Joint generalized models for multidimensional outcomes: A case study of neuroscience data from multimodalities

This paper is motivated from the analysis of neuroscience data in a study of neural and muscular mechanisms of muscle fatigue. Multidimensional outcomes of different natures were obtained simultaneously from multiple modalities, including handgrip force, electromyography (EMG), and functional magnetic resonance imaging (fMRI). We first study individual modeling of the univariate response depending on its nature. A mixed‐effects beta model and a mixed‐effects simplex model are compared for modeling the force/EMG percentages. A mixed‐effects negative‐binomial model is proposed for modeling the fMRI counts. Then, I present a joint modeling approach to model the multidimensional outcomes together, which allows us to not only estimate the covariate effects but also to evaluate the strength of association among the multiple responses from different modalities. A simulation study is conducted to quantify the possible benefits by the new approaches in finite sample situations. Finally, the analysis of the fatigue data is illustrated with the use of the proposed methods.     

Validation of elk resource selection models with spatially independent data

Knowledge of how landscape features affect wildlife resource use is essential for informed management. Resource selection functions often are used to make and validate predictions about landscape use; however, resource selection functions are rarely validated with data from landscapes independent of those from which the models were built. This problem has severely limited the application of resource selection functions over larger geographic areas for widely distributed species. North American elk (Cervus elaphus) is an example of a widely-distributed species of keen interest to managers and for which validation of resource selection functions over large geographic areas is important. We evaluated the performance of resource selection functions developed for elk on one landscape in northeast Oregon with independent data from a different landscape in the same region. We compared predicted versus observed elk resource use for 9 monthly or seasonal periods across 3 yr. Results showed strong, positive agreement between predicted and observed use for 2 spring and 3 late summer-early fall models (3-yr r = 0.81–0.95). Predicted versus observed use was negatively or weakly positively correlated for 3 summer models and 1 mid-fall model (3-yr r = −0.57–0.14). Predicted and observed use correlated well when forage was limited (spring and late summer or early fall), corresponding to important biological stages for elk (parturition and breeding seasons). For these seasonal periods, model covariates such as rate of motorized traffic and canopy closure often were effective predictors of elk resource selection. The models we validated for spring and late summer-early fall may be used to evaluate management activities in areas with similar landscape characteristics. © 2010 The Wildlife Society.     

Characterizing and modeling hydrogen sulfide production in anaerobic digestion of livestock manure,agro-industrial wastes,and wastewater sludge

Hydrogen sulfide (H₂S) is the most undesirable inorganic gas in biogas from anaerobic digestion (AD). However, H₂S production in AD is complex and understanding of its processes is still limited. This study performed six controlled batch anaerobic co-digestion experiments to investigate H₂S production. Materials were obtained from four field anaerobic digester systems and co-digestion feedstocks from agroindustry. An additional precipitation experiment was conducted to further examine H₂S production dynamics. Digesters containing highly soluble, carbohydrate-based wastes had a high H₂S final specific production (FSP) value. Additionally, the FSP values were negatively correlated with the initial Fe(II):S ratios in the digester liquid of the batch tests. The precipitation experiment indicated that iron sulfide precipitation was preferred in the presence of an anaerobic community. The H₂S production as a time series was successfully modeled using a generalized additive model (R² > 0.82). This study revealed that sulfate, phosphorus, and iron concentrations are important predictors and potential inhibitors of H₂S production in AD. Further examination of real-time H₂S modeling in AD is warranted.     

Performance of the marginal structural models under various scenarios of incomplete marker's values: A simulation study

Marginal structural models (MSMs) have been proposed for estimating a treatment's effect, in the presence of time‐dependent confounding. We aimed to evaluate the performance of the Cox MSM in the presence of missing data and to explore methods to adjust for missingness. We simulated data with a continuous time‐dependent confounder and a binary treatment. We explored two classes of missing data: (i) missed visits, which resemble clinical cohort studies; (ii) missing confounder's values, which correspond to interval cohort studies. Missing data were generated under various mechanisms. In the first class, the source of the bias was the extreme treatment weights. Truncation or normalization improved estimation. Therefore, particular attention must be paid to the distribution of weights, and truncation or normalization should be applied if extreme weights are noticed. In the second case, bias was due to the misspecification of the treatment model. Last observation carried forward (LOCF), multiple imputation (MI), and inverse probability of missingness weighting (IPMW) were used to correct for the missingness. We found that alternatives, especially the IPMW method, perform better than the classic LOCF method. Nevertheless, in situations with high marker's variance and rarely recorded measurements none of the examined method adequately corrected the bias.     

Is adaptation to climate change really constrained in niche specialists?

Species with restricted distributions make up the vast majority of biodiversity. Recent evidence suggests that Drosophila species with restricted tropical distributions lack genetic variation in the key trait of desiccation resistance. It has therefore been predicted that tropically restricted species will be limited in their evolutionary response to future climatic changes and will face higher risks of extinction. However, these assessments have been made using extreme levels of desiccation stress (less than 10% relative humidity (RH)) that extend well beyond the changes projected for the wet tropics under climate change scenarios over the next 30 years. Here, we show that significant evolutionary responses to less extreme (35% RH) but more ecologically realistic levels of climatic change and desiccation stress are in fact possible in two species of rainforest restricted Drosophila. Evolution may indeed be an important means by which sensitive rainforest-restricted species are able to mitigate the effects of climate change.     

Trafficking mechanisms of extracellular matrix macromolecules: Insights from vertebrate development and human diseases

Cellular life depends on protein transport and membrane traffic. In multicellular organisms, membrane traffic is required for extracellular matrix deposition, cell adhesion, growth factor release, and receptor signaling, which are collectively required to integrate the development and physiology of tissues and organs. Understanding the regulatory mechanisms that govern cargo and membrane flow presents a prime challenge in cell biology. Extracellular matrix (ECM) secretion remains poorly understood, although given its essential roles in the regulation of cell migration, differentiation, and survival, ECM secretion mechanisms are likely to be tightly controlled.Recent studies in vertebrate model systems, from fishes to mammals and in human patients, have revealed complex and diverse loss-of-function phenotypes associated with mutations in components of the secretory machinery. A broad spectrum of diseases from skeletal and cardiovascular to neurological deficits have been linked to ECM trafficking. These discoveries have directly challenged the prevailing view of secretion as an essential but monolithic process. Here, we will discuss the latest findings on mechanisms of ECM trafficking in vertebrates.     

Large-scale production of mouse phenotypes: the search for animal models for inherited diseases in humans

This paper is aimed principally at bioinformaticians and biologists as an introduction to recent advances in mouse mutagenesis, concentrating on genome-wide screens utilising the powerful mutagen N-ethyl-N-nitroso-urea (ENU). It contains a brief background to the underlying genetics as well as details of the practical aspects of organisation and data capture for such projects.     

Statistical methods for detecting molecular adaptation

The past few years have seen the development of powerful statistical methods for detecting adaptive molecular evolution. These methods compare synonymous and nonsynonymous substitution rates in protein-coding genes, and regard a nonsynonymous rate elevated above the synonymous rate as evidence for darwinian selection. Numerous cases of molecular adaptation are being identified in various systems from viruses to humans. Although previous analyses averaging rates over sites and time have little power, recent methods designed to detect positive selection at individual sites and lineages have been successful. Here, we summarize recent statistical methods for detecting molecular adaptation, and discuss their limitations and possible improvements.