Euler analysis of the three dimensional flow field of a high-speed propeller: Boundary condition effects

The results of an investigation of the effects of far field boundary conditions on the solution of the three dimensional Euler equations governing the flow field of a high speed single rotation propeller are presented. The results show that the solutions obtained with the nonreflecting boundary conditions are in good agreement with experimental data. The specification of nonreflecting boundary conditions is effective in reducing the dependence of the solution on the location of the far field boundary. Details of the flow field within the blade passage and the tip vortex are presented. The dependence of the computed power coefficient on the blade passage and the tip vortex are presented. The dependence of the computed power coefficient on the blade setting angle is examined

Near-field noise of a single-rotation propfan at an angle of attack

The near field noise characteristics of a propfan operating at an angle of attack are examined utilizing the unsteady pressure field obtained from a 3-D Euler simulation of the propfan flowfield. The near field noise is calculated employing three different procedures: a direct computation method in which the noise field is extracted directly from the Euler solution, and two acoustic-analogy-based frequency domain methods which utilize the computed unsteady pressure distribution on the propfan blades as the source term. The inflow angles considered are -0.4, 1.6, and 4.6 degrees. The results of the direct computation method and one of the frequency domain methods show qualitative agreement with measurements. They show that an increase in the inflow angle is accompanied by an increase in the sound pressure level at the outboard wing boom locations and a decrease in the sound pressure level at the (inboard) fuselage locations. The trends in the computed azimuthal directivities of the noise field also conform to the measured and expected results

Notch signaling in serous ovarian cancer

Ovarian cancer is the most lethal of all gynecologic malignancies because women commonly present with advanced stage disease and develop chemotherapy refractory tumors. While cytoreductive surgery followed by platinum based chemotherapy are initially effective, ovarian tumors have a high propensity to recur highlighting the distinct need for novel therapeutics to improve outcomes for affected women. The Notch signaling pathway plays an established role in embryologic development and deregulation of this signaling cascade has been linked to many cancers. Recent genomic profiling of serous ovarian carcinoma revealed that Notch pathway alterations are among the most prevalent detected genomic changes. A growing body of scientific literature has confirmed heightened Notch signaling activity in ovarian carcinoma, and has utilized in vitro and in vivo models to suggest that targeting this pathway with gamma secretase inhibitors (GSIs) leads to anti-tumor effects. While it is currently unknown if Notch pathway inhibition can offer clinical benefit to women with ovarian cancer, several GSIs are currently in phase I and II trials across many disease sites including ovary. This review will provide background on Notch pathway function and will focus on the pre-clinical literature that links altered Notch signaling to ovarian cancer progression

Inhibition of Notch Signaling in Combination with Paclitaxel Reduces Platinum-Resistant Ovarian Tumor Growth

Introduction: Ovarian cancer (OvCa) is the most lethal gynecologic malignancy in the United States because of chemoresistant recurrent disease. Our objective was to investigate the efficacy of inhibiting the Notch pathway with a γ-secretase inhibitor (GSI) in an OvCa patient-derived xenograft model as a single agent therapy and in combination with standard chemotherapy. Methods: Immunocompromised mice bearing xenografts derived from clinically platinum-sensitive human ovarian serous carcinomas were treated with vehicle, GSI (MRK-003) alone, paclitaxel and carboplatin (P/C) alone, or the combination of GSI and P/C. Mice bearing platinum-resistant xenografts were given GSI with or without paclitaxel. Gene transcript levels of the Notch pathway target Hes1 were analyzed using RT-PCR. Notch1 and Notch3 protein levels were evaluated. The Wilcoxon rank-sum test was used to assess significance between the different treatment groups. Results: Expression of Notch1 and 3 was variable. GSI alone decreased tumor growth in two of three platinum-sensitive ovarian tumors (p < 0.05), as well as in one of three platinum-sensitive tumors (p = 0.04). The combination of GSI and paclitaxel was significantly more effective than GSI alone and paclitaxel alone in all platinum-resistant ovarian tumors (all p < 0.05). The addition of GSI did not alter the effect of P/C in platinum-sensitive tumors. Interestingly, although the response of each tumor to chronic GSI exposure did not correlate with its endogenous level of Notch expression, GSI did negatively affect Notch signaling in an acute setting. Conclusion: Inhibiting the Notch signaling cascade with a GSI reduces primary human xenograft growth in vivo. GSI synergized with conventional cytotoxic chemotherapy only in the platinum-resistant OvCa models with single agent paclitaxel. These findings suggest inhibition of the Notch pathway in concert with taxane therapy may hold promise for treatment of platinum-resistant OvCa

Randomized controlled trials reflected clinical practice when comparing the course of low back pain symptoms in similar populations.

OBJECTIVE:This study compares participants in randomized controlled trials (RCTs) (the Minimal Invasive Treatment [MinT] trials) to participants in a related observational study with regard to their low back pain (LBP) symptom course. STUDY DESIGN AND SETTING:Eligible patients were diagnosed with chronic LBP originating from the facet joints (N = 615) or sacroiliac (SI) joints (N = 533) and were treated with radiofrequency denervation and an exercise program. Randomized patients were compared to patients in the related observational study who fulfilled all RCT eligibility criteria (observational group 1) and to patients who did not fulfill at least one of the RCT eligibility criteria (observational group 2). Outcomes were pain intensity, treatment success, and functional status over a 3-month period. Longitudinal mixed-model analyses and linear regression models were applied to analyze the differences in outcomes between the RCT and observational study groups. RESULTS:No differences in symptom course were found between patients in the RCTs and patients in observational group 1. Patients with facet joint pain in observational group 2 had overall less treatment success (odds ratios [OR], 0.67; 95% confidence interval [CI], 0.50-0.90), and less improvement in physical functioning (mean difference [MD], 5.82; 95% CI, 2.54-9.11) compared to the RCT patients. Patients with SI joint pain in observational group 2 had higher pain scores (MD, 0.40; 95% CI, 0.09-0.72), less treatment success (OR, 0.72; 95% CI, 0.54-0.96), and less improvement in physical functioning (MD, 7.16; 95% CI, 3.84-10.47) compared to the RCT patients. CONCLUSION:This supports the generalizability of results from the MinT RCTs as this study suggests that these RCTs reflect clinical practice when comparing similar populations. To what extent this holds true for all RCTs in LBP should be further explored

Pharmacogenomic testing in paediatrics: Clinical implementation strategies

Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited. As with most paediatric pharmacological studies, there are well-recognised barriers to obtaining high-quality PGx evidence, particularly when patient numbers may be small, and off-label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential. This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences. Improving the evidence base demonstrating the clinical utility and cost-effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy

Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

Background. During the chronic stage of Complex Regional Pain Syndrome (CRPS), impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS. Discussion. The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin. Summary. The origin of the pain should be the basis of the symptomatic therapy. Since the difference in temperature between both hands fluctuates over time in cold CRPS, when in doubt, the clinician should prioritize the patient's report of a persistent cold extremity over clinical tests that show no difference. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients

Modeling surf zone tracer plumes : 1. Waves, mean currents, and low-frequency eddies

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): C11027, doi:10.1029/2011JC007210.A model that accurately simulates surf zone waves, mean currents, and low-frequency eddies is required to diagnose the mechanisms of surf zone tracer transport and dispersion. In this paper, a wave-resolving time-dependent Boussinesq model is compared with waves and currents observed during five surf zone dye release experiments. In a companion paper, Clark et al. (2011) compare a coupled tracer model to the dye plume observations. The Boussinesq model uses observed bathymetry and incident random, directionally spread waves. For all five releases, the model generally reproduces the observed cross-shore evolution of significant wave height, mean wave angle, bulk directional spread, mean alongshore current, and the frequency-dependent sea surface elevation spectra and directional moments. The largest errors are near the shoreline where the bathymetry is most uncertain. The model also reproduces the observed cross-shore structure of rotational velocities in the infragravity (0.004 < f < 0.03 Hz) and very low frequency (VLF) (0.001 < f < 0.004 Hz) bands, although the modeled VLF energy is 2–3 times too large. Similar to the observations, the dominant contributions to the modeled eddy-induced momentum flux are in the VLF band. These eddies are elliptical near the shoreline and circular in the mid surf zone. The model-data agreement for sea swell waves, low-frequency eddies, and mean currents suggests that the model is appropriate for simulating surf zone tracer transport and dispersion.This research was supported by SCCOOS, CA Coastal Conservancy, NOAA, NSF, ONR, and CA Sea Grant.2012-05-1