Searches for Dark Matter production in events with top quarks in the final state with the ATLAS detector at the LHC

Many cosmological observations give convincing evidence for the existence of dark matter (DM), estimated to constitute around 26% of the Universe by measurements of the cosmic microwave background. While the existence of DM thus seems well established, very little is known about its nature. Numerous models of DM have been proposed, and a possible strategy to test them is to use particle accelerators. This thesis focuses in particular on the detection of DM produced in the ATLAS experiment at the Large Hadron Collider, studying signatures with top quarks in the final state in the framework of a two-Higgs-doublet model with an additional pseudoscalar mediator, called 2HDMa. The first part of the work consisted in the study of the production of DM in association with a pair of top quarks, trying to assess the sensitivity in the parameters space of 2HDMa of already existing ATLAS analyses. These analyses were performed in the framework of a different model, similar to the 2HDMa model since it included a pseudoscalar mediator. The production of DM in association with a pair of top quarks was chosen because it is directly sensitive to the nature of the mediator through the polarization of the two top quarks, which can be reconstructed from their decays products. The model employed in the existing analyses and the 2HDMa model were thus compared in detail, and after that a recasting strategy to translate the existing results in the parameter space of 2HDMa was developed and validated. The second part of the present study focused instead on a new search channel for the 2HDMa model, never explored before, including the production of dark matter associated with a single top quark. This signature was identified as the only one sensitive to the production of charged Higgs bosons, and thus holds a key role in the ATLAS research program dedicated to the 2HDMa model. Being a new and challenging signature, dedicated strategies were developed to maximise the sensitivity of the analyses focusing on the different final states.Many cosmological observations give convincing evidence for the existence of dark matter (DM), estimated to constitute around 26% of the Universe by measurements of the cosmic microwave background. While the existence of DM thus seems well established, very little is known about its nature. Numerous models of DM have been proposed, and a possible strategy to test them is to use particle accelerators. This thesis focuses in particular on the detection of DM produced in the ATLAS experiment at the Large Hadron Collider, studying signatures with top quarks in the final state in the framework of a two-Higgs-doublet model with an additional pseudoscalar mediator, called 2HDMa. The first part of the work consisted in the study of the production of DM in association with a pair of top quarks, trying to assess the sensitivity in the parameters space of 2HDMa of already existing ATLAS analyses. These analyses were performed in the framework of a different model, similar to the 2HDMa model since it included a pseudoscalar mediator. The production of DM in association with a pair of top quarks was chosen because it is directly sensitive to the nature of the mediator through the polarization of the two top quarks, which can be reconstructed from their decays products. The model employed in the existing analyses and the 2HDMa model were thus compared in detail, and after that a recasting strategy to translate the existing results in the parameter space of 2HDMa was developed and validated. The second part of the present study focused instead on a new search channel for the 2HDMa model, never explored before, including the production of dark matter associated with a single top quark. This signature was identified as the only one sensitive to the production of charged Higgs bosons, and thus holds a key role in the ATLAS research program dedicated to the 2HDMa model. Being a new and challenging signature, dedicated strategies were developed to maximise the sensitivity of the analyses focusing on the different final states

The Vernacularization of Learned Medicine in Late-Seventeenth-Century England. Accommodating Translation Procedures and Popularizing Strategies

The late seventeenth century was a fundamental moment for the popularization and democratization of learned medicine in England. Growing levels of literacy among the upper-middle classes, coupled with the diffusion of the ideal of serving the common good, resulted in an unprecedented flourishing of the vernacular specialized publishing market. Medicine, which until that time had been confined to Latin texts and elite readers, was thus rendered accessible to a wider audience, which included not only less prestigious medical practitioners, but also lay readers. The present work, following historical discourse analytic and pragmatic methods, provides an overview of how learned medicine was actually accommodated to this new audience in late-seventeenth-century England. To do so, it collects a corpus of medical vernacularizations published between 1649 and 1699 and analyzes it in order to delineate the context of production and identify the translation procedures and popularizing strategies that were exploited to accommodate the specialized language and knowledge of medicine to a lay readership. The study revealed that, although literalism still largely dominated early modern translating practice, translators also endeavored to accommodate the specialized notions of medicine to the new target audience by implementing a number of sometimes slight but meaningful changes that rendered the source texts more accessible for an audience which was literate, but not university-educated

Single-top final states as a probe of top-flavoured dark matter models at the LHC

Models incorporating flavoured dark matter provide an elegant solution to the dark matter problem, evading the tight LHC and direct direction constraints on simple WIMP models. In Dark Minimal Flavour Violation, a simple framework of flavoured dark matter with new sources of flavour violation, the constraints from thermal freeze-out, direct detection experiments, and flavour physics create well-defined benchmark scenarios for these models. We study the LHC phenomenology of four such scenarios, focusing on final states where a single top quark is produced accompanied by no jets, one jet from the fragmentation of light quarks or a $b$-tagged jet. For each of these signatures we develop a realistic LHC analysis, and we show that the proposed analyses would increase the parameter space coverage for the four benchmarks, compared to existing flavour-conserving LHC analyses. Finally we show the projected discovery potential of the considered signatures for the full LHC statistics at 14 TeV, and for the High Luminosity LHC.Comment: 25 pages, 14 figures, 2 tables. v2: clarifying comments and few references added, matches published versio

Discreteness of area in noncommutative space

We introduce an area operator for the Moyal noncommutative plane. We find that the spectrum is discrete, but, contrary to the expectation formulated by other authors, not characterized by a "minimum-area principle". We show that an intuitive analysis of the uncertainty relations obtained from Moyal-plane noncommutativity is fully consistent with our results for the spectrum, and we argue that our area operator should be generalizable to several other noncommutative spaces. We also observe that the properties of distances and areas in the Moyal plane expose some weaknesses in the line of reasoning adopted in some of the heuristic analyses of the measurability of geometric spacetime observables in the quantum-gravity realm

Phenylketonuria Diet Promotes Shifts in Firmicutes Populations

Low-phenylalanine diet, the mainstay of treatment for phenylketonuria (PKU), has been shown to increase glycemic index and glycemic load, affecting the availability of substrates for microbial fermentation. Indeed, changes in the PKU gut microbiota compared with healthy controls have been previously reported. In this study we compared the gut microbial communities of children with PKU and with mild hyperphenylalaninemia (MHP, unrestricted diet). For each group, we enrolled 21 children (4–18 years old), for a total dataset of 42 subjects. We assessed dietary intake and performed gut microbiota analysis by sequencing the V3–V4 hypervariable regions of the 16S rRNA gene. Short chain fatty acids (SCFAs) were quantified by gas chromatographic analysis. While alpha-diversity analysis showed no significant differences between PKU and MHP groups, microbial community analysis highlighted a significant separation of the gut microbiota according to both unweighted (p = 0.008) and weighted Unifrac distances (p = 0.033). Major differences were seen within the Firmicutes phylum. Indeed, PKU children were depleted in Faecalibacterium spp. and enriched in Blautia spp. and Clostridium spp (family Lachnospiraceae). We found a divergent response of members of the Firmicutes phylum with respect to daily glycemic index, higher in PKU children. Faecalibacterium prausnitzii, unclassified Ruminococcaceae and, to a lesser extent Roseburia spp. negatively correlated with glycemic index, whereas unclassified Lachnospiraceae were positively associated. Indicator species analysis suggested F. prausnitzii be related to MHP status and Ruminococcus bromii to be associated with PKU. Despite PKU children having a higher vegetable and fiber intake, resembling a vegan diet, their gut microbial profile is different from the microbiota reported in the literature for individuals consuming a high-fiber/low-protein diet. Indeed, beneficial microorganisms, such as F. prausnitzii, considered a biomarker for a healthy status and one of the main butyrate producers, are depleted in PKU gut microbiota. We suggest that both the quality and quantity of carbohydrates ingested participate in determining the observed Firmicutes shifts on the PKU population

Interplay between curvature and Planck-scale effects in astrophysics and cosmology

Several recent studies have considered the implications for astrophysics and cosmology of some possible nonclassical properties of spacetime at the Planck scale. The new effects, such as a Planck-scale-modified energy-momentum (dispersion) relation, are often inferred from the analysis of some quantum versions of Minkowski spacetime, and therefore the relevant estimates depend heavily on the assumption that there could not be significant interplay between Planck-scale and curvature effects. We here scrutinize this assumption, using as guidance a quantum version of de Sitter spacetime with known Inonu-Wigner contraction to a quantum Minkowski spacetime. And we show that, contrary to common (but unsupported) beliefs, the interplay between Planck-scale and curvature effects can be significant. Within our illustrative example, in the Minkowski limit the quantum-geometry deformation parameter is indeed given by the Planck scale, while in the de Sitter picture the parameter of quantization of geometry depends both on the Planck scale and the curvature scalar. For the much-studied case of Planck-scale effects that intervene in the observation of gamma-ray bursts we can estimate the implications of "quantum spacetime curvature" within robust simplifying assumptions. For cosmology at the present stage of the development of the relevant mathematics one cannot go beyond semiheuristic reasoning, and we here propose a candidate approximate description of a quantum FRW geometry, obtained by patching together pieces (with different spacetime curvature) of our quantum de Sitter. This semiheuristic picture, in spite of its limitations, provides rather robust evidence that in the early Universe the interplay between Planck-scale and curvature effects could have been particularly significant.Comment: 26 pages

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT