Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

A precision medicine initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling

After intense scientific exploration and more than a decade of failed trials, Alzheimer’s disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer’s Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials

High rate, fast timing Glass RPC for the high {\eta} CMS muon detectors

The HL-LHC phase is designed to increase by an order of magnitude the amount of data to be collected by the LHC experiments. To achieve this goal in a reasonable time scale the instantaneous luminosity would also increase by an order of magnitude up to $6.10^{34} cm^{-2} s^{-1}$ . The region of the forward muon spectrometer ($|{\eta}| > 1.6$) is not equipped with RPC stations. The increase of the expected particles rate up to $2 kHz/cm^{2}$ (including a safety factor 3) motivates the installation of RPC chambers to guarantee redundancy with the CSC chambers already present. The actual RPC technology of CMS cannot sustain the expected background level. The new technology that will be chosen should have a high rate capability and provides a good spatial and timing resolution. A new generation of Glass-RPC (GRPC) using low-resistivity (LR) glass is proposed to equip at least the two most far away of the four high ${\eta}$ muon stations of CMS. First the design of small size prototypes and studies of their performance in high-rate particles flux is presented. Then the proposed designs for large size chambers and their fast-timing electronic readout are examined and preliminary results are provided.Comment: 14 pages, 11 figures, Conference proceeding for the 2016 Resistive Plate Chambers and Related Detector

Constraining Supersymmetry

We review constraints on the minimal supersymmetric extension of the Standard Model (MSSM) coming from direct searches at accelerators such as LEP, indirect measurements such as b -> s gamma decay and the anomalous magnetic moment of the muon. The recently corrected sign of pole light-by-light scattering contributions to the latter is taken into account. We combine these constraints with those due to the cosmological density of stable supersymmetric relic particles. The possible indications on the supersymmetric mass scale provided by fine-tuning arguments are reviewed critically. We discuss briefly the prospects for future accelerator searches for supersymmetry.Comment: 21 LaTeX pages, 9 eps figures, Invited Contribution to the New Journal of Physics Focus Issue on Supersymmetr

Measurement of Exclusive rho^0 rho^0 Production in Two-Photon Collisions at High Q^2 at LEP

Exclusive rho rho production in two-photon collisions involving a single highly virtual photon is studied with data collected at LEP at centre-of-mass energies 89GeV < \sqrt{s} < 209GeV with a total integrated luminosity of 854.7pb^-1 The cross section of the process gamma gamma^* -> rho rho is determined as a function of the photon virtuality, Q^2 and the two-photon centre-of-mass energy, Wgg, in the kinematic region: 1.2GeV^2 < Q^2 < 30GeV^2 and 1.1GeV < Wgg < 3GeV

Determining Supersymmetric Parameters With Dark Matter Experiments

In this article, we explore the ability of direct and indirect dark matter experiments to not only detect neutralino dark matter, but to constrain and measure the parameters of supersymmetry. In particular, we explore the relationship between the phenomenological quantities relevant to dark matter experiments, such as the neutralino annihilation and elastic scattering cross sections, and the underlying characteristics of the supersymmetric model, such as the values of mu (and the composition of the lightest neutralino), m_A and tan beta. We explore a broad range of supersymmetric models and then focus on a smaller set of benchmark models. We find that by combining astrophysical observations with collider measurements, mu can often be constrained far more tightly than it can be from LHC data alone. In models in the A-funnel region of parameter space, we find that dark matter experiments can potentially determine m_A to roughly +/-100 GeV, even when heavy neutral MSSM Higgs bosons (A, H_1) cannot be observed at the LHC. The information provided by astrophysical experiments is often highly complementary to the information most easily ascertained at colliders.Comment: 46 pages, 76 figure

Search for Branons at LEP

We search, in the context of extra-dimension scenarios, for the possible existence of brane fluctuations, called branons. Events with a single photon or a single Z-boson and missing energy and momentum collected with the L3 detector in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are analysed. No excess over the Standard Model expectations is found and a lower limit at 95% confidence level of 103 GeV is derived for the mass of branons, for a scenario with small brane tensions. Alternatively, under the assumption of a light branon, brane tensions below 180 GeV are excluded

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE