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The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p<0.01. There were no effects of ozone on the three primary markers of systemic inflammation and a prothrombotic state: C-reactive protein, monocyte-platelet conjugates, and microparticle-associated tissue factor activity. However, among the secondary endpoints, endothelin-1, a potent vasoconstrictor, increased from pre- to post-exposure with ozone concentration (120 vs 0 ppb: 0.07 pg/mL, 95% confidence interval [CI] 0.01, 0.14; 70 vs 0 ppb: -0.03 pg/mL, CI -0.09, 0.04; p = 0.008). Nitrotyrosine, a marker of oxidative and nitrosative stress, decreased with increasing ozone concentrations, with marginal significance (120 vs 0 ppb: -41.5, CI -70.1, -12.8; 70 vs 0 ppb: -14.2, CI -42.7, 14.2; p = 0.017). GSTM1 status did not modify the effect of ozone exposure on any of the outcomes. These findings from healthy older adults fail to identify any mechanistic basis for the epidemiologically described cardiovascular effects of exposure to ozone. The findings, however, may not be applicable to adults with cardiovascular disease.

Background Reduced arm swing movements during gait are an early motor manifestation of Parkinson’s disease (PD). The clinical evolution, response to L-Dopa and pathophysiological underpinning of abnormal arm swing movements in PD remain largely unclear. By using a network of wearable sensors, this study objectively assesses arm swing movements during gait in PD patients across different disease stages and therapeutic conditions. Methods Twenty healthy subjects (HS) and 40 PD patients, including 20 early-stage and 20 mid-advanced subjects, underwent a 6-m Timed Up and Go test while monitored through a network of wearable inertial sensors. Arm swing movements were objectively evaluated in both hemibodies and different upper limb joints (shoulder and elbow), using specific time-domain (range of motion and velocity) and frequency-domain measures (harmonics and total harmonic distortion). To assess the effects of L-Dopa, patients under chronic dopaminergic therapy were randomly examined when OFF and ON therapy. Finally, clinical-behavioral correlations were investigated, primarily focusing on the relationship between arm swing movements and cardinal L-Dopa-responsive motor signs, including bradykinesia and rigidity. Results Compared to HS, the whole group of PD patients showed reduced range of motion and velocity, alongside increased asymmetry of arm swing movements during gait. Additionally, a distinct increase in total harmonic distortion was found in patients. The kinematic changes were prominent in the early stage of the disease and progressively worsened owing to the involvement of the less affected hemibody. The time- and frequency-domain abnormalities were comparable in the two joints (i.e., shoulder and elbow). In the subgroup of patients under chronic dopaminergic treatment, L-Dopa restored patterns of arm swing movements. Finally, the kinematic alterations in arm swing movements during gait correlated with the clinical severity of bradykinesia and rigidity. Conclusions Arm swing movements during gait in PD are characterized by narrow, slow, and irregular patterns. As the disease progresses, arm swing movements deteriorate also in the less affected hemibody, without any joint specificity. The positive response to L-Dopa along with the significant correlation between kinematics and bradykinesia/rigidity scores points to the involvement of dopaminergic pathways in the pathophysiology of abnormal arm swing movements in PD.

The mechanism of antiproton–nucleus annihilation at rest is not fully understood, despite substantial previous experimental and theoretical work. In this study we used slow extracted antiprotons from the ASACUSA apparatus at CERN to measure the charged particle multiplicities and their energy deposits from antiproton annihilations at rest on three different nuclei: carbon, molybdenum and gold. The results are compared with predictions from different models in the simulation tools Geant4 and FLUKA. A model that accounts for all the observed features is still missing, as well as measurements at low energies, to validate such models.

The right hemisphere is involved with the integrative processes necessary to achieve global coherence during reasoning and discourse processing. Specifically, the right temporal lobe has been proven to facilitate the processing of distant associate relationships, such as generating novel ideas. Previous studies showed a specific swing of alpha and gamma oscillatory activity over the right parieto-occipital lobe and the right anterior temporal lobe respectively, when people solve semantic problems with a specific strategy, i.e., insight problem-solving. In this study, we investigated the specificity of the right parietal and temporal lobes for semantic integration using transcranial Random Noise Stimulation (tRNS). We administered a set of pure semantics (i.e., Compound Remote Associates [CRA]) and visuo-semantic problems (i.e., Rebus Puzzles) to a sample of 31 healthy volunteers. Behavioral results showed that tRNS stimulation over the right temporal lobe enhances CRA accuracy (+12%), while stimulation on the right parietal lobe causes a decrease of response time on the same task (−2,100 ms). No effects were detected for Rebus Puzzles. Our findings corroborate the involvement of the right temporal and parietal lobes when solving purely semantic problems but not when they involve visuo-semantic material, also providing causal evidence for their postulated different roles in the semantic integration process and promoting tRNS as a candidate tool to boost verbal reasoning in humans.

BackgroundDimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing–remitting multiple sclerosis (MS) in randomized clinical trials.ObjectivesTo track and evaluate post-market DMF profile in real-world setting.Materials and methodsPatients receiving DMF referred to Italian MS centres were enrolled and prospectively followed, collecting demographic clinical and radiological data.ResultsAmong the 735 included patients, 45.4% were naïve to disease-modifying therapies, 17.8% switched to DMF because of tolerance, 27.4% switched to DMF because of lack of efficacy, and 9.4% switched to DMF because of safety concerns. Median DMF exposure was 17 months (0–33). DMF reduced the annual relapse rate (ARR) by 63.2%. At 12 and 24 months, 85 and 76% of patients were relapse-free. NEDA-3 status after 12 months of DMF treatment was maintained by 47.5% of patients. 89 and 70% of patients at 12 and 24 months regularly continued DMF. Most frequent adverse events (AEs) were flushing (37.2%) and gastro-enteric AEs (31.1%).ConclusionOur post-market study corroborated that DMF is a safe and effective drug. Additionally, the study suggested that naïve patients strongly benefit from DMF and that DMF improved ARR also in patients who were horizontally switched from injectable therapies due to tolerability and efficacy issues.

We study the interaction between a positron beam in the single-particle regime in an interferometric configuration and a microwave electromagnetic field. We discuss the conditions under which quantum interference can be affected by the field and we outline its possible experimental study in the framework of QUantum interferometry and gravitation with Positrons and LASers (QUPLAS) experiment.

The double-spin-polarization observable E for γ→p→→pπ0 has been measured with the CEBAF Large Acceptance Spectrometer (CLAS) at photon beam energies Eγ from 0.367 to 2.173GeV (corresponding to center-of-mass energies from 1.240 to 2.200GeV) for pion center-of-mass angles, cosθπ0c.m., between - 0.86 and 0.82. These new CLAS measurements cover a broader energy range and have smaller uncertainties compared to previous CBELSA data and provide an important independent check on systematics. These measurements are compared to predictions as well as new global fits from The George Washington University, Mainz, and Bonn-Gatchina groups. Their inclusion in multipole analyses will allow us to refine our understanding of the single-pion production contribution to the Gerasimov-Drell-Hearn sum rule and improve the determination of resonance properties, which will be presented in a future publication.

Methods for reducing the radius, temperature and space charge of a non-neutral plasma are usually reported for conditions which approximate an ideal Penning Malmberg trap. Here, we show that (i) similar methods are still effective under surprisingly adverse circumstances: we perform strong drive regime (SDR) compression and SDREVC in a strong magnetic mirror field using only 3 out of 4 rotating wall petals. In addition, we demonstrate (ii) an alternative to SDREVC, using e-kick instead of evaporative cooling (EVC) and (iii) an upper limit for how much plasma can be cooled to $T<20\\ \\mathrm {K}$ using EVC. This limit depends on the space charge, not on the number of particles or the plasma density.

The ASACUSA (atomic spectroscopy and collisions using slow antiprotons) Cusp experiment requires the production of dense positron plasmas with a high repetition rate to produce a beam of antihydrogen. In this work, details of the positron production apparatus used for the first observation of the antihydrogen beam, and subsequent measurements, are described in detail. This apparatus replaced the previous compact trap design resulting in an improvement in the positron accumulation rate by a factor of $52\\pm 3$.

The ASACUSA collaboration produces a beam of antihydrogen atoms by mixing pure positron and antiproton plasmas in a strong magnetic field with a double cusp geometry. The positrons cool via cyclotron radiation inside the cryogenic trap. Low positron temperature is essential for increasing the fraction of antihydrogen atoms which reach the ground state prior to exiting the trap. Many experimental groups observe that such plasmas reach equilibrium at a temperature well above the temperature of the surrounding electrodes. This problem is typically attributed to electronic noise and plasma expansion, which heat the plasma. The present work reports anomalous heating far beyond what can be attributed to those two sources. The heating seems to be a result of the axially open trap geometry, which couples the plasma to the external (300 K) environment via microwave radiation.