Likelihood estimators for multivariate extremes

The main approach to inference for multivariate extremes consists in approximating the joint upper tail of the observations by a parametric family arising in the limit for extreme events. The latter may be expressed in terms of componentwise maxima, high threshold exceedances or point processes, yielding different but related asymptotic characterizations and estimators. The present paper clarifies the connections between the main likelihood estimators, and assesses their practical performance. We investigate their ability to estimate the extremal dependence structure and to predict future extremes, using exact calculations and simulation, in the case of the logistic model

Composite likelihood estimation for the Brown-Resnick process

Genton et al. (2011) investigated the gain in efficiency when triplewise, rather than pairwise, likelihood is used to fit the popular Smith max-stable model for spatial extremes. We generalize their results to the Brown-Resnick model and show that the efficiency gain is substantial only for very smooth processes, which are generally unrealistic in application

The Use of Participatory Methods in Researching the Experiences of Children and Young People

Participatory research methods offer a very promising approach for gaining in-depth understanding of young people’s lives. However, when adopting such approaches, researchers need to be aware of methodological and theoretical issues. The aim of this article is to present a discussion of ways in which participatory methods may be used as a research strategy when investigating young people’s experiences and emotions. We explore the potential of these methods as well as some of their limitations

Управління трудовим потенціалом при створенні інноваційної продукції

Super-resolution microscopy (SRM) bypasses the diffraction limit, a physical barrier that restricts the optical resolution to roughly 250 nm and was previously thought to be impenetrable. SRM techniques allow the visualization of subcellular organization with unprecedented detail, but also confront biologists with the challenge of selecting the best-suited approach for their particular research question. Here, we provide guidance on how to use SRM techniques advantageously for investigating cellular structures and dynamics to promote new discoveries

Democratic Argentina\u27s Global Reach

Seven years earlier, such sentiments by an Argentine Army chief of staff would have been unthinkable. Argentina, althoiugh returned to civilian rule, was still dealing with civil-military crisis of the first order, and the recently passed Lae of National Defense did not list international peacekeeping among the roles and missions of the Argentine military

The Relationship between Fenestrations, Sieve Plates and Rafts in Liver Sinusoidal Endothelial Cells

Fenestrations are transcellular pores in endothelial cells that facilitate transfer of substrates between blood and the extravascular compartment. In order to understand the regulation and formation of fenestrations, the relationship between membrane rafts and fenestrations was investigated in liver sinusoidal endothelial cells where fenestrations are grouped into sieve plates. Three dimensional structured illumination microscopy, scanning electron microscopy, internal reflectance fluorescence microscopy and two-photon fluorescence microscopy were used to study liver sinusoidal endothelial cells isolated from mice. There was an inverse distribution between sieve plates and membrane rafts visualized by structured illumination microscopy and the fluorescent raft stain, Bodipy FL C5 ganglioside GM1. 7-ketocholesterol and/or cytochalasin D increased both fenestrations and lipid-disordered membrane, while Triton X-100 decreased both fenestrations and lipid-disordered membrane. The effects of cytochalasin D on fenestrations were abrogated by co-administration of Triton X-100, suggesting that actin disruption increases fenestrations by its effects on membrane rafts. Vascular endothelial growth factor (VEGF) depleted lipid-ordered membrane and increased fenestrations. The results are consistent with a sieve-raft interaction, where fenestrations form in non-raft lipid-disordered regions of endothelial cells once the membrane-stabilizing effects of actin cytoskeleton and membrane rafts are diminished.Full Tex

PatientExploreR: an extensible application for dynamic visualization of patient clinical history from electronic health records in the OMOP common data model.

MotivationElectronic health records (EHRs) are quickly becoming omnipresent in healthcare, but interoperability issues and technical demands limit their use for biomedical and clinical research. Interactive and flexible software that interfaces directly with EHR data structured around a common data model (CDM) could accelerate more EHR-based research by making the data more accessible to researchers who lack computational expertise and/or domain knowledge.ResultsWe present PatientExploreR, an extensible application built on the R/Shiny framework that interfaces with a relational database of EHR data in the Observational Medical Outcomes Partnership CDM format. PatientExploreR produces patient-level interactive and dynamic reports and facilitates visualization of clinical data without any programming required. It allows researchers to easily construct and export patient cohorts from the EHR for analysis with other software. This application could enable easier exploration of patient-level data for physicians and researchers. PatientExploreR can incorporate EHR data from any institution that employs the CDM for users with approved access. The software code is free and open source under the MIT license, enabling institutions to install and users to expand and modify the application for their own purposes.Availability and implementationPatientExploreR can be freely obtained from GitHub: https://github.com/BenGlicksberg/PatientExploreR. We provide instructions for how researchers with approved access to their institutional EHR can use this package. We also release an open sandbox server of synthesized patient data for users without EHR access to explore: http://patientexplorer.ucsf.edu.Supplementary informationSupplementary data are available at Bioinformatics online

Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

Low Dose Coagulant and Local Soil Ballast Effectively Remove Cyanobacteria (Microcystis) from Tropical Lake Water without Cell Damage

The combination of a low dose of coagulant with a ballast, also known as "flock and sink," has been proposed as a lake restoration and cyanobacteria bloom management strategy. The effectiveness of this technique using aluminum sulfate (alum) as a coagulant and a local soil (LS) from Thailand as a ballast in eutrophic water dominated by positively buoyant Microcystis colonies collected from a tropical lake was investigated by measuring changes in chlorophyll-a (chl-a), pH, and zeta potential. Cell integrity was also evaluated using scanning electron microscopy. Results showed that alum alone could reduce chl-a (up to 60% to 83%) at doses (higher than 3 to 6 mg Al/L) dependent on the initial pH (7.6 to 8.2) and initial chl-a concentration (138 to 615 mu g/L) of the lake water but resulted in morphological changes to cellular structure and generally required a dose that reduced pH to <7. LS ballast alone was able to reduce chl-a concentrations (up to 26% at highest dose of 400 mg/L) and caused no significant changes to pH or zeta potential. Combining a low dose of alum (2 mg Al/L) with some amount of LS ballast (50 to 400 mg/L) created an interaction effect that resulted in 81 to 88% reduction in chl-a without changes to zeta potential or morphological changes to cellular structure. Flock and sink may serve a niche role in lake restoration when positively buoyant cyanobacteria are present in the water column during time of treatment. This research showed that an 800% increase in ballast dose resulted in about an 8% reduction in chl-a when combined with 2 mg Al/L of alum. Therefore, it is recommended that ballast dose should be determined by considering its phosphorus sorption capacity and the potentially releasable phosphorus in the lake sediment in order to realize long-term reductions in sediment nutrient release

Field Application of Spent Lime Water Treatment Residual for the Removal of Phosphorus and other Pollutants in Urban Stormwater Runoff

The threat of anthropogenic eutrophication and harmful algal blooms in lakes requires the development of innovative stormwater best management practices (BMPs) to reduce the external loading of phosphorus (P). This paper presents the findings of a 5-year study of a full-scale P removal structure constructed in Minnesota, USA with spent lime drinking water treatment residual (DWTR), a by-product of water softening at a local water treatment plant. Influent and effluent water samples were collected by auto-samplers during 43 storm events during the growing season. Samples were analyzed for P constituents, heavy metals, total suspended solids (TSS), and pH. Toxicity of the effluent was assessed using Ceriodaphnia dubia. Flow-weighted removal effectiveness was calculated for each storm event. Overall, the spent lime DWTR reduced total P loading by 70.9%, dissolved reactive P by 78.5%, dissolved P by 74.7%, and TSS by 58.5%. A significant reduction in heavy metals was also observed. Toxicity tests indicated the aquatic toxicity of the effluent treated with spent lime DWTR was not different from untreated stormwater. This study provided long-term real-world data that demonstrated that a full-scale P removal structure with spent lime DWTR significantly reduced P and other pollutants in stormwater discharging to an urban lake. Therefore, spent lime DWTR, which is currently treated as a waste product, is a promising filter material for stormwater treatment