A randomised trial evaluating Bevacizumab as adjuvant therapy following resection of AJCC stage IIB, IIC and III cutaneous melanoma : an update

At present, there are no standard therapies for the adjuvant treatment of malignant melanoma. Patients with primary tumours with a high-Breslow thickness (stages IIB and IIC) or with resected loco-regional nodal disease (stage III) are at high risk of developing metastasis and subsequent disease-related death. Given this, it is important that novel therapies are investigated in the adjuvant melanoma setting. Since angiogenesis is essential for primary tumour growth and the development of metastasis, anti-angiogenic agents are attractive potential therapeutic candidates for clinical trials in the adjuvant setting. Therefore, we initiated a phase II trial in resected high-risk cutaneous melanoma, assessing the efficacy of bevacizumab versus observation. In the interim safety data analysis, we demonstrate that bevacizumab is a safe therapy in the adjuvant melanoma setting with no apparent increase in the surgical complication rate after either primary tumour resection and/or loco-regional lymphadenectomy

Is preparing for a language switch like preparing for a task switch? (article)

This is the author accepted manuscript. The final version is available from APA via the DOI in this recordThe dataset associated with this article is located in ORE at https://doi.org/10.24378/exe.403There is another ORE record for this publication: http://hdl.handle.net/10871/36569A key index of top-down control in task switching-preparation for a switch-is underexplored in language switching. The well-documented EEG "signature" of preparation for a task switch-a protracted positive-polarity modulation over the posterior scalp-has thus far not been reported in language switching, and the interpretation of previously reported effects of preparation on language switching performance is complicated by confounding factors. In an experiment using event-related potentials (ERPs) and an optimized picture-naming paradigm that addressed these confounds the language was specified by an auditory cue on every trial and changed unpredictably. There were two key manipulations. First, the cue-stimulus interval allowed either generous (1,500 ms) or little (100 ms) opportunity for preparation. Second, to explore the interplay between bottom-up and top-down language selection, we compared a highly transparent and familiar "supercue"-the name of the language spoken in that language to a relatively opaque cue (short speeded-up fragment of national anthem). Preparation for a switch elicited a brain potential strongly reminiscent of the posterior switch positivity documented in task switching. As previously shown in task switching, its amplitude inversely predicted the performance "switch cost," demonstrated by our ERP analyses contingent on reaction time (RT). This overlap in the electrophysiological correlates of preparing to switch tasks and languages suggests domain-general processes for top-down selection of task-set and language for production. But, the surprisingly small language switch cost following the supercue in the short CSI suggests that rapid and (possibly automatic) bottom-up selection-not typically observed in task switching-may also occur. (PsycINFO Database RecordThe research described in this paper was supported by a PhD scholarship to the second author from the Economic and Social Research Council (ESRC, UK)

A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling

The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca2+ signaling leading to a parallel increase in the cytosolic Ca2+ pools that activate the Ca2+-dependent NADPH oxidase (NOX) thereby increasing ROS. The inhibition of mitochondrial Ca2+ uptake by TSPO is a consequence of the phosphorylation of the voltage-dependent anion channel (VDAC1) by the protein kinase A (PKA), which is recruited to the mitochondria, in complex with the Acyl-CoA binding domain containing 3 (ACBD3). Notably, the neurotransmitter glutamate, which contributes neuronal toxicity in age-dependent conditions, triggers this TSPO-dependent mechanism of cell signaling leading to cellular demise. TSPO is therefore proposed as a novel OMM-based pathway to control intracellular Ca2+ dynamics and redox transients in neuronal cytotoxicity

Case 3: North Middlesex University Hospital Trust and MiddlesexUniversity: a blended learning language skills programme

A case study is presented of a blended learning course, English Language and Communication for Clinical Practice, which was provided for North Middlesex University Hospital by the Academic Writing and Language Team at Middesex Universit

Measured g factors and the tidal-wave description of transitional nuclei near A = 100

The transient-field technique has been used in both conventional kinematics and inverse kinematics to measure the g factors of the 2+ states in the stable even isotopes of Ru, Pd and Cd. The statistical precision of the g(2+) values has been significantly improved, allowing a critical comparison with the tidal-wave version of the cranking model recently proposed for transitional nuclei in this region.Comment: Accepted for publication in Physical Review C, April 201

The first quadrupole excitations in spherical nuclei and nuclear pairing

Excitation energies and transition probabilities of the first 2+ excitations in even lead, tin and nickel isotopes are calculated within the self-consistent Theory of Finite Fermi Systems based on the Energy Density Functional by Fayans et al. A reasonable agreement with available experimental data is obtained. The effect of the density dependence of the effective pairing interaction is analyzed in detail by comparing results obtained with volume and surface pairing. The effect is found to be noticeable, especially for the 2+ energies which are systematically higher at 200-300 keV for the volume paring as compared with the surface pairing case, the latter being in a better agreement with the data.Comment: Presented at International Conference on Nuclear Structure and Related Topics, Dubna, July 2 - 7, 201

Transplant Coordinators' Perceived Impact of Availability of Multiple Generic Immunosuppression Therapies on Patients, Workload, and Posttransplant Maintenance Therapy

Background. No studies have evaluated the impact of multiple generic immunosuppression medications on transplant coordinators (TCs) and patients. Methods. A cross-sectional, multicenter online survey of TCs managing transplant recipients' outpatient immunosuppression was undertaken to assess TCs' perceptions of the impact of multiple generic immunosuppression therapies on patients and workload. Results. Forty-six of 106 transplant centers contacted (43%) completed the survey, with usable information from 34 TCs (53% in centers performing >100 solid organ transplants annually, 82% registered nurses, and 68% with >5-year experience working with transplant patients). TCs indicated that “change in strength,� “switching from branded to generics,� “heavy pill burden,� and “switching from one generic to another� were the four most frequent reasons for patient confusion regarding immunosuppression. TCs reported increased patient confusion over the previous year for patients on generic immunosuppression therapy: 44% answered ≥3 patient calls/day regarding confusion over immunosuppression therapy. Most TCs indicated increased workload since the introduction of generic immunosuppression therapy. TCs perceived “acute rejection rates,� “rate of graft loss,� and “poor patient adherence� as the three most likely consequences of multiple generic immunosuppression therapy. Conclusion. TCs associated availability of multiple generic immunosuppression therapy with increased patient confusion and time spent addressing patient concerns

In-Training Practice Patterns of Combined Emergency Medicine/Internal Medicine Residents, 2003–2007

<p>Introduction: This study seeks to evaluate the practice patterns of current combined emergency medicine/internal medicine (EM/IM) residents during their training and compare them to the typical practice patterns of EM/IM graduates. We further seek to characterize how these current residents perceive the EM/IM physician’s niche.</p> <p>Methods: This is a multi-institution, cross-sectional, survey-based cohort study. Between June 2008 and July 2008, all 112 residents of the 11 EM/IM programs listed by the Accreditation Council for Graduate Medical Education were contacted and asked to complete a survey concerning plans for certification, fellowship, and practice setting.</p> <p>Results: The adjusted response rate was 71%. All respondents anticipated certifying in both specialties, with 47% intending to pursue fellowships. Most residents (97%) allotted time to both EM and IM, with a median time of 70% and 30%, respectively. Concerning academic medicine, 81% indicated intent to practice academic medicine, and 96% planned to allocate at least 10% of their future time to a university/academic setting. In evaluating satisfaction, 94% were (1) satisfied with their residency choice, (2) believed that a combined residency will advance their career, and (3) would repeat a combined residency if given the opportunity.</p> <p>Conclusion: Current EM/IM residents were very content with their training and the overwhelming majority of residents plan to devote time to the practice of academic medicine. Relative to the practice patterns previously observed in EM/IM graduates, the current residents are more inclined toward pursuing fellowships and practicing both specialties. [West J Emerg Med. 2011;12(4):530–536.]</p

Droplet Generation by Disintegration of Oil Films at the Rim of a Rotating Disk

ABSTRACT A fundamental study has been performed to examine oil film disintegration mechanisms at the rim of a rotating disk. The configuration investigated is an abstraction of one of the droplet generation sources in an aero-engine bearing compartment. The paper aims to contribute to both the determination of directly applicable droplet characteristics and the establishment of a data-base that can be used for the development of droplet generation models. The near-term objectives of the study are (i) to identify disintegration modes relevant with respect to aeroengine bearing compartment operating conditions, (ii) to determine droplet sizes under those operating conditions, and (iii) to measure individual droplet diameter/velocity relationships. The long-term objective is to incorporate this information into advanced CFD-based design tools. The disintegration modes identified here were similar to previously reported flow regimes generated by rotary atomizer