A deletion at Adamts9-magi1 Locus is associated with psoriatic arthritis risk

Objective: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. Methods: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ2 test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). Results: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). Conclusions: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk

In silico mechanistic assessment of imaging-based measures of cardiac (patho) physiology

To contribute on personalising medicine, understanding the mechanisms underlying cardiac dysfunction is key for accurate personalization of clinical decision-making. This dissertation focuses on unravelling mechanisms of imaging-based observations measured in the presence of cardiac pathologies. These physiological mechanisms have direct clinical benefits on clinical conditions like aortic regurgitation, pulmonary hypertension and intense exercise. The computational CircAdapt model was used to simulate human physiology of the heart and circulation and explore those mechanisms. We also present a novel hypothesis on the right ventricular dysfunction induced by extreme intensity exercise, which offers an explanation for the disproportionately low exercise tolerance in a number of cardiovascular diseases

Creació d'un festival co-inclusiu de música i cultura i la seva identitat visual i sensorial.

Treball de fi de grau en Publicitat i Relacions PúbliquesTutor: Carlos Alberto Scolar

Why septal motion is a marker of right ventricular failure in pulmonary arterial hypertension: mechanistic analysis using a computer model

Rapid leftward septal motion (RLSM) during early left ventricular (LV) diastole is observed in patients with pulmonary arterial hypertension (PAH). RLSM exacerbates right ventricular (RV) systolic dysfunction and impairs LV filling. Increased RV wall tension caused by increased RV afterload has been suggested to cause interventricular relaxation dyssynchrony and RLSM in PAH. Simulations using the CircAdapt computational model were used to unravel the mechanism underlying RLSM by mechanistically linking myocardial tissue and pump function. Simulations of healthy circulation and mild, moderate, and severe PAH were performed. We also assessed the effects on RLSM when PAH coexists with RV or LV contractile dysfunction. Our results showed prolonged RV shortening in PAH causing interventricular relaxation dyssynchrony and RLSM. RLSM was observed in both moderate and severe PAH. A negative transseptal pressure gradient only occurred in severe PAH, demonstrating that negative pressure gradient does not entirely explain septal motion abnormalities. PAH coexisting with RV contractile dysfunction exacerbated both interventricular relaxation dyssynchrony and RLSM. LV contractile dysfunction reduced both interventricular relaxation dyssynchrony and RLSM. In conclusion, dyssynchrony in ventricular relaxation causes RLSM in PAH. Onset of RLSM in patients with PAH appears to indicate a worsening in RV function and hence can be used as a sign of RV failure. However, altered RLSM does not necessarily imply an altered RV afterload, but it can also indicate altered interplay of RV and LV contractile function. Reduction of RLSM can result from either improved RV function or a deterioration of LV function.NEW &amp; NOTEWORTHY A novel approach describes the mechanism underlying abnormal septal dynamics in pulmonary arterial hypertension. Change in motion is not uniquely induced by altered right ventricular afterload, but also by altered ventricular relaxation dyssynchrony. Extension or change in motion is a marker reflecting interplay between right and left ventricular contractility.</p

Hemodynamics in aortic regurgitation simulated using a computational cardiovascular system model

The influence of left ventricular and aortic tissue properties on hemodynamics in patients with aortic regurgitation (AR) is unclear. In this study we aim: (1) to assess the capability of the CircAdapt model of the heart and circulation to simulate hemodynamics in AR; (2) to determine the interaction between aortic compliance and AR using CircAdapt. We simulated three degrees of AR by changing the aortic regurgitant orifice area (ROA) with normal and low aortic compliance. The higher the ROA is, the higher the systolic left ventricular and aortic pressures, the lower the diastolic aortic pressures and the higher the diastolic left ventricular pressures are. For low aortic compliance, those effects are exacerbated, but the regurgitant blood volume is decreased. These simulation data show the capability of CircAdapt to simulate hemodynamics in AR, and suggest that patient-to-patient variability in aortic compliance should be taken into account when assessing AR severity using imaging-based hemodynamic metrics

A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to/nmaintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial/nconnection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this/nbrain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental/nunderstanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has/nbeen limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since/nthey allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be/ndirectly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed,/nincluding the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow/npersonalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to/nunderstand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery/n(MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this/naffects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the/nproposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The/nresults support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance/nbetween increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying/nthe balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid/nclinical follow up.This study was partially supported by grants from Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (ref. PI11/00051, PI11//n01709, PI12/00801 and SAF2012-37196); Fondo Europeo de Desarrollo Regional de la Unio/ń/nn Europea ‘‘Una manera de hacer Europa’’, Spain; Obra Social ‘La Caixa’,/nSpain; Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); and the Seventh Framework Programme (FP7/2007-2013) under grant agr/neement/nNo. 611823. PGC was supported by the Programa de Ayudas Predoctorales de Formacio/ń/nn en investigacio/ń/nn en Salud (FI12/00362) from the Instituto Carlos III,/nSpain. MCL wishes to express her gratitude to the Mexican National Council for Science and Technology (CONACyT, Mexico City, Mexico) for supporting h/ner/npredoctoral stay at Hospital Clinic, Barcelona, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or/npreparation of/nthe manuscrip

The therapeutic relationship at the heart of nursing care: a participatory action research in acute mental health units

Aims and Objectives: To explore the process of change within the clinical practice of nurses in mental health inpatient units in the context of a participatory process to improve the nurse-patient therapeutic relationship. Design: Participatory Action Research. Methods: Ninety-six nurses from 18 mental health units participated. Data were collected through focus groups and eflective diaries between March 2018 and January 2020. Data were analysed using inductive content analysis. The COREQ guidelines were used. Results: The research process was carried out through two cycles of four stages each in which the nurses were able to identify the facilitating and limiting elements of their practice in relation to the therapeutic relationship. They then proposed two consensual improvement strategies for all the units, which they called reserved therapeutic space and postincident analysis. Finally, they implemented and evaluated the two strategies for change. Conclusions: This study has shown that, despite the different cultural and structural realities of the participating units, it is possible to implement a collaborative process of change, provided the needs and expectations of both the participants and the organisations are similar. Relevance to Clinical Practice: The results obtained through Participatory Action Research were directly transferred to clinical practice, thus having an impact on individual nurses and patients, as well as on the collective dynamics of the teams and aspects related to the management of the units