Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case–control analysis

PURPOSES: We conducted a case–control analysis to explore the association between occupational exposure to asbestos and cholangiocarcinoma (CC). METHODS: The study was based on historical data from 155 consecutive patients with CC [69 intrahepatic CC (ICC) and 86 extrahepatic CC (ECC)] referred to Sant’Orsola-Malpighi University Hospital between 2006 and 2010. The cases were individually matched by calendar period of birth, sex, and region of residence to historical hospital and population controls. Occupational exposure to asbestos was retrospectively assessed considering job titles obtained from work histories. Separate conditional logistic regression models were applied for ECC and ICC. Estimates were adjusted for smoking status and socioeconomic class. RESULTS: We matched 149 controls (median birth year: 1947; males: 56 %) to 41 cases of ICC (median birth year: 1946; males: 56 %) and 212 controls (median birth year: 1945; males: 48 %) to 59 cases of ECC (median birth year: 1945; males 51 %); 53 cases were not matched due to residence or birth year. We found an increased risk of ICC in workers exposed to asbestos (adjusted OR 4.81, 95 % CI 1.73–13.33); we also observed suggestive evidence that asbestos exposure might be associated with ECC (adjusted OR 2.09, 95 % CI 0.83–5.27). Sensitivity analysis restricted to patients from the Province of Bologna produced confirmatory figures. CONCLUSIONS: Our findings suggest that ICC could be associated with asbestos exposure; a chronic inflammatory pathway is hypothesized. Exposure to asbestos could be one of the determinants of the progressive rise in the incidence of ICC during the last 30 years

Channel estimation, data detection and carrier frequency offset estimation in OFDM systems

Orthogonal Frequency Division Multiplexing (OFDM) plays an important role in the implementation of high data rate communication. In this thesis, the problems of data detection and channel and carrier frequency offset estimation in OFDM systems are studied. Multi-symbol non-coherent data detection is studied which performs data detection by processing multiple symbols without the knowledge of the channel impulse response (CIR). For coherent data detection, the CIR needs to be estimated. Our objective in this thesis is to work on blind channel estimators which can extract the CIR using just one block of received OFDM data. A blind channel estimator for (Single Input Multi Output) SIMO OFDM systems is derived. The conditions under which the estimator is identifiable is studied and solutions to resolve the phase ambiguity of the proposed estimator are given.A channel estimator for superimposed OFDM systems is proposed and its CRB is derived. The idea of simultaneous transmission of pilot and data symbols on each subcarrier, the so called superimposed technique, introduces the efficient use of bandwidth in OFDM context. Pilot symbols can be added to data symbols to enable CIR estimation without sacrificing the data rate. Despite the many advantages of OFDM, it suffers from sensitivity to carrier frequency offset (CFO). CFO destroys the orthogonality between the subcarriers. Thus, it is necessary for the receiver to estimate and compensate for the frequency offset. Several high accuracy estimators are derived. These include CFO estimators, as well as a joint iterative channel/CFO estimator/data detector for superimposed OFDM. The objective is to achieve CFO estimation with using just one OFDM block of received data and without the knowledge of CIR

Contribució de la P-selectina en els processos inflamatoris

[cat] La P-selectina és una molècula d'adhesió que mitjança la interacció de les cèl·lules endotelials i plaquetes activades amb els leucòcits. Desenvolupa un paper determinant en la resposta inflamatòria, ja que possibilita l'adhesió inicial dels leucòcits circulants a l'endoteli activat, generant un rodament deis leucòcits sobre la paret vascular que és clau per la posterior migració i acumulació deis leucòcits als lIocs de lesió, on desenvolupen la seva resposta immunològica. La P-selectina també participa en la trombogènesi, promovent la interacció entre els leucòcits i les plaquetes, de manera que afavoreix la incorporació dels leucòcits als trombes en formació i la seva activació. La P-selectina juga un paper important en diversos models inflamatoris experimentals i s'ha vist que la seva inhibició, bé mitjançant anticossos que bloquegen la seva funció o generant animals genèticament deficients en la proteïna, millora l'evolució de la inflamació. Per tant, el bloqueig de la P-selectina en humans podria tenir un elevat potencial terapèutic. Però abans és important definir amb precisió la seva funció específica en el desenvolupament de respostes inflamatòries concretes, de cara a avaluar l’eficàcia del seu bloqueig com a tractament en desordres inflamatoris. És per això que l'objectiu general de la present tesi és caracteritzar la contribució de la P-selectina als processos inflamatoris

Multichannel bioimpedance measurement

This thesis is a research about the possibility of measure bioimpedance simultaneously in different body locations. It first rises a theoretical study facing the problem as a classic multichannel communication system with share channel, analysing the software and hardware problems involved for all the possibilities. The more suitable configuration chosen is based on frequency multiplexation, it consists of injecting isolated sine waves with different frequencies for each channel and uses a bandpass filter to get only the required one. About the signal processing the best option found is to record the signal using undersampling techniques and implements the filter digitally. Moreover a three channel test device has been made following the calculations for a eight channels one, in order to test the theoretical research and to find possible practical limitations. Finally this test device has been used for a concrete purpose, the breathing measuring in three points on the thorax

Rôle pathogénique de l’IL-15 dans la stéatose hépatique

Abstract : Pro-inflammatory cytokines play a key role in pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD). IL-15 is a pro-inflammatory cytokine, which signals through a receptor complex composed of the IL-15 receptor (IL-15R) alpha chain, the IL-2/IL-15R beta chain and the common gamma chain. The functions of IL-15 have been extensively described in immune cells but less is known about its functions in others tissues such as the liver. The aim of this thesis is to investigate the role of IL-15 in fatty liver disease. C57BL/6 wildtype (WT) and IL-15 knockout (Il15[superscript -/-]) mice were maintained on high fat diet (HFD) or normal control diet (NCD). After 16 weeks, body weight, liver mass, fat accumulation in the liver, serum lipid levels and gene expression in the liver were evaluated. Intrahepatic lymphocytes (IHL) were also analysed. Primary hepatocytes were stimulated with IL-15 and chemokines gene expression was studied. IHLs were examined in WT, Il15[superscript -/-] and Il15ra[superscript -/-], as well as in macrophage- and hepatocyte-specific Il15ra[superscript -/-] mice. We found that IL-15 deficiency prevents weight gain and accumulation of lipids in the liver. Circulating levels of cholesterol and non-esterified fatty acids were elevated in WT mice but not in Il15[superscript -/-] mice. Hepatic expression of chemokines such as Ccl2, Ccl5 and Cxcl10 was increased in WT mice under HFD, but not in Il15[superscript -/-] mice. The livers of Il15[superscript -/-] and Il15ra[superscript -/-] mice also showed decreased expression of Tnfa and iNOS, and macrophage markers Cd68 and F4/80. Accordingly, stimulation of primary hepatocytes with IL-15 induced chemokine gene expression in WT but not in Il15ra[superscript -/-] hepatocytes. Furthermore, hepatocyte-specific ablation of IL-15Rαreduced infiltration of NK and NKT cells in the liver, suggesting that IL15Rα expression in the hepatocytes is needed for the recruitment and/or maintenance of the NK cell population in the liver. In conclusion, IL-15 promotes fat accumulation in the liver, and this is associated with increased inflammatory response in the liver. Increased availability of IL-15 in obesity may stimulate hepatocytes to secrete chemokines that promote hepatic inflammation resulting in fatty liver disease. IL-15Rα expression in hepatocytes appears to play a role in the maintenance of NK, NKT and iNKT cells. // Résumé : Les cytokines pro-inflammatoires jouent un rôle important dans la pathogenèse de l’obésité et la stéatose hépatique. L'IL-15 est une cytokine pro-inflammatoire qui est trans-présentée par l'IL-15Rα aux chaines IL-2/IL-15Rβ et γc. La fonction de l'IL-15 a été largement décrite dans les cellules immunitaires, mais ses fonctions dans d'autres tissus sont moins connues. Le but de ce mémoire est d'élucider le rôle de l'IL-15 dans la stéatose hépatique. Les souris C57BL/6 de type sauvage (WT) et Il15[indice supérieur -/-] ont été soumises à un régimehyperlipidique (HFD) ou à un régime normal. Après 16 semaines, le poids corporel, lamasse hépatique, l'accumulation de lipides dans le foie, les taux de lipides sériques et l'expression des différents gènes reliés à l’inflammation et au métabolisme dans le foie ont été évalués. Les lymphocytes intra-hépatiques (IHL) ont été également étudiés. Des hépatocytes primaires ont été stimulés avec IL-15, et l'expression génique de chimiokines a été déterminée. Les populations de IHLs ont été également caractérisées chez les souris WT, Il15[indice supérieur -/-] et Il15ra[indice supérieur -/-], ainsi que chez des souris dont la déficience dans l’expression d’IL-15Rα est ciblée aux macrophages ou aux hépatocytes. Nos résultats montrent que la déficience en IL-15 empêche l'accumulation de lipides dans le foie. Les taux de cholestérol et d’acides gras non estérifiés dans le sang étaient élevés chez les souris WT, mais pas chez les souris Il15[indice supérieur -/-]. L'expression hépatique des chimiokines Ccl2, Ccl5, Cxcl10 et des marqueurs de macrophages était augmentée chez les souris WT sous HFD, mais pas chez les souris Il15[indice supérieur -/-]. La stimulation des hépatocytes primaires avec l'IL-15 induit l'expression des gènes des chimiokines chez les hépatocytes WT, mais pas chez les Il15ra[indice supérieur -/-]. En outre, nous avons trouvé une infiltration réduite des cellules NK et NKT dans le foie des souris déficientes en Il15ra[indice supérieur -/-] dans les hépatocytes, ce qui suggère que l'expression d’IL15Rα chez les hépatocytes est nécessaire aurecrutement des cellules NK, NKT et / ou à leur maintien. En conclusion, nous proposons que l’IL-15 favorise l'accumulation de lipides dans le foie, et que ceci est associée à une réponse inflammatoire accrue. La disponibilité accrue de l'IL-15 dans l'obésité pourrait stimuler les hépatocytes à secréter des chimiokines ce qui favorise l'inflammation hépatique et conduirait à la stéatose hépatique. L’expression de l'IL-15Rα dans les hépatocytes semble jouer un rôle principal dans l’infiltration des cellules NK, NKT et iNKT dans le foie