Analysis of BRAF and NRAS Mutation Status in Advanced Melanoma Patients Treated with Anti-CTLA-4 Antibodies: Association with Overall Survival?

Ipilimumab and tremelimumab are human monoclonal antibodies (Abs) against cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show a statistically significant benefit in overall survival in advanced melanoma patients. Currently, there is no proven association between the BRAFV600 mutation and the disease control rate in response to ipilimumab. This analysis was carried out to assess if BRAFV600 and NRAS mutation status affects the clinical outcome of anti-CTLA-4-treated melanoma patients. This is a retrospective multi-center analysis of 101 patients, with confirmed BRAF and NRAS mutation status, treated with anti-CTLA-4 antibodies from December 2006 until August 2012. The median overall survival, defined from the treatment start date with the anti-CTLA-4. Abs-treatment to death or till last follow up, of BRAFV600 or NRAS mutant patients (n = 62) was 10.12 months (95% CI 6.78-13.2) compared to 8.26 months (95% CI 6.02-19.9) in BRAFV600/NRASwt subpopulation (n = 39) (p = 0.67). The median OS of NRAS mutated patients (n = 24) was 12.1 months and although was prolonged compared to the median OS of BRAF mutated patients (n = 38, mOS = 8.03 months) or BRAFV600/NRASwt patients (n = 39, mOS = 8.26 months) the difference didn't reach statistical significance (p = 0.56). 69 patients were able to complete 4 cycles of anti-CTLA-4 treatment. Of the 24 patients treated with selected BRAF- or MEK-inhibitors, 16 patients received anti-CTLA 4 Abs following either a BRAF or MEK inhibitor with only 8 of them being able to finish 4 cycles of treatment. Based on our results, there is no difference in the median OS in patients treated with anti-CTLA-4 Abs implying that the BRAF/NRAS mutation status alone is not sufficient to predict the outcome of patients treated with anti-CTLA-4 Abs.

O papel da ecoendoscopia no diagnóstico das neoplasias císticas primárias do pâncreas

O diagnóstico das lesões císticas pancreáticas pelos métodos de imagem, especialmente as de pequeno tamanho, é cada vez mais freqüente. Em alguns casos, ele representa um dilema em relação à terapêutica, podendo ser pseudocistos inflamatórios, neoplasias primárias ou secundárias. Para a decisão terapêutica, é necessário definir se a neoplasia é benigna, maligna ou potencialmente maligna. Hoje, a ecoendoscopia é considerada o exame padrão-ouro para a investigação do pâncreas, fornecendo dados sobre a morfologia destas lesões e possibilitando, por meio da punção guiada em tempo real, a colheita de material para avaliação citológica e dos marcadores tumorais. Este procedimento é considerado seguro e eficiente e apresenta taxas de sensibilidade e especificidade altas e de morbidade e de complicações baixas. No diagnóstico das lesões mucinosas do pâncreas, os fatores preditivos mais significativos para o diagnóstico diferencial são a presença de septos, os nódulos murais e as alterações parenquimatosas, para o qual as taxas de sensibilidade, especificidade e grau de exatidão são, respectivamente, 94%, 85% e 88%. Os autores têm por objetivo revisar as principais neoplasias císticas primárias do pâncreas, enfatizando a aplicação da ecoendoscopia no diagnóstico definitivo dessas neoplasias.

Serlianas durante el Renacimiento italiano y español: del triunfo de la religión católica al lenguaje imperial

This article presents a panoramic view of the development of the so-called serliana or Serlian motif throughout the Italian Renaissance, focusing on the most relevant examples in the architecture of that period. The use of this motif during the Early Renaissance was pioneered by Filippo Brunelleschi in religious buildings. As its employment become widespread in a range of different settings, architects frequently incorporated local building traditions. It was only during the last twenty years of the Quattrocento that Giuliano da Sangallo and Leonardo da Vinci adopted the Serlian arch in residential architecture designed for the ruling elites. Thanks to Bramante and other artists such as Raphael, Baldassare Peruzzi, Antonio da Sangallo the Younger and Giulio Romano, the motif was extraordinarily popular during the High Renaissance period. Ever-increasingly complex and monumental compositions eased the adaptation of the serliana to both exterior and interior spaces, and in works such as the design by Galeazzo Alessi in Genoa, the imperial connotation of the motif is clear. This process illustrates the progressive transfer from the religious to the courtly sphere, and, at the same time, the permeability between the sacred and the profane. During the sixteenth century, Spain too was at the European avant-garde, due to its contacts with Italy and the latest fashions, such as the employment of the serliana in residential architecture, were followed in the fortified palace at La Calahorra, the Vich palace in Valencia, or the palace of Charles V in Granada, as part of a complex iconography of power. Throughout the sixteenth century, the serliana featured in that specifically-Spanish typology, the monumental altarpiece or retablo, as well as in monumental tombs. Italy was certainly the leading force in the process and had an indisputable influence on Spanish art, but the latter would develop its own original solutions in the sixteenth century, which matched the innovative character of Italian creations.

Quando a fase de equilíbrio pode ser suprimida nos exames de tomografia computadorizada de abdome?

OBJETIVO: Avaliar a necessidade de realização da fase de equilíbrio nos exames de tomografia computadorizada de abdome. MATERIAIS E MÉTODOS: Realizou-se estudo retrospectivo, transversal e observacional, avaliando 219 exames consecutivos de tomografia computadorizada de abdome com contraste intravenoso, realizados num período de três meses, com diversas indicações clínicas. Para cada exame foram emitidos dois pareceres, um avaliando o exame sem a fase de equilíbrio (primeira análise) e o outro avaliando todas as fases em conjunto (segunda análise). Ao final de cada avaliação, foi estabelecido se houve mudança nos diagnósticos principais e secundários, entre a primeira e a segunda análise. Foi utilizada a extensão do teste exato de Fisher para avaliar a modificação dos diagnósticos principais (p < 0,05 como significante). RESULTADOS: Entre os 219 casos avaliados, a supressão da fase de equilíbrio provocou alteração no diagnóstico principal em apenas um exame (0,46%; p > 0,999). Com relação aos diagnósticos secundários, cinco exames (2,3%) foram modificados. CONCLUSÃO: Para indicações clínicas como estadiamento tumoral, abdome agudo e pesquisa de coleção abdominal, a fase de equilíbrio não acrescenta contribuição diagnóstica expressiva, podendo ser suprimida dos protocolos de exame.

Diagnosis of hepatic steatosis by contrast-enhanced abdominal computed tomography

Objective To evaluate the diagnostic capacity of abdominal computed tomography in the assessment of hepatic steatosis using the portal phase with a simplified calculation method as compared with the non-contrast-enhanced phase. Materials and Methods In the present study, 150 patients were retrospectively evaluated by means of non-contrast-enhanced and contrast-enhanced computed tomography. One hundred patients had hepatic steatosis and 50 were control subjects. For the diagnosis of hepatic steatosis in the portal phase, the authors considered a result of < 104 HU calculated by the formula [L - 0.3 × (0.75 × P + 0.25 × A)] / 0.7, where L, P and A represent the attenuation of the liver, of the main portal vein and abdominal aorta, respectively. Sensitivity, specificity, positive and negative predictive values were calculated, using non-contrast-enhanced computed tomography as the reference standard. Results The simplified calculation method with portal phase for the diagnosis of hepatic steatosis showed 100% sensitivity, 36% specificity, negative predictive value of 100% and positive predictive value of 75.8%. The rate of false positive results was 64%. False negative results were not observed. Conclusion The portal phase presents an excellent sensitivity in the diagnosis of hepatic steatosis, as compared with the non-contrast-enhanced phase of abdominal computed tomography. However, the method has low specificity.

Tools and data services registry: a community effort to document bioinformatics resources.

Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand.Here we present a community-driven curation effort, supported by ELIXIR-the European infrastructure for biological information-that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners.As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools.

Enhanced capture of healthcare-related harms and injuries in the 11th revision of the International Classification of Diseases (ICD-11).

The World Health Organization (WHO) plans to submit the 11th revision of the International Classification of Diseases (ICD) to the World Health Assembly in 2018. The WHO is working toward a revised classification system that has an enhanced ability to capture health concepts in a manner that reflects current scientific evidence and that is compatible with contemporary information systems. In this paper, we present recommendations made to the WHO by the ICD revision's Quality and Safety Topic Advisory Group (Q&S TAG) for a new conceptual approach to capturing healthcare-related harms and injuries in ICD-coded data. The Q&S TAG has grouped causes of healthcare-related harm and injuries into four categories that relate to the source of the event: (a) medications and substances, (b) procedures, (c) devices and (d) other aspects of care. Under the proposed multiple coding approach, one of these sources of harm must be coded as part of a cluster of three codes to depict, respectively, a healthcare activity as a 'source' of harm, a 'mode or mechanism' of harm and a consequence of the event summarized by these codes (i.e. injury or harm). Use of this framework depends on the implementation of a new and potentially powerful code-clustering mechanism in ICD-11. This new framework for coding healthcare-related harm has great potential to improve the clinical detail of adverse event descriptions, and the overall quality of coded health data.

Readjustment of abdominal computed tomography protocols in a university hospital: impact on radiation dose

AbstractObjective:To assess the reduction of estimated radiation dose in abdominal computed tomography following the implementation of new scan protocols on the basis of clinical suspicion and of adjusted images acquisition parameters.Materials and Methods:Retrospective and prospective review of reports on radiation dose from abdominal CT scans performed three months before (group A – 551 studies) and three months after (group B – 788 studies) implementation of new scan protocols proposed as a function of clinical indications. Also, the images acquisition parameters were adjusted to reduce the radiation dose at each scan phase. The groups were compared for mean number of acquisition phases, mean CTDIvol per phase, mean DLP per phase, and mean DLP per scan.Results:A significant reduction was observed for group B as regards all the analyzed aspects, as follows: 33.9%, 25.0%, 27.0% and 52.5%, respectively for number of acquisition phases, CTDIvol per phase, DLP per phase and DLP per scan (p < 0.001).Conclusion:The rational use of abdominal computed tomography scan phases based on the clinical suspicion in conjunction with the adjusted images acquisition parameters allows for a 50% reduction in the radiation dose from abdominal computed tomography scans.

Courts and Courtly Cultures in Early Modern Italy and Europe: Models and Languages

This volume deals with the forms of propaganda and self-representation, through words and images, during the rise of the 'civiltà delle corti' and through processes typical of the time, such as confrontation, adaptation, competition and rivalry. This period, which marked the passage of Italian and European culture from the Middle Ages to the Renaissance, is fundamental in the development of Modern Europe, and it lasted up to the XVIII century and beyond. At the heart of many matters debated here lies the relationship between culture and politics. The formation of a 'Lombard identity', central to the Sinergia project which was the frame of the whole research and its conferences, is closely linked to this broad general context. It places the so called 'questione milanese' - above the traditional hierarchies 'Toscana oriented' - at the centre of many questions regarding Northern Italy as a whole, starting from the dissolution of the Medieval communes, through to the rise of the signorie, from the end of the XIII century and the beginning of the XIV century up to the early XVI century.

Cabouret, Bernadette, Groslambert, Agnès, Wolff, Catherine (eds.), Visions de l’Occident romain. Hommages à Yann Le Bohec. Collection Études et Recherches sur l’Occident Romain, 2 vol. Paris, De Boccard 2012, págs. 959.

Este libro, en dos volúmenes, es un merecido homenaje al profesor Yann LE BOHEC (professeur émérite, Paris IV-La Sorbonne), jubilado forzosamente de la docencia universitaria en septiembre de 2011. La carrera investigadora del profesor Le Bohec que naturalmente continua en la actualidad ha tratado multitud de temas relacionados con el Imperio Romano, aunque deben ser destacadas en especial dos temáticas: el norte de África y el ejército romano. Y obviamente estos asuntos se ven también muy reflejados en los artículos de todos aquellos colegas y amigos que colaboran en el homenaje.

Cabouret, Bernadette, Groslambert, Agnès, Wolff, Catherine (eds.), Visions de l"Occident romain. Hommages à Yann Le Bohec. Collection Études et Recherches sur l"Occident Romain, 2 vol. Paris, De Boccard 2012, págs. 959. 27 x 17 cm. Prefacio de André Laronde ( ).

Este libro, en dos volúmenes, es un merecido homenaje al profesor Yann LE BOHEC (professeur émérite, Paris IV-La Sorbonne), jubilado forzosamente de la docencia universitaria en septiembre de 2011. La carrera investigadora del profesor Le Bohec que naturalmente continua en la actualidad ha tratado multitud de temas relacionados con el Imperio Romano, aunque deben ser destacadas en especial dos temáticas: el norte de África y el ejército romano. Y obviamente estos asuntos se ven también muy reflejados en los artículos de todos aquellos colegas y amigos que colaboran en el homenaje.

Spectroscopic characterization of phases formed by high-dose carbon ion implantation in silicon

High-dose carbon-ion-implanted Si samples have been analyzed by infrared spectroscopy, Raman scattering, and x-ray photoelectron spectroscopy (XPS) correlated with transmission electron microscopy. Samples were implanted at room temperature and 500°C with doses between 1017 and 1018 C+/cm2. Some of the samples were implanted at room temperature with the surface covered by a capping oxide layer. Implanting at room temperature leads to the formation of a surface carbon-rich amorphous layer, in addition to the buried implanted layer. The dependence of this layer on the capping oxide suggests this layer to be determined by carbon migration toward the surface, rather than surface contamination. Implanting at 500°C, no carbon-rich surface layer is observed and the SiC buried layer is formed by crystalline ßSiC precipitates aligned with the Si matrix. The concentration of SiC in this region as measured by XPS is higher than for the room-temperature implantation.