Near-Horizon Extremal Geometries: Coadjoint Orbits and Quantization

The NHEG algebra is an extension of Virasoro introduced in [arXiv:1503.07861]; it describes the symplectic symmetries of $(n+4)$-dimensional Near Horizon Extremal Geometries with $SL(2,R)\times U(1)^{n+1}$ isometry. In this work we construct the NHEG group and classify the (coadjoint) orbits of its action on phase space. As we show, the group consists of maps from an $n$-torus to the Virasoro group, so its orbits are bundles of standard Virasoro coadjoint orbits over $T^n$. We also describe the unitary representations that are expected to follow from the quantization of these orbits, and display their characters. Along the way we show that the NHEG algebra can be built from u(1) currents using a twisted Sugawara construction.Comment: 22 pages, one figure. v2: Title expanded, various minor clarifications added. Published in JHE

Diffraction effects on light-atomic ensemble quantum interface

We present a simple method to include the effects of diffraction into the description of a light-atomic ensemble quantum interface in the context of collective variables. Carrying out a scattering calculation we single out the purely geometrical effect. We apply our method to the experimentally relevant case of Gaussian shaped atomic samples stored in single beam optical dipole traps and probed by a Gaussian beam. We derive analytical scaling relations for the effect of the interaction geometry and compare our findings to results from 1-dimensional models of light propagation.Comment: 13 pages, 7 figures, comments welcom

HD 174005: another binary classified as lambda Boo

We demonstrate that HD 174005, a star recently classified as belonging to the lambda Boo group, is in reality a double lined spectroscopic binary; at some phases, the observed composite spectrum may be similar to that of a single star with weak metal lines.Comment: Accepted by A&

Paper and electronic versions of HM-PRO, a novel patient-reported outcome measure for hematology: an equivalence study.

© 2019 Goswami, Oliva, Ionova et al.Aim:To determine measurement equivalence of paper and electronic application of the hematologi-cal malignancy-patient-reported outcome (HM-PRO), a specific measure for the evaluation of patient-reported outcomes in HMs.Patients & methods:Following International Society of Pharmacoeconomicsand Outcomes Research ePRO Good Research Practice Task Force guidelines, a total of 193 adult patientswith different HMs were recruited into a multicenter prospective study. The paper and the electronic ver-sion of the instrument were completed in the outpatient clinics in a randomized crossover design with a30-min time interval to minimize the learning effect. Those who completed the paper version first, com-pleted the electronic version after 30 min and vice versa. Instrument version and order effects were testedon total score of the two parts of the HM-PRO (Part A: quality of life and Part B: signs & symptoms) in atwo-way ANOVA with patients as random effects. Intraclass correlation coefficients (95% CI) and Spear-man’s rank correlation coefficients were used to evaluate test–retest reliability and reproducibility. Theeffects of instrument version and order were tested on total score of the two parts of HM-PRO.Results:The questionnaire version and administration order effects were not significant at the 5% level. Therewere no interactions found between these two factors for HM-PRO (Part A [quality of life]; p=0.95); and(part B [signs and symptoms]; p=0.72]. Spearman’s rank correlation coefficients were greater than 0.9, andintraclass correlation coefficients ranged from 0.94 to 0.98; furthermore, the scores were not statisticallydifferent between the two versions, showing acceptable reliability indexes. Noteworthy, the differencebetween the completion time for both paper (mean=6:38 min) and electronic version (mean=7:29 min)was not statistically significant (n=100; p=0.11). Patients did not report any difficulty in completing theelectronic version during cognitive interviews and were able to understand and respond spontaneously.Conclusion:Measurement equivalence has been demonstrated for the paper and electronic applicationof the HM-PRO.Peer reviewe

Highly multimode memory in a crystal

We experimentally demonstrate the storage of 1060 temporal modes onto a thulium-doped crystal using an atomic frequency comb (AFC). The comb covers 0.93 GHz defining the storage bandwidth. As compared to previous AFC preparation methods (pulse sequences i.e. amplitude modulation), we only use frequency modulation to produce the desired optical pumping spectrum. To ensure an accurate spectrally selective optical pumping, the frequency modulated laser is self-locked on the atomic comb. Our approach is general and should be applicable to a wide range of rare-earth doped material in the context of multimode quantum memory

Improving preclinical to clinical translation in Alzheimer\u27s disease research.

Introduction: Preclinical testing in animal models is a critical component of the drug discovery and development process. While hundreds of interventions have demonstrated preclinical efficacy for ameliorating cognitive impairments in animal models, none have confirmed efficacy in Alzheimer\u27s disease (AD) clinical trials. Critically this lack of translation to the clinic points in part to issues with the animal models, the preclinical assays used, and lack of scientific rigor and reproducibility during execution. In an effort to improve this translation, the Preclinical Testing Core (PTC) of the Model Organism Development and Evaluation for Late-onset AD (MODEL-AD) consortium has established a rigorous screening strategy with go/no-go decision points that permits unbiased assessments of therapeutic agents. Methods: An initial screen evaluates drug stability, formulation, and pharmacokinetics (PK) to confirm appreciable brain exposure in the disease model at the pathologically relevant ages, followed by pharmacodynamics (PD) and predictive PK/PD modeling to inform the dose regimen for long-term studies. The secondary screen evaluates target engagement and disease modifying activity using non-invasive positron emission tomography/magnetic resonance imaging (PET/MRI). Provided the compound meets its go criteria for these endpoints, evaluation for efficacy on behavioral endpoints are conducted. Results: Validation of this pipeline using tool compounds revealed the importance of critical quality control (QC) steps that researchers need to be aware of when executing preclinical studies. These include confirmation of the active pharmaceutical ingredient and at the precise concentration expected; and an experimental design that is well powered and in line with the Animal Research Reporting of In vivo Experiments (ARRIVE) guidelines. Discussion: Taken together our experience executing a rigorous screening strategy with QC checkpoints provides insight to the challenges of conducting translational studies in animal models. The PTC pipeline is a National Institute on Aging (NIA)-supported resource accessible to the research community for investigators to nominate compounds for testing (https://stopadportal.synapse.org/), and these resources will ultimately enable better translational studies to be conducted

STOP-AD portal: Selecting the optimal pharmaceutical for preclinical drug testing in Alzheimer\u27s disease.

We propose an unbiased methodology to rank compounds for advancement into comprehensive preclinical testing for Alzheimer\u27s disease (AD). Translation of compounds to the clinic in AD has been hampered by poor predictive validity of models, compounds with limited pharmaceutical properties, and studies that lack rigor. To overcome this, MODEL-AD\u27s Preclinical Testing Core developed a standardized pipeline for assessing efficacy in AD mouse models. We hypothesize that rank-ordering compounds based upon pharmacokinetic, efficacy, and toxicity properties in preclinical models will enhance successful translation to the clinic. Previously compound selection was based solely on physiochemical properties, with arbitrary cutoff limits, making ranking challenging. Since no gold standard exists for systematic prioritization, validating a selection criteria has remained elusive. The STOP-AD framework evaluates the drug-like properties to rank compounds for in vivo studies, and uses an unbiased approach that overcomes the validation limitation by performing Monte-Carlo simulations. HIGHLIGHTS: Promising preclinical studies for AD drugs have not translated to clinical success. Systematic assessment of AD drug candidates may increase clinical translatability. We describe a well-defined framework for compound selection with clear selection metrics

[(11)C]PiB PET in Gerstmann-Sträussler-Scheinker disease

Gerstmann-Sträussler-Scheinker Disease (GSS) is a familial neurodegenerative disorder characterized clinically by ataxia, parkinsonism, and dementia, and neuropathologically by deposition of diffuse and amyloid plaques composed of prion protein (PrP). The purpose of this study was to evaluate if [(11)C]Pittsburgh Compound B (PiB) positron emission tomography (PET) is capable of detecting PrP-amyloid in PRNP gene carriers. Six individuals at risk for GSS and eight controls underwent [(11)C]PiB PET scans using standard methods. Approximately one year after the initial scan, each of the three asymptomatic carriers (two with PRNP P102L mutation, one with PRNP F198S mutation) underwent a second [(11)C]PiB PET scan. Three P102L carriers, one F198S carrier, and one non-carrier of the F198S mutation were cognitively normal, while one F198S carrier was cognitively impaired during the course of this study. No [(11)C]PiB uptake was observed in any subject at baseline or at follow-up. Neuropathologic study of the symptomatic individual revealed PrP-immunopositive plaques and tau-immunopositive neurofibrillary tangles in cerebral cortex, subcortical nuclei, and brainstem. PrP deposits were also numerous in the cerebellar cortex. This is the first study to investigate the ability of [(11)C]PiB PET to bind to PrP-amyloid in GSS F198S subjects. This finding suggests that [(11)C]PiB PET is not suitable for in vivo assessment of PrP-amyloid plaques in patients with GSS