Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation

Objectives: To evaluate the clinical and costeffectiveness of capecitabine and tegafur with uracil (UFT/LV) as first-line treatments for patients with metastatic colorectal cancer, as compared with 5- fluorouracil/folinic acid (5-FU/FA) regimens. Data sources: Electronic databases, reference lists of relevant articles and sponsor submissions were also consulted. Review methods: Systematic searches, selection against criteria and quality assessment were performed to obtain data from relevant studies. Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to compare the cost-effectiveness of capecitabine and UFT/LV with three intravenous 5- FU/LV regimens widely used in the UK: the Mayo, the modified de Gramont regimen and the inpatient de Gramont regimens. Results: The evidence suggests that treatment with capecitabine improves overall response rates and has an improved adverse effect profile in comparison with 5-FU/LV treatment with the Mayo regimen, with the exception of hand–foot syndrome. Time to disease progression or death after treatment with UFT/LV in one study appears to be shorter than after treatment with 5-FU/LV with the Mayo regimen, although it also had an improved adverse effect profile. Neither capecitabine nor UFT/LV appeared to improve healthrelated quality of life. Little information on patient preference was available for UFT/LV, but there was indicated a strong preference for this over 5-FU/LV. The total cost of capecitabine and UFT/LV treatments were estimated at £2111 and £3375, respectively, compared with the total treatment cost for the Mayo regimen of £3579. Cost estimates were also presented for the modified de Gramont and inpatient de Gramont regimens. These were £3684 and £6155, respectively. No survival advantage was shown in the RCTs of the oral drugs against the Mayo regimen. Cost savings of capecitabine and UFT/LV over the Mayo regimen were estimated to be £1461 and £209, respectively. Drug acquisition costs were higher for the oral therapies than for the Mayo regimen, but were offset by lower administration costs. Adverse event treatment costs were similar across the three regimens. It was inferred that there was no survival difference between the oral drugs and the de Gramont regimens. Cost savings of capecitabine and UFT/LV over the modified de Gramont regimen were estimated to be £1353 and £101, respectively, and over the inpatient de Gramont regimen were estimated to be £4123 and £2870, respectively. Conclusions: The results show that there are cost savings associated with the use of oral therapies. No survival difference has been proven between the oral drugs and the Mayo regimen. In addition, no evidence of a survival difference between the Mayo regimen and the de Gramont regimens has been identified. However, improved progression-free survival and an improved adverse event profile have been shown for the de Gramont regimen over the Mayo regimen. Further research is recommended into the following areas: quality of life data should be included in trials of colorectal cancer treatments; the place of effective oral treatments in the treatment of colorectal cancer, the safety mechanisms needed to ensure compliance and the monitoring of adverse effects; the optimum duration of treatment; the measurement of patient preference; and a phase III comparative trial of capecitabine and UFT/LV versus modified de Gramont treatment to determine whether there was any survival advantage and to collate the necessary economic data

Effects of motion on jet exhaust noise from aircraft

The various problems involved in the evaluation of the jet noise field prevailing between an observer on the ground and an aircraft in flight in a typical takeoff or landing approach pattern were studied. Areas examined include: (1) literature survey and preliminary investigation, (2) propagation effects, (3) source alteration effects, and (4) investigation of verification techniques. Sixteen problem areas were identified and studied. Six follow-up programs were recommended for further work. The results and the proposed follow-on programs provide a practical general technique for predicting flyover jet noise for conventional jet nozzles

From life [solo exhibition]

The exhibition which combines sculpture and photography and a lithograph was curated by Simonetta Lux and Stella Santacatterina. The lithograph, H.I.S.T.O.R.Y M.A.T.T.E.R.S, sited in the museums’s entrance, has now become a permanent exhibit at the MLAC Museum in Rome. The installation ‘From life ‘ drew on political images from her personal archive of newspaper cuttings and her research into oral history during a study visit to the International Marionette Museum, Sicily. 'From life' derived from research into the temporality of space using the conventions and language of theatre, such as lighting, audience, stage, scenery. Selected newspaper images of significant political events were distilled into a single gesture and re-enacted by a model whose cast legs revealed the tension of the original moment. Cowan works across media exploring the relations between the body and space as a series of fragments, gestures and boundaries

Functional imaging reveals working memory and attention interact to produce the attentional blink

Copyright @ 2012 Massachusetts Institute of Technology PressIf two centrally presented visual stimuli occur within approximately half a second of each other, the second target often fails to be reported correctly. This effect, called the attentional blink (AB; Raymond, J. E., Shapiro, K. L., & Arnell, K. M. Temporary suppression of visual processing in an RSVP task: An attentional blink? Journal of Experimental Psychology, Human Perception and Performance, 18, 849-860, 1992], has been attributed to a resource "bottleneck," likely arising as a failure of attention during encoding into or retrieval from visual working memory (WM). Here we present participants with a hybrid WM-AB study while they undergo fMRI to provide insight into the neural underpinnings of this bottleneck. Consistent with a WM-based bottleneck account, fronto-parietal brain areas exhibited a WM load-dependent modulation of neural responses during the AB task. These results are consistent with the view that WM and attention share a capacity-limited resource and provide insight into the neural structures that underlie resource allocation in tasks requiring joint use of WM and attention.This research was supported by a project grant (071944) from the Wellcome Trust to Kimron Shapiro

Walking dynamics are symmetric (enough)

Many biological phenomena such as locomotion, circadian cycles, and breathing are rhythmic in nature and can be modeled as rhythmic dynamical systems. Dynamical systems modeling often involves neglecting certain characteristics of a physical system as a modeling convenience. For example, human locomotion is frequently treated as symmetric about the sagittal plane. In this work, we test this assumption by examining human walking dynamics around the steady-state (limit-cycle). Here we adapt statistical cross validation in order to examine whether there are statistically significant asymmetries, and even if so, test the consequences of assuming bilateral symmetry anyway. Indeed, we identify significant asymmetries in the dynamics of human walking, but nevertheless show that ignoring these asymmetries results in a more consistent and predictive model. In general, neglecting evident characteristics of a system can be more than a modeling convenience---it can produce a better model.Comment: Draft submitted to Journal of the Royal Society Interfac

C-reactive protein as a predictor of disease in smokers and former smokers: a review

BACKGROUND:Cigarette smoking is a classical and a major risk factor in the development of several diseases with an inflammatory component, including cardiovascular disease and chronic obstructive pulmonary disease. Improvements in assays for protein markers of inflammation have led to many studies on these factors and their roles in disease.AIMS:C-reactive protein (CRP) is one such marker and this review focuses on the evidence for using CRP as a diagnostic marker and how levels of this protein are modified according to the smoking status of the patient, both in terms of the current amount of cigarettes smoked and how CRP levels change following smoking cessation.CONCLUSIONS:Assay of CRP levels may be useful in monitoring disease progression and determining risk of future cardiovascular complications. However, as this marker is also an indicator of acute inflammation and challenges to the immune system, some caution must be exercised in interpreting the available data on CRP levels in patients with different chronic comorbidities

F_B from moving B mesons

We show results for the B meson decay constant calculated both for B mesons at rest and those with non-zero momentum and using both the temporal and spatial components of the axial vector current. It is an important check of lattice systematic errors that all these determinations of f_B should agree. We also describe how well different smearings for the B meson work at non-zero momentum - the optimal smearing has a narrow smearing for the b quark.Comment: Lattice2001(heavyquark

Reexamining the temperature and neutron density conditions for r-process nucleosynthesis with augmented nuclear mass models

We explore the effects of nuclear masses on the temperature and neutron density conditions required for r-process nucleosynthesis using four nuclear mass models augmented by the latest atomic mass evaluation. For each model we derive the conditions for producing the observed abundance peaks at mass numbers A ~ 80, 130, and 195 under the waiting-point approximation and further determine the sets of conditions that can best reproduce the r-process abundance patterns (r-patterns) inferred for the solar system and observed in metal-poor stars of the Milky Way halo. In broad agreement with previous studies, we find that (1) the conditions for producing abundance peaks at A ~ 80 and 195 tend to be very different, which suggests that, at least for some nuclear mass models, these two peaks are not produced simultaneously; (2) the typical conditions required by the critical waiting-point (CWP) nuclei with the N = 126 closed neutron shell overlap significantly with those required by the N=82 CWP nuclei, which enables coproduction of abundance peaks at A ~ 130 and 195 in accordance with observations of many metal-poor stars; and (3) the typical conditions required by the N = 82 CWP nuclei can reproduce the r-pattern observed in the metal-poor star HD 122563, which differs greatly from the solar r-pattern. We also examine how nuclear mass uncertainties affect the conditions required for the r-process and identify some key nuclei including76Ni to 78Ni, 82Zn, 131Cd, and 132Cd for precise mass measurements at rare-isotope beam facilities.Comment: 28 pages,9 figures,1 tabl

Making automation pay - cost & throughput trade-offs in the manufacture of large composite components

The automation of complex manufacturing operations can provide significant savings over manual processes, and there remains much scope for increasing automation in the production of large scale structural composites. However the relationships between driving variables are complex, and the achievable throughput rate and corresponding cost for a given design are often not apparent. The deposition rate, number of machines required and unit production rates needed are interrelated and consequently the optimum unit cost is difficult to predict. A detailed study of the costs involved for a series of composite wing cover panels with different manufacturing requirements was undertaken. Panels were sized to account for manufacturing requirements and structural load requirements allowing both manual and automated lay-up procedures to influence design. It was discovered that the introduction of automated tape lay-up can significantly reduce material unit cost, and improve material utilisation, however higher production rates are needed to see this benefit