A graph-based integration of multimodal brain imaging data for the detection of early mild cognitive impairment (E-MCI)

Alzheimer's disease (AD) is the most common cause of dementia in older adults. By the time an individual has been diagnosed with AD, it may be too late for potential disease modifying therapy to strongly influence outcome. Therefore, it is critical to develop better diagnostic tools that can recognize AD at early symptomatic and especially pre-symptomatic stages. Mild cognitive impairment (MCI), introduced to describe a prodromal stage of AD, is presently classified into early and late stages (E-MCI, L-MCI) based on severity. Using a graph-based semi-supervised learning (SSL) method to integrate multimodal brain imaging data and select valid imaging-based predictors for optimizing prediction accuracy, we developed a model to differentiate E-MCI from healthy controls (HC) for early detection of AD. Multimodal brain imaging scans (MRI and PET) of 174 E-MCI and 98 HC participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were used in this analysis. Mean targeted region-of-interest (ROI) values extracted from structural MRI (voxel-based morphometry (VBM) and FreeSurfer V5) and PET (FDG and Florbetapir) scans were used as features. Our results show that the graph-based SSL classifiers outperformed support vector machines for this task and the best performance was obtained with 66.8% cross-validated AUC (area under the ROC curve) when FDG and FreeSurfer datasets were integrated. Valid imaging-based phenotypes selected from our approach included ROI values extracted from temporal lobe, hippocampus, and amygdala. Employing a graph-based SSL approach with multimodal brain imaging data appears to have substantial potential for detecting E-MCI for early detection of prodromal AD warranting further investigation

Probing semiclassical analogue gravity in Bose--Einstein condensates with widely tunable interactions

Bose-Einstein condensates (BEC) have recently been the subject of considerable study as possible analogue models of general relativity. In particular it was shown that the propagation of phase perturbations in a BEC can, under certain conditions, closely mimic the dynamics of scalar quantum fields in curved spacetimes. In two previous articles [gr-qc/0110036, gr-qc/0305061] we noted that a varying scattering length in the BEC corresponds to a varying speed of light in the ``effective metric''. Recent experiments have indeed achieved a controlled tuning of the scattering length in Rubidium 85. In this article we shall discuss the prospects for the use of this particular experimental effect to test some of the predictions of semiclassical quantum gravity, for instance, particle production in an expanding universe. We stress that these effects are generally much larger than the Hawking radiation expected from causal horizons, and so there are much better chances for their detection in the near future.Comment: 18 pages; uses revtex4. V2: Added brief discussion of "Bose-Nova" phenomenon, and appropriate reference

Quantum coherent control of highly multipartite continuous-variable entangled states by tailoring parametric interactions

The generation of continuous-variable multipartite entangled states is important for several protocols of quantum information processing and communication, such as one-way quantum computation or controlled dense coding. In this article we theoretically show that multimode optical parametric oscillators can produce a great variety of such states by an appropriate control of the parametric interaction, what we accomplish by tailoring either the spatio-temporal shape of the pump, or the geometry of the nonlinear medium. Specific examples involving currently available optical parametric oscillators are given, hence showing that our ideas are within reach of present technology.Comment: 14 pages, 5 figure

Calculation of the interspecies s-wave scattering length in an ultracold Na-Rb vapor

We report the calculation of the interspecies scattering length for the sodium-rubidium (Na-Rb) system. We present improved hybrid potentials for the singlet $X^1\Sigma^+$ and triplet $a^3\Sigma^+$ ground states of the NaRb molecule, and calculate the singlet and triplet scattering lengths $a_{s}$ and $a_{t}$ for the isotopomers $^{23}$Na$^{87}$Rb and $^{23}$Na$^{85}$Rb. Using these values, we assess the prospects for producing a stable two-species Bose-Einstein condensate in the Na-Rb system.Comment: v2: report correct units in Table captions, fix error in conclusions for $^{23}$Na$^{85}$Rb TBEC. Otherwise, more concise presentation, typos fixed. 6 pages, 1 figur

Self-consistent model of ultracold atomic collisions and Feshbach resonances in tight harmonic traps

We consider the problem of cold atomic collisions in tight traps, where the absolute scattering length may be larger than the trap size. As long as the size of the trap ground state is larger than a characteristic length of the van der Waals potential, the energy eigenvalues can be computed self-consistently from the scattering amplitude for untrapped atoms. By comparing with the exact numerical eigenvalues of the trapping plus interatomic potentials, we verify that our model gives accurate eigenvalues up to milliKelvin energies for single channel s-wave scattering of $^{23}$Na atoms in an isotropic harmonic trap, even when outside the Wigner threshold regime. Our model works also for multi-channel scattering, where the scattering length can be made large due to a magnetically tunable Feshbach resonance.Comment: 7 pages, 4 figures (PostScript), submitted to Physical Review

Optimization and Evaluation of Antiparasitic Benzamidobenzoic Acids as Inhibitors of Kinetoplastid Hexokinase 1

Kinetoplastid-based infections are neglected diseases that represent a significant human health issue. Chemotherapeutic options are limited due to toxicity, parasite susceptibility, and poor patient compliance. In response, we studied a molecular-target-directed approach involving intervention of hexokinase activity—a pivotal enzyme in parasite metabolism. A benzamidobenzoic acid hit with modest biochemical inhibition of Trypanosoma brucei hexokinase 1 (TbHK1, IC50=9.1 μm), low mammalian cytotoxicity (IMR90 cells, EC50>25 μm), and no appreciable activity on whole bloodstream-form (BSF) parasites was optimized to afford a probe with improved TbHK1 potency and, significantly, efficacy against whole BSF parasites (TbHK1, IC50=0.28 μm; BSF, ED50=1.9 μm). Compounds in this series also inhibited the hexokinase enzyme from Leishmania major (LmHK1), albeit with less potency than toward TbHK1, suggesting that inhibition of the glycolytic pathway may be a promising opportunity to target multiple disease-causing trypanosomatid protozoa

Adaptation of Brucella melitensis Antimicrobial Susceptibility Testing to the ISO 20776 Standard and Validation of the Method

This article belongs to the Special Issue Emerging Themes in Brucella and Brucellosis.Brucellosis, mainly caused by Brucella (B.) melitensis, is associated with a risk of chronification and relapses. Antimicrobial susceptibility testing (AST) standards for B. melitensis are not available, and the agent is not yet listed in the EUCAST breakpoint tables. CLSI recommendations for B. melitensis exist, but they do not fulfill the requirements of the ISO 20776 standard regarding the culture medium and the incubation conditions. Under the third EU Health Programme, laboratories specializing in the diagnostics of highly pathogenic bacteria in their respective countries formed a working group within a Joint Action aiming to develop a suitable method for the AST of B. melitensis. Under the supervision of EUCAST representatives, this working group adapted the CLSI M45 document to the ISO 20776 standard after testing and validation. These adaptations included the comparison of various culture media, culture conditions and AST methods. A Standard Operation Procedure was derived and an interlaboratory validation was performed in order to evaluate the method. The results showed pros and cons for both of the two methods but also indicate that it is not necessary to abandon Mueller–Hinton without additives for the AST of B. melitensis.This research was funded by the EU Health Programme 2014–2020, through the Consumers, Health, Agriculture and Food Executive Agency (CHAFEA, European Commission), the Joint Action EMERGE (CHAFEA n° 677 066) and the Joint Action SHARP (848096-SHARP JA).info:eu-repo/semantics/publishedVersio

Genuine Correlations of Like-Sign Particles in Hadronic Z0 Decays

Correlations among hadrons with the same electric charge produced in Z0 decays are studied using the high statistics data collected from 1991 through 1995 with the OPAL detector at LEP. Normalized factorial cumulants up to fourth order are used to measure genuine particle correlations as a function of the size of phase space domains in rapidity, azimuthal angle and transverse momentum. Both all-charge and like-sign particle combinations show strong positive genuine correlations. One-dimensional cumulants initially increase rapidly with decreasing size of the phase space cells but saturate quickly. In contrast, cumulants in two- and three-dimensional domains continue to increase. The strong rise of the cumulants for all-charge multiplets is increasingly driven by that of like-sign multiplets. This points to the likely influence of Bose-Einstein correlations. Some of the recently proposed algorithms to simulate Bose-Einstein effects, implemented in the Monte Carlo model PYTHIA, are found to reproduce reasonably well the measured second- and higher-order correlations between particles with the same charge as well as those in all-charge particle multiplets.Comment: 26 pages, 6 figures, Submitted to Phys. Lett.

Customer emotions in service failure and recovery encounters

Emotions play a significant role in the workplace, and considerable attention has been given to the study of employee emotions. Customers also play a central function in organizations, but much less is known about customer emotions. This chapter reviews the growing literature on customer emotions in employee–customer interfaces with a focus on service failure and recovery encounters, where emotions are heightened. It highlights emerging themes and key findings, addresses the measurement, modeling, and management of customer emotions, and identifies future research streams. Attention is given to emotional contagion, relationships between affective and cognitive processes, customer anger, customer rage, and individual differences

Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers

Introduction: Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer’s disease (AD) including neuroinflammation and amyloid-b deposition. Method: Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n 5 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the “A/T/N” (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([18F]FDG PET). Results: Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSF Ab1-42 (“A”) and three with CSF p-tau181 (“T”) (corrected P ,.05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy (“N”), respectively (corrected P , .05). Discussion: This is the first study to show serum-based BA metabolites are associated with “A/T/N” AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association