Gravitational Shock Waves and Holography

[ES]La primera parte de la tesis discute la creación de superficies atrapadas en la colisión de ondas de choque gravitacionales en el espacio de anti-de Sitter en dimensión arbitraria. En concreto, se busca la superficie atrapada de Penrose antes de la colisión, y cómo ésta depende de los parámetros de la colisión. Las ondas de choque gravitacionales se obtienen a partir de una adaptación del límite de Aichelburg-Sexl a espacios no asintóticamente planos. En particular, el límite ultrarrelativista se lleva a cabo sobre las soluciones de Schwarzschild y Reissner-Nordström. La colisión de las primeras con parámetro de impacto espacial (paralelo a la frontera del espacio de anti-de Sitter) lleva a una dependencia de la formación de la superficie atrapada con el parámetro de impacto y la energía, de tal forma que existe un valor crítico por encima del cual no hay formación de superficie atrapada. Además, este valor crítico escala con la energía con una potencia dependiente de la dimensión. Las isometrías del espacio de anti-de Sitter se usan para relacionar este tipo de colisiones con colisiones en las que el parámetro de impacto está dirigido también en la dirección holográfica, encontrándose igualemente un valor crítico. Vía la correspondencia AdS/CFT, la colisión de ondas analizada sirve como modelo sencillo para la creación de plasmas termalizados en colisiones de alta energía en teorías fuertemente acopladas. Sobre el supuesto de que la formación de una superficie de Penrose implica la aparición de un horizonte de eventos después de la colisión, y dado que un horizonte de eventos en el espacio de anti-de Sitter corresponde a una teoría a temperatura finita en la frontera, la formación de la superficie de Penrose se toma como señal de termalización en la teoría de la frontera. De esta forma, el estudio llevado acabo establece que debe haber un límite para la termalización después de un choque dependiente del parámetro de impacto, la energía y los tamaños relativos de los objetos que colisionan. En particular, en D = 5 dimensiones, obtenemos un modelo sencillo para la generación de sQGP en colisiones de iones pesados a altas energías. El modelo desarrollado en base a ondas gravitacionales obtenidas a partir de la solución de Schwarzschild es el más sencillo posible. Considerando la colisión entre ondas de choque gravitacionales de Reissner-Nordström podemos ir un paso más allá. Sin embargo, no es posible encontrar una solución a la superficie de Penrose tanto para colisiones frontales como con parámetro de impacto. La presencia de un halo de energía heredada de la carga de la solución de Reissner-Norström parece prevenir por completo cualquier superficie de Penrose, si bien la creacción de alguna superficie atrapada en el cono de luz futuro podría ser posible. La segunda parte de la tesis estudia cómo implementar simetrías gauge en teorías de campos en espacios no conmutativos. El problema radica fundamentalmente en que en teorías en espacios no conmutativos la noción de localidad se pierde totalmente y sin embargo esta resulta fundamental para construir clásicamente las teorías gauge. En la literatura científica habitualmente se han presentado dos formas de solucionar el problema: o bien deformando no-localmente la acción del grupo gauge (invariancia star-gauge), o bien mediante un twist de la regla de Leibniz sobre el álgebra de campos (invariancia twist-gauge). La ausencia de corrientes de Noether para la segunda invariancia parecía indicar que la primera era la verdadera simetría gauge de la teoría, cumpliendo un rol de custodia sobre la segunda. En la tesis se desarrolla una tercera opción para construir invariancias gauge en la que tanto la acción del grupo gauge como la regla de Leibniz se deforman (invariancias star-twisted gauge). El resultado es una familia continua de invariancias que interpolan continuamente entre la simetría star-gauge y la invariancia twist-gauge, todas ellas custodiadas por la simetría star-gauge

A Note on the Collision of Reissner-Nordstr\"om Gravitational Shock Waves in AdS

We study the collision of two Reissner-Nordstr\"om gravitational shock waves in AdS and show that the charge completely prevents the formation of marginally trapped surfaces of the Penrose type with topology S^(D-2), independently of the energy and the value of the impact parameter. In the case of head-on collisions, a numerical analysis shows that no trapped surfaces with topology S^1 \times S^(D-3) form either.Comment: 13 pages, 6 figures. LaTeX. v2: major change

Colliding AdS gravitational shock waves in various dimensions and holography

The formation of marginally trapped surfaces in the off-center collision of two shock waves on AdS_D (with D=4,5,6,7 and 8) is studied numerically. We focus on the case when the two waves collide with nonvanishing impact parameter while the sources are located at the same value of the holographic coordinate. In all cases a critical value of the impact parameter is found above which no trapped surface is formed. The numerical results show the existence of a simple scaling relation between the critical impact parameter and the energy of the colliding waves. Using the isometries of AdS_D we relate the solutions obtained to the ones describing the collision of two waves with a purely holographic impact parameter. This provides a gravitational dual for the head-on collision of two lumps of energy of unequal size.Comment: 25 pages, 11 figures. v2: minor changes, typos corrected. To appear in JHE

An Integrated Approach for the Early Detection of Endometrial and Ovarian Cancers (Screenwide Study): Rationale, Study Design and Pilot Study

Screenwide is a case-control study (2017-2021) including women with incident endometrial and ovarian cancers (EC and OC), BRCA1/2 and MMR pathogenic variant carriers, and age-matched controls from three centers in Spain. Participants completed a personal interview on their sociodemographic factors, occupational exposure, medication, lifestyle, and medical history. We collected biological specimens, including blood samples, self-collected vaginal specimens, cervical pap-brush samples, uterine specimens, and, when available, tumor samples. The planned analyses included evaluation of the potential risk factors for EC/OC; evaluation of molecular biomarkers in minimally invasive samples; evaluation of the cost-effectiveness of molecular tests; and the generation of predictive scores to integrate different epidemiologic, clinical, and molecular factors. Overall, 182 EC, 69 OC, 98 BRCA pathogenic variant carriers, 104 MMR pathogenic variant carriers, and 385 controls were enrolled. The overall participation rate was 85.7%. The pilot study using 61 samples from nine EC cases and four controls showed that genetic variants at the variant allele fraction > 5% found in tumors (n = 61 variants across the nine tumors) were detected in paired endometrial aspirates, clinician-collected cervical samples, and vaginal self-samples with detection rates of 90% (55/61), 79% (48/61), and 72% (44/61) by duplex sequencing, respectively. Among the controls, only one somatic mutation was detected in a cervical sample. We enrolled more than 800 women to evaluate new early detection strategies. The preliminary data suggest that our methodological approach could be useful for the early detection of gynecological cancers

Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

Background The incidence of endometrial cancer is increasing worldwide. While delays in diagnosis reduce survival, case molecular misclassification might be associated with under- and over-treatment. The objective of this study was to evaluate genetic alterations to detect and molecularly classify cases of endometrial cancer using non-invasive samples. Methods Consecutive patients with incident endometrial cancer (N = 139) and controls (N = 107) from a recent Spanish case–control study were included in this analysis. Overall, 339 cervicovaginal samples (out of which 228 were clinician-collected and 111 were self-collected) were analysed using a test based on next-generation sequencing (NGS), which targets 47 genes. Immunohistochemical markers were evaluated in 133 tumour samples. A total of 159 samples were used to train the detection algorithm and 180 samples were used for validation. Findings Overall, 73% (N = 94 out of 129 clinician-collected samples, and N = 66 out of 90 self-collected samples) of endometrial cancer cases had detectable mutations in clinician-collected and self-collected samples, while the specificity was 80% (79/99) for clinician-collected samples and 90% (19/21) for self-collected samples. The molecular classifications obtained using tumour samples and non-invasive gynaecologic samples in our study showed moderate-to-good agreement. The molecular classification of cases of endometrial cancer into four groups using NGS of both clinician-collected and self-collected cervicovaginal samples yielded significant differences in disease-free survival. The cases with mutations in POLE had an excellent prognosis, whereas the cases with TP53 mutations had the poorest clinical outcome, which is consistent with the data on tumour samples. Interpretation This study classified endometrial cancer cases into four molecular groups based on the analysis of cervicovaginal samples that showed significant differences in disease-free survival. The molecular classification of endometrial cancer in non-invasive samples may improve patient care and survival by indicating the early need for aggressive surgery, as well as reducing referrals to highly specialized hospitals in cancers with good prognosis. Validation in independent sets will confirm the potential for molecular classification in non-invasive samples. Funding This study was funded by a competitive grant from Instituto de Salud Carlos III through the projects PI19/01835, PI23/00790, and FI20/00031, CIBERESP CB06/02/0073 and CIBERONC CB16/12/00231, CB16/12/00234 (Co-funded by European Regional Development Fund. ERDF: A way to build Europe). Samples and data were provided by Biobank HUB-ICO-IDIBELL, integrated into the Spanish Biobank Network, and funded by the Instituto de Salud Carlos III (PT20/00171) and by Xarxa de Bancs de Tumors de Catalunya (XBTC) sponsored by Pla Director d’Oncologia de Catalunya. This work was supported in part by the AECC, Grupos estables (GCTRA18014MATI). It also counts with the support of the Secretariat for Universities and Research of the Department of Business and Knowledge of the Generalitat de Catalunya, and grants to support the activities of research groups 2021SGR01354 and 2021SGR1112

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols