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Background. Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. Methods. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). Results. After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10-6 (95% CI 3.3 × 10-7-1.1 × 10-5)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Conclusions. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD. © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD.

El desbridament és la tècnica que elimina el teixit desvitalitzat, danyat o amb presència d’infecció. S’utilitza en qualsevol tipus de ferida que presenti aquests teixits i ajuda a reduir el temps de curació de les úlceres gràcies a promoure l’aparició del teixit de granulació. És una tècnica segura, fàcil de dur a terme i en determinades ocasions econòmica, la qual cosa pot reduir els costos que es destinen en la curació de les úlceres. Millora també la qualitat de vida de les persones. L’objectiu general de l’estudi és estudiar la contribució que realitza el desbridament en relació a l’àrea de les úlceres. De manera específica s’estudia la millora que aporta la tècnica en les úlceres de manera general. Consisteix en un estudi observacional prospectiu de 6 mesos de durada. Es realitza una recollida de dades amb diferents variables abans durant i després del desbridament i es mesura l’àrea de les ferides (n=18) durant les sessions de cura que es duen a terme a la unitat de ferides de l’Hospital Universitari de la Santa Creu. S’ha vist que el desbridament, en la majoria de les úlceres, se’ls hi reduïa l’àrea. A més també millora l’estat general de les úlceres. Concloure que el desbridament ajuda a reduir l’àrea de les úlceres i ajuda a millorar l’estat general, a més de reduir el teixit desvitalitzat.

The aim of this thesis is to present a solution for the readout of Silicon Photo-Multipliers (SiPMs) arrays improving currently implemented systems. Using as a starting point previous designs with similar objectives a novel current mode input stage has been designed and tested. To start with the design a valid model has been used to generate realistic output from the SiPMs depending on light input. Design has been performed in first place focusing in general applications for medical imaging Positron Emission Tomography (PET) and then using the same topology for a more constrained design in particle detectors (upgrade of Tracker detector at LHCb experiment). A 16 channel ASIC for PET applications including the novel input stage has demonstrated an excellent timing measurement with good energy resolution measurement and pile-up detection. This document starts with the analysis of the requirements needed to fit such a system. Followed by a detailed description of the input stage and analog processing. Signal is divided in the input stage into three different signal paths: timing, energy and pile-up. Every channel performs different signal analysis to deliver; a fast time signal output (digital edge), energy output (a linear time over threshold digital output) and a \mbox{digital} bit to signal pile-up. The time information is then ORed between all channels to generate a single timing output. All the pile-up bits are combined in a digital word ready to be readout for the 16 channels. Design has been optimized for reduced power consumption and no components needed to interface inputs and outputs. Digital slow control to tune the circuit behaviour is also included. The prototype measurements have proved to be a valid option for integration in a full system scanner. An adapted prototype of the input stage using different technology and adapted to the different constraints from a particle detector is also presented. Only simulation results are available since device is still under production. An analysis of the different requirements needed by the SciFi tracker design is summarized. Current specifications are still evolving since final sensor is still not defined, but other requirements and some tunable elements permits to design such prototypes.