A computational group theoretic symmetry reduction package for the SPIN model checker

Symmetry reduced model checking is hindered by two problems: how to identify state space symmetry when systems are not fully symmetric, and how to determine equivalence of states during search. We present TopSpin, a fully automatic symmetry reduction package for the Spin model checker. TopSpin uses the Gap computational algebra system to effectively detect state space symmetry from the associated Promela specification, and to choose an efficient symmetry reduction strategy by classifying automorphism groups as a disjoint/wreath product of subgroups. We present encouraging experimental results for a variety of Promela examples

Assessment of groundwater discharges into West Neck Bay, New York, via natural tracers

Author Posting. © Elsevier B.V., 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Continental Shelf Research 29 (2006): 1971-1983, doi:10.1016/j.csr.2006.07.011.A field experiment to compare methods of assessing submarine groundwater discharge (SGD) was held on Shelter Island, NY, in May 2002. We evaluated the use of radon, radium isotopes, and methane to assess SGD rates and dynamics from a glacial aquifer in the coastal zone. Fluxes of radon across the sediment-water interface were calculated from changes in measured surface water inventories following evaluation and correction for tidal effects, atmospheric evasion, and mixing with offshore waters. These fluxes were then converted to SGD rates using the measured radon concentration in the groundwater. We used the short-lived radium isotopes to calculate a horizontal mixing coefficient to assess radon loss by mixing between nearshore and offshore waters. We also made an independent calculation of SGD using the Ra-derived mixing coefficient and the long-lived 226Ra concentration gradient in the bay. Seepage rates were calculated to range between 0 and 34 cm.day-1 using the radon measurements and 15 cm.day-1 as indicated by the radium isotopes. The radiotracer results were consistent and comparable to SGD rates measured directly with vented benthic chambers (seepage meters) deployed during this experiment. These meters indicated rates between 2 and 200 cm.day-1 depending on their location. Both the calculated radon fluxes and rates measured directly by the automated seepage meters revealed a clear reproducible pattern of higher fluxes during low tides. Considering that the two techniques are completely independent, the agreement in the SGD dynamics is significant. Methane concentration in groundwater was very low (~30 nM) and not suitable as SGD tracer at this study site.The SGD intercomparison experiment was partially funded by SCOR, LOICZ, and UNESCO (IOC and IHP). W. C. Burnett acknowledges support from CICEET (Grant# 1368-810-41) and ONR (Grant# 1368-769-27). J. P. Chanton acknowledges support from Seagrant (R\C-E-44). The WHOI researchers acknowledge funding from CICEET (#NA07OR0351, NA17OZ2507)

Sensitivity analyses for effect modifiers not observed in the target population when generalizing treatment effects from a randomized controlled trial: Assumptions, models, effect scales, data scenarios, and implementation details

Background inform policy and practice for broad populations. The average treatment effect (ATE) for a target population, however, may be different from the ATE observed in a trial if there are effect modifiers whose distribution in the target population is different that from that in the trial. Methods exist to use trial data to estimate the target population ATE, provided the distributions of treatment effect modifiers are observed in both the trial and target population—an assumption that may not hold in practice. Methods The proposed sensitivity analyses address the situation where a treatment effect modifier is observed in the trial but not the target population. These methods are based on an outcome model or the combination of such a model and weighting adjustment for observed differences between the trial sample and target population. They accommodate several types of outcome models: linear models (including single time outcome and pre- and post-treatment outcomes) for additive effects, and models with log or logit link for multiplicative effects. We clarify the methods’ assumptions and provide detailed implementation instructions. Illustration We illustrate the methods using an example generalizing the effects of an HIV treatment regimen from a randomized trial to a relevant target population. Conclusion These methods allow researchers and decision-makers to have more appropriate confidence when drawing conclusions about target population effects

Sensitivity analyses for misclassification of cause of death in the parametric G-formula

Cause-specific mortality is an important outcome in studies of interventions to improve survival, yet causes of death can be misclassified. Here, we present an approach to performing sensitivity analyses formisclassification of cause of death in the parametric g-formula. The g-formula is a useful method to estimate effects of interventions in epidemiologic research because it appropriately accounts for time-varying confounding affected by prior treatment and can estimate risk under dynamic treatment plans.We illustrate our approach using an example comparing acquired immune deficiency syndrome (AIDS)-related mortality under immediate and delayed treatment strategies in a cohort of therapy-naive adults entering care for human immunodeficiency virus infection in the United States. In the standard g-formula approach, 10-year risk of AIDSrelatedmortality under delayed treatment was 1.73 (95% CI: 1.17, 2.54) times the risk under immediate treatment. In a sensitivity analysis assuming that AIDS-related death was measured with sensitivity of 95% and specificity of 90%, the 10-year risk ratio comparing AIDS-related mortality between treatment plans was 1.89 (95% CI: 1.13, 3.14). When sensitivity and specificity are unknown, this approach can be used to estimate the effects of dynamic treatment plans under a range of plausible values of sensitivity and specificity of the recorded event type

Isotope tracing of submarine groundwater discharge offshore Ubatuba, Brazil : results of the IAEA–UNESCO SGD project

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Journal of Environmental Radioactivity 99 (2008): 1596-1610, doi:10.1016/j.jenvrad.2008.06.010.Results of groundwater and seawater analyses for radioactive (3H, 222Rn, 223Ra, 224Ra, 226Ra, 228Ra) and stable (2H, 18O) isotopes are presented together with in situ spatial mapping and time-series 222Rn measurements in seawater, direct seepage measurements using manual and automated seepage meters, pore water investigations using different tracers and piezometric techniques, and geoelectric surveys probing the coast. This study represents first time that such a new complex arsenal of radioactive and non-radioactive tracer techniques and geophysical methods have been used for simultaneous submarine groundwater discharge (SGD) investigations. Large fluctuations of SGD fluxes were observed at sites situated only a few meters apart (from 0 cm d-1 to 360 cm d-1; the unit represents cm3/cm2/day), as well as during a few hours (from 0 cm d-1 to 110 cm d-1), strongly depending on the tidal fluctuations. The average SGD flux estimated from continuous 222Rn measurements is 17±10 cm d-1. Integrated coastal SGD flux estimated for the Ubatuba coast using radium isotopes is about 7x103 m3 d-1 per km of the coast. The isotopic composition (δ2H and δ18O) of submarine waters was characterised by significant variability and heavy isotope enrichment, indicating that the contribution of groundwater in submarine waters varied from a small percentage to 20%. However, this contribution with increasing offshore distance became negligible. Automated seepage meters and time-series measurements of 222Rn activity concentration showed a negative correlation between the SGD rates and tidal stage. This is likely caused by sea level changes as tidal effects induce variations of hydraulic gradients. The geoelectric probing and piezometric measurements contributed to better understanding of the spatial distribution of different water masses present along the coast. The radium isotope data showed scattered distributions with offshore distance, which imply that seawater in a complex coast with many small bays and islands was influenced by local currents and groundwater/seawater mixing. This has also been confirmed by a relatively short residence time of 1-2 weeks for water within 25 km offshore, as obtained by short-lived radium isotopes. The irregular distribution of SGD seen at Ubatuba is a characteristic of fractured rock aquifers, fed by coastal groundwater and recirculated seawater with small admixtures of groundwater, which is of potential environmental concern and has implications on the management of freshwater resources in the region.This research was supported by IAEA and UNESCO (IOC and IHP) in the framework of the joint SGD project. Science support for some U.S. investigators was provided by grants from the National Science Foundation (OCE03-50514 to WCB and OCE02-33657 to WSM)

Virologic suppression and CD4 + cell count recovery after initiation of raltegravir or efavirenz-containing HIV treatment regimens

Objective: To explore the effectiveness of raltegravir-based antiretroviral therapy (ART) on treatment response among ART-naive patients seeking routine clinical care. Design: Cohort study of adults enrolled in HIV care in the United States. Methods: We compared virologic suppression and CD4 + cell count recovery over a 2.5 year period after initiation of an ART regimen containing raltegravir or efavirenz using observational data from a US clinical cohort, generalized to the US population of people with diagnosed HIV. We accounted for nonrandom treatment assignment, informative censoring, and nonrandom selection from the US target population using inverse probability weights. Results: Of the 2843 patients included in the study, 2476 initiated the efavirenz-containing regimen and 367 initiated the raltegravir-containing regimen. In the weighted intent-To-Treat analysis, patients spent an average of 74 (95% confidence interval: 41, 106) additional days alive with a suppressed viral load on the raltegravir regimen than on the efavirenz regimen over the 2.5-year study period. CD4 + cell count recovery was also superior under the raltegravir regimen. Conclusion: Patients receiving raltegravir spent more time alive and suppressed than patients receiving efavirenz, but the probability of viral suppression by 2.5 years after treatment was similar between groups. Optimizing the amount of time spent in a state of viral suppression is important to improve survival among people living with HIV and to reduce onward transmission

Fredholm Determinants, Differential Equations and Matrix Models

Orthogonal polynomial random matrix models of NxN hermitian matrices lead to Fredholm determinants of integral operators with kernel of the form (phi(x) psi(y) - psi(x) phi(y))/x-y. This paper is concerned with the Fredholm determinants of integral operators having kernel of this form and where the underlying set is a union of open intervals. The emphasis is on the determinants thought of as functions of the end-points of these intervals. We show that these Fredholm determinants with kernels of the general form described above are expressible in terms of solutions of systems of PDE's as long as phi and psi satisfy a certain type of differentiation formula. There is also an exponential variant of this analysis which includes the circular ensembles of NxN unitary matrices.Comment: 34 pages, LaTeX using RevTeX 3.0 macros; last version changes only the abstract and decreases length of typeset versio

Compound retention in care and all-cause mortality among persons living with human immunodeficiency virus

Background: To obtain optimal health outcomes, persons living with human immunodeficiency virus (HIV) must be retained in clinical care. We examined the relationships between 4 possible combinations of 2 separate retention measures (missed visits and the Institute of Medicine [IOM] indicator) and all-cause mortality. Methods: The sample included 4162 antiretroviral therapy (ART)–naive patients who started ART between January 2000 and July 2010 at any of 5 US sites of the Center for AIDS Research Network of Integrated Clinical Systems. The independent variable of interest was retention, captured over the 12-month period after the initiation of ART. The study outcome, all-cause mortality 1 year after ART initiation, was determined by querying the Social Security Death Index or the National Death Index. We evaluated the associations of the 4 categories of retention with all-cause mortality, using the Cox proportional hazards models. Results: Ten percent of patients did not meet retention standards for either measure (hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.59–3.21). Patients retained by the IOM but not the missed-visits measure (42%) had a higher HR for mortality (1.72; 95% CI, 1.33–2.21) than patients retained by both measures (41%). Patients retained by the missed-visits but not the IOM measure (6%) had the same mortality hazards as patients retained by both measures (HR, 1.01; 95% CI, .54–1.87). Conclusions: Missed visits within the first 12 months of ART initiation are a major risk factor for subsequent death. Incorporating missed visits in clinical and public health retention and viral suppression programming is advised

Isotopic, geophysical and biogeochemical investigation of submarine groundwater discharge : IAEA-UNESCO intercomparison exercise at Mauritius Island

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Journal of Environmental Radioactivity 104 (2012): 24-45, doi:10.1016/j.jenvrad.2011.09.009.Submarine groundwater discharge (SGD) into a shallow lagoon on the west coast of Mauritius Island (Flic-en-Flac) was investigated using radioactive (3H, 222Rn, 223Ra, 224Ra, 226Ra, 228Ra) and stable (2H, 18O) isotopes and nutrients. SGD intercomparison exercises were carried out to validate the various approaches used to measure SGD including radium and radon measurements, seepage-rate measurements using manual and automated meters, sediment bulk conductivity and salinity surveys. SGD measurements using benthic chambers placed on the floor of the Flic-en-Flac Lagoon showed discharge rates up to 500 cm/day. Large variability in SGD was observed over distances of a few meters, which were attributed to different geomorphological features. Deployments of automated seepage meters captured the spatial and temporal variability of SGD with a mean seepage rate of 10 cm/day. The stable isotopic composition of submarine waters was characterized by significant variability and heavy isotope enrichment and was used to predict the contribution of fresh terrestrially derived groundwater to SGD (range from a few % to almost 100 %). The integrated SGD flux, estimated from seepage meters placed parallel to the shoreline, was 35 m3/m day, which was in a reasonable agreement with results obtained from hydrologic water balance calculation (26 m3/m day). SGD calculated from the radon inventory method using in situ radon measurements were between 5 and 56 m3/m per day. Low concentrations of radium isotopes observed in the lagoon water reflected the low abundance of U and Th in the basalt that makes up the island. High SGD rates contribute to high nutrients loading to the lagoon, potentially leading to eutrophication. Each of the applied methods yielded unique information about the character and magnitude of SGD. The results of the intercomparison studies have resulted a better understanding of groundwater-seawater interactions in coastal regions. Such information is an important pre-requisite for the protection management of coastal freshwater resources.The financial support provided by the IOC and IHP of UNESCO for travel arrangements, and by the IAEA’s Marine Environment Laboratories for logistics is highly acknowledged. MAC and MEG were supported in part by the US National Science Foundation (OCE-0425061 and OCE-0751525). PPP acknowledges a support provided by the EU Research & Development Operational Program funded by the ERDF (project No. 26240220004), and the Slovak Scientific Agency VEGA (grant No. 1/108/08). The International Atomic Energy Agency is grateful to the Government of the Principality of Monaco for support provided to its Marine Environment Laboratories