140 research outputs found
Application of kriging to motorsport aerodynamic analysis
Aerodynamic analysis in motorsport is conducted using three methods, computational, scaled experimental and full-scale operational. However, the varying fidelity, different sampling resolutions and unavoidable errors of each technique make valid comparisons between datasets from each method difficult and time consuming. Kriging is a geostatistical method to estimate values within a data field by examining and applying the trends of the dataset. This research examines how such techniques can be used to aid comparison between aerodynamic measurements of a race car. It examines how kriging can be used to transform discrete measurements, of varying fidelity and sampling resolution, into semi-continuous measurements, thus allowing computational results to be compared across a wider range of conditions than initially tested. This work explores how kriging can allow the trends from highly sampled data, such as track running, to be applied to less sampled data, such as CFD to improve computational and overall aerodynamic analysis
Breast cancer follow-up after a primary diagnosis: A confused picture
The follow-up care of people diagnosed with early breast cancer varies across the world. In the UK, services have evolved in an ad hoc way, with no standardized approach nationally. Some people are seen face to face at regular intervals, others are discharged at two years, while others are followed up over the telephone. This is creating confusion for patients as to what is best practice. The lack of evidence to support intensive surveillance is frequently cited as the main reason to reduce or indeed review the benefits of face to face clinical consultations in the hospital/community setting. In addition, a lack of specific recommendations in current guidelines compounds this. Although primary disease stage and treatment are strong indicators of survival, and time to recurrence (both local and distant) is extending, patterns of follow-up care in the UK differ depending on where you live. Yet, European and American guidelines, where survival is frequently reported as being better than the UK, continue to recommend follow-up at regular intervals as part of their overall management approach; to ensure new and changing ways of treating early breast cancer are initiated, managed and monitored accordingly. Indeed their guidelines are increasing rather than decreasing follow-up. While their health systems may differ, survival outcome reporting is not adjusted to reflect these differences. This paper provides an overview of breast cancer follow-up guidance across the world and opens up a debate about whether patterns of follow up care will affect survival outcomes into the future
Cutaneous Nod2 expression regulates the skin microbiome and wound healing in a murine model
The skin microbiome exists in dynamic equilibrium with the host but when the skin is compromised, bacteria can colonise the wound and impair wound healing. Thus the interplay between normal skin-microbial interactions versus pathogenic-microbial interactions in wound repair is important. Bacteria are recognised by innate host pattern recognition receptors (PRRs) and we previously demonstrated an important role for the PRR NOD2 (nucleotide-binding oligomerisation domains-containing protein 2) in skin wound repair. NOD2 is implicated in changes in the composition of the intestinal microbiota in Crohn’s disease but its role on skin microbiota is unknown. Nod2-deficient (Nod2-/-) mice had an inherently altered skin microbiome compared with wild-type (WT) controls. Furthermore, we found Nod2-/- skin microbiome dominated and caused impaired healing, revealed in cross-fostering experiments of WT with Nod2-/- pups which then acquired altered cutaneous bacteria and delayed healing. High-throughput sequencing and qPCR revealed a significant compositional shift, specifically in the genus Pseudomonas in Nod2-/- mice. To confirm whether Pseudomonas directly impairs wound healing, WT mice were infected with P. aeruginosa biofilms and akin to Nod2-/- mice, were found to exhibit a significant delay in wound repair. Collectively, these studies demonstrate the importance of the microbial communities in skin wound healing outcome
Polymorphism of the azobenzene dye compound methyl yellow
The crystal structure and polymorphism of the well-known aminoazobenzene, N,N-dimethyl-4-aminoazobenzene (DAB) are studied; a second polymorph of DAB reported and the relationship between the two polymorphs studied using differential scanning calorimetry and by evaluating their lattice energies and absorption spectra. Without significantly strong intermolecular interactions present in the two forms of DAB, a balance between conformational strain and a cumulative π-orbital overlapping effect results in the existence of the enantiotropically related polymorphs and their alternative packing arrangements. The UV/vis spectra of the two polymorphs are different, thus illustrating the significance of small structural changes on the colour of a material, which could behave differently under particular sensing conditions. DAB has been used primarily as an acid/base indicator solution and a dye molecule and the implications of the polymorphic relationships established here are discussed with respect to the range of applications this molecule finds as a sensor and for its incorporation into various functional films and devices
Defining the genetic susceptibility to cervical neoplasia - a genome-wide association study
Funding: MAB was funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. Support was also received from the Australian Cancer Research Foundation. JL holds a Tier 1 Canada Research Chair in Human Genome Epidemiology. The Seattle study was supported by the following grants: NIH, National Cancer Institute grants P01CA042792 and R01CA112512. Cervical Health Study (from which the NSW component was obtained) was funded by NHMRC Grant 387701, and CCNSW core grant. The Montreal study was funded by the Canadian Institutes of Health Research (grant MOP-42532) and sample processing was funded by the Reseau FRQS SIDA-MI. The Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg and Umeå, the Lundberg Foundation, the Torsten and Ragnar Soderberg’s Foundation, the Novo Nordisk Foundation, and the European Commission grant HEALTH-F2-2008-201865-GEFOS, BBMRI.se, the Swedish Society of Medicine, the KempeFoundation (JCK-1021), the Medical Faculty of Umeå University, the County Council of Vasterbotten (Spjutspetsanslag VLL:159:33-2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PDFPublisher PD
Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom collaborative trial of ovarian cancer screening
PURPOSE: Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates.
PATIENTS AND METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves.
RESULTS: After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869).
CONCLUSION: Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded
Phonon excitations of Floquet-driven superfluids in a tilted optical lattice
Tilted lattice potentials with periodic driving play a crucial role in the study of artificial gauge fields and topological phases with ultracold quantum gases. However, driving-induced heating and the growth of phonon modes restrict their use for probing interacting many-body states. Here, we experimentally investigate phonon modes and interaction-driven instabilities of superfluids in the lowest band of a shaken optical lattice. We identify stable and unstable parameter regions and provide a general resonance condition. In contrast to the high-frequency approximation of a Floquet description, we use the micromotion of the superfluids to analyze the growth of phonon modes from slow- to fast-driving frequencies. The model describes phonon excitations in both resonantly and nonresonantly driven systems, with or without a tilted potential. Our observations enable the prediction of stable parameter regimes for quantum-simulation experiments aimed at studying driven systems with strong interactions over extended time scales
The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
Background: To assess the within trial cost-effectiveness of an NHS ovarian cancer screening (OCS) programme using data from UKCTOCS and extrapolate results based on average life expectancy.
Methods: Within trial economic evaluation of no screening (C) versus either (1) an annual OCS programme using transvaginal ultrasound (USS) or (2) an annual ovarian cancer multimodal screening programme with serum CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a second line test (MMS), plus comparison of lifetime extrapolation of the no screening arm and the MMS programme using both a predictive and a Markov model.
Results: Using a CA125-ROCA cost of £20, the within trial results show USS to be strictly dominated by MMS, with the MMS versus C comparison returning an Incremental Cost-Effectiveness ratio (ICER) of £91,452 per life year gained (LYG). If the CA125-ROCA unit cost is reduced to £15 the ICER becomes £77,818 per LYG. Predictive extrapolation over the expected lifetime of the UKCTOCS women returns an ICER of £30,033 per LYG, while Markov modelling produces an ICER of £46,922 per QALY.
Conclusions: Analysis suggests that, after accounting for the lead-time required to establish full mortality benefits, a national OCS programme based on the MMS strategy quickly approaches the current NICE thresholds for cost-effectiveness when extrapolated out to lifetime as compared to the within trial ICER estimates. Whether MMS could be recommended on economic grounds would depend on the confirmation and size of the mortality benefit at the end of an ongoing follow-up of the UKCTOCS cohort
Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials
PURPOSE: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS: Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. RESULTS: Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION: ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT
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