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

NÚMERO TOTAL DE ESPERMATOZÓIDES DE GARANHÕES OBTIDOS ATRAVÉS DA COLHEITA COM VAGINA ARTIFICIAL E POR FLUXO RETRÓGRADO DA CAUDA DO EPIDÍDIMO

The aim of the present research work, carried out with 7 stud-horses, was to compare the total number of spermatozzoa recovered from the artificial vagina. In a preliminary phase, evaluation of the semen harvested with the artificial vagina was carried out. After 7 days of this procedure, the stallions underwent bilateral orchiectomy for recovery and evaluation of the epididymal tail spermatozooa. For the latter procedure, the spermatic cells had been harvested through the segmentation in 3 parts of the epididymal tail and its washing through a feedback flow with proper diluents. The counting of the total number of spermatozoa was carried out immediately after the procedures of their harvesting. It was concluded that there was a statistical difference (pNeste trabalho foram utilizados 7 garanhões com o objetivo de se comparar o número total de espermatozóides recuperados através da técnica de fluxo retrógrado da cauda do epidídimo com os colhidos com a vagina artificial. Numa fase preliminar foi realizada avaliação do sêmen colhido com a vagina artificial e 7 dias após os garanhões foram submetidos ao procedimento de orquiectomia bilateral para recuperação e avaliação dos espermatozóides da cauda do epidídimo. As células espermáticas foram colhidas através da segmentação em 3 partes da cauda do epidídimo e sua lavagem por fluxo retrógrado com diluente. A contagem do número total de espermatozóides colhidos com a vagina artificial da cauda do epidídimo foi realizada imediatamente após a colheita. Concluiu-se que houve diferença significativa (

A Helminth-Derived Chitinase Structurally Similar to Mammalian Chitinase Displays Immunomodulatory Properties in Inflammatory Lung Disease

The authors gratefully thank Marion Müller, Christiane Palissa, Yvonne Weber, Bettina Sonnenburg, and Beate Anders for the excellent technical assistance and Franziska Rohr for her help within the animal facility. We also thank Prof. Judith E. Allen for her expertise, critical advice, and intellectual discussion of the topic.Peer reviewe

Self-Organized Branching Processes: A Mean-Field Theory for Avalanches

We discuss mean-field theories for self-organized criticality and the connection with the general theory of branching processes. We point out that the nature of the self-organization is not addressed properly by the previously proposed mean-field theories. We introduce a new mean-field model that explicitly takes the boundary conditions into account; in this way, the local dynamical rules are coupled to a global equation that drives the control parameter to its critical value. We study the model numerically, and analytically we compute the avalanche distributions.Comment: 4 pages + 4 ps figure

Stokes Diagnostis of 2D MHD-simulated Solar Magnetogranulation

We study the properties of solar magnetic fields on scales less than the spatial resolution of solar telescopes. A synthetic infrared spectropolarimetric diagnostics based on a 2D MHD simulation of magnetoconvection is used for this. We analyze two time sequences of snapshots that likely represent two regions of the network fields with their immediate surrounding on the solar surface with the unsigned magnetic flux density of 300 and 140 G. In the first region we find from probability density functions of the magnetic field strength that the most probable field strength at logtau_5=0 is equal to 250 G. Weak fields (B < 500 G) occupy about 70% of the surface, while stronger fields (B 1000 G) occupy only 9.7% of the surface. The magnetic flux is -28 G and its imbalance is -0.04. In the second region, these parameters are correspondingly equal to 150 G, 93.3 %, 0.3 %, -40 G, and -0.10. We estimate the distribution of line-of-sight velocities on the surface of log tau_5=-1. The mean velocity is equal to 0.4 km/s in the first simulated region. The averaged velocity in the granules is -1.2 km/s and in the intergranules is 2.5 km/s. In the second region, the corresponding values of the mean velocities are equal to 0, -1.8, 1.5 km/s. In addition we analyze the asymmetry of synthetic Stokes-V profiles of the Fe I 1564.8 nm line. The mean values of the amplitude and area asymmetry do not exceed 1%. The spatially smoothed amplitude asymmetry is increased to 10% while the area asymmetry is only slightly varied.Comment: 24 pages, 12 figure

A Helminth Derived Chitinase Structurally Similar to Mammalian Chitinase Displays Immunomodulatory Properties in Inflammatory Lung Disease

Immunomodulation of airway hyperreactivity by excretory secretory ES products of the first larval stage L1 of the gastrointestinal nematode Trichuris suis is reported by us and others. Here, we aimed to identify the proteins accounting for the modulatory effects of the T. suis L1 ES proteins and studied six selected T. suis L1 proteins for their immunomodulatory efficacy in a murine OVA induced allergic airway disease model. In particular, an enzymatically active T. suis chitinase mediated amelioration of clinical signs of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung, the associated chemokines, and increased numbers of RELM amp; 945; interstitial lung macrophages. While there is no indication of T. suis chitinase directly interfering with dendritic cell activation or antigen presentation to CD4 T cells, treatment of allergic mice with the worm chitinase influenced the hosts own chitinase activity in the inflamed lung. The three dimensional structure of the T. suis chitinase as determined by high resolution X ray crystallography revealed high similarities to mouse acidic mammalian chitinase AMCase but a unique ability of T. suis chitinase to form dimers. Our data indicate that the structural similarities between the parasite and host chitinase contribute to the disease ameliorating effect of the helminth derived chitinase on allergic lung inflammatio

Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays

Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing (NGS) assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired Foundation Medicine NGS assays. Experimental Design: This was a retrospective cohort study of individuals undergoing NGS of solid tumors from two large cancer centers. We identified and quantified mutations in genes known to be frequently altered in clonal hematopoiesis (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) that were returned to physicians on clinical Foundation Medicine reports. For a subset of patients, we explored the frequency of true clonal hematopoiesis by comparing mutations on Foundation Medicine reports with matched blood sequencing. Results: Mutations in genes that are frequently altered in clonal hematopoiesis were identified in 65% (1,139/1,757) of patients undergoing NGS. When excluding TP53, which is often mutated in solid tumors, these events were still seen in 35% (619/1,757) of patients. Utilizing paired blood specimens, we were able to confirm that 8% (18/226) of mutations reported in these genes were true clonal hematopoiesis events. The majority of DNMT3A mutations (64%, 7/11) and minority of TP53 mutations (4%, 2/50) were clonal hematopoiesis. Conclusions: Clonal hematopoiesis mutations are commonly reported on unpaired NGS testing. It is important to recognize clonal hematopoiesis as a possible cause of misattribution of mutation origin when applying NGS findings to a patient's care

Limits to the sensitivity of a low noise compact atomic gravimeter

A detailed analysis of the most relevant sources of phase noise in an atomic interferometer is carried out, both theoretically and experimentally. Even a short interrogation time of 100 ms allows our cold atom gravimeter to reach an excellent short term sensitivity to acceleration of $1.4\times 10^{-8}$g at 1s. This result relies on the combination of a low phase noise laser system, efficient detection scheme and good shielding from vibrations. In particular, we describe a simple and robust technique of vibration compensation, which is based on correcting the interferometer signal by using the AC acceleration signal measured by a low noise seismometer.Comment: 30 pages, 14 figure

Premature and early menopause among US women with or at risk for HIV

Objective:Little is known about the prevalence and treatment of premature and early menopause among people with HIV. We described premature and early menopause and subsequent hormonal treatment in a longitudinal cohort of women living with or at risk for HIV in the US.Methods:Data from the Women's Interagency HIV Study between 2008 and 2020 were analyzed to describe premature and early menopause among cohort participants under the age of 51.Results:Of 3,059 eligible women during the study period, 1% (n=35) underwent premature menopause before age 41, 3% (n=101) underwent menopause between ages 41 and 46, and 21% (n=442) underwent menopause between ages 46 and 50, inclusive. Of participants who experienced menopause before age 41, between age 41 and 45, and between ages 46 and 50, 51%, 24%, and 7% (respectively) received either menopausal hormone therapy or hormonal contraception.Conclusion:These findings suggest that disparities in receipt of recommended hormone therapy for premature and early menopause may contribute, in part, to evident health disparities, such as cardiovascular disease, osteoporosis, and overall mortality. They also suggest a substantial need for education among people experiencing early menopause and their providers, with the goal of improving access to hormone therapy based on guidelines to address health disparities and minimize future health consequences