Analysis of the impact of the Asset Health Index in a Maintenance Strategy

Hosted by the Johannes Kepler University, Linz, Austria. May 23-24, 2019 - European Safety, Reliability & Data Association (ESReDA)During many years, asset management methodologies used in industry were focused on knowing and analysing the operational control of the daily work and the impact of the maintenance on the availability. Later, the costs turn into the priority, and strategies were focused on assesses a longer lifecycle and optimizing processes and contracts. Finally, recent normative have included concepts as “knowing and managing the risks” and the target is to prioritize the maintenance tasks to the critical assets. However, taking a balanced asset management model for the operational environment, quite a lot of facilities of Oil & Gas sector are reaching the end of their initially estimated lifecycle. New challenges are related to extend the life of the main items of the facilities or at least, to find the optimal replacement moment that guarantees that the maintenance strategy is being optimized. Asset Health Index methodology considers a theoretical lifecycle of an item, in which depending on the proximity to the end of the useful life, the probability of failure increases. But take this theoretical lifecycle as a base, different operation location factors or O&M aspects can modify this period. All these factor are quantified and permit us to calculate a new theoretical profile. This paper is about assess the impact of the AHI into the maintenance strategy optimisation. AHI enables us to compare future alternative cost profiles and assess the impact in the failure probability of the item. As a result, we are able to know the risk that is taken when we enlarge the operation of an item, and the impact in the operational costs

Implicaciones clínicopatologicas del gen TMPRSS2-ERG y perfil molecular asociado en cáncer de próstata

El cáncer de próstata (CaP) es un problema sanitario de primer orden. Mundialmente, cada año se diagnostican aproximadamente 700.000 casos, de los cuales, 13.300 corresponden a España. En cuanto al manejo clínico, esta enfermedad presenta una serie de problemas que conducen tanto al infraestadiaje como al sobretratamiento de un porcentaje significativo de tumores. En este contexto, en 2005 se descubrió un gen quimérico formado por TMPRSS2 y ERG, presente en aproximadamente la mitad de tumores prostáticos y totalmente específico de este tipo de cáncer. La presente tesis, caracteriza clínica y biológicamente este reordenamiento y un perfil de expresión de genes relacionados a fin de mejorar el manejo clínico del CaP. Para ello, se analizaron 314 muestras retrospectivas de tejido fijado en formol e incluido en parafina (FFPE) proveniente de prostatectomías radicales, dando como resultado una frecuencia del 46.2% y objetivando la relación entre la presencia de este reordenamiento con una mayor infiltración perineural. Como objetivo metodológico secundario, se compararon las técnicas FISH y RT-PCR en la detección del gen de fusión mostrándose una concordancia entre ambas del 80,9%. En cuanto al análisis de la expresión de TMPRSS2, ERG, ETV1, ETV4, PCA3, HEPSIN, PAR-2, GSTP-1, AMACR y Cav-1 y las proteínas PTEN, Ki-67, Cav-1, CD-99 y TPD-52, como potenciales biomarcadores, se objetivaron las siguientes relaciones: el estadio de Gleason está relacionado con la expresión de PCA3, Hepsin y Cav-1, la concentración sérica de PSA correlaciona con la expresión de PCA3, Hepsin, AMACR y de las proteínas Cav-1 y TPD52. En cuanto al estadio clínico, correlaciona con la expresión de AMACR, TMPRSS2 y ERG, por su parte, el estadio patológico está significativamente relacionado con la expresión de Hepsin, AMACR, ERG y Cav-1. Por último, la presencia de infiltración perineural correlaciona con la expresión de ETV4, Hepsin, PAR-2, GSTP-1 y TMPRSS2. Por otro lado, tomando la expresión génica global, mediante un análisis por clusters no supervisados, la serie queda estratificada en 3 grupos que correlacionan con los estadios clínico y patológico y con la presencia de infiltración perineural y TMPRSS2-ERG en la muestra. De hecho, en un análisis de supervivencia multivariante sobre la serie global, tienen valor pronóstico independiente de recaída bioquímica, el estadio de Gleason, la concentración sérica de PSA y la presencia de invasión perineural, los casos que no portan el gen de fusión, tienen como factores de riesgo; la concentración inicial de PSA, el estadio clínico y la presencia de invasión perineural. Por último en los casos portadores del reordenamiento génico, presentan valor pronóstico, el estadio de Gleason, la concentración sérica inicial de PSA, la expresión génica de GSTP-1 y la de la proteína TPD-52. Aprovechando que TMPRSS2-ERG es un biomarcador de gran especificidad, se cuantificó su presencia para la detección de células tumorales circulantes (CTC) en 275 muestras de sangre periférica. En el ámbito de la oncología clínica, la detección de este tipo de células es importante para la monitorización de enfermedad mínima residual, que es aquella no detectable por las técnicas diagnósticas usadas en la actualidad. Para llevar a cabo la detección de CTCs, se puso a punto una técnica de cuantificación absoluta del gen de fusión en CTC por PCR cuantitativa extrapolando los resultados en una curva patrón obtenida por clonación de la secuencia específica del gen de fusión. En este trabajo 33 pacientes presentaron CTC, once de los cuales también portaban el gen en muestras FFPE provenientes de prostatectomía radical y otros 5 pacientes han presentado CTC en algún momento del seguimiento pero las han negativizado. Sólo uno de los pacientes portadres de CTC presentó progresión bioquímica durante su seguimiento. Por otro lado, la presencia de CTC no correlacionó con ninguno de los parámetros clínicopatologicos estudiados.Prostate cancer (PCa) is a major health problem. Globally, each year approximately 700,000 cases are diagnosed, 13,300 of which correspond to Spain. In terms of clinical management, this disease presents problems that lead to both over treatment and understaging of a significant percentage of tumors. In this context, it was discovered in 2005 a chimeric gene called TMPRSS2-ERG, present in approximately half of prostate tumors. This gene is specific for this kind of cancer. This thesis, characterizes clinically and biologically this rearrangement and a gene expression profile in order to improve the clinical management of PCa. For this purpose, 314 samples from radical prostatectomies were analyzed retrospectively. TMPRSS2-ERG was detected in 46.2% of the cases. This finding was related with an increased perineural infiltration rate. Methodological secondary objective was to compare both FISH and RT-PCR techniques in the detection of this fusion gene showing a match between techniques of a 80.9%. In the analysis of the expression of TMPRSS2, ERG, ETV1, ETV4, PCA3, hepsin, PAR-2, GSTP-1, AMACR and Cav-1 and the following proteins: PTEN, Ki-67, Cav-1, CD-99 and TPD-52 as potential biomarkers, the following relations were observed: Gleason stage is related to the expression of PCA3, Hepsin and Cav-1. PSA serum level correlates with the expression of PCA3, Hepsin, and AMACR, and the proteins: Cav-1 and TPD52. Regarding the clinical stage, it correlates with the expression of AMACR, TMPRSS2 and ERG. Meanwhile, pathologic stage is significantly related to the expression of Hepsin, AMACR, ERG and Cav-1. Finally, the presence of perineural invasion correlates with ETV4, Hepsin, PAR-2, GSTP-1 and TMPRSS2 expression. Furthermore, by analyzing the global gene expression using an unsupervised clustering test, this series is stratified into 3 groups that correlate with clinical and pathological stage and the presence of perineural invasion and TMPRSS2-ERG in the sample. Otherwise, in a multivariate survival analysis on the global series, present independent prognostic value of biochemical failure, Gleason stage, serum PSA and the presence of perineural invasion, cases that do not carry the gene fusion have as risk factors, the initial concentration of PSA, clinical stage and the presence of perineural invasion. Finally, in the cases which harbors the gene rearrangement, retains its prognostic value the following parameters, Gleason stage, initial serum PSA gene expression of GSTP-1 and the TPD-52 protein. Taking advantage of the TMPRSS2-ERG high specificity as biomarker, its expression was quantified in order to detect circulating tumor cells (CTC) in 275 peripheral blood samples. In the field of clinical oncology, the detection of this kind of cells is a very useful tool for monitoring minimal residual disease, which is the one not detectable by standard diagnostic techniques. To carry out the detection of CTCs, we develop a technique for absolute quantification of the fusion gene by quantitative PCR. We built a standard curve by cloning TMPRSS2-ERG sequence. In this study, 33 cases showed CTC, eleven of whom also carried the rearrangement in paired FFPE samples. Another 5 patients have CTCs at some point of the track but negativized it later. Only one patient carrying CTCs had biochemical progression during follow-up. On the other hand, the presence of CTCs did not correlate with any of the clinicopathological parameters studied

Genetic Counseling in Renal Masses

All urologists have faced patients suffering a renal cancer asking for the occurrence of the disease in their offspring and very often the answer to this question has not been well founded from the scientific point of view, and only in few cases a familial segregation tree is performed. The grate shift seen in the detection of small renal masses and renal cancer in the last decades will prompt us to know the indications for familial studies, which and when are necessary, and probably to refer those patients with a suspected familial syndrome to specialized oncological centers where the appropriate molecular and familial studies could be done. Use of molecular genetic testing for early identification of at-risk family members improves diagnostic certainty and would reduce costly screening procedures in at-risk members who have not inherited disease-causing mutations. This review will focus on the molecular bases of familial syndromes associated with small renal masses and the indications of familial studies in at-risk family members

Using Inverse Reinforcement Learning with Real Trajectories to Get More Trustworthy Pedestrian Simulation

Reinforcement learning is one of the most promising machine learning techniques to get intelligent behaviors for embodied agents in simulations. The output of the classic Temporal Difference family of Reinforcement Learning algorithms adopts the form of a value function expressed as a numeric table or a function approximator. The learned behavior is then derived using a greedy policy with respect to this value function. Nevertheless, sometimes the learned policy does not meet expectations, and the task of authoring is difficult and unsafe because the modification of one value or parameter in the learned value function has unpredictable consequences in the space of the policies it represents. This invalidates direct manipulation of the learned value function as a method to modify the derived behaviors. In this paper, we propose the use of Inverse Reinforcement Learning to incorporate real behavior traces in the learning process to shape the learned behaviors, thus increasing their trustworthiness (in terms of conformance to reality). To do so, we adapt the Inverse Reinforcement Learning framework to the navigation problem domain. Specifically, we use Soft Q-learning, an algorithm based on the maximum causal entropy principle, with MARL-Ped (a Reinforcement Learning-based pedestrian simulator) to include information from trajectories of real pedestrians in the process of learning how to navigate inside a virtual 3D space that represents the real environment. A comparison with the behaviors learned using a Reinforcement Learning classic algorithm (Sarsa(λ)) shows that the Inverse Reinforcement Learning behaviors adjust significantly better to the real trajectories

Molecular characterization and clinical impact of TMPRSS2-ERG rearrangement on prostate cancer: comparison between FISH and RT-PCR

Prostate cancer (PCa) is a very heterogeneous disease, and there are constraints in its current diagnosis. Serum PSA levels, digital rectal examination (DRE), and histopathologic analysis often drive to overdiagnosis and overtreatment. Since 2005, the presence of the genetic rearrangement between transmembrane-serine protease gene (TMPRSS2) and the erythroblast transformation-specific (ETS)member ERG (v-ets erythroblastosis virus E26 oncogene homolog avian) has been demonstrated in almost half of PCa cases. Both FISH and RT-PCR are useful tools for detecting these rearrangements, but very few comparatives between both techniques have been published. In this study, we included FFPE tumors from 294 PCa patients treated with radical prostatectomy with more than 5 years of followup.We constructed a total of 20 tissue microarrays in order to perform break-apart and tricolor probe FISH approaches that were compared with RT-PCR, showing a concordance of 80.6% ( P < 0.001). The presence of TMPRSS2-ERG rearrangement was observed in 56.6% of cases. No association between TMPRSS2-ERG status and clinicopathological parameters nor biochemical progression and clinical progression free survival was found. In conclusion, this study demonstrates that both FISH and RT-PCR are useful tools in the assessment of the TMPRSS2-ERG fusion gene status in PCa patients and that this genetic feature per se lacks prognostic value.This study has been funded by the Grants FIS PI06/01619 and PI10/01206 from the Instituto de Salud Carlos III, Madrid, ACOMP 12/029 from the Generalitat Valenciana, Valencia, and Astra Zeneca, Spain

Crystallographic information data of natural occurring zaccariniite (RhNiAs) obtained by means of precession electron diffraction

The crystal structure of naturally occurring zaccariniite (RhNiAs) has been studied in Transmission Electron Microscopy (TEM) with variable angle Precession Electron Diffraction (PED) techniques. The analysis of the data has yielded tetragonal cell parameters of 3.86, 3.86, 6.77 Å and space group of P4/nmm for the basic structure, and its constituent atom positions for Ni, As and Rh were determined as well by ab-initio structure resolution method. The data is related to "Structural characterization and ab-initio resolution of natural occurring zaccariniite (RhNiAs) by means of Precession Electron Diffraction" (Roqué Rosell et al., 2019)

Treatment of small vessel disease with the paclitaxel drug-eluting balloon: 6-month angiographic and 1-year clinical outcomes of the Spanish multicenter registry

Background: small vessel disease (SMD) remains a major challenge because of the increased risk of restenosis. We sought to assess the efficacy and safety of a paclitaxel-eluting balloon (PEB) in patients with SMD. Methods and results: one-hundred and four patients with native coronary lesions in small vessels treated by using a PEB were included in this prospective multicenter registry. In each case, after regular balloon dilatation, a larger PEB was inflated for a minimum of 45-60 seconds. Patients were 65 ± 10 years old, 43% diabetic, and 58% presented acutely. Angiographic success was 93% (7% bailout BMS implantation due to coronary dissection). The rate of major adverse cardiac events (MACE) at 12 months was 4.8% (1.9% cardiac death, 1.0% MI, and 2.9% TLR). One definite stent thrombosis was reported at 6 months in a patient with bailout BMS implantation. At 7 months, late loss was 0.31 ± 0.2 mm. Bail-out BMS after DEB use, was an independent predictor of MACE, HR 18.74, 95%CI (2.58-135.84) and TLR, HR 30.99, 95%CI (2.79-344.07). Conclusion: the use of this PEB for the treatment of SMD provides excellent 1-year outcomes with only 4.8% MACE. The need for a bailout BMS was a strong predictor of MACE and TLR

Fractal dimension analysis of malignant and benign endobronchial ultrasound nodes

Background: Endobronchial ultrasonography (EBUS) has been applied as a routine procedure for the diagnostic of hiliar and mediastinal nodes. The authors assessed the relationship between the echographic appearance of mediastinal nodes, based on endobronchial ultrasound images, and the likelihood of malignancy.; Methods: The images of twelve malignant and eleven benign nodes were evaluated. A previous processing method was applied to improve the quality of the images and to enhance the details. Texture and morphology parameters analyzed were: the image texture of the echographies and a fractal dimension that expressed the relationship between area and perimeter of the structures that appear in the image, and characterizes the convoluted inner structure of the hiliar and mediastinal nodes.; Results: Processed images showed that relationship between log perimeter and log area of hilar nodes was lineal (i.e. perimeter vs. area follow a power law). Fractal dimension was lower in the malignant nodes compared with non-malignant nodes (1.47(0.09), 1.53(0.10) mean(SD), Mann-Whitney U test p < 0.05)).; Conclusion: Fractal dimension of ultrasonographic images of mediastinal nodes obtained through endobronchial ultrasound differ in malignant nodes from non-malignant. This parameter could differentiate malignat and non-malignat mediastinic and hiliar nodes.Peer ReviewedPostprint (published version

3D-printed PLA medical devices: physicochemical changes and biological response after sterilisation treatments

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGPolylactic acid (PLA) has become one of the most commonly used polymers in medical devices given its biocompatible, biodegradable and bioabsorbable properties. In addition, due to PLA’s thermoplastic behaviour, these medical devices are now obtained using 3D printing technologies. Once obtained, the 3D-printed PLA devices undergo different sterilisation procedures, which are essential to prevent infections. This work was an in-depth study of the physicochemical changes caused by novel and conventional sterilisation techniques on 3D-printed PLA and their impact on the biological response in terms of toxicity. The 3D-printed PLA physicochemical (XPS, FTIR, DSC, XRD) and mechanical properties as well as the hydrophilic degree were evaluated after sterilisation using saturated steam (SS), low temperature steam with formaldehyde (LTSF), gamma irradiation (GR), hydrogen peroxide gas plasma (HPGP) and CO2 under critical conditions (SCCO). The biological response was tested in vitro (fibroblasts NCTC-929) and in vivo (embryos and larvae wild-type zebrafish Danio rerio). The results indicated that after GR sterilisation, PLA preserved the O:C ratio and the semi-crystalline structure. Significant changes in the polymer surface were found after HPGP, LTSF and SS sterilisations, with a decrease in the O:C ratio. Moreover, the FTIR, DSC and XRD analysis revealed PLA crystallisation after SS sterilisation, with a 52.9% increase in the crystallinity index. This structural change was also reflected in the mechanical properties and wettability. An increase in crystallinity was also observed after SCCO and LTSF sterilisations, although to a lesser extent. Despite these changes, the biological evaluation revealed that none of the techniques were shown to promote the release of toxic compounds or PLA modifications with toxicity effects. GR sterilisation was concluded as the least reactive technique with good perspectives in the biological response, not only at the level of toxicity but at all levels, since the 3D-printed PLA remained almost unaltered.POCTEP INTERREG España- Portugal | Ref. BLUEBIOLABInterreg Atlantic Area | Ref. BLUEHUMAN EAPA_151/2016Ministerio de Ciencia e Innovación | Ref. PID 2020-115415RB-100Xunta de Galicia | Ref. ED431C 2021/49Xunta de Galicia | Ref. ED481A 2019/314Xunta de Galicia | Ref. IN606A-2017/011Fundação para a Ciência e a Tecnologia | Ref. UIDB/50016/202

Estudio de la citotoxicidad de cerámicas biomórficas de SiC recubiertas con vidrio bioactivo

La necesidad de desarrollar nuevos implantes basados en materiales bioactivos que sean capaces de soportar grandes cargas mecánicas ha llevado a la producción de sustratos metálicos recubiertos con cerámicas bioactivas. Recientemente se ha propuesto un dispositivo alternativo que consiste en un sustrato de carburo de silicio (SiC) biomórfico recubierto con vidrio bioactivo, mediante la técnica de Depósito por Láser Pulsado (PLD), y que dispone de la resistencia mecánica adecuada, además de gran ligereza y una porosidad intrínseca muy favorable de cara a la implantación. En este trabajo se presenta un estudio interdisciplinar de este nuevo material centrado en la morfología y porosidad de sustratos de SiC provenientes de diferentes maderas, la bioactividad de los recubrimientos producidos por PLD y en la evaluación in vitro con células de osteosarcoma MG-63 con la que se ha determinado la citotoxicidad de estos materiales y se ha estudiado la influencia de los mismos en la adhesión y la proliferación celular.In the past years there was a need to develop new tough bioactive materials capable to resist high loads when implanted in the body, that led to the production of bioactive coatings on metallic substrates. A new approach, which consists of biomorphic silicon carbide (SiC) coated with bioactive glass by Pulsed Laser Deposition (PLD), was recently presented. This new material joins the high mechanical strength, lightness and porosity of biomorphic SiC and the bioactive properties of PLD glass films. In this work, a multiple evaluation of this new material is presented starting from the biomorphic SiC morphology and porosity, following with the bioactivity in simulated body fluid of the coatings, and ending with a deep in vitro study with MG-63 cells. The citotoxicity of the SiC coated and uncoated and the cell proliferation and attachment were studied