Galanin N-Terminal fragment (1-15) enhances the antidepressant effects of the 5-HT1A receptor agonist 8-OH-DPAT in the Forced Swimming Test.

Galanin and Galanin (1-15) [GAL(1-15)] are implicated in anxiety- and depression related behaviors. Moreover, Galanin modulates 5-HT1A receptor (5-HT1AR) function at autorreceptor and postsynaptic level in the brain. In this study, we have analysed the ability of GAL(1-15) to modulate the effects of the 8-OH-DPAT agonist in the Forced Swimming Test (FST). Groups of rats were assessed in the FST. In the first set of experiments, to evaluate the interactions of 8-OH-DPAT and GAL(1-15), rats received subcutaneously (s.c) the effective doses of 8-OH-DPAT (0.25mg/Kg) 60min before the test and intracerebroventricularly (icv) GAL(1-15)1nmol 15min before the tests alone or in combination. In the second set of experiments, groups of rats received s.c. 8-OH-DPAT (0.125mg/Kg), icv GAL(1-15) 1nmol and icv the GALR2 antagonist M871 3 nmol alone or in combination. The locomotor activity was analysed in the open field test. GAL(1-15) 1nmol enhanced the antidepressant-like effects mediated by the effective dose of the 8-OH-DPAT. GAL(1-15) significantly decreased the immobility (p<0.05) and climbing (p<0.05) and increased the swimming (p<0.01) behaviour induced by an effective dose of 8-OH-DPAT (0.25mg/Kg) in FST. Moreover, after coadministration of GAL(1-15) and threshold dose of 8-OH-DPAT (0.125mg/Kg) a significant decreased appeared in immobility (p<0.01) and climbing (p<0.01) and increased the swimming behavior (p<0.001) vs 8-OH-DPAT group. Moreover, M871 blocked completely this interaction. These results indicate that GAL(1-15) enhances the antidepressant effects induced by 8-OH-DPAT in the FST. These findings may give the basis for the development of novel therapeutic drugs. This study was supported by Junta de Andalucía CVI6476.

Development and optimization of fluoxetine orally disintegrating tablets using Box-Behnken design

Purpose: To develop and optimise some variables that influence fluoxetine orally disintegrating tablets (ODTs) formulation. Methods: Fluoxetine ODTs tablets were prepared using direct compression method. Three-factor, 3- level Box-Behnken design was used to optimize and develop fluoxetine ODT formulation. The design suggested 15 formulations of different lubricant concentration (X1), lubricant mixing time (X2), and compression force (X3) and then their effect was monitored on tablet weight (Y1), thickness (Y2), hardness (Y3), % friability (Y4), and disintegration time (Y5). Results: All powder blends showed acceptable flow properties, ranging from good to excellent. The disintegration time (Y5) was affected directly by lubricant concentration (X1). Lubricant mixing time (X2) had a direct effect on tablet thickness (Y2) and hardness (Y3), while compression force (X3) had a direct impact on tablet hardness (Y3), % friability (Y4) and disintegration time (Y5). Accordingly, Box-Behnken design suggested an optimized formula of 0.86 mg (X1), 15.3 min (X2), and 10.6 KN (X3). Finally, the prediction error percentage responses of Y1, Y2, Y3, Y4, and Y5 were 0.31, 0.52, 2.13, 3.92 and 3.75 %, respectively. Formula 4 and 8 achieved 90 % of drug release within the first 5 min of dissolution test. Conclusion: Fluoxetine ODT formulation has been developed and optimized successfully using Box- Behnken design and has also been manufactured efficiently using direct compression technique.

Development of new scenario decomposition techniques for linear and nonlinear stochastic programming

Une approche classique pour traiter les problèmes d’optimisation avec incertitude à deux- et multi-étapes est d’utiliser l’analyse par scénario. Pour ce faire, l’incertitude de certaines données du problème est modélisée par vecteurs aléatoires avec des supports finis spécifiques aux étapes. Chacune de ces réalisations représente un scénario. En utilisant des scénarios, il est possible d’étudier des versions plus simples (sous-problèmes) du problème original. Comme technique de décomposition par scénario, l’algorithme de recouvrement progressif est une des méthodes les plus populaires pour résoudre les problèmes de programmation stochastique multi-étapes. Malgré la décomposition complète par scénario, l’efficacité de la méthode du recouvrement progressif est très sensible à certains aspects pratiques, tels que le choix du paramètre de pénalisation et la manipulation du terme quadratique dans la fonction objectif du lagrangien augmenté. Pour le choix du paramètre de pénalisation, nous examinons quelques-unes des méthodes populaires, et nous proposons une nouvelle stratégie adaptive qui vise à mieux suivre le processus de l’algorithme. Des expériences numériques sur des exemples de problèmes stochastiques linéaires multi-étapes suggèrent que la plupart des techniques existantes peuvent présenter une convergence prématurée à une solution sous-optimale ou converger vers la solution optimale, mais avec un taux très lent. En revanche, la nouvelle stratégie paraît robuste et efficace. Elle a convergé vers l’optimalité dans toutes nos expériences et a été la plus rapide dans la plupart des cas. Pour la question de la manipulation du terme quadratique, nous faisons une revue des techniques existantes et nous proposons l’idée de remplacer le terme quadratique par un terme linéaire. Bien que qu’il nous reste encore à tester notre méthode, nous avons l’intuition qu’elle réduira certaines difficultés numériques et théoriques de la méthode de recouvrement progressif.

DEVELOPMENT AND VALIDATION OF THE ANTERIOR CRUCIATE LIGAMENT INJURY-RISK-ESTIMATION QUIZ (ACL-IQ)

Over 2 million Anterior Cruciate Ligament (ACL) injuries occur annually worldwide resulting in considerable economic and health burdens (e.g., suffering, surgery, loss of function, risk for re-injury, and osteoarthritis). Current screening methods are effective but they generally rely on expensive and time-consuming biomechanical movement analysis, and thus are impractical solutions. In this dissertation, I report on a series of studies that begins to investigate one potentially efficient alternative to biomechanical screening, namely skilled observational risk assessment (e.g., having experts estimate risk based on observations of athletes movements). Specifically, in Study 1 I discovered that ACL injury risk can be accurately and reliably estimated with nearly instantaneous visual inspection when observed by skilled and knowledgeable professionals. Modern psychometric optimization techniques were then used to develop a robust and efficient 5-item test of ACL injury risk prediction skill—i.e., the ACL Injury-Risk-Estimation Quiz or ACL-IQ. Study 2 cross-validated the results from Study 1 in a larger representative sample of both skilled (Exercise Science/Sports Medicine) and un-skilled (General Population) groups. In accord with research on human expertise, quantitative structural and process modeling of risk estimation indicated that superior performance was largely mediated by specific strategies and skills (e.g., ignoring irrelevant information), independent of domain general cognitive abilities (e.g., metal rotation, general decision skill). These cognitive models suggest that ACL-IQ is a trainable skill, providing a foundation for future research and applications in training, decision support, and ultimately clinical screening investigations. Overall, I present the first evidence that observational ACL injury risk prediction is possible including a robust technology for fast, accurate and reliable measurement—i.e., the ACL-IQ. Discussion focuses on applications and outreach including a web platform that was developed to house the test, provide a repository for further data collection, and increase public and professional awareness and outreach (www.ACL-IQ.org). Future directions and general applications of the skilled movement analysis approach are also discussed.

Development and testing of a Fourier trasform based experimental system for Dynamic Mechanical Thermal Analysis tests

Altough nowadays DMTA is one of the most used techniques to characterize polymers thermo-mechanical behaviour, it is only effective for small amplitude oscillatory tests and limited to a single frequency analysis (linear regime). In this thesis work a Fourier transform based experimental system has proven to give hint on structural and chemical changes in specimens during large amplitude oscillatory tests exploiting multi frequency spectral analysis turning out in a more sensitive tool than classical linear approach. The test campaign has been focused on three test typologies: Strain sweep tests, Damage investigation and temperature sweep tests.

Development and Verification of Control and Protection Strategies in Hybrid AC/DC Power Systems for Smart Grid Applications

Modern power networks incorporate communications and information technology infrastructure into the electrical power system to create a smart grid in terms of control and operation. The smart grid enables real-time communication and control between consumers and utility companies allowing suppliers to optimize energy usage based on price preference and system technical issues. The smart grid design aims to provide overall power system monitoring, create protection and control strategies to maintain system performance, stability and security. This dissertation contributed to the development of a unique and novel smart grid test-bed laboratory with integrated monitoring, protection and control systems. This test-bed was used as a platform to test the smart grid operational ideas developed here. The implementation of this system in the real-time software creates an environment for studying, implementing and verifying novel control and protection schemes developed in this dissertation. Phasor measurement techniques were developed using the available Data Acquisition (DAQ) devices in order to monitor all points in the power system in real time. This provides a practical view of system parameter changes, system abnormal conditions and its stability and security information system. These developments provide valuable measurements for technical power system operators in the energy control centers. Phasor Measurement technology is an excellent solution for improving system planning, operation and energy trading in addition to enabling advanced applications in Wide Area Monitoring, Protection and Control (WAMPAC). Moreover, a virtual protection system was developed and implemented in the smart grid laboratory with integrated functionality for wide area applications. Experiments and procedures were developed in the system in order to detect the system abnormal conditions and apply proper remedies to heal the system. A design for DC microgrid was developed to integrate it to the AC system with appropriate control capability. This system represents realistic hybrid AC/DC microgrids connectivity to the AC side to study the use of such architecture in system operation to help remedy system abnormal conditions. In addition, this dissertation explored the challenges and feasibility of the implementation of real-time system analysis features in order to monitor the system security and stability measures. These indices are measured experimentally during the operation of the developed hybrid AC/DC microgrids. Furthermore, a real-time optimal power flow system was implemented to optimally manage the power sharing between AC generators and DC side resources. A study relating to real-time energy management algorithm in hybrid microgrids was performed to evaluate the effects of using energy storage resources and their use in mitigating heavy load impacts on system stability and operational security.

Development of new scenario decomposition techniques for linear and nonlinear stochastic programming

Une approche classique pour traiter les problèmes d’optimisation avec incertitude à deux- et multi-étapes est d’utiliser l’analyse par scénario. Pour ce faire, l’incertitude de certaines données du problème est modélisée par vecteurs aléatoires avec des supports finis spécifiques aux étapes. Chacune de ces réalisations représente un scénario. En utilisant des scénarios, il est possible d’étudier des versions plus simples (sous-problèmes) du problème original. Comme technique de décomposition par scénario, l’algorithme de recouvrement progressif est une des méthodes les plus populaires pour résoudre les problèmes de programmation stochastique multi-étapes. Malgré la décomposition complète par scénario, l’efficacité de la méthode du recouvrement progressif est très sensible à certains aspects pratiques, tels que le choix du paramètre de pénalisation et la manipulation du terme quadratique dans la fonction objectif du lagrangien augmenté. Pour le choix du paramètre de pénalisation, nous examinons quelques-unes des méthodes populaires, et nous proposons une nouvelle stratégie adaptive qui vise à mieux suivre le processus de l’algorithme. Des expériences numériques sur des exemples de problèmes stochastiques linéaires multi-étapes suggèrent que la plupart des techniques existantes peuvent présenter une convergence prématurée à une solution sous-optimale ou converger vers la solution optimale, mais avec un taux très lent. En revanche, la nouvelle stratégie paraît robuste et efficace. Elle a convergé vers l’optimalité dans toutes nos expériences et a été la plus rapide dans la plupart des cas. Pour la question de la manipulation du terme quadratique, nous faisons une revue des techniques existantes et nous proposons l’idée de remplacer le terme quadratique par un terme linéaire. Bien que qu’il nous reste encore à tester notre méthode, nous avons l’intuition qu’elle réduira certaines difficultés numériques et théoriques de la méthode de recouvrement progressif.

Favorability conditions in the adoption of agile method practices for software development in a public banking

The main purpose of this paper is to propose and test a model to assess the degree of conditions favorability in the adoption of agile methods to develop software where traditional methods predominate. In order to achieve this aim, a survey was applied on software developers of a Brazilian public retail bank. Two different statistical techniques were used in order to assess the quantitative data from the closed questions in the survey. The first, exploratory factorial analysis validated the structure of perspectives related to the agile model of the proposed assessment. The second, frequency distribution analysis to categorize the answers. Qualitative data from the survey opened question were analyzed with the technique of qualitative thematic content analysis. As a result, the paper proposes a model to assess the degree of favorability conditions in the adoption of Agile practices within the context of the proposed study.

Development of a framework to create plugins in Android Apps

The present work aims to allow developers to implement small features on a certain Android application in a fast and easy manner, as well as provide their users to install them ondemand, i.e., they can install the ones they are interested in. These small packages of features are called plugins, and the chosen development language to develop these in was JavaScript. In order to achieve that, an Android framework was developed that enables the host application to install, manage and run these plugins at runtime. This framework was designed to have a very clean and almost readable API, which allowed for better code organization and maintainability. The implementation used the Google’s engine “V8” to interpret the JavaScript code and through a set of JNI calls made that code call certain Android methods previously registered in the runtime. In order to test the framework, it was integrated with the client’s communication application RCS+ using two plugins developed alongside the framework. Although these plugins had only the more common requirements, they were proven to work successfully as intended. Concluding, the framework although successful made it clear that this kind of development through a non-native API has its set of difficulties especially regarding the implementation of complex features.

The role of area-level deprivation and gender in participation in population-based faecal immunochemical test (FIT) colorectal cancer screening

This study aimed to investigate the effects of sex and deprivation on participation in a population-based faecal immunochemical test (FIT) colorectal cancer screening programme. The study population included 9785 individuals invited to participate in two rounds of a population-based biennial FIT-based screening programme, in a relatively deprived area of Dublin, Ireland. Explanatory variables included in the analysis were sex, deprivation category of area of residence and age (at end of screening). The primary outcome variable modelled was participation status in both rounds combined (with “participation” defined as having taken part in either or both rounds of screening). Poisson regression with a log link and robust error variance was used to estimate relative risks (RR) for participation. As a sensitivity analysis, data were stratified by screening round. In both the univariable and multivariable models deprivation was strongly associated with participation. Increasing affluence was associated with higher participation; participation was 26% higher in people resident in the most affluent compared to the most deprived areas (multivariable RR = 1.26: 95% CI 1.21–1.30). Participation was significantly lower in males (multivariable RR = 0.96: 95%CI 0.95–0.97) and generally increased with increasing age (trend per age group, multivariable RR = 1.02: 95%CI, 1.01–1.02). No significant interactions between the explanatory variables were found. The effects of deprivation and sex were similar by screening round. Deprivation and male gender are independently associated with lower uptake of population-based FIT colorectal cancer screening, even in a relatively deprived setting. Development of evidence-based interventions to increase uptake in these disadvantaged groups is urgently required.

Development of an ecotoxicological protocol for the deep-sea fauna using the hydrothermal vent shrimp Rimicaris exoculata

In light of deep-sea mining industry development, particularly interested in massive-sulphide deposits enriched in metals with high commercial value, efforts are increasing to better understand potential environmental impacts to local fauna. The aim of this study was to assess the natural background levels of biomarkers in the hydrothermal vent shrimp Rimicaris exoculata and their responses to copper exposure at in situ pressure (30MPa) as well as the effects of depressurization and pressurization of the high-pressure aquarium IPOCAMP. R. exoculata were collected from the chimney walls of the hydrothermal vent site TAG (Mid Atlantic Ridge) at 3630m depth during the BICOSE cruise in 2014. Tissue metal accumulation was quantified in different tissues (gills, hepatopancreas and muscle) and a battery of biomarkers was measured: metal exposure (metallothioneins), oxidative stress (catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase) and oxidative damage (lipid peroxidation). Data show a higher concentration of Cu in the hepatopancreas and a slight increase in the gills after incubations (for both exposed groups). Significant induction of metallothioneins was observed in the gills of shrimps exposed to 4μM of Cu compared to the control group. Moreover, activities of enzymes were detected for the in situ group, showing a background protection against metal toxicity. Results suggest that the proposed method, including a physiologically critical step of pressurizing and depressurizing the test chamber to enable the seawater exchange during exposure to contaminants, is not affecting metal accumulation and biomarkers response and may prove a useful method to assess toxicity of contaminants in deep-sea species.

Normative reference values for the 20-meter shuttlerun test in a population-based sample of schoolchildren in Bogota, Colombia: The FUPRECOL Study

Our aim was to determine the normative reference values of cardiorespiratory fitness (CRF) and to establish the proportion of subjects with low CRF suggestive of future cardio-metabolic risk.

Test of Emotion Comprehension: Exploring the underlying structure through Confirmatory Factor Analysis and Similarity Structure Analysis

Some decades of research on emotional development have underlined the contribution of several domains to emotional understanding in childhood. Based on this research, Pons and colleagues (Pons & Harris, 2002; Pons, Harris & Rosnay, 2004) have proposed the Test of Emotion Comprehension (TEC) which assesses nine domains of emotional understanding, namely the recognition of emotions, based on facial expressions; the comprehension of external emotional causes; impact of desire on emotions; emotions based on beliefs; memory influence on emotions; possibility of emotional regulation; possibility of hiding an emotional state; having mixed emotions; contribution of morality to emotional experiences. This instrument was administered individually to 182 Portuguese children aged between 8 and 11 years, of 3rd and 4th grades, in public schools. Additionally, we used the Socially in Action-Peers (SAp) (Rocha, Candeias & Lopes da Silva, 2012) to assess TEC’s criterion-related validity. Mean differences results in TEC by gender and by socio-economic status (SES) were analyzed. The results of the TEC’s psychometric analysis were performed in terms of items’ sensitivity and reliability (stability, test-retest). Finally, in order to explore the theoretical structure underlying TEC a Confirmatory Factor Analysis and a Similarity Structure Analysis were computed. Implications of these findings for emotional understanding assessment and intervention in childhood are discussed.

Development of Core Design Methods and Tools for Gen-IV Heavy Liquid Metal Cooled Reactors

Heavy Liquid Metal Cooled Reactors are among the concepts, fostered by the GIF, as potentially able to comply with stringent safety, economical, sustainability, proliferation resistance and physical protection requirements. The increasing interest around these innovative systems has highlighted the lack of tools specifically dedicated to their core design stage. The present PhD thesis summarizes the three years effort of, partially, closing the mentioned gap, by rationally defining the role of codes in core design and by creating a development methodology for core design-oriented codes (DOCs) and its subsequent application to the most needed design areas. The covered fields are, in particular, the fuel assembly thermal-hydraulics and the fuel pin thermo-mechanics. Regarding the former, following the established methodology, the sub-channel code ANTEO+ has been conceived. Initially restricted to the forced convection regime and subsequently extended to the mixed one, ANTEO+, via a thorough validation campaign, has been demonstrated a reliable tool for design applications. Concerning the fuel pin thermo-mechanics, the will to include safety-related considerations at the outset of the pin dimensioning process, has given birth to the safety-informed DOC TEMIDE. The proposed DOC development methodology has also been applied to TEMIDE; given the complex interdependence patterns among the numerous phenomena involved in an irradiated fuel pin, to optimize the code final structure, a sensitivity analysis has been performed, in the anticipated application domain. The development methodology has also been tested in the verification and validation phases; the latter, due to the low availability of experiments truly representative of TEMIDE's application domain, has only been a preliminary attempt to test TEMIDE's capabilities in fulfilling the DOC requirements upon which it has been built. In general, the capability of the proposed development methodology for DOCs in delivering tools helping the core designer in preliminary setting the system configuration has been proven.

Design and Development of a Research Framework for Prototyping Control Tower Augmented Reality Tools

The purpose of the air traffic management system is to ensure the safe and efficient flow of air traffic. Therefore, while augmenting efficiency, throughput and capacity in airport operations, attention has rightly been placed on doing it in a safe manner. In the control tower, many advances in operational safety have come in the form of visualization tools for tower controllers. However, there is a paradox in developing such systems to increase controllers' situational awareness: by creating additional computer displays, the controller's vision is pulled away from the outside view and the time spent looking down at the monitors is increased. This reduces their situational awareness by forcing them to mentally and physically switch between the head-down equipment and the outside view. This research is based on the idea that augmented reality may be able to address this issue. The augmented reality concept has become increasingly popular over the past decade and is being proficiently used in many fields, such as entertainment, cultural heritage, aviation, military & defense. This know-how could be transferred to air traffic control with a relatively low effort and substantial benefits for controllers’ situation awareness. Research on this topic is consistent with SESAR objectives of increasing air traffic controllers’ situation awareness and enable up to 10 % of additional flights at congested airports while still increasing safety and efficiency. During the Ph.D., a research framework for prototyping augmented reality tools was set up. This framework consists of methodological tools for designing the augmented reality overlays, as well as of hardware and software equipment to test them. Several overlays have been designed and implemented in a simulated tower environment, which is a virtual reconstruction of Bologna airport control tower. The positive impact of such tools was preliminary assessed by means of the proposed methodology.