A new regression model for overdispersed binomial data accounting for outliers and an excess of zeros.

Binary outcomes are extremely common in biomedical research. Despite its popularity, binomial regression often fails to model this kind of data accurately due to the overdispersion problem. Many alternatives can be found in the literature, the beta-binomial (BB) regression model being one of the most popular. The additional parameter of this model enables a better fit to overdispersed data. It also exhibits an attractive interpretation in terms of the intraclass correlation coefficient. Nonetheless, in many real data applications, a single additional parameter cannot handle the entire excess of variability. In this study, we propose a new finite mixture distribution with BB components, namely, the flexible beta-binomial (FBB), which is characterized by a richer parameterization. This allows us to enhance the variance structure to account for multiple causes of overdispersion while also preserving the intraclass correlation interpretation. The novel regression model, based on the FBB distribution, exploits the flexibility and large variety of the distribution's possible shapes (which includes bimodality and various tail behaviors). Thus, it succeeds in accounting for several (possibly concomitant) sources of overdispersion stemming from the presence of latent groups in the population, outliers, and excessive zero observations. Adopting a Bayesian approach to inference, we perform an intensive simulation study that shows the superiority of the new regression model over that of the existing ones. Its better performance is also confirmed by three applications to real datasets extensively studied in the biomedical literature, namely, bacteria data, atomic bomb radiation data, and control mice data.

Eutrophic status influences the impact of pesticide mixtures and predation on Daphnia pulex populations.

Pesticides, nutrients, and ecological stressors such as competition or predation co-occur in freshwater ecosystems impacted by agriculture. The extent to which combinations of these stressors affect aquatic populations and the role of nutrients availability in modulating these responses requires further understanding. In this study, we assessed how pesticides affecting different taxonomic groups and predation influence the response of Daphnia pulex populations under different trophic conditions. An outdoor experiment was designed following a factorial design, with the insecticide chlorpyrifos, the herbicide diuron, and the predation by Notonecta sp. individuals as key stressors. The single impact of each of these stressors, and their binary and tertiary combinations, was evaluated on D. pulex abundance and population structure under mesotrophic and eutrophic conditions for 21 days. Data were analyzed using generalized linear mixed models estimated by means of a novel Bayesian shrinkage technique. Our study shows a significant influence of each of the evaluated stressors on D. pulex abundance; however, the impacts of the herbicide and predation were lower under eutrophic conditions as compared to the mesotrophic ones. We found that binary stressor interactions were generally additive in the mesotrophic scenario, except for the herbicide-predation combination, which resulted in synergistic effects. The impacts of the binary stressor combinations in the eutrophic scenario were classified as antagonistic, except for the insecticide-herbicide combination, which was additive. The tertiary interaction resulted in significant effects on some sampling dates; however, these were rather antagonistic and resembled the most important binary stressor combination in each trophic scenario. Our study shows that the impact of pesticides on freshwater populations depends on the predation pressure, and demonstrates that the combined effect of pesticides and ecological stressors is influenced by the food availability and organism fitness related to the trophic status of freshwater ecosystems.

Microglial Heterogeneity and Its Potential Role in Driving Phenotypic Diversity of Alzheimer's Disease.

Alzheimer's disease (AD) is increasingly recognized as a highly heterogeneous disorder occurring under distinct clinical and neuropathological phenotypes. Despite the molecular determinants of such variability not being well defined yet, microglial cells may play a key role in this process by releasing distinct pro- and/or anti-inflammatory cytokines, potentially affecting the expression of the disease. We carried out a neuropathological and biochemical analysis on a series of AD brain samples, gathering evidence about the heterogeneous involvement of microglia in AD. The neuropathological studies showed differences concerning morphology, density and distribution of microglial cells among AD brains. Biochemical investigations showed increased brain levels of IL-4, IL-6, IL-13, CCL17, MMP-7 and CXCL13 in AD in comparison with control subjects. The molecular profiling achieved by measuring the brain levels of 25 inflammatory factors known to be involved in neuroinflammation allowed a stratification of the AD patients in three distinct "neuroinflammatory clusters". These findings strengthen the relevance of neuroinflammation in AD pathogenesis suggesting, in particular, that the differential involvement of neuroinflammatory molecules released by microglial cells during the development of the disease may contribute to modulate the characteristics and the severity of the neuropathological changes, driving-at least in part-the AD phenotypic diversity.

Cardiac surgery in 260 octogenarians: a case series.

BACKGROUND: The elderly undergo cardiac surgery more and more frequently, often present multiple comorbidities, assume chronic therapies, and present a unique physiology. Aim of our study was to analyze the experience of a referral cardiac surgery center with all types of cardiac surgery interventions performed in patients ≥80 years old over a six years' period. METHODS: A retrospective observational study performed in a university hospital. 260 patients were included in the study (3.5% of the patients undergoing cardiac surgery in the study period). RESULTS: Mean age was 82 ± 1.8 years. Eighty-five percent of patients underwent elective surgery, 15% unplanned surgery and 4.2% redo surgery. Intervention for aortic valve pathology and coronary artery bypass grafting were performed in 51% and 46% of the patients, respectively. Interventions involving the mitral valve were the 26% of the total, those on the tricuspid valve were 13% and those on the ascending aortic arch the 9.6%. Postoperative low output syndrome was identified in 44 patients (17%). Mortality was 3.9% and most of the patients (91%) were discharged from hospital in good clinical conditions. Hospital mortality was lower in planned vs unplanned surgery: 3.8% vs 14% respectively. Chronic obstructive pulmonary disease (OR 9.106, CI 2.275 - 36.450) was the unique independent predictor of mortality. CONCLUSIONS: Clinicians should be aware that cardiac surgery can be safely performed at all ages, that risk stratification is mandatory and that hemodynamic treatment to avoid complications is expected.