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 Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions.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

Models of verbal working memory capacity: What does it take to make them work?

Theories of working memory (WM) capacity limits will be more useful when we know what aspects of performance are governed by the limits and what aspects are governed by other memory mechanisms. Whereas considerable progress has been made on models of WM capacity limits for visual arrays of separate objects, less progress has been made in understanding verbal materials, especially when words are mentally combined to form multiword units or chunks. Toward a more comprehensive theory of capacity limits, we examined models of forced-choice recognition of words within printed lists, using materials designed to produce multiword chunks in memory (e.g., leather brief case). Several simple models were tested against data from a variety of list lengths and potential chunk sizes, with test conditions that only imperfectly elicited the interword associations. According to the most successful model, participants retained about 3 chunks on average in a capacity-limited region of WM, with some chunks being only subsets of the presented associative information (e.g., leather brief case retained with leather as one chunk and brief case as another). The addition to the model of an activated long-term memory component unlimited in capacity was needed. A fixed-capacity limit appears critical to account for immediate verbal recognition and other forms of WM. We advance a model-based approach that allows capacity to be assessed despite other important processing contributions. Starting with a psychological-process model of WM capacity developed to understand visual arrays, we arrive at a more unified and complete model

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

Effective Labor Regulation and Microeconomic Flexibility

Microeconomic flexibility, by facilitating the process of creative-destruction, is at the core of economic growth in modern market economies. The main reason for why this process is not infinitely fast, is the presence of adjustment costs, some of them technological, other institutional. Chief among the latter is labor market regulation. While few economists would object to such a view, its empirical support is rather weak. In this paper we revisit this hypothesis and find strong evidence for it. We use a new sectoral panel for 60 countries and a methodology suitable for such a panel. We find that job security regulation clearly hampers the creative-destruction process, especially in countries where regulations are likely to be enforced. Moving from the 20th to the 80th percentile in job security, in countries with strong rule of law, cuts the annual speed of adjustment to shocks by a third while shaving off about one percent from annual productivity growth. The same movement has negligible effects in countries with weak rule of law.

A theory of the electric quadrupole contribution to resonant x-ray scattering: Application to multipole ordering phases in Ce_{1-x}La_{x}B_{6}

We study the electric quadrupole (E2) contribution to resonant x-ray scattering (RXS). Under the assumption that the rotational invariance is preserved in the Hamiltonian describing the intermediate state of scattering, we derive a useful expression for the RXS amplitude. One of the advantages the derived expression possesses is the full information of the energy dependence, lacking in all the previous studies using the fast collision approximation. The expression is also helpful to classify the spectra into multipole order parameters which are brought about. The expression is suitable to investigate the RXS spectra in the localized f electron systems. We demonstrate the usefulness of the formula by calculating the RXS spectra at the Ce L_{2,3} edges in Ce_{1-x}La_{x}B_{6} on the basis of the formula. We obtain the spectra as a function of energy in agreement with the experiment of Ce_{0.7}La_{0.3}B_{6}. Analyzing the azimuthal angle dependence, we find the sixfold symmetry in the \sigma-\sigma' channel and the threefold onein the \sigma-\pi' channel not only in the antiferrooctupole (AFO) ordering phase but also in the antiferroquadrupole (AFQ) ordering phase, which behavior depends strongly on the domain distribution. The sixfold symmetry in the AFQ phase arises from the simultaneously induced hexadecapole order. Although the AFO order is plausible for phase IV in Ce_{1-x}La_{x}B_{6}, the possibility of the AFQ order may not be ruled out on the basis of azimuthal angle dependence alone.Comment: 12 pages, 6 figure

With development, list recall includes more chunks, not just larger ones.

The nature of the childhood development of immediate recall has been difficult to determine. There could be a developmental increase in either the number of chunks held in working memory or the use of grouping to make the most of a constant capacity. In 3 experiments with children in the early elementary school years and adults, we show that improvements in the immediate recall of word and picture lists come partly from increases in the number of chunks of items retained in memory. This finding was based on a distinction between access to a studied group of items (i.e., recall of at least 1 item from the group) and completion of the accessed group (i.e., the proportion of the items recalled from the group). Access rates increased with age, even with statistical controls for completion rates, implicating development of capacity in chunks. (PsycINFO Database Record (c) 2010 APA, all rights reserved

Non-resonant inelastic x-ray scattering involving excitonic excitations

In a recent publication Larson \textit{et al.} reported remarkably clear $d$-$d$ excitations for NiO and CoO measured with x-ray energies well below the transition metal $K$ edge. In this letter we demonstrate that we can obtain an accurate quantitative description based on a local many body approach. We find that the magnitude of $\vec{q}$ can be tuned for maximum sensitivity for dipole, quadrupole, etc. excitations. We also find that the direction of $\vec{q}$ with respect to the crystal axes can be used as an equivalent to polarization similar to electron energy loss spectroscopy, allowing for a determination of the local symmetry of the initial and final state based on selection rules. This method is more generally applicable and combined with the high resolution available, could be a powerful tool for the study of local distortions and symmetries in transition metal compounds including also buried interfaces

Thermal Phase Variations of WASP-12b: Defying Predictions

[Abridged] We report Warm Spitzer full-orbit phase observations of WASP-12b at 3.6 and 4.5 micron. We are able to measure the transit depths, eclipse depths, thermal and ellipsoidal phase variations at both wavelengths. The large amplitude phase variations, combined with the planet's previously-measured day-side spectral energy distribution, is indicative of non-zero Bond albedo and very poor day-night heat redistribution. The transit depths in the mid-infrared indicate that the atmospheric opacity is greater at 3.6 than at 4.5 micron, in disagreement with model predictions, irrespective of C/O ratio. The secondary eclipse depths are consistent with previous studies. We do not detect ellipsoidal variations at 3.6 micron, but our parameter uncertainties -estimated via prayer-bead Monte Carlo- keep this non-detection consistent with model predictions. At 4.5 micron, on the other hand, we detect ellipsoidal variations that are much stronger than predicted. If interpreted as a geometric effect due to the planet's elongated shape, these variations imply a 3:2 ratio for the planet's longest:shortest axes and a relatively bright day-night terminator. If we instead presume that the 4.5 micron ellipsoidal variations are due to uncorrected systematic noise and we fix the amplitude of the variations to zero, the best fit 4.5 micron transit depth becomes commensurate with the 3.6 micron depth, within the uncertainties. The relative transit depths are then consistent with a Solar composition and short scale height at the terminator. Assuming zero ellipsoidal variations also yields a much deeper 4.5 micron eclipse depth, consistent with a Solar composition and modest temperature inversion. We suggest future observations that could distinguish between these two scenarios.Comment: 19 pages, 10 figures, ApJ in press. Improved discussion of gravity brightenin

Mannitol in diuretic resistant nephrotic syndrome: a case report

A 6 year old presented with generalized oedema to Kagando hospital, Uganda, and was diagnosed with nephrotic syndrome. Despite treatment with a fluid restriction, prednisolone and furosemide, the oedema worsened and the weight increased. Mannitol was added to the treatment regime and the oedema improved. The patient was able to be discharged four days later without any diuretic therapy. The case highlights the use of mannitol in the treatment of diuretic resistant oedema with nephrotic syndrome. It provides an alternative therapy for the resource-poor setting to the expensive albumin-furosemide combination often used elsewhere