63 research outputs found
The role of CMB spectral distortions in the Hubble tension: a proof of principle
Although both early and late-time modifications of the 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 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 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
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 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
km/(s Mpc), which reduces the Hubble tension to . Furthermore, we
also perform a statistical model comparison, finding a of
(corresponding to a significance of 1.5) with the inclusion of
one additional free parameter, showing no clear preference for this model with
respect to 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 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 keV to 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 studyâs 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 Grayâs 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, 8.8â11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7â21.0) and 9.3 (95% CI, 7.9â11.0) 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, 1.018â3.140; 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 inâhospital mortality rate in patients with COVIDâ19 receiving thromboprophylaxis: data from the multicentre observational STARTâCOVID 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 ⼠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
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