Development and evaluation of probability density functions for a set of human exposure factors

The purpose of this report is to describe efforts carried out during 1998 and 1999 at the Lawrence Berkeley National Laboratory to assist the U.S. EPA in developing and ranking the robustness of a set of default probability distributions for exposure assessment factors. Among the current needs of the exposure-assessment community is the need to provide data for linking exposure, dose, and health information in ways that improve environmental surveillance, improve predictive models, and enhance risk assessment and risk management (NAS, 1994). The U.S. Environmental Protection Agency (EPA) Office of Emergency and Remedial Response (OERR) plays a lead role in developing national guidance and planning future activities that support the EPA Superfund Program. OERR is in the process of updating its 1989 Risk Assessment Guidance for Superfund (RAGS) as part of the EPA Superfund reform activities. Volume III of RAGS, when completed in 1999 will provide guidance for conducting probabilistic risk assessments. This revised document will contain technical information including probability density functions (PDFs) and methods used to develop and evaluate these PDFs. The PDFs provided in this EPA document are limited to those relating to exposure factors

Integration of DFDs into a UML - based model-driven engineering approach

The main aim of this article is to discuss how the functional and the object-oriented views can be inter-played to represent the various modeling perspectives of embedded systems.We discuss whether the object-oriented modeling paradigm, the predominant one to develop software at the present time, is also adequate for modeling embedded software and how it can be used with the functional paradigm.More specifically, we present how the main modeling tool of the traditional structured methods, data flow diagrams, can be integrated in an object-oriented development strategy based on the unified modeling language. The rationale behind the approach is that both views are important for modeling purposes in embedded systems environments, and thus a combined and integrated model is not only useful, but also fundamental for developing complex systems. The approach was integrated in amodel-driven engineering process, where tool support for the models used was provided. In addition, model transformations have been specified and implemented to automate the process.We exemplify the approach with an IPv6 router case study.FEDER -Fundação para a Ciência e a Tecnologia(HH-02-383

Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice

Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice. HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected. Adoptive transfer of human immunocytes from dual treated, virus-free animals to uninfected humanized mice fails to produce infectious progeny virus. In contrast, HIV-1 is readily detected following sole LASER ART or CRISPR-Cas9 treatment. These data provide proof-of-concept that permanent viral elimination is possible

Physics with the KLOE-2 experiment at the upgraded DAϕ\phiNE

Investigation at a $\phi$--factory can shed light on several debated issues in particle physics. We discuss: i) recent theoretical development and experimental progress in kaon physics relevant for the Standard Model tests in the flavor sector, ii) the sensitivity we can reach in probing CPT and Quantum Mechanics from time evolution of entangled kaon states, iii) the interest for improving on the present measurements of non-leptonic and radiative decays of kaons and eta/eta$^\prime$ mesons, iv) the contribution to understand the nature of light scalar mesons, and v) the opportunity to search for narrow di-lepton resonances suggested by recent models proposing a hidden dark-matter sector. We also report on the $e^+ e^-$ physics in the continuum with the measurements of (multi)hadronic cross sections and the study of gamma gamma processes.Comment: 60 pages, 41 figures; added affiliation for one of the authors; added reference to section

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Time-series analysis of ion and isotope geochemistry of selected springs of the Nevada Test Site, Nye County, Nevada

The temporal variations of ion and isotope geochemistry were observed at six selected springs on the Nevada Test Site, Nye County, Nevada and included: Cane, Whiterock, Captain Jack, Topopah, Tippipah, and Oak Springs. The sites were monitored from 1980 to 1982 and the following parameters were measured: temperature, pH, electrical conductance, discharge, cations (Ca{sup 2+}, Mg{sup 2+}. Na{sup +}, K{sup +}), anions Cl{sup {minus}}, SO{sub 4}{sup 2{minus}}. HCO{sub 3}{sup {minus}}, silica, stable isotopes ({delta}{sup 18}O, {delta}D, {delta}{sup 13}C), and radioactive isotopes ({sup 3}H, {sup 14}C). A more detailed study was continued from 1982 to 1988 at Cane and Whiterock Springs. Field microloggers were installed at these sites in 1985 to measure the high frequency response of temperature, electrical conductance, and discharge to local precipitation. Stage fluctuations near the discharge point dissolve minerals/salts as groundwater inundates the mineralized zone immediately above the equilibrium water table. This phenomena was most noticeable at Whiterock Spring and lagged the discharge response by several hours. Stable isotope analysis of precipitation and groundwater suggests a 1.5 to 2 month travel time for meteoric water to migrate from the recharge area to the discharge point. Groundwater age determinations suggest a mean age of approximately 30 years at Whiterock Spring and possibly older at Cane Spring. However, the short travel time and geochemical integrity of recharge pulses suggest that the waters are poorly mixed along the flow paths. 25 refs., 25 figs., 24 tabs

Evaluation of technologies for volume reduction of plutonium-contaminated soils from the Nevada Test Site

Nuclear testing at and around the Nevada Test Site (NTS) resulted in plutonium (Pu) contamination of the soil over an area of several thousands of acres. The objective of this project was to evaluate the potential of five different processes to reduce the volume of Pu-contaminated soil from three different areas, namely Areas 11, 13, and 52. Volume reduction was to be accomplished by concentrating the Pu into a small but highly contaminated soil fraction, thereby greatly reducing the volume of soil requiring disposal. The processes tested were proposed by Paramag Corp. (PARAMAG), Advanced Processing Technologies Inc. (APT), Lockheed Environmental Systems and Technologies (LESAT), Nuclear Remediation Technologies (NRT), and Scientific Ecology Group (SEG). Because of time and budgetary restraints, the NRT and SEG processes were tested with soil from Area 11 only. These processes typically included a preliminary soil conditioning step (e.g., attrition scrubbing, wet sieving), followed by a more advanced process designed to separate Pu from the soil, based on physiochemical properties of Pu compounds (e.g., magnetic susceptibility, specific gravity). Analysis of the soil indicates that a substantial fraction of the total Pu contamination is typically confined in a relatively narrow and small particle size range. Processes which were able to separate this highly contaminated soil fraction (using physical methods, e.g., attrition scrubbing, wet sieving), from the rest of the soil achieved volume (mass) reductions on the order of 70%. The advanced, more complex processes tested did not enhance volume reduction. The primary reason why processes that rely on the dependence of settling velocity on density differences failed was the very fine grain size of the Pu-rich particles

Species-specific detection of Leishmania in sandflies using an enzyme-linked immunosorbent assay

PubMedID: 9692146A direct enzyme-linked immunosorbent assay (ELISA) using species-specific monoclonal antibodies was developed for the detection and identification of Leishmania in sandflies. A titration of mock-infected Phlebotomus papatasi showed that fewer than 2000 L. major promastigotes could be detected. The percentage of infected P. papatasi collected in the field, as determined by dissection, was compared to that revealed by the ELISA. Both methods gave similar results, irrespective of whether the flies were caught by sticky papers or light-traps. The percentage of infected flies determined by either method was also similar in experimentally infected colony reared sandflies. The ELISA can be carried out using multiple species-specific antibodies, and is as accurate as identification of infected sandflies by microscopical examination. The technique should be useful for identifying sandfly species involved in transmitting different species of Leishmania, and for rapid assessment of leishmanial infection rates in endemic regions.Acknowledgements This work was supported by the Middle East Regional (MERC) Project, NIH-NIAID contract nos. AOl-Al-4518