1,497 research outputs found

    Adjuvant chemotherapy for colorectal cancer

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    Utilization and Standardization of Beverage Based Containers

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    The purpose of this document is to formally describe and explain all of the decisions associated with the data collection and analysis for this Cal Poly Senior Project. Throughout the project, we will utilize and hone the skills that each team member has developed during our time in Cal Poly\u27s Engineering program. In addition, this document will briefly describe some of Blue Diamond’s history as one of the biggest almond companies in the world. The statement of work will introduce and describe the current status of the beverage base container process and international beverage container design. Next it will discuss the problem statement and what the project’s expected scope and objectives will be. Finally, the literature review outlines the research and ends with the possible solution designs for the project. To obtain the best results in this project, we will analyze, observe, and come to a recommendation for a better processing system for the beverage base containers. We will also be just as scrupulous when recommending a new container for international shipping and standardization. Through observation, design, and experiments we will produce standards to measure our success. This project will take place during the Fall Quarter of 2019 and the Winter Quarter of 2020

    Images, structural properties and metal abundances of galaxy clusters observed with Chandra ACIS-I at 0.1<z<1.3

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    We have assembled a sample of 115 galaxy clusters at 0.1<z<1.3 with archived Chandra ACIS-I observations. We present X-ray images of the clusters and make available region files containing contours of the smoothed X-ray emission. The structural properties of the clusters were investigated and we found a significant absence of relaxed clusters (as determined by centroid shift measurements) at z>0.5. The slope of the surface brightness profiles at large radii were steeper on average by 15% than the slope obtained by fitting a simple beta-model to the emission. This slope was also found to be correlated with cluster temperature, with some indication that the correlation is weaker for the clusters at z>0.5. We measured the mean metal abundance of the cluster gas as a function of redshift and found significant evolution, with the abundances dropping by 50% between z=0.1 and z~1. This evolution was still present (although less significant) when the cluster cores were excluded from the abundance measurements, indicating that the evolution is not solely due to the disappearance of relaxed, cool core clusters (which are known to have enhanced core metal abundances) from the population at z>0.5.Comment: 23 pages, 12 figures. Accepted for publication in ApJS. Updated to match published version. Redshifts of two clusters (RXJ1701 and CL0848) corrected and two observations of MACSJ0744.8 have been combined into one. Conclusions unchanged. A version with images of all of the clusters is available at http://hea-www.harvard.edu/~bmaughan/clusters.htm

    A phase II study of capecitabine and oxalplatin combination chemotherapy in patients with inoperable adenocarcinoma of the gall bladder or biliary tract

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    Background: Advanced biliary tract carcinomas are associated with a poor prognosis, and palliative chemotherapy has only modest benefit. This multi-centre phase II study was conducted to determine the efficacy of capecitabine in combination with oxaliplatin in patients with inoperable gall bladder or biliary tract cancer. Methods: This was a Phase II, non-randomised, two-stage Simon design, multi-centre study. Ethics approval was sought and obtained by the North West MREC, and then locally by the West Glasgow Hospitals Research Ethics Com mittee. Eligible patients with inoperable locally advanced or metastatic adenocarcinoma of the gall bladder or biliary tract and with adequate performance status, haematologic, renal, and hepatic function were treated with capecit abine (1000 mg/m2 po, twice daily, days 1–14) and oxaliplatin (130 mg/m2 i.v., day 1) every 3 weeks for up to six cycles. The primary objective of the study was to determine the objective tumour response rates (complete and partial). The secondary objectives included assessment of toxicity, progression-free survival, and overall survival. Results: Forty-three patients were recruited between July 2003 and December 2005. The regimen was well tolerated with no grade 3/4 neutropenia or thrombocytopenia. Grade 3/4 sensory neuropathy was observed in six patients. Two-thirds of patients received their chemotherapy without any dose delays. Overall response rate was 23.8 % (95 % CI 12.05–39.5 %). Stable disease was observed in a further 13 patients (31 %) and progressive disease observed in 12 (28.6 %) of patients. The median progression-free survival was 4.6 months (95 % CI 2.8–6.4 months; Fig. 1) and the median overall survival 7.9 months (95 % CI 5.3–10.4 months; Fig. 2). Conclusion: Capecitabine combined with oxaliplatin has a lower disease control and shorter overall survival than the combination of cisplatin with gemcitabine which has subsequently become the standard of care in this disease. How ever, capecitabine in combination with oxaliplatin does have modest activity in this disease, and can be considered as an alternative treatment option for patients in whom cisplatin and/or gemcitabine are contra-indicated

    South-West extension of the hard X-ray emission from the Coma cluster

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    We explore the morphology of hard (18-30 keV) X-ray emission from the Coma cluster of galaxies. We analyze a deep (1.1 Ms) observation of the Coma cluster with the ISGRI imager on board the \emph{INTEGRAL} satellite. We show that the source extension in the North-East to South-West (SW) direction (∼17′\sim 17') significantly exceeds the size of the point spread function of ISGRI, and that the centroid of the image of the source in the 18-30 keV band is displaced in the SW direction compared to the centroid in the 1-10 keV band. To test the nature of the SW extension we fit the data assuming different models of source morphology. The best fit is achieved with a diffuse source of elliptical shape, although an acceptable fit can be achieved assuming an additional point source SW of the cluster core. In the case of an elliptical source, the direction of extension of the source coincides with the direction toward the subcluster falling onto the Coma cluster. If the SW excess is due to the presence of a point source with a hard spectrum, we show that there is no obvious X-ray counterpart for this additional source, and that the closest X-ray source is the quasar EXO 1256+281, which is located 6.1′6.1' from the centroid of the excess. The observed morphology of the hard X-ray emission clarifies the nature of the hard X-ray "excess" emission from the Coma cluster, which is due to the presence of an extended hard X-ray source SW of the cluster core.Comment: 7pages, 10 figure

    The XMM-LSS survey: the Class 1 cluster sample over the extended 11 deg2^2 and its spatial distribution

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    This paper presents 52 X-ray bright galaxy clusters selected within the 11 deg2^2 XMM-LSS survey. 51 of them have spectroscopic redshifts (0.05<z<1.060.05<z<1.06), one is identified at zphot=1.9z_{\rm phot}=1.9, and all together make the high-purity "Class 1" (C1) cluster sample of the XMM-LSS, the highest density sample of X-ray selected clusters with a monitored selection function. Their X-ray fluxes, averaged gas temperatures (median TX=2T_X=2 keV), luminosities (median LX,500=5×1043L_{X,500}=5\times10^{43} ergs/s) and total mass estimates (median 5×1013h−1M⊙5\times10^{13} h^{-1} M_{\odot}) are measured, adapting to the specific signal-to-noise regime of XMM-LSS observations. The redshift distribution of clusters shows a deficit of sources when compared to the cosmological expectations, regardless of whether WMAP-9 or Planck-2013 CMB parameters are assumed. This lack of sources is particularly noticeable at 0.4≲z≲0.90.4 \lesssim z \lesssim 0.9. However, after quantifying uncertainties due to small number statistics and sample variance we are not able to put firm (i.e. >3σ>3 \sigma) constraints on the presence of a large void in the cluster distribution. We work out alternative hypotheses and demonstrate that a negative redshift evolution in the normalization of the LX−TXL_{X}-T_X relation (with respect to a self-similar evolution) is a plausible explanation for the observed deficit. We confirm this evolutionary trend by directly studying how C1 clusters populate the LX−TX−zL_{X}-T_X-z space, properly accounting for selection biases. We point out that a systematically evolving, unresolved, central component in clusters and groups (AGN contamination or cool core) can impact the classification as extended sources and be partly responsible for the observed redshift distribution.[abridged]Comment: 33 pages, 21 figures, 3 tables ; accepted for publication in MNRA

    Manipulating O3/P2 phase ratio in bi-phasic sodium layered oxides via ionic radius control

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    Funding: This work was supported by the Faraday Institution (Grant number FIRG018). The authors would like to thank Dr. David Rochester at Lancaster University for conducting the ICP-OES experiments. A.B.N. would like to acknowledge funding by the Engineering and Physical Sciences Research Council under grant numbers EP/L017008/1, EP/R023751/1, and EP/T019298/1 for the electron microscopy analysis.Bi-phasic O3/P2 sodium layered oxides have emerged as leading candidates for the commercialisation of next-generation sodium-ion batteries. However, beyond simply altering the sodium content, rational control of the O3/P2 ratio in these materials has proven particularly challenging despite being crucial for the realization of high-performance electrode materials. Here, using abundant elements, we manipulate the O3/P2 ratio using the average ionic radius of the transition metal layer and different synthesis conditions. These methods allow deterministic control over the O3/P2 ratio, even for constant Na contents. In addition, tuning the O3/P2 ratio yields high-performing materials with different performance characteristics, with a P2-rich material achieving high rate capabilities and excellent cycling stability (92% retention, 50 cycles), while an O3-rich material displayed an energy density up to 430 Wh kg−1, (85%, 50 cycles). These insights will help guide the rational design of future high-performance materials for sodium-ion batteries.Publisher PDFPeer reviewe

    NRF2 metagene signature is a novel prognostic biomarker in colorectal cancer

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    We hypothesise that the NRF2 transcription factor would act a biomarker of poor prognosis in colorectal cancer. We derived and validated an mRNA based metagene signature of NRF2 signalling and validated it in 1360 patients from 4 different datasets as an independent biomarker of poor prognosis. This is a novel insight into the molecular signalling of colorectal cancer. Background: NRF2 over activity confers poor prognosis in some cancers but its prognostic role in colorectal cancer (CRC) is unknown. As a transcription factor, we hypothesise a signature of NRF2 regulated genes could act as a prognostic biomarker in CRC and reveal novel biological insights. Methods: Using known NRF2 regulated genes, differentially expressed in CRC, we defined a signature of NRF2 pathway activity using principal component analysis and Cox proportional hazard models and tested it in four independent mRNA datasets, profiled on three different mRNA platforms. Results: 36 genes comprised the final NRF2 signature. 1360 patients were included in the validation. High NRF2 was associated with worse disease free survival (DFS) and/or overall survival (OS) in all datasets: (GSE14333 HR=1.55, 95% C.I 1.2–2.004, p = 0.0008; GSE39582 HR=1.24, 95% C.I 1.086–1.416, p = 0.001; GSE87211 HR=1.431, 95% C.I 1.06–1.93, p = 0.056; MRC FOCUS trial HR=1.14, 95% C.I 1.04–1.26, p = 0.008). In multivariate analyses, NRF2 remained significant when adjusted for stage and adjuvant chemotherapy in stage I-III disease, and BRAF V600E mutation and sidedness in stage IV disease. NRF2 activity was particularly enriched in Consensus Molecular Subtype (CMS) 4. Conclusion: For the first time, NRF2 is shown to be a consistent, robust prognostic biomarker across all stages of colorectal cancer with additional clinical value to current known prognostic biomarkers. High NRF2 signalling in CMS 4 further refines the molecular taxonomy of CRC, a new biological insight, suggesting avenues of further study

    A phase I/II study of irinotecan when added to 5-fluorouracil and leucovorin and pelvic radiation in locally advanced rectal cancer: a Colorectal Clinical Oncology Group Study

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    The objective of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of irinotecan administered as a 5-day schedule synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation (45 Gy) for primary borderline/unresectable, locally advanced rectal cancer. The study used escalating doses of intravenous irinotecan (6, 8, 10, 12, 14, 16, 18, and 20 mg m−2) administered on days 1–5 and 29–33 followed by low dose LV (20 mg m−2) and 5FU (350 mg m−2 over 1 h) in sequential cohorts. Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction. Surgery in the form of mesorectal excision was performed 6–10 weeks later. Histopathological examination of the resected specimen was performed according to techniques of Quirke, and compared with clinical staging. A distance of 1 mm or less between the peripheral extent of the tumour and the radial resection margin defined an involved circumferential resection margin (CRM). The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT) defined as specific grade 3 or 4 toxicities. Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In total, 57 patients received irinotecan at the eight dose levels. The final cohort reached DLT after only four patients had been enrolled. The median age was 62 years (range 26–75), 37 male and 20 female subjects. The MTD of irinotecan in this schedule was 20 mg m−2 when three out of four patients experienced DLT. Dose limiting grade 3 or 4 diarrhoea was reported in seven out of 57 patients, three at the 20 mg m−2 dose level. Serious haematological toxicity (grade 3) was minimal and reported in only three patients; one grade 3 neutropaenia, one grade 4 neutropaenia and one grade 3 febrile neutropaenia and anaemia. Compliance was good with 93 and 89% of patients completing radiotherapy and chemotherapy, respectively. The remaining patients had only minor deviations from protocol therapy. Eight patients did not proceed to surgery, in six cases because they remained unresectable or had developed metastatic disease, one patient was unfit for surgery and one died as a result of complications from radiotherapy. Forty-nine patients underwent a potentially curative surgical resection. Histopathological examination of the resected specimen demonstrated pCR 12 out of 49 (24%) and 12 out of 57 (21%) overall. A histologically confirmed clear circumferential resection margin (CRM) was achieved in 39 out of 49 (80%) of those resected, and 39 out of 57 (68%) overall. In conclusion, MTD with this scheduled regimen of irinotecan is 20 mg m−2 (days 1–5 and 29–33). The acceptable toxicity and compliance at 18 mg m−2 recommend testing this dose in future phase III studies. The tumour downstaging and complete resection rates (negative CRM) are encouragingly high for this very locally advanced group
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