The role of CMB spectral distortions in the Hubble tension: a proof of principle

Although both early and late-time modifications of the $\Lambda$CDM model have been proposed to address the Hubble tension, compelling arguments suggest that for a solution to be successful it needs to modify the expansion history of the universe prior to recombination. This greatly increases the importance of precise CMB observations, and in this letter we make the argument for CMB spectral distortions, highlighting their potential role in constraining models that introduce significant shifts in the standard $\Lambda$CDM parameters, such as the scalar spectral index, in attempt to solve the Hubble tension.Comment: 6 pages with 2 figures and 1 table, published versio

The future of cosmology? A case for CMB spectral distortions

This thesis treats the topic of CMB Spectral Distortions (SDs), which represent any deviation from a pure black body shape of the CMB energy spectrum. As such, they can be used to probe the inflationary, expansion and thermal evolution of the universe both within $\Lambda$CDM and beyond it. The currently missing observation of this rich probe of the universe makes of it an ideal target for future observational campaigns. In fact, while the $\Lambda$CDM signal guarantees a discovery, the sensitivity to a wide variety of new physics opens the door to an enormous uncharted territory. In light of these considerations, the thesis opens by reviewing the topic of CMB SDs in a pedagogical and illustrative fashion, aimed at waking the interest of the broader community. This introductory premise sets the stage for the first main contribution of the thesis to the field of SDs: their implementation in the Boltzmann solver CLASS and the parameter inference code MontePython. The CLASS+MontePython pipeline is publicly available, fast, it includes all sources of SDs within $\Lambda$CDM and many others beyond that, and allows to consistently account for any observational setup. By means of these numerical tools, the second main contribution of the thesis consists in showcasing the versatility and competitiveness of SDs for several cosmological models as well as for a number of different mission designs. Among others, the results cover features in the primordial power spectrum, primordial gravitational waves, non-standard dark matter properties, primordial black holes, primordial magnetic fields and Hubble tension. Finally, the manuscript is disseminated with (20) follow-up ideas that naturally extend the work carried out so far, highlighting how rich of unexplored possibilities the field of CMB SDs still is. The hope is that these suggestions will become a propeller for further interesting developments.Comment: PhD thesis. Pedagogical review of theory, experimental status and numerical tools (CLASS+MontePython) with broad overview of applications. Includes 20 original follow-up idea

Tensions in the dark: shedding light on Dark Matter-Dark Energy interactions

The emergence of an increasingly strong tension between the Hubble rate inferred from early- and late-time observations has reinvigorated interest in nonstandard scenarios, with the aim of reconciling these measurements. One such model involves interactions between Dark Matter and Dark Energy. Here we consider a specific form of the coupling between these two fluids proportional to the Dark Energy energy density, which has been studied extensively in the literature and claimed to substantially alleviate the Hubble tension. We complement the work already discussed in several previous analyses and show that, once all relevant cosmological probes are included simultaneously, the value of the Hubble parameter in this model is $H_0=69.82_{-0.76}^{+0.63}$ km/(s Mpc), which reduces the Hubble tension to $2.5\sigma$. Furthermore, we also perform a statistical model comparison, finding a $\Delta\chi^2$ of $-2.15$ (corresponding to a significance of 1.5$\sigma$) with the inclusion of one additional free parameter, showing no clear preference for this model with respect to $\Lambda$CDM, which is further confirmed with an analysis of the Bayes ratio.Comment: 6+3 pages with 2 figures and 2 tables, published versio

Dark matter as a heavy thermal hot relic

If, during the early Universe epoch, the dark matter particle thermalizes in a hidden sector which does not thermalize with the Standard Model thermal bath, its relativistic thermal decoupling can easily lead to the observed relic density, even if the dark matter particle mass is many orders of magnitude heavier than the usual $\sim$ eV hot relic mass scale. This straightforward scenario simply requires that the temperature of the hidden sector thermal bath is one to five orders of magnitude cooler than the temperature of the Standard Model thermal bath. In this way the resulting relic density turns out to be determined only by the dark matter mass scale and the ratio of the temperatures of both sectors. In a model independent way we determine that this can work for a dark matter mass all the way from $\sim 1$ keV to $\sim 30$ PeV. We also show how this scenario works explicitly in the framework of two illustrative models. One of them can lead to a PeV neutrino flux from dark matter decay of the order of the one needed to account for the high energy neutrinos observed by IceCube.Comment: 6 pages with 2 figures, published versio

One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids

Optimization of CRISPR/Cas9-mediated genome engineering has resulted in base editors that hold promise for mutation repair and disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived organoids. First we show efficacy of cytosine and adenine base editors in modeling CTNNB1 hot-spot mutations in hepatocyte organoids. Next, we use C > T base editors to insert nonsense mutations in PTEN in endometrial organoids and demonstrate tumorigenicity even in the heterozygous state. Moreover, drug sensitivity assays on organoids harboring either PTEN or PTEN and PIK3CA mutations reveal the mechanism underlying the initial stages of endometrial tumorigenesis. To further increase the scope of base editing we combine SpCas9 and SaCas9 for simultaneous C > T and A > G editing at individual target sites. Finally, we show that base editor multiplexing allow modeling of colorectal tumorigenesis in a single step by simultaneously transfecting sgRNAs targeting five cancer genes

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

Low in‑hospital mortality rate in patients with COVID‑19 receiving thromboprophylaxis: data from the multicentre observational START‑COVID Register

Abstract COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years