Better null models for assessing predictive accuracy of disease models.

Null models provide a critical baseline for the evaluation of predictive disease models. Many studies consider only the grand mean null model (i.e. R2) when evaluating the predictive ability of a model, which is insufficient to convey the predictive power of a model. We evaluated ten null models for human cases of West Nile virus (WNV), a zoonotic mosquito-borne disease introduced to the United States in 1999. The Negative Binomial, Historical (i.e. using previous cases to predict future cases) and Always Absent null models were the strongest overall, and the majority of null models significantly outperformed the grand mean. The length of the training timeseries increased the performance of most null models in US counties where WNV cases were frequent, but improvements were similar for most null models, so relative scores remained unchanged. We argue that a combination of null models is needed to evaluate the forecasting performance of predictive models for infectious diseases and the grand mean is the lowest bar.

Patterns of West Nile Virus in the Northeastern United States Using Negative Binomial and Mechanistic Trait-Based Models.

West Nile virus (WNV) primarily infects birds and mosquitoes but has also caused over 2,000 human deaths, and >50,000 reported human cases in the United States. Expected numbers of WNV neuroinvasive cases for the present were described for the Northeastern United States, using a negative binomial model. Changes in temperature-based suitability for WNV due to climate change were examined for the next decade using a temperature-trait model. WNV suitability was generally expected to increase over the next decade due to changes in temperature, but the changes in suitability were generally small. Many, but not all, populous counties in the northeast are already near peak suitability. Several years in a row of low case numbers is consistent with a negative binomial, and should not be interpreted as a change in disease dynamics. Public health budgets need to be prepared for the expected infrequent years with higher-than-average cases. Low-population counties that have not yet had a case are expected to have similar probabilities of having a new case as nearby low-population counties with cases, as these absences are consistent with a single statistical distribution and random chance.

Evaluation of an open forecasting challenge to assess skill of West Nile virus neuroinvasive disease prediction.

BACKGROUND: West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental USA. WNV occurrence has high spatiotemporal variation, and current approaches to targeted control of the virus are limited, making forecasting a public health priority. However, little research has been done to compare strengths and weaknesses of WNV disease forecasting approaches on the national scale. We used forecasts submitted to the 2020 WNV Forecasting Challenge, an open challenge organized by the Centers for Disease Control and Prevention, to assess the status of WNV neuroinvasive disease (WNND) prediction and identify avenues for improvement. METHODS: We performed a multi-model comparative assessment of probabilistic forecasts submitted by 15 teams for annual WNND cases in US counties for 2020 and assessed forecast accuracy, calibration, and discriminatory power. In the evaluation, we included forecasts produced by comparison models of varying complexity as benchmarks of forecast performance. We also used regression analysis to identify modeling approaches and contextual factors that were associated with forecast skill. RESULTS: Simple models based on historical WNND cases generally scored better than more complex models and combined higher discriminatory power with better calibration of uncertainty. Forecast skill improved across updated forecast submissions submitted during the 2020 season. Among models using additional data, inclusion of climate or human demographic data was associated with higher skill, while inclusion of mosquito or land use data was associated with lower skill. We also identified population size, extreme minimum winter temperature, and interannual variation in WNND cases as county-level characteristics associated with variation in forecast skill. CONCLUSIONS: Historical WNND cases were strong predictors of future cases with minimal increase in skill achieved by models that included other factors. Although opportunities might exist to specifically improve predictions for areas with large populations and low or high winter temperatures, areas with high case-count variability are intrinsically more difficult to predict. Also, the prediction of outbreaks, which are outliers relative to typical case numbers, remains difficult. Further improvements to prediction could be obtained with improved calibration of forecast uncertainty and access to real-time data streams (e.g. current weather and preliminary human cases).

SARS-CoV-2 Vaccine Breakthrough by Omicron and Delta Variants, New York, USA.

Recently emerged SARS-CoV-2 variants have greater potential than earlier variants to cause vaccine breakthrough infections. During emergence of the Delta and Omicron variants, a matched case-control analysis used a viral genomic sequence dataset linked with demographic and vaccination information from New York, USA, to examine associations between virus lineage and patient vaccination status, patient age, vaccine type, and time since vaccination. Case-patients were persons infected with the emerging virus lineage, and controls were persons infected with any other virus lineage. Infections in fully vaccinated and boosted persons were significantly associated with the Omicron lineage. Odds of infection with Omicron relative to Delta generally decreased with increasing patient age. A similar pattern was observed with vaccination status during Delta emergence but was not significant. Vaccines offered less protection against Omicron, thereby increasing the number of potential hosts for emerging variants.

Transcriptomic analysis of the Myxococcus xanthus FruA regulon, and comparative developmental transcriptomic analysis of two fruiting body forming species, Myxococcus xanthus and Myxococcus stipitatus.

BACKGROUND: The Myxococcales are well known for their predatory and developmental social processes, and for the molecular complexity of regulation of these processes. Many species within this order have unusually large genomes compared to other bacteria, and their genomes have many genes that are unique to one specific sequenced species or strain. Here, we describe RNAseq based transcriptome analysis of the FruA regulon of Myxococcus xanthus and a comparative RNAseq analysis of two Myxococcus species, M. xanthus and Myxococcus stipitatus, as they respond to starvation and begin forming fruiting bodies. RESULTS: We show that both species have large numbers of genes that are developmentally regulated, with over half the genome showing statistically significant changes in expression during development in each species. We also included a non-fruiting mutant of M. xanthus that is missing the transcriptional regulator FruA to identify the direct and indirect FruA regulon and to identify transcriptional changes that are specific to fruiting and not just the starvation response. We then identified Interpro gene ontologies and COG annotations that are significantly up- or down-regulated during development in each species. Our analyses support previous data for M. xanthus showing developmental upregulation of signal transduction genes, and downregulation of genes related to cell-cycle, translation, metabolism, and in some cases, DNA replication. Gene expression in M. stipitatus follows similar trends. Although not all specific genes show similar regulation patterns in both species, many critical developmental genes in M. xanthus have conserved expression patterns in M. stipitatus, and some groups of otherwise unstudied orthologous genes share expression patterns. CONCLUSIONS: By identifying the FruA regulon and identifying genes that are similarly and uniquely regulated in two different species, this work provides a more complete picture of transcription during Myxococcus development. We also provide an R script to allow other scientists to mine our data for genes whose expression patterns match a user-selected gene of interest.

A proposed framework for the development and qualitative evaluation of West Nile virus models and their application to local public health decision-making.

West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m-km, days-weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input.

West Nile virus is predicted to be more geographically widespread in New York State and Connecticut under future climate change.

The effects of climate change on infectious diseases are a topic of considerable interest and discussion. We studied West Nile virus (WNV) in New York (NY) and Connecticut (CT) using a Weather Research and Forecasting (WRF) model climate change scenario, which allows us to examine the effects of climate change and variability on WNV risk at county level. We chose WNV because it is well studied, has caused over 50,000 reported human cases, and over 2200 deaths in the United States. The ecological impacts have been substantial (e.g., millions of avian deaths), and economic impacts include livestock deaths, morbidity, and healthcare-related expenses. We trained two Random Forest models with observational climate data and human cases to predict future levels of WNV based on future weather conditions. The Regional Model used present-day data from NY and CT, whereas the Analog Model was fit for states most closely matching the predicted future conditions in the region. Separately, we predicted changes to mosquito-based WNV risk using a trait-based thermal biology approach (Mosquito Model). The WRF model produced control simulations (present day) and pseudo-global warming simulations (future). The Regional and Analog Models predicted an overall increase in human cases of WNV under future warming. However, the Analog Model did not predict as strong of an increase in the number of human cases as the Regional Model, and predicted a decrease in cases in some counties that currently experience high numbers of WNV cases. The Mosquito Model also predicted a decrease in risk in current high-risk areas, with an overall reduction in the population-weighted relative risk (but an increase in area-weighted risk). The Mosquito Model supports the Analog Model as making more realistic predictions than the Regional Model. All three models predicted a geographic increase in WNV cases across NY and CT.

The Role of Temperature in Transmission of Zoonotic Arboviruses.

We reviewed the literature on the role of temperature in transmission of zoonotic arboviruses. Vector competence is affected by both direct and indirect effects of temperature, and generally increases with increasing temperature, but results may vary by vector species, population, and viral strain. Temperature additionally has a significant influence on life history traits of vectors at both immature and adult life stages, and for important behaviors such as blood-feeding and mating. Similar to vector competence, temperature effects on life history traits can vary by species and population. Vector, host, and viral distributions are all affected by temperature, and are generally expected to change with increased temperatures predicted under climate change. Arboviruses are generally expected to shift poleward and to higher elevations under climate change, yet significant variability on fine geographic scales is likely. Temperature effects are generally unimodal, with increases in abundance up to an optimum, and then decreases at high temperatures. Improved vector distribution information could facilitate future distribution modeling. A wide variety of approaches have been used to model viral distributions, although most research has focused on the West Nile virus. Direct temperature effects are frequently observed, as are indirect effects, such as through droughts, where temperature interacts with rainfall. Thermal biology approaches hold much promise for syntheses across viruses, vectors, and hosts, yet future studies must consider the specificity of interactions and the dynamic nature of evolving biological systems.

Seasonal temperatures and hydrological conditions improve the prediction of West Nile virus infection rates in Culex mosquitoes and human case counts in New York and Connecticut.

West Nile virus (WNV; Flaviviridae: Flavivirus) is a widely distributed arthropod-borne virus that has negatively affected human health and animal populations. WNV infection rates of mosquitoes and human cases have been shown to be correlated with climate. However, previous studies have been conducted at a variety of spatial and temporal scales, and the scale-dependence of these relationships has been understudied. We tested the hypothesis that climate variables are important to understand these relationships at all spatial scales. We analyzed the influence of climate on WNV infection rate of mosquitoes and number of human cases in New York and Connecticut using Random Forests, a machine learning technique. During model development, 66 climate-related variables based on temperature, precipitation and soil moisture were tested for predictive skill. We also included 20-21 non-climatic variables to account for known environmental effects (e.g., land cover and human population), surveillance related information (e.g., relative mosquito abundance), and to assess the potential explanatory power of other relevant factors (e.g., presence of wastewater treatment plants). Random forest models were used to identify the most important climate variables for explaining spatial-temporal variation in mosquito infection rates (abbreviated as MLE). The results of the cross-validation support our hypothesis that climate variables improve the predictive skill for MLE at county- and trap-scales and for human cases at the county-scale. Of the climate-related variables selected, mean minimum temperature from July-September was selected in all analyses, and soil moisture was selected for the mosquito county-scale analysis. Models demonstrated predictive skill, but still over- and under-estimated WNV MLE and numbers of human cases. Models at fine spatial scales had lower absolute errors but had greater errors relative to the mean infection rates.

A review of the ecosystem functions in oil palm plantations, using forests as a reference system.

Oil palm plantations have expanded rapidly in recent decades. This large-scale land-use change has had great ecological, economic, and social impacts on both the areas converted to oil palm and their surroundings. However, research on the impacts of oil palm cultivation is scattered and patchy, and no clear overview exists. We address this gap through a systematic and comprehensive literature review of all ecosystem functions in oil palm plantations, including several (genetic, medicinal and ornamental resources, information functions) not included in previous systematic reviews. We compare ecosystem functions in oil palm plantations to those in forests, as the conversion of forest to oil palm is prevalent in the tropics. We find that oil palm plantations generally have reduced ecosystem functioning compared to forests: 11 out of 14 ecosystem functions show a net decrease in level of function. Some functions show decreases with potentially irreversible global impacts (e.g. reductions in gas and climate regulation, habitat and nursery functions, genetic resources, medicinal resources, and information functions). The most serious impacts occur when forest is cleared to establish new plantations, and immediately afterwards, especially on peat soils. To variable degrees, specific plantation management measures can prevent or reduce losses of some ecosystem functions (e.g. avoid illegal land clearing via fire, avoid draining of peat, use of integrated pest management, use of cover crops, mulch, and compost) and we highlight synergistic mitigation measures that can improve multiple ecosystem functions simultaneously. The only ecosystem function which increases in oil palm plantations is, unsurprisingly, the production of marketable goods. Our review highlights numerous research gaps. In particular, there are significant gaps with respect to socio-cultural information functions. Further, there is a need for more empirical data on the importance of spatial and temporal scales, such as differences among plantations in different environments, of different sizes, and of different ages, as our review has identified examples where ecosystem functions vary spatially and temporally. Finally, more research is needed on developing management practices that can offset the losses of ecosystem functions. Our findings should stimulate research to address the identified gaps, and provide a foundation for more systematic research and discussion on ways to minimize the negative impacts and maximize the positive impacts of oil palm cultivation.

Land-use intensification causes multitrophic homogenization of grassland communities.

Land-use intensification is a major driver of biodiversity loss. Alongside reductions in local species diversity, biotic homogenization at larger spatial scales is of great concern for conservation. Biotic homogenization means a decrease in ß-diversity (the compositional dissimilarity between sites). Most studies have investigated losses in local (α)-diversity and neglected biodiversity loss at larger spatial scales. Studies addressing ß-diversity have focused on single or a few organism groups (for example, ref. 4), and it is thus unknown whether land-use intensification homogenizes communities at different trophic levels, above- and belowground. Here we show that even moderate increases in local land-use intensity (LUI) cause biotic homogenization across microbial, plant and animal groups, both above- and belowground, and that this is largely independent of changes in α-diversity. We analysed a unique grassland biodiversity dataset, with abundances of more than 4,000 species belonging to 12 trophic groups. LUI, and, in particular, high mowing intensity, had consistent effects on ß-diversity across groups, causing a homogenization of soil microbial, fungal pathogen, plant and arthropod communities. These effects were nonlinear and the strongest declines in ß-diversity occurred in the transition from extensively managed to intermediate intensity grassland. LUI tended to reduce local α-diversity in aboveground groups, whereas the α-diversity increased in belowground groups. Correlations between the ß-diversity of different groups, particularly between plants and their consumers, became weaker at high LUI. This suggests a loss of specialist species and is further evidence for biotic homogenization. The consistently negative effects of LUI on landscape-scale biodiversity underscore the high value of extensively managed grasslands for conserving multitrophic biodiversity and ecosystem service provision. Indeed, biotic homogenization rather than local diversity loss could prove to be the most substantial consequence of land-use intensification.

Testing the role of patch openness as a causal mechanism for apparent area sensitivity in a grassland specialist.

Area sensitivity, species being disproportionately present on larger habitat patches, has been identified in many taxa. We propose that some apparently area-sensitive species are actually responding to how open a habitat patch is, rather than to patch size. We tested this hypothesis for Bobolinks (Dolichonyx oryzivorus) by comparing density and occupancy to a novel openness index, patch area, and edge effects. Bobolink density and occupancy showed significant relationships with openness, but logistic models based on an openness occupancy threshold had greater explanatory power. Thresholds remained approximately consistent from June through August, and shifted to be more open in September. Variance partitioning supported the openness index as unique and relevant. We found no relationships between measures of body condition (body mass, body size, circulating corticosterone levels) and either openness or area. Our findings have implications for studies of area sensitivity, especially with regards to inconsistencies reported within species: specifically, (1) whether or not a study finds a species to be area sensitive may depend on whether small, open sites were sampled, and (2) area regressions were sensitive to observed densities at the largest sites, suggesting that variation in these fields could lead to inconsistent area sensitivity responses. Responses to openness may be a consequence of habitat selection mediated by predator effects. Finally, openness measures may have applications for predicting effects of habitat management or development, such as adding wind turbines, in open habitat.