Prolonged treadmill running in normobaric hypoxia causes gastrointestinal barrier permeability and elevates circulating levels of pro- and anti-inflammatory cytokines

PURPOSE: This study examined the impact of treadmill running in normobaric hypoxia on gastrointestinal barrier permeability and the systemic inflammatory response. METHODS: Ten recreationally-active participants completed two 1h bouts of matched-workload treadmill exercise(65% normoxic VO2max) in counterbalanced order. One bout was performed in normoxia(NORM: FIO2=20.9%) and the other in normobaric hypoxia(HYP: FIO2=13.5%). Minute ventilation(VE), respiratory rate(RR), tidal volume(VT), oxygen consumption(VO2), carbon dioxide production(VCO2), respiratory quotient(RQ), and heart rate(HR) were measured with a metabolic cart. Peripheral oxygen saturation(SpO2) was measured with pulse oximetry. Absolute tissue saturation(StO2) was measured with near-infrared spectroscopy. Fatty acid-binding protein(I-FABP) and circulating cytokine concentrations(IL-1Ra, IL-6, IL-10, TNFα) were assayed from plasma samples collected Pre, Post, 1h-Post, and 4h-Post exercise. Data were analyzed with 2-Way(Condition*Time) RM ANOVAs and Newman-Keuls post hocs were run where appropriate(p<0.05). RESULTS: As compared to NORM, 1h of treadmill exercise in HYP caused greater(p<0.05) changes in VE(+30%), RR(+16%), VT(+10%), VCO2(+18%), RQ(+16%), HR(+4%), SpO2(-16%) and StO2(-10%). Gut barrier permeability and circulating cytokine concentrations were also greater(p<0.05) following HYP exercise, where I-FABP was shown increased at Post(+68%) and IL-1Ra at 1h-Post(+266%). IFABP and IL-1Ra did not change following NORM exercise. IL-6 and IL-10 increased with exercise in both study conditions but were increased more(p<0.05) following HYP exercise at Post(+705% and +127%; respectively) and 1h-Post(+400% and +128%; respectively). KEY FINDINGS: Normobaric hypoxia caused significant desaturation and increased most cardiopulmonary responses by 10-30%. Significant gut barrier permeability and increased pro- and anti-inflammatory cytokine concentrations could promote an "open window" in the hours following HYP exercise

Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

BACKGROUND: Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined. METHODS: To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated. RESULTS: Thirty-nine patients with uveal melanoma were identified, including 34 patients who received 3 mg/kg ipilimumab and 5 who received 10 mg/kg ipilimumab. Immune-related response criteria and modified World Health Organization criteria were used to assess the response rate (RR) and the combined response plus stable disease (SD) rate after 12 weeks, after 23 weeks, and overall (median follow-up, 50.4 weeks [12.6 months]). At week 12, the RR was 2.6%, and the response plus SD rate was 46.%; at week 23, the RR was 2.6%, and the response plus SD rate was 28.2%. There was 1 complete response and 1 late partial response (at 100 weeks after initial SD) for an immune-related RR of 5.1%. Immune-related adverse events were observed in 28 patients (71.8%) and included 7 (17.9%) grade 3 and 4 events. Immune-related adverse events were more frequent in patients who received 10 mg/kg ipilimumab than in those who received 3 mg/kg ipilimumab. The median overall survival from the first dose of ipilimumab was 9.6 months (95% confidence interval, 6.3-13.4 months; range, 1.6-41.6 months). Performance status, lactate dehydrogenase level, and an absolute lymphocyte count ≥ 1000 cells/μL at week 7 were associated significantly with survival. CONCLUSIONS: In this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed

A Parametric Study of Erupting Flux Rope Rotation. Modeling the "Cartwheel CME" on 9 April 2008

The rotation of erupting filaments in the solar corona is addressed through a parametric simulation study of unstable, rotating flux ropes in bipolar force-free initial equilibrium. The Lorentz force due to the external shear field component and the relaxation of tension in the twisted field are the major contributors to the rotation in this model, while reconnection with the ambient field is of minor importance. Both major mechanisms writhe the flux rope axis, converting part of the initial twist helicity, and produce rotation profiles which, to a large part, are very similar in a range of shear-twist combinations. A difference lies in the tendency of twist-driven rotation to saturate at lower heights than shear-driven rotation. For parameters characteristic of the source regions of erupting filaments and coronal mass ejections, the shear field is found to be the dominant origin of rotations in the corona and to be required if the rotation reaches angles of order 90 degrees and higher; it dominates even if the twist exceeds the threshold of the helical kink instability. The contributions by shear and twist to the total rotation can be disentangled in the analysis of observations if the rotation and rise profiles are simultaneously compared with model calculations. The resulting twist estimate allows one to judge whether the helical kink instability occurred. This is demonstrated for the erupting prominence in the "Cartwheel CME" on 9 April 2008, which has shown a rotation of \approx 115 degrees up to a height of 1.5 R_sun above the photosphere. Out of a range of initial equilibria which include strongly kink-unstable (twist Phi=5pi), weakly kink-unstable (Phi=3.5pi), and kink-stable (Phi=2.5pi) configurations, only the evolution of the weakly kink-unstable flux rope matches the observations in their entirety.Comment: Solar Physics, submitte

New results from the NA57 experiment

We report results from the experiment NA57 at CERN SPS on hyperon production at midrapidity in Pb-Pb collisions at 158 $A$ GeV/$c$ and 40 $A$ GeV/$c$. $\Lambda$, $\Xi$ and $\Omega$ yields are compared with those from the STAR experiment at the higher energy of the BNL RHIC. $\Lambda$, $\Xi$, $\Omega$\ and preliminary $K_S^0$ transverse mass spectra are presented and interpreted within the framework of a hydro-dynamical blast wave model.Comment: 8 pages, 3 figures, contribution to the proceedings of The XXXVIIIth Rencontres de Moriond "QCD and High Energy Hadronic Interactions

Results on hyperon production from the NA57 experiment

Recent results on hyperon production in Pb--Pb collisions from the NA57 experiment are reported. Strangeness enhancement and the transverse mass spectra properties at 158 GeV per nucleon are described.Comment: submitted to Acta Phys. Hung. A (Heavy Ion Physics

Strange particle production in 158 and 40 AA GeV/cc Pb-Pb and p-Be collisions

Results on strange particle production in Pb-Pb collisions at 158 and 40 $A$ GeV/$c$ beam momentum from the NA57 experiment at CERN SPS are presented. Particle yields and ratios are compared with those measured at RHIC. Strangeness enhancements with respect to p-Be reactions at the same beam momenta have been also measured: results about their dependence on centrality and collision energy are reported and discussed.Comment: Contribution to the proceedings of the "Hot Quarks 2004" Conference, July 18-24 2004, New Mexico, USA, submitted to Journal of Physics G 7 pages, 5 figure

The Swift X-Ray Te1escope: Status and Performance

We present science highlights and performance from the Swift X-ray Telescope (XRT), which was launched on November 20,2004. The XRT covers the 0.2-10 keV band, and spends most of its time observing gamma-ray burst (GRB) afterglows, though it has also performed observations of many other objects. By mid-August 2007, the XRT had observed over 220 GRB afterglows, detecting about 96% of them. The XRT positions enable followup ground-based optical observations, with roughly 60% of the afterglows detected at optical or near IR wavelengths. Redshifts are measured for 33% of X-ray afterglows. Science highlights include the discovery of flaring behavior at quite late times, with implications for GRB central engines; localization of short GRBs, leading to observational support for compact merger progenitors for this class of bursts; a mysterious plateau phase to GRB afterglows; as well as many other interesting observations such as X-ray emission from comets, novae, galactic transients, and other objects

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02