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P.T.P.R. and P.J.B. acknowledge financial support from Diamond Light Source and EPSRC. G.C. acknowledges financial support from the EU through the ERC Grant “VISUAL-MS” (Project ID: 308115). B.S. and R.J.M. acknowledge doctoral studentship funding from the EPSRC and the National Productivity Investment Fund (NPIF). R.J.M. acknowledges financial support via a UKRI Future Leaders Fellowship (MR/S016023/1). The results are presented of a detailed combined experimental and theoretical investigation of the influence of coadsorbed electron-donating alkali atoms and the prototypical electron acceptor molecule 7,7,8,8-tetracyanoquinodimethane (TCNQ) on the Ag(100) surface. Several coadsorption phases were characterized by scanning tunneling microscopy, low-energy electron diffraction, and soft X-ray photoelectron spectroscopy. Quantitative structural data were obtained using normal-incidence X-ray standing wave (NIXSW) measurements and compared with the results of density functional theory (DFT) calculations using several different methods of dispersion correction. Generally, good agreement between theory and experiment was achieved for the quantitative structures, albeit with the prediction of the alkali atom heights being challenging for some methods. The adsorption structures depend sensitively on the interplay of molecule–metal charge transfer and long-range dispersion forces, which are controlled by the composition ratio between alkali atoms and TCNQ. The large difference in atomic size between K and Cs has negligible effects on stability, whereas increasing the ratio of K/TCNQ from 1:4 to 1:1 leads to a weakening of molecule–metal interaction strength in favor of stronger ionic bonds within the two-dimensional alkali–organic network. A strong dependence of the work function on the alkali donor–TCNQ acceptor coadsorption ratio is predicted. Publisher PDF

A novel way for calculating the diffusion-weighted nuclear magnetic resonance (NMR) attenuation signal expression in the presence of a background gradient is developed. This method is easily applicable to NMR-attenuated signals arising from any pulse field gradient sequence experiments. Here, we provide detailed calculations for the classical pulsed gradient stimulated echo and the pulsed gradient spin echo, as the particular cases. Within this general theoretical framework, devised for Gaussian processes with stationary increments, we recover and extend the previous Stejskal–Tanner results in the case of normal diffusion and we furnish a new expression in the case of anomalous diffusion.

The goal of the ASACUSA (Atomic Spectroscopy And Collisions Using Slow Antiprotons) CUSP experiment at CERN's Antiproton Decelerator is to measure the ground state hyperfine splitting of antihydrogen in order to test whether CPT invariance is broken. The ASACUSA hodoscope is a detector consisting of two layers of 32 plastic scintillator bars individually read out by two serially connected silicon photo multipliers (SiPMs) on each end. Two additional layers for position resolution along the beam axis were scintillator fibres, which will now be replaced by scintillating tiles placed onto the existing bars and also read out by SiPMs. If the antiproton of antihydrogen annihilates in the center of the hodoscope, particles (mostly pions) are produced and travel through the various layers of the detector and produce signals. The hodoscope was successfully used during the last data taking period at CERN. The necessary time resolution to discriminate between particles travelling through the detector from outside and particles produced in the center of the detector was achieved by the use of waveform digitisers and software constant fraction discrimination. The disadvantage of this readout scheme was the slow readout speed, which was improved by two orders of magnitude. This was done by omitting the digitisers and replacing them with TDCs reading out the digital time-over-threshold (ToT) signal using leading edge discrimination., Submitted to VCI2022 Proceedings in NIM A

International audience; Several factors can contribute to the difficulty of aligning the sensors of tracking detectors, including a large number of modules, multiple types of detector technologies, and non-linear strip patterns on the sensors. The latter two of these three factors apply to the CLAS12 CVT, which is a hybrid detector consisting of planar silicon sensors with non-parallel strips, and cylindrical micromegas sensors with longitudinal and arc-shaped strips located within a 5 T superconducting solenoid. To align this detector, we used the Kalman Alignment Algorithm, which accounts for correlations between the alignment parameters without requiring the time-consuming inversion of large matrices. This is the first time that this algorithm has been adapted for use with hybrid technologies, non-parallel strips, and curved sensors. We present the results for the first alignment of the CLAS12 CVT using straight tracks from cosmic rays and from a target with the magnetic field turned off. After running this procedure, we achieved alignment at the level of l. 967 10μm, and the widths of the residual spectra were greatly reduced. These results attest to the flexibility of this algorithm and its applicability to future use in the CLAS12 CVT and other hybrid or curved trackers, such as those proposed for the future Electron-Ion Collider.

To evaluate the content, sources, and quality of contact lens (CL)-related videos on TikTok, the fastest growing social media platform worldwide.TikTok was queried on October 25, 2021 for the top 200 posts with the hashtag "#contactlenses." Posts meeting inclusion criteria were characterized and assessed for quality with DISCERN, a validated scoring instrument for the appraisal of consumer health information (score range 1-5 with a higher score indicating a higher quality video).The included 113 posts showed a mean quality of 1.94±0.44. Content included product displays (42%), patient experiences (23%), educational (22%), and comedy (12%). Most product displays featured decorative lenses (98%). Although videos by eye-care providers (ECPs) accounted for most educational content (52%) and showed significantly higher mean quality compared with posts by non-ECPs (2.57±0.18 vs. 1.85±0.13, P0.001), they were a minority (12%) and showed poor overall quality. Contact lens representation was greatly skewed toward decorative lenses (74%), whereas only 3.5% of videos promoted seeing an ECP.Poor quality and skewed representation of posts indicate that CL-related information on TikTok has serious shortcomings. These findings are particularly concerning given that most TikTok users are adolescents and young adults, the same population who tend to be decorative lens wearers and who are at increased risk of CL-related complications. Eye-care providers, professional organizations, and regulatory agencies should be urged to increase their engagement with the platform, especially regarding educational content creation and CL marketing oversight.

We present the first measurement of di-hadron angular correlations in electron-nucleus scattering. The data were taken with the CLAS detector and a 5.0 GeV electron beam incident on deuterium, carbon, iron, and lead targets. Relative to deuterium, the nuclear yields of charged-pion pairs show a strong suppression for azimuthally opposite pairs, no suppression for azimuthally nearby pairs, and an enhancement of pairs with large invariant mass. These effects grow with increased nuclear size. The data are qualitatively described by the GiBUU model, which suggests that hadrons form near the nuclear surface and undergo multiple-scattering in nuclei. These results show that angular correlation studies can open a new way to elucidate how hadrons form and interact inside nuclei, Comment: 6 pages, 4 figures

We discuss two complementary strategies to search for light dark matter (LDM) exploiting the positron beam possibly available in the future at Jefferson Laboratory. LDM is a new compelling hypothesis that identifies dark matter with new sub-GeV "hidden sector" states, neutral under standard model interactions and interacting with our world through a new force. Accelerator-based searches at the intensity frontier are uniquely suited to explore it. Thanks to the high intensity and the high energy of the CEBAF (Continuous Electron Beam Accelerator Facility) beam, and relying on a novel LDM production mechanism via positron annihilation on target atomic electrons, the proposed strategies will allow us to explore new regions in the LDM parameters space, thoroughly probing the LDM hypothesis as well as more general hidden sector scenarios., 11 pages, 8 figures. Prepared for submission in EPJA. This work supersedes the corresponding contribution in arXiv:2007.15081. Added aknowledgement to Jefferson Lab

Magnetized nonneutral plasma composed of electrons or positrons couples to the local microwave environment via cyclotron radiation. The equilibrium plasma temperature depends on the microwave energy density near the cyclotron frequency. Fine copper meshes and cryogenic microwave absorbing material were used to lower the effective temperature of the radiation environment in ASACUSA's Cusp trap, resulting in significantly reduced plasma temperature.

AIM To characterize the neuro-ophthalmological phenotype of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) and assess visual acuity as a reproducible, quantitative outcome measure. METHOD We retrospectively analyzed clinical data from patients with CDD. Complete neuro-ophthalmological assessments, including visual acuity, were evaluated. RESULTS Of 26 patients (22 females, four males; median age 4y, interquartile range 2y 1mo-7y 10mo), cerebral visual impairment (CVI), defined as visual dysfunction in the absence of ocular or anterior visual pathway abnormalities, was diagnosed in all those over 2 years of age. Ophthalmological examinations revealed nystagmus in 10 patients and strabismus in 24 patients. Visual acuity was measured in 24 patients, by preferential looking in all and by sweep visual evoked potential in 13. Visual acuities were lower than age expectations and demonstrated improvement in the first 3 years. Adjusting for age and sex, average preferential looking visual acuity after 2 years of age was higher in patients with intact mobility than in those who were non-mobile. INTERPRETATION CVI was observed in patients with CDD. Visual acuity improved over time and correlated with mobility. Visual acuity, as a quantifiable measure of visual function, should be considered as an outcome measure in pre-clinical and clinical studies for CDD. What this paper adds Cerebral visual impairment is highly prevalent in cyclin-dependent kinase-like 5 deficiency disorder (CDD). Visual acuity is a measurable quantitative outcome measure in CDD. Visual acuity in CDD correlates with gross motor ability.

The observation of beam spin asymmetries in two-pion production in semi-inclusive deep inelastic scattering off an unpolarized proton target is reported for the first time. The data presented here were taken in the fall of 2018 with the CLAS12 spectrometer using a 10.6 GeV longitudinally spin-polarized electron beam delivered by CEBAF at JLab. The measured asymmetries provide the first observation of a signal that can be used to extract the PDF $e(x)$ in a collinear framework and the helicity-dependent two-pion fragmentation function $G_1^\perp$.

Wood is a hygroscopic, multi-scale and anisotropic natural material composed of pores with different size and differently oriented. In particular, archaeologically excavated wood generally is waterlogged wood with very high moisture content (400%-800%) that need to have a rapid investigation at the microstructural level to obtain the best treatment with preservative agents. Time-dependent diffusion coefficient D(t) quantified by Pulse Field Gradient (PFG) Nuclear Magnetic Resonance (NMR) techniques provides useful information about complex porous media, such as the tortuosity (τ) describing pore connectivity and fluid transport through media, the average-pore size, the anisotropic degree (an). However, diffusion NMR is intrinsically limited since it is an indirect measure of medium microstructure and relies on inferences from models and estimation of relevant diffusion parameters. Therefore, it is necessary to validate the information obtained from NMR diffusion parameters through complementary investigations. In this work, the structures of five waterlogged wood species were studied by PFG of absorbed water. D(t) and τ of water diffusing along and perpendicular to vessels/tracheids main axes together with relaxation times and an were quantified. From these parameters, the pore sizes distribution and the wood microstructure characterization were obtained. Results among wood species were compared, validated and integrated by micro-imaging NMR (μ-MRI), environmental-scanning electron-microscope (ESEM) images, wood dry density and imbibition times measurement of all woods. The work suggests that an vs τ rather than the estimated pore size diversifies and characterize the different wood species. As a consequence diffusion-anisotropy vs tortuosity could be an alternative method to characterize and differentiate wood species of waterlogged wood when high resolution images (μ-MRI and ESEM) are not available. Moreover, the combined use of D(t) and micro-MRI expands the scale of dimensions observable by NMR covering all the interesting length scales of wood.

The ASACUSA (Atomic Spectroscopy And Collisions Using Slow Antiprotons) collaboration plans to measure the ground-state hyperfine splitting of antihydrogen in a beam at the CERN Antiproton Decelerator with initial relative precision of 10-6 or better, to test the fundamental CPT (combination of charge conjugation, parity transformation and time reversal) symmetry between matter and antimatter. This challenging goal requires a polarised antihydrogen beam with a sufficient number of antihydrogen atoms in the ground state. The first measurement of the quantum state distribution of antihydrogen atoms in a low magnetic field environment of a few mT is described. Furthermore, the data-driven machine learning analysis to identify antihydrogen events is discussed., 18 pages, 10 figures

Positron beams, both polarized and unpolarized, are identified as essential ingredients for the experimental programs at the next generation of lepton accelerators. In the context of the hadronic physics program at Jefferson Lab (JLab), positron beams are complementary, even essential, tools for a precise understanding of the electromagnetic structure of nucleons and nuclei, in both the elastic and deep-inelastic regimes. For instance, elastic scattering of polarized and unpolarized electrons and positrons from the nucleon enables a model independent determination of its electromagnetic form factors. Also, the deeply-virtual scattering of polarized and unpolarized electrons and positrons allows unambiguous separation of the different contributions to the cross section of the lepto-production of photons and of lepton-pairs, enabling an accurate determination of the nucleons and nuclei generalized parton distributions, and providing an access to the gravitational form factors. Furthermore, positron beams offer the possibility of alternative tests of the Standard Model of particle physics through the search of a dark photon, the precise measurement of electroweak couplings, and the investigation of charged lepton flavor violation. This document discusses the perspectives of an experimental program with high duty-cycle positron beams at JLab., Comment: 18 pages, 7 figures This version superseeds the previous version which scientific content was decomposed into several more elaborated articles. All of these articles will be collected in the EPJ A Topical Issue about "Positron beam and physics at Jefferson Lab (e+@Jlab)"

Exposure to air pollution is a well-established risk factor for cardiovascular morbidity and mortality. Most of the evidence supporting an association between air pollution and adverse cardiovascular effects involves exposure to particulate matter (PM). To date, little attention has been paid to acute cardiovascular responses to ozone, in part due to the notion that ozone causes primarily local effects on lung function, which are the basis for the current ozone National Ambient Air Quality Standards (NAAQS). There is evidence from a few epidemiological studies of adverse health effects of chronic exposure to ambient ozone, including increased risk of mortality from cardiovascular disease. However, in contrast to the well-established association between ambient ozone and various nonfatal adverse respiratory effects, the observational evidence for impacts of acute (previous few days) increases in ambient ozone levels on total cardiovascular mortality and morbidity is mixed.Ozone is a prototypic oxidant gas that reacts with constituents of the respiratory tract lining fluid to generate reactive oxygen species (ROS) that can overwhelm antioxidant defenses and cause local oxidative stress. Pathways by which ozone could cause cardiovascular dysfunction include alterations in autonomic balance, systemic inflammation, and oxidative stress. These initial responses could lead ultimately to arrhythmias, endothelial dysfunction, acute arterial vasoconstriction, and procoagulant activity. Individuals with impaired antioxidant defenses, such as those with the null variant of glutathione S-transferase mu 1 (GSTM1), may be at increased risk for acute health effects.The Multicenter Ozone Study in oldEr Subjects (MOSES) was a controlled human exposure study designed to evaluate whether short-term exposure of older, healthy individuals to ambient levels of ozone induces acute cardiovascular responses. The study was designed to test the a priori hypothesis that short-term exposure to ambient levels of ozone would induce acute cardiovascular responses through the following mechanisms: autonomic imbalance, systemic inflammation, and development of a prothrombotic vascular state. We also postulated a priori the confirmatory hypothesis that exposure to ozone would induce airway inflammation, lung injury, and lung function decrements. Finally, we postulated the secondary hypotheses that ozone-induced acute cardiovascular responses would be associated with: (a) increased systemic oxidative stress and lung effects, and (b) the GSTM1-null genotype.The study was conducted at three clinical centers with a separate Data Coordinating and Analysis Center (DCAC) using a common protocol. All procedures were approved by the institutional review boards (IRBs) of the participating centers. Healthy volunteers 55 to 70 years of age were recruited. Consented participants who successfully completed the screening and training sessions were enrolled in the study. All three clinical centers adhered to common standard operating procedures (SOPs) and used common tracking and data forms. Each subject was scheduled to participate in a total of 11 visits: screening visit, training visit, and three sets of exposure visits, each consisting of the pre-exposure day, the exposure day, and the post-exposure day. The subjects spent the night in a nearby hotel the night of the pre-exposure day.On exposure days, the subjects were exposed for three hours in random order to 0 ppb ozone (clean air), 70 ppb ozone, and 120 ppm ozone, alternating 15 minutes of moderate exercise with 15 minutes of rest. A suite of cardiovascular and pulmonary endpoints was measured on the day before, the day of, and up to 22 hours after, each exposure. The endpoints included: (1) electrocardiographic changes (continuous Holter monitoring: heart rate variability [HRV], repolarization, and arrhythmia); (2) markers of inflammation and oxidative stress (C-reactive protein [CRP], interleukin-6 [IL-6], 8-isoprostane, nitrotyrosine, and P-selectin); (3) vascular function measures (blood pressure [BP], flow-mediated dilatation [FMD] of the brachial artery, and endothelin-1 [ET-1]; (4) venous blood markers of platelet activation, thrombosis, and microparticle-associated tissue factor activity (MP-TFA); (5) pulmonary function (spirometry); (6) markers of airway epithelial cell injury (increases in plasma club cell protein 16 [CC16] and sputum total protein); and (7) markers of lung inflammation in sputum (polymorphonuclear leukocytes [PMN], IL-6, interleukin-8 [IL-8], and tumor necrosis factor-alpha [TNF-α]). Sputum was collected only at 22 hours after exposure.The analyses of the continuous electrocardiographic monitoring, the brachial artery ultrasound (BAU) images, and the blood and sputum samples were carried out by core laboratories. The results of all analyses were submitted directly to the DCAC.The variables analyzed in the statistical models were represented as changes from pre-exposure to post-exposure (post-exposure minus pre-exposure). Mixed-effect linear models were used to evaluate the impact of exposure to ozone on the prespecified primary and secondary continuous outcomes. Site and time (when multiple measurements were taken) were controlled for in the models. Three separate interaction models were constructed for each outcome: ozone concentration by subject sex; ozone concentration by subject age; and ozone concentration by subject GSTM1 status (null or sufficient). Because of the issue of multiple comparisons, the statistical significance threshold was set a priori atSubject recruitment started in June 2012, and the first subject was randomized on July 25, 2012. Subject recruitment ended on December 31, 2014, and testing of all subjects was completed by April 30, 2015. A total of 87 subjects completed all three exposures. The mean age was 59.9 ± 4.5 years, 60% of the subjects were female, 88% were white, and 57% were GSTM1 null. Mean baseline body mass index (BMI), BP, cholesterol (total and low-density lipoprotein), and lung function were all within the normal range.We found no significant effects of ozone exposure on any of the primary or secondary endpoints for autonomic function, repolarization, ST segment change, or arrhythmia. Ozone exposure also did not cause significant changes in the primary endpoints for systemic inflammation (CRP) and vascular function (systolic blood pressure [SBP] and FMD) or secondary endpoints for systemic inflammation and oxidative stress (IL-6, P-selectin, and 8-isoprostane). Ozone did cause changes in two secondary endpoints: a significant increase in plasma ET-1 (Although our hypothesis focused on possible acute cardiovascular effects of exposure to low levels of ozone, we recognized that the initial effects of inhaled ozone involve the lower airways. Therefore, we looked for: (a) changes in lung function, which are known to occur during exposure to ozone and are maximal at the end of exposure; and (b) markers of airway injury and inflammation. We found an increase in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV₁) after exposure to 0 ppb ozone, likely due to the effects of exercise. The FEV₁ increased significantly 15 minutes after 0 ppb exposure (85 mL; 95% confidence interval [CI], 64 to 106;In this multicenter clinical study of older healthy subjects, ozone exposure caused concentration-related reductions in lung function and presented evidence for airway inflammation and injury. However, there was no convincing evidence for effects on cardiovascular function. Blood levels of the potent vasoconstrictor, ET-1, increased with ozone exposure (with marginal statistical significance), but there were no effects on BP, FMD, or other markers of vascular function. Blood levels of nitrotyrosine decreased with ozone exposure, the opposite of our hypothesis. Our study does not support acute cardiovascular effects of low-level ozone exposure in healthy older subjects. Inclusion of only healthy older individuals is a major limitation, which may affect the generalizability of our findings. We cannot exclude the possibility of effects with higher ozone exposure concentrations or more prolonged exposure, or the possibility that subjects with underlying vascular disease, such as hypertension or diabetes, would show effects under these conditions.

Acute respiratory effects of low-level ozone exposure are not well defined in older adults.MOSES (The Multicenter Ozone Study in Older Subjects), although primarily focused on acute cardiovascular effects, provided an opportunity to assess respiratory responses to low concentrations of ozone in older healthy adults.We performed a randomized crossover, controlled exposure study of 87 healthy adults (59.9 ± 4.5 yr old; 60% female) to 0, 70, and 120 ppb ozone for 3 hours with intermittent exercise. Outcome measures included spirometry, sputum markers of airway inflammation, and plasma club cell protein-16 (CC16), a marker of airway epithelial injury. The effects of ozone exposure on these outcomes were evaluated with mixed-effect linear models. A P value less than 0.01 was chosen a priori to define statistical significance.The mean (95% confidence interval) FEVExposure to ozone at near ambient levels induced lung function effects, airway injury, and airway inflammation in older healthy adults. Clinical trial registered with www.clinicaltrials.gov (NCT01487005).

The geometrical interpretation of density operators for open quantum system is investigated. After the discussion of stochastic mapping and the purifying lifts of curves of density matrices, the quantum analog of the classical recipe for the construction of an infinitesimal generator has been established. Despite the main contribution of the present paper in providing the formal expression of such generator, a simple experimental realization of a geometrically intuitive approach to variational inference also established. Nonetheless, the numerical results given here are competitive with those from the other methods used for quantum and classical systems and provide insight into the origin of properties of open quantum systems.

Dexamethasone Suppression Test (DST), recommended for Cushing’s Syndrome (CS) diagnosis, explores the pituitary feedback to glucocorticoids. Its diagnostic accuracy could be affected by dexamethasone bioavailability, and therefore, we have developed and validated a dexamethasone threshold after 1-mg DST. We studied 200 subjects: 125 patients were considered retrospectively and 75 were enrolled prospectively as the validation cohort. Serum dexamethasone, Late Night Salivary Cortisol (LNSC), and Urinary Free Cortisol (UFC) were measured with LC–MS/MS. Normal LNSC and UFC levels were used to exclude CS. The lower 2.5th percentile of dexamethasone distribution in non-CS patients with cortisol ≤ 50 nmol/L after 1-mg DST was used as threshold. 16 patients were CS and 184 non-CS (108 adrenal incidentaloma and 76 excluded CS); 4.5 nmol/L resulted the calculated threshold. Cortisol after 1-mg DST confirmed high sensitivity (100% at 50 nmol/L cut-off) and moderate–low specificity (63%, increased to 91% at 138 nmol/L) to diagnose CS in the whole cohort of patients. We could reduce the number of false-positive results (from 10 to 6 and from 7 to 4 in AI and excluded CS) considering adequate dexamethasone levels. Dexamethasone levels were not affected by hypercortisolism, age, gender, smoke, weight, and creatinine. 6% of non-CS patients did not achieve adequate dexamethasone levels (40% of tests with serum cortisol > 138 nmol/L after 1-mg DST). We developed and validated the routine dexamethasone measurement during 1-mg DST: it is independent from patient’s clinical presentation, and it should be used to increase the specificity of serum cortisol levels.

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

In 2001, the US Environmental Protection Agency (EPA) adopted stringent new standards for on-highway heavy heavy-duty diesel engine (HHDDE) emissions of particulate matter (PM) and oxides of nitrogen (NOx) that were to become effective during the 2007–2010 time period. The Advanced Collaborative Emissions Study (ACES) was a cooperative, multiparty effort to characterize the emissions (in Phases 1 and 2) and assess the possible health impacts (in Phase 3) of the new, advanced HHDDE technologies, after introducing them to the market. Phase 1 demonstrated that the regulated emissions from four 2007-compliant engines tested were all below the 2007 standards. Both regulated and unregulated emissions were substantially reduced relative to pre-2007 technology engines, except for nitrogen dioxide (NO2) emissions that were higher compared to 2004 technology engines due to the use of diesel oxidation catalyst (DOC) and catalyzed diesel particulate filter (DPF) exhaust aftertreatment technologies. Phase 2 showed another large step in emissions reductions for 2010-compliant diesel engines. The three 2010-compliant engines tested had substantially lower regulated emissions of NOx, CO, NMHC, and PM relative to the emission standards and also relative to the 2007-compliant engines. NOx reductions were achieved using urea-based selective catalytic reduction (SCR) and an ammonia oxidation catalyst (AMOX). A wide spectrum of particle and gas phase unregulated emissions species, including NO2, were also reduced relative to 2007-compliant engines and older engines. Phase 3 consisted of an inhalation bioassay in which rats were exposed for their lifetime to the diluted exhaust from one of the 2007-compliant engines tested in Phase 1. Three exhaust dilutions were selected based on the nitrogen dioxide (NO2) concentrations to achieve three exposure levels: 4.2 ppm (high-DE exposure), 0.8 ppm (mid-DE exposure), and 0.1 ppm (low-DE exposure) NO2. The control exposure consisted of filtered air. NO2 was chosen because the particle concentrations in the exhaust were too low to set the dilution levels. Exposures were conducted 16 h/day, 5 days/week. Rats were evaluated histopathologically and for respiratory function, a large number of noncancer endpoints, and genotoxicity, at interim time points up to the final sacrifice at 28 months (males) and 30 months (females). Histopathological analyses found that exposure to exhaust from a 2007-compliant engine produced no tumors or precancerous effects in lungs and no increase in tumor incidence outside the lung, but induced mild epithelial hyperplasia in the central acinus region of the lung, interstitial fibrosis, and bronchiolization at the high exposure level. The lung histologic changes were consistent with previous findings in rats after long-term exposure to NO2—a major component of the chamber exposure atmosphere, which is substantially reduced in 2010-compliant engines. The majority of the biological endpoints were unchanged with exposure and little inflammation was observed. In summary, the ACES study shows that emissions from 2007- and 2010-compliant HHDDE have been reduced dramatically and that exhaust from a 2007-compliant engine produced no tumors or precancerous effects in rats exposed over their lifetime.

The K free light chains index (K-FLC index) has been proposed as an alternative test for intrathecal immunoglobulin synthesis in MS diagnosis. Aim of the study was to assess the accuracy of the K-FLC index in differentiating MS from other immune-mediated CNS disorders and NMOSD. Data were available from a cohort of 371 patients. K-FLC index was significantly higher in MS: MS mean K-FLC index 90.897 ± 134.198; NMOSD 17.992 ± 15.103; other immune-mediated CNS disorders 12.568 ± 24.440. The overall diagnostic accuracy of the K-FLC index was similar to intrathecal oligoclonal bands detection. However, as a quantitative variable, K-FLC index allowed easier discrimination of MS from other immune-mediated CNS disorders: highest K-FLC index values (> 100) were observed almost only in MS and are therefore strongly predictive of MS, in patients with the appropriate clinical presentation.

QUPLAS (QUantum interferometry and gravitation with Positrons and LASers) is an experimental project for the study of antimatter; it makes use of positrons and positronium and mainly aims at performing quantum interferometry, decoherence and gravitational studies. The first phase of the project, called QUPLAS-0, consisted in the first successful demonstration of quantum interference of an antimatter particle: the positron. The experimental apparatus is composed by the positron beam, the interferometer, and the detector. This paper describes these three elements of QUPLAS-0 and how they were combined to achieve the goal of positron interference.

Dimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing–remitting multiple sclerosis (MS) in randomized clinical trials. To track and evaluate post-market DMF profile in real-world setting. Patients receiving DMF referred to Italian MS centres were enrolled and prospectively followed, collecting demographic clinical and radiological data. Among the 735 included patients, 45.4% were naive 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%). Our post-market study corroborated that DMF is a safe and effective drug. Additionally, the study suggested that naive 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.

Background To date, there have been relatively few studies of acute cardiovascular responses to controlled ozone inhalation, although a number of observational studies have reported significant positive associations between both ambient ozone levels and acute cardiovascular events and long-term ozone exposure and cardiovascular mortality. Objectives We hypothesized that short-term controlled exposure to low levels of ozone in filtered air would induce autonomic imbalance, repolarization abnormalities, arrhythmia, and vascular dysfunction. Methods This randomized crossover study of 87 healthy volunteers 55–70 years of age was conducted at three sites using a common protocol, from June 2012 to April 2015. Subjects were exposed for 3 h in random order to 0 ppb (filtered air), 70 ppb ozone, and 120 ppb ozone, alternating 15 min of moderate exercise with 15 min of rest. A suite of cardiovascular endpoints was measured the day before, the day of, and up to 22 h after each exposure. Mixed effect linear and logit models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. Site and time were included in the models. Results We found no significant effects of ozone exposure on any of the primary or secondary measures of autonomic function, repolarization, ST segment change, arrhythmia, or vascular function (systolic blood pressure and flow-mediated dilation). Conclusions In this multicenter study of older healthy women and men, there was no convincing evidence for acute effects of 3-h, relatively low-level ozone exposures on cardiovascular function. However, we cannot exclude the possibility of effects with higher ozone concentrations, more prolonged exposure, or in subjects with underlying cardiovascular disease. Further, we cannot exclude the possibility that exposure to ambient ozone and other pollutants in the days before the experimental exposures obscured or blunted cardiovascular biomarker response to the controlled ozone exposures.

Background and aims To explore predictors of renal remission, insufficiency and damage in lupus nephritis (LN). Methods We retrospectively analysed our lupus cohort and studied LN patients with at least one renal biopsy since 1990 until 2016. Follow-up ended at last patient visit. Complete renal remission (CRR) was defined as proteinuria 0.5 g/day and/or requirement for treatment modifications. Damage was measured by SLICC damage index (SDI). Results 81 patients were studied (Table) who underwent 110 biopies. Forty patients (49.3%) went into CRR by the end of follow-up. Thirty-six (44.5%) had 2 renal flares while 21≥3 (26%). Six patients developed renal failure preceded by ≥3 flares in 5. One case of ESRD was reported. By the end of follow-up 30 patients (37%) had SDI≥2. At univariate analysis, increased proteinuria at 12 and 24 months from first biopsy and higher flare number were inversely associated with CRR, while long-lasting hypertension, abnormal SCr, decreased GFR and C4 at time of first biopsy were associated with renal failure. At multivariate analysis 24h-proteinuria at 24 months independently predicted lack of CRR (OR 3.7), while a higher number of renal flares (OR 5.27), higher SCr at 6 months from renal biopsy (OR 5.01) and a longer disease duration (OR 6.34) were independently associated with damage accrual. Conclusions Increased proteinuria and abnormal baseline renal function make CRR unlikely. Suboptimal control of LN activity and longer disease duration are associated with severe damage accrual.

Let $${{\fancyscript{S}}}$$ be an ideal of subsets of a metric space $${{\langle X, d \rangle}}$$ , and for $${{E \subseteq X}}$$ , let $${{E^{\varepsilon}}}$$ denote the $${{\varepsilon}}$$ -enlargement of E. A net of subsets $${\langle A_{i} \rangle}$$ of X is called $${{\fancyscript{S}^{-}}}$$ -convergent (resp. $${{\fancyscript{S}^{+}}}$$ -convergent) to a subset A of X if for each $${{S \in \fancyscript{S}}}$$ and each $${{\varepsilon > 0}}$$ , we have eventually $${{A \cap S \subseteq A^{\varepsilon}_{i}}}$$ (resp $${{A_{i}S \cap A \subseteq A^{\varepsilon})}}$$ . The purpose of this article is to give simple necessary and sufficient conditions for the lower and upper $${{\fancyscript{S}}}$$ -convergences to be topological on the power set of X and on the closed subsets of X. In the first environment, the condition for upper convergence is stronger than that for lower convergence, while in the second more restrictive environment, it is stronger if and only if $${{\cup\fancyscript{S}}}$$ is an open subset of X. In our analysis there arises a pregnant new idea – that of one set serving to shield a fixed subset from closed sets – that we study in detail, and which plays an interesting role in the upper semicontinuity of multifunctions.

“Air Pollution and Health: Bridging the Gap from Sources to Health Outcomes,” an international specialty conference sponsored by the American Association for Aerosol Research, was held to address key uncertainties in our understanding of adverse health effects related to air pollution and to integrate and disseminate results from recent scientific studies that cut across a range of air pollution-related disciplines. The Conference addressed the science of air pollution and health within a multipollutant framework (herein “multipollutant” refers to gases and particulate matter mass, components, and physical properties), focusing on five key science areas: sources, atmospheric sciences, exposure, dose, and health effects. Eight key policy-relevant science questions integrated across various parts of the five science areas and a ninth question regarding findings that provide policy-relevant insights served as the framework for the meeting. Results synthesized from this Conference provide new evidence, reaffirm past findings, and offer guidance for future research efforts that will continue to incrementally advance the science required for reducing uncertainties in linking sources, air pollutants, human exposure, and health effects. This paper summarizes the Conference findings organized around the science questions. A number of key points emerged from the Conference findings. First, there is a need for greater focus on multipollutant science and management approaches that include more direct studies of the mixture of pollutants from sources with an emphasis on health studies at ambient concentrations. Further, a number of research groups reaffirmed a need for better understanding of biological mechanisms and apparent associations of various health effects with components of particulate matter (PM), such as elemental carbon, certain organic species, ultrafine particles, and certain trace elements such as Ni, V, and Fe(II), as well as some gaseous pollutants. Although much debate continues in this area, generation of reactive oxygen species induced by these and other species present in air pollution and the resulting oxidative stress and inflammation were reiterated as key pathways leading to respiratory and cardiovascular outcomes. The Conference also underscored significant advances in understanding the susceptibility of populations, including the role of genetics and epigenetics and the influence of socioeconomic and other confounding factors and their synergistic interactions with air pollutants. Participants also pointed out that short- and long-term intervention episodes that reduce pollution from sources and improve air quality continue to indicate that when pollution decreases so do reported adverse health effects. In the limited number of cases where specific sources or PM2.5 species were included in investigations, specific species are often associated with the decrease in effects. Other recent advances for improved exposure estimates for epidemiological studies included using new technologies such as microsensors combined with cell phone and integrated into real-time communications, hybrid air quality modeling such as combined receptor- and emission-based models, and surface observations used with remote sensing such as satellite data.

The Advanced Collaborative Emissions Study was designed to determine whether new technology heavy-duty diesel engines (NTDE) that are compliant with 2007 and 2010 EPA emissions standards for PM and...

The objective of the Advanced Collaborative Emissions Study (ACES) was to determine before widespread commercial deployment whether or not the new, energy-efficient, heavy duty diesel engines (2007 and 2010 EPA Emissions Standards Compliant) may generate anticipated toxic emissions that could adversely affect the environment and human health. ACES was planned to take place in three phases. In Phase 1, extensive emissions characterization of four production-intent prototype engine and control systems designed to meet 2007 standards for nitrogen oxides (NOx) and particulate matter (PM) was conducted at an existing emissions characterization facility: Southwest Research Institute (SwRI). One of the tested engines was selected (at random, after careful comparison of results) for health testing in Phase 3. In Phase 2, extensive emission characterization of three production-intent prototype engine and control systems meeting the 2010 standards (including more advanced NOx controls to meet the more stringent 2010 NOx standards) was conducted at the same test facility. In Phase 3, one engine/aftertreatment system selected from Phase 1 was further characterized during health effects studies (at an existing inhalation toxicology laboratory: Lovelace Respiratory Research Institute, [LRRI]) to form the basis of the ACES safety assessment. The Department of Energy (DOE) award provided funding for emissionsmore » characterization in Phases 1 and 2 as well as exposure characterization in Phase 3. The main health analyses in Phase 3 were funded separately and are not reported here.« less

Thermal nucleation of kink-antikink pairs in an elastic string subjected to a washboard potential is analyzed in the limit of low temperature and high damping. The pair nucleation rate is calculated analytically for any value of the tilt up to close the instability threshold. Finite-size effects are quantified by computing the relevant end-point nucleation rate under a wide class of boundary conditions. Applications to the physics of lattice dislocations and flux lines in type-II superconducting materials are outlined.

The use of oxygenated fuels is anticipated to increase over the next decades. This paper reviews the toxicological and exposure information for methyl tertiary-butyl ether (MTBE), a fuel additive, and methanol, a replacement fuel, and discusses the possible health consequences of exposure of the general public to these compounds. For MTBE, the health effects information available is derived almost exclusively from rodent studies, and the exposure data are limited to a few measurements at some service stations. Based on these data, it appears unlikely that the normal population is at high risk of exposure to MTBE vapor. However, in the absence of health and pharmacokinetic data in humans or in nonhuman primates, this conclusion is not strongly supported. Similarly, there are a number of uncertainties to take into consideration in estimating human risk from the use of methanol as a fuel. Although methanol may be toxic to humans at concentrations that overwhelm certain enzymes involved in methanol metabolism, the data available provide little evidence to indicate that exposure to methanol vapors from the use of methanol as a motor vehicle fuel will result in adverse health effects. The uncertainties in this conclusion are based on the lack of information on dose-response relationship at reasonable, projected exposure levels and of studies examining end points of concern in sensitive species. In developing a quantitative risk assessment, more needs to be known about health effects in primates or humans and the range of exposure expected for the general public for both compounds.

We diagonalize the XX model with a finite number of spins and periodic boundary conditions. We solve for the ground state, focus on the rapidity of the convergence to the thermodynamic limit and study the features of multipartite entanglement., Comment: 12 pages, 11 figures

The 4S polycyclic aromatic hydrocarbon (PAH)-binding protein (PBP) is a cytoplasmic protein that binds PAHs with specificity and high affinity. We have used antisera for the PBP and unlabeled peroxidase anti-peroxidase immunohistochemistry to demonstrate its possible localization in cell types known to have xenobiotic metabolizing capabilities. Cellular sites of the PBP in liver, lung and kidney of C57BL/6 and DBA/2 mice were probed. The PBP was visualized in hepatocytes throughout the liver lobule and was not preferentially located in either centrilobular or periportal areas. However, cellular heterogeneity with respect to PBP content was clearly evident in the hepatocyte population. The positive reactivity correlated with substantial levels of benzo[a]pyrene (B[a]P) binding in liver cytosol. In the lung, the PBP was found in the bronchiolar epithelium and the alveolar septa, and was localized in ciliated and non-ciliated Clara and alveolar type II cells as well as in alveolar macrophages. In the kidney, the glomeruli and epithelia of proximal and distal convoluted tubules and collecting ducts were labeled. Staining for the PBP was greatest in the apical region of the pyramid and was localized in the epithelial lining of the collecting ducts. Relatively lower levels of the PBP were detected in the lung and kidney than in the liver. Staining was localized in the cytoplasmic compartment of cells in all tissues examined. Similar immunoreactivities were exhibited in the tissues of both C57BL/6 and DBA/2 mice. Treatment with beta-naphthoflavone (beta NF) altered neither the intensity nor pattern of immunostaining. Furthermore, treatment with beta NF or isosafrole has no effect on the Kd and Bmax of B[a]P binding to liver cytosolic PBP. The results of our experiments demonstrate localization of the PBP to sites of active physiological response to PAH exposure.

In this paper, we present a tabu-search based algorithm that optimizes routing for packet switching networks. The problem of routing optimization can be seen as the search of the shortest path in a graph, where the bandwidths of connections, together with their traffic, can be considered as weights. This kind of optimization is usually carried out by means of the well-known Dijkstra algorithm or its various implementations. However, an exhaustive research tends to be very heavy, from a computational point of view, when the number of nodes gets high. For this reason, we opt for a meta-heuristic algorithm, particularly tabu search, capable of finding a non-optimal solution, that can be considered quite good, even without the need of an exhaustive research.

In this paper, we present an innovative Neural Network system interface that allows an electronic music composer to plan and conduct the musical expressivity of a performer. For musical expressivity we mean all those execution techniques and modalities that a performer has to follow in order to satisfy common musical aesthetics, as well as the desiderata of the composer. The proposed interface or virtual musical instrument is able to transform two input parameters in many sound synthesis parameters. Especially, we focus our attention on mapping strategies based on Neural Network to solve the problem of electronic music expressivity.