Evaluation and construction of diagnostic criteria for inclusion body myositis

OBJECTIVE: To use patient data to evaluate and construct diagnostic criteria for inclusion body myositis (IBM), a progressive disease of skeletal muscle. METHODS: The literature was reviewed to identify all previously proposed IBM diagnostic criteria. These criteria were applied through medical records review to 200 patients diagnosed as having IBM and 171 patients diagnosed as having a muscle disease other than IBM by neuromuscular specialists at 2 institutions, and to a validating set of 66 additional patients with IBM from 2 other institutions. Machine learning techniques were used for unbiased construction of diagnostic criteria. RESULTS: Twenty-four previously proposed IBM diagnostic categories were identified. Twelve categories all performed with high (≥97%) specificity but varied substantially in their sensitivities (11%-84%). The best performing category was European Neuromuscular Centre 2013 probable (sensitivity of 84%). Specialized pathologic features and newly introduced strength criteria (comparative knee extension/hip flexion strength) performed poorly. Unbiased data-directed analysis of 20 features in 371 patients resulted in construction of higher-performing data-derived diagnostic criteria (90% sensitivity and 96% specificity). CONCLUSIONS: Published expert consensus-derived IBM diagnostic categories have uniformly high specificity but wide-ranging sensitivities. High-performing IBM diagnostic category criteria can be developed directly from principled unbiased analysis of patient data. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that published expert consensus-derived IBM diagnostic categories accurately distinguish IBM from other muscle disease with high specificity but wide-ranging sensitivities

Collisional Velocities and Rates in Resonant Planetesimal Belts

We consider a belt of small bodies around a star, captured in one of the external or 1:1 mean-motion resonances with a massive perturber. The objects in the belt collide with each other. Combining methods of celestial mechanics and statistical physics, we calculate mean collisional velocities and collisional rates, averaged over the belt. The results are compared to collisional velocities and rates in a similar, but non-resonant belt, as predicted by the particle-in-a-box method. It is found that the effect of the resonant lock on the velocities is rather small, while on the rates more substantial. The collisional rates between objects in an external resonance are by about a factor of two higher than those in a similar belt of objects not locked in a resonance. For Trojans under the same conditions, the collisional rates may be enhanced by up to an order of magnitude. Our results imply, in particular, shorter collisional lifetimes of resonant Kuiper belt objects in the solar system and higher efficiency of dust production by resonant planetesimals in debris disks around other stars.Comment: 31 pages, 11 figures (some of them heavily compressed to fit into arxiv-maximum filesize), accepted for publication at "Celestial Mechanics and Dynamical Astronomy

Asymptotic Freedom for Non-Relativistic Confinement

Some aspects of asymptotic freedom are discussed in the context of a simple two-particle non-relativisitic confining potential model. In this model asymptotic freedom follows from the similarity of the free-particle and bound state radial wave functions at small distances and for the same angular momentum and the same large energy. This similarity, which can be understood using simple quantum mechanical arguments, can be used to show that the exact response function approaches that obtained when final state interactions are ignored. A method of calculating corrections to this limit is given and explicit examples are given for the case of the harmonic oscillator.Comment: 16 pages, 5 figures, RevTex

Confinement and scaling in deep inelastic scattering

We show that parton confinement in the final state generates large $1/Q^2$ corrections to Bjorken scaling, thus leaving less room for the logarithmic corrections. In particular, the $x$-scaling violations at large $x$ are entirely described in terms of power corrections. For treatment of these non-perturbative effects, we derive a new expansion in powers of $1/Q^2$ for the structure function that is free of infra-red singularities and which reduces corrections to the leading term. The leading term represents scattering from an off-mass-shell parton, which keeps the same virtual mass in the final state. It is found that this quasi-free term is a function of a new variable $\bar x$, which coincides with the Bjorken variable $x$ for $Q^2\to\infty$. The two variables are very different, however, at finite $Q^2$. In particular, the variable $\bar x$ depends on the invariant mass of the spectator particles. Analysis of the data at large $x$ shows excellent scaling in the variable $\bar x$, and determines the value of the diquark mass to be close to zero. $\bar x$-scaling allows us to extract the structure function near the elastic threshold. It is found to behave as $F_2\sim (1-x)^{3.7}$. Predictions for the structure functions based on $\bar x$-scaling are made.Comment: Discussion of target mass corrections is added. Accepted for publication in Phys. Rev.

Probleme bei sozialen Experimenten: Lehren aus US-amerikanischen Arbeitsmarktprogrammen

When evaluating a pilot or demonstration program, there are risks from drawing inferences from a single test. This paper reviews the experiences of replication efforts from demonstrations using randomized controlled trials in the initial evaluation and the replications. Although replications of promising programs are primarily gathered to increase sample size, replications are also used to learn if the intervention is successful for other target groups and geographic locations, and to vary some of the intervention's features. In many cases, replications fail to achieve the same success as the original evaluation, and the paper reviews reasons that have been suggested for such failures. The paper reviews what has been learned from replications where random assignment was used in six instances: income maintenance experiments, unemployment insurance bonus experiments, the Center for Employment Training program, job clubs, job search experiments, and the Quantum Opportunity Program. The paper concludes by summarizing lessons learned from the review and areas where more research is needed

Structure function of a damped harmonic oscillator

Following the Caldeira-Leggett approach to describe dissipative quantum systems the structure function for a harmonic oscillator with Ohmic dissipation is evaluated by an analytic continuation from euclidean to real time. The analytic properties of the Fourier transform of the structure function with respect to the energy transfer (the ``characteristic function'') are studied and utilized. In the one-parameter model of Ohmic dissipation we show explicitly that the broadening of excited states increases with the state number without violating sum rules. Analytic and numerical results suggest that this is a phenomenologically relevant, consistent model to include the coupling of a single (sub-)nuclear particle to unobserved and complex degrees of freedom.Comment: 23 pages, 5 figures, RevTex4, minor changes following referee's comments and by PRC: the definite article in the original title has been droppe

Modeling quark-hadron duality for relativistic, confined fermions

We discuss a model for the study of quark-hadron duality in inclusive electron scattering based on solving the Dirac equation numerically for a scalar confining linear potential and a vector color Coulomb potential. We qualitatively reproduce the features of quark-hadron duality for all potentials considered, and discuss similarities and differences to previous models that simplified the situation by treating either the quarks or all particles as scalars. We discuss the scaling results for PWIA and FSI, and the approach to scaling using the analog of the Callan-Gross relation for y-scaling.Comment: 38 pages, 21 figure

Systematic Analysis of Mobile Genetic Elements Mediating β-Lactamase Gene Amplification in Noncarbapenemase-Producing Carbapenem-Resistant Enterobacterales Bloodstream Infections

Noncarbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE) are increasingly recognized as important contributors to prevalent carbapenem-resistant Enterobacterales (CRE) infections. However, there is limited understanding of mechanisms underlying non-CP-CRE causing invasive disease. Long- and short-read whole-genome sequencing was used to elucidate carbapenem nonsusceptibility determinants in Enterobacterales bloodstream isolates at MD Anderson Cancer Center in Houston, Texas. We investigated carbapenem nonsusceptible Enterobacterales (CNSE) mechanisms (i.e., isolates with carbapenem intermediate resistance phenotypes or greater) through a combination of phylogenetic analysis, antimicrobial resistance gene detection/copy number quantification, porin assessment, and mobile genetic element (MGE) characterization. Most CNSE isolates sequenced were non-CP-CRE (41/79; 51.9%), whereas 25.3% (20/79) were Enterobacterales with intermediate susceptibility to carbapenems (CIE), and 22.8% (18/79) were carbapenemase-producing Enterobacterales (CPE). Statistically significant copy number variants (CNVs) of extended-spectrum β-lactamase (ESBL) genes (Wilcoxon Test; P-value < 0.001) were present in both non-CP-CR E. coli (median CNV = 2.6×; n = 17) and K. pneumoniae (median CNV = 3.2×, n = 17). All non-CP-CR E. coli and K. pneumoniae had predicted reduced expression of at least one outer membrane porin gene (i.e., ompC/ompF or ompK36/ompK35). Completely resolved CNSE genomes revealed that IS26 and ISEcp1 structures harboring blaCTX-M variants along with other antimicrobial resistance elements were associated with gene amplification, occurring in mostly IncFIB/IncFII plasmid contexts. MGE-mediated β-lactamase gene amplifications resulted in either tandem arrays, primarily mediated by IS26 translocatable units, or segmental duplication, typically due to ISEcp1 transposition units. Non-CP-CRE strains were the most common cause of CRE bacteremia with carbapenem nonsusceptibility driven by concurrent porin loss and MGE-mediated amplification of blaCTX-M genes. IMPORTANCE Carbapenem-resistant Enterobacterales (CRE) are considered urgent antimicrobial resistance (AMR) threats. The vast majority of CRE research has focused on carbapenemase-producing Enterobacterales (CPE) even though noncarbapenemase-producing CRE (non-CP-CRE) comprise 50% or more of isolates in some surveillance studies. Thus, carbapenem resistance mechanisms in non-CP-CRE remain poorly characterized. To address this problem, we applied a combination of short- and long-read sequencing technologies to a cohort of CRE bacteremia isolates and used these data to unravel complex mobile genetic element structures mediating β-lactamase gene amplification. By generating complete genomes of 65 carbapenem nonsusceptible Enterobacterales (CNSE) covering a genetically diverse array of isolates, our findings both generate novel insights into how non-CP-CRE overcome carbapenem treatments and provide researchers scaffolds for characterization of their own non-CP-CRE isolates. Improved recognition of mechanisms driving development of non-CP-CRE could assist with design and implementation of future strategies to mitigate the impact of these increasingly recognized AMR pathogens

Uncommon genetic syndromes and narrative production - Case Studies with Williams, Smith-Magenis and Prader- Willi Syndromes

This study compares narrative production among three syndromes with genetic microdeletions: Williams syndrome (WS), Smith-Magenis syndrome (SMS), and Prader-Willi syndrome (PWS), characterized by intellectual disabilities and relatively spared language abilities. Our objective is to study the quality of narrative production in the context of a common intellectual disability. To elicit a narrative production, the task Frog! Where Are You was used. Then, structure, process, and content of the narrative process were analysed in the three genetic disorders:WS (n52), SMS (n52), and PWS (n52). Data show evidence of an overall low narrative quality in these syndromes, despite a high variability within different measures of narrative production. Results support the hypothesis that narrative is a highly complex cognitive process and that, in a context of intellectual disability, there is no evidence of particular ‘hypernarrativity’ in these syndromes.This research was supported by the grants FEDER –

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions