Probing Early Dark Energy and primordial non-Gaussianity with cosmological simulations

Die Entwicklung des ersten präzisen kosmologischen Modells, des LCDM Modells, ist eine bedeutende Errungenschaft der modernen, beobachtenden Kosmologie. Trotzdem bleiben eine Reihe von wichtigen Fragen über Zusammensetzung und Entwicklungsgeschichte des Universums unbeantwortet: Abgesehen von der Natur der Dunklen Materie ist der physikalische Ursprung der Dunklen Energie eine der ganz großen Fragen der theoretischen Physik. Ebenso bedürfen die statistischen Eigenschaften der anfänglichen Dichtefluktuationen im frühen Universum einer genauen überprüfung. Kleinste Abweichungen von den Gauß'schen Fluktuationen des Standardmodells würden, sofern sie nachgewiesen werden, eine Vielzahl von Informationen über die Physik des frühen Universums enthalten. In dieser Arbeit benutze ich numerische Verfahren, um neue, hochpräzise Vorhersagen zur kosmischen Strukturbildung in generalisierten Dunkle Energie Kosmologien zu treffen. Außerdem berücksichtige ich Modelle mit nicht-Gauß'schen Anfangbedingungen. Im ersten Abschnitt untersuche ich die nicht-lineare Strukturentstehung in sogenannten `Early Dark Energy' (EDE) Modellen und vergleiche sie mit dem LCDM Standardmodell. Interessanterweise zeigen meine Ergebnisse, dass der Sheth and Tormen (1999) Formalismus, mit dem üblicherweise die Anzahldichte von Halos aus Dunkler Materie geschätzt wird, in EDE Kosmologien weiterhin anwendbar ist, im Widerspruch zu analytischen Berechnungen. In diesem Zusammenhang untersuche ich auch das Verhältnis zwischen Masse und Geschwindigkeitsdispersion der Dunklen Materie in Halos. Dabei stelle ich eine gute übereinstimmung mit der Normalisierung der LCDM Kosmologien fest, wie sie in Evrard et al. (2008) beschrieben ist. Allerdings führt das frühere Anwachsen der Dichtestrukturen in EDE Modellen zu großen Unterschieden in der Massenfunktion der Halos bei hohen Rotverschiebungen. Dies könnte direkt in Beobachtungen gemessen werden, indem man die Anzahl der Gruppen als Funktion der Geschwindigkeitsdispersion der enthaltenen Galaxien entlang der Sichtlinie bestimmt. Insbesondere würde dadurch das Problem der mehrdeutigen Massebestimmung von Halos umgangen. Schließlich ermittele ich die Beziehung zwischen dem Konzentrationsparameter von Halos und der Halomasse in den EDE Kosmologien. Im zweiten Teil meiner Arbeit verwende ich ein Set an hochaufgelöste hydrodynamische Simulationen um die globalen Eigenschaften der thermischen und kinetischen Sunyaev Zeldovich (SZ) Effekte zu untersuchen. Dabei stellen wir fest, dass in den SZ-Beobachtungskarten der EDE Modelle der Compton-y-Parameter systematisch größer ist als im LCDM Modell. Erwartungsgemäß finde ich daher auch, dass das Leistungsspektrum der thermischen und kinetischen SZ Fluktuationen in EDE Kosmologien größer ist als im Standardmodell. Allerdings reicht diese Steigerung für realistische EDE Modelle nicht aus, um die theoretischen Voraussagen in übereinstimmung mit aktuellen Messungen der Mikrowellenhintergrundanisotropie bei großen Multipolwerten zu bringen. Eine Zählung der durch den SZ Effekt detektierbaren Halos in den simulierten Karten zeigt nur einen leichten Anstieg in den massereichsten Haufen für EDE Kosmologien. Ebenso sind Voraussagen für zukünftige Zählungen von SZ-detektierten Haufen durch das South Pole Telescope (SPT Ruhl, 2004) stark durch Unsicherheiten in der Kosmologie beeinträchtigt. Schließlich finde ich, dass die Normalisierung und die Steigung der Relation zwischen thermischem SZ-Effekt und Halomasse in vielen EDE Kosmologien unverändert bleibt, was die Interpretation von Beobachtungen des SZ Effekts in Galaxienhaufen vereinfacht. In weiteren Untersuchungen berechne ich eine Reihe von hochaufgelösten Vielteilchensimulationen für physikalisch motivierte nicht-Gauß'sche Kosmologien. In umfangreichen Studien untersuche ich die Massenverteilungsfunktion der Halos und deren Entwicklung in nicht-Gauß'schen Modellen. Zudem vergleiche ich meine numerischen Experimente mit analytischen Vorhersagen von Matarrese et al. (2000) und LoVerde et al. (2008). Dabei finde ich eine sehr gute übereinstimmung zwischen Simulation und analytischer Vorhersage, vorausgesetzt bestimmte Korrekturen für die Dynamik des nicht-sphärischen Kollapses werden berücksichtigt. Dazu werden die Vorhersagen dahingehend modifiziert, dass sie im Grenzfall sehr seltener Ereignisse einem geeignet veränderten Grenzwert der kritischen Dichte entsprechen. Desweiteren bestätige ich jüngste Ergebnisse, nach denen primordiale nicht-Gauß'sche Dichtefluktuationen eine starke skalenabhänginge Verzerrung auf großen Skalen verursachen, und ich lege einen physikalisch motivierten mathematischen Ausdruck vor, der es erlaubt, die Verzerrung zu messen und der eine gute Näherung für die Simulationsergebnisse darstellt

Variable Selection in Maximum Mean Discrepancy for Interpretable Distribution Comparison

Two-sample testing decides whether two datasets are generated from the same distribution. This paper studies variable selection for two-sample testing, the task being to identify the variables (or dimensions) responsible for the discrepancies between the two distributions. This task is relevant to many problems of pattern analysis and machine learning, such as dataset shift adaptation, causal inference and model validation. Our approach is based on a two-sample test based on the Maximum Mean Discrepancy (MMD). We optimise the Automatic Relevance Detection (ARD) weights defined for individual variables to maximise the power of the MMD-based test. For this optimisation, we introduce sparse regularisation and propose two methods for dealing with the issue of selecting an appropriate regularisation parameter. One method determines the regularisation parameter in a data-driven way, and the other aggregates the results of different regularisation parameters. We confirm the validity of the proposed methods by systematic comparisons with baseline methods, and demonstrate their usefulness in exploratory analysis of high-dimensional traffic simulation data. Preliminary theoretical analyses are also provided, including a rigorous definition of variable selection for two-sample testing

The impact of Early Dark Energy on non-linear structure formation

We study non-linear structure formation in high-resolution simulations of Early Dark Energy (EDE) cosmologies and compare their evolution with the standard LCDM model. Extensions of the spherical top-hat collapse model predict that the virial overdensity and linear threshold density for collapse should be modified in EDE model, yielding significant modifications in the expected halo mass function. Here we present numerical simulations that directly test these expectations. Interestingly, we find that the Sheth & Tormen formalism for estimating the abundance of dark matter halos continues to work very well in its standard form for the Early Dark Energy cosmologies, contrary to analytic predictions. The residuals are even slightly smaller than for LCDM. We also study the virial relationship between mass and dark matter velocity dispersion in different dark energy cosmologies, finding excellent agreement with the normalization for Lambda as calibrated by Evrard et al.(2008). The earlier growth of structure in EDE models relative to LCDM produces large differences in the mass functions at high redshift. This could be measured directly by counting groups as a function of the line-of-sight velocity dispersion, skirting the ambiguous problem of assigning a mass to the halo. Using dark matter substructures as a proxy for member galaxies, we demonstrate that even with 3-5 members sufficiently accurate measurements of the halo velocity dispersion function are possible. Finally, we determine the concentration-mass relationship for our EDE cosmologies. Consistent with the earlier formation time, the EDE halos show higher concentrations at a given halo mass. We find that the magnitude of the difference in concentration is well described by the prescription of Eke et al.(2001) for estimating halo concentrations.Comment: 17 pages,17 figure

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

Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population