Artrite idiopática juvenil

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

Fitoterapia aplicada ao tratamento da osteoartrite

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

A FLOW-THROUGH ACOUSTIC WAVEGUIDE FOR TWO-PHASE BUBBLY FLOW VOID FRACTION MEASUREMENT

In the Spallation Neutron Source (SNS) facility at Oak Ridge National Laboratory (ORNL), the deposition of a high-energy proton beam into the liquid mercury target forms bubbles whose asymmetric collapse cause Cavitation Damage Erosion (CDE) to the container walls, thereby reducing its usable lifetime. One proposed solution for mitigation of this damage is to inject a population of microbubbles into the mercury, yielding a compliant and attenuative medium that will reduce the resulting cavitation damage. This potential solution presents the task of creating a diagnostic tool to monitor bubble population in the mercury flow in order to correlate void fraction and damage. Details of an acoustic waveguide for the eventual measurement of two-phase mercury-helium flow void fraction are discussed. The assembly’s waveguide is a vertically oriented stainless steel cylinder with 5.08cm ID, 1.27cm wall thickness and 40cm length. For water experiments, a 2.54cm thick stainless steel plate at the bottom supports the fluid, provides an acoustically rigid boundary condition, and is the mounting point for a hydrophone. A port near the bottom is the inlet for the fluid of interest. A spillover reservoir welded to the upper portion of the main tube allows for a flow-through design, yielding a pressure release top boundary condition for the waveguide. A cover on the reservoir supports an electrodynamic shaker that is driven by linear frequency sweeps to excite the tube. The hydrophone captures the frequency response of the waveguide. The sound speed of the flowing medium is calculated, assuming a linear dependence of axial mode number on modal frequency (plane wave). Assuming that the medium has an effective-mixture sound speed, and that it contains bubbles which are much smaller than the resonance radii at the highest frequency of interest (Wood’s limit), the void fraction of the flow is calculated. Results for water and bubbly water of varying void fraction are presented, and serve to demonstrate the accuracy and precision of the apparatus.

Inferring Body Pose without Tracking Body Parts

A novel approach for estimating articulated body posture and motion from monocular video sequences is proposed. Human pose is defined as the instantaneous two dimensional configuration (i.e., the projection onto the image plane) of a single articulated body in terms of the position of a predetermined set of joints. First, statistical segmentation of the human bodies from the background is performed and low-level visual features are found given the segmented body shape. The goal is to be able to map these, generally low level, visual features to body configurations. The system estimates different mappings, each one with a specific cluster in the visual feature space. Given a set of body motion sequences for training, unsupervised clustering is obtained via the Expectation Maximation algorithm. Then, for each of the clusters, a function is estimated to build the mapping between low-level features to 3D pose. Currently this mapping is modeled by a neural network. Given new visual features, a mapping from each cluster is performed to yield a set of possible poses. From this set, the system selects the most likely pose given the learned probability distribution and the visual feature similarity between hypothesis and input. Performance of the proposed approach is characterized using a new set of known body postures, showing promising results.

A Self-Organizing Neural Network Model for Redundant Sensory-Motor Control, Motor Equivalence, and Tool Use

A neural network is introduced which provides a solution of the classical motor equivalence problem, whereby many different joint configurations of a redundant manipulator can all be used to realize a desired trajectory in 3-D space. To do this, the network self-organizes a mapping from motion directions in 3-D space to velocity commands in joint space. Computer simulations demonstrate that, without any additional learning, the network can generate accurate movement commands that compensate for variable tool lengths, clamping of joints, distortions of visual input by a prism, and unexpected limb perturbations. Blind reaches have also been simulated.

A Self-Organizing Neural Model of Motor Equivalent Reaching and Tool Use by a Multijoint Arm

This paper describes a self-organizing neural model for eye-hand coordination. Called the DIRECT model, it embodies a solution of the classical motor equivalence problem. Motor equivalence computations allow humans and other animals to flexibly employ an arm with more degrees of freedom than the space in which it moves to carry out spatially defined tasks under conditions that may require novel joint configurations. During a motor babbling phase, the model endogenously generates movement commands that activate the correlated visual, spatial, and motor information that are used to learn its internal coordinate transformations. After learning occurs, the model is capable of controlling reaching movements of the arm to prescribed spatial targets using many different combinations of joints. When allowed visual feedback, the model can automatically perform, without additional learning, reaches with tools of variable lengths, with clamped joints, with distortions of visual input by a prism, and with unexpected perturbations. These compensatory computations occur within a single accurate reaching movement. No corrective movements are needed. Blind reaches using internal feedback have also been simulated. The model achieves its competence by transforming visual information about target position and end effector position in 3-D space into a body-centered spatial representation of the direction in 3-D space that the end effector must move to contact the target. The spatial direction vector is adaptively transformed into a motor direction vector, which represents the joint rotations that move the end effector in the desired spatial direction from the present arm configuration. Properties of the model are compared with psychophysical data on human reaching movements, neurophysiological data on the tuning curves of neurons in the monkey motor cortex, and alternative models of movement control.

Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist.

Interleukin-1 beta (IL1β) is a proinflammatory cytokine that mediates arthritic pathologies. Our objectives were to evaluate pain and limb dysfunction resulting from IL1β over-expression in the rat knee and to investigate the ability of local IL1 receptor antagonist (IL1Ra) delivery to reverse-associated pathology. IL1β over-expression was induced in the right knees of 30 Wistar rats via intra-articular injection of rat fibroblasts retrovirally infected with human IL1β cDNA. A subset of animals received a 30 µl intra-articular injection of saline or human IL1Ra on day 1 after cell delivery (0.65 µg/µl hIL1Ra, n = 7 per group). Joint swelling, gait, and sensitivity were investigated over 1 week. On day 8, animals were sacrificed and joints were collected for histological evaluation. Joint inflammation and elevated levels of endogenous IL1β were observed in knees receiving IL1β-infected fibroblasts. Asymmetric gaits favoring the affected limb and heightened mechanical sensitivity (allodynia) reflected a unilateral pathology. Histopathology revealed cartilage loss on the femoral groove and condyle of affected joints. Intra-articular IL1Ra injection failed to restore gait and sensitivity to preoperative levels and did not reduce cartilage degeneration observed in histopathology. Joint swelling and degeneration subsequent to IL1β over-expression is associated limb hypersensitivity and gait compensation. Intra-articular IL1Ra delivery did not result in marked improvement for this model; this may be driven by rapid clearance of administered IL1Ra from the joint space. These results motivate work to further investigate the behavioral consequences of monoarticular arthritis and sustained release drug delivery strategies for the joint space.

Functional properties of cell-seeded three-dimensionally woven poly(epsilon-caprolactone) scaffolds for cartilage tissue engineering.

Articular cartilage possesses complex mechanical properties that provide healthy joints the ability to bear repeated loads and maintain smooth articulating surfaces over an entire lifetime. In this study, we utilized a fiber-reinforced composite scaffold designed to mimic the anisotropic, nonlinear, and viscoelastic biomechanical characteristics of native cartilage as the basis for developing functional tissue-engineered constructs. Three-dimensionally woven poly(epsilon-caprolactone) (PCL) scaffolds were encapsulated with a fibrin hydrogel, seeded with human adipose-derived stem cells, and cultured for 28 days in chondrogenic culture conditions. Biomechanical testing showed that PCL-based constructs exhibited baseline compressive and shear properties similar to those of native cartilage and maintained these properties throughout the culture period, while supporting the synthesis of a collagen-rich extracellular matrix. Further, constructs displayed an equilibrium coefficient of friction similar to that of native articular cartilage (mu(eq) approximately 0.1-0.3) over the prescribed culture period. Our findings show that three-dimensionally woven PCL-fibrin composite scaffolds can be produced with cartilage-like mechanical properties, and that these engineered properties can be maintained in culture while seeded stem cells regenerate a new, functional tissue construct.

Progress in intra-articular therapy.

Diarthrodial joints are well suited to intra-articular injection, and the local delivery of therapeutics in this fashion brings several potential advantages to the treatment of a wide range of arthropathies. Possible benefits over systemic delivery include increased bioavailability, reduced systemic exposure, fewer adverse events, and lower total drug costs. Nevertheless, intra-articular therapy is challenging because of the rapid egress of injected materials from the joint space; this elimination is true of both small molecules, which exit via synovial capillaries, and of macromolecules, which are cleared by the lymphatic system. In general, soluble materials have an intra-articular dwell time measured only in hours. Corticosteroids and hyaluronate preparations constitute the mainstay of FDA-approved intra-articular therapeutics. Recombinant proteins, autologous blood products and analgesics have also found clinical use via intra-articular delivery. Several alternative approaches, such as local delivery of cell and gene therapy, as well as the use of microparticles, liposomes, and modified drugs, are in various stages of preclinical development.

Implant healing in experimental animal models of diabetes.

Diabetes mellitus is becoming increasingly prevalent worldwide. Additionally, there is an increasing number of patients receiving implantable devices such as glucose sensors and orthopedic implants. Thus, it is likely that the number of diabetic patients receiving these devices will also increase. Even though implantable medical devices are considered biocompatible by the Food and Drug Administration, the adverse tissue healing that occurs adjacent to these foreign objects is a leading cause of their failure. This foreign body response leads to fibrosis, encapsulation of the device, and a reduction or cessation of device performance. A second adverse event is microbial infection of implanted devices, which can lead to persistent local and systemic infections and also exacerbates the fibrotic response. Nearly half of all nosocomial infections are associated with the presence of an indwelling medical device. Events associated with both the foreign body response and implant infection can necessitate device removal and may lead to amputation, which is associated with significant morbidity and cost. Diabetes mellitus is generally indicated as a risk factor for the infection of a variety of implants such as prosthetic joints, pacemakers, implantable cardioverter defibrillators, penile implants, and urinary catheters. Implant infection rates in diabetic patients vary depending upon the implant and the microorganism, however, for example, diabetes was found to be a significant variable associated with a nearly 7.2% infection rate for implantable cardioverter defibrillators by the microorganism Candida albicans. While research has elucidated many of the altered mechanisms of diabetic cutaneous wound healing, the internal healing adjacent to indwelling medical devices in a diabetic model has rarely been studied. Understanding this healing process is crucial to facilitating improved device design. The purpose of this article is to summarize the physiologic factors that influence wound healing and infection in diabetic patients, to review research concerning diabetes and biomedical implants and device infection, and to critically analyze which diabetic animal model might be advantageous for assessing internal healing adjacent to implanted devices.

Unipedal balance is affected by lower extremity joint arthroplasty procedure 1 year following surgery.

Lower Extremity Joint Arthroplasty (LEJA) surgery is an effective way to alleviate painful osteoarthritis. Unfortunately, these surgeries do not normalize the loading asymmetry during the single leg stance phase of gait. Therefore, we examined single leg balance in 234 TJA patients (75 hips, 65 knees, 94 ankles) approximately 12 months following surgery. Patients passed if they maintained single leg balance for 10s with their eyes open. Patients one year following total hip arthroplasty (THA-63%) and total knee arthroplasty (TKA-69%) had similar pass rates compared to a total ankle arthroplasty (TAA-9%). Patients following THA and TKA exhibit better unilateral balance in comparison with TAA patients. It may be beneficial to include a rigorous proprioception and balance training program in TAA patients to optimize functional outcomes.

Modelling technology to predict flip-chip assembly

This paper describes modelling technology and its use in providing data governing the assembly of flip-chip components. Details are given on the reflow and curing stages as well as the prediction of solder joint shapes. The reflow process involves the attachment of a die to a board via solder joints. After a reflow process, underfill material is placed between the die and the substrate where it is heated and cured. Upon cooling the thermal mismatch between the die, underfill, solder bumps, and substrate will result in a nonuniform deformation profile across the assembly and hence stress. Shape predictions then thermal solidification and stress prediction are undertaken on solder joints during the reflow process. Both thermal and stress calculations are undertaken to predict phenomena occurring during the curing of the underfill material. These stresses may result in delamination between the underfill and its surrounding materials leading to a subsequent reduction in component performance and lifetime. Comparisons between simulations and experiments for die curvature will be given for the reflow and curing process

The effect of reflow process on the contact resistance and reliability of anisotropic conductive film interconnection for flip chip on flex applications

The work presented in this paper focuses on the effect of reflow process on the contact resistance and reliability of anisotropic conductive film (ACF) interconnection. The contact resistance of ACF interconnection increases after reflow process due to the decrease in contact area of the conducting particles between the mating I/O pads. However, the relationship between the contact resistance and bonding parameters of the ACF interconnection with reflow treatment follows the similar trend to that of the as-bonded (i.e. without reflow) ACF interconnection. The contact resistance increases as the peak temperature of reflow profile increases. Nearly 40% of the joints were found to be open after reflow with 260 °C peak temperature. During the reflow process, the entrapped (between the chip and substrate) adhesive matrix tries to expand much more than the tiny conductive particles because of the higher coefficient of thermal expansion, the induced thermal stress will try to lift the bump from the pad and decrease the contact area of the conductive path and eventually, leading to a complete loss of electrical contact. In addition, the environmental effect on contact resistance such as high temperature/humidity aging test was also investigated. Compared with the ACF interconnections with Ni/Au bump, higher thermal stress in the Z-direction is accumulated in the ACF interconnections with Au bump during the reflow process owing to the higher bump height, thus greater loss of contact area between the particles and I/O pads leads to an increase of contact resistance and poorer reliability after reflow.

Experimental and modeling analysis of the reliability of the anisotropic conductive films

Experiments as well as computer modeling methods have been used to investigate the effect of the solder reflow process on the electrical characteristics and reliability of anisotropic conductive film (ACF) interconnections. In the experiments, the contact resistance of the ACF interconnections was found to increase after a subsequent reflow and the magnitude of this increase was strongly correlated to the peak temperature of the reflow profile. In fact, nearly 40 percent of the joints were opened (i.e. lifted away from the pad) after the reflow with a peak temperature of 260 OC while no openings was observed when the peak temperature was 210 "C. It is believed that the CTE mismatch between the polymer particle and the adhesive matrix is the main cause of this contact degradation. To understand this phenomenon better, a 3-D model of an ACF joint structure was built and Finite Element Analysis was used to predict the stress distrihution in the conductive particles, adhesive matrix and metal pads during the reflow process. The effects of the peak temperature, the CTE of the adhesive matrix and the bump height on the reliability of the ACF interconnections were discussed.

Modelling the performance of lead-Free solder interconnects for copper bumped flip-chip devices

Traditionally, before flip chips can be assembled the dies have to be attached with solder bumps. This process involves the deposition of metal layers on the Al pads on the dies and this is called the under bump metallurgy (UBM). In an alternative process, however, Copper (Cu) columns can be used to replace solder bumps and the UBM process may be omitted altogether. After the bumping process, the bumped dies can be assembled on to the printed circuit board (PCB) by using either solder or conductive adhesives. In this work, the reliability issues of flip chips with Cu column bumped dies have been studied. The flip chip lifetime associated with the solder fatigue failure has been modeled for a range of geometric parameters. The relative importance of these parameters is given and solder volume has been identified as the most important design parameter for long-term reliability. Another important problem that has been studied in this work is the dissolution of protection metals on the pad and Cu column in the reflow process. For small solder joints the amount of Cu which dissolves into the molten solder after the protection layers have worn out may significantly affect solder joint properties.