262 research outputs found

    SafeOCS Industry Safety Data: The Value Proposition for the Oil & Gas Industry

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    PresentationThis paper summarizes efforts by the U.S. Department of Transportation, Bureau of Transportation Statistics (BTS) to develop and manage an industry-wide safety data framework under an agreement with the U.S. Department of the Interior’s Bureau of Safety and Environmental Enforcement (BSEE). The Industry Safety Data (ISD) program provides a trusted, proactive means for the oil and gas industry to voluntarily and securely report safety information to identify early warnings of safety problems by uncovering hidden at-risk conditions not previously exposed from analysis of reportable accidents and incidents. Besides agency-reportable incidents, this program captures near miss and other significant safety event information that is maintained by individual companies as part of their internal safety programs. Phase I of this program was completed in June 2019, and plans are progressing to expand industry participation. Companies have long realized the benefits of collecting and analyzing data around safety and environmental incidents to identify risk, then develop systems and processes to prevent recurrence. These activities have been supported and supplemented by industry associations that collect and share event information and develop recommended practices to aid in performance improvement. In high-reliability industries, such as aviation and nuclear, it is common practice to report and share events among companies and regulators to identify hidden trends and create or update existing recommended practices or regulations. The challenge for the oil and gas industry operating within the U.S. Gulf of Mexico Outer Continental Shelf (OCS) was that, while industry associations and the regulator were collecting data on significant incidents, lesser safety events or observed unsafe conditions/behaviors are not required to be reported and therefore may go unnoticed as a trend until a major event occurs. This represented an opportunity for industry, BSEE, and BTS to collaborate on a means of gathering incident data that would allow for analysis and identification of trends or events of significance enabling appropriate interventions to prevent major incidents. The value proposition of this effort is development of a comprehensive safety data repository that facilitates the continual improvement in safety and environmental performance from the implementation of learnings shared from trends or lesser incidents and events occurring within industry

    Search for Doubly-Charged Higgs Boson Production at HERA

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    A search for the single production of doubly-charged Higgs bosons H^{\pm \pm} in ep collisions is presented. The signal is searched for via the Higgs decays into a high mass pair of same charge leptons, one of them being an electron. The analysis uses up to 118 pb^{-1} of ep data collected by the H1 experiment at HERA. No evidence for doubly-charged Higgs production is observed and mass dependent upper limits are derived on the Yukawa couplings h_{el} of the Higgs boson to an electron-lepton pair. Assuming that the doubly-charged Higgs only decays into an electron and a muon via a coupling of electromagnetic strength h_{e \mu} = \sqrt{4 \pi \alpha_{em}} = 0.3, a lower limit of 141 GeV on the H^{\pm\pm} mass is obtained at the 95% confidence level. For a doubly-charged Higgs decaying only into an electron and a tau and a coupling h_{e\tau} = 0.3, masses below 112 GeV are ruled out.Comment: 15 pages, 3 figures, 1 tabl

    Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

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    An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic epep scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil

    Haemodynamic effects of plasma-expansion with hyperoncotic albumin in cirrhotic patients with renal failure: a prospective interventional study

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    <p>Abstract</p> <p>Background</p> <p>Patients with advanced cirrhosis of the liver typically display circulatory disturbance. Haemodynamic management may be critical for avoiding and treating functional renal failure in such patients. This study investigated the effects of plasma expansion with hyperoncotic albumin solution and the role of static haemodynamic parameters in predicting volume responsiveness in patients with advanced cirrhosis.</p> <p>Methods</p> <p>Patients with advanced cirrhosis (Child B and C) of the liver receiving albumin substitution because of renal compromise were studied using trans-pulmonary thermodilution. Paired measurements before and after two infusions of 200 ml of 20% albumin per patient were recorded and standard haemodynamic parameters such as central venous pressure (CVP), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), cardiac index (CI) and derived variables were assessed, including global end-diastolic blood volume index (GEDVI), a parameter that reflects central blood volume</p> <p>Results</p> <p>100 measurements in 50 patients (33 m/17 w; age 56 years (± 8); Child-Pugh-score 12 (± 2), serum creatinine 256 μmol (± 150) were analyzed. Baseline values suggested decreased central blood volumes GEDVI = 675 ml/m<sup>2 </sup>(± 138) despite CVP within the normal range (11 mmHg (± 5). After infusion, GEDVI, CI and CVP increased (682 ml/m<sup>2 </sup>(± 128) vs. 744 ml/m<sup>2 </sup>(± 171), p < 0.001; 4.3 L/min/m<sup>2 </sup>(± 1.1) vs. 4.7 L/min/m<sup>2 </sup>(± 1.1), p < 0.001; 12 mmHg (± 6) vs. 14 mmHg (± 6), p < 0.001 respectively) and systemic vascular resistance decreased (1760 dyn s/cm<sup>5</sup>/m<sup>2 </sup>(± 1144) vs. 1490 dyn s/cm<sup>5</sup>/m<sup>2 </sup>(± 837); p < 0.001). Changes in GEDVI, but not CVP, correlated with changes in CI (r<sup>2 </sup>= 0.51; p < 0.001). To assess the value of static haemodynamic parameters at baseline in predicting an increase in CI of 10%, receiver-operating-characteristic curves were constructed. The areas under the curve were 0.766 (p < 0.001) for SVRI, 0.723 (p < 0.001) for CI, 0.652 (p = 0.010) for CVP and 0.616 (p = 0.050) for GEDVI.</p> <p>Conclusion</p> <p>In a substantial proportion of patients with advanced cirrhosis, plasma expansion results in an increase in central blood volume. GEDVI but not CVP behaves as an indicator of cardiac preload, whereas high baseline SVRI is predictive of fluid responsiveness.</p

    Low loss coatings for the VIRGO large mirrors

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    présentée par L. PinardThe goal of the VIRGO program is to build a giant Michelson type interferometer (3 kilometer long arms) to detect gravitational waves. Large optical components (350 mm in diameter), having extremely low loss at 1064 nm, are needed. Today, the Ion beam Sputtering is the only deposition technique able to produce optical components with such performances. Consequently, a large ion beam sputtering deposition system was built to coat large optics up to 700 mm in diameter. The performances of this coater are described in term of layer uniformity on large scale and optical losses (absorption and scattering characterization). The VIRGO interferometer needs six main mirrors. The first set was ready in June 2002 and its installation is in progress on the VIRGO site (Italy). The optical performances of this first set are discussed. The requirements at 1064 nm are all satisfied. Indeed, the absorption level is close to 1 ppm (part per million), the scattering is lower than 5 ppm and the R.M.S. wavefront of these optics is lower than 8 nm on 150 mm in diameter. Finally, some solutions are proposed to further improve these performances, especially the absorption level (lower than 0.1 ppm) and the mechanical quality factor Q of the mirrors (thermal noise reduction)

    Curvature of Double-Membrane Organelles Generated by Changes in Membrane Size and Composition

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    Transient double-membrane organelles are key players in cellular processes such as autophagy, reproduction, and viral infection. These organelles are formed by the bending and closure of flat, double-membrane sheets. Proteins are believed to be important in these morphological transitions but the underlying mechanism of curvature generation is poorly understood. Here, we describe a novel mechanism for this curvature generation which depends primarily on three membrane properties: the lateral size of the double-membrane sheets, the molecular composition of their highly curved rims, and a possible asymmetry between the two flat faces of the sheets. This mechanism is evolutionary advantageous since it does not require active processes and is readily available even when resources within the cell are restricted as during starvation, which can induce autophagy and sporulation. We identify pathways for protein-assisted regulation of curvature generation, organelle size, direction of bending, and morphology. Our theory also provides a mechanism for the stabilization of large double-membrane sheet-like structures found in the endoplasmic reticulum and in the Golgi cisternae

    Dual Hypocretin Receptor Antagonism Is More Effective for Sleep Promotion than Antagonism of Either Receptor Alone

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    The hypocretin (orexin) system is involved in sleep/wake regulation, and antagonists of both hypocretin receptor type 1 (HCRTR1) and/or HCRTR2 are considered to be potential hypnotic medications. It is currently unclear whether blockade of either or both receptors is more effective for promoting sleep with minimal side effects. Accordingly, we compared the properties of selective HCRTR1 (SB-408124 and SB-334867) and HCRTR2 (EMPA) antagonists with that of the dual HCRTR1/R2 antagonist almorexant in the rat. All 4 antagonists bound to their respective receptors with high affinity and selectivity in vitro. Since in vivo pharmacokinetic experiments revealed poor brain penetration for SB-408124, SB-334867 was selected for subsequent in vivo studies. When injected in the mid-active phase, SB-334867 produced small increases in rapid-eye-movement (REM) and non-REM (NR) sleep. EMPA produced a significant increase in NR only at the highest dose studied. In contrast, almorexant decreased NR latency and increased both NR and REM proportionally throughout the subsequent 6 h without rebound wakefulness. The increased NR was due to a greater number of NR bouts; NR bout duration was unchanged. At the highest dose tested (100 mg/kg), almorexant fragmented sleep architecture by increasing the number of waking and REM bouts. No evidence of cataplexy was observed. HCRTR1 occupancy by almorexant declined 4–6 h post-administration while HCRTR2 occupancy was still elevated after 12 h, revealing a complex relationship between occupancy of HCRT receptors and sleep promotion. We conclude that dual HCRTR1/R2 blockade is more effective in promoting sleep than blockade of either HCRTR alone. In contrast to GABA receptor agonists which induce sleep by generalized inhibition, HCRTR antagonists seem to facilitate sleep by reducing waking “drive”

    Tumour macrophages as potential targets of bisphosphonates

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    Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use

    Testing association of rare genetic variants with resistance to three common antiseizure medications

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    Abstract Objective Drug resistance is a major concern in the treatment of individuals with epilepsy. No genetic markers for resistance to individual antiseizure medication (ASM) have yet been identified. We aimed to identify the role of rare genetic variants in drug resistance for three common ASMs: levetiracetam (LEV), lamotrigine (LTG), and valproic acid (VPA). Methods A cohort of 1622 individuals of European descent with epilepsy was deeply phenotyped and underwent whole exome sequencing (WES), comprising 575 taking LEV, 826 LTG, and 782 VPA. We performed gene- and gene set–based collapsing analyses comparing responders and nonresponders to the three drugs to determine the burden of different categories of rare genetic variants. Results We observed a marginally significant enrichment of rare missense, truncating, and splice region variants in individuals who were resistant to VPA compared to VPA responders for genes involved in VPA pharmacokinetics. We also found a borderline significant enrichment of truncating and splice region variants in the synaptic vesicle glycoprotein (SV2) gene family in nonresponders compared to responders to LEV. We did not see any significant enrichment using a gene-based approach. Significance In our pharmacogenetic study, we identified a slightly increased burden of damaging variants in gene groups related to drug kinetics or targeting in individuals presenting with drug resistance to VPA or LEV. Such variants could thus determine a genetic contribution to drug resistance
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