genes amplified in B. pertussis include those involved in motility and respiration, whilst in M. tuberuclosis, functions included intracellular growth and regulation of virulence. Using publicly available short-read data we predicted previously unrecognized, large amplifications in B. pertussis and M. tuberculosis. This reveals the unrecognized and dynamic genetic diversity of B. pertussis and M. tuberculosis, highlighting the need for a more holistic understanding of bacterial genetics. |
Frequency of early intervention sessions and vocabulary skills in children with hearing loss
Wiggin M , Sedey AL , Yoshinaga-Itano C , Mason CA , Gaffney M , Chung W . J Clin Med 2021 10 (21) Background: A primary goal of early intervention is to assist children in achieving age-appropriate language skills. The amount of intervention a child receives is ideally based on his or her individual needs, yet it is unclear if language ability impacts amount of intervention and/or if an increased frequency of intervention sessions results in better outcomes. The purpose of this study was to determine the relationship between the frequency of early intervention sessions and vocabulary outcomes in young children with hearing loss. Methods: This was a longitudinal study of 210 children 9 to 36 months of age with bilateral hearing loss living in 12 different states. Expressive vocabulary skills were evaluated using the MacArthur–Bates Communicative Development Inven-tories. Results: A higher number of intervention sessions reported at the first assessment predicted better vocabulary scores at the second assessment, and more sessions reported at the second assessment predicted better scores at the third assessment. For each increase in the number of sessions reported, there was a corresponding, positive increase in vocabulary quotient. In contrast, children’s vocabulary ability at an earlier time point did not predict intervention session frequency at a later point in time. Conclusions: A significant prospective effect was apparent with more therapy sessions resulting in improved vocabulary scores 9 months later. These findings underscore the importance of early intervention. Pediatricians and other health care professionals can help apply these findings by counseling parents regarding the value of frequent and consistent participation in early inter-vention. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
Improving reporting standards for polygenic scores in risk prediction studies.
Wand H , Lambert SA , Tamburro C , Iacocca MA , O'Sullivan JW , Sillari C , Kullo IJ , Rowley R , Dron JS , Brockman D , Venner E , McCarthy MI , Antoniou AC , Easton DF , Hegele RA , Khera AV , Chatterjee N , Kooperberg C , Edwards K , Vlessis K , Kinnear K , Danesh JN , Parkinson H , Ramos EM , Roberts MC , Ormond KE , Khoury MJ , Janssens Acjw , Goddard KAB , Kraft P , MacArthur JAL , Inouye M , Wojcik GL . Nature 2021 591 (7849) 211-219 Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice. |
Clinical Characteristics of Patients Hospitalized with Coronavirus Disease, Thailand.
Pongpirul WA , Mott JA , Woodring JV , Uyeki TM , MacArthur JR , Vachiraphan A , Suwanvattana P , Uttayamakul S , Chunsuttiwat S , Chotpitayasunondh T , Pongpirul K , Prasithsirikul W . Emerg Infect Dis 2020 26 (7) 1580-1585 Among 11 patients in Thailand infected with severe acute respiratory syndrome coronavirus 2, we detected viral RNA in upper respiratory specimens a median of 14 days after illness onset and 9 days after fever resolution. We identified viral co-infections and an asymptomatic person with detectable virus RNA in serial tests. We describe implications for surveillance. |
Insular microbiogeography: Three pathogens as exemplars
Kaufman JH , Elkins CA , Davis M , Weis AM , Huang BC , Mammel MK , Patel IR , Beck KL , Edlund S , Chambliss D , Douglas J , Bianco S , Kunitomi M , Weimer BC . Curr Issues Mol Biol 2019 36 89-108 Traditional taxonomy in biology assumes that life is organized in a simple tree. Attempts to classify microorganisms in this way in the genomics era led microbiologists to look for finite sets of 'core' genes that uniquely group taxa as clades in the tree. However, the diversity revealed by large-scale whole genome sequencing is calling into question the long-held model of a hierarchical tree of life, which leads to questioning of the definition of a species. Large-scale studies of microbial genome diversity reveal that the cumulative number of new genes discovered increases with the number of genomes studied as a power law and subsequently leads to the lack of evidence for a unique core genome within closely related organisms. Sampling 'enough' new genomes leads to the discovery of a replacement or alternative to any gene. This power law behaviour points to an underlying self-organizing critical process that may be guided by mutation and niche selection. Microbes in any particular niche exist within a local web of organism interdependence known as the microbiome. The same mechanism that underpins the macro-ecological scaling first observed by MacArthur and Wilson also applies to microbial communities. Recent metagenomic studies of a food microbiome demonstrate the diverse distribution of community members, but also genotypes for a single species within a more complex community. Collectively, these results suggest that traditional taxonomic classification of bacteria could be replaced with a quasispecies model. This model is commonly accepted in virology and better describes the diversity and dynamic exchange of genes that also hold true for bacteria. This model will enable microbiologists to conduct population-scale studies to describe microbial behaviour, as opposed to a single isolate as a representative. |
Prenatal exposure to organochlorine pesticides and early childhood communication development in British girls
Jeddy Z , Kordas K , Allen K , Taylor EV , Northstone K , Dana Flanders W , Namulanda G , Sjodin A , Hartman TJ . Neurotoxicology 2018 69 121-129 BACKGROUND: The developing brain is susceptible to exposure to neurodevelopmental toxicants such as pesticides. AIMS: We explored associations of prenatal serum concentrations of hexachlorobenzene (HCB), beta-Hexachlorocyclohexane (beta-HCH), 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) and 2,2-Bis(4-chlorophenyl-1,1,1-trichloroethane (p,p'-DDT) with maternal-reported measures of verbal and non-verbal communication in young girls. STUDY DESIGN AND METHODS: We studied a sample of 400 singleton girls and their mothers participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) using multivariable linear regression models adjusting for parity, Home Observation Measurement of the Environment (HOME) score, maternal age and education status, and maternal tobacco use during the first trimester of pregnancy. EXPOSURE AND OUTCOME MEASURES: Maternal serum samples (collected at median 15 wks. gestation [IQR 10, 28]) were assessed for selected organochlorine pesticide levels. Communication was assessed at 15 and 38 months, using adapted versions of the MacArthur Bates Communicative Development Inventories for Infants and Toddlers (MCDI). RESULTS: At 15 months, girls born to mothers with prenatal concentrations of HCB in the highest tertile had vocabulary comprehension and production scores approximately 16% (p = 0.007) lower than girls born to mothers with concentrations in the lowest tertile. This association varied by maternal parity in that the evidence was stronger for daughters of nulliparous mothers. At 38 months, girls born to mothers with prenatal concentrations of HCB in the highest tertile had mean adjusted intelligibility scores that were 3% (p = 0.03) lower than those born to mothers with concentrations in the lowest tertile; however, results did not vary significantly by parity. Maternal concentrations of beta-HCH and p,p'-DDE were not significantly associated with MCDI scores at 15 or 36 months. p,p'-DDT had an inconsistent pattern of association; a significant positive association was observed between p,p'-DDT with verbal comprehension scores at 15 months; however, at 38 months a significant inverse association was observed for p,p'-DDT with communicative scores. This inverse association for p,p'-DDT among older girls tended to be stronger among daughters of mothers who had lower depression scores. CONCLUSIONS: Organochlorine pesticide exposure in utero may affect communication development. |
Hospitalized bacteremic melioidosis in rural Thailand; 2009-2013
Jatapai A , Gregory CJ , Thamthitiwat S , Tanwisaid K , Bhengsri S , Baggett HC , Sangwichian O , Jorakate P , MacArthur JR . Am J Trop Med Hyg 2018 98 (6) 1585-1591 Melioidosis incidence and mortality have reportedly been increasing in endemic areas of Thailand, but little population-based data on culture-confirmed Burkholderia pseudomallei infections exist. We provide updated estimates of melioidosis bacteremia incidence and in-hospital mortality rate using integration of two population-based surveillance databases in Nakhon Phanom, Thailand, since automated blood culture became available in 2005. From 2009 to 2013, 564 hospitalized bacteremic melioidosis patients were identified. The annual incidence of bacteremic melioidosis ranged from 14 to 17 per 100,000 persons, and average population mortality rate was 2 per 100,000 persons per year. In-hospital mortality rate declined nonsignificantly from 15% (15/102) to 13% (15/118). Of 313 (56%) bacteremic melioidosis patients who met criteria for acute lower respiratory infection and were included in the hospital-based pneumonia surveillance system, 65% (202/313) had a chest radiograph performed within 48 hours of admission; 46% (92/202) showed radiographic evidence of pneumonia. Annual incidence of bacteremic melioidosis with pneumonia was 2.4 per 100,000 persons (95% confidence intervals; 1.9-2.9). In-hospital death was more likely among bacteremic melioidosis patients with pneumonia (34%; 20/59) compared with non-pneumonia patients (18%; 59/321) (P-value = 0.007). The overall mortality could have been as high as 46% (257/564) if patients with poor clinical condition at the time of discharge had died. The continued high incidence of bacteremic melioidosis, pneumonia, and deaths in an endemic area highlights the need for early diagnosis and treatment and additional interventions for the prevention and control for melioidosis. |
The emergence and spread of kelch 13 mutations associated with artemisinin resistance in Plasmodium falciparum parasites in twelve Thai provinces from 2007 - 2016.
Kobasa T , Talundzic E , Sug-Aram R , Boondat P , Goldman IF , Lucchi NW , Dharmarak P , Sintasath D , Fukuda M , Whistler T , MacArthur J , Udhayakumar V , Prempree P , Chinanonwait N . Antimicrob Agents Chemother 2018 62 (4) Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated Plasmodium falciparum (Pf) malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS), which manifest as slow parasite clearance in patients and reduced ring-stage susceptibility to artemisinins in survival assays. The Pf kelch 13 gene mutations associated with artemisinin resistant parasites are now wide-spread in the GMS. We genotyped 277 samples collected during an observational study from 2012-2016 from eight provinces in Thailand to identify Pf kelch 13 mutations. The results were combined with previously reported genotyping results from Thailand to construct a map illustrating the evolution of Pf kelch 13 mutations from 2007 - 2016 in the country. Different mutant alleles were found in strains with different geographical origins. The artemisinin resistant Y493H and R539T mutations were detected mainly in eastern Thailand (bordering Cambodia), while P574L was only found in western Thailand and R561H in northwestern Thailand. The C580Y mutation was found across the entire country and was nearing fixation along the Thai-Cambodia border. Overall the prevalence of artemisinin resistant mutations increased over the last ten years across Thailand, especially along the Thai-Cambodia border. Molecular surveillance and therapeutic efficacy monitoring should be intensified in the region to further assess the extent and spread of artemisinin resistance. |
Prenatal concentrations of perfluoroalkyl substances and early communication development in British girls
Jeddy Z , Hartman TJ , Taylor EV , Poteete C , Kordas K . Early Hum Dev 2017 109 15-20 Perfluoroalkyl substances (PFAS), found in many household products and classed as endocrine disrupting chemicals, can be transferred through the placenta and are associated with multiple developmental deficits in offspring. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the association between intrauterine exposure to PFAS and early communication development in 432 mother-daughter dyads at 15 and 38months of age. Concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) were measured in maternal serum collected during pregnancy. Early communication development was measured with the ALSPAC-adapted MacArthur Communicative Development Inventories for Infants and Toddlers. The infant questionnaire measured verbal comprehension, vocabulary comprehension and production, nonverbal communication, and social development. The toddler questionnaire measured language, intelligibility, and communicative sub-scores. Multivariable linear regression was used to examine associations between each PFAS exposure and each communication sub-scale score. The association between maternal PFAS concentrations and early communication development at 15 and 38months of age varied by maternal age at delivery. In daughters of younger mothers (<25years of age), every 1ng/mL of PFOS was associated with a 3.82 point (95% confidence interval (CI): -6.18, -1.47) lower vocabulary score at 15months and a 0.80 point (95% CI: -1.74, 0.14) lower language score at 38months. Prenatal exposure to select PFAS was positively and negatively associated with communication development among girls, with inconsistent pattern of association across all measured PFAS and endpoints. |
Using respondent driven sampling to identify malaria risks and occupational networks among migrant workers in Ranong, Thailand
Wangroongsarb P , Hwang J , Thwing J , Karuchit S , Kumpetch S , Rand A , Drakeley C , MacArthur JR , Kachur SP , Satimai W , Meek S , Sintasath DM . PLoS One 2016 11 (12) e0168371 BACKGROUND: Ranong Province in southern Thailand is one of the primary entry points for migrants entering Thailand from Myanmar, and borders Kawthaung Township in Myanmar where artemisinin resistance in malaria parasites has been detected. Areas of high population movement could increase the risk of spread of artemisinin resistance in this region and beyond. METHODS: A respondent-driven sampling (RDS) methodology was used to compare migrant populations coming from Myanmar in urban (Site 1) vs. rural (Site 2) settings in Ranong, Thailand. The RDS methodology collected information on knowledge, attitudes, and practices for malaria, travel and occupational histories, as well as social network size and structure. Individuals enrolled were screened for malaria by microscopy, Real Time-PCR, and serology. RESULTS: A total of 619 participants were recruited in Ranong City and 623 participants in Kraburi, a rural sub-district. By PCR, a total of 14 (1.1%) samples were positive (2 P. falciparum in Site 1; 10 P. vivax, 1 Pf, and 1 P. malariae in Site 2). PCR analysis demonstrated an overall weighted prevalence of 0.5% (95% CI, 0-1.3%) in the urban site and 1.0% (95% CI, 0.5-1.7%) in the rural site for all parasite species. PCR positivity did not correlate with serological positivity; however, as expected there was a strong association between antibody prevalence and both age and exposure. Access to long-lasting insecticidal treated nets remains low despite relatively high reported traditional net use among these populations. CONCLUSIONS: The low malaria prevalence, relatively smaller networks among migrants in rural settings, and limited frequency of travel to and from other areas of malaria transmission in Myanmar, suggest that the risk for the spread of artemisinin resistance from this area may be limited in these networks currently but may have implications for regional malaria elimination efforts. |
Reply to "No robust evidence of lumefantrine resistance"
Plucinski MM , Talundzic E , Morton L , Dimbu PR , Macaia AP , Fortes F , Goldman I , Lucchi N , Stennies G , MacArthur JR , Udhayakumar V . Antimicrob Agents Chemother 2015 59 (9) 5867-8 Results from regular drug efficacy monitoring should always be interpreted in the context of the many limitations inherent to attributing apparent treatment failures to antimalarial resistance, as concisely summarized by Hamed and Kuhen (1). Notably, in study settings where direct supervision of the evening doses of artemether-lumefantrine (AL) is operationally infeasible or culturally unacceptable, low efficacy can also potentially be attributed to inaccurate dosing or underdosing. Details of how we strived to guarantee participant compliance with evening doses in lieu of direct supervision are found in our original report (2). Importantly, procedures were identical in both provinces, and we have no indication that participant adherence to the evening doses or food consumption guidelines was different in Zaire Province, where we found lower efficacy of AL. While lack of direct observation of doses and nonadherence to guidelines regarding food consumption with drug administration have been shown to be associated with lower blood lumefantrine levels, they have not been directly associated with decreased efficacy of AL (3, 4). | | While in vitro susceptibility testing requires infrastructure rarely found at drug efficacy monitoring sites, there is a long history of complementing clinical outcome data with testing for known molecular markers of resistance (5). Samples from treatment failures with mutations associated with resistance provide more evidence of resistance than clinical outcome data alone. In our study, the detection of pfmdr1 haplotypes previously associated with decreased sensitivity to lumefantrine (6) and the absence of mutations associated with artemisinin resistance in AL treatment failures support the hypothesis of lumefantrine resistance. | | Notably, the NFD and NYD pfmdr1 haplotypes predominated not only in recrudescent infections but also in reinfections in the AL arms. Contrary to Hamed and Kuhen's assertion, reinfections observed during follow-up do provide important data on efficacy. For the calculation of uncorrected efficacy, an important outcome for therapeutic efficacy studies, both reinfections and recrudescences are considered treatment failures. The reporting and interpretation of uncorrected efficacy results are standard components of drug efficacy monitoring for two primary reasons (7,–9). First, uncorrected efficacy estimates are not subject to the limitations and potential biases of using genotyping data to differentiate reinfection from recrudescence. Second, uncorrected efficacy results provide data concerning the posttreatment prophylactic effect of the partner drug in artemisinin-based combination therapies and thus the proportion of clients that will require retreatment, data of increasing interest to malaria control programs. The reinfection rates in the AL arms in Zaire and Uíge Provinces provide a good example of the potential utility of reinfection rates. The reinfection rate in Zaire (13%) was measured as more than twice the rate in Uíge (5.1%). This was despite our screening data, where 67% of the children screened tested positive for malaria in Uíge, compared to 53% in Zaire, indicating that transmission was almost certainly higher in Uíge at the time of our study. This unexpectedly high rate of reinfection in Zaire could therefore point to a parasite population that is less sensitive to lumefantrine and that consequently has a higher likelihood of successfully invading patients with subtherapeutic doses of lumefantrine following AL treatment (10). | | Finally, we would like to reaffirm that while certain screened children had parasitemia levels above 100,000 parasites/μl, only children with parasitemia levels between 2,000 and 100,000 parasites/μl were enrolled in the study, as described in Materials and Methods. Given that no children with parasitemia levels above 100,000 parasites/μl were enrolled in any of the study arms at either site, differences in hyperparasitemia rates between the Uíge and Zaire AL arms cannot explain the difference in efficacy as Hamed and Kuhen suggest. |
The Global Trachoma Mapping Project: methodology of a 34-country population-based study
Solomon AW , Pavluck AL , Courtright P , Aboe A , Adamu L , Alemayehu W , Alemu M , Alexander ND , Kello AB , Bero B , Brooker SJ , Chu BK , Dejene M , Emerson PM , Flueckiger RM , Gadisa S , Gass K , Gebre T , Habtamu Z , Harvey E , Haslam D , King JD , Mesurier RL , Lewallen S , Lietman TM , MacArthur C , Mariotti SP , Massey A , Mathieu E , Mekasha A , Millar T , Mpyet C , Muñoz BE , Ngondi J , Ogden S , Pearce J , Sarah V , Sisay A , Smith JL , Taylor HR , Thomson J , West SK , Willis R , Bush S , Haddad D , Foster A . Ophthalmic Epidemiol 2015 22 (3) 214-25 PURPOSE: To complete the baseline trachoma map worldwide by conducting population-based surveys in an estimated 1238 suspected endemic districts of 34 countries. METHODS: A series of national and sub-national projects owned, managed and staffed by ministries of health, conduct house-to-house cluster random sample surveys in evaluation units, which generally correspond to "health district" size: populations of 100,000-250,000 people. In each evaluation unit, we invite all residents aged 1 year and older from h households in each of c clusters to be examined for clinical signs of trachoma, where h is the number of households that can be seen by 1 team in 1 day, and the product h x c is calculated to facilitate recruitment of 1019 children aged 1-9 years. In addition to individual-level demographic and clinical data, household-level water, sanitation and hygiene data are entered into the purpose-built LINKS application on Android smartphones, transmitted to the Cloud, and cleaned, analyzed and ministry-of-health-approved via a secure web-based portal. The main outcome measures are the evaluation unit-level prevalence of follicular trachoma in children aged 1-9 years, prevalence of trachomatous trichiasis in adults aged 15 + years, percentage of households using safe methods for disposal of human feces, and percentage of households with proximate access to water for personal hygiene purposes. RESULTS: In the first year of fieldwork, 347 field teams commenced work in 21 projects in 7 countries. CONCLUSION: With an approach that is innovative in design and scale, we aim to complete baseline mapping of trachoma throughout the world in 2015. |
Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria in children in Zaire and Uige provinces, Angola
Plucinski MM , Talundzic E , Morton L , Dimbu PR , Macaia AP , Fortes F , Goldman I , Lucchi N , Stennies G , MacArthur JR , Udhayakumar V . Antimicrob Agents Chemother 2014 59 (1) 437-43 The development of resistance to antimalarials is a major challenge for global malaria control. Artemisinin-based combination therapies, the newest class of antimalarials, are used worldwide but there have been reports of artemisinin resistance in Southeast Asia. In February-May 2013, we conducted open-label, nonrandomized therapeutic efficacy studies of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in Zaire and Uige Provinces in northern Angola. The parasitological and clinical responses to treatment in children with uncomplicated P. falciparum monoinfection were measured over 28 days and the main outcome was PCR-corrected adequate clinical and parasitological response (ACPR) proportion on day 28. Parasites from treatment failures were analyzed for the presence of putative molecular markers of resistance to lumefantrine and artemisinins, including the recently identified mutations in the K13-propeller gene. In the 320 children finishing the study, 25 treatment failures were observed, 24 in the AL arms and one in the DP arm. The PCR-corrected ACPR proportion on day 28 for AL was 88% (95% CI: 78-95) in Zaire and 97% (91-100) in Uige. For DP, it was 100% (95-100) in Zaire, and 100% (96-100) in Uige. None of the treatment failures had molecular evidence of artemisinin resistance. In contrast, 91% of AL treatment failures had markers associated with lumefantrine resistance on day of failure. The absence of molecular markers for artemisinin resistance and the observed efficacies of both drug combinations suggest no evidence of artemisinin resistance in northern Angola. There is evidence of increased lumefantrine resistance in Zaire, which should continue to be monitored. |
The challenge of artemisinin resistance can only be met by eliminating Plasmodium falciparum malaria across the Greater Mekong subregion
Smith Gueye C , Newby G , Hwang J , Phillips AA , Whittaker M , MacArthur JR , Gosling RD , Feachem RG . Malar J 2014 13 286 Artemisinin-based combinations are currently the most effective anti-malarials and, in addition to vector control, have led to significant declines in malaria morbidity and mortality. However, foci of artemisinin drug resistance have been identified in the Greater Mekong subregion (GMS) of the Asia Pacific, threatening the major gains made in malaria control and potentially creating a parasite pool that is more difficult to treat and eliminate. Efforts are underway to halt the spread of artemisinin resistance, including coordination of activities and funding, and identification of areas of suspected artemisinin resistance, now using a newly identified molecular marker. However, targeting resources to the containment of resistant parasites is likely inefficient and monitoring impact is challenging. A more sustainable solution is the rapid elimination of all Plasmodium falciparum parasites from the GMS. This strategy is more efficient for several reasons. First, a subregional strategy is in line with current commitment to elimination and will build upon the existing national political support for elimination as well as enhancing collaboration among countries. Second, the challenge of human mobility in the GMS is subregional in scope and requires a harmonized elimination strategy. Third, countries will need to improve and intensify malaria operations to reach elimination, and this will be a singular goal across the subregion. Rallying around the goal of P. falciparum elimination will not only utilize existing regional bodies to catalyze political and funding support, but will also leverage the funding already in place to achieve this subregional goal. |
Adverse drug events resulting from use of drugs with sulphonamide-containing anti-malarials and artemisinin-based ingredients: findings on incidence and household costs from three districts with routine demographic surveillance systems in rural Tanzania
Njau JD , Kabanywanyi AM , Goodman CA , MacArthur JR , Kapella BK , Gimnig JE , Kahigwa E , Bloland PB , Abdulla SM , Kachur SP . Malar J 2013 12 (1) 236 BACKGROUND: Anti-malarial regimens containing sulphonamide or artemisinin ingredients are widely used in malaria-endemic countries. However, evidence of the incidence of adverse drug reactions (ADR) to these drugs is limited, especially in Africa, and there is a complete absence of information on the economic burden such ADR place on patients. This study aimed to document ADR incidence and associated household costs in three high malaria transmission districts in rural Tanzania covered by demographic surveillance systems. METHODS: Active and passive surveillance methods were used to identify ADR from sulphadoxine-pyrimethamine (SP) and artemisinin (AS) use. ADR were identified by trained clinicians at health facilities (passive surveillance) and through cross-sectional household surveys (active surveillance). Potential cases were followed up at home, where a complete history and physical examination was undertaken, and household cost data collected. Patients were classified as having 'possible' or 'probable' ADR by a physician. RESULTS: A total of 95 suspected ADR were identified during a two-year period, of which 79 were traced, and 67 reported use of SP and/or AS prior to ADR onset. Thirty-four cases were classified as 'probable' and 33 as 'possible' ADRs. Most (53) cases were associated with SP monotherapy, 13 with the AS/SP combination (available in one of the two areas only), and one with AS monotherapy. Annual ADR incidence per 100,000 exposures was estimated based on 'probable' ADR only at 5.6 for AS/SP in combination, and 25.0 and 11.6 for SP monotherapy. Median ADR treatment costs per episode ranged from US$2.23 for those making a single provider visit to US$146.93 for patients with four visits. Seventy-three per cent of patients used out-of-pocket funds or sold part of their farm harvests to pay for treatment, and 19% borrowed money. CONCLUSION: Both passive and active surveillance methods proved feasible methods for anti-malarial ADR surveillance, with active surveillance being an important complement to facility-based surveillance, given the widespread practice of self-medication. Household costs associated with ADR treatment were high and potentially catastrophic. Efforts should be made to both improve pharmacovigilance across Africa and to identify strategies to reduce the economic burden endured by households suffering from ADR. |
Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: systematic review and meta-analysis
Kayentao K , Garner P , van Eijk AM , Naidoo I , Roper C , Mulokozi A , MacArthur JR , Luntamo M , Ashorn P , Doumbo OK , ter Kuile FO . JAMA 2013 309 (6) 594-604 IMPORTANCE: Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain. OBJECTIVE: To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for intermittent preventive therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) (<2500 g) than standard 2-dose regimens. DATA SOURCES AND STUDY SELECTION: ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine monotherapy. DATA EXTRACTION: Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models. RESULTS: Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722-3239 g) and on average 56 g higher (95% CI, 29-83 g; I2 = 0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR, 0.80; 95% CI, 0.69-0.94; I 2 = 0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10-52]; number needed to treat = 31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had less placental malaria (RR, 0.51; 95% CI, 0.38-0.68; I 2 = 0%, in 6 trials, 63 vs 32 per 1000; absolute risk reduction, 31 per 1000 [95% CI, 20-39]). In primigravid plus secundigravid women, the risk of moderate to severe maternal anemia was lower in the ≥3-dose group (RR, 0.60; 95% CI, 0.36-0.99; I2 = 20%; in 6 trials, 36 vs 22 per 1000; absolute risk reduction, 14 per 1000 [95% CI, 0.4-23]). There were no differences in rates of serious adverse events. CONCLUSIONS AND RELEVANCE: Among pregnant women in sub-Saharan Africa, intermittent preventive therapy with 3 or more doses of sulfadoxine-pyrimethamine was associated with a higher birth weight and lower risk of LBW than the standard 2-dose regimens. These data provide support for the new WHO recommendations to provide at least 3 doses of intermittent preventive therapy during pregnancy at each scheduled antenatal care visit in the second and third trimester. |
New global estimates of malaria deaths
Lynch M , Korenromp E , Eisele T , Newby H , Steketee R , Kachur SP , Nahlen B , Yoon S , MacArthur J , Newman R , Cibulskis R . Lancet 2012 380 (9841) 559 Christopher Murray and colleagues' paper (Feb 4, p 413)1 estimating the number of malaria deaths worldwide, 1980–2010, invites caution in its interpretation. Murray and colleagues estimate that there were 1 238 000 malaria deaths worldwide in 2010, compared with WHO's estimate of 655 000.2 However, wide uncertainty ranges accompany both the Murray and colleagues and WHO estimates, and with one exception—for deaths in people older than 5 years in Africa—these ranges overlap, so the estimates cannot be regarded as significantly different (figure). |
Immunogenicity of hepatitis B vaccine among hemodialysis patients: effect of revaccination of non-responders and duration of protection
Chaves SS , Daniels D , Cooper BW , Malo-Schlegel S , Macarthur S , Robbins KC , Kobetitsch JF , McDaniel A , D'Avella JF , Alter MJ . Vaccine 2011 29 (52) 9618-23 BACKGROUND: Hepatitis B vaccination is recommended for patients on hemodialysis, however, seroprotection after a primary vaccine series is suboptimum. Limited data are available on the effect of revaccination of non-responders and on persistence of immunity in this population. METHODS: Hepatitis B vaccine (40mcg/dose) was given to 77 susceptible patients on hemodialysis (0, 1, and 6 month schedule). Levels of hepatitis B surface antibody (anti-HBs) were tested ≥28 days after the third dose was administered, and non-responders revaccinated with an additional 3-dose series. Vaccine responders (anti-HBs ≥10mIU/mL) were re-tested every 6 months and booster doses given as needed. Kaplan-Meier survival curve was used to estimate the probability of maintaining protective antibody level. Cox-proportional hazards models were used to assess the association between time to loss of protective antibody levels and certain explanatory variables. RESULTS: Overall primary vaccine-induced response was 79.2% (95% CI 68.2%, 87.3%), including 49/77 (63.6%; 95% CI 51.8%, 74.7%) patients who received the initial primary hepatitis B vaccine series and 12/21 (57.1%; 95% CI 34.4%, 77.4%) non-responders who were revaccinated with an additional series. Among weak responders (anti-HBs level 10.0-99.9mIU/mL), protective antibody levels persisted in 44% for 12 months post-vaccination; whereas among strong responders (anti-HBs level ≥100mIU/mL), protective antibody levels persisted in 92% for 12 months, and 68% for 24 months post-vaccination. A weak post-vaccination response increased the risk of losing protective antibody levels (adjusted hazard ratio, 9.7; 95% confidence interval, 3.5-28.5; p<0.0001). CONCLUSION: Revaccinating patients undergoing hemodialysis who do not respond to a primary vaccine series substantially increases the pool of protected patients. The threshold for defining hepatitis B vaccine-induced immunity should be revisited in this patient population to maximize the duration of protection. |
The threat of artemisinin-resistant malaria
Dondorp AM , Fairhurst RM , Slutsker L , Macarthur JR , M DJg , Guerin PJ , Wellems TE , Ringwald P , Newman RD , Plowe CV . N Engl J Med 2011 365 (12) 1073-5 In the 1970s, Chinese government scientists working on a secret “Project 523” developed a new class of potent antimalarial drugs, the artemisinins or qinghaosu derivatives. In mostly unpublished work that has just been recognized by a 2011 Lasker Award to Tu Youyou, researchers in China isolated the active compounds from the plant Artemisia annua, tested them in mice, analyzed the chemical structure of the artemisinins, and demonstrated their high potency and rapid efficacy in human trials. Although they were widely used in China during the 1980s, only in the 1990s did the artemisinins come to wider global attention in the form of artemisinin-based combination therapies. Over the past decade, these highly efficacious treatments, along with other malaria-control measures, have contributed to significant reductions of the malaria burden in many areas of the world, including parts of Africa. | Together, these successes and increased funding have revived the bold aspiration to eradicate malaria. About one quarter of malaria-afflicted countries are already shifting their focus from malaria control to elimination. Past successful malaria-elimination schemes have all depended on reliable curative drugs, used in conjunction with vector-control methods. Similarly, current elimination plans rely on the long-term availability of effective antimalarial drugs — a requirement that is pivotally dependent on the efficacy of artemisinins. The artemisinin derivative artesunate has also proven to be the best drug against severe falciparum malaria. Losing the artemisinins to resistance would be a disaster for the control and treatment of malaria and would bring eradication efforts to a standstill. |
Extensive drug resistance in malaria and tuberculosis
Wongsrichanalai C , Varma JK , Juliano JJ , Kimerling ME , Macarthur JR . Emerg Infect Dis 2010 16 (7) 1063-7 Drug resistance in malaria and in tuberculosis (TB) are major global health problems. Although the terms multidrug-resistant TB and extensively drug-resistant TB are precisely defined, the term multidrug resistance is often loosely used when discussing malaria. Recent declines in the clinical effectiveness of antimalarial drugs, including artemisinin-based combination therapy, have prompted the need to revise the definitions of and/or to recategorize antimalarial drug resistance to include extensively drug-resistant malaria. Applying precise case definitions to different levels of drug resistance in malaria and TB is useful for individual patient care and for public health. |
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