Myeloma bone disease : the osteoblast in the spotlight

Lytic bone disease remains a life-altering complication of multiple myeloma, with up to 90% of sufferers experiencing skeletal events at some point in their cancer journey. This tumour-induced bone disease is driven by an upregulation of bone resorption (via increased osteoclast (OC) activity) and a downregulation of bone formation (via reduced osteoblast (OB) activity), leading to phenotypic osteolysis. Treatments are limited, and currently exclusively target OCs. Despite existing bone targeting therapies, patients successfully achieving remission from their cancer can still be left with chronic pain, poor mobility, and reduced quality of life as a result of bone disease. As such, the field is desperately in need of new and improved bone-modulating therapeutic agents. One such option is the use of bone anabolics, drugs that are gaining traction in the osteoporosis field following successful clinical trials. The prospect of using these therapies in relation to myeloma is an attractive option, as they aim to stimulate OBs, as opposed to existing therapeutics that do little to orchestrate new bone formation. The preclinical application of bone anabolics in myeloma mouse models has demonstrated positive outcomes for bone repair and fracture resistance. Here, we review the role of the OB in the pathophysiology of myeloma-induced bone disease and explore whether novel OB targeted therapies could improve outcomes for patients

CsI(Tl) for WIMP dark matter searches

We report a study of CsI(Tl) scintillator to assess its applicability in experiments to search for dark matter particles. Measurements of the mean scintillation pulse shapes due to nuclear and electron recoils have been performed. We find that, as with NaI(Tl), pulse shape analysis can be used to discriminate between electron and nuclear recoils down to 4 keV. However, the discrimination factor is typically (10-15)% better than in NaI(Tl) above 4 keV. The quenching factor for caesium and iodine recoils was measured and found to increase from 11% to ~17% with decreasing recoil energy from 60 to 12 keV. Based on these results, the potential sensitivity of CsI(Tl) to dark matter particles in the form of neutralinos was calculated. We find an improvement over NaI(Tl) for the spin independent WIMP-nucleon interactions up to a factor of 5 assuming comparable electron background levels in the two scintillators.Comment: 16 pages, 8 figures, to be published in Nucl. Instrum. and Meth. in Phys. Res.

Simulations of neutron background in a time projection chamber relevant to dark matter searches

Presented here are results of simulations of neutron background performed for a time projection chamber acting as a particle dark matter detector in an underground laboratory. The investigated background includes neutrons from rock and detector components, generated via spontaneous fission and (alpha, n) reactions, as well as those due to cosmic-ray muons. Neutrons were propagated to the sensitive volume of the detector and the nuclear recoil spectra were calculated. Methods of neutron background suppression were also examined and limitations to the sensitivity of a gaseous dark matter detector are discussed. Results indicate that neutrons should not limit sensitivity to WIMP-nucleon interactions down to a level of (1 - 3) x 10^{-8} pb in a 10 kg detector.Comment: 27 pages (total, including 3 tables and 11 figures). Accepted for publication in Nuclear Instruments and Methods in Physics Research - Section

The Pt isotopes: comparing the Interacting Boson Model with Configuration Mixing and the Extended Consistent-Q formalism

The role of intruder configurations in the description of energy spectra and B(E2) values in the Pt region is analyzed. In particular, we study the differences between Interacting Boson Model calculations with or without the inclusion of intruder states in the even Pt nuclei $^{172-194}$Pt. As a result, it shows that for the description of a subset of the existing experimental data, i.e., energy spectra and absolute B(E2) values up to an excitation energy of about 1.5 MeV, both approaches seem to be equally valid. We explain these similarities between both model spaces through an appropriate mapping. We point out the need for a more extensive comparison, encompassing a data set as broad (and complete) as possible to confront with both theoretical approaches in order to test the detailed structure of the nuclear wave functions.Comment: To be published in NP

Measurements of Scintillation Efficiency and Pulse-Shape for Low Energy Recoils in Liquid Xenon

Results of observations of low energy nuclear and electron recoil events in liquid xenon scintillator detectors are given. The relative scintillation efficiency for nuclear recoils is 0.22 +/- 0.01 in the recoil energy range 40 keV - 70 keV. Under the assumption of a single dominant decay component to the scintillation pulse-shape the log-normal mean parameter T0 of the maximum likelihood estimator of the decay time constant for 6 keV < Eee < 30 keV nuclear recoil events is equal to 21.0 ns +/- 0.5 ns. It is observed that for electron recoils T0 rises slowly with energy, having a value ~ 30 ns at Eee ~ 15 keV. Electron and nuclear recoil pulse-shapes are found to be well fitted by single exponential functions although some evidence is found for a double exponential form for the nuclear recoil pulse-shape.Comment: 11 pages, including 5 encapsulated postscript figure

Neutron background in large-scale xenon detectors for dark matter searches

Simulations of the neutron background for future large-scale particle dark matter detectors are presented. Neutrons were generated in rock and detector elements via spontaneous fission and (alpha,n) reactions, and by cosmic-ray muons. The simulation techniques and results are discussed in the context of the expected sensitivity of a generic liquid xenon dark matter detector. Methods of neutron background suppression are investigated. A sensitivity of $10^{-9}-10^{-10}$ pb to WIMP-nucleon interactions can be achieved by a tonne-scale detector.Comment: 35 pages, 13 figures, 2 tables, accepted for publication in Astroparticle Physic

The ZEPLIN II dark matter detector: data acquisition system and data reduction

ZEPLIN-II is a two-phase (liquid/gas) xenon dark matter detector searching for WIMP-nucleon interactions. In this paper we describe the data acquisition system used to record the data from ZEPLIN-II and the reduction procedures which parameterise the data for subsequent analysis.Comment: 11 pages, 10 figure

The ZEPLIN II dark matter detector: data acquisition system and data reduction

ZEPLIN-II is a two-phase (liquid/gas) xenon dark matter detector searching for WIMP-nucleon interactions. In this paper we describe the data acquisition system used to record the data from ZEPLIN-II and the reduction procedures which parameterise the data for subsequent analysis.Comment: 11 pages, 10 figure