90 research outputs found

    Calculation of Weibull strength parameters, Batdorf flaw density constants and related statistical quantities using PC-CARES

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    This manual describes the operation and theory of the PC-CARES (Personal Computer-Ceramic Analysis and Reliability Evaluation of Structures) computer program for the IBM PC and compatibles running PC-DOS/MS-DOR OR IBM/MS-OS/2 (version 1.1 or higher) operating systems. The primary purpose of this code is to estimate Weibull material strength parameters, the Batdorf crack density coefficient, and other related statistical quantities. Included in the manual is the description of the calculation of shape and scale parameters of the two-parameter Weibull distribution using the least-squares analysis and maximum likelihood methods for volume- and surface-flaw-induced fracture in ceramics with complete and censored samples. The methods for detecting outliers and for calculating the Kolmogorov-Smirnov and the Anderson-Darling goodness-of-fit statistics and 90 percent confidence bands about the Weibull line, as well as the techniques for calculating the Batdorf flaw-density constants are also described

    Innate Immune Mechanisms in the Pathogenesis and Management of Acute Pancreatitis

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    Acute pancreatitis is a common, debilitating condition characterised in its most severe form by organ necrosis as well as systemic inflammation, organ failure and death. The innate immune system, predominantly mediated through neutrophils, has been shown to contribute significantly to both pancreatic injury and respiratory failure: the leading cause of death in severe acute pancreatitis. Neutrophil extracellular traps, anti-microbial nuclear chromatin laced with proteases, are a recent discovery and contribute to the genesis of extracellular free radicals, microvascular thrombosis and abscess formation. Histones and histone fragments are critical active components of neutrophil extracellular traps. They are amongst the most widely conserved biochemical structures, are released as antimicrobial agents by a wide range of organisms and are uniquely toxic to cellular organisms. A central hypothesis for this work, is that the release of neutrophil extracellular traps, and their histone component in particular, is central to the way by which the innate immune response exacerbates acute pancreatitis. By using a 12-injection model of cerulein pancreatitis in mice depleted of specific innate immune cell subsets (Ly6G neutrophils, Ly6C monocytes and CCR2hi inflammatory monocytes), cytokine feedback mechanisms were identified and differential effects on pancreas and lung demonstrated by different cell types. In particular, CCR2hi pro-inflammatory monocytes appeared to contribute greatest to pancreatic injury, whereas Ly6Ghi neutrophils contributed most to lung injury. Using selective simultaneous measurement of portal, systemic venous and arterial blood, the liver was identified as the predominant source of circulating histones in acute pancreatitis, although hepatic immune cells are likely responsible for this signal amplification, similar to that seen with cytokines. Systemic injection of FITC-labelled histones demonstrated concentration within the pancreas only in concomitant pancreatitis. In (acinar) cellular isolates, histones led to dose-dependent necrosis by disrupting the plasmalemma. This in turn led to calcium currents across the membrane, which were not necessary to achieve cytotoxicity. By developing novel methodologies of measuring perfusion on a whole-organ level in mouse pancreas, an overall reduction in pancreatic perfusion is observed in cerulein AP, with patches of ischaemia resulting in focal necrosis on the same time-scale as maximal histone release. Pre-treatment with NETosis inhibitors reduced pancreatic injury, but histone detoxification as treatment (3-hours after induction of acute pancreatitis) was not effective. These results indicate modulation of innate immune mechanisms may allow future therapies to be targeted selectively at different phases of acute pancreatitis, to control extra-pancreatic effects and organ failure independently from pancreatic injury. Significant challenges remain to deliver therapies to a poorly perfused pancreas

    RR Lyrae stars in the southern globular cluster NGC 362

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    NGC 362 is a bright southern globular cluster for which no extensive variability survey has ever been done. Time-series CCD photometric observations have been obtained. Light curves have been derived with both profile fitting photometry and image subtraction. We developed a simple method to convert flux phase curves to magnitudes, which allows the use of empirical light curve shape vs. physical parameters calibrations. Using the RR Lyrae metallicity and luminosity calibrations, we have determined the relative iron abundances and absolute magnitudes of the stars. The color-magnitude diagram has been fitted with Yale-Yonsei isochrones to determine reddening and distance independently. For five RR Lyrae stars we obtained radial velocity measurements from optical spectra. We found 45 RR Lyr stars, of which the majority are new discoveries. About half of the RR Lyraes exhibit light curve changes (Blazhko effect). The RR Lyrae-based metallicity of the cluster is [Fe/H]=-1.16 +/- 0.25, the mean absolute magnitude of the RR Lyrae stars is M_V=0.82 +/- 0.04 mag implying a distance of 7.9 +/- 0.6 kpc. The mean period of RRab stars is 0.585 +/- 0.081 days. These properties place NGC 362 among the Oosterhoff type I globular clusters. The isochrone fit implies a slightly larger distance of 9.2 +/- 0.5 kpc and an age of 11 +/- 1 Gyr. We also found 11 eclipsing binaries, 14 pulsating stars of other types, including classical Cepheids in the SMC and 15 variable stars with no firm classification

    Quantitative Mapping of Pore Fraction Variations in Silicon Nitride Using an Ultrasonic Contact Scan Technique

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    An ultrasonic scan procedure using the pulse-echo contact configuration was employed to obtain maps of pore fraction variations in sintered silicon nitride samples in terms of ultrasonic material properties. Ultrasonic velocity, attenuation coefficient, and reflection coefficient images were obtained simultaneously over a broad band of frequencies (e.g., 30 to 110 MHz) by using spectroscopic analysis. Liquid and membrane (dry) coupling techniques and longitudinal and shear-wave energies were used. The major results include the following: Ultrasonic velocity (longitudinal and shear wave) images revealed and correlated with the extent of average through-thickness pore fraction variations in the silicon nitride disks. Attenuation coefficient images revealed pore fraction nonuniformity due to the scattering that occurred at boundaries between regions of high and low pore fraction. Velocity and attenuation coefficient images were each nearly identical for machined and polished disks, making the method readily applicable to machined materials. Velocity images were similar for wet and membrane coupling. Maps of apparent Poisson's ratio constructed from longitudinal and shear-wave velocities quantified Poisson's ratio variations across a silicon nitride disk. Thermal wave images of a disk indicated transient thermal behavior variations that correlated with observed variations in pore fraction and velocity and attenuation coefficients

    Enhanced Recovery After Surgery Program in Patients Undergoing Pancreaticoduodenectomy A PRISMA-Compliant Systematic Review and Meta-Analysis

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    Enhanced recovery after surgery (ERAS) pathways are multimodal, evidence-based approaches to optimize patient outcome after surgery. However, the use of ERAS protocols to improve morbidity and recovery time without compromising safety following pancreaticoduodenectomy (PD) remains to be elucidated. We conducted a systemic review and meta-analysis to assess the safety and efficacy of ERAS protocols compared with conventional perioperative care (CPC) in patients following PD. PubMed, Medline, Embase, and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched between January 2000 and June 2015. The patients who underwent PD with ERAS protocols or CPC were eligible. The studies that compared postoperative length of hospital stay (PLOS), postoperative complications, or in-hospital costs in the 2 groups were included. A meta-analysis, meta-regression, sensitivity analysis, and subgroup analysis were performed to estimate the postoperative outcomes between the 2 groups and identified the potential confounders. We used the methodological index for nonrandomized studies checklist to assess methodological qualities. Weighted mean differences (WMD) or odds ratios (OR) were calculated with their corresponding 95% confidence intervals (CI). The publication bias tests were also performed through the funnel plots. In total, 14 nonrandomized comparative studies with 1409 ERAS cases and 1310 controls were analyzed. Implementation of an ERAS protocol significantly reduced PLOS (WMD: −4.17 days; 95%CI: −5.72 to −2.61), delayed gastric emptying (OR: 0.56; 95%CI: 0.44–0.71), overall morbidity (OR: 0.63; 95% CI: 0.54–0.74), and in-hospital costs compared to CPC (all P < 0.001). There were no statistically significant differences in other postoperative outcomes. Age, gender, and ERAS component implementation did not significantly contribute to heterogeneity for PLOS as shown by meta-regression analysis. Our study suggested that ERAS was as safe as CPC and improved recovery of patients undergoing PD, thus reducing in-hospital costs. General adoption of ERAS protocols during PD should be recommended

    Adaptive and Phase Selective Spike Timing Dependent Plasticity in Synaptically Coupled Neuronal Oscillators

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    We consider and analyze the influence of spike-timing dependent plasticity (STDP) on homeostatic states in synaptically coupled neuronal oscillators. In contrast to conventional models of STDP in which spike-timing affects weights of synaptic connections, we consider a model of STDP in which the time lags between pre- and/or post-synaptic spikes change internal state of pre- and/or post-synaptic neurons respectively. The analysis reveals that STDP processes of this type, modeled by a single ordinary differential equation, may ensure efficient, yet coarse, phase-locking of spikes in the system to a given reference phase. Precision of the phase locking, i.e. the amplitude of relative phase deviations from the reference, depends on the values of natural frequencies of oscillators and, additionally, on parameters of the STDP law. These deviations can be optimized by appropriate tuning of gains (i.e. sensitivity to spike-timing mismatches) of the STDP mechanism. However, as we demonstrate, such deviations can not be made arbitrarily small neither by mere tuning of STDP gains nor by adjusting synaptic weights. Thus if accurate phase-locking in the system is required then an additional tuning mechanism is generally needed. We found that adding a very simple adaptation dynamics in the form of slow fluctuations of the base line in the STDP mechanism enables accurate phase tuning in the system with arbitrary high precision. Adaptation operating at a slow time scale may be associated with extracellular matter such as matrix and glia. Thus the findings may suggest a possible role of the latter in regulating synaptic transmission in neuronal circuits

    Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study

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    Objective: UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design: RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Results: Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5–7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion: Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required
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