Assessment by doppler ultrasound of entheseal lesions in spondyloarthritis : a longitudial study to determine structural damage and disease activity lesions

RESUMO: Enthesitis is the hallmark of spondyloarthritis (SpA), and is observed in all subtypes. Wide information on SpA abnormalities, including synovitis, tendinitis and enthesitis, can be efficiently perceived by Doppler ultrasound. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect enthesis alterations; and vascularized enthesitis detected by Doppler ultrasound appears to be a valuable diagnostic tool to confirm SpA diagnosis. However, data published until now concerning entheseal elementary alterations that characterize SpA enthesitis (enthesis inflammatory activity) or enthesopathy (permanent structural changes) reflect rather the authors’ empiric opinion than a methodological validation process. In this sense it seems crucial to identify elementary entheseal lesions associated with activity or damage, in order to improve monitoring and treatment response in SpA patients. The development of better assessment tools is today a challenge and a need in SpA. The first study of this thesis focused on the analysis of the reliability of inter-lector and inter-ultrasonography equipment of Madrid sonography enthesitis index (MASEI). Fundamental data for the remaining unrolling project validity. In the second and third studies we concerned about two entheseal elemental lesions: erosions and bursa. In literature erosions represent a permanent structural damage, being useful for monitoring joint injury, disease activity and therapeutic response in many rheumatic diseases; and to date, this concept has been mostly applied in rheumatoid arthritis (RA). Unquestionably, erosion is a tissue-related damage and a structural change. However, the hypothesis that we decided to test was if erosions represent a permanent structural change that can only grow and worsen over time, as occurs in RA, or a transitory alteration. A longitudinal study of early SpA patients was undertaken, and the Achilles enthesis was used as a model. Our results strongly suggested that previously detected erosions could disappear during the course of the disease, being consistent with the dynamic behavior of erosion over time. Based on these striking results it seems reasonable to suggest that the new-bone formation process in SpA could be associated with the resolution of cortical entheseal erosion over time. These results could also be in agreement with the apparent failure of anti-tumor necrosis factor (TNF) therapies to control bone proliferation in SpA; and with the relation of TNF-α, Dickkopf-related protein 1 (Dkk-1) and the regulatory molecule of the Wnt signaling pathway in the bone proliferation in SpA. In the same model, we then proceeded to study the enthesis bursa. Interestingly, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) enthesopathy definition does not include bursa as an elementary entheseal lesion. Nonetheless, bursa was included in 46% of the enthesis studies in a recently systematic literature review, being in agreement with the concept of “synovio-entheseal complex” that includes the link between enthesitis and osteitis in SpA. It has been clarified in recent data that there is not only a close functional integration of the enthesis with the neighboring bone, but also a connection between enthesitis and synovitis. Therefore, we tried to assess the prevalence and relevance of the bursa-synovial lesion in SpA. Our findings showed a significant increase of Achilles bursa presence and thickness in SpA patients compared to controls (healthy/mechanical controls and RA controls). These results raise awareness to the need to improve the enthesopathy ultrasonographic definition. In the final work of this thesis, we have explored new perspectives, not previously reported, about construct validity of enthesis ultrasound as a possible activity outcome in SpA. We performed a longitudinal Achilles enthesis ultrasound study in patients with early SpA. Achilles ultrasound examinations were performed at baseline, six- and twelve-month time periods and compared with clinical outcome measures collected at basal visit. Our results showed that basal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are higher in patients with Doppler signal in enthesis, and even that higher basal ESR, CRP and Ankylosing Spondylitis Disease Activity Score (ASDAS) predicted a higher Doppler signal (an ultrasound alteration accepted as representative of inflammation) six months later. Patients with very high disease activity assessed by ASDAS (>3.5) at baseline had significantly higher Achilles total ultrasound score verified at the same time; and ASDAS <1.3 predicted no Doppler signal at six and twelve months. This seems to represent a connection between classical biomarkers and clinical outcomes associated with SpA activity and Doppler signal, not only at the same time, but also for the following months. Remarkably, patients with inactive disease (ASDAS < 1.3) at baseline had no Doppler signal at six and twelve months. These findings reinforce the potential use of ultrasound related techniques for disease progression assessment and prognosis purposes. Intriguingly, Ankylosing Spondylitis Disease Activity Index (BASDAI) didn’t show significant differences between different cut-offs concerning ultrasound lesions or Doppler signal, while verified with ASDAS. These results seem to indicate that ASDAS reflects better than BASDAI what happens in the enthesis. The work herein discussed clearly shows the potential utility of ultrasound in enthesis assessment in SpA patients, and can be important for the development of ultrasound activity and structural damage scores for diagnosis and monitoring purposes. Therefore, local promotion of this technique constitutes a medical intervention that is worth being tested in SpA patients for diagnosis, monitoring and prognosis purposes.

Psychological safety, authentic leadership and social networks : A psycho-structural approach to the study of groups

Tese de Doutoramento em Psicologia na área de especialização de Psicologia das Organizações apresentada ao ISPA - Instituto Universitário

The role of individual ability and structural embeddedness on entrepreneurial success

In the present thesis I analyse the roles of individual ability and structural embeddedness on entrepreneurial success. The results retrieved from a matched employer-employee longitudinal data set show prior worker productivities and environmental embeddedness to have a persistent positive impact on the size and growth rates of new firms. What is more, embeddedness facilitates the impact of ability on start-up performance with outsiders of comparable abilities starting smaller and slower growing firms. Those in higher ability categories are more likely to transfer and also, albeit to a lesser extent, close their ventures, an effect attributed to the higher opportunity costs associated with the group. Firms managed by embedded agents enjoy longer longevities and have better chances of finding a new owner after the departure of the previous one. Finally, higher ability types show evidence of specialisation in serial entrepreneurship.

Structural connectivity based on diffusion Kurtosis imaging

Structural connectivity models based on Diffusion Tensor Imaging (DTI) are strongly affected by the technique’s inability to resolve crossing fibres, either intra- or inter-hemispherical connections. Several models have been proposed to address this issue, including an algorithm aiming to resolve crossing fibres which is based on Diffusion Kurtosis Imaging (DKI). This technique is clinically feasible, even when multi-band acquisitions are not available, and compatible with multi-shell acquisition schemes. DKI is an extension of DTI enabling the estimation of diffusion tensor and diffusion kurtosis metrics. In this study we compare the performance of DKI and DTI in performing structural brain connectivity. Six healthy subjects were recruited, aged between 25 and 35 (three females). The MRI experiments were performed using a 3T Siemens Trio with a 32-channel head coil. The scans included a T1-weighted sequence (1mm3), and a DWI with b-values 0, 1000 and 2000 s:mm

Prenatal tracheal ligation or intra-amniotic administration of surfactant or dexamethasone prevents some structural changes in the pulmonary arteries of surgically created diaphragmatic hernia in rabbits

PURPOSE: Characterization of the structural changes occurring in the pulmonary arteries resulting from surgically produced congenital diaphragmatic hernia in rabbits, with particular emphasis on the preventive effects of prenatal tracheal ligation or administration of intra-amniotic dexamethasone or surfactant. METHODS: Twenty rabbit fetuses underwent surgical creation of a left-sided congenital diaphragmatic hernia on the 24th or 25th gestational day. They were divided according to the following procedures: congenital diaphragmatic hernia (n = 5), congenital diaphragmatic hernia plus tracheal ligation (n = 5), congenital diaphragmatic hernia plus intra-amniotic administration of dexamethasone 0.4 mg (n = 5) or surfactant (Curosurf 40 mg, n = 5). On gestational day 30, all the fetuses were delivered by caesarean section and killed. A control group consisted of five nonoperated fetuses. Histomorphometric analysis of medial thickness, cell nuclei density, and elastic fiber density of pulmonary arterial walls was performed. RESULTS: Arteries with an external diameter > 100 mum have a decreased medial thickness, lower cell nuclei density, and greater elastic fiber density when compared with arteries with external diameter <= 100 mum. Congenital diaphragmatic hernia promoted a significant decrease in medial thickness and an increase in cell nuclei density in artery walls with external diameter > 100 mum. Prenatal treatments with tracheal ligation or intra-amniotic administration of dexamethasone or surfactant prevented these changes. In arteries with external diameter <= 100 mum, congenital diaphragmatic hernia promoted a significant increase in medial thickness and in cell nuclei density and a decrease in elastic fiber density. The prenatal treatments with tracheal ligation or intra-amniotic administration of dexamethasone or surfactant prevented these changes, although no effect was observed in elastic fiber density in the congenital diaphragmatic hernia plus dexamethasone group. CONCLUSIONS: Congenital diaphragmatic hernia promoted different structural changes for large or small arteries. The prenatal intra-amniotic administration of dexamethasone or surfactant had positive effects on the lung structural changes promoted by congenital diaphragmatic hernia, and these effects were comparable to the changes induced by tracheal ligation.

Electro-Optical/Infrared sensor turret integration on an aircraft - structural im-pact on LOCKHEED MARTIN C-130H and design methodology

The growing need to patrol and survey large maritime and terrestrial areas increased the need to integrate external sensors on aircraft in order to accomplish those patrols at increasingly higher altitudes, longer range and not depending upon vehicle type. The main focus of this work is to elaborate a practical, simple, effective and efficient methodology for the aircraft modification procedure resulting from the integration of an Elec-tro-Optical/Infra-Red (EO/IR) turret through a support structure. The importance of the devel-opment of a good methodology relies on the correct management of project variables as time, available resources and project complexity. The key is to deliver a proper tool for a project de-sign team that will be used to create a solution that fulfils all technical, non-technical and certi-fication requirements present in this field of transportation. The created methodology is inde-pendent of two main inputs: sensor model and aircraft model definition, and therefore it is in-tended to deliver the results for different projects besides the one that was presented in this work as a case study. This particular case study presents the development of a structure support for FLIR STAR SAPHIRE III turret integration on the front lower fuselage bulkhead (radome) of the LOCKHEED MARTIN C-130 H. Development of the case study focuses on the study of local structural analysis through the use of Finite Element Method (FEM). Development of this Dissertation resulted in a cooperation between Faculty of Science and Technology - Universidade Nova de Lisboa and the company OGMA - Indústria Aeronáutica de Portugal

Monitoring the early stiffness development in epoxy adhesives for structural strengthening

The present work aimed to assess the early-age evolution of E-modulus of epoxy adhesives used for Fibre-Reinforced Polymer (FRP) strengthening applications. The study involved adapting an existing technique devised for continuous monitoring of concrete stiffness since casting, called EMM-ARM (Elasticity Modulus Measurement through Ambient Response Method) for evaluation of epoxy stiffness. Furthermore, monotonic tensile tests according to ISO standards and cyclic tensile tests were carried out at several ages. A comparison between the obtained results was performed in order to better understand the performance of the several techniques in the assessment of stiffness of epoxy resins. When compared to the other methodologies, the method for calculation of E-modulus recommended by ISO standard led to lower values, since in the considered strain interval, the adhesive had a non-linear stress–strain relationship. The EMM-ARM technique revealed its capability in clearly identifying the hardening kinetics of epoxy adhesives, measuring the material stiffness growth during the entire curing period. At very early ages the values of Young׳s modulus obtained with quasi-static tests were lower than the values collected by EMM-ARM, due to the fact that epoxy resin exhibited a significant visco-elastic behaviour.

Experimental and numerical approaches for structural assessment in new footbridge designs (SFRSCC–GFPR hybrid structure)

Within the civil engineering field, the use of the Finite Element Method has acquired a significant importance, since numerical simulations have been employed in a broad field, which encloses the design, analysis and prediction of the structural behaviour of constructions and infrastructures. Nevertheless, these mathematical simulations can only be useful if all the mechanical properties of the materials, boundary conditions and damages are properly modelled. Therefore, it is required not only experimental data (static and/or dynamic tests) to provide references parameters, but also robust calibration methods able to model damage or other special structural conditions. The present paper addresses the model calibration of a footbridge bridge tested with static loads and ambient vibrations. Damage assessment was also carried out based on a hybrid numerical procedure, which combines discrete damage functions with sets of piecewise linear damage functions. Results from the model calibration shows that the model reproduces with good accuracy the experimental behaviour of the bridge.

Structural assessment of a masonry vault in Portugal

This paper reports on a structural safety assessment and performance evaluation of the upper choir of the Santa Maria de Belém Church in the Jerónimos monastery, Lisbon, one of the most important cultural heritage buildings in Portugal. The possibility of adding a new 20 t organ to the upper choir and its effects on the church structure's response are presented. A refined and a simplified finite-element model is developed to investigate the structure's performance under self-weight and seismic actions. A sensitivity analysis is performed to investigate the effect of masonry mechanical properties and rib cross-sections on the structural response, given the difficulty in accurately obtaining this information. The results show that the safety level of the structure is acceptable, even in the case of adding a heavy new organ.

Tensile creep of a structural epoxy adhesive: experimental and analytical characterization

Epoxy adhesives are nowadays being extensively used in Civil Engineering applications, mostly in the scope of the rehabilitation of reinforced concrete (RC) structures. In this context, epoxy adhesives are used to provide adequate stress transference from fibre reinforced polymers (FRP) to the surrounding concrete substrate. Most recently, the possibility of using prestressed FRPs bonded with these epoxy adhesives is also being explored in order to maximize the potentialities of this strengthening approach. In this context, the understanding of the long term behaviour of the involved materials becomes essential. Even when non-prestressed FRPs are used a certain amount of stress is permanently applied on the adhesive interface during the serviceability conditions of the strengthened structure, and the creep of the adhesive may cause a continuous variation in the deformational response of the element. In this context, this paper presents a study aiming to experimentally characterize the tensile creep behaviour of an epoxy-based adhesive currently used in the strengthening of concrete structures with carbon FRP (CFRP) systems. To analytically describe the tensile creep behaviour, the modified Burgers model was fitted to the experimental creep curves, and the obtained results revealed that this model is capable of predicting with very good accuracy the long term behaviour of this material up to a sustained stress level of 60% of the adhesive’s tensile strength.

Refinement and variability techniques in model transformation of software requirements

Tese de Doutoramento em Tecnologias e Sistemas de Informação

Floristic, edaphic and structural characteristics of flooded and unflooded forests in the lower Rio Purús region of central Amazonia, Brazil

Despite a natural history interest in the early 1900s, relatively little ecological research has been carried out in the Rio Purús basin of central Amazonia, Brazil. Here we describe a new study area in the region of Lago Uauaçú with an emphasis on the climate, forest structure and composition, and soil characteristics between adjacent unflooded (terra firme) and seasonally inundated forests; situated within both the white-water (várzea) and black-water (igapó) drainage systems that dominate the landscape. The climate was found to be typical of that of the central Amazon. Várzea forest soils had high concentrations of nutrients, while terra firme and igapó soils were comparatively nutrient-poor. Terra firme forests were the most floristically diverse forest type, whereas várzea was intermediate, and igapó the most species-poor. The Lecythidaceae was the most important family in terra firme while the Euphorbiaceae was the most important in both várzea and igapó. There were significant differences between forest types in terms of number of saplings, canopy cover and understorey density. In contrasting our results with other published information, we conclude that the Lago Uauaçú region consists of a typical central Amazonian forest macro-mosaic, but is a unique area with high conservation value due to the intimate juxtaposition of terra firme, várzea and igapó forests.

Structural, optical and magnetic properties of pulsed laser deposited Co-doped ZnO films

Zn1−xCoxO films with different Co concentrations (with x=0.00, 0.10, 0.15, and 0.30) were grown by pulsed laser deposition (PLD) technique. The structural and optical properties of the films were investigated by grazing incidence X-ray diffraction (GIXRD), Raman spectroscopy and photoluminescence (PL). The magnetic properties were measured by conventional magnetometry using a SQUID and simulated by ab-initio calculations using Korring–Khon–Rostoker (KKR) method combined with coherent potential approximation (CPA). The effect of Co-doping on the GIXRD and Raman peaks positions, shape and intensity is discussed. PL studies demonstrate that Co-doping induces a decrease of the bandgap energy and quenching of the UV emission. They also suggest the presence of Zn interstitials when x≥0.15. The 10% Co-doped ZnO film shows ferromagnetism at 390 K with a spontaneous magnetic moment ≈4×10−5 emu and coercive field ≈0.17 kOe. The origin of ferromagnetism is explained based on the calculations using KKR method.

Structural, mechanical and piezoelectric properties of polycrystalline AlN films sputtered on titanium bottom electrodes

Polycrystalline AlN coatings deposited on Ti-electrodes films were sputtered by using nitrogen both as reactive gas and sputtering gas, in order to obtain high purity coatings with appropriate properties to be further integrated into wear resistance coatings as a piezoelectric monitoring wear sensor. The chemical composition, the structure and the morphology of the films were investigated by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy and atomic force microscopy techniques. These measurements show the formation of highly (101), (102) and (103) oriented AlN films with good piezoelectric and mechanical properties suitable for applications in electronic devices. Through the use of lower nitrogen flow a densification of the AlN coating occurs in the microstructure, with an improvement of the crystallinity along with the increase of the hardness. Thermal stability of aluminum nitride coatings at high temperature was also examined. It was found an improvement of the piezoelectric properties of the highly (10x) oriented AlN films which became c-axis (002) oriented after annealing. The mechanical behavior after heat treatment shows an important enhancement of the surface hardness and Young’s modulus, which decrease rapidly with the increase of the indentation depth until approach constant values close to the substrate properties after annealing. Thus, thermal annealing energy promotes not only the rearrangement of Al–N network, but also the occurrence of a nitriding process of unsaturated Al atoms which cause a surface hardening of the film.