Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; PPeer reviewe

Interpreting in Austrian and Spanish Hospitals: Healthcare Providers’ Attitude Towards Working Professional with Interpreters

En el ámbito de la interpretación en los servicios públicos, la interpretación sanitaria constituye un campo extendido y, dentro de él, la interpretación en hospitales. Mientras que existen ya varios estudios centrados en los mismos intérpretes, investigando su formación, papel y sus capacidades, se detectó que los trabajos enfocados en los médicos y enfermeros en el contexto de la interpretación sanitaria son todavía escasos. Para que funcione bien la comunicación mediada por un intérprete en el ámbito sanitario, sin embargo, es de suma importancia que no solo los intérpretes estén bien formados y conozcan su papel, sino que el personal sanitario sepa también cómo actuar a la hora de colaborar con un intérprete. El primer paso en esta dirección consiste en que los médicos, enfermeros y demás trabajadores sanitarios estén conscientes de las ventajas que aporta un intérprete profesional y tengan una idea de esta figura que corresponda a la realidad más bien que una influida por clichés carentes de veracidad. Por tanto, el presente estudio tiene por objetivo analizar qué opinión el personal sanitario tiene de la figura del intérprete profesional, y hasta qué punto el inglés empleado como lengua franca constituye, en su opinión, una alternativa a un intérprete. Con este propósito, se eligieron varios hospitales en Austria y España, dos países que, respecto a su evolución de la interpretación en los servicios públicos, se pueden considerar similares. El estudio parte de dos hipótesis: primero, que el personal sanitario en los hospitales austríacos y españoles todavía no está plenamente consciente de las ventajas que aporta un intérprete profesional. La segunda hipótesis se puede considerar parte de la primera, pero se formuló de manera más específica y enfocada en el inglés en su función de lengua franca que, según esta hipótesis, está sobrevalorado por parte de los médicos y enfermeros, sobre todo en Austria. Con fines de comprobar estas hipótesis, tras establecer un marco teórico con base en literatura científica específica, se emplearon dos tipos de metodología que, aunque sean distintas, se complementan una a otra. Principalmente, se llevó a cabo una encuesta mediante cuestionarios bilingües (en español y alemán para España y Austria, respectivamente). En el caso de Austria, además se realizaron entrevistas por vía telefónica para obtener respuestas más detalladas. Finalmente, se pudieron confirmar ambas hipótesis, constatando que efectivamente, todavía existen dudas sustanciales por parte del personal sanitario hacia los intérpretes profesionales, lo que puede traducirse en posteriores problemas a la hora de colaborar o incluso el hecho de evitar el servicio de un intérprete y en su vez, por ejemplo, recurrir al uso de inglés como lengua de comunicaciónWithin public service interpreting, healthcare interpreting represents a broad field and, as part of it, the interpreting for hospitals. While there are already numerous studies focused on the interpreters themselves, investigating their training and education, role, and capabilities, academic studies on the healthcare staff in situations of communicating through interpreters are rather scarce. In order to achieve a successful interpreter-mediated communication in the healthcare sector, however, it is not only essential that the interpreters be well trained and know their role, but also that the healthcare staff be informed on how to act when working with an interpreter. The first step in this direction consists in doctors, nurses and other healthcare workers being aware of the advantages that a professional interpreter brings and having an opinion of this figure that corresponds to reality rather than being based on clichés that lack truth. Thus, this study is aimed at analyzing what the healthcare staff thinks of professional interpreters, and to what point, in their opinion, the use of English as a lingua franca can substitute an interpreter. To this end, several hospitals in Spain and Austria were selected, seeing that the two countries can be considered comparable regarding their evolution of public service interpreting. For this study, two hypotheses have been formed: first, that the healthcare staff in Spanish and Austrian hospitals still is not fully aware of the advantages of a professional interpreter. The second hypothesis can be considered part of the first one, but has been phrased in a more specific way, focusing on English in its role as a lingua franca which, according to this hypothesis, is overvalued by doctors and nurses, especially in Austria. To proof these hypotheses, after having established the theoretical framework based on specialized academic literature, two kinds of methodology have been employed that, although different, complement one another. Mainly, a questionnaire study has been conducted using bilingual questionnaires (in Spanish and English for Spain and Austria, respectively). In Austria, some participants have additionally been interviewed in order to obtain more detailed responses. Finally, both hypotheses could be proofed – it has been shown that the healthcare staff has indeed still serious concerns regarding professional interpreters, which in turn might lead to problems when collaborating or even avoiding an interpreter’s services altogether and instead using English as a vehicular language for the communication.Máster Universitario en Comunicación Intercultural, Interpretación y Traducción en los Servicios Públicos. Especialidad en Inglés-Español (M045

Single-copy locus proteomics of early- and late-firing DNA replication origins identifies a role of Ask1/DASH complex in replication timing control

Summary: The chromatin environment at origins of replication is thought to influence DNA replication initiation in eukaryotic genomes. However, it remains unclear how and which chromatin features control the firing of early-efficient (EE) or late-inefficient (LI) origins. Here, we use site-specific recombination and single-locus chromatin isolation to purify EE and LI replication origins in Saccharomyces cerevisiae. Using mass spectrometry, we define the protein composition of native chromatin regions surrounding the EE and LI replication start sites. In addition to known origin interactors, we find the microtubule-binding Ask1/DASH complex as an origin-regulating factor. Strikingly, tethering of Ask1 to individual origin sites advances replication timing (RT) of the targeted chromosomal domain. Targeted degradation of Ask1 globally changes RT of a subset of origins, which can be reproduced by inhibiting microtubule dynamics. Thus, our findings mechanistically connect RT and chromosomal organization via Ask1/DASH with the microtubule cytoskeleton

Soluble Axl is an accurate biomarker of cirrhosis and hepatocellular carcinoma development: results from a large scale multicenter analysis

Patients with chronic liver disease (CLD) and cirrhosis are at high risk for hepatocellular carcinoma (HCC). Current diagnostic tools for HCC detection include imaging techniques and serum biomarkers such as a-fetoprotein (AFP). Yet, these methods are limited in sensitivity and specificity to accurately detect early HCC. Here we focused on the potential of soluble Axl (sAxl) as a biomarker in CLD patients by analyzing serum samples of 1067 patients and healthy controls from centers in Europe and Asia. We show that serum concentrations of sAxl were significantly increased at early (82.57 ng/mL) and later stages of HCC (114.50 ng/mL) as compared to healthy controls (40.15 ng/mL). Notably, no elevated sAxl levels were detected in patients with CLD including chronic viral hepatitis, autoimmune hepatitis, cholestatic liver disease, or non-alcoholic fatty liver disease versus healthy controls. Furthermore, sAxl did not rise in liver adenomas or cholangiocarcinoma (CCA). Yet, patients with advanced fibrosis (F3) or cirrhosis (F4) showed enhanced sAxl concentrations (F3: 54.67 ng/mL; F4: 94.74 ng/mL). Hepatic myofibroblasts exhibited an increased release of sAxl, suggesting that elevated sAxl levels arise from these cells during fibrosis. Receiver operating characteristic curve analysis of sAxl displayed a strongly increased sensitivity and specificity to detect both cirrhosis (80.8%/92.0%) and HCC (83.3%/86.7%) with an area under the curve of 0.935/0.903 as compared to AFP. In conclusion, sAxl shows high diagnostic accuracy at early stage HCC as well as cirrhosis, thereby outperforming AFP. Importantly, sAxl remains normal in most common CLDs, liver adenomas and CCA

Graphics, Visualization, and Usability Center

Graphics, Visualization, and Usability (GVU) is an interdisciplinary area which draws its intellectual foundations from Computer Science, Psychology, Industrial and Systems Engineering, and Computer Engineering, and which has application to any use of computers to graphically convey information to users. Typical applications are computer aided design, scientific and business data visualization, multimedia, computer-supported cooperative work, computer-based teaching, image understanding, medical imaging, and user interface design. The GVU Center has three missions: education, service, and research. In our educational role, we teach the principles and methods of computer graphics, visualization, and usability to members of the academic community ranging from undergraduate students to graduate students and faculty. Center members teach dozens of courses and seminars among the wide offering of relevant courses listed in Section F. A set of continuing education short courses (Section G) are provided to assist practitioners to stay abreast of current developments. Our service mission is carried out through the Scientific Visualization Lab, a joint undertaking with Information Technology (the campus-wide computer service), to provide state of the art computer graphics hardware and software capabilities to the entire Georgia Tech Community. Over 150 faculty, graduate students and staff use the visualization lab's facilities. Our research, described in Section B, spans the areas of realistic imagery, computer-supported collaborative work, algorithm animation, medical imaging, image understanding, scientific data visualization, animation, user interface software, usability, adaptive user interfaces, multimedia, stereo graphics, virtual environments, image quality, and expert systems in graphics and user interfaces. The twenty faculty and staff who are actively developing the lab's programs are drawn from Psychology, Mechanical Engineering, Office of Interdisciplinary Programs, Physics, Mathematics, Information Technology, and the College of Computing. An active seminar series and brown-bag lunches brings us together every week to discuss current research topics. By integrating these three missions together in a single unit, the Center is developing a highly interactive and collaborative environment where researchers unfamiliar with computer graphics can come for help in integrating scientific visualization into their research work, graphics experts and graduate students can share thier knowledge with one another and find new and interesting problems on which to work, and students can learn in a melting pot of closely-related ideas and collaborations between researchers from multiple disciplines. This intellectually-stimulating environment, complemented by over 40 workstations and other pieces of equipment and over 3000 square feet of newly-renovated lab space, provides a paradigm for the use of interactive computer graphics systems which will be necessary for engineering and scientific research in the 21st century

Chitosan-based nanogels for selective delivery of photosensitizers to macrophages and improved retention in and therapy of articular joints.

Macrophages play key roles in inflammatory disorders. Therefore, they are targets of treatments aiming at their local destruction in inflammation sites. However, injection of low molecular mass therapeutics, including photosensitizers, in inflamed joints results in their rapid efflux out of the joints, and poor therapeutic index. To improve selective uptake and increase retention of therapeutics in inflamed tissues, hydrophilic nanogels based on chitosan, of which surface was decorated with hyaluronate and which were loaded with one of three different anionic photosensitizers were developed. Optimal uptake of these functionalized nanogels by murine RAW 264.7 or human THP-1 macrophages as models was achieved after <4h incubation, whereas only negligible uptake by murine fibroblasts used as control cells was observed. The uptake by cells and the intracellular localization of the photosensitizers, of the fluorescein-tagged chitosan and of the rhodamine-tagged hyaluronate were confirmed by fluorescence microscopy. Photodynamic experiments revealed good cell photocytotoxicity of the photosensitizers entrapped in the nanogels. In a mouse model of rheumatoid arthritis, injection of free photosensitizers resulted in their rapid clearance from the joints, while nanogel-encapsulated photosensitizers were retained in the inflamed joints over a longer period of time. The photodynamic treatment of the inflamed joints resulted in a reduction of inflammation comparable to a standard corticoid treatment. Thus, hyaluronate-chitosan nanogels encapsulating therapeutic agents are promising materials for the targeted delivery to macrophages and long-term retention of therapeutics in leaky inflamed articular joints