LHCb upgrade software and computing : technical design report

This document reports the Research and Development activities that are carried out in the software and computing domains in view of the upgrade of the LHCb experiment. The implementation of a full software trigger implies major changes in the core software framework, in the event data model, and in the reconstruction algorithms. The increase of the data volumes for both real and simulated datasets requires a corresponding scaling of the distributed computing infrastructure. An implementation plan in both domains is presented, together with a risk assessment analysis

Physics case for an LHCb Upgrade II - Opportunities in flavour physics, and beyond, in the HL-LHC era

The LHCb Upgrade II will fully exploit the flavour-physics opportunities of the HL-LHC, and study additional physics topics that take advantage of the forward acceptance of the LHCb spectrometer. The LHCb Upgrade I will begin operation in 2020. Consolidation will occur, and modest enhancements of the Upgrade I detector will be installed, in Long Shutdown 3 of the LHC (2025) and these are discussed here. The main Upgrade II detector will be installed in long shutdown 4 of the LHC (2030) and will build on the strengths of the current LHCb experiment and the Upgrade I. It will operate at a luminosity up to 2×1034 cm−2s−1, ten times that of the Upgrade I detector. New detector components will improve the intrinsic performance of the experiment in certain key areas. An Expression Of Interest proposing Upgrade II was submitted in February 2017. The physics case for the Upgrade II is presented here in more depth. CP-violating phases will be measured with precisions unattainable at any other envisaged facility. The experiment will probe b → sl+l−and b → dl+l− transitions in both muon and electron decays in modes not accessible at Upgrade I. Minimal flavour violation will be tested with a precision measurement of the ratio of B(B0 → μ+μ−)/B(Bs → μ+μ−). Probing charm CP violation at the 10−5 level may result in its long sought discovery. Major advances in hadron spectroscopy will be possible, which will be powerful probes of low energy QCD. Upgrade II potentially will have the highest sensitivity of all the LHC experiments on the Higgs to charm-quark couplings. Generically, the new physics mass scale probed, for fixed couplings, will almost double compared with the pre-HL-LHC era; this extended reach for flavour physics is similar to that which would be achieved by the HE-LHC proposal for the energy frontier

Plasma Treatment of Metal Oxide Nanoparticles: Development of Core–Shell Structures for a Better and Similar Dispersibility

Low-pressure plasma polymerization of cyclopropylamine was employed for the surface functionalization of commercial ZnO, Al₂O₃, and ZrO₂ nanoparticles in a homemade hollow cathode plasma reactor. The analysis of the modified nanoparticles by X-ray photoelectron spectroscopy (XPS) revealed the incorporation of reactive functional groups such as primary and secondary amines, which was confirmed by Fourier transform infrared spectroscopy (FTIR). The raw and the plasma functionalized nanoparticles were evaluated in terms of dispersibility. Application of Hansen solubility parameters (HSP) theory showed that the efficient plasma polymerization that led to the deposition of an approximately 5 nm thick plasma polymer film, as determined by transmission electron microscopy (TEM), causes a similar shift toward the Hansen solubility space for the functionalized nanoparticles and changes their physicochemical affinity within selected solvents, regardless of the kind of nanoparticles used. Hence, a combined exploitation of nanoparticles having different cores is feasible in applications such as nanocomposites and bioapplications having certain reactivity after grafting an amine-based plasma polymer film that allows achieving a similar dispersibility

Layer-by-Layer Enzymatic Platform for Stretched-Induced Reactive Release

An original “all-in-one” platform combining polymers, enzymes, and enzymatic substrates in a unique film is designed. A polymeric barrier stratum prevents any contact between enzymes adsorbed on top of the film and substrates loaded in an underlying reservoir. Upon stretching of the film, a continuous diffusion of substrates through the barrier is triggered, followed by a catalytic reaction. This leads to the formation of products that are released from the film. This new platform acts as a stretch-induced reactive release system and emerges as an innovative concept in mechano-responsive materials

Electrochemical, Linear Optical, and Nonlinear Optical Properties and Interpretation by Density Functional Theory Calculations of (4-<i>N,N</i>-Dimethylaminostyryl)-Pyridinium Pendant Group Associated with Polypyridinic Ligands and Respective Multifunctional Metal Complexes (Ru^II or Zn^II)

The synthesis, linear optical and nonlinear optical properties, as well as the electrochemical behavior of a series of pro-ligands containing the 4-(4-N,N-dimethylaminostyryl)-1-methyl pyridinium (DASP+) group as a push−pull moiety covalently linked to terpyridine or bipyridine as chelating ligands are reported in this full paper. The corresponding multifunctional RuII and ZnII complexes were prepared and investigated. The structural, electronic, and optical properties of the pro-ligands and the ruthenium complexes were investigated using density functional theory (DFT) and time-dependent (TD) DFT calculations. A fairly good agreement was observed between the experimental and the calculated electronic spectra of the pro-ligands and their corresponding ruthenium complexes. A quenching of luminescence was evidenced in all ruthenium complexes compared with the free pro-ligands but even the terpyridine-functionalized metal complexes exhibited detectable luminescence at room temperature. Second order nonlinear optical (NLO) measurements were performed by Harmonic Light Scattering and the contribution of the DASP+ moieties (and their relative ordering) and the metal-polypyridyl core need to be considered to explain the nonlinear optical properties of the metal complexes

Pyrazolo[1,5-<i>a</i>]-1,3,5-triazine as a Purine Bioisostere: Access to Potent Cyclin-Dependent Kinase Inhibitor (<i>R</i>)-Roscovitine Analogue

Pharmacological inhibitors of cyclin-dependent kinases (CDKs) have a wide therapeutic potential. Among the CDK inhibitors currently under clinical trials, the 2,6,9-trisubstituted purine (R)-roscovitine displays rather high selectivity, low toxicity, and promising antitumor activity. In an effort to improve this structure, we synthesized several bioisosteres of roscovitine. Surprisingly, one of them, pyrazolo[1,5-a]-1,3,5-triazine 7a (N-&-N1, GP0210), displayed significantly higher potency, compared to (R)-roscovitine and imidazo[2,1-f]-1,2,4-triazine 13 (N-&-N2, GP0212), at inhibiting various CDKs and at inducing cell death in a wide variety of human tumor cell lines. This approach may thus provide second generation analogues with enhanced biomedical potential

Sex differences in post-acute neurological sequelae of SARS-CoV-2 and symptom resolution in adults after coronavirus disease 2019 hospitalization: an international multi-centre prospective observational study

: Although it is known that coronavirus disease 2019 can present with a range of neurological manifestations and in-hospital complications, sparse data exist on whether these initial neurological symptoms of coronavirus disease 2019 are closely associated with post-acute neurological sequelae of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; PANSC) and whether female versus male sex impacts symptom resolution. In this international, multi-centre, prospective, observational study across 407 sites from 15 countries (30 January 2020 to 30 April 2022), we report the prevalence and risk factors of PANSC among hospitalized adults and investigate the differences between males and females on neurological symptom resolution over time. PANSC symptoms included altered consciousness/confusion, fatigue/malaise, anosmia, dysgeusia and muscle ache/joint pain, on which information was collected at index hospitalization and during follow-up assessments. The analysis considered a time to the resolution of individual and all neurological symptoms. The resulting times were modelled by Weibull regression, assuming mixed-case interval censoring, with sex and age included as covariates. The model results were summarized as cumulative probability functions and age-adjusted and sex-adjusted median times to resolution. We included 6862 hospitalized adults with coronavirus disease 2019, who had follow-up assessments. The median age of the participants was 57 years (39.2% females). Males and females had similar baseline characteristics, except that more males (versus females) were admitted to the intensive care unit (30.5 versus 20.3%) and received mechanical ventilation (17.2 versus 11.8%). Approximately 70% of patients had multiple neurological symptoms at the first follow-up (median = 102 days). Fatigue (49.9%) and myalgia/arthralgia (45.2%) were the most prevalent symptoms of PANSC at the initial follow-up. The reported prevalence in females was generally higher (versus males) for all symptoms. At 12 months, anosmia and dysgeusia were resolved in most patients, although fatigue, altered consciousness and myalgia remained unresolved in &gt;10% of the cohort. Females had a longer time to the resolution (5.2 versus 3.4 months) of neurological symptoms at follow-up for those with more than one neurological symptom. In the multivariable analysis, males were associated with a shorter time to the resolution of symptoms (hazard ratio = 1.53; 95% confidence interval = 1.39-1.69). Intensive care unit admission was associated with a longer time to the resolution of symptoms (hazard ratio = 0.68; 95% confidence interval = 0.60-0.77). Post-discharge stroke was uncommon (0.3% in females and 0.5% in males). Despite the methodological challenges involved in the collection of survey data, this international multi-centre prospective cohort study demonstrated that PANSC following index hospitalization was high. Symptom prevalence was higher and took longer to resolve in females than in males. This supported the fact that while males were sicker during acute illness, females were disproportionately affected by PANSC

I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

background and aims: there is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. the primary objective of I-CARE (IBD cancer and serious infections in europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators. methods: I-CARE was designed as a european prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment. results: a total of 10,206 patients were enrolled between march 2016 and april 2019, including 6169 (60.4%) patients with crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. at inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. sixty-six percent of patients had been previously treated with systemic steroids. three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia. conclusions: I-CARE is an ongoing investigator-initiated observational european prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (eudra CT, Number: 2014-004728-23; clinical trials.gov, number: NCT02377258)

Liver injury in hospitalized patients with COVID-19: An International observational cohort study

Background: Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes.MethodsWe included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component &amp; GE;3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI).ResultsOf 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]), and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45). Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]).ConclusionsLiver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

International audienc