657 research outputs found
Relating the Green-Schwarz and Pure Spinor Formalisms for the Superstring
Although it is not known how to covariantly quantize the Green-Schwarz (GS)
superstring, there exists a semi-light-cone gauge choice in which the GS
superstring can be quantized in a conformally invariant manner. In this paper,
we prove that BRST quantization of the GS superstring in semi-light-cone gauge
is equivalent to BRST quantization using the pure spinor formalism for the
superstring.Comment: 16 pages, JHEP format, fixed typos and added 2 footnote
"The first ones now, will later be last":understanding the importance of historical context when reading ESMO-MCBS scores
SCOPUS: ed.jinfo:eu-repo/semantics/publishe
A low background Micromegas detector for the CAST experiment
A low background Micromegas detector has been operating on the CAST
experiment at CERN for the search of solar axions during the first phase of the
experiment (2002-2004). The detector operated efficiently and achieved a very
low level of background rejection ( counts
keVcms) thanks to its good spatial and energy resolution
as well as the low radioactivity materials used in the construction of the
detector. For the second phase of the experiment (2005-2007), the detector will
be upgraded by adding a shielding and including focusing optics. These
improvements should allow for a background rejection better than two orders of
magnitude.Comment: 6 pages, 3 figures To appear on the proceedings of the 9th ICATPP
Conference on AStroparticle, Particle, Space Physics, Detectors and Medical
Physics Application
RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2
Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. BRCA2 has a fundamental role in error-free DNA repair but also sustains genome integrity by promoting RAD51 nucleofilament formation at stalled replication forks. CDK2 phosphorylates BRCA2 (pS3291-BRCA2) to limit stabilizing contacts with polymerized RAD51; however, how replication stress modulates CDK2 activity and whether loss of pS3291-BRCA2 regulation results in genomic instability of tumours are not known. Here we demonstrate that the Hippo pathway kinase LATS1 interacts with CDK2 in response to genotoxic stress to constrain pS3291-BRCA2 and support RAD51 nucleofilaments, thereby maintaining genomic fidelity during replication stalling. We also show that LATS1 forms part of an ATR-mediated response to replication stress that requires the tumour suppressor RASSF1A. Importantly, perturbation of the ATR–RASSF1A–LATS1 signalling axis leads to genomic defects associated with loss of BRCA2 function and contributes to genomic instability and ‘BRCA-ness’ in lung cancers
New solar axion search in CAST with He filling
The CERN Axion Solar Telescope (CAST) searches for conversion in
the 9 T magnetic field of a refurbished LHC test magnet that can be directed
toward the Sun. Two parallel magnet bores can be filled with helium of
adjustable pressure to match the X-ray refractive mass to the axion
search mass . After the vacuum phase (2003--2004), which is optimal for
eV, we used He in 2005--2007 to cover the mass range of
0.02--0.39 eV and He in 2009--2011 to scan from 0.39--1.17 eV. After
improving the detectors and shielding, we returned to He in 2012 to
investigate a narrow range around 0.2 eV ("candidate setting" of our
earlier search) and 0.39--0.42 eV, the upper axion mass range reachable with
He, to "cross the axion line" for the KSVZ model. We have improved the
limit on the axion-photon coupling to (95% C.L.), depending on the pressure settings. Since 2013, we
have returned to vacuum and aim for a significant increase in sensitivity.Comment: CAST Collaboration 6 pages 3 figure
Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring
BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, implementation, or data analysis and identify shortcomings in need of amendment. METHODS: As part of a refinement of the ESMO-MCBS, we reviewed trial design, implementation, and data analysis issues that could bias the results. For each issue of concern, we reviewed the ESMO-MCBS v1.1 approach against standards derived from Helsinki guidelines for ethical human research and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the Food and Drugs Administration, the European Medicines Agency, and European Network for Health Technology Assessment. RESULTS: Six design, two implementation, and two data analysis and interpretation issues were evaluated and in three, the ESMO-MCBS provided adequate protections. Seven shortcomings in the ability of the ESMO-MCBS to identify and address bias were identified. These related to (i) evaluation of the control arm, (ii) crossover issues, (iii) criteria for non-inferiority, (iv) substandard post-progression treatment, (v) post hoc subgroup findings based on biomarkers, (vi) informative censoring, and (vii) publication bias against quality-of-life data. CONCLUSION: Interpretation of the ESMO-MCBS scores requires critical appraisal of trials to understand caveats in trial design, implementation, and data analysis that may have biased results and conclusions. These will be addressed in future iterations of the ESMO-MCBS.SCOPUS: re.jinfo:eu-repo/semantics/publishe
Results and perspectives of the solar axion search with the CAST experiment
The status of the solar axion search with the CERN Axion Solar Telescope
(CAST) will be presented. Recent results obtained by the use of He as a
buffer gas has allowed us to extend our sensitivity to higher axion masses than
our previous measurements with He. With about 1 h of data taking at each of
252 different pressure settings we have scanned the axion mass range 0.39 eV 0.64 eV. From the absence of an excess of x rays when the
magnet was pointing to the Sun we set a typical upper limit on the axion-photon
coupling of g GeV at 95% C.L., the
exact value depending on the pressure setting. CAST published results represent
the best experimental limit on the photon couplings to axions and other similar
exotic particles dubbed WISPs (Weakly Interacting Slim Particles) in the
considered mass range and for the first time the limit enters the region
favored by QCD axion models. Preliminary sensitivities for axion masses up to
1.16 eV will also be shown reaching mean upper limits on the axion-photon
coupling of g GeV at 95% C.L.
Expected sensibilities for the extension of the CAST program up to 2014 will be
presented. Moreover long term options for a new helioscope experiment will be
evoked.Comment: 4 pages, 2 pages, to appear in the proceedings of the 24th Rencontres
de Blois V2 A few affiliations were not corrected in previous version V3
Author adde
EHA evaluation of the ESMO—Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies
Objective: Value frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology—Magnitude of Clinical Benefit Scale (ESMO-MCBS). Methods: Here we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies. Results: In general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described. Conclusions: Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials
EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies
Objective Value frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Methods Here we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies. Results In general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described. Conclusions Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials
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