Radion Dynamics and Phenomenology in the Linear Dilaton Model

We investigate the properties of the radion in the 5D linear dilaton model arising from Little String Theory. A Goldberger-Wise type mechanism is used to stabilise a large interbrane distance, with the dilaton now playing the role of the stabilising field. We consider the coupled fluctuations of the metric and dilaton fields and identify the physical scalar modes of the system. The wavefunctions and masses of the radion and Kaluza-Klein modes are calculated, giving a radion mass of order the curvature scale. As a result of the direct coupling between the dilaton and Standard Model fields, the radion couples to the SM Lagrangian, in addition to the trace of the energy-momentum tensor. The effect of these additional interaction terms on the radion decay modes is investigated, with a notable increase in the branching fraction to photons. We also consider the effects of a non-minimal Higgs coupling to gravity, which introduces a mixing between the Higgs and radion modes. Finally, we calculate the production cross section of the radion at the LHC and use the current Higgs searches to place constraints on the parameter space.Comment: 28 pages, 7 figures; v2: error in radion-gauge boson Feynman rules corrected, version published in JHE

Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology

BackgroundIn recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations.MethodsA joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose “Accept Completely” (Option A) or “Accept with Some Reservation” (Option B).ResultsThe consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients.ConclusionThis consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications

Advanced Telecommunications and Signal Processing Program

Contains an introduction and reports on twelve research projects.AT&T FellowshipAdvanced Telecommunications Research ProgramINTEL FellowshipU.S. Navy - Office of Naval Research NDSEG Graduate FellowshipMaryland Procurement Office Contract MDA904-93-C-418

Advanced Television and Signal Processing Program

Contains an introduction and reports on two research projects.Advanced Television Research Progra

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

The contribution of Fermi-2LAC blazars to the diffuse TeV-PeV neutrino flux

The recent discovery of a diffuse cosmic neutrino flux extending up to PeV energies raises the question of which astrophysical sources generate this signal. One class of extragalactic sources which may produce such high-energy neutrinos are blazars. We present a likelihood analysis searching for cumulative neutrino emission from blazars in the 2nd Fermi-LAT AGN catalogue (2LAC) using an IceCube neutrino dataset 2009-12 which was optimised for the detection of individual sources. In contrast to previous searches with IceCube, the populations investigated contain up to hundreds of sources, the largest one being the entire blazar sample in the 2LAC catalogue. No significant excess is observed and upper limits for the cumulative flux from these populations are obtained. These constrain the maximum contribution of the 2LAC blazars to the observed astrophysical neutrino flux to be $27 \%$ or less between around 10 TeV and 2 PeV, assuming equipartition of flavours at Earth and a single power-law spectrum with a spectral index of $-2.5$. We can still exclude that the 2LAC blazars (and sub-populations) emit more than $50 \%$ of the observed neutrinos up to a spectral index as hard as $-2.2$ in the same energy range. Our result takes into account that the neutrino source count distribution is unknown, and it does not assume strict proportionality of the neutrino flux to the measured 2LAC $\gamma$-ray signal for each source. Additionally, we constrain recent models for neutrino emission by blazars.Comment: 18 pages, 22 figure

All-sky search for time-integrated neutrino emission from astrophysical sources with 7 years of IceCube data

Since the recent detection of an astrophysical flux of high energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small event sample of high neutrino purity, good energy resolution, but large angular uncertainties. In searches for point-like sources, on the other hand, the best performance is given by using large statistics and good angular reconstructions. Track-like muon events produced in neutrino interactions satisfy these requirements. We present here the results of searches for point-like sources with neutrinos using data acquired by the IceCube detector over seven years from 2008--2015. The discovery potential of the analysis in the northern sky is now significantly below $E_\nu^2d\phi/dE_\nu=10^{-12}\:\mathrm{TeV\,cm^{-2}\,s^{-1}}$, on average $38\%$ lower than the sensitivity of the previously published analysis of four years exposure. No significant clustering of neutrinos above background expectation was observed, and implications for prominent neutrino source candidates are discussed.Comment: 19 pages, 17 figures, 3 tables; ; submitted to The Astrophysical Journa

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response