The predominance of M2-polarized macrophages in the stroma of low-hypoxic bladder tumors is associated with BCG immunotherapy failure

OBJECTIVE: Bacillus Calmette-Guérin (BCG) immunotherapy is the gold standard treatment for superficial bladder tumors with intermediate/high risk of recurrence or progression. However, approximately 30% of patients fail to respond to the treatment. Effective BCG therapy needs precise activation of the type 1 helper cells immune pathway. Tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phenotype and may directly interfere with the BCG-induced antitumor immune response. Thus, we aim to clarify the influence of TAMs, in particular of the M2 phenotype in stroma and tumor areas, in BCG treatment outcome. PATIENTS AND METHODS: The study included 99 patients with bladder cancer treated with BCG. Tumors resected before treatment were evaluated using immunohistochemistry for CD68 and CD163 antigens, which identify a lineage macrophage marker and a M2-polarized specific cell surface receptor, respectively. CD68+ and CD163+ macrophages were evaluated within the stroma and tumor areas, and high density of infiltrating cells spots were selected for counting. Hypoxia, an event known to modulate macrophage phenotype, was also assessed through hypoxia induced factor (HIF)-1α expression. RESULTS: Patients in whom BCG failed had high stroma-predominant CD163+ macrophage counts (high stroma but low tumor CD163+ macrophages counts) when compared with the ones with a successful treatment (71% vs. 47%, P = 0.017). Furthermore, patients presenting this phenotype showed decreased recurrence-free survival (log rank, P = 0.008) and a clear 2-fold increased risk of BCG treatment failure was observed in univariate analysis (hazard ratio = 2.343; 95% CI: 1.197-4.587; P = 0.013). Even when adjusted for potential confounders, such as age and therapeutic scheme, multivariate analysis revealed 2.6-fold increased risk of recurrence (hazard ratio = 2.627; 95% CI: 1.340-5.150; P = 0.005). High stroma-predominant CD163+ macrophage counts were also associated with low expression of HIF-1α in tumor areas, whereas high counts of CD163+ in the tumor presented high expression of HIF-1α in tumor nests. CONCLUSIONS: TAMs evaluation using CD163 is a good indicator of BCG treatment failure. Moreover, elevated infiltration of CD163+ macrophages, predominantly in stroma areas but not in the tumor, may be a useful indicator of BCG treatment outcome, possibly owing to its immunosuppressive phenotype.

Análise dos modos de falha e seus efeitos (FMEA) aplicada a um secador industrial

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Avaliação da torção miocárdica, por Spekle Tracking, em doentes com HTA

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Ramo de especialização: Ultrassonografia Cardiovascular

Timing analysis of a multiple logical ring wired/wireless PROFIBUS network

Recently, there have been a few research efforts towards extending the capabilities of fieldbus networks to encompass wireless support. In previous works we have proposed a hybrid wired/wireless PROFIBUS network solution where the interconnection between the heterogeneous communication media was accomplished through bridge-like interconnecting devices. The resulting networking architecture embraced a multiple logical ring (MLR) approach, thus with multiple independent tokens, to which a specific bridging protocol extension, the inter-domain protocol (IDP), was proposed. The IDP offers compatibility with standard PROFIBUS, and includes mechanisms to support inter-cell mobility of wireless nodes. We advance that work by proposing a worst-case response timing analysis of the IDP.

Biochemistry of adipose tissue: an endocrine organ

Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance.

Static-priority scheduling over wireless networks with multiple broadcast domains

We propose a wireless medium access control (MAC) protocol that provides static-priority scheduling of messages in a guaranteed collision-free manner. Our protocol supports multiple broadcast domains, resolves the wireless hidden terminal problem and allows for parallel transmissions across a mesh network. Arbitration of messages is achieved without the notion of a master coordinating node, global clock synchronization or out-of-band signaling. The protocol relies on bit-dominance similar to what is used in the CAN bus except that in order to operate on a wireless physical layer, nodes are not required to receive incoming bits while transmitting. The use of bit-dominance efficiently allows for a much larger number of priorities than would be possible using existing wireless solutions. A MAC protocol with these properties enables schedulability analysis of sporadic message streams in wireless multihop networks.

Psychological well-being and perception of disease severity in people with multiple sclerosis, who underwent a program of self-regulation to promote physical activity

Rehabilitation is very important for in the results of treatment in individuals with multiple sclerosis. Rehabilitation processes occur through gradual changes. These changes integrate intrinsic and extrinsic mechanisms of the individual, promoting adaptations to the needs and activities of daily living according to individual goals. Recommendations for exercise in multiple sclerosis: these recommendations apply only to patients with EDSS less than 7; moderate intensity aerobic exercise for a total of 20 to 30 minutes, twice or three times for week; the resistance training with low or moderate intensity is well tolerated by patients with MS; associated with these exercises were recommended flexibility exercises of moderate intensity, as well as strengthening exercises. The aim of this study is to examine the implications of the program of self-regulation in the perception of illness and mental health (psychological well-being domain) in multiple sclerosis patients.

Importance of program physical activity in quality of life in multiple sclerosis patients, six months after the intervention

Background: Multiple Sclerosis (MS) is a chronic disease of the central nervous system that affects more often young adults in the prime of his career and personal development, with no cure and unknown causes. The most common signs and symptoms are fatigue, muscle weakness, changes in sensation, ataxia, changes in balance, gait difficulties, memory difficulties, cognitive impairment and difficulties in problem solving MS is a relatively common neurological disorder in which various impairments and disabilities impact strongly on function and daily life activities. Purpose: The aim of this study is to examine the implications of an Intervention Program of Physical Activity (IPPA) in quality of life in MS patients, six months after the intervention.

Evidence based for exercise program in physical therapy in patients with multiple sclerosis

Background: Multiple sclerosis is a disease of the central nervous system that affects more frequently young women. It is a progressive and unpredictable disease, resulting in some cases of disabilities and limitations to physical, psychological and social level. Purpose: To review the literature for evidence based of the effectiveness of physiotherapy intervention in multiple sclerosis.

Failure on clinical image quality criteria in digital mammography: how can radiographers do better?

Purpose: To assess image quality using PGMI (perfect, good, moderate, inadequate) scale in digital mammography examinations acquired in DR systems. Identify the main failures and propose corrective actions. Evaluate the most typical breast density. Methods and Materials: Clinical image quality criteria were evaluated considering mammograms acquired in 13 DR systems and classified according to PGMI scale using the criteria described in European Commission guidelines for radiographers. The breast density was assessed according to ACR recommendations. The data were collected on the acquisition system monitor to reproduce the daily practice of the radiographer. Results: The image quality criteria were evaluated in 3044 images. The criteria were fully achieved in 41% of the images that were classified as P (perfect), 31 % of the images were classified as M (moderate), 20% G (good) and 9% I (inadequate). The main cause of inadequate image quality was absence of all breast tissue in the image, skin folders in the pectoral muscle and in the infra-mammary angle. The higher number of failures occurred in MLO projections (809 out of 1022). The most represented (36%) breast type was type 2 (25-50% glandular tissue). Conclusion: Incorrect radiographic technique was frequently detected suggesting potential training needs and poor communication between the team members (radiographer and radiologists). Further correlations are necessary to identify the main causes for the failures, namely specific education and training in digital mammography and workload.

Object transportation by multiple mobile robots controlled by attractor dynamics: theory and implementation

Dynamical systems theory is used as a theoretical language and tool to design a distributed control architecture for teams of mobile robots, that must transport a large object and simultaneously avoid collisions with (either static or dynamic) obstacles. Here we demonstrate in simulations and implementations in real robots that it is possible to simplify the architectures presented in previous work and to extend the approach to teams of n robots. The robots have no prior knowledge of the environment. The motion of each robot is controlled by a time series of asymptotical stable states. The attractor dynamics permits the integration of information from various sources in a graded manner. As a result, the robots show a strikingly smooth an stable team behaviour.

Enabling Global Experiments With Interactive Reconfiguration And Steering By Multiple Users

In global scientific experiments with collaborative scenarios involving multinational teams there are big challenges related to data access, namely data movements are precluded to other regions or Clouds due to the constraints on latency costs, data privacy and data ownership. Furthermore, each site is processing local data sets using specialized algorithms and producing intermediate results that are helpful as inputs to applications running on remote sites. This paper shows how to model such collaborative scenarios as a scientific workflow implemented with AWARD (Autonomic Workflow Activities Reconfigurable and Dynamic), a decentralized framework offering a feasible solution to run the workflow activities on distributed data centers in different regions without the need of large data movements. The AWARD workflow activities are independently monitored and dynamically reconfigured and steering by different users, namely by hot-swapping the algorithms to enhance the computation results or by changing the workflow structure to support feedback dependencies where an activity receives feedback output from a successor activity. A real implementation of one practical scenario and its execution on multiple data centers of the Amazon Cloud is presented including experimental results with steering by multiple users.

Aplicação do Failure Mode and Effect Analysis (FMEA) na demolição, movimento de terras e execução da estrutura em edifícios

Mestrado em Engenharia Civil - Ramo Tecnologia e gestão das Construções

Auxiliary mechanisms for telerobotics

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia Electrotécnica e de Computadores

The extended unsymmetric frontal solution for multiple-point constraints

The purpose of this paper is to discuss the linear solution of equality constrained problems by using the Frontal solution method without explicit assembling. Design/methodology/approach - Re-written frontal solution method with a priori pivot and front sequence. OpenMP parallelization, nearly linear (in elimination and substitution) up to 40 threads. Constraints enforced at the local assembling stage. Findings - When compared with both standard sparse solvers and classical frontal implementations, memory requirements and code size are significantly reduced. Research limitations/implications - Large, non-linear problems with constraints typically make use of the Newton method with Lagrange multipliers. In the context of the solution of problems with large number of constraints, the matrix transformation methods (MTM) are often more cost-effective. The paper presents a complete solution, with topological ordering, for this problem. Practical implications - A complete software package in Fortran 2003 is described. Examples of clique-based problems are shown with large systems solved in core. Social implications - More realistic non-linear problems can be solved with this Frontal code at the core of the Newton method. Originality/value - Use of topological ordering of constraints. A-priori pivot and front sequences. No need for symbolic assembling. Constraints treated at the core of the Frontal solver. Use of OpenMP in the main Frontal loop, now quantified. Availability of Software.