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 Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions.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

Performance of a 28-inch ramjet utilizing gaseous hydrogen at a mach number of 3.6, angles of attack up to 12 deg, and pressure altitudes up to 110,000 feet

Combustion efficiency of gaseous hydrogen fuel for ramjets at very high altitudes and high distortio

From 2D Integrable Systems to Self-Dual Gravity

We explain how to construct solutions to the self-dual Einstein vacuum equations from solutions of various two-dimensional integrable systems by exploiting the fact that the Lax formulations of both systems can be embedded in that of the self-dual Yang--Mills equations. We illustrate this by constructing explicit self-dual vacuum metrics on $\R^2\times \Sigma$, where $\Sigma$ is a homogeneous space for a real subgroup of SL(2, \C) associated with the two-dimensional system.Comment: 9 pages, LaTex, no figure

Transformative learning through university and prison partnerships: reflections from ‘Learning Together’ pedagogical practice

This paper critically discusses two London-based “Learning Together” prison university partnerships—Middlesex University with Her Majesty’s Prison (HMP) Wandsworth and London South Bank University (LSBU) with HMP Pentonville. The paper documents how students experienced the shared classroom learning approach designed on principles of “transformative pedagogy”, and how students interpret their personal development and the knowledge and skills gained as a result. We share the steps taken to bring the learning together pedagogical philosophy to life and use evidence from module evaluation findings and critical reflections to demonstrate the transformations that happen. We interpret our findings through the lens of a transformative ripples model. In addition to exploring personal transformation, the wider transformations that occur within the public institutions at the centre of these collaborations—the prisons and the universities —are discussed. We argue that for prison and university partnerships to be truly effective, they must embed transformative pedagogic practices at their heart, ensuring the “how”we teach is as important, and deliberately considered, as the “what” we teach

Yeah, Right, Uh-Huh: A Deep Learning Backchannel Predictor

Using supporting backchannel (BC) cues can make human-computer interaction more social. BCs provide a feedback from the listener to the speaker indicating to the speaker that he is still listened to. BCs can be expressed in different ways, depending on the modality of the interaction, for example as gestures or acoustic cues. In this work, we only considered acoustic cues. We are proposing an approach towards detecting BC opportunities based on acoustic input features like power and pitch. While other works in the field rely on the use of a hand-written rule set or specialized features, we made use of artificial neural networks. They are capable of deriving higher order features from input features themselves. In our setup, we first used a fully connected feed-forward network to establish an updated baseline in comparison to our previously proposed setup. We also extended this setup by the use of Long Short-Term Memory (LSTM) networks which have shown to outperform feed-forward based setups on various tasks. Our best system achieved an F1-Score of 0.37 using power and pitch features. Adding linguistic information using word2vec, the score increased to 0.39

Calculating photonic Green's functions using a non-orthogonal finite difference time domain method

In this paper we shall propose a simple scheme for calculating Green's functions for photons propagating in complex structured dielectrics or other photonic systems. The method is based on an extension of the finite difference time domain (FDTD) method, originally proposed by Yee, also known as the Order-N method, which has recently become a popular way of calculating photonic band structures. We give a new, transparent derivation of the Order-N method which, in turn, enables us to give a simple yet rigorous derivation of the criterion for numerical stability as well as statements of charge and energy conservation which are exact even on the discrete lattice. We implement this using a general, non-orthogonal co-ordinate system without incurring the computational overheads normally associated with non-orthogonal FDTD. We present results for local densities of states calculated using this method for a number of systems. Firstly, we consider a simple one dimensional dielectric multilayer, identifying the suppression in the state density caused by the photonic band gap and then observing the effect of introducing a defect layer into the periodic structure. Secondly, we tackle a more realistic example by treating a defect in a crystal of dielectric spheres on a diamond lattice. This could have application to the design of super-efficient laser devices utilising defects in photonic crystals as laser cavities.Comment: RevTex file. 10 pages with 8 postscript figures. Submitted to Phys Rev

Kink dynamics in a novel discrete sine-Gordon system

A spatially-discrete sine-Gordon system with some novel features is described. There is a topological or Bogomol'nyi lower bound on the energy of a kink, and an explicit static kink which saturates this bound. There is no Peierls potential barrier, and consequently the motion of a kink is simpler, especially at low speeds. At higher speeds, it radiates and slows down.Comment: 10 pages, 7 figures, archivin

Scalar--Flat Lorentzian Einstein--Weyl Spaces

We find all three-dimensional Einstein--Weyl spaces with the vanishing scalar curvatureComment: 4 page