Myelodysplastic Syndrome and Autoimmune Disorders: Causal Relationship or Coincidence?

Myelodysplastic syndromes are heterogeneous group of clonal hematologic malignancies characterized by peripheral blood cytopenias secondary to the ineffective hematopoiesis. ADs are frequently reported in MDS, the incidence ranging from 10 to 30%, and particularly ADs are more frequently seen at CMML. ADs may prone patient to MDS, especially when immune suppressors such as azathioprine are used for the underlying AD. Both innate and adaptive immune systems, and different cytokines including interleukins, TNF-α, and C-X-C motif chemokine 10 (CXCL10) contribute in immune dysregulation of MDS. Vasculitis, seronegative rheumatoid arthritis, SLE, Behçet’s disease, RP, and AIHA are just some of the ADs occurring concomitantly with MDS. Although hematopoietic growth factors are recommended by the American Society of Clinical Oncology (ASCO), it has been recognized from several case reports that treatment of the underlying MDS may resolve the associated autoimmune disorders. The heterogeneity and complexity of pathology, clinical manifestations, response to therapy, and prognosis of MDS and its immune dysregulation make the prognosis of MDS with autoimmune diseases a matter of debate. Better understanding of the immune dysregulation of MDS in the molecular level may help to design prospective, double blind clinical trials to find the best treatment options for autoimmune disorders associated with MDS

Aerosol scattering effects on water vapor retrievals over the Los Angeles Basin

In this study, we propose a novel approach to describe the scattering effects of atmospheric aerosols in a complex urban environment using water vapor (H_2O) slant column measurements in the near infrared. This approach is demonstrated using measurements from the California Laboratory for Atmospheric Remote Sensing Fourier Transform Spectrometer on the top of Mt. Wilson, California, and a two-stream-exact single scattering (2S-ESS) radiative transfer (RT) model. From the spectral measurements, we retrieve H_2O slant column density (SCD) using 15 different absorption bands between 4000 and 8000 cm^(−1). Due to the wavelength dependence of aerosol scattering, large variations in H_2O SCD retrievals are observed as a function of wavelength. Moreover, the variations are found to be correlated with aerosol optical depths (AODs) measured at the AERONET-Caltech station. Simulation results from the RT model reproduce this correlation and show that the aerosol scattering effect is the primary contributor to the variations in the wavelength dependence of the H_2O SCD retrievals. A significant linear correlation is also found between variations in H_2O SCD retrievals from different bands and corresponding AOD data; this correlation is associated with the asymmetry parameter, which is a first-order measure of the aerosol scattering phase function. The evidence from both measurements and simulations suggests that wavelength-dependent aerosol scattering effects can be derived using H_2O retrievals from multiple bands. This understanding of aerosol scattering effects on H_2O retrievals suggests a promising way to quantify the effect of aerosol scattering on greenhouse gas retrievals and could potentially contribute towards reducing biases in greenhouse gas retrievals from space

Reliability and Validity of the Chinese (Mandarin) Tinnitus Handicap Inventory

ObjectivesThe Tinnitus Handicap Inventory (THI) is a commonly used self-reporting tinnitus questionnaire. We undertook this study to determine the reliability and validity of the Chinese-Mandarin version of the Tinnitus Handicap Inventory (THI-CM) for measuring tinnitus-related handicaps.MethodsWe tested the test-retest reliability, internal reliability, and construct validity of the THI-CM. Two-hundred patients seeking treatment for primary or secondary tinnitus in Southwest China were asked to complete THI-CM prior to clinical evaluation. Patients were evaluated by a clinician using standard methods, and 40 patients were asked to complete THI-CM a second time 14±3 days after the initial interview.ResultsThe test-retest reliability of THI-CM was high (Pearson correlation, 0.98), as was the internal reliability (Cronbach's α, 0.93). Factor analysis indicated that THI-CM has a unifactorial structure.ConclusionThe THI-CM version is reliable. The total score in THI-CM can be used to measure tinnitus-related handicaps in Mandarin-speaking populations

Laser ablation of Dbx1 neurons in the pre-Botzinger complex stops inspiratory rhythm and impairs output in neonatal mice

To understand the neural origins of rhythmic behavior one must characterize the central pattern generator circuit and quantify the population size needed to sustain functionality. Breathing-related interneurons of the brainstem pre-Botzinger complex (preBotC) that putatively comprise the core respiratory rhythm generator in mammals are derived from Dbx1-expressing precursors. Here, we show that selective photonic destruction of Dbx1 preBotC neurons in neonatal mouse slices impairs respiratory rhythm but surprisingly also the magnitude of motor output; respiratory hypoglossal nerve discharge decreased and its frequency steadily diminished until rhythm stopped irreversibly after 85 +/- 20 (mean +/- SEM) cellular ablations, which corresponds to similar to 15% of the estimated population. These results demonstrate that a single canonical interneuron class generates respiratory rhythm and contributes in a premotor capacity, whereas these functions are normally attributed to discrete populations. We also establish quantitative cellular parameters that govern network viability, which may have ramifications for respiratory pathology in disease states

Development of a coupled simulation toolkit for computational radiation biology based on Geant4 and CompuCell3D

RL acknowledges support from Consortium for Risk Evaluation and Stakeholder Participation (http://cresp.org). JAG acknowledges support from National Science Foundation grant NSF 1720625 and National Institutes of Health, National Institute of General Medical Sciences grants U01 GM111243 and R01 GM076692, JAG and MS acknowledge support from National Institutes of Health, National Institute of General Medical Sciences grant R01 GM122424.Understanding and designing clinical radiation therapy is one of the most important areas of state-of-the-art oncological treatment regimens. Decades of research have gone into developing sophisticated treatment devices and optimization protocols for schedules and dosages. In this paper, we presented a comprehensive computational platform that facilitates building of the sophisticated multi-cell-based model of how radiation affects the biology of living tissue. We designed and implemented a coupled simulation method, including a radiation transport model, and a cell biology model, to simulate the tumor response after irradiation. The radiation transport simulation was implemented through Geant4 which is an open-source Monte Carlo simulation platform that provides many flexibilities for users, as well as low energy DNA damage simulation physics, Geant4-DNA. The cell biology simulation was implemented using CompuCell3D (CC3D) which is a cell biology simulation platform. In order to couple Geant4 solver with CC3D, we developed a "bridging" module, RADCELL, that extracts tumor cellular geometry of the CC3D simulation (including specification of the individual cells) and ported it to the Geant4 for radiation transport simulation. The cell dose and cell DNA damage distribution in multicellular system were obtained using Geant4. The tumor response was simulated using cell-based tissue models based on CC3D, and the cell dose and cell DNA damage information were fed back through RADCELL to CC3D for updating the cell properties. By merging two powerful and widely used modeling platforms, CC3D and Geant4, we delivered a novel tool that can give us the ability to simulate the dynamics of biological tissue in the presence of ionizing radiation, which provides a framework for quantifying the biological consequences of radiation therapy. In this introductory methods paper, we described our modeling platform in detail and showed how it can be applied to study the application of radiotherapy to a vascularized tumor.PostprintPeer reviewe

Los Angeles megacity: a high-resolution land–atmosphere modelling system for urban CO_2 emissions

Megacities are major sources of anthropogenic fossil fuel CO_2 (FFCO_2) emissions. The spatial extents of these large urban systems cover areas of 10000 km^2 or more with complex topography and changing landscapes. We present a high-resolution land–atmosphere modelling system for urban CO_2 emissions over the Los Angeles (LA) megacity area. The Weather Research and Forecasting (WRF)-Chem model was coupled to a very high-resolution FFCO_2 emission product, Hestia-LA, to simulate atmospheric CO_2 concentrations across the LA megacity at spatial resolutions as fine as  ∼ 1 km. We evaluated multiple WRF configurations, selecting one that minimized errors in wind speed, wind direction, and boundary layer height as evaluated by its performance against meteorological data collected during the CalNex-LA campaign (May–June 2010). Our results show no significant difference between moderate-resolution (4 km) and high-resolution (1.3 km) simulations when evaluated against surface meteorological data, but the high-resolution configurations better resolved planetary boundary layer heights and vertical gradients in the horizontal mean winds. We coupled our WRF configuration with the Vulcan 2.2 (10 km resolution) and Hestia-LA (1.3 km resolution) fossil fuel CO_2 emission products to evaluate the impact of the spatial resolution of the CO_2 emission products and the meteorological transport model on the representation of spatiotemporal variability in simulated atmospheric CO_2 concentrations. We find that high spatial resolution in the fossil fuel CO_2 emissions is more important than in the atmospheric model to capture CO_2 concentration variability across the LA megacity. Finally, we present a novel approach that employs simultaneous correlations of the simulated atmospheric CO_2 fields to qualitatively evaluate the greenhouse gas measurement network over the LA megacity. Spatial correlations in the atmospheric CO_2 fields reflect the coverage of individual measurement sites when a statistically significant number of sites observe emissions from a specific source or location. We conclude that elevated atmospheric CO_2 concentrations over the LA megacity are composed of multiple fine-scale plumes rather than a single homogenous urban dome. Furthermore, we conclude that FFCO_2 emissions monitoring in the LA megacity requires FFCO_2 emissions modelling with  ∼ 1 km resolution because coarser-resolution emissions modelling tends to overestimate the observational constraints on the emissions estimates

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Dijet Resonance Search with Weak Supervision Using root S=13 TeV pp Collisions in the ATLAS Detector

This Letter describes a search for narrowly resonant new physics using a machine-learning anomaly detection procedure that does not rely on signal simulations for developing the analysis selection. Weakly supervised learning is used to train classifiers directly on data to enhance potential signals. The targeted topology is dijet events and the features used for machine learning are the masses of the two jets. The resulting analysis is essentially a three-dimensional search A → BC, for mA ∼ OðTeVÞ, mB; mC ∼ Oð100 GeVÞ and B, C are reconstructed as large-radius jets, without paying a penalty associated with a large trials factor in the scan of the masses of the two jets. The full run 2 ffiffi s p ¼ 13 TeV pp collision dataset of 139 fb−1 recorded by the ATLAS detector at the Large Hadron Collider is used for the search. There is no significant evidence of a localized excess in the dijet invariant mass spectrum between 1.8 and 8.2 TeV. Cross-section limits for narrow-width A, B, and C particles vary with mA, mB, and mC. For example, when mA ¼ 3 TeV and mB ≳ 200 GeV, a production cross section between 1 and 5 fb is excluded at 95% confidence level, depending on mC. For certain masses, these limits are up to 10 times more sensitive than those obtained by the inclusive dijet search. These results are complementary to the dedicated searches for the case that B and C are standard model boson