646 research outputs found
A Scanned Perturbation Technique For Imaging Electromagnetic Standing Wave Patterns of Microwave Cavities
We have developed a method to measure the electric field standing wave
distributions in a microwave resonator using a scanned perturbation technique.
Fast and reliable solutions to the Helmholtz equation (and to the Schrodinger
equation for two dimensional systems) with arbitrarily-shaped boundaries are
obtained. We use a pin perturbation to image primarily the microwave electric
field amplitude, and we demonstrate the ability to image broken time-reversal
symmetry standing wave patterns produced with a magnetized ferrite in the
cavity. The whole cavity, including areas very close to the walls, can be
imaged using this technique with high spatial resolution over a broad range of
frequencies.Comment: To be published in Review of Scientific Instruments,September, 199
Current standards and future perspectives in adjuvant treatment for biliary tract cancers
Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only âŒ20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60-70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, including a variety of additional tumours (e.g. pancreatic and ampullary tumours) and most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies. Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community. This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored
A phase 1b study of Selumetinib in combination with Cisplatin and Gemcitabine in advanced or metastatic biliary tract cancer: the ABC-04 study
BACKGROUND: Combined treatment with cisplatin and gemcitabine (CisGem) is the standard of care for patients with advanced biliary tract cancer (ABC). Selumetinib (AZD6244, ARRY-142886) potently and selectively inhibits MEK1/2, an intracellular kinase and has shown activity in ABC. The objective of the ABC-04 trial was to establish the recommended dose of selumetinib in combination with CisGem in patients with ABC. METHODS: Eligible patients wereââ„â18Â years, had histologically or cytologically-confirmed unresectable recurrent or metastatic biliary tract, gallbladder or ampullary carcinoma, WHO performance status 0-2, and adequate major organ function. Patients may have had prior surgery, radiotherapy or adjuvant chemotherapy, but no prior CisGem and no prior chemotherapy for locally advanced or metastatic disease. Patients received cisplatin 25Â mg/m(2) plus gemcitabine 1000Â mg/m(2) intravenously on days 1 and 8 of a 21-day cycle. Selumetinib capsules were taken daily. Patients received up to 8Â cycles of CisGem and could receive selumetinib until disease progression. A dose de-escalation scheme was used to determine the recommended dose of selumetinib. The first dose level was 75Â mg bd. Patients were recruited in cohorts of 3 and assessed for dose limiting toxicity (DLT) during the first cycle of treatment. RESULTS: Thirteen patients were recruited, of whom 12 were evaluable for DLT (1 did not start treatment). All evaluable patients received the starting dose of selumetinib 75Â mg bd and one patient experienced a DLT (cardiac chest pain). The median number of days selumetinib was taken (adjusted for the number of days of dose interruptions) was 171.5 (IQR: 75.5 to 344). Two patients remained on treatment at 14 and 19Â months post registration. There were 3 temporary and 1 permanent interruptions of selumetinib in cycle 1. Eight patients were evaluable for objective response (RECIST v1.1): 3 had a partial response and 5 stable disease. The median PFS was 6.4Â months (IQR 5.2 to 13.7). Toxicities related to selumetinib were mostly related to oedema and rash, grade 1-2 and manageable. Pharmacokinetic analysis showed that the AUC(0-t), AUC(0-â) and Cmax of selumetinib increased by 12, 11 and 30Â % respectively when it was administered with CisGem, while Cmax for the N-desmethyl metabolite of selumetinib decreased by 40Â %. There was no evidence that the time of Cmax for selumetinib or N-desmethyl metabolite of selumetinib were different when selumetinib was administered alone or with CisGem. CONCLUSION: The recommended dose of selumetinib when combined with CisGem was 75Â mg bd. Translational studies are underway to identify biomarkers that may predict outcome (ClinicalTrials.gov identifier: NCT01242605 July 6(th) 2010)
Angle of repose and segregation in cohesive granular matter
We study the effect of fluids on the angle of repose and the segregation of
granular matter poured into a silo. The experiments are conducted in two
regimes where: (i) the volume fraction of the fluid is small and it forms
liquid bridges between particles, and (ii) the particles are completely
immersed in the fluid. The data is obtained by imaging the pile formed inside a
quasi-two dimensional silo through the transparent glass side walls. In the
first series of experiments, the angle of repose is observed to increase
sharply with the volume fraction of the fluid and then saturates at a value
that depends on the size of the particles. We systematically study the effect
of viscosity by using water-glycerol mixtures to vary it over at least three
orders of magnitude while keeping the surface tension almost constant. Besides
surface tension, the viscosity of the fluid is observed to have an effect on
the angle of repose and the extent of segregation. In case of bidisperse
particles, segregation is observed to decrease and finally saturate depending
on the size ratio of the particles and the viscosity of the fluid. The sharp
initial change and the subsequent saturation in the extent of segregation and
angle of repose occurs over similar volume fraction of the fluid. In the second
series of experiments, particles are poured into a container filled with a
fluid. Although the angle of repose is observed to be unchanged, segregation is
observed to decrease with an increase in the viscosity of the fluid.Comment: 9 pages, 12 figure
Traveling Granular Segregation Patterns in a Long Drum Mixer
Mixtures of granular media often exhibit size segregation along the axis of a
partially-filled, horizontal, rotating cylinder. Previous experiments have
observed axial bands of segregation that grow from concentration fluctuations
and merge in a manner analogous to spinodal decomposition. We have observed
that a new dynamical state precedes this effect in certain mixtures:
bi-directional traveling waves. By preparing initial conditions, we found that
the wave speed decreased with wavelength. Such waves appear to be inconsistent
with simple PDE models which are first order in time.Comment: 11 page
Albumin-mediated extracellular zinc speciation drives cellular zinc uptake
This work was financially supported by the Leverhulme Trust (RPG-2017-214) and BBSRC (BB/J006467/1 and BB/V014684/1). We thank Prof. Andrew Riches (University of St. Andrews) for provision of materials, and Dr. Elizabeth Bolitho (University of Warwick) for assistance with cell culture experiments.The role of the extracellular medium in influencing metal uptake into cells has not been described quantitatively. In a chemically defined model system containing albumin, zinc influx into endothelial cells correlates with the extracellular free zinc concentration. Allosteric inhibition of zinc-binding to albumin by free fatty acids increased zinc flux.Publisher PDFPeer reviewe
Predictors of patient preference for either whole body magnetic resonance imaging (WB-MRI) or CT/ PET-CT for staging colorectal or lung cancer.
INTRODUCTION: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer. METHODS: Patients recruited prospectively to two multicentre trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patients' beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT/ PET-CT was analysed using logistic regression. RESULTS: Baseline and post-staging questionnaires were completed by 97 and 107 patients, respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006-2.284, P = 0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099-8.288, P = 0.032), although only 45/107 (42%) patients were aware of this attribute. CONCLUSIONS: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionizing radiation, could influence preference
Predictors of patient preference for either whole body magnetic resonance imaging (WB-MRI) or CT/ PET-CT for staging colorectal or lung cancer
Introduction: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer.
Methods: Patients recruited prospectively to two multicenter trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level, and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patientsâ beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT / PET-CT were analysed using logistic regression.
Results: Baseline and post-staging questionnaires were completed by 97 and 107 patients respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans, and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI, and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006 to 2.284, p=0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099 to 8.288, p=0.032), yet only 45/107 (42%) patients were aware of this attribute.
Conclusions: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionising radiation, could influence preference
A photo- and electrochemically-active porphyrinâfullerene dyad electropolymer
A hole- and electron-conducting polymer has been prepared by electropolymerization of aporphyrinâfullerene monomer. The porphyrin units are linked by aminophenyl groups to form a linear chain in which the porphyrin is an integral part of the polymer backbone. The absorption spectrum of a film formed on indium-tin-oxide-coated glass resembles that of a model porphyrinâfullerene dyad, but with significant peak broadening. The film demonstrates a first oxidation potential of 0.75 V vs. SCE, corresponding to oxidation of the porphyrin polymer, and a first reduction potential of -0.63 V vs. SCE, corresponding to fullerene reduction. Time-resolved fluorescence studies show that the porphyrin first excited singlet state is strongly quenched by photoinduced electron transfer to fullerene. Transient absorption investigations reveal that excitation generates mobile charge carriers that recombine by both geminate and nongeminate pathways over a large range of time scales. Similar studies on a related polymer that lacks the fullerene component show complex, laser-intensity-dependent photoinduced electron transfer behavior. The properties of the porphyrinâfullerene electropolymer suggest that it maybe useful in organic photovoltaic applications, wherein light absorption leads to charge separationwithin picoseconds in a âmolecular heterojunctionâ with no requirement for exciton migration.Fil: Gervaldo, Miguel Andres. Universidad Nacional de RĂo Cuarto. Facultad de Ciencias Exactas FisicoquĂmicas y Naturales. Instituto de Investigaciones en TecnologĂas EnergĂ©ticas y Materiales Avanzados. - Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de Investigaciones en TecnologĂas EnergĂ©ticas y Materiales Avanzados; ArgentinaFil: Liddell, Paul A.. Arizona State University; Estados UnidosFil: Kodis, Gerdenis. Arizona State University; Estados UnidosFil: Brennan, Bradley J.. Arizona State University; Estados UnidosFil: Johnson, Christopher R.. Arizona State University; Estados UnidosFil: Bridgewater, James W.. Arizona State University; Estados UnidosFil: Moore, Ana L.. Arizona State University; Estados UnidosFil: Moore, Thomas A.. Arizona State University; Estados UnidosFil: Gust, Devens. Arizona State University; Estados Unido
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