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 ($5\times 10^{-5}$ counts keV$^{-1}$cm$^{-2}$s$^{-1}$) 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 4^4He filling

The CERN Axion Solar Telescope (CAST) searches for $a\to\gamma$ 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 $m_\gamma$ to the axion search mass $m_a$. After the vacuum phase (2003--2004), which is optimal for $m_a\lesssim0.02$ eV, we used $^4$He in 2005--2007 to cover the mass range of 0.02--0.39 eV and $^3$He in 2009--2011 to scan from 0.39--1.17 eV. After improving the detectors and shielding, we returned to $^4$He in 2012 to investigate a narrow $m_a$ range around 0.2 eV ("candidate setting" of our earlier search) and 0.39--0.42 eV, the upper axion mass range reachable with $^4$He, to "cross the axion line" for the KSVZ model. We have improved the limit on the axion-photon coupling to $g_{a\gamma}< 1.47\times10^{-10} {\rm GeV}^{-1}$ (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 $^3$He as a buffer gas has allowed us to extend our sensitivity to higher axion masses than our previous measurements with $^4$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$\le m_{a} \le$ 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$_{a\gamma} \le 2.3\times 10^{-10}$ GeV$^{-1}$ 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$_{a\gamma} \le 3.5\times 10^{-10}$ GeV$^{-1}$ 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