Probing of dark energy properties in the Universe using astrophysical observations

The astrophysical data of the last two decades have allowed cosmologists to conclude that the present Universe is accelerating. The research carried out to find the origin of this phenomenon has led to the creation of a vast number of dark energy and modified gravity theories, of which the simplest is the ˄CDM model. The latter is, however, plagued with very difficult problems awaiting a solution. The work here presented seeks to contribute to the discussion of the possible explanation for the Cosmos' acceleration and other important questions in modern cosmology using the newest astrophysical observations available. This thesis starts by exploring a dark energy model dubbed thawing quintessence which is characterised by allowing a non constant ratio of pressure to density for dark energy that is however still close to -1 for most of the cosmological evolution, shifting away from this value when the domination of the radiation and matter components fades away. The findings are the most up-to-date constraints for which this model gives a viable theory for dark energy, including a bound on the equation of state at present of w < -0:88. This exact approach was contrasted with the use of an approximate equation-of-state parametrisation for thawing theories. The analysis also includes different parametrisation choices, and comments on the accuracy of the constraints imposed by CMB anisotropies alone. Next, the cosmology of hybrid metric-Palatini gravity is presented. This is a type of Modified Gravity theory in which the Lagrangian density for the gravitational action is a function of the Ricci scalars of both the connection and the metric. The background evolution of two models of this kind is examined explicitly showing the recovery of standard General Relativity at late times. The maximum deviation from the gravitational constant G at early times is constrained using a combination of geometrical data, finding it to be around 1%. A designer scenario, also introduced under the hybrid metric-Palatini formulation, is then used to explore to what extent early modifications of gravity, which become significant after recombination but then decay towards the present, can be constrained by current and future cosmological observations. This model is embedded in the effective field theory description of Horndeski scalar-tensor gravity with an early-time decoupling of the gravitational modification. Applying cosmological data, the constraints on the early-time deviations from General Relativity are obtained. These are dependent on the redshift at which the oscillations in the slip between the gravitational potentials are turned on. For zon = 1000, the deviation from Einstein's theory is ≤ 10-2 with 95% confidence. An explanation of the effect that these divergences have on the CMB power spectrum are discussed, as well as the effect that future 21 cm survey data will have on this study. The last part of this work is a move towards inflation, the early epoch of accelerated expansion undergone by the Universe. Here a parametrisation of the acceleration trajectory is investigated with the aim of measuring the rolling of the inflaton corresponding to the value of the tensor-to-scalar ratio r to be compared with future observations. Considering five ln ε amplitudes and 14 e-foldings, it was found that the posterior distribution of (r,∆Φ) is in very good agreement with Lyth's bound. The analysis included a histogram depiction of the latter result, from which later a minimum constraint on ∆ϕ for each of the bins was found. These outcomes constitute the intermediate step of this project which will be made more accurate by extending it to ~ 50 e-folds, a larger set of cosmological parameters and observational bounds that are restrictive on small scales

Cytoplasmic innate immune sensing by the caspase-4 non-canonical inflammasome promotes cellular senescence

Cytoplasmic recognition of microbial lipopolysaccharides (LPS) in human cells is elicited by the caspase-4 and caspase-5 noncanonical inflammasomes, which induce a form of inflammatory cell death termed pyroptosis. Here we show that LPS-mediated activation of caspase-4 also induces a stress response promoting cellular senescence, which is dependent on the caspase-4 substrate gasdermin-D and the tumor suppressor p53. Furthermore, we found that the caspase-4 noncanonical inflammasome is induced and assembled in response to oncogenic RAS signaling during oncogene-induced senescence (OIS). Moreover, targeting caspase-4 expression in OIS showed its critical role in the senescence-associated secretory phenotype and the cell cycle arrest induced in cellular senescence. Finally, we observed that caspase-4 induction occurs in vivo in mouse models of tumor suppression and ageing. Altogether, we are showing that cellular senescence is induced by cytoplasmic LPS recognition by the noncanonical inflammasome and that this pathway is conserved in the cellular response to oncogenic stress.This work was funded by Cancer Research UK (CRUK) (C47559/A16243 Training & Career Development Board - Career Development Fellowship), the University of Edinburgh Chancellor’s Fellowship R42576 MRC, and the Ministry of Science and Innovation of the Government of Spain (Proyecto PID2020-117860GB-I00 financiado por MCIN/ AEI /10.13039/501100011033). J.C.A. was supported by CRUK, the University of Edinburgh and is supported by the Spanish National Research Council (CSIC). P.H., I.F.D and N.T. were funded by the University of Edinburgh. A.Q. was funded by CRUK. J.F.P and A.B.L. are funded by NIH grants: 1R01AG068048-01; P01 AG062413; 1UG3 CA268103-01. J.B. was funded by BBSRC (BB/K017314/1). V.S-B is supported by funding from the University of Edinburgh and Medical Research Council (MC_UU_00009/2). F.R.M is funded by a Wellcome Trust Clinical Research Fellowship through the Edinburgh Clinical Academic Track (ECAT) (203913/Z/16/Z). M.M. was supported by CRUK Edinburgh Centre Award (C157/A25140). V.G.B. is funded by CRUK (C157/A24837) and the University of Edinburgh

Acute Amiodarone Pulmonary Toxicity after Drug Holiday: A Case Report and Review of the Literature

Amiodarone is reported to cause a wide continuum of serious clinical effects. It is often challenging to detect Amiodarone-induced pulmonary toxicity (AIPT). Typically, the diagnosis is made based on the clinical settings and may be supported by histopathology results, if available. We describe a 57-year-old patient who developed severe rapidly progressive respiratory failure secondary to AIPT with acute bilateral infiltrates and nodular opacities on chest imaging. Interestingly, Amiodarone was discontinued 3 weeks prior to his presentation. He had normal cardiac filling pressures confirmed by echocardiography. To our knowledge, this is the first case of isolated acute lung injury induced by Amiodarone, three weeks after therapy cessation, with adequate clinical improvement after supportive management and high dose steroid therapy

Malignant Course of Anomalous Left Coronary Artery Causing Sudden Cardiac Arrest: A Case Report and Review of the Literature

Sudden cardiac arrest has been reported to occur in patients with congenital anomalous coronary artery disease. About 80% of the anomalies are benign and incidental findings at the time of catheterization. We present a case of sudden cardiac arrest caused by anomalous left anterior descending artery. 61-year-old African American female was brought to the emergency department after sudden cardiac arrest. Initial EKG showed sinus rhythm with RBBB and LAFB with nonspecific ST-T wave changes. Coronary angiogram revealed no atherosclerotic disease. The left coronary artery was found to originate from the right coronary cusp. Cardiac CAT scan revealed similar findings with interarterial and intramural course. Patient received one-vessel arterial bypass graft to her anomalous coronary vessel along with a defibrillator for secondary prevention. Sudden cardiac arrest secondary to congenital anomalous coronary artery disease is characterized by insufficient coronary flow by the anomalous left coronary artery to meet elevated left ventricular (LV) myocardial demand. High risk defects include those involved with the proximal coronary artery or coursing of the anomalous artery between the aorta and pulmonary trunk. Per guidelines, our patient received one vessel bypass graft to her anomalous vessel. It is important for clinicians to recognize such presentations of anomalous coronary artery