Aphasia Recovery: When, How and Who to Treat?

PURPOSE OF REVIEW: We now know that speech and language therapy (SALT) is effective in the rehabilitation of aphasia; however, there remains much individual variability in the response to interventions. So, what works for whom, when and how? RECENT FINDINGS: This review evaluates the current evidence for the efficacy of predominantly impairment-focused aphasia interventions with respect to optimal dose, intensity, timing and distribution or spacing of treatment. We conclude that sufficient dose of treatment is required to enable clinical gains and that e-therapies are a promising and practical way to achieve this goal. In addition, aphasia can be associated with other cognitive deficits and may lead to secondary effects such as low mood and social isolation. In order to personalise individual treatments to optimise recovery, we need to develop a greater understanding of the interactions between these factors

Spontaneous DC Current Generation in a Resistively Shunted Semiconductor Superlattice Driven by a TeraHertz Field

We study a resistively shunted semiconductor superlattice subject to a high-frequency electric field. Using a balance equation approach that incorporates the influence of the electric circuit, we determine numerically a range of amplitude and frequency of the ac field for which a dc bias and current are generated spontaneously and show that this region is likely accessible to current experiments. Our simulations reveal that the Bloch frequency corresponding to the spontaneous dc bias is approximately an integer multiple of the ac field frequency.Comment: 8 pages, Revtex, 3 Postscript figure

Tunneling control and localization for Bose-Einstein condensates in a frequency modulated optical lattice

The similarity between matter waves in periodic potential and solid-state physics processes has triggered the interest in quantum simulation using Bose-Fermi ultracold gases in optical lattices. The present work evidences the similarity between electrons moving under the application of oscillating electromagnetic fields and matter waves experiencing an optical lattice modulated by a frequency difference, equivalent to a spatially shaken periodic potential. We demonstrate that the tunneling properties of a Bose-Einstein condensate in shaken periodic potentials can be precisely controlled. We take additional crucial steps towards future applications of this method by proving that the strong shaking of the optical lattice preserves the coherence of the matter wavefunction and that the shaking parameters can be changed adiabatically, even in the presence of interactions. We induce reversibly the quantum phase transition to the Mott insulator in a driven periodic potential.Comment: Laser Physics (in press

Dynamical phenomena in Fibonacci Semiconductor Superlattices

We present a detailed study of the dynamics of electronic wavepackets in Fibonacci semiconductor superlattices, both in flat band conditions and subject to homogeneous electric fields perpendicular to the layers. Coherent propagation of electrons is described by means of a scalar Hamiltonian using the effective-mass approximation. We have found that an initial Gaussian wavepacket is filtered selectively when passing through the superlattice. This means that only those components of the wavepacket whose wavenumber belong to allowed subminibands of the fractal-like energy spectrum can propagate over the entire superlattice. The Fourier pattern of the transmitted part of the wavepacket presents clear evidences of fractality reproducing those of the underlying energy spectrum. This phenomenon persists even in the presence of unintentional disorder due to growth imperfections. Finally, we have demonstrated that periodic coherent-field induced oscillations (Bloch oscillations), which we are able to observe in our simulations of periodic superlattices, are replaced in Fibonacci superlattices by more complex oscillations displaying quasiperiodic signatures, thus sheding more light onto the very peculiar nature of the electronic states in these systems.Comment: 7 pagex, RevTex, 5 Postscript figures. Physical Review B (in press

Outcomes Among Black Patients With Stage II and III Colon Cancer Receiving Chemotherapy: An Analysis of ACCENT Adjuvant Trials

Among patients with resected colon cancer, black patients have worse survival than whites. We investigated whether disparities in survival and related endpoints would persist when patients were treated with identical therapies in controlled clinical trials

Legal determinants of external finance revisited : the inverse relationship between investor protection and societal well-being

This paper investigates relationships between corporate governance traditions and quality of life as measured by a number of widely reported indicators. It provides an empirical analysis of indicators of societal health in developed economies using a classification based on legal traditions. Arguably the most widely cited work in the corporate governance literature has been the collection of papers by La Porta et al. which has shown, inter alia, statistically significant relationships between legal traditions and various proxies for investor protection. We show statistically significant relationships between legal traditions and various proxies for societal health. Our comparative evidence suggests that the interests of investors may not be congruent with the interests of wider society, and that the criteria for judging the effectiveness of approaches to corporate governance should not be restricted to financial metrics

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)

Dynamic Localization in Anisotropic Coulomb Systems: Field Induced Crossover of the Exciton Dimension

The effective dimensionality of excitons can be drastically changed by applying an alternating electric field. On the basis of a full three-dimensional description of both coherent and incoherent phenomena in anisotropic structures it is found that appropriate applied oscillating fields change the exciton wave function from anisotropic three dimensional to basically two dimensional. This effective-dimension change is caused by dynamic localization which leads to an increase of the exciton binding energy and of the corresponding oscillator strength

Analysis and design of randomised clinical trials involving competing risks endpoints

<p>Abstract</p> <p>Background</p> <p>In randomised clinical trials involving time-to-event outcomes, the failures concerned may be events of an entirely different nature and as such define a classical competing risks framework. In designing and analysing clinical trials involving such endpoints, it is important to account for the competing events, and evaluate how each contributes to the overall failure. An appropriate choice of statistical model is important for adequate determination of sample size.</p> <p>Methods</p> <p>We describe how competing events may be summarised in such trials using cumulative incidence functions and Gray's test. The statistical modelling of competing events using proportional cause-specific and subdistribution hazard functions, and the corresponding procedures for sample size estimation are outlined. These are illustrated using data from a randomised clinical trial (SQNP01) of patients with advanced (non-metastatic) nasopharyngeal cancer.</p> <p>Results</p> <p>In this trial, treatment has no effect on the competing event of loco-regional recurrence. Thus the effects of treatment on the hazard of distant metastasis were similar via both the cause-specific (unadjusted <it>csHR </it>= 0.43, 95% CI 0.25 - 0.72) and subdistribution (unadjusted <it>subHR </it>0.43; 95% CI 0.25 - 0.76) hazard analyses, in favour of concurrent chemo-radiotherapy followed by adjuvant chemotherapy. Adjusting for nodal status and tumour size did not alter the results. The results of the logrank test (<it>p </it>= 0.002) comparing the cause-specific hazards and the Gray's test (<it>p </it>= 0.003) comparing the cumulative incidences also led to the same conclusion. However, the subdistribution hazard analysis requires many more subjects than the cause-specific hazard analysis to detect the same magnitude of effect.</p> <p>Conclusions</p> <p>The cause-specific hazard analysis is appropriate for analysing competing risks outcomes when treatment has no effect on the cause-specific hazard of the competing event. It requires fewer subjects than the subdistribution hazard analysis for a similar effect size. However, if the main and competing events are influenced in opposing directions by an intervention, a subdistribution hazard analysis may be warranted.</p

A randomized trial of bevacizumab for newly diagnosed glioblastoma.

BACKGROUND: Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. METHODS: In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary end points, with the addition of bevacizumab. RESULTS: A total of 978 patients were registered, and 637 underwent randomization. There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group (median, 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13). Progression-free survival was longer in the bevacizumab group (10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79). There were modest increases in rates of hypertension, thromboembolic events, intestinal perforation, and neutropenia in the bevacizumab group. Over time, an increased symptom burden, a worse quality of life, and a decline in neurocognitive function were more frequent in the bevacizumab group. CONCLUSIONS: First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged but did not reach the prespecified improvement target. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00884741.)