385 research outputs found

    Delayed Sampling and Automatic Rao-Blackwellization of Probabilistic Programs

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    We introduce a dynamic mechanism for the solution of analytically-tractable substructure in probabilistic programs, using conjugate priors and affine transformations to reduce variance in Monte Carlo estimators. For inference with Sequential Monte Carlo, this automatically yields improvements such as locally-optimal proposals and Rao-Blackwellization. The mechanism maintains a directed graph alongside the running program that evolves dynamically as operations are triggered upon it. Nodes of the graph represent random variables, edges the analytically-tractable relationships between them. Random variables remain in the graph for as long as possible, to be sampled only when they are used by the program in a way that cannot be resolved analytically. In the meantime, they are conditioned on as many observations as possible. We demonstrate the mechanism with a few pedagogical examples, as well as a linear-nonlinear state-space model with simulated data, and an epidemiological model with real data of a dengue outbreak in Micronesia. In all cases one or more variables are automatically marginalized out to significantly reduce variance in estimates of the marginal likelihood, in the final case facilitating a random-weight or pseudo-marginal-type importance sampler for parameter estimation. We have implemented the approach in Anglican and a new probabilistic programming language called Birch.Comment: 13 pages, 4 figure

    Incorporation of metals into calcite in a deep anoxic granite aquifer

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    Understanding metal scavenging by calcite in deep aquifers in granite is of importance for deciphering and modeling hydrochemical fluctuations and water–rock interaction in the upper crust and for retention mechanisms associated with underground repositories for toxic wastes. Metal scavenging into calcite has generally been established in the laboratory or in natural environments that cannot be unreservedly applied to conditions in deep crystalline rocks, an environment of broad interest for nuclear waste repositories. Here, we report a microanalytical study of calcite precipitated over a period of 17 years from anoxic, low-temperature (14 °C), neutral (pH: 7.4–7.7), and brackish (Cl: 1700–7100 mg/L) groundwater flowing in fractures at >400 m depth in granite rock. This enabled assessment of the trace metal uptake by calcite under these deep-seated conditions. Aquatic speciation modeling was carried out to assess influence of metal complexation on the partitioning into calcite. The resulting environment-specific partition coefficients were for several divalent ions in line with values obtained in controlled laboratory experiments, whereas for several other ions they differed substantially. High absolute uptake of rare earth elements and U(IV) suggests that coprecipitation into calcite can be an important sink for these metals and analogousactinides in the vicinity of geological repositories

    Isotopic evidence for microbial production and consumption of methane in the upper continental crust throughout the Phanerozoic eon

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    Microorganisms produce and consume methane in terrestrial surface environments, sea sediments and, as indicated by recent discoveries, in fractured crystalline bedrock. These processes in the crystalline bedrock remain, however, unexplored both in terms of mechanisms and spatiotemporal distribution. Here we have studied these processes via a multi-method approach including microscale analysis of the stable isotope compositions of calcite and pyrite precipitated in bedrock fractures in the upper crust (down to 1.7 km) at three sites on the Baltic Shield. Microbial processes have caused an intriguing variability of the carbon isotopes in the calcites at all sites, with δ13C spanning as much as −93.1‰ (related to anaerobic oxidation of methane) to +36.5‰ (related to methanogenesis). Spatiotemporal coupling between the stable isotope measurements and radiometric age determinations (micro-scale dating using new high-spatial methods: LA-ICP-MS U–Pb for calcite and Rb–Sr for calcite and co-genetic adularia) enabled unprecedented direct timing constraints of the microbial processes to several periods throughout the Phanerozoic eon, dating back to Devonian times. These events have featured variable fluid salinities and temperatures as shown by fluid inclusions in the calcite; dominantly 70–85 °C brines in the Paleozoic and lower temperatures (<50–62 °C) and salinities in the Mesozoic. Preserved organic compounds, including plant signatures, within the calcite crystals mark the influence of organic matter in descending surficial fluids on the microbial processes in the fracture system, thus linking processes in the deep and surficial biosphere. These findings substantially extend the recognized temporal and spatial range for production and consumption of methane within the upper continental crust

    Recirculation in single lumen cannula venovenous extracorporeal membrane oxygenation: A non-randomized bi-centric trial

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    Background: Recirculation is a common problem in venovenous (VV) extracorporeal membrane oxygenation (ECMO). The aims of this study were to compare recirculation fraction (Rf) between femoro-jugular and jugulo-femoral VV ECMO configurations, to identify risk factors for recirculation and to assess the impact on hemolysis. Methods: Patients in the medical intensive care unit (ICU) at the University Medical Center Regensburg, Germany receiving VV ECMO with femoro-jugular, and jugulo-femoral configuration at the ECMO Center Karolinska, Sweden, were included in this non-randomized prospective study. Total ECMO flow (QEC), recirculated flow (QREC), and recirculation fraction Rf = QREC/QEC were determined using ultrasound dilution technology. Effective ECMO flow (QEFF) was defined as QEFF = QEC * (1–Rf). Demographics, cannula specifics, and markers of hemolysis were assessed. Survival was evaluated at discharge from ICU. Results: Thirty-seven patients with femoro-jugular configuration underwent 595 single-point measurements and 18 patients with jugulo-femoral configuration 231 measurements. Rf was lower with femoro-jugular compared to jugulo-femoral configuration [5 (0, 11) vs. 19 (13, 28) %, respectively (p 8 vs. ≤ 8%. Explorative data on survival showed comparable results in the femoro-jugular and the jugulo-femoral group (81 vs. 72%, p = 0.455). Conclusion: VV ECMO with femoro-jugular configuration caused less recirculation. Further risk factors for higher Rf were shorter distance between the two cannula tips, higher ECMO flow, and lower heart rate. Rf did not affect hemolysis

    Identification of known and novel recurrent viral sequences in data from multiple patients and multiple cancers

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    Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified

    Cost-effectiveness of monitoring glaucoma patients in shared care: an economic evaluation alongside a randomized controlled trial

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    Background. Population aging increases the number of glaucoma patients which leads to higher workloads of glaucoma specialists. If stable glaucoma patients were monitored by optometrists and ophthalmic technicians in a glaucoma follow-up unit (GFU) rather than by glaucoma specialists, the specialists' workload and waiting lists might be reduced. We compared costs and quality of care at the GFU with those of usual care by glaucoma specialists in the Rotterdam Eye Hospital (REH) in a 30-month randomized clinical trial. Because quality of care turned out to be similar, we focus here on the costs. Methods. Stable glaucoma patients were randomized between the GFU and the glaucoma specialist group. Costs per patient year were calculated from four perspectives: those of patients, the Rotterdam Eye Hospital (REH), Dutch healthcare system, and society. The outcome measures were: compliance to the protocol; patient satisfaction; stability according to the practitioner; mean difference in IOP; results of the examinations; and number of treatment changes. Results. Baseline characteristics (such as age, intraocular pressure and target pressure) were comparable between the GFU group (n = 410) and the glaucoma specialist group (n = 405). Despite a higher number of visits per year, mean hospital costs per patient year were lower in the GFU group (€139 vs. €161). Patients' time and travel costs were similar. Healthcare costs were significantly lower for the GFU group (€230 vs. €251), as were societal costs (€310 vs. €339) (p < 0.01). Bootstrap-, sensitivity- and scenario-analyses showed that the costs were robust when varying hospital policy and the duration of visits and tests. Conclusion. We conclude that this GFU is cost-effective and deserves to be considered for implementation in other hospitals

    Pressure and Flow Properties of Cannulae for Extracorporeal Membrane Oxygenation I: Return (Arterial) Cannulae

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    Adequate extracorporeal membrane oxygenation support in the adult requires cannulae permitting blood flows up to 6-8 L/minute. In accordance with Poiseuille's law, flow is proportional to the fourth power of cannula inner diameter and inversely proportional to its length. Poiseuille's law can be applied to obtain the pressure drop of an incompressible, Newtonian fluid (such as water) flowing in a cylindrical tube. However, as blood is a pseudoplastic non-Newtonian fluid, the validity of Poiseuille's law is questionable for prediction of cannula properties in clinical practice. Pressure-flow charts with non-Newtonian fluids, such as blood, are typically not provided by the manufacturers. A standardized laboratory test of return (arterial) cannulae for extracorporeal membrane oxygenation was performed. The aim was to determine pressure-flow data with human whole blood in addition to manufacturers' water tests to facilitate an appropriate choice of cannula for the desired flow range. In total, 14 cannulae from three manufacturers were tested. Data concerning design, characteristics, and performance were graphically presented for each tested cannula. Measured blood flows were in most cases 3-21% lower than those provided by manufacturers. This was most pronounced in the narrow cannulae (15-17 Fr) where the reduction ranged from 27% to 40% at low flows and 5-15% in the upper flow range. These differences were less apparent with increasing cannula diameter. There was a marked disparity between manufacturers. Based on the measured results, testing of cannulae including whole blood flows in a standardized bench test would be recommended.info:eu-repo/semantics/publishedVersio
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