Cardiopulmonary responses to maximal aerobic exercise in patients with cystic fibrosis (article)

This is the final version. Available from Public Library of Science via the DOI in this record.The dataset associated with this article is located in ORE at: https://doi.org/10.24378/exe.1105Cystic fibrosis (CF) is a debilitating chronic condition, which requires complex and expensive disease management. Exercise has now been recognised as a critical factor in improving health and quality of life in patients with CF. Hence, cardiopulmonary exercise testing (CPET) is used to determine aerobic fitness of young patients as part of the clinical management of CF. However, at present there is a lack of conclusive evidence for one limiting system of aerobic fitness for CF patients at individual patient level. Here, we perform detailed data analysis that allows us to identify important systems-level factors that affect aerobic fitness. We use patients’ data and principal component analysis to confirm the dependence of CPET performance on variables associated with ventilation and metabolic rates of oxygen consumption. We find that the time at which participants cross the gas exchange threshold (GET) is well correlated with their overall performance. Furthermore, we propose a predictive modelling framework that captures the relationship between ventilatory dynamics, lung capacity and function and performance in CPET within a group of children and adolescents with CF. Specifically, we show that using Gaussian processes (GP) we can predict GET at the individual patient level with reasonable accuracy given the small sample size of the available group of patients. We conclude by presenting an example and future perspectives for improving and extending the proposed framework. The modelling and analysis have the potential to pave the way to designing personalised exercise programmes that are tailored to specific individual needs relative to patient’s treatment therapies.Wellcome TrustEngineering and Physical Sciences Research Counci

Genome-Wide Identification of R2R3-MYB Genes and Expression Analyses During Abiotic Stress in

The R2R3-MYB is one of the largest families of transcription factors, which have been implicated in multiple biological processes. There is great diversity in the number of R2R3-MYB genes in different plants. However, there is no report on genome-wide characterization of this gene family in cotton. In the present study, a total of 205 putative R2R3-MYB genes were identified in cotton D genome (Gossypium raimondii), that are much larger than that found in other cash crops with fully sequenced genomes. These GrMYBs were classified into 13 groups with the R2R3-MYB genes from Arabidopsis and rice. The amino acid motifs and phylogenetic tree were predicted and analyzed. The sequences of GrMYBs were distributed across 13 chromosomes at various densities. The results showed that the expansion of the G. Raimondii R2R3-MYB family was mainly attributable to whole genome duplication and segmental duplication. Moreover, the expression pattern of 52 selected GrMYBs and 46 GaMYBs were tested in roots and leaves under different abiotic stress conditions. The results revealed that the MYB genes in cotton were differentially expressed under salt and drought stress treatment. Our results will be useful for determining the precise role of the MYB genes during stress responses with crop improvement

Search for Cosmic-ray Boosted Sub-GeV Dark Matter using Recoil Protons at Super-Kamiokande

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton$\times$years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross-section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross-section between $10^{-33}\text{ cm}^{-2}$ and $10^{-27}\text{ cm}^{-2}$ for dark matter mass from 10 MeV/$c^2$ to 1 GeV/$c^2$.Comment: With 1-page appendi

Measurement of the cosmogenic neutron yield in Super-Kamiokande with gadolinium loaded water

Cosmic-ray muons that enter the Super-Kamiokande detector cause hadronic showers due to spallation in water, producing neutrons and radioactive isotopes. Those are a major background source for studies of MeV-scale neutrinos and searches for rare events. Since 2020, gadolinium was introduced in the ultra-pure water in the Super-Kamiokande detector to improve the detection efficiency of neutrons. In this study, the cosmogenic neutron yield was measured using data acquired during the period after the gadolinium loading. The yield was found to be $(2.76 \pm 0.02\,\mathrm{(stat.) \pm 0.19\,\mathrm{(syst.)}}) \times 10^{-4}\,\mu^{-1} \mathrm{g^{-1} cm^{2}}$ at 259 GeV of average muon energy at the Super-Kamiokande detector.Comment: 10 pages, 10 figures, 3 table

Search for proton decay into three charged leptons in 0.37 megaton-years exposure of the Super-Kamiokande

A search for proton decay into three charged leptons has been performed by using 0.37 Mton⋅years of data collected in Super-Kamiokande. All possible combinations of electrons, muons, and their antiparticles consistent with charge conservation were considered as decay modes. No significant excess of events has been found over the background, and lower limits on the proton lifetime divided by the branching ratio have been obtained. The limits range between 9.2×10^33 and 3.4×10^34 years at 90% confidence level, improving by more than an order of magnitude upon limits from previous experiments. A first limit has been set for the p→μ^−e^+e^+ mode

Search for astrophysical electron antineutrinos in Super-Kamiokande with 0.01wt% gadolinium-loaded water

We report the first search result for the flux of astrophysical electron antineutrinos for energies O(10) MeV in the gadolinium-loaded Super-Kamiokande (SK) detector. In June 2020, gadolinium was introduced to the ultra-pure water of the SK detector in order to detect neutrons more efficiently. In this new experimental phase, SK-Gd, we can search for electron antineutrinos via inverse beta decay with efficient background rejection and higher signal efficiency thanks to the high efficiency of the neutron tagging technique. In this paper, we report the result for the initial stage of SK-Gd with a $22.5\times552$ $\rm kton\cdot day$ exposure at 0.01% Gd mass concentration. No significant excess over the expected background in the observed events is found for the neutrino energies below 31.3 MeV. Thus, the flux upper limits are placed at the 90% confidence level. The limits and sensitivities are already comparable with the previous SK result with pure-water ($22.5 \times 2970 \rm kton\cdot day$) owing to the enhanced neutron tagging

Search for Periodic Time Variations of the Solar 8^8B Neutrino Flux Between 1996 and 2018 in Super-Kamiokande

We report a search for time variations of the solar $^8$B neutrino flux using 5,804 live days of Super-Kamiokande data collected between May 31, 1996, and May 30, 2018. Super-Kamiokande measured the precise time of each solar neutrino interaction over 22 calendar years to search for solar neutrino flux modulations with unprecedented precision. Periodic modulations are searched for in a data set comprised of five-day interval solar neutrino flux measurements with a maximum likelihood method. We also applied the Lomb-Scargle method to this data set to compare it with previous reports. The only significant modulation found is due to the elliptic orbit of the Earth around the Sun. The observed modulation is consistent with astronomical data: we measured an eccentricity of (1.53$\pm$0.35)\,\%, and a perihelion shift is ($-$1.5$\pm$13.5)\,days.Comment: 8 pages, 5 figures, 2 tables, and data file: "sksolartimevariation5804d.txt

TITUS: the Tokai Intermediate Tank for the Unoscillated Spectrum

68 pages.38 figures68 pages.38 figures68 pages.38 figures70 pages, 41 figuresThe TITUS, Tokai Intermediate Tank for Unoscillated Spectrum, detector, is a proposed Gd-doped Water Cherenkov tank with a magnetised muon range detector downstream. It is located at J-PARC at about 2 km from the neutrino target and it is proposed as a potential near detector for the Hyper-Kamiokande experiment. Assuming a beam power of 1.3 MW and 27.05 x 10^{21} protons-on-target the sensitivity to CP and mixing parameters achieved by Hyper-Kamiokande with TITUS as a near detector is presented. Also, the potential of the detector for cross sections and Standard Model parameter determination, supernova neutrino and dark matter are shown

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months