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| Open AccessDeclines in mental health associated with air pollution and temperature variability in China
Recent efforts to link mental health to environmental factors have focused on single predictors such as pollution or temperature anomalies. Here, the authors show that declines in self-assessed mental health scores were linked to increases in air pollution and temperature variability.
- Tao Xue
- , Tong Zhu
- & Qiang Zhang
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Article
| Open AccessMeta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
Birthweight has been found to associate with later-life health outcomes. Here the authors perform a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, identifying differentially methylated CpGs in neonatal blood that associate with birthweight.
- Leanne K. Küpers
- , Claire Monnereau
- & Janine F. Felix
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Article
| Open AccessAge-specific differences in the dynamics of protective immunity to influenza
Protective immunity after influenza virus infection is poorly understood. Here, the authors quantify the dynamics of immunity against influenza A virus infections by fitting individual-level mechanistic models to longitudinal serology, and find that the form and dynamics of protection differ between children and adults.
- Sylvia Ranjeva
- , Rahul Subramanian
- & Sarah Cobey
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Article
| Open AccessAdjustment for index event bias in genome-wide association studies of subsequent events
Different from GWAS for susceptibility to disease, GWAS for prognosis or survival may be vulnerable to selection bias. Here, Dudbridge et al present an approach to reduce index event bias in simulated and realistic situations, and apply it to GWAS of survival with idiopathic pulmonary fibrosis and Crohn’s disease prognosis.
- Frank Dudbridge
- , Richard J. Allen
- & Riyaz S. Patel
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Article
| Open AccessGenome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
The genetic underpinnings of alcohol use disorder and consumption are incompletely understood. Here, the authors perform GWAS for Alcohol Use Disorder (AUD) Identification Test-Consumption scores and AUD diagnosis from electronic health records of 274,424 individuals and identify a total of 18 associated loci.
- Henry R. Kranzler
- , Hang Zhou
- & Joel Gelernter
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Article
| Open AccessEffects of infection history on dengue virus infection and pathogenicity
Lack of knowledge of individual infection history hinders understanding of immunological interactions among DENV serotypes. Here, the authors introduce a framework to infer the relationship between unobserved infection history and subsequent infection and disease risk, and find complex dependencies.
- Tim K. Tsang
- , Samson L. Ghebremariam
- & Yang Yang
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Article
| Open AccessInter-annual variation in seasonal dengue epidemics driven by multiple interacting factors in Guangzhou, China
In 2014 Guangzhou, China experienced its worse dengue epidemic on record. To determine the reasons for this the authors model historical data under combinations of four time-varying factors and find that past epidemics were limited by one or more unfavourable conditions, but the 2014 epidemic faced none of these restraints.
- Rachel J. Oidtman
- , Shengjie Lai
- & Hongjie Yu
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Article
| Open AccessGenome wide analysis for mouth ulcers identifies associations at immune regulatory loci
Oral ulcerations are sores of the mucous membrane of the mouth and highly prevalent in the population. Here, in a genome-wide association study, the authors identify 97 loci associated with mouth ulcers highlighting genes involved in T cell-mediated immunity and TH1 responses.
- Tom Dudding
- , Simon Haworth
- & Nicholas J. Timpson
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Article
| Open AccessThe indirect health effects of malaria estimated from health advantages of the sickle cell trait
Estimates of the burden of malaria often don't take wider, indirect effects on overall health into consideration. Here, Uyoga et al. estimate the indirect impact of malaria on children’s health in a case-control study, using the sickle cell trait as a proxy indicator for an effective intervention.
- Sophie Uyoga
- , Alex W. Macharia
- & Thomas N. Williams
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Article
| Open AccessMulti-cohort study identifies social determinants of systemic inflammation over the life course
Here, the authors explore the relationship between socioeconomic position (SEP) across the life course and inflammation in a multi-cohort study and show that educational attainment is most strongly related to inflammation, suggesting that socioeconomic disadvantage in young adulthood is independently associated with later life inflammation.
- Eloïse Berger
- , Raphaële Castagné
- & Michelle Kelly-Irving
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Article
| Open AccessPopulation-wide analysis of differences in disease progression patterns in men and women
Sex-stratified medicine is an important and understudied field. Here the authors investigate in a systematic study of the Danish population differences in incidence, risk, and several aspects of diagnoses between sexes and find differences across all areas of disease.
- David Westergaard
- , Pope Moseley
- & Søren Brunak
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Article
| Open AccessNeurodevelopmental milestones and associated behaviours are similar among healthy children across diverse geographical locations
It is unclear whether the sequence and timing of early life neurodevelopment varies across human populations, excluding the effects of disease or malnutrition. Here, the authors show that children of healthy, urban, educated mothers show very similar development across five geographically diverse populations.
- José Villar
- , Michelle Fernandes
- & Stephen Kennedy
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Article
| Open AccessShared heritability and functional enrichment across six solid cancers
Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.
- Xia Jiang
- , Hilary K. Finucane
- & Sara Lindström
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Article
| Open AccessApparent latent structure within the UK Biobank sample has implications for epidemiological analysis
Population structure can bias the results of genetic and epidemiological analysis. Here, Haworth et al. report that fine-scale structure is detectable in apparently homogeneous samples such as ALSPAC when measured very precisely, and remains detectable in UK Biobank despite conventional approaches to account for it.
- Simon Haworth
- , Ruth Mitchell
- & Nicholas J. Timpson
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Article
| Open AccessImproved state-level influenza nowcasting in the United States leveraging Internet-based data and network approaches
Real-time disease surveillance can aid mitigation of outbreaks. Here, Lu et al. combine an approach using Google search and EHR data with an approach leveraging spatiotemporal synchronicities of influenza activity across states to improve state-level influenza activity estimates in the US.
- Fred S. Lu
- , Mohammad W. Hattab
- & Mauricio Santillana
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Article
| Open AccessIndirect protection from vaccinating children against influenza in households
Relevance of indirect protection of household members of vaccinees is unclear. Here, Tsang et al. quantify the direct and indirect protection of vaccination in a randomized controlled trial and show that benefits of individual vaccination remain important even when other household members are vaccinated.
- Tim K. Tsang
- , Vicky J. Fang
- & Simon Cauchemez
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Article
| Open AccessLongevity defined as top 10% survivors and beyond is transmitted as a quantitative genetic trait
While human lifespan is only moderately heritable, “getting old” runs in families. Here, van den Berg et al. study mortality data from three-generation cohorts to define a threshold for longevity and find that individuals have an increasing survival advantage with each additional relative in the top 10% survivors of their birth cohort.
- Niels van den Berg
- , Mar Rodríguez-Girondo
- & P. Eline Slagboom
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Article
| Open AccessThe utility of serology for elimination surveillance of trachoma
Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, Pinsent et al. analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low transmission and post-elimination settings.
- Amy Pinsent
- , Anthony W. Solomon
- & Michael. T. White
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Article
| Open AccessPaternal grandfather’s access to food predicts all-cause and cancer mortality in grandsons
Nutritional experience can have phenotypic consequences in subsequent generations, as is evident from studies in animals and plants. Here, Vågerö et al. find in a large three-generation cohort that access to food in the paternal grandfather associates with all-cause and cancer mortality in male grandchildren.
- Denny Vågerö
- , Pia R. Pinger
- & Gerard J. van den Berg
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Article
| Open AccessGWAS identifies 14 loci for device-measured physical activity and sleep duration
Studying the genetic underpinnings of physical activity and sleep duration can be confounded by self-reporting. Here, Doherty et al. use data from 91,105 UK Biobank participants, whose activity had been monitored for a week by a wearable device, for genome-wide association analysis and identify 14 loci.
- Aiden Doherty
- , Karl Smith-Byrne
- & Cecilia M. Lindgren
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Article
| Open AccessThe phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa
Typhoid fever is caused by the bacterium Salmonella Typhi. Here, Park et al. analyse the genomes of 249 S. Typhi isolates from 11 sub-Saharan African countries, identifying genes and plasmids associated with antibiotic resistance and showing that multi-drug resistance is highly pervasive in sub-Saharan Africa.
- Se Eun Park
- , Duy Thanh Pham
- & Stephen Baker
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Article
| Open AccessSystematic review of indoor residual spray efficacy and effectiveness against Plasmodium falciparum in Africa
Indoor residual spraying is a commonly used method for mosquito, and malaria, control and there are a number of available insecticides that are available for this. Here, the authors evaluate the efficacy of widely-used and novel insecticides against pyrethroid-resistant mosquitoes.
- Ellie Sherrard-Smith
- , Jamie T. Griffin
- & Thomas S. Churcher
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Article
| Open AccessNational and sub-national variation in patterns of febrile case management in sub-Saharan Africa
Treatment-seeking for fever is widely used to estimate treatment of childhood infections, but cross-country comparisons are problematic. Here, the authors estimate the probability of seeking treatment for fever at public facilities across 29 countries by quantifying person-level latent variables.
- Victor A. Alegana
- , Joseph Maina
- & Andrew J. Tatem
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Article
| Open AccessSubstantiating freedom from parasitic infection by combining transmission model predictions with disease surveys
The decision when to stop an intervention is a critical component of parasite elimination programmes, but reliance on surveillance data alone can be inaccurate. Here, Michael et al. combine parasite transmission model predictions with disease survey data to more reliably determine when interventions can be stopped.
- Edwin Michael
- , Morgan E. Smith
- & Frank O. Richards
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Article
| Open AccessFine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
The basis for associations between lung cancer and major histocompatibility complex genes is not completely understood. Here the authors further consider genetic variation within the MHC region in lung cancer patients and identify independent associations within HLA genes that explain MHC lung cancer associations in Europeans and Asian populations.
- Aida Ferreiro-Iglesias
- , Corina Lesseur
- & Paul Brennan
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Article
| Open AccessMultiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function
Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.
- Annah B. Wyss
- , Tamar Sofer
- & Stephanie J. London
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Article
| Open AccessQuantifying the spatial spread of dengue in a non-endemic Brazilian metropolis via transmission chain reconstruction
There is increasing urgency to understand the spatiotemporal dynamics of dengue in non-endemic regions. Here, the authors reconstruct likely dengue transmission chains in the city of Porto Alegre based on geo-located cases only, and find that most transmission events occur over short-distances.
- Giorgio Guzzetta
- , Cecilia A. Marques-Toledo
- & Stefano Merler
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Article
| Open AccessGenomic analysis of a pre-elimination Malaysian Plasmodium vivax population reveals selective pressures and changing transmission dynamics
Plasmodium vivax incidence in Malaysia has declined markedly over the last decade, despite evidence of chloroquine resistance. Here, Auburn et al. compare population structure of P. vivax in Malaysia to regions with intermediate and high transmission and identify genetic regions under putative selection.
- Sarah Auburn
- , Ernest D. Benavente
- & Ric N. Price
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Article
| Open AccessPhylodynamic assessment of intervention strategies for the West African Ebola virus outbreak
During the last Ebola virus outbreak in West Africa, a large amount of viral genomic data was obtained. Here, Dellicour et al. use phylodynamic approaches to assess effect of intervention strategies such as border closures.
- Simon Dellicour
- , Guy Baele
- & Philippe Lemey
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Article
| Open AccessHorizontal antimicrobial resistance transfer drives epidemics of multiple Shigella species
Antimicrobial resistance (AMR) in Shigella species is a public health concern. Here, Baker et al. show how horizontal transfer of an AMR plasmid among Shigella species contributes to epidemics in men who have sex with men in England.
- Kate S. Baker
- , Timothy J. Dallman
- & Nicholas Thomson
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Article
| Open AccessRole of monkeys in the sylvatic cycle of chikungunya virus in Senegal
The authors examine the role of monkey populations in the sylvatic cycle of chikungunya virus in the Kédougou region, Senegal. The authors show that monkeys are amplification hosts, as opposed to reservoir hosts for infection. These findings expand our knowledge of the transmission dynamics of chikungunya virus in this region of Senegal.
- Benjamin M. Althouse
- , Mathilde Guerbois
- & Kathryn A. Hanley
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Article
| Open AccessGene-by-environment interactions in urban populations modulate risk phenotypes
Individuals with different genotypes may respond differently to environmental variation. Here, Favé et al. find substantial impacts of different environment exposures on the transcriptome and clinical endophenotypes when controlling for genetic ancestry by analyzing data from ∼1000 individuals from a founder population in Quebec.
- Marie-Julie Favé
- , Fabien C. Lamaze
- & Philip Awadalla
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Review Article
| Open AccessFormalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
Recall-by-Genotype (RbG) is an approach to recall participants from genetic studies based on their specific genotype for further, more extensive phenotyping. Here, the authors discuss examples of RbG as well as practical and ethical considerations and provide an online tool to aid in designing RbG studies.
- Laura J. Corbin
- , Vanessa Y. Tan
- & Nicholas J. Timpson
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Article
| Open AccessGenome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Vitamin D deficiency is associated with multiple human pathologic conditions. In a genome-wide association study of 79,366 individuals, Jiang et al. replicate four and identify two new genetic loci for serum levels of 25-hydroxyvitamin D and find evidence for a shared genetic basis with autoimmune diseases.
- Xia Jiang
- , Paul F. O’Reilly
- & Douglas P. Kiel
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Article
| Open AccessCharacterizing the dynamics underlying global spread of epidemics
Understanding global epidemics spread is crucial for preparedness and response. Here the authors introduce an analytical framework to study epidemic spread on air transport networks, and demonstrate its power to estimate key epidemic parameters by application to the recent influenza pandemic and Ebola outbreak.
- Lin Wang
- & Joseph T. Wu
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Article
| Open AccessInequality in genetic cancer risk suggests bad genes rather than bad luck
Cancer heritability estimates can be obtained via decomposing trait variance into genetic and other factors. Here, the authors obtain the distribution of absolute genetic risk for 15 common cancers, and they use a number of metrics to show that the genetic risk varies considerably across individuals.
- Mats Julius Stensrud
- & Morten Valberg
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Article
| Open AccessCounteracting structural errors in ensemble forecast of influenza outbreaks
Inaccuracy of influenza forecasts based on dynamical models is partly due to nonlinear error growth. Here the authors address the error structure of a compartmental influenza model, and develop a new improved forecast approach combining dynamical error correction and statistical filtering techniques.
- Sen Pei
- & Jeffrey Shaman
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Article
| Open AccessRegional variation in health is predominantly driven by lifestyle rather than genetics
Health-related traits are known to vary geographically. Here, Amador and colleagues show that regional variation of obesity-related traits in a Scottish population is influenced more by lifestyle differences than it is by genetic differences.
- Carmen Amador
- , Charley Xia
- & Chris S. Haley
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Article
| Open AccessCharacterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource
Sleep patterns vary and are associated with health and disease. Here Purcellet alcharacterize sleep spindle activity in 11,630 individuals and describe age-related changes, genetic influences, and possible confounding effects, serving as a resource for further understanding the physiology of sleep.
- S. M. Purcell
- , D. S. Manoach
- & R. Stickgold
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Article
| Open AccessGenome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth
Preterm birth (PTB) has high prevalence and PTB infants have greater risk for mortality. Here, Hong and colleagues perform a genome-wide gene × environment interaction analysis and find that maternalCOL24A1variants have a significant interaction with maternal pre-pregnancy obesity in increasing PTB risk.
- Xiumei Hong
- , Ke Hao
- & Xiaobin Wang
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Article
| Open AccessGenome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.
- Anne E. Justice
- , Thomas W. Winkler
- & L Adrienne Cupples
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Article
| Open AccessExercise contagion in a global social network
Some argue that health-related behaviours, such as obesity, are contagious, but empirical evidence of health contagion remains inconclusive. Here, using a large scale quasi-experiment in a global network of runners, Aral and Nicolaides show that this type of contagion exists in fitness behaviours.
- Sinan Aral
- & Christos Nicolaides
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Article
| Open AccessDNA methylation signatures in peripheral blood strongly predict all-cause mortality
DNA methylation is modulated by environmental factors and has a role in many complex diseases. Here, the authors find that methylation at specific DNA sites is associated with all-cause mortality, and a methylation-based risk score may be informative for risk assessment and stratification.
- Yan Zhang
- , Rory Wilson
- & Hermann Brenner
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Article
| Open AccessAn extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid
Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi). This study examines ∼2,000 clinical isolates of S. Typhi to show highly structured/geographically restricted genomes except rapidly disseminating H58 subclade, and design a genotyping framework for tracking the disease.
- Vanessa K. Wong
- , Stephen Baker
- & Ben Amos
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Article
| Open AccessProjected increase in amyotrophic lateral sclerosis from 2015 to 2040
The socioeconomic burden of amyotrophic lateral sclerosis (ALS) is high, but the projected number of cases in the upcoming years is unclear. Here, the authors estimate the number and distribution of ALS cases to 2040, and show that cases are projected to increase, particularly in developing nations.
- Karissa C. Arthur
- , Andrea Calvo
- & Bryan J. Traynor
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Article
| Open AccessIntestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children
The impact of antibiotics on the microbiome and health of children is poorly understood. Here, Korpela et al. study the gut microbiome of 142 children and show that the use of macrolides, but not penicillins, is associated with long-lasting shifts in microbiota composition and increased risk of asthma and overweight.
- Katri Korpela
- , Anne Salonen
- & Willem M. de Vos
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Article
| Open AccessExome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese
An important risk factor for coronary artery disease is the level of blood lipids. Here the authors conduct an exome-wide association study in Chinese cohorts and identify three novel loci associated with lipid levels as well as three Asian-specific variants in known loci.
- Clara S. Tang
- , He Zhang
- & Wei Gao
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Article
| Open AccessGenome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls
The authors perform a genome-wide association study of adolescent idiopathic scoliosis patients of Han Chinese descent, and identify 3 new loci for disease susceptibility.
- Zezhang Zhu
- , Nelson Leung-Sang Tang
- & Jack Chun-Yiu Cheng
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Article
| Open AccessDefining the relationship between infection prevalence and clinical incidence of Plasmodium falciparum malaria
Mathematical models are used to predict malaria burden to inform disease control efforts. Here, Cameron et al. use Bayesian statistics to calibrate previous models against a data set of age-structured prevalence and incidence, generating stratified forecasts of the prevalence–incidence relationship.
- Ewan Cameron
- , Katherine E. Battle
- & Peter W. Gething