ESTRATÉGIAS DE TROCA PARA SEGUNDO IMUNOBIOLÓGICO NA ARTRITE REUMATOIDE: RESULTADOS DO REGISTRO BRASILEIRO DE AGENTES IMUNOBIOLÓGICOS EM DOENÇAS REUMÁTICAS BIOBADABRASIL

OBJETIVOS: Comparar as diferentes estratégias de troca para a segunda Terapia Imunobiológica (TIB) na Artrite Reumatoide (AR), do registro BIOBADABRASIL. MÉTODOS: Coorte de base populacional incluindo 1.109 pacientes com AR que preencheram os critérios classificatórios da American College of Rheumatology / European League Against Rheumatism (ACR/EULAR) 2010 e que iniciaram a primeira TIB. Os pacientes foram acompanhados em até 7 anos, no período de janeiro de 2009 até dezembro de 2015. Foram consideradas as variáveis sexo, idade, duração da doença, Disease Activity Score 28 (DAS 28), além de tratamentos concomitantes, que também foram avaliados. Foram aplicados testes Kaplan-Meier, Qui-Quadrado, Kruskal-Wallis, Wilcoxon-Mann-Whitney e análise de regressão de Cox. As drogas Golimumabe (GOLI) e Certolizumabe (CERTO) foram excluídas da análise de sobrevida em função da pequena amostra. RESULTADOS: Da amostra estudada, 85% dos pacientes eram mulheres com idade média de 50 anos e 11 anos de diagnóstico. O Fator Reumatoide (FR) positivo do grupo foi de 87%, DAS 28 de 5,36 ±1,35, 76% estavam em uso de corticoide e 71% foram avaliados em uso de Metotrexate (MTX). Noventa e um porcento iniciaram agente Anti-fator de Necrose Tumoral (Anti-TNF), nas seguintes proporções: Adalimumabe (ADA) 33% (370), Infliximabe (INF) 32 % (356), Etanercepte (ETA) 23% (258), Rituximabe (RTX) 4% (48), Tocilizumabe (TOCI) 3% (35), Golimumabe(GOLI) 2% (19), Abatacepte (ABA), 1% (14) e Certolizumabe (CERTO) 1% (9). No primeiro tratamento, a sobrevida foi maior para o grupo de não anti-TNF (58,50 ± 3,46 e 95%CI 51,71 65,28) que o grupo de anti-TNF (53,43 ± 1,21 e 95%CI 51,05 55,77), p=0,042. O Tocilimumabe (TOCI) apresentou maior sobrevida (57,22 ± 4,57 e 95%CI 48,27 66,17) quando comparado ao grupo dos antiTNF (53,41±1,21 95%CI 51,05 55,77) e p=0,023. Apenas 32,28% (358) trocaram para um segundo IB (Imunobiológico). Destes, 65,92% (236) mudaram de anti-TNF para anti-TNF (ETA=105, ADA=83, INF=33, outros anti-TNF=15); 27,93% (100) trocaram de anti-TNF para não anti-TNF (RTX=38, TOCI=32, ABA=30) e um menor número de apenas 6,13% (22) mudaram de não anti-TNF para outra classe. Em função da pequena amostra, GOLI e CERTO foram excluídos da segunda análise de sobrevida. A melhor estratégia de troca foi de anti-TNF para não-anti-TNF: 50,72 ± 3 meses (CI 95% 44,84-56,60) vs 44,67±2,46 meses (CI 95% 39,85-49,49) p=0,010. Apesar de usarem menos corticoide e terem maior DAS 28 no início do tratamento, os pacientes que migraram de anti TNF para TOCI apresentaram melhor sobrevida (55,80 ± 4,74 IC 95% 46,51,65,09 meses, p=0,029) comparado ao ETA (50,06 ±3,61 IC 95% 42,99-57,14), RTX (47,75 ± 4,93 IC 95% 38,10-57,40), ABA (44,89±5,94 IC 95% 33,25-56,53), ADA (39,45±3,89 IC 95% 31,83-47,08) e INF (34,43±4,65 IC 95% 25,31-43,55). O principal motivo da troca do primeiro IB foi por ineficácia ou perda de eficácia (64%, n = 216), seguido de efeitos adversos (26%, n=87) e outros motivos (10%, n = 33). Quando o motivo da troca se deu por evento adverso, a melhor alternativa foi observada com a troca para um agente não anti- TNF com 50,29 ± 4,93 meses (95%IC=40,62 59,95) vs 43,23 ± 4,22 meses (95%IC= 34,96 51,51) , p=0,038. CONCLUSÃO: Os agentes anti-TNF são as drogas mais prescritas no registro brasileiro BIOBADABRASIL como primeira e segunda TIB. A opção por um agente não anti TNF como primeira TIB foi a melhor alternativa. A Troca de anti-TNF para não anti-TNF também representou a melhor opção. TOCI mostrou melhor sobrevida como segundo IB. O principal motivo da troca ocorreu por ineficácia ou perda de eficácia. Quando o motivo da troca foi evento adverso , optar por um agente não anti-TNF foi melhor alternativa. Palavras-chave: Artrite reumatoide. Terapia biológica. Sobrevida. Troca. Anti TNF. Não Anti-TNF, Tocilizumabe

Portable parallel kernels for high-speed beamforming in synthetic aperture ultrasound imaging

In medical ultrasound, synthetic aperture (SA) imaging is well-considered as a novel image formation technique for achieving superior resolution than that offered by existing scanners. However, its intensive processing load is known to be a challenging factor. To address such a computational demand, this paper proposes a new parallel approach based on the design of OpenCL signal processing kernels that can compute SA image formation in real-time. We demonstrate how these kernels can be ported onto different classes of parallel processors, namely multi-core CPUs and GPUs, whose multi-thread computing resources are able to process more than 250 fps. Moreover, they have strong potential to support the development of more complex algorithms, thus increasing the depth range of the inspected human volume and the final image resolution observed by the medical practitioner.published_or_final_versio

Enteral enriched nutrition to prevent cognitive dysfunction after surgery:A study in rats

BACKGROUND: Inflammation plays an important role in postoperative cognitive dysfunction (POCD), particularly in elderly patients. Enteral enriched nutrition was shown to inhibit the response on inflammatory stimuli. Aim of the present study was to explore the therapeutic potential of enteral enriched nutrition in our rat model for POCD. The anticipated mechanism of action was examined in young rats, while responses in the target group of elderly patients were evaluated in old rats. METHODS: Male 3 and 23 months old Wistar rats received a bolus of enteral fat/protein-enriched nutrition 2 ​h and 30 ​min before surgery. The inflammatory response was evaluated by systemic inflammation markers and brain microglia activity. Additionally, in old rats, the role of the gut-brain axis was studied by microbiome analyses of faecal samples. Days 9–14 after surgery, rats were subjected to cognitive testing. Day 16, rats were sacrificed and brains were collected for immunohistochemistry. RESULTS: In young rats, enriched nutrition improved long-term spatial learning and memory in the Morris Water Maze, reduced plasma IL1-β and VEGF levels, but left microglia activity and neurogenesis unaffected. In contrast, in old rats, enriched nutrition improved short-term memory in the novel object- and novel location recognition tests, but impaired development of long-term memory in the Morris Water Maze. Systemic inflammation was not affected, but microglia activity seemed even increased. Gut integrity and microbiome were not affected. CONCLUSION: Enteral enriched nutrition before surgery in young rats indeed reduced systemic inflammation and improved cognitive performance after surgery, whereas old rats showed a mixed favorable/unfavorable cognitive response, without effect on systemic inflammation. Anti-inflammatory effects of enriched nutrition were not reflected in decreased microglia activity. Neither was an important role for the gut-brain axis observed. Since the relatively straight forward effects of enriched nutrition in young rats could not be shown in old rats, as indicated by a mixed beneficial/detrimental cognitive outcome in the latter, caution is advised by translating effects seen in younger patients to older ones

Structural and optical characterization of Mg-doped GaAs nanowires grown on GaAs and Si substrates

We report an investigation on the morphological, structural, and optical properties of large size wurtzite GaAs nanowires, low doped with Mg, grown on GaAs(111) B and Si(111) substrates. A higher density of vertical nanowires was observed when grown upon GaAs(111) B. Very thin zinc-blende segments are observed along the axis of the nanowires with a slightly higher linear density being found on the nanowires grown on Si(111). Low temperature cathodoluminescence and photoluminescence measurements reveal an emission in the range 1.40-1.52 eV related with the spatial localization of the charge carriers at the interfaces of the two crystalline phases. Mg related emission is evidenced by cathodoluminescence performed on the GaAs epilayer. However, no direct evidence for a Mg related emission is found for the nanowires. The excitation power dependency on both peak energy and intensity of the photoluminescence gives a clear evidence for the type II nature of the radiative transitions. From the temperature dependence on the photoluminescence intensity, non-radiative de-excitation channels with different activation energies were found. The fact that the estimated energies for the escape of the electron are higher in the nanowires grown on Si(111) suggests the presence of wider zinc-blende segments. (C) 2013 AIP Publishing LLC

New Results in Sasaki-Einstein Geometry

This article is a summary of some of the author's work on Sasaki-Einstein geometry. A rather general conjecture in string theory known as the AdS/CFT correspondence relates Sasaki-Einstein geometry, in low dimensions, to superconformal field theory; properties of the latter are therefore reflected in the former, and vice versa. Despite this physical motivation, many recent results are of independent geometrical interest, and are described here in purely mathematical terms: explicit constructions of infinite families of both quasi-regular and irregular Sasaki-Einstein metrics; toric Sasakian geometry; an extremal problem that determines the Reeb vector field for, and hence also the volume of, a Sasaki-Einstein manifold; and finally, obstructions to the existence of Sasaki-Einstein metrics. Some of these results also provide new insights into Kahler geometry, and in particular new obstructions to the existence of Kahler-Einstein metrics on Fano orbifolds.Comment: 31 pages, no figures. Invited contribution to the proceedings of the conference "Riemannian Topology: Geometric Structures on Manifolds"; minor typos corrected, reference added; published version; Riemannian Topology and Geometric Structures on Manifolds (Progress in Mathematics), Birkhauser (Nov 2008

Mechanisms for collaboration: a design and evaluation framework for multi-user interfaces

Multi-user interfaces are said to provide “natural” interaction in supporting collaboration, compared to individual and noncolocated technologies. We identify three mechanisms accounting for the success of such interfaces: high awareness of others' actions and intentions, high control over the interface, and high availability of background information. We challenge the idea that interaction over such interfaces is necessarily “natural” and argue that everyday interaction involves constraints on awareness, control, and availability. These constraints help people interact more smoothly. We draw from social developmental psychology to characterize the design of multi-user interfaces in terms of how constraints on these mechanisms can be best used to promote collaboration. We use this framework of mechanisms and constraints to explain the successes and failures of existing designs, then apply it to three case studies of design, and finally derive from them a set of questions to consider when designing and analysing multi-user interfaces for collaboration

Handbook for Aboriginal Alcohol and Drug Work

The Handbook for Aboriginal Alcohol and Drug Work is a practical tool written for Aboriginal drug and alcohol workers, mental health workers and others working in this field. It offers a detailed look at alcohol and drug work from clinical, through to prevention, early intervention and harm reduction. This handbook is also likely to help people working to improve policy and those advocating for change. The idea for it came from workers all over Australia. They told us that they needed an easy to use handbook that can help them respond to the range of alcohol and drug issues they face every day. They also told us that such a book needs to take into account the complex challenges facing workers when helping clients, their families and, sometimes, whole communities