2020
Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden
Qing T, Mohsen H, Marczyk M, Ye Y, O’Meara T, Zhao H, Townsend JP, Gerstein M, Hatzis C, Kluger Y, Pusztai L. Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden. Nature Communications 2020, 11: 2438. PMID: 32415133, PMCID: PMC7228928, DOI: 10.1038/s41467-020-16293-7.Peer-Reviewed Original ResearchConceptsAge groupsGermline variantsSomatic mutationsLate-onset cancerEarly-onset cancersCancer hallmark genesSomatic mutation burdenMutation burdenMalignant transformationCancer genesYounger ageGermline alterationsCancerVariant burdenBurdenAverage numberHallmark genesAgeNegative correlationStrong negative correlationMutationsPatientsGroup
2019
Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma
Lu L, Gaffney SG, Cannataro VL, Townsend J. Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma. Oral Oncology 2019, 101: 104554. PMID: 31887619, PMCID: PMC7273869, DOI: 10.1016/j.oraloncology.2019.104554.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkersFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateLymphocyte ActivationMaleMethyltransferasesMiddle AgedNeoplasm GradingNeoplasm StagingPrognosisProportional Hazards ModelsSquamous Cell Carcinoma of Head and NeckT-LymphocytesYoung AdultConceptsT cell activation scoreT cell activation statusAdjusted hazard ratioPatient survivalHPV statusHazard ratioActivation statusActivation scoresKaplan-Meier survival curvesImmune checkpoint blockadeCox regression modelNeck squamous carcinomaPotential therapeutic targetT cell activationHNSCC patientsSquamous carcinomaPatient mortalityLonger survivalExhaustion groupsTherapeutic targetSurvival curvesSignificant associationMRNA expressionPatientsSurvival
2018
Potential effectiveness of long-acting injectable pre-exposure prophylaxis for HIV prevention in men who have sex with men: a modelling study
Marshall BDL, Goedel WC, King MRF, Singleton A, Durham DP, Chan PA, Townsend JP, Galvani AP. Potential effectiveness of long-acting injectable pre-exposure prophylaxis for HIV prevention in men who have sex with men: a modelling study. The Lancet HIV 2018, 5: e498-e505. PMID: 29908917, PMCID: PMC6138558, DOI: 10.1016/s2352-3018(18)30097-3.Peer-Reviewed Original ResearchConceptsNew HIV infectionsInjectable PrEPPre-exposure prophylaxisOral PrEPHIV infectionHIV transmissionInjectable pre-exposure prophylaxisOral pre-exposure prophylaxisAbsence of PrEPDaily oral PrEPTime-varying efficacyPhase 3 trialRetention of patientsNational InstituteDiscontinuation ratesSafety trialMacaque modelHIV preventionCumulative numberClinical carePharmacokinetic dataCoverage levelsPotential effectivenessPopulation-level impactInfectionHeterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C
Cannataro VL, Gaffney SG, Stender C, Zhao ZM, Philips M, Greenstein AE, Townsend JP. Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C. Oncogene 2018, 37: 2444-2455. PMID: 29453361, DOI: 10.1038/s41388-017-0105-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SubstitutionAnimalsCase-Control StudiesDisease ProgressionDrug Resistance, NeoplasmFemaleGenetic HeterogeneityHigh-Throughput Nucleotide SequencingHumansMaleMiceMice, Inbred BALB CMice, NudeNeoplasmsOncogenesPoint MutationPolymorphism, Single NucleotideProto-Oncogene Proteins p21(ras)Sequence Analysis, DNAYoung AdultConceptsTime of treatmentTargeted therapyLung tumorsDe novo mutationsNew targeted therapiesPatient-derived xenograftsHighest fitness advantageKRAS G12C variantNovo mutationsEvidence of heterogeneityNovel KRAS mutationPreclinical promiseSuch therapyHigh prevalenceKRAS mutationsTreatment resistanceBRAF V600EKRASTherapyTargeted inhibitorsTumorsAssociated oncogeneRAS genesHuman cancersOncogenic mutations
2016
Vaccination strategies against respiratory syncytial virus
Yamin D, Jones FK, DeVincenzo JP, Gertler S, Kobiler O, Townsend JP, Galvani AP. Vaccination strategies against respiratory syncytial virus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 13239-13244. PMID: 27799521, PMCID: PMC5135296, DOI: 10.1073/pnas.1522597113.Peer-Reviewed Original ResearchConceptsRespiratory syncytial virusSyncytial virusVaccination strategiesAge-specific vaccination strategiesRSV vaccine candidatesSubstantial indirect protectionInfectious viral loadOngoing clinical trialsWeekly incidence ratesTargeting of childrenDifferent age groupsInfected childrenRSV vaccinationVaccination uptakeInfant hospitalizationViral loadVaccine mechanismVaccination programClinical trialsIncidence rateCommon causeRSV incidenceVaccine candidatesAge groupsRSV symptomsCost-Effectiveness of Pertussis Vaccination During Pregnancy in the United States
Atkins KE, Fitzpatrick MC, Galvani AP, Townsend JP. Cost-Effectiveness of Pertussis Vaccination During Pregnancy in the United States. American Journal Of Epidemiology 2016, 183: 1159-1170. PMID: 27188951, PMCID: PMC4908210, DOI: 10.1093/aje/kwv347.Peer-Reviewed Original ResearchConceptsMaternal vaccinationAdult vaccinationWorld Health Organization criteriaPrimary vaccination seriesVaccination of mothersRecent epidemiologic evidenceAge-stratified transmission modelMaternal antibody transferPertussis vaccinationPostpartum vaccinationVaccination seriesAntibody transferEpidemiologic evidenceOrganization criteriaPertussis incidenceDisease burdenCurrent recommendationsSevere casesVaccinationInfantsPregnancyDirect protectionUS mothersMothersPertussisCost-effectiveness of next-generation vaccines: The case of pertussis
Fitzpatrick MC, Wenzel NS, Scarpino SV, Althouse BM, Atkins KE, Galvani AP, Townsend JP. Cost-effectiveness of next-generation vaccines: The case of pertussis. Vaccine 2016, 34: 3405-3411. PMID: 27087151, DOI: 10.1016/j.vaccine.2016.04.010.Peer-Reviewed Original ResearchConceptsNext-generation vaccinesDuration of protectionAdult boostersChildhood seriesAge-structured transmission modelVaccination coverage ratesCases of pertussisPublic health challengePerfect efficacyPertussis vaccinationPertussis vaccinePertussis incidenceCurrent vaccinesNew vaccinesPotential vaccinesGreater efficacyVaccineVaccine improvementHealth challengesAverage durationHealth benefitsEfficacyDoseShort durationPertussis
2015
The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States
Durham DP, Skrip LA, Bruce RD, Vilarinho S, Elbasha EH, Galvani AP, Townsend JP. The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States. Clinical Infectious Diseases 2015, 62: 298-304. PMID: 26628566, PMCID: PMC4706637, DOI: 10.1093/cid/civ894.Peer-Reviewed Original ResearchConceptsHepatitis C virusInterferon-free DAAsHCV incidenceTreatment ratesChronic hepatitis C virusCases of cirrhosisInjection drug useImpact of administrationAnnual treatment ratesEnhanced screeningHCV prevalenceHCV screeningDecompensated cirrhosisHCV infectionHCV transmissionHepatitis CLiver transplantActing antiviralsLevels of screeningPatients 4C virusHepatocellular carcinomaEpidemiological dataUniversal screeningDrug useOptimizing age of cytomegalovirus screening and vaccination to avert congenital disease in the US
Alfaro-Murillo JA, Townsend JP, Galvani AP. Optimizing age of cytomegalovirus screening and vaccination to avert congenital disease in the US. Vaccine 2015, 34: 225-229. PMID: 26631416, DOI: 10.1016/j.vaccine.2015.11.039.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overChildChild, PreschoolCytomegalovirus InfectionsCytomegalovirus VaccinesDisease Transmission, InfectiousFemaleHumansImmunization ScheduleInfantInfant, NewbornInfectious Disease Transmission, VerticalMaleMass ScreeningMiddle AgedUnited StatesYoung AdultConceptsVaccine waningVaccine efficacyOptimal ageCMV vaccine candidatesLongitudinal clinical evaluationChild-bearing yearsYears of ageTransmission dynamicsCMV prevalenceCMV vaccinationCytomegalovirus ScreeningSeronegative femalesCongenital infectionCytomegalovirus infectionVaccine protectionSuch vaccinationClinical evaluationClinical trialsHearing lossVaccine candidatesVaccinationDemographic dataCongenital diseaseCognitive deficitsIndirect protectionIntegrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa
Gilbert JA, Long EF, Brooks RP, Friedland GH, Moll AP, Townsend JP, Galvani AP, Shenoi SV. Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa. PLOS ONE 2015, 10: e0126267. PMID: 25938501, PMCID: PMC4418809, DOI: 10.1371/journal.pone.0126267.Peer-Reviewed Original ResearchConceptsTB/HIVHIV control strategiesMDR-TBXDR-TBHIV deathsHIV casesHIV epidemicRural South AfricaTB/HIV casesTB treatment delayIsoniazid preventive therapyDrug-resistant TBHIV treatment programsTreatment cure ratesHIV case findingHIV control effortsNovel screening programPreventive therapyTB casesTB treatmentTreatment delayHIV transmissionCure rateQuestionnaire's sensitivityScreening program
2013
Potential Cost-Effectiveness of Schistosomiasis Treatment for Reducing HIV Transmission in Africa – The Case of Zimbabwean Women
Mbah M, Poolman EM, Atkins KE, Orenstein EW, Meyers LA, Townsend JP, Galvani AP. Potential Cost-Effectiveness of Schistosomiasis Treatment for Reducing HIV Transmission in Africa – The Case of Zimbabwean Women. PLOS Neglected Tropical Diseases 2013, 7: e2346. PMID: 23936578, PMCID: PMC3731236, DOI: 10.1371/journal.pntd.0002346.Peer-Reviewed Original ResearchConceptsFemale genital schistosomiasisHIV infectionPraziquantel administrationHIV transmissionSchool-aged childrenAnnual administrationHIV prevalenceSchistosoma haematobiumCost-effective public health interventionsAntenatal clinic dataReducing HIV TransmissionBurden of HIVCases of HIVTen-year periodPublic health interventionsCost-effectiveness analysisNovel intervention strategiesGenital schistosomiasisGenital infectionSaharan AfricaCost-saving strategyNet savingsSchistosomiasis treatmentEpidemiological dataClinic dataOptimal targeting of seasonal influenza vaccination toward younger ages is robust to parameter uncertainty
Mbah M, Medlock J, Meyers LA, Galvani AP, Townsend JP. Optimal targeting of seasonal influenza vaccination toward younger ages is robust to parameter uncertainty. Vaccine 2013, 31: 3079-3089. PMID: 23684837, PMCID: PMC3764605, DOI: 10.1016/j.vaccine.2013.04.052.Peer-Reviewed Original ResearchConceptsOptimal vaccine allocationParameter uncertaintiesMathematical modelProbability distributionConsideration of uncertaintiesOutcome measuresVaccine allocationHuman population immunitySeasonal influenza vaccinationControl of influenzaUncertainty analysisFace of uncertaintyInfluenza vaccinationVaccine efficacySeasonal influenzaPopulation immunityUncertaintyEpidemiological dataHigh riskYounger ageYoung adultsEpidemiological parametersOptimal agePrevious recommendationsVaccine
2012
The influence of altruism on influenza vaccination decisions
Shim E, Chapman GB, Townsend JP, Galvani AP. The influence of altruism on influenza vaccination decisions. Journal Of The Royal Society Interface 2012, 9: 2234-2243. PMID: 22496100, PMCID: PMC3405754, DOI: 10.1098/rsif.2012.0115.Peer-Reviewed Original ResearchConceptsInfluenza vaccination decisionsVaccination decisionsImpact of altruismInfluence of altruismVaccination policyGame theoryPersonal payoffAltruismInfluenza vaccinationOptimal vaccination policiesDisease burdenPublic health outcomesHealth outcomesAltruistic motivationTotal costPolicyDecisionsEpidemiological modelPotential strategyPayoffsAssumptionSurvey studyMorbidityVaccinationFundamental assumptions