Zero‐inflated spatio‐temporal models for disease mapping

In this paper, our aim is to analyze geographical and temporal variability of disease incidence when spatio‐temporal count data have excess zeros. To that end, we consider random effects in zero‐inflated Poisson models to investigate geographical and temporal patterns of disease incidence. Spatio‐temporal models that employ conditionally autoregressive smoothing across the spatial dimension and B‐spline smoothing over the temporal dimension are proposed. The analysis of these complex models is computationally difficult from the frequentist perspective. On the other hand, the advent of the Markov chain Monte Carlo algorithm has made the Bayesian analysis of complex models computationally convenient. Recently developed data cloning method provides a frequentist approach to mixed models that is also computationally convenient. We propose to use data cloning, which yields to maximum likelihood estimation, to conduct frequentist analysis of zero‐inflated spatio‐temporal modeling of disease incidence. One of the advantages of the data cloning approach is that the prediction and corresponding standard errors (or prediction intervals) of smoothing disease incidence over space and time is easily obtained. We illustrate our approach using a real dataset of monthly children asthma visits to hospital in the province of Manitoba, Canada, during the period April 2006 to March 2010. Performance of our approach is also evaluated through a simulation study.     

Linking demographic and food‐web models to understand management trade‐offs

Alternatives in ecosystem‐based management often differ with respect to trade‐offs between ecosystem values. Ecosystem or food‐web models and demographic models are typically employed to evaluate alternatives, but the approaches are rarely integrated to uncover conflicts between values. We applied multistate models to a capture–recapture dataset on common guillemots Uria aalge breeding in the Baltic Sea to identify factors influencing survival. The estimated relationships were employed together with Ecopath‐with‐Ecosim food‐web model simulations to project guillemot survival under six future scenarios incorporating climate change. The scenarios were based on management alternatives for eutrophication and cod fisheries, issues considered top priority for regional management, but without known direct effects on the guillemot population. Our demographic models identified prey quantity (abundance and biomass of sprat Sprattus sprattus) as the main factor influencing guillemot survival. Most scenarios resulted in projections of increased survival, in the near (2016–2040) and distant (2060–2085) future. However, in the scenario of reduced nutrient input and precautionary cod fishing, guillemot survival was projected to be lower in both future periods due to lower sprat stocks. Matrix population models suggested a substantial decline of the guillemot population in the near future, 24% per 10 years, and a smaller reduction, 1.1% per 10 years, in the distant future. To date, many stakeholders and Baltic Sea governments have supported reduced nutrient input and precautionary cod fishing and implementation is underway. Negative effects on nonfocal species have previously not been uncovered, but our results show that the scenario is likely to negatively impact the guillemot population. Linking model results allowed identifying trade‐offs associated with management alternatives. This information is critical to thorough evaluation by decision‐makers, but not easily obtained by food‐web models or demographic models in isolation. Appropriate datasets are often available, making it feasible to apply a linked approach for better‐informed decisions in ecosystem‐based management.     

One method to establish Epstein‐Barr virus‐associated NK/T cell lymphoma mouse models

Novel nude mice model of human NK/T cell lymphoma were established by subcutaneously injecting two NK/T cell lymphoma cell lines into the right axillary region of mice and successful passages were completed by injecting cell suspension which was obtained through a 70‐μm cell strainer. These mice models and corresponding cell clones have been successfully developed for more than 8 generations. The survival rates of both resuscitation and transplantation in NKYS and YT models were 90% and 70% correspondingly. Pathologically, the tumour cells in all passages of the lymphoma‐bearing mice and cell lines obtained from tumours were parallel to initial cell lines. Immunologically, the tumour cells expressed the characteristics of the primary and essential NK/T lymphomas. The novel mice models maintained the essential features of human NK/T cell lymphoma, and they would be ideal tools in vivo for further research of human NK/T cell lymphoma.     

Mixed‐Effects State‐Space Models for Analysis of Longitudinal Dynamic Systems

Summary The rapid development of new biotechnologies allows us to deeply understand biomedical dynamic systems in more detail and at a cellular level. Many of the subject‐specific biomedical systems can be described by a set of differential or difference equations that are similar to engineering dynamic systems. In this article, motivated by HIV dynamic studies, we propose a class of mixed‐effects state‐space models based on the longitudinal feature of dynamic systems. State‐space models with mixed‐effects components are very flexible in modeling the serial correlation of within‐subject observations and between‐subject variations. The Bayesian approach and the maximum likelihood method for standard mixed‐effects models and state‐space models are modified and investigated for estimating unknown parameters in the proposed models. In the Bayesian approach, full conditional distributions are derived and the Gibbs sampler is constructed to explore the posterior distributions. For the maximum likelihood method, we develop a Monte Carlo EM algorithm with a Gibbs sampler step to approximate the conditional expectations in the E‐step. Simulation studies are conducted to compare the two proposed methods. We apply the mixed‐effects state‐space model to a data set from an AIDS clinical trial to illustrate the proposed methodologies. The proposed models and methods may also have potential applications in other biomedical system analyses such as tumor dynamics in cancer research and genetic regulatory network modeling.     

Effect of detection heterogeneity in occupancy‐detection models: an experimental test of time‐to‐first‐detection methods

Imperfect detection can bias estimates of site occupancy in ecological surveys but can be corrected by estimating detection probability. Time‐to‐first‐detection (TTD) occupancy models have been proposed as a cost–effective survey method that allows detection probability to be estimated from single site visits. Nevertheless, few studies have validated the performance of occupancy‐detection models by creating a situation where occupancy is known, and model outputs can be compared with the truth. We tested the performance of TTD occupancy models in the face of detection heterogeneity using an experiment based on standard survey methods to monitor koala Phascolarctos cinereus populations in Australia. Known numbers of koala faecal pellets were placed under trees, and observers, uninformed as to which trees had pellets under them, carried out a TTD survey. We fitted five TTD occupancy models to the survey data, each making different assumptions about detectability, to evaluate how well each estimated the true occupancy status. Relative to the truth, all five models produced strongly biased estimates, overestimating detection probability and underestimating the number of occupied trees. Despite this, goodness‐of‐fit tests indicated that some models fitted the data well, with no evidence of model misfit. Hence, TTD occupancy models that appear to perform well with respect to the available data may be performing poorly. The reason for poor model performance was unaccounted for heterogeneity in detection probability, which is known to bias occupancy‐detection models. This poses a problem because unaccounted for heterogeneity could not be detected using goodness‐of‐fit tests and was only revealed because we knew the experimentally determined outcome. A challenge for occupancy‐detection models is to find ways to identify and mitigate the impacts of unobserved heterogeneity, which could unknowingly bias many models.     

Large‐scale prerain vegetation green‐up across Africa

Information on the response of vegetation to different environmental drivers, including rainfall, forms a critical input to ecosystem models. Currently, such models are run based on parameters that, in some cases, are either assumed or lack supporting evidence (e.g., that vegetation growth across Africa is rainfall‐driven). A limited number of studies have reported that the onset of rain across Africa does not fully explain the onset of vegetation growth, for example, drawing on the observation of prerain flush effects in some parts of Africa. The spatial extent of this prerain green‐up effect, however, remains unknown, leaving a large gap in our understanding that may bias ecosystem modelling. This paper provides the most comprehensive spatial assessment to‐date of the magnitude and frequency of the different patterns of phenology response to rainfall across Africa and for different vegetation types. To define the relations between phenology and rainfall, we investigated the spatial variation in the difference, in number of days, between the start of rainy season (SRS) and start of vegetation growing season (SOS); and between the end of rainy season (ERS) and end of vegetation growing season (EOS). We reveal a much more extensive spread of prerain green‐up over Africa than previously reported, with prerain green‐up being the norm rather than the exception. We also show the relative sparsity of postrain green‐up, confined largely to the Sudano‐Sahel region. While the prerain green‐up phenomenon is well documented, its large spatial extent was not anticipated. Our results, thus, contrast with the widely held view that rainfall drives the onset and end of the vegetation growing season across Africa. Our findings point to a much more nuanced role of rainfall in Africa's vegetation growth cycle than previously thought, specifically as one of a set of several drivers, with important implications for ecosystem modelling.     

Use of time‐at‐temperature data to describe dive behavior in five species of sympatric deep‐diving toothed whales

This paper develops and validates a method of using time‐at‐temperature (TAT) histograms from satellite transmitter tags to describe the dive activity patterns and approximate depth distributions of five deep‐diving toothed whale species in the northern Bahamas. TAT histograms represent a bandwidth‐conserving method of recovering a long‐term proxy record of dive activity. However, using temperature to interpret TAT on a scale of approximate depths required the complex estimation of TAT histogram bin boundary depths in a dynamic oceanographic region. Here we evaluated the relative performance of four interpolation methods and a global reanalysis data assimilation model in estimating climatological isotherm depth surfaces within our study area. TAT‐derived approximate time‐at‐depth (TAD) distributions aligned closely with directly observed TAD distributions from a smaller sample of depth‐recording satellite tags deployed on separate individuals of each species. TAT‐derived approximate depth distributions were also consistent with various published accounts for this suite of species. Estimating dive ranges and time budgets are important components of (1) understanding habitat overlap between species, (2) evaluating the potential role of these predators in meso‐ and bathypelagic ecosystems, and (3) assessing vulnerability and exposure to anthropogenic impacts.     

Robust Tests for Candidate‐Gene Association Using Case‐Parents Trios with a Multi‐Allelic Marker

In case‐parents trios design, the association between a multi‐allelic candidate‐gene and a disease can be detected by using maximum of score tests (max‐score) when the mode of inheritance is known. We apply the maximum of the max‐score statistics and the maximum of likelihood ratio statistics when the genetic model is unknown and examine their robust properties compared to max‐score statistics. The simulation results demonstrate that the two maximum robust tests are more efficacious and robust across all genetic models compared with the three max‐score tests. Moreover, in most situations, the maximum of the max‐score tests seems to be more powerful than the maximum of the likelihood ratio tests. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Seasonal temperature and precipitation regulate brook trout young‐of‐the‐year abundance and population dynamics

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Individual‐based ecology of coastal birds

Conservation objectives for non‐breeding coastal birds (shorebirds and wildfowl) are determined from their population size at coastal sites. To advise coastal managers, models must predict quantitatively the effects of environmental change on population size or the demographic rates (mortality and reproduction) that determine it. As habitat association models and depletion models are not able to do this, we developed an approach that has produced such predictions thereby enabling policy makers to make evidence‐based decisions. Our conceptual framework is individual‐based ecology, in which populations are viewed as having properties (e.g. size) that arise from the traits (e.g. behaviour, physiology) and interactions of their constituent individuals. The link between individuals and populations is made through individual‐based models (IBMs) that follow the fitness‐maximising decisions of individuals and predict population‐level consequences (e.g. mortality rate) from the fates of these individuals. Our first IBM was for oystercatchers Haematopus ostralegus and accurately predicted their density‐dependent mortality. Subsequently, IBMs were developed for several shorebird and wildfowl species at several European sites, and were shown to predict accurately overwinter mortality, and the foraging behaviour from which predictions are derived. They have been used to predict the effect on survival in coastal birds of sea level rise, habitat loss, wind farm development, shellfishing and human disturbance. This review emphasises the wider applicability of the approach, and identifies other systems to which it could be applied. We view the IBM approach as a very useful contribution to the general problem of how to advance ecology to the point where we can routinely make meaningful predictions of how populations respond to environmental change.     

Model‐Assisted Ranked Survey Sampling

The problem of Ranked Set Sampling [RSS] is analyzed and a ratio estimator is proposed. A simple linear regression superpopulation model is proposed as a counterpart to the design approach. A predictor is developed by using shrinkage techniques.     

Evaluating and presenting uncertainty in model‐based unconstrained ordination

Variability in ecological community composition is often analyzed by recording the presence or abundance of taxa in sample units, calculating a symmetric matrix of pairwise distances or dissimilarities among sample units and then mapping the resulting matrix to a low‐dimensional representation through methods collectively called ordination. Unconstrained ordination only uses taxon composition data, without any environmental or experimental covariates, to infer latent compositional gradients associated with the sampling units. Commonly, such distance‐based methods have been used for ordination, but recently there has been a shift toward model‐based approaches. Model‐based unconstrained ordinations are commonly formulated using a Bayesian latent factor model that permits uncertainty assessment for parameters, including the latent factors that correspond to gradients in community composition. While model‐based methods have the additional benefit of addressing uncertainty in the estimated gradients, typically the current practice is to report point estimates without summarizing uncertainty. To demonstrate the uncertainty present in model‐based unconstrained ordination, the well‐known spider and dune data sets were analyzed and shown to have large uncertainty in the ordination projections. Hence to understand the factors that contribute to the uncertainty, simulation studies were conducted to assess the impact of additional sampling units or species to help inform future ordination studies that seek to minimize variability in the latent factors. Accurate reporting of uncertainty is an important part of transparency in the scientific process; thus, a model‐based approach that accounts for uncertainty is valuable. An R package, UncertainOrd , contains visualization tools that accurately represent estimates of the gradients in community composition in the presence of uncertainty.     

Should ecologists prefer model‐ over distance‐based multivariate methods?

Ecological data sets often record the abundance of species, together with a set of explanatory variables. Multivariate statistical methods are optimal to analyze such data and are thus frequently used in ecology for exploration, visualization, and inference. Most approaches are based on pairwise distance matrices instead of the sites‐by‐species matrix, which stands in stark contrast to univariate statistics, where data models, assuming specific distributions, are the norm. However, through advances in statistical theory and computational power, models for multivariate data have gained traction. Systematic simulation‐based performance evaluations of these methods are important as guides for practitioners but still lacking. Here, we compare two model‐based methods, multivariate generalized linear models (MvGLMs) and constrained quadratic ordination (CQO), with two distance‐based methods, distance‐based redundancy analysis (dbRDA) and canonical correspondence analysis (CCA). We studied the performance of the methods to discriminate between causal variables and noise variables for 190 simulated data sets covering different sample sizes and data distributions. MvGLM and dbRDA differentiated accurately between causal and noise variables. The former had the lowest false‐positive rate (0.008), while the latter had the lowest false‐negative rate (0.027). CQO and CCA had the highest false‐negative rate (0.291) and false‐positive rate (0.256), respectively, where these error rates were typically high for data sets with linear responses. Our study shows that both model‐ and distance‐based methods have their place in the ecologist's statistical toolbox. MvGLM and dbRDA are reliable for analyzing species–environment relations, whereas both CQO and CCA exhibited considerable flaws, especially with linear environmental gradients.