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2.
Nat Commun ; 14(1): 4279, 2023 07 17.
Article in English | MEDLINE | ID: mdl-37460537

ABSTRACT

As the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.3 (95% credible interval (CrI) 7.7-8.8). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of immunity in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (2.9%, 95% CrI 2.7-3.2), followed by Delta (2.2%, 95% CrI 2.0-2.4), Wildtype (1.2%, 95% CrI 1.1-1.2), and Omicron (0.7%, 95% CrI 0.6-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Bayes Theorem , COVID-19/epidemiology , England/epidemiology
3.
Lancet Public Health ; 8(3): e174-e183, 2023 03.
Article in English | MEDLINE | ID: mdl-36774945

ABSTRACT

BACKGROUND: The UK was the first country to start national COVID-19 vaccination programmes, initially administering doses 3 weeks apart. However, early evidence of high vaccine effectiveness after the first dose and the emergence of the SARS-CoV-2 alpha variant prompted the UK to extend the interval between doses to 12 weeks. In this study, we aimed to quantify the effect of delaying the second vaccine dose in England. METHODS: We used a previously described model of SARS-CoV-2 transmission, calibrated to COVID-19 surveillance data from England, including hospital admissions, hospital occupancy, seroprevalence data, and population-level PCR testing data, using a Bayesian evidence-synthesis framework. We modelled and compared the epidemic trajectory in the counterfactual scenario in which vaccine doses were administered 3 weeks apart against the real reported vaccine roll-out schedule of 12 weeks. We estimated and compared the resulting numbers of daily infections, hospital admissions, and deaths. In sensitivity analyses, we investigated scenarios spanning a range of vaccine effectiveness and waning assumptions. FINDINGS: In the period from Dec 8, 2020, to Sept 13, 2021, the number of individuals who received a first vaccine dose was higher under the 12-week strategy than the 3-week strategy. For this period, we estimated that delaying the interval between the first and second COVID-19 vaccine doses from 3 to 12 weeks averted a median (calculated as the median of the posterior sample) of 58 000 COVID-19 hospital admissions (291 000 cumulative hospitalisations [95% credible interval 275 000-319 000] under the 3-week strategy vs 233 000 [229 000-238 000] under the 12-week strategy) and 10 100 deaths (64 800 deaths [60 200-68 900] vs 54 700 [52 800-55 600]). Similarly, we estimated that the 3-week strategy would have resulted in more infections compared with the 12-week strategy. Across all sensitivity analyses the 3-week strategy resulted in a greater number of hospital admissions. In results by age group, the 12-week strategy led to more hospitalisations and deaths in older people in spring 2021, but fewer following the emergence of the delta variant during summer 2021. INTERPRETATION: England's delayed-second-dose vaccination strategy was informed by early real-world data on vaccine effectiveness in the context of limited vaccine supplies in a growing epidemic. Our study shows that rapidly providing partial (single-dose) vaccine-induced protection to a larger proportion of the population was successful in reducing the burden of COVID-19 hospitalisations and deaths overall. FUNDING: UK National Institute for Health Research; UK Medical Research Council; Community Jameel; Wellcome Trust; UK Foreign, Commonwealth and Development Office; Australian National Health and Medical Research Council; and EU.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Aged , Infant , Bayes Theorem , Seroepidemiologic Studies , Australia , SARS-CoV-2 , England
4.
Lancet ; 398(10313): 1825-1835, 2021 11 13.
Article in English | MEDLINE | ID: mdl-34717829

ABSTRACT

BACKGROUND: England's COVID-19 roadmap out of lockdown policy set out the timeline and conditions for the stepwise lifting of non-pharmaceutical interventions (NPIs) as vaccination roll-out continued, with step one starting on March 8, 2021. In this study, we assess the roadmap, the impact of the delta (B.1.617.2) variant of SARS-CoV-2, and potential future epidemic trajectories. METHODS: This mathematical modelling study was done to assess the UK Government's four-step process to easing lockdown restrictions in England, UK. We extended a previously described model of SARS-CoV-2 transmission to incorporate vaccination and multi-strain dynamics to explicitly capture the emergence of the delta variant. We calibrated the model to English surveillance data, including hospital admissions, hospital occupancy, seroprevalence data, and population-level PCR testing data using a Bayesian evidence synthesis framework, then modelled the potential trajectory of the epidemic for a range of different schedules for relaxing NPIs. We estimated the resulting number of daily infections and hospital admissions, and daily and cumulative deaths. Three scenarios spanning a range of optimistic to pessimistic vaccine effectiveness, waning natural immunity, and cross-protection from previous infections were investigated. We also considered three levels of mixing after the lifting of restrictions. FINDINGS: The roadmap policy was successful in offsetting the increased transmission resulting from lifting NPIs starting on March 8, 2021, with increasing population immunity through vaccination. However, because of the emergence of the delta variant, with an estimated transmission advantage of 76% (95% credible interval [95% CrI] 69-83) over alpha, fully lifting NPIs on June 21, 2021, as originally planned might have led to 3900 (95% CrI 1500-5700) peak daily hospital admissions under our central parameter scenario. Delaying until July 19, 2021, reduced peak hospital admissions by three fold to 1400 (95% CrI 700-1700) per day. There was substantial uncertainty in the epidemic trajectory, with particular sensitivity to the transmissibility of delta, level of mixing, and estimates of vaccine effectiveness. INTERPRETATION: Our findings show that the risk of a large wave of COVID-19 hospital admissions resulting from lifting NPIs can be substantially mitigated if the timing of NPI relaxation is carefully balanced against vaccination coverage. However, with the delta variant, it might not be possible to fully lift NPIs without a third wave of hospital admissions and deaths, even if vaccination coverage is high. Variants of concern, their transmissibility, vaccine uptake, and vaccine effectiveness must be carefully monitored as countries relax pandemic control measures. FUNDING: National Institute for Health Research, UK Medical Research Council, Wellcome Trust, and UK Foreign, Commonwealth and Development Office.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , COVID-19/transmission , Communicable Disease Control/organization & administration , SARS-CoV-2 , Vaccination Coverage/organization & administration , COVID-19/epidemiology , COVID-19/mortality , England/epidemiology , Hospital Mortality/trends , Hospitalization/statistics & numerical data , Humans , Models, Theoretical , Patient Admission/statistics & numerical data
5.
J Int AIDS Soc ; 24 Suppl 5: e25788, 2021 09.
Article in English | MEDLINE | ID: mdl-34546657

ABSTRACT

INTRODUCTION: HIV planning requires granular estimates for the number of people living with HIV (PLHIV), antiretroviral treatment (ART) coverage and unmet need, and new HIV infections by district, or equivalent subnational administrative level. We developed a Bayesian small-area estimation model, called Naomi, to estimate these quantities stratified by subnational administrative units, sex, and five-year age groups. METHODS: Small-area regressions for HIV prevalence, ART coverage and HIV incidence were jointly calibrated using subnational household survey data on all three indicators, routine antenatal service delivery data on HIV prevalence and ART coverage among pregnant women, and service delivery data on the number of PLHIV receiving ART. Incidence was modelled by district-level HIV prevalence and ART coverage. Model outputs of counts and rates for each indicator were aggregated to multiple geographic and demographic stratifications of interest. The model was estimated in an empirical Bayes framework, furnishing probabilistic uncertainty ranges for all output indicators. Example results were presented using data from Malawi during 2016-2018. RESULTS: Adult HIV prevalence in September 2018 ranged from 3.2% to 17.1% across Malawi's districts and was higher in southern districts and in metropolitan areas. ART coverage was more homogenous, ranging from 75% to 82%. The largest number of PLHIV was among ages 35 to 39 for both women and men, while the most untreated PLHIV were among ages 25 to 29 for women and 30 to 34 for men. Relative uncertainty was larger for the untreated PLHIV than the number on ART or total PLHIV. Among clients receiving ART at facilities in Lilongwe city, an estimated 71% (95% CI, 61% to 79%) resided in Lilongwe city, 20% (14% to 27%) in Lilongwe district outside the metropolis, and 9% (6% to 12%) in neighbouring Dowa district. Thirty-eight percent (26% to 50%) of Lilongwe rural residents and 39% (27% to 50%) of Dowa residents received treatment at facilities in Lilongwe city. CONCLUSIONS: The Naomi model synthesizes multiple subnational data sources to furnish estimates of key indicators for HIV programme planning, resource allocation, and target setting. Further model development to meet evolving HIV policy priorities and programme need should be accompanied by continued strengthening and understanding of routine health system data.


Subject(s)
Epidemics , HIV Infections , Adult , Anti-Retroviral Agents/therapeutic use , Bayes Theorem , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Malawi/epidemiology , Male , Pregnancy , Prevalence
6.
Am Nat ; 198(2): 253-267, 2021 08.
Article in English | MEDLINE | ID: mdl-34260875

ABSTRACT

AbstractIn community ecology, it is widely assumed that organisms with similar traits compete more intensely with one another for resources. This assumption is often encoded into theory and empirical tests via a unimodal competition function, which predicts that per capita competitive effect declines with separation in traits. Yet it remains unknown how well this function represents the true effect of traits on competitive outcomes, especially for long-lived plant communities, where lifetime fitness is difficult to estimate. Here, we evaluate the shape of competition functions embedded in two resource-based (RB) models, wherein plants compete for shared, essential resources. In the first RB model individuals compete for two essential nutrients, and in the second they compete for light in a size-based successional setting. We compared the shapes of the competition functions that emerged from interactions within these RB models to the unimodal function and others shapes commonly applied. In few instances did the trait-based competition function emerging from the RB model even vaguely resemble any of the shapes previously used. The mismatch between these two approaches suggests that theory derived using fixed competition functions based on trait separation may not apply well to plant systems, where individuals compete for shared resources. The more promising path will be to model depletion of resources by populations in relation to their traits, with its consequences for fitness landscapes and competitive exclusion.


Subject(s)
Ecology , Plants , Humans , Phenotype
7.
Sci Transl Med ; 13(602)2021 07 14.
Article in English | MEDLINE | ID: mdl-34158411

ABSTRACT

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modeling framework, allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rt eff) below 1 consistently; if introduced 1 week earlier, it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 [95% credible interval (CrI): 15,900 to 38,400]. The infection fatality ratio decreased from 1.00% (95% CrI: 0.85 to 1.21%) to 0.79% (95% CrI: 0.63 to 0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95% CrI: 14.7 to 35.2%) than those residing in the community (7.9%, 95% CrI: 5.9 to 10.3%). On 2 December 2020, England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95% CrI: 5.4 to 10.2%) and 22.3% (95% CrI: 19.4 to 25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow nonpharmaceutical interventions to be lifted without a resurgence of transmission.


Subject(s)
COVID-19 , Epidemics , Aged , Communicable Disease Control , England/epidemiology , Humans , SARS-CoV-2
8.
Nat Commun ; 12(1): 2394, 2021 04 22.
Article in English | MEDLINE | ID: mdl-33888698

ABSTRACT

The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported considerably lower mortality rates than in Europe and the Americas. Motivated by reports of an overwhelmed health system, we estimate the likely under-ascertainment of COVID-19 mortality in Damascus, Syria. Using all-cause mortality data, we fit a mathematical model of COVID-19 transmission to reported mortality, estimating that 1.25% of COVID-19 deaths (sensitivity range 1.00% - 3.00%) have been reported as of 2 September 2020. By 2 September, we estimate that 4,380 (95% CI: 3,250 - 5,550) COVID-19 deaths in Damascus may have been missed, with 39.0% (95% CI: 32.5% - 45.0%) of the population in Damascus estimated to have been infected. Accounting for under-ascertainment corroborates reports of exceeded hospital bed capacity and is validated by community-uploaded obituary notifications, which confirm extensive unreported mortality in Damascus.


Subject(s)
COVID-19/mortality , Mortality/trends , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , COVID-19/virology , Humans , Pandemics , Population Surveillance/methods , SARS-CoV-2/physiology , Survival Rate , Syria/epidemiology
9.
Nat Commun ; 12(1): 1090, 2021 02 17.
Article in English | MEDLINE | ID: mdl-33597546

ABSTRACT

In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts. Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world. Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27-77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49-91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12-48%]) post-relaxation. In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.


Subject(s)
COVID-19/transmission , Communicable Disease Control/methods , Pandemics/prevention & control , SARS-CoV-2/isolation & purification , Algorithms , COVID-19/epidemiology , COVID-19/virology , Communicable Disease Control/statistics & numerical data , Global Health , Humans , Models, Theoretical , Physical Distancing , Quarantine/methods , SARS-CoV-2/physiology
10.
Int J Infect Dis ; 102: 463-471, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33130212

ABSTRACT

OBJECTIVES: In this data collation study, we aimed to provide a comprehensive database describing the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19) throughout the main provinces in China. METHODS: From mid-January to March 2020, we extracted publicly available data regarding the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted descriptive analyses of the epidemic in the six most-affected provinces. RESULTS: School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends differed among provinces. Compared with Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as the local transmission of COVID-19 declined, switching the focus of measures to the testing and quarantine of inbound travellers may have helped to sustain the control of the epidemic. CONCLUSIONS: Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database containing these indicators and information regarding control measures is a useful resource for further research and policy planning in response to the COVID-19 epidemic.


Subject(s)
COVID-19/epidemiology , SARS-CoV-2 , COVID-19/prevention & control , China/epidemiology , Contact Tracing , Databases, Factual , Humans
11.
Nat Commun ; 11(1): 6189, 2020 12 03.
Article in English | MEDLINE | ID: mdl-33273462

ABSTRACT

As of 1st June 2020, the US Centres for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available death data within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on the rate of transmission of SARS-CoV-2. We estimate that Rt was only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%-4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.


Subject(s)
COVID-19/epidemiology , Pandemics/statistics & numerical data , Bayes Theorem , COVID-19/transmission , Humans , Models, Statistical , United States/epidemiology , Virus Diseases/epidemiology
12.
BMC Med ; 18(1): 321, 2020 10 09.
Article in English | MEDLINE | ID: mdl-33032601

ABSTRACT

BACKGROUND: After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the USA. This has led to substantial interest in their "test, trace, isolate" strategy. However, it is important to understand the epidemiological peculiarities of South Korea's outbreak and characterise their response before attempting to emulate these measures elsewhere. METHODS: We systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, Rt, using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. RESULTS: We estimated that after the initial rapid growth in cases, Rt dropped below one in early April before increasing to a maximum of 1.94 (95%CrI, 1.64-2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June, Rt was back below one where it remained until the end of our study (July 13th). Despite less stringent "lockdown" measures, strong social distancing measures were implemented in high-incidence areas and studies measured a considerable national decrease in movement in late February. Testing the capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly; however, we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. CONCLUSIONS: Whilst early adoption of testing and contact tracing is likely to be important for South Korea's successful outbreak control, other factors including regional implementation of strong social distancing measures likely also contributed. The high volume of testing and the low number of deaths suggest that South Korea experienced a small epidemic relative to other countries. Caution is needed in attempting to replicate the South Korean response in populations with larger more geographically widespread epidemics where finding, testing, and isolating cases that are linked to clusters may be more difficult.


Subject(s)
Betacoronavirus , Contact Tracing/methods , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Quarantine/methods , Bayes Theorem , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Contact Tracing/trends , Coronavirus Infections/diagnosis , Disease Outbreaks/prevention & control , Humans , Pneumonia, Viral/diagnosis , Quarantine/trends , Republic of Korea/epidemiology , SARS-CoV-2
13.
Wellcome Open Res ; 5: 170, 2020.
Article in English | MEDLINE | ID: mdl-32954015

ABSTRACT

Background: Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of social distancing policies, which have resulted in reduced mobility across different regions. Crowd level data on mobile phone usage can be used as a proxy for actual population mobility patterns and provide a way of quantifying the impact of social distancing measures on changes in mobility. Methods: Here, we use two mobile phone-based datasets (anonymised and aggregated crowd level data from O2 and from the Facebook app on mobile phones) to assess changes in average mobility, both overall and broken down into high and low population density areas, and changes in the distribution of journey lengths. Results: We show that there was a substantial overall reduction in mobility, with the most rapid decline on the 24th March 2020, the day after the Prime Minister's announcement of an enforced lockdown. The reduction in mobility was highly synchronized across the UK. Although mobility has remained low since 26th March 2020, we detect a gradual increase since that time. We also show that the two different datasets produce similar trends, albeit with some location-specific differences. We see slightly larger reductions in average mobility in high-density areas than in low-density areas, with greater variation in mobility in the high-density areas: some high-density areas eliminated almost all mobility. Conclusions: These analyses form a baseline from which to observe changes in behaviour in the UK as social distancing is eased and inform policy towards the future control of SARS-CoV-2 in the UK.

14.
Lancet Glob Health ; 8(9): e1132-e1141, 2020 09.
Article in English | MEDLINE | ID: mdl-32673577

ABSTRACT

BACKGROUND: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. METHODS: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. FINDINGS: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. INTERPRETATION: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.


Subject(s)
Coronavirus Infections/epidemiology , Developing Countries , HIV Infections/prevention & control , Health Services Accessibility , Malaria/prevention & control , Pandemics , Pneumonia, Viral/epidemiology , Tuberculosis/prevention & control , COVID-19 , HIV Infections/epidemiology , HIV Infections/mortality , Humans , Malaria/epidemiology , Malaria/mortality , Models, Theoretical , Tuberculosis/epidemiology , Tuberculosis/mortality
15.
Wellcome Open Res ; 5: 288, 2020.
Article in English | MEDLINE | ID: mdl-34761122

ABSTRACT

State space models, including compartmental models, are used to model physical, biological and social phenomena in a broad range of scientific fields. A common way of representing the underlying processes in these models is as a system of stochastic processes which can be simulated forwards in time. Inference of model parameters based on observed time-series data can then be performed using sequential Monte Carlo techniques. However, using these methods for routine inference problems can be made difficult due to various engineering considerations: allowing model design to change in response to new data and ideas, writing model code which is highly performant, and incorporating all of this with up-to-date statistical techniques. Here, we describe a suite of packages in the R programming language designed to streamline the design and deployment of state space models, targeted at infectious disease modellers but suitable for other domains. Users describe their model in a familiar domain-specific language, which is converted into parallelised C++ code. A fast, parallel, reproducible random number generator is then used to run large numbers of model simulations in an efficient manner. We also provide standard inference and prediction routines, though the model simulator can be used directly if these do not meet the user's needs. These packages provide guarantees on reproducibility and performance, allowing the user to focus on the model itself, rather than the underlying computation. The ability to automatically generate high-performance code that would be tedious and time-consuming to write and verify manually, particularly when adding further structure to compartments, is crucial for infectious disease modellers. Our packages have been critical to the development cycle of our ongoing real-time modelling efforts in the COVID-19 pandemic, and have the potential to do the same for models used in a number of different domains.

16.
Gigascience ; 8(5)2019 05 01.
Article in English | MEDLINE | ID: mdl-31042286

ABSTRACT

The sharing and re-use of data has become a cornerstone of modern science. Multiple platforms now allow easy publication of datasets. So far, however, platforms for data sharing offer limited functions for distributing and interacting with evolving datasets- those that continue to grow with time as more records are added, errors fixed, and new data structures are created. In this article, we describe a workflow for maintaining and distributing successive versions of an evolving dataset, allowing users to retrieve and load different versions directly into the R platform. Our workflow utilizes tools and platforms used for development and distribution of successive versions of an open source software program, including version control, GitHub, and semantic versioning, and applies these to the analogous process of developing successive versions of an open source dataset. Moreover, we argue that this model allows for individual research groups to achieve a dynamic and versioned model of data delivery at no cost.


Subject(s)
Computational Biology , Information Dissemination , Software , Humans , Workflow
17.
Proc Natl Acad Sci U S A ; 115(49): 12459-12464, 2018 12 04.
Article in English | MEDLINE | ID: mdl-30446609

ABSTRACT

Tree death drives population dynamics, nutrient cycling, and evolution within plant communities. Mortality variation across species is thought to be influenced by different factors relative to variation within species. The unified model provided here separates mortality rates into growth-dependent and growth-independent hazards. This model creates the opportunity to simultaneously estimate these hazards both across and within species. Moreover, it provides the ability to examine how species traits affect growth-dependent and growth-independent hazards. We derive this unified mortality model using cross-validated Bayesian methods coupled with mortality data collected over three census intervals for 203 tropical rainforest tree species at Barro Colorado Island (BCI), Panama. We found that growth-independent mortality tended to be higher in species with lower wood density, higher light requirements, and smaller maximum diameter at breast height (dbh). Mortality due to marginal carbon budget as measured by near-zero growth rate tended to be higher in species with lower wood density and higher light demand. The total mortality variation attributable to differences among species was large relative to variation explained by these traits, emphasizing that much remains to be understood. This additive hazards model strengthens our capacity to parse and understand individual-level mortality in highly diverse tropical forests and hence to predict its consequences.


Subject(s)
Rainforest , Trees/growth & development , Islands , Longevity , Panama , Species Specificity
18.
Proc Natl Acad Sci U S A ; 115(29): E6789-E6798, 2018 07 17.
Article in English | MEDLINE | ID: mdl-29959205

ABSTRACT

Plant species differ in many functional traits that drive differences in rates of photosynthesis, biomass allocation, and tissue turnover. However, it remains unclear how-and even if-such traits influence whole-plant growth, with the simple linear relationships predicted by existing theory often lacking empirical support. Here, we present a theoretical framework for understanding the effect of diverse functional traits on plant growth and shade tolerance by extending a widely used model, linking growth rate in seedlings with a single leaf trait, to explicitly include influences of size, light environment, and five prominent traits: seed mass, height at maturation, leaf mass per unit leaf area, leaf nitrogen per unit leaf area, and wood density. Based on biomass growth and allocation, this framework explains why the influence of traits on growth rate and shade tolerance often varies with plant size and why the impact of size on growth varies among traits. Specifically, we demonstrate why for height growth the influence of: (i) leaf mass per unit leaf area is strong in small plants but weakens with size; (ii) leaf nitrogen per unit leaf area does not change with size; (iii) wood density is present across sizes; (iv) height at maturation strengthens with size; and (v) seed mass decreases with size. Moreover, we show how traits moderate plant responses to light environment and also determine shade tolerance, supporting diverse empirical results.


Subject(s)
Adaptation, Biological/physiology , Models, Biological , Plant Development/physiology , Plants/genetics , Quantitative Trait, Heritable
19.
Methods Ecol Evol ; 7(6): 693-699, 2016 06.
Article in English | MEDLINE | ID: mdl-27499839

ABSTRACT

Phylogenetic comparative methods are becoming increasingly popular for investigating evolutionary patterns and processes. However, these methods are not infallible - they suffer from biases and make assumptions like all other statistical methods.Unfortunately, although these limitations are generally well known in the phylogenetic comparative methods community, they are often inadequately assessed in empirical studies leading to misinterpreted results and poor model fits. Here, we explore reasons for the communication gap dividing those developing new methods and those using them.We suggest that some important pieces of information are missing from the literature and that others are difficult to extract from long, technical papers. We also highlight problems with users jumping straight into software implementations of methods (e.g. in r) that may lack documentation on biases and assumptions that are mentioned in the original papers.To help solve these problems, we make a number of suggestions including providing blog posts or videos to explain new methods in less technical terms, encouraging reproducibility and code sharing, making wiki-style pages summarising the literature on popular methods, more careful consideration and testing of whether a method is appropriate for a given question/data set, increased collaboration, and a shift from publishing purely novel methods to publishing improvements to existing methods and ways of detecting biases or testing model fit. Many of these points are applicable across methods in ecology and evolution, not just phylogenetic comparative methods.

20.
Am Nat ; 186(2): E33-50, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26655160

ABSTRACT

Making meaningful inferences from phylogenetic comparative data requires a meaningful model of trait evolution. It is thus important to determine whether the model is appropriate for the data and the question being addressed. One way to assess this is to ask whether the model provides a good statistical explanation for the variation in the data. To date, researchers have focused primarily on the explanatory power of a model relative to alternative models. Methods have been developed to assess the adequacy, or absolute explanatory power, of phylogenetic trait models, but these have been restricted to specific models or questions. Here we present a general statistical framework for assessing the adequacy of phylogenetic trait models. We use our approach to evaluate the statistical performance of commonly used trait models on 337 comparative data sets covering three key angiosperm functional traits. In general, the models we tested often provided poor statistical explanations for the evolution of these traits. This was true for many different groups and at many different scales. Whether such statistical inadequacy will qualitatively alter inferences drawn from comparative data sets will depend on the context. Regardless, assessing model adequacy can provide interesting biological insights-how and why a model fails to describe variation in a data set give us clues about what evolutionary processes may have driven trait evolution across time.


Subject(s)
Biological Evolution , Magnoliopsida/classification , Models, Theoretical , Computer Simulation , Phenotype , Phylogeny , Plant Leaves/anatomy & histology , Plant Leaves/chemistry , Reproducibility of Results , Seeds/physiology
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