Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

Modélisation du poly-époxy DGEBA-EDA et de sa réactivité vis-à-vis du cuivre : approche expérimentale et numérique

Grâce à la métallisation de leur surface, des pièces en polymères peuvent substituer certains composants métalliques dans les industries de l'aérospatiale et du transport. Les polymères ont des masses volumiques plus faibles que les métaux et une réactivité chimique limitée, ce qui en fait des candidats idéaux pour les applications spatiales. En combinant techniques expérimentales et simulations numériques, nous avons étudié les mécanismes fondamentaux de la métallisation de surface d'un polymère poly-époxy (DGEBA / EDA). L'objectif de notre étude était de développer un modèle non empirique prenant en compte les mécanismes régissant la nucléation et la croissance des films minces métalliques. Notre groupe a une longue expérience des dépôts chimiques en phase vapeur, CVD. Mais cette technique n'a pas été choisie pour la métallisation de nos surfaces de polymères car les températures requises dans le réacteur étaient trop élevées. Comme alternative, nous avons effectué une évaporation sous ultravide de Cu à température ambiante, conduisant à une diffusion des atomes en phase gazeuse sans énergie cinétique. Les processus d'adsorption et de diffusion sont donc plus proches des conditions thermodynamiques associées aux calculs. Un protocole expérimental a été mis en place afin de créer une surface polymère chimiquement homogène présentant une faible rugosité. Le polymère obtenu a été caractérisé (i) par spectroscopie infrarouge à transformée de Fourier, pour déterminer le taux de polymérisation (supérieur à 90%), (ii) par calorimétrie différentielle à balayage pour obtenir la température de transition vitreuse (Tg) ( 118,1 °C), (iii) par microscopie à force atomique (AFM) pour estimer la rugosité de la surface (Ra ˜ 1 nm), et (iv) par spectroscopie de photoélectrons X (XPS) pour caractériser les liaisons chimiques de surface. La surface de polymère a ensuite été métallisée. Grâce à des analyses AFM, l'épaisseur du film mince a été estimée à 6 nm. Nous avons ensuite utilisé l'XPS pour caractériser les liaisons interfaciales Cu / Poly-époxy. Nous avons déduit de l'interprétation des spectres XPS que le Cu est adsorbé préférentiellement sur un atome d'oxygène spécifique du polymère. Pour identifier clairement ces sites d'adsorption de Cu, nous avons ensuite simulé les spectres XPS du polymère non revêtu, par des calculs quantiques, en utilisant un modèle moléculaire (dimère : 1 molécule de DGEBA liée à 1 molécule d'EDA). Les méthodes Hartree-Fock (HF) et de la théorie de la fonctionnelle de la densité (DFT) nous ont permis de simuler des spectres XPS pour la surface nue, en prenant en compte les effets d'état final et initial. Grâce à ces résultats, nous avons pu décomposer le spectre expérimental en 8 contributions, ce qui conduit à des résultats beaucoup plus précis que les résultats habituels obtenus par l'utilisation exclusive des expériences et de la littérature. Nous avons ensuite effectué des simulations de dynamique moléculaire classique (MD) pour passer d'un modèle moléculaire (dimère) à un modèle de polymère amorphe. Nous avons utilisé le champ de force Amber généralisé (GAFF) et nous avons développé un code de réticulation des molécules de monomères. Le système initial était un mélange stœchiométrique de molécules DGEBA et EDA qui a été équilibré à 700K. Lorsque l'équilibre a été atteint, certaines propriétés structurales (par exemple, la distribution des liaisons) ont été extraites des simulations NPT. À partir de ce mélange liquide de monomères, notre code de réticulation a identifié et relié les atomes réactifs (à une distance interatomique prédéfinie < 3 Å). Après chaque étape de polymérisation, le système a été rééquilibré à 700K (simulations NPT). Après plusieurs cycles de réticulation/simulation de dynamique moléculaire, nous avons pu atteindre un taux de polymérisation de 93% et la fonction de distribution radiale (RDF), la masse volumique (1.115 à 300K) et la température de transition vitreuse Tg (115,5 °C) ont été calculées. La Tg est en accord avec la valeur expérimentale de 118,1 °C, validant notre approche numérique pour développer un modèle pour les polymères poly-époxy.Metallization of polymer surfaces can lead to the substitution of metallic components. Polymers have lower densities and limited chemical reactivity, making them ideal candidates for the space applications. Through experiments and calculations, we studied the fundamental mechanisms of surface metallization of a poly-epoxy polymer (DGEBA/EDA). The objective of our study was to develop a non-empirical model that could take into account the mechanisms governing the nucleation and growth of thin metal films. Our group has a long experience in chemical vapor deposition, CVD, and metallization of polymer composites. But we did not applied CVD at first because of the high temperatures required in the reactor. We alternatively used ultrahigh vacuum evaporation of Cu at ambient temperature. Therefore, we make sure that atoms diffuse in the gas phase without kinetic energy. Adsorption and diffusion processes are thus closer to thermodynamic conditions that prevails in calculations. An experimental protocol was refined in order to create a chemically homogeneous polymer surface with a low roughness (Ra<1nm). The bulk and the surface of the pristine polymer were characterized (i) by Fourier Transform Infrared Spectroscopy, to determine the polymerization rate (above 90%), (ii) by differential scanning calorimetry in order to obtain the glass transition temperature (Tg) (118.1 °C), (iii) by atomic force microscopy (AFM) to calculate surface roughness (Ra ˜ 1 nm), and (iv) by X-ray photoelectron spectroscopy (XPS) to characterize surface chemical bonding. The surface was then metallized. Through AFM, the thickness of the thin film was estimated at 6 nm. We then used XPS to characterize the Cu/Poly-epoxy interfacial bonding. We deduced that Cu adsorbed preferentially on a specific oxygen atom of the polymer. To clearly identify this Cu adsorption site, we further simulated the XPS spectra of our clean or metallized polymer by quantum calculations, using a dimer model (1 molecule of DGEBA connected to 1 molecule of EDA). In the Hartree-Fock (HF) and Density Functional Theory (DFT) framework, we first simulated the XPS spectra for the pristine surface taking into account initial and final state effects. Thanks to these results, we were able to analyze the experimental spectrum with 8 contributions, leading to much more accurate results than the usual results obtained by the exclusive use of experiments and literature. We then performed classical Molecular Dynamics (MD) simulations to move from a dimer model to an amorphous polymer model. We used the general Amber force field (GAFF) and we developed a code to mimic the reticulation of monomers molecules. We started from a stoichiometric mixture of DGEBA and EDA molecules. When equilibration was reached, structural properties at 700K (e.g. distribution of bonds) were extracted from the results of the NPT simulations. From this melt of monomers, the homemade reticulation code identified and connected reactive atoms (at a pre-defined inter-atomic distance < 3Å). After each step of polymerization, the system was equilibrated at 700K (NPT simulations). After multiple reticulation/MD cycles we could achieve a polymerization rate of 93% and the Radial Distribution Function (RDF), the density and the glass transition temperature Tg were calculated. The value of the computed density was 1.115 at 300K and the calculated Tg (115.5 °C) was in good agreement with the experimental Tg of 118.1 °C, validating our numerical approach to develop a model for poly-epoxies

Characterization of the Clinical and Immunologic Phenotype and Management of 157 Individuals with 56 Distinct Heterozygous NFKB1 Mutations

Background: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. Objective: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. Methods: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. Results: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. Conclusions: We present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.info:eu-repo/semantics/publishedVersio

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2