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[Background] Gastrointestinal stromal tumor (GIST) initiation and evolution is commonly framed by KIT/PDGFRA oncogenic activation, and in later stages by the polyclonal expansion of resistant subpopulations harboring KIT secondary mutations after the onset of imatinib resistance. Thus, circulating tumor (ct)DNA determination is expected to be an informative non-invasive dynamic biomarker in GIST patients., [Methods] We performed amplicon-based next-generation sequencing (NGS) across 60 clinically relevant genes in 37 plasma samples from 18 GIST patients collected prospectively. ctDNA alterations were compared with NGS of matched tumor tissue samples (obtained either simultaneously or at the time of diagnosis) and cross-validated with droplet digital PCR (ddPCR)., [Results] We were able to identify cfDNA mutations in five out of 18 patients had detectable in at least one timepoint. Overall, NGS sensitivity for detection of cell-free (cf)DNA mutations in plasma was 28.6%, showing high concordance with ddPCR confirmation. We found that GIST had relatively low ctDNA shedding, and mutations were at low allele frequencies. ctDNA was detected only in GIST patients with advanced disease after imatinib failure, predicting tumor dynamics in serial monitoring. KIT secondary mutations were the only mechanism of resistance found across 10 imatinib-resistant GIST patients progressing to sunitinib or regorafenib., [Conclusions] ctDNA evaluation with amplicon-based NGS detects KIT primary and secondary mutations in metastatic GIST patients, particularly after imatinib progression. GIST exhibits low ctDNA shedding, but ctDNA monitoring, when positive, reflects tumor dynamics.

This is the peer reviewed version of the following article: Bendezú, R. A., Barba, E., Burri, E., Cisternas, D., Accarino, A., Quiroga, S., Monclus, E., Navazo, I., Malagelada, J.-R. and Azpiroz, F. (2016), Colonic content in health and its relation to functional gut symptoms. Neurogastroenterol. Motil., 28: 849–854, which has been published in final form at [doi:10.1111/nmo.12782]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving, Gut content may be determinant in the generation of digestive symptoms, particularly in patients with impaired gut function and hypersensitivity. Since the relation of intraluminal gas to symptoms is only partial, we hypothesized that non-gaseous component may play a decisive role. Methods: Abdominal computed tomography scans were evaluated in healthy subjects during fasting and after a meal (n = 15) and in patients with functional gut disorders during basal conditions (when they were feeling well) and during an episode of abdominal distension (n = 15). Colonic content and distribution were measured by an original analysis program. Key results: In healthy subjects both gaseous (87 ± 24 mL) and non-gaseous colonic content (714 ± 34 mL) were uniformly distributed along the colon. In the early postprandial period gas volume increased (by 46 ± 23 mL), but non-gaseous content did not, although a partial caudad displacement from the descending to the pelvic colon was observed. No differences in colonic content were detected between patients and healthy subjects. Symptoms were associated with discrete increments in gas volume. However, no consistent differences in non-gaseous content were detected in patients between asymptomatic periods and during episodes of abdominal distension. Conclusions & inferences: In patients with functional gut disorders, abdominal distension is not related to changes in non-gaseous colonic content. Hence, other factors, such as intestinal hypersensitivity and poor tolerance of small increases in luminal gas may be involved., Peer Reviewed, Postprint (author's final draft)

BACKGROUND & AIMS: In patients with functional gut disorders, abdominal distension has been associated with descent of the diaphragm and protrusion of the anterior abdominal wall. We investigated mechanisms of abdominal distension in these patients. METHODS: We performed a prospective study of 45 patients (42 women, 24-71 years old) with functional intestinal disorders (27 with irritable bowel syndrome with constipation, 15 with functional bloating, and 3 with irritable bowel syndrome with alternating bowel habits) and discrete episodes of visible abdominal distension. Subjects were assessed by abdominothoracic computed tomography (n = 39) and electromyography (EMG) of the abdominothoracic wall (n = 32) during basal conditions (without abdominal distension) and during episodes of severe abdominal distension. Fifteen patients received a median of 2 sessions (range, 1-3 sessions) of EMG-guided, respiratory-targeted biofeedback treatment; 11 received 1 control session before treatment. RESULTS: Episodes of abdominal distension were associated with diaphragm contraction (19% +/- 3% increase in EMG score and 12 +/- 2 mm descent; P < .001 vs basal values) and intercostal contraction (14% +/- 3% increase in EMG scores and 6 +/- 1 mm increase in thoracic antero-posterior diameter; P < .001 vs basal values). They were also associated with increases in lung volume (501 +/- 93 mL; P < .001 vs basal value) and anterior abdominal wall protrusion (32 +/- 3 mm increase in girth; P < .001 vs basal). Biofeedback treatment, but not control sessions, reduced the activity of the intercostal muscles (by 19% +/- 2%) and the diaphragm (by 18% +/- 4%), activated the internal oblique muscles (by 52% +/- 13%), and reduced girth (by 25 +/- 3 mm) (P <= .009 vs pretreatment for all). CONCLUSIONS: In patients with functional gut disorders, abdominal distension is a behavioral response that involves activity of the abdominothoracic wall. This distension can be reduced with EMG-guided, respiratory, Peer Reviewed, Postprint (published version)

Background: The precise relation of intestinal gas to symptoms, particularly abdominal bloating and distension remains incompletely elucidated. Our aim was to define the normal values of intestinal gas volume and distribution and to identify abnormalities in relation to functional-type symptoms. Methods:Abdominal computed tomography scans were evaluated in healthy subjects (n = 37) and in patients in three conditions: basal (when they were feeling well; n = 88), during an episode of abdominal distension (n = 82) and after a challenge diet (n = 24). Intestinal gas content and distribution were measured by an original analysis program. Identification of patients outside the normal range was performed by machine learning techniques (one-class classifier). Results are expressed as median (IQR) or mean ± SE, as appropriate. Key Results: In healthy subjects the gut contained 95 (71, 141) mL gas distributed along the entire lumen. No differences were detected between patients studied under asymptomatic basal conditions and healthy subjects. However, either during a spontaneous bloating episode or once challenged with a flatulogenic diet, luminal gas was found to be increased and/or abnormally distributed in about one-fourth of the patients. These patients detected outside the normal range by the classifier exhibited a significantly greater number of abnormal features than those within the normal range (3.7 ± 0.4 vs 0.4 ± 0.1; p < 0.001). Conclusions & Inferences: The analysis of a large cohort of subjects using original techniques provides unique and heretofore unavailable information on the volume and distribution of intestinal gas in normal conditions and in relation to functional gastrointestinal symptoms., Peer Reviewed, Postprint (author's final draft)

[ANGLÈS] This project details the design, implementation and measures to characterize the hardware for the acquisition of the electrical impedance spectrum. It also includes the signal generation using an arbitrary multifrequency generator, the acquisition and the signal processing. The system is based on a Field Programmable Gate Array (FPGA). An embedded processor has been implemented inside the FPGA, which manages all the other blocks that comprise the system. It also includes hardware design, FPGA programming using VHDL code and predefined blocks and communicating with the computer via the USB port. Finally, measurements were carried out to characterize the system to verify its performance., [CASTELLÀ] El presente proyecto detalla el diseño, la implementación y las medidas de caracterización del hardware para la adquisición de espectros de impedancia eléctrica. Incluye la generación de señal mediante un generador arbitrario multifrecuencia, la adquisición y el procesado de señal. Está basado en una Field Programmable Gate Array (FPGA). Se ha implementado un procesador embebido dentro de la FPGA que gestiona los otros bloques de los que consta el sistema. También incluye el diseño del hardware, programación de la FPGA mediante código VHDL y bloques predefinidos y comunicación con el ordenador a través del puerto USB. Finalmente, se han realizado medidas de caracterización del sistema para verificar sus prestaciones., [CATALÀ] El present projecte detalla el disseny, la implementació i les mesures de caracterització del hardware per a l’adquisició d’espectres d’impedància elèctrica. Inclou la generació del senyal mitjançant un generador arbitrari multifreqüència, l’adquisició i el processament del senyal. Està basat en una Field Programmable Gate Array (FPGA). S’ha implementat un processador embegut dins la FPGA que gestiona els altres blocs dels que consta el sistema. També inclou el disseny del hardware, programació de la FPGA mitjançant codi VHDL i blocs predefinits i comunicació amb l’ordinador a través del port USB. Finalment, s’han realitzat mesures de caracterització del sistema per verificar les seves prestacions.

[ANGLÈS] This project describes the development and validation, using experimental measurements, of the software (user interface, PC and Field Programmable Gate Array (FPGA) communication and embedded software programming) of an arbitrary multifrequency analyzer for electrical impedance spectrum measurements based in FPGA. To manage all the hardware components used for the impedance measurements, a code has been developed and implemented inside a embedded processor inside FPGA and also the corresponding part of the communication between the PC via USB port. This project includes control software implemented with the computer using LabVIEW. To conclude, characterization measures are made to verify the system specifications., [CASTELLÀ] El proyecto realizado describe el desarrollo y la validación mediante medidas experimentales del programario (interficie de usuario, comunicación entre el PC y la placa donde reside el dispositivo programable llamado Field Programmable Gate Array(FPGA) y el programario de éste) de un analizador arbitrario multifrecuencia basado en FPGA para la medida de espectros de impedancia eléctrica. Para gestionar los componentes hardware que se encargan de la medida de impedancia se ha diseñado el código del programa del procesador embebido dentro da la FPGA i también la parte correspondiente a la comunicación con el ordenador a través del puerto USB. El proyecto también incluye un diseño de un programa de control del sistema implementado a través del ordenador mediante LabVIEW: Finalmente, se han realizado medidas de caracterización del sistema para verificar sus especificaciones., [CATALÀ] El projecte realitzat descriu el desenvolupament i validació mitjançant mesures experimentals del programari(interfície d'usuari, comunicació entre el PC i la placa on hi ha el dispositiu programable anomenat Field Programmable Gate Array (FPGA)i el programari d’aquest) d'un analitzador arbitrari multifreqüència basat en FPGA per a la mesura d’espectres d'impedància elèctrica. Per tal de gestionar els components hardware encarregats de la mesura d’impedància s’ha dissenyat el codi del programa del processador embegut dins de la FPGA i també la part corresponent a la comunicació amb l’ordinador a través del port USB. El projecte també inclou el disseny d’un software de control del sistema implementat a l’ordinador mitjançant Labview. Finalment, s’han realitzat mesures de caracterització del sistema per verificar les seves especificacions.

La domòtica és un camp d'aplicació de l'electrònica que ha experimentat un creixement molt ràpid en els últims anys. La necessitat d'estalviar energia tant elèctrica com de gas i la comoditat de disposar de vivendes intel·ligents automatitzades són alguns dels motius que expliquen aquest creixement. Aquest projecte tracta sobre la gestió domòtica d’una vivenda fictícia que permeti, d'una banda establir rutines d'estalvis d'energia tant en il·luminació com en climatització i, de l'altra, garantir la seguretat dels seus habitants controlant de manera automàtica l'accés a ella. Es col·locaran sensors de llum i de temperatura a les diferents estances de la vivenda per controla aquests dos paràmetres i també hi haurà col·locats uns detectors d’obertura a les portes i finestres per tal de saber si entra algú dins la vivenda mentre l’alarma està activada. Tot això serà controlat i gestionat per un microcontrolador PIC que, alhora, s'encarregarà del control dels actuadors que garantiran el correcte funcionament de l'alarma, la climatització i la seguretat. A més, serà capaç de comunicar-se amb un ordinador personal perquè l'usuari pugui veure l'estat de la vivenda.