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BACKGROUND: Reverse transcription polymerase chain reaction (RT-PCR) tests are the gold standard for detecting recent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Reverse transcription PCR sensitivity varies over the course of an individual's infection, related to changes in viral load. Differences in testing methods, and individual-level variables such as age, may also affect sensitivity. METHODS: Using data from New Zealand, we estimate the time-varying sensitivity of SARS-CoV-2 RT-PCR under varying temporal, biological, and demographic factors. RESULTS: Sensitivity peaks 4-5 days postinfection at 92.7% (91.4%-94.0%) and remains over 88% between 5 and 14 days postinfection. After the peak, sensitivity declined more rapidly in vaccinated cases compared with unvaccinated, females compared with males, those aged under 40 compared with over 40s, and Pacific peoples compared with other ethnicities. CONCLUSIONS: Reverse transcription PCR remains a sensitive technique and has been an effective tool in New Zealand's border and postborder measures to control coronavirus disease 2019. Our results inform model parameters and decisions concerning routine testing frequency.
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COVID-19 , SARS-CoV-2 , Masculino , Feminino , Humanos , Idoso , SARS-CoV-2/genética , COVID-19/diagnóstico , Teste para COVID-19 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Reversa , Técnicas de Laboratório Clínico/métodos , Sensibilidade e Especificidade , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
Predation by invasive species is a major threat to the persistence of naïve prey. Typically, this negative effect is addressed by suppressing the population size of the invasive predator to a point where the predation pressure does not hinder the viability of the prey. However, this type of intervention may not be effective whenever a few specialised predators are the cause of the decline. We investigated the effects of varying levels of specialised invasive stoats (Mustela erminea) abundance on the long-term viability of simulated kiwi (Apteryx spp.) populations. We explored four scenarios with different proportions of highly specialised stoats, which were those that had a ≥ 0.75 probability of predating kiwi eggs and chicks if they were within their home range: (i) a stoat population composed mostly of generalists (mean: 0.5 probability of predation across the population); (ii) 5% of highly specialised stoats and the remaining being generalists; (iii) 10% of highly specialised stoats and the remaining being generalists; and, (iv) half highly specialised stoats and half generalists. We found that stoat home range sizes, rather than stoat density or the density of highly specialised stoats, was the main driver of kiwi population trends. Stoats with large home ranges were more likely to predate kiwi eggs and chicks as these were more likely to fall within a large home range. More broadly, our findings show how the daily individual ranging and foraging behaviour of an invasive predator can scale-up to shape population trends of naïve prey.
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Mustelidae , Comportamento Predatório , Animais , Espécies Introduzidas , Densidade Demográfica , Dinâmica PopulacionalRESUMO
Collective cell spreading takes place in spatially continuous environments, yet it is often modelled using discrete lattice-based approaches. Here, we use data from a series of cell proliferation assays, with a prostate cancer cell line, to calibrate a spatially continuous individual based model (IBM) of collective cell migration and proliferation. The IBM explicitly accounts for crowding effects by modifying the rate of movement, direction of movement, and the rate of proliferation by accounting for pair-wise interactions. Taking a Bayesian approach we estimate the free parameters in the IBM using rejection sampling on three separate, independent experimental data sets. Since the posterior distributions for each experiment are similar, we perform simulations with parameters sampled from a new posterior distribution generated by combining the three data sets. To explore the predictive power of the calibrated IBM, we forecast the evolution of a fourth experimental data set. Overall, we show how to calibrate a lattice-free IBM to experimental data, and our work highlights the importance of interactions between individuals. Despite great care taken to distribute cells as uniformly as possible experimentally, we find evidence of significant spatial clustering over short distances, suggesting that standard mean-field models could be inappropriate.
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Algoritmos , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Modelos Biológicos , Teorema de Bayes , Linhagem Celular Tumoral , Simulação por Computador , Humanos , Fatores de TempoRESUMO
If a browse damage index indicates that a tree has been 50% browsed by herbivores, does this mean half the leaves are entirely eaten or are all the leaves half eaten? Were the affected leaves old or young? Large or small? In sunshine or shade? Understanding what effect browsing will have on the photosynthetic capacity and the plant's survival ability clearly requires a greater understanding of browsing strategy across the canopy than can be given by a single index value. We developed stochastic models of leaf production, growth and consumption using data from kamahi (Weinmannia racemosa) trees in New Zealand which have been browsed by possums (Trichosurus vulpecula), to ascertain which of six feasible browsing strategies possums are most likely to be employing. We compared the area distribution of real fallen leaves to model output in order to select the best model, and used the model to predict the age distribution of leaves on the tree and thus infer its photosynthetic capability. The most likely browsing strategy that possums employ on kamahi trees is a preference for virgin (i.e. previously unbrowsed) leaves, consistent with the idea that browsing increases the production of chemical plant defences. More generally, our results show that herbivore browsing strategy can significantly change the whole-plant photosynthetic capability of any plant and hence its ability to survive, and therefore, herbivore damage indices should be used in conjunction with more detailed information about herbivore browsing strategy.
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Herbivoria , Fotossíntese , Plantas , Animais , Folhas de Planta , Processos Estocásticos , ÁrvoresRESUMO
Collective cell migration and proliferation are integral to tissue repair, embryonic development, the immune response and cancer. Central to collective cell migration and proliferation are interactions among neighbouring cells, such as volume exclusion, contact inhibition and adhesion. These individual-level processes can have important effects on population-level outcomes, such as growth rate and equilibrium density. We develop an individual-based model of cell migration and proliferation that includes these interactions. This is an extension of a previous model with neighbour-dependent directional bias to incorporate neighbour-dependent proliferation and death. A deterministic approximation to this individual-based model is derived using a spatial moment dynamics approach, which retains information about the spatial structure of the cell population. We show that the individual-based model and spatial moment model match well across a range of parameter values. The spatial moment model allows insight into the two-way interaction between spatial structure and population dynamics that cannot be captured by traditional mean-field models.
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Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Adesão Celular/fisiologia , Morte Celular/fisiologia , Inibição de Contato/fisiologia , Humanos , Conceitos Matemáticos , Modelos BiológicosRESUMO
For the first 18 months of the COVID-19 pandemic, New Zealand used an elimination strategy to suppress community transmission of SARS-CoV-2 to zero or very low levels. In late 2021, high vaccine coverage enabled the country to transition away from the elimination strategy to a mitigation strategy. However, given negligible levels of immunity from prior infection, this required careful planning and an effective public health response to avoid uncontrolled outbreaks and unmanageable health impacts. Here, we develop an age-structured model for the Delta variant of SARS-CoV-2 including the effects of vaccination, case isolation, contact tracing, border controls and population-wide control measures. We use this model to investigate how epidemic trajectories may respond to different control strategies, and to explore trade-offs between restrictions in the community and restrictions at the border. We find that a low case tolerance strategy, with a quick change to stricter public health measures in response to increasing cases, reduced the health burden by a factor of three relative to a high tolerance strategy, but almost tripled the time spent in national lockdowns. Increasing the number of border arrivals was found to have a negligible effect on health burden once high vaccination rates were achieved and community transmission was widespread.
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One Biosecurity is an interdisciplinary approach to policy and research that builds on the interconnections between human, animal, plant, and ecosystem health to effectively prevent and mitigate the impacts of invasive alien species. To support this approach requires that key cross-sectoral research innovations be identified and prioritized. Following an interdisciplinary horizon scan for emerging research that underpins One Biosecurity, four major interlinked advances were identified: implementation of new surveillance technologies adopting state-of-the-art sensors connected to the Internet of Things, deployable handheld molecular and genomic tracing tools, the incorporation of wellbeing and diverse human values into biosecurity decision-making, and sophisticated socio-environmental models and data capture. The relevance and applicability of these innovations to address threats from pathogens, pests, and weeds in both terrestrial and aquatic ecosystems emphasize the opportunity to build critical mass around interdisciplinary teams at a global scale that can rapidly advance science solutions targeting biosecurity threats.
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We couple a simple model of quarantine and testing strategies for international travellers with a model for transmission of SARS-CoV-2 in a partly vaccinated population. We use this model to estimate the risk of an infectious traveller causing a community outbreak under various border control strategies and different levels of vaccine coverage in the population. Results are calculated from N = 100,000 independent realisations of the stochastic model. We find that strategies that rely on home isolation are significantly higher risk than the current mandatory 14-day stay in government-managed isolation. Nevertheless, combinations of testing and home isolation can still reduce the risk of a community outbreak to around one outbreak per 100 infected travellers. We also find that, under some circumstances, using daily lateral flow tests or a combination of lateral flow tests and polymerase chain reaction (PCR) tests can reduce risk to a comparable or lower level than using PCR tests alone. Combined with controls on the number of travellers from countries with high prevalence of COVID-19, our results allow different options for managing the risk of COVID-19 at the border to be compared. This can be used to inform strategies for relaxing border controls in a phased way, while limiting the risk of community outbreaks as vaccine coverage increases.
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New Zealand delayed the introduction of the Omicron variant of SARS-CoV-2 into the community by the continued use of strict border controls through to January 2022. This allowed time for vaccination rates to increase and the roll out of third doses of the vaccine (boosters) to begin. It also meant more data on the characteristics of Omicron became available prior to the first cases of community transmission. Here we present a mathematical model of an Omicron epidemic, incorporating the effects of the booster roll out and waning of vaccine-induced immunity, and based on estimates of vaccine effectiveness and disease severity from international data. The model considers differing levels of immunity against infection, severe illness and death, and ignores waning of infection-induced immunity. This model was used to provide an assessment of the potential impact of an Omicron wave in the New Zealand population, which helped inform government preparedness and response. At the time the modelling was carried out, the date of introduction of Omicron into the New Zealand community was unknown. We therefore simulated outbreaks with different start dates, as well as investigating different levels of booster uptake. We found that an outbreak starting on 1 February or 1 March led to a lower health burden than an outbreak starting on 1 January because of increased booster coverage, particularly in older age groups. We also found that outbreaks starting later in the year led to worse health outcomes than an outbreak starting on 1 March. This is because waning immunity in older groups started to outweigh the increased protection from higher booster coverage in younger groups. For an outbreak starting on 1 February and with high booster uptake, the number of occupied hospital beds in the model peaked between 800 and 3,300 depending on assumed transmission rates. We conclude that combining an accelerated booster programme with public health measures to flatten the curve are key to avoid overwhelming the healthcare system.
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BACKGROUND: Digital tools are being developed to support contact tracing as part of the global effort to control the spread of COVID-19. These include smartphone apps, Bluetooth-based proximity detection, location tracking and automatic exposure notification features. Evidence on the effectiveness of alternative approaches to digital contact tracing is so far limited. METHODS: We use an age-structured branching process model of the transmission of COVID-19 in different settings to estimate the potential of manual contact tracing and digital tracing systems to help control the epidemic. We investigate the effect of the uptake rate and proportion of contacts recorded by the digital system on key model outputs: the effective reproduction number, the mean outbreak size after 30 days and the probability of elimination. RESULTS: Effective manual contact tracing can reduce the effective reproduction number from 2.4 to around 1.5. The addition of a digital tracing system with a high uptake rate over 75% could further reduce the effective reproduction number to around 1.1. Fully automated digital tracing without manual contact tracing is predicted to be much less effective. CONCLUSIONS: For digital tracing systems to make a significant contribution to the control of COVID-19, they need be designed in close conjunction with public health agencies to support and complement manual contact tracing by trained professionals.
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COVID-19 , Epidemias , Número Básico de Reprodução , COVID-19/epidemiologia , COVID-19/prevenção & controle , Busca de Comunicante , Surtos de Doenças/prevenção & controle , HumanosRESUMO
We develop a mathematical model to estimate the effect of New Zealand's vaccine rollout on the potential spread and health impacts of COVID-19. The main purpose of this study is to provide a basis for policy advice on border restrictions and control measures in response to outbreaks that may occur during the vaccination roll-out. The model can be used to estimate the theoretical population immunity threshold, which represents a point in the vaccine rollout at which border restrictions and other controls could be removed and only small, occasional outbreaks would take place. We find that, with a basic reproduction number of 6, approximately representing the Delta variant of SARS-CoV-2, and under baseline vaccine effectiveness assumptions, reaching the population immunity threshold would require close to 100% of the total population to be vaccinated. Since this coverage is not likely to be achievable in practice, relaxing controls completely would risk serious health impacts. However, the higher vaccine coverage is, the more collective protection the population has against adverse health outcomes from COVID-19, and the easier it will become to control outbreaks. There remains considerable uncertainty in model outputs, in part because of the potential for the evolution of new variants. If new variants arise that are more transmissible or vaccine resistant, an increase in vaccine coverage will be needed to provide the same level of protection.
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Vacinas contra COVID-19 , COVID-19/prevenção & controle , Modelos Teóricos , Quarentena , Vacinação , COVID-19/epidemiologia , COVID-19/transmissão , Surtos de Doenças , Humanos , Nova Zelândia/epidemiologiaRESUMO
Epidemiological models range in complexity from relatively simple statistical models that make minimal assumptions about the variables driving epidemic dynamics to more mechanistic models that include effects such as vaccine-derived and infection-derived immunity, population structure and heterogeneity. The former are often fitted to data in real-time and used for short-term forecasting, while the latter are more suitable for comparing longer-term scenarios under differing assumptions about control measures or other factors. Here, we present a mechanistic model of intermediate complexity that can be fitted to data in real-time but is also suitable for investigating longer-term dynamics. Our approach provides a bridge between primarily empirical approaches to forecasting and assumption-driven scenario models. The model was developed as a policy advice tool for New Zealand's 2021 outbreak of the Delta variant of SARS-CoV-2 and includes the effects of age structure, non-pharmaceutical interventions, and the ongoing vaccine rollout occurring during the time period studied. We use an approximate Bayesian computation approach to infer the time-varying transmission coefficient from real-time data on reported cases. We then compare projections of the model with future, out-of-sample data. We find that this approach produces a good fit with in-sample data and reasonable forward projections given the inherent limitations of predicting epidemic dynamics during periods of rapidly changing policy and behaviour. Results from the model helped inform the New Zealand Government's policy response throughout the outbreak.
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COVID-19 , SARS-CoV-2 , Humanos , Teorema de Bayes , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação , ConvulsõesRESUMO
During an epidemic, real-time estimation of the effective reproduction number supports decision makers to introduce timely and effective public health measures. We estimate the time-varying effective reproduction number, Rt , during Aotearoa New Zealand's August 2021 outbreak of the Delta variant of SARS-CoV-2, by fitting the publicly available EpiNow2 model to New Zealand case data. While we do not explicitly model non-pharmaceutical interventions or vaccination coverage, these two factors were the leading drivers of variation in transmission in this period and we describe how changes in these factors coincided with changes in Rt . Alert Level 4, New Zealand's most stringent restriction setting which includes stay-at-home measures, was initially effective at reducing the median Rt to 0.6 (90% CrI 0.4, 0.8) on 29 August 2021. As New Zealand eased certain restrictions and switched from an elimination strategy to a suppression strategy, Rt subsequently increased to a median 1.3 (1.2, 1.4). Increasing vaccination coverage along with regional restrictions were eventually sufficient to reduce Rt below 1. The outbreak peaked at an estimated 198 (172, 229) new infected cases on 10 November, after which cases declined until January 2022. We continue to update Rt estimates in real time as new case data become available to inform New Zealand's ongoing pandemic response.
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COVID-19 , Aranhas , Animais , SARS-CoV-2 , COVID-19/epidemiologia , Número Básico de Reprodução , Nova Zelândia/epidemiologiaRESUMO
New Zealand had 1499 cases of COVID-19 before eliminating transmission of the virus. Extensive contract tracing during the outbreak has resulted in a dataset of epidemiologically linked cases. This data contains useful information about the transmission dynamics of the virus, its dependence on factors such as age, and its response to different control measures. We use Monte-Carlo network construction techniques to provide an estimate of the number of secondary cases for every individual infected during the outbreak. We then apply standard statistical techniques to quantify differences between groups of individuals. Children under 10 years old are significantly under-represented in the case data. Children infected fewer people on average and had a lower probability of transmitting the disease in comparison to adults and the elderly. Imported cases infected fewer people on average and also had a lower probability of transmitting than domestically acquired cases. Superspreading is a significant contributor to the epidemic dynamics, with 20% of cases among adults responsible for 65-85% of transmission. Subclinical cases infected fewer individuals than clinical cases. After controlling for outliers serial intervals were approximated with a normal distribution (µ = 4.4 days, σ = 4.7 days). Border controls and strong social distancing measures, particularly when targeted at superspreading, play a significant role in reducing the spread of COVID-19.
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COVID-19/epidemiologia , COVID-19/transmissão , Surtos de Doenças/prevenção & controle , COVID-19/prevenção & controle , Busca de Comunicante/métodos , Busca de Comunicante/estatística & dados numéricos , Epidemias/prevenção & controle , Humanos , Método de Monte Carlo , Nova Zelândia/epidemiologia , Distanciamento Físico , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidadeRESUMO
In an attempt to maintain the elimination of COVID-19 in New Zealand, all international arrivals are required to spend 14 days in government-managed quarantine and to return a negative test result before being released. We model the testing, isolation and transmission of COVID-19 within quarantine facilities to estimate the risk of community outbreaks being seeded at the border. We use a simple branching process model for COVID-19 transmission that includes a time-dependent probability of a false-negative test result. We show that the combination of 14-day quarantine with two tests is highly effective in preventing an infectious case entering the community, provided there is no transmission within quarantine facilities. Shorter quarantine periods, or reliance on testing only with no quarantine, substantially increases the risk of an infectious case being released. We calculate the fraction of cases detected in the second week of their two-week stay and show that this may be a useful indicator of the likelihood of transmission occurring within quarantine facilities. Frontline staff working at the border risk exposure to infected individuals and this has the potential to lead to a community outbreak. We use the model to test surveillance strategies and evaluate the likely size of the outbreak at the time it is first detected. We conclude with some recommendations for managing the risk of potential future outbreaks originating from the border.
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COVID-19 , Surtos de Doenças , Humanos , Nova Zelândia/epidemiologia , Quarentena , SARS-CoV-2RESUMO
Throughout 2020 and the first part of 2021, Australia and New Zealand have followed a COVID-19 elimination strategy. Both countries require overseas arrivals to quarantine in government-managed facilities at the border. In both countries, community outbreaks of COVID-19 have been started via infection of a border worker. This workforce is rightly being prioritized for vaccination. However, although vaccines are highly effective in preventing disease, their effectiveness in preventing infection with and transmission of SARS-CoV-2 is less certain. There is a danger that vaccination could prevent symptoms of COVID-19 but not prevent transmission. Here, we use a stochastic model of SARS-CoV-2 transmission and testing to investigate the effect that vaccination of border workers has on the risk of an outbreak in an unvaccinated community. We simulate the model starting with a single infected border worker and measure the number of people who are infected before the first case is detected by testing. We show that if a vaccine reduces transmission by 50%, vaccination of border workers increases the risk of a major outbreak from around 7% per seed case to around 9% per seed case. The lower the vaccine effectiveness against transmission, the higher the risk. The increase in risk as a result of vaccination can be mitigated by increasing the frequency of routine testing for high-exposure vaccinated groups.
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New Zealand responded to the COVID-19 pandemic with a combination of border restrictions and an Alert Level (AL) system that included strict stay-at-home orders. These interventions were successful in containing an outbreak and ultimately eliminating community transmission of COVID-19 in June 2020. The timing of interventions is crucial to their success. Delaying interventions may reduce their effectiveness and mean that they need to be maintained for a longer period. We use a stochastic branching process model of COVID-19 transmission and control to simulate the epidemic trajectory in New Zealand's March-April 2020 outbreak and the effect of its interventions. We calculate key measures, including the number of reported cases and deaths, and the probability of elimination within a specified time frame. By comparing these measures under alternative timings of interventions, we show that changing the timing of AL4 (the strictest level of restrictions) has a far greater impact than the timing of border measures. Delaying AL4 restrictions results in considerably worse outcomes. Implementing border measures alone, without AL4 restrictions, is insufficient to control the outbreak. We conclude that the early introduction of stay-at-home orders was crucial in reducing the number of cases and deaths, enabling elimination.
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AIMS: We aim to quantify differences in clinical outcomes from COVID-19 infection in Aotearoa New Zealand by ethnicity and with a focus on risk of hospitalisation. METHODS: We used data on age, ethnicity, deprivation index, pre-existing health conditions and clinical outcomes on 1,829 COVID-19 cases reported in New Zealand. We used a logistic regression model to calculate odds ratios for the risk of hospitalisation by ethnicity. We also considered length of hospital stay and risk of fatality. RESULTS: After controlling for age and pre-existing conditions, we found that Maori have 2.50 times greater odds of hospitalisation (95% CI 1.39-4.51) than non-Maori non-Pacific people. Pacific people have three times greater odds (95% CI 1.75-5.33). CONCLUSIONS: Structural inequities and systemic racism in the healthcare system mean that Maori and Pacific communities face a much greater health burden from COVID-19. Older people and those with pre-existing health conditions are also at greater risk. This should inform future policy decisions including prioritising groups for vaccination.
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COVID-19/etnologia , Hospitalização/estatística & dados numéricos , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , COVID-19/mortalidade , COVID-19/terapia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Medição de Risco , Fatores de Risco , SARS-CoV-2 , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
AIMS: There is limited evidence as to how clinical outcomes of COVID-19 including fatality rates may vary by ethnicity. We aim to estimate inequities in infection fatality rates (IFR) in New Zealand by ethnicity. METHODS: We combine existing demographic and health data for ethnic groups in New Zealand with international data on COVID-19 IFR for different age groups. We adjust age-specific IFRs for differences in unmet healthcare need, and comorbidities by ethnicity. We also adjust for life expectancy reflecting evidence that COVID-19 amplifies the existing mortality risk of different groups. RESULTS: The IFR for Maori is estimated to be 50% higher than that of non-Maori, and could be even higher depending on the relative contributions of age and underlying health conditions to mortality risk. CONCLUSIONS: There are likely to be significant inequities in the health burden from COVID-19 in New Zealand by ethnicity. These will be exacerbated by racism within the healthcare system and other inequities not reflected in official data. Highest risk communities include those with elderly populations, and Maori and Pacific communities. These factors should be included in future disease incidence and impact modelling.
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Betacoronavirus , Infecções por Coronavirus/etnologia , Etnicidade/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Expectativa de Vida/etnologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Pneumonia Viral/etnologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Pandemias , Pneumonia Viral/mortalidade , SARS-CoV-2 , Taxa de Sobrevida , Adulto JovemRESUMO
Quantitative models are powerful tools for informing conservation management and decision-making. As applied modeling is increasingly used to address conservation problems, guidelines are required to clarify the scope of modeling applications and to facilitate the impact and acceptance of models by practitioners. We identify three key roles for quantitative models in conservation management: (a) to assess the extent of a conservation problem; (b) to provide insights into the dynamics of complex social and ecological systems; and, (c) to evaluate the efficacy of proposed conservation interventions. We describe 10 recommendations to facilitate the acceptance of quantitative models in conservation management, providing a basis for good practice to guide their development and evaluation in conservation applications. We structure these recommendations within four established phases of model construction, enabling their integration within existing workflows: (a) design (two recommendations); (b) specification (two); (c) evaluation (one); and (d) inference (five). Quantitative modeling can support effective conservation management provided that both managers and modelers understand and agree on the place for models in conservation. Our concise review and recommendations will assist conservation managers and modelers to collaborate in the development of quantitative models that are fit-for-purpose, and to trust and use these models appropriately while understanding key drivers of uncertainty.