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Abstract Molecular clock models undergird modern methods of divergence-time estimation. Local clock models propose that the rate of molecular evolution is constant within phylogenetic subtrees. Current local clock inference procedures exhibit one or more weaknesses, namely they achieve limited scalability to trees with large numbers of taxa, impose model misspecification, or require a priori knowledge of the existence and location of clocks. To overcome these challenges, we present an autocorrelated, Bayesian model of heritable clock rate evolution that leverages heavy-tailed priors with mean zero to shrink increments of change between branch-specific clocks. We further develop an efficient Hamiltonian Monte Carlo sampler that exploits closed form gradient computations to scale our model to large trees. Inference under our shrinkage clock exhibits a speed-up compared to the popular random local clock when estimating branch-specific clock rates on a variety of simulated datasets. This speed-up increases with the size of the problem. We further show our shrinkage clock recovers known local clocks within a rodent and mammalian phylogeny. Finally, in a problem that once appeared computationally impractical, we investigate the heritable clock structure of various surface glycoproteins of influenza A virus in the absence of prior knowledge about clock placement. We implement our shrinkage clock and make it publicly available in the BEAST software package.

Relaxed randomwalk (RRW) models of trait evolution introduce branch-specific rate multipliers tomodulate the variance of a standard Brownian diffusion process along a phylogeny and more accurately model overdispersed biological data. Increased taxonomic sampling challenges inference under RRWs as the number of unknown parameters grows with the number of taxa. To solve this problem, we present a scalable method to efficiently fit RRWs and infer this branch-specific variation in a Bayesian framework. We develop a Hamiltonian Monte Carlo (HMC) sampler to approximate the high-dimensional, correlated posterior that exploits a closed-form evaluation of the gradient of the trait data log-likelihood with respect to all branch-ratemultipliers simultaneously. Our gradient calculation achieves computational complexity that scales only linearly with the number of taxa under study. We compare the efficiency of our HMC sampler to the previously standard univariable Metropolis–Hastings approach while studying the spatial emergence of the West Nile virus in North America in the early 2000s. Our method achieves at least a 6-fold speed increase over the univariable approach. Additionally, we demonstrate the scalability of our method by applying the RRW to study the correlation between five mammalian life history traits in a phylogenetic tree with 3650 tips.

Computational analyses of pathogen genomes are increasingly used to unravel the dispersal history and transmission dynamics of epidemics. Here, we show how to go beyond historical reconstructions and use spatially-explicit phylogeographic and phylodynamic approaches to formally test epidemiological hypotheses. We illustrate our approach by focusing on the West Nile virus (WNV) spread in North America that has substantially impacted public, veterinary, and wildlife health. We apply an analytical workflow to a comprehensive WNV genome collection to test the impact of environmental factors on the dispersal of viral lineages and on viral population genetic diversity through time. We find that WNV lineages tend to disperse faster in areas with higher temperatures and we identify temporal variation in temperature as a main predictor of viral genetic diversity through time. By contrasting inference with simulation, we find no evidence for viral lineages to preferentially circulate within the same migratory bird flyway, suggesting a substantial role for non-migratory birds or mosquito dispersal along the longitudinal gradient. Classical epidemiological approaches have been limited in their ability to formally test hypotheses. Here, Dellicour et al. illustrate how phylodynamic and phylogeographic analyses can be leveraged for hypothesis testing in molecular epidemiology using West Nile virus in North America as an example.

This narrative review summarises the benefits, risks and appropriate use of acid-suppressing drugs (ASDs), proton pump inhibitors and histamine-2 receptor antagonists, advocating a rationale balanced and individualised approach aimed to minimise any serious adverse consequences. It focuses on current controversies on the potential of ASDs to contribute to infections—bacterial, parasitic, fungal, protozoan and viral, particularly in the elderly, comprehensively and critically discusses the growing body of observational literature linking ASD use to a variety of enteric, respiratory, skin and systemic infectious diseases and complications ( Clostridium difficile diarrhoea, pneumonia, spontaneous bacterial peritonitis, septicaemia and other). The proposed pathogenic mechanisms of ASD-associated infections (related and unrelated to the inhibition of gastric acid secretion, alterations of the gut microbiome and immunity), and drug-drug interactions are also described. Both probiotics use and correcting vitamin D status may have a significant protective effect decreasing the incidence of ASD-associated infections, especially in the elderly. Despite the limitations of the existing data, the importance of individualised therapy and caution in long-term ASD use considering the balance of benefits and potential harms, factors that may predispose to and actions that may prevent/attenuate adverse effects is evident. A six-step practical algorithm for ASD therapy based on the best available evidence is presented.

Chronic seasonal low oxygen condition (hypoxia) occurs in the deep waters of Chesapeake Bay as a result of eutrophication-induced phytoplankton blooms and their subsequent decomposition. Summertime hypoxia has been observed in Chesapeake Bay for over 80 years, with scientific attention and understanding increasing substantially during the past several decades after rigorous and routine monitoring programs were put in place. More recently, annual forecasts of the severity of summer hypoxia and anoxia (no oxygen) from simple empirically derived nutrient load-response models have been made. A review of these models over the past decade indicates that they have been generally accurate, with the exception of a few summers when wind events or storms significantly disrupted the water column. Hypoxic and anoxic conditions, as well as their forecasts, have received increased media attention over the past 5 years, contributing to an ongoing public dialogue about Chesapeake Bay restoration progress.

Measurements just beneath the ocean surface demonstrate that the primary mechanism by which energy from breaking waves is transmitted into the water column is through the work done by the covariance of turbulent pressure and velocity fluctuations. The convergence in the vertical transport of turbulent kinetic energy (TKE) balances the dissipation rate of TKE at first order and is nearly an order of magnitude greater than the sum of the integrated Eulerian and Stokes shear production. The measured TKE transport is consistent with a simple conceptual model that assumes roughly half of the surface flux of TKE by wave breaking is transmitted to depths greater than the significant wave height. During conditions when breaking waves are inferred, the direction of momentum flux is more aligned with the direction of wave propagation than with the wind direction. Both the energy and momentum fluxes occur at frequencies much lower than the wave band, consistent with the time scales associated with wave breaking. The largest instantaneous values of momentum flux are associated with strong downward vertical velocity perturbations, in contrast to the pressure work, which is associated with strong drops in pressure and upward vertical velocity perturbations.

Objective. Although the association between chronic kidney disease (CKD) and osteoporotic fractures is well established, data on CKD combined with hip fracture (HF) are scarce and controversial. We aimed to assess in patients with HF the prevalence of CKD, its impact on hospital mortality and length of stay (LOS) and to determine the prognostic value of CKD to predict hospital outcomes. Methods. Prospectively collected clinical data were analysed in 3623 consecutive HF patients aged ≥65 years (mean age 83.4 ± 7.50 [standard deviation] years; 74.4% females). Results. CKD among older patients with HF is highly prevalent (39.9%), has different clinical characteristics, a 2.5-fold higher mortality rate, and 40% greater risk of prolonged LOS. The strongest risk for a poor outcome was advanced age (>80 years). The risk of death substantially increases in combination with chronic disorders, especially coronary artery disease, anaemia, hyperparathyroidism, and atrial fibrillation; models based only on three variables—CKD stage, age >80, and presence of a specific chronic condition—predicted in-hospital death with good discrimination capability (AUC ≥ 0.700) and reasonable accuracy, the number needed to predict ranged between 5.7 and 14.5. Only 12% of HF patients received osteoporotic drugs prefracture. Conclusion. In HF patients with CKD, the risk of adverse outcomes largely increases in parallel with worsening kidney function and, especially, in combination with comorbidities; models based on three admission variables predict a fatal outcome. Assessment of renal function is essential to preventing osteoporotic fractures.

Background While pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer, many other histologic forms of pancreatic cancer are also recognized. These histologic variants portray unique characteristics in terms of patient demographics, tumor behavior, survival, and responsiveness to treatments. Materials and Methods Patients who underwent surgical resection of the pancreas for non-metastatic, invasive pancreatic cancer between 2004 and 2014 were selected from the National Cancer Data Base and categorized by histologic variant according to WHO classification guidelines. Patient demographics, tumor variables, treatment characteristics, and survival were compared between histologic groups and subgroups. Results A total of 57,804 patients met inclusion and exclusion criteria and were grouped into eight major histologic categories. Survival analysis by the histologic group showed median overall survival of 20.2 months for ductal adenocarcinoma, 20.5 months for squamous cell carcinoma, 26.8 months for mixed acinar-neuroendocrine carcinomas, 52.6 months for cystic mucinous neoplasms with an associated invasive carcinoma, 67.5 months for acinar cell carcinoma, and 69.3 months for mesenchymal tumors. Median survival was not reached for neuroendocrine tumors and solid-pseudopapillary neoplasms, with 5-year overall survival rates of 84% and 97% respectively. Conclusions Rare subtypes of pancreatic cancer present unique clinicopathologic characteristics and display distinct tumor biologies. This study presents data on demographic, prognostic, treatment, and survival outcomes between rare forms of pancreatic neoplasms in order to aid understanding of the natural history and behavior of these neoplasms, with the hope of serving as a reference in clinical decision-making and ability to provide accurate prognostic information to patients.

Background Documenting the spectrum of ecosystem management, the roles of forestry and agricultural biodiversity, TEK, and human culture for food sovereignty, are all priority challenges for contemporary science and society. Ethnoagroforestry is a research approach that provides a theoretical framework integrating socio-ecological disciplines and TEK. We analyze in this study general types of Agroforestry Systems of México, in which peasants, small agriculturalist, and indigenous people are the main drivers of AFS and planning of landscape diversity use. We analyzed the actual and potential contribution of ethnoagroforestry for maintaining diversity of wild and domesticated plants and animals, ecosystems, and landscapes, hypothesizing that ethnoagroforestry management forms may be the basis for food sufficiency and sovereignty in Mexican communities, regions and the whole nation. Methods We conducted research and systematization of information on Mexican AFS, traditional agriculture, and topics related to food sovereignty from August 2011 to May 2015. We constructed the database Ethnoagroforestry based on information from our own studies, other databases, Mexican and international specialized journals in agroforestry and ethnoecology, catalogues and libraries of universities and research centers, online information, and unpublished theses. We analyzed through descriptive statistical approaches information on agroforestry systems of México including 148 reports on use of plants and 44 reports on use of animals. Results Maize, beans, squashes and chili peppers are staple Mesoamerican food and principal crops in ethnoagroforestry systems practiced by 21 cultural groups throughout Mexico (19 indigenous people) We recorded on average 121 ± 108 (SD) wild and domesticated plant species, 55 ± 27% (SD) of them being native species; 44 ± 23% of the plant species recorded provide food, some of them having also medicinal, firewood and fodder uses. A total of 684 animal species has been recorded (17 domestic and 667 wild species), mainly used as food (34%). Conclusions Ethnoagroforestry an emergent research approach aspiring to establish bases for integrate forestry and agricultural diversity, soil, water, and cultural richness. Its main premise is that ethnoagroforestry may provide the bases for food sovereignty and sustainable ecosystem management.

Creating a sustainable community cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) program that reaches underserved communities poses a challenge for the emergency medical services (EMS) community. Attendance, funding, and resources have all been linked to struggles surrounding community CPR/AED programs. Through our experience in conducting CPR/AED trainings in underserved regions of eastern North Carolina, we propose a method of effectively utilizing existing organizations and institutions of learning to expand and maintain a sustainable community CPR/AED program. Furthermore, we demonstrate 10 cornerstones in developing relationships within the community to increase attendance and participation in diverse communities.