Practical Management of the Endangered African Wild Dog (Lycaon Pictus): Implementation of Research Methodologies, Management Tools and Validation of Non-Invasive Endocrinology Applications

The porpoise of this study was to implement research methodologies and assess the effectiveness and impact of management tools to promote best practices for the long term conservation of the endangered African wild dog (Lycaon pictus). Different methods were included in the project framework to investigate and expand the applicability of these methodologies to free-ranging African wild dogs in the southern African region: ethology, behavioural endocrinology and ecology field methodologies were tested and implemented. Additionally, research was performed to test the effectiveness and implication of a contraceptive implant (Suprenolin) as a management tool for the species of a subpopulation hosted in fenced areas. Attention was especially given to social structure and survival of treated packs. This research provides useful tools and advances the applicability of these methods for field studies, standardizing and improving research instruments in the field of conservation biology and behavioural endocrinology. Results reported here provide effective methodologies to expand the applicability of non-invasive endocrine assessment to previously prohibited fields, and validation of sampling methods for faecal hormone analysis. The final aim was to fill a knowledge gap on behaviours of the species and provide a common ground for future researchers to apply non-invasive methods to this species research and to test the effectiveness of the contraception on a managed metapopulation.

Development and validation of an echocardiography score for diagnosis of cardiac masses

Background Echocardiography is the cornerstone in the evaluation of cardiac masses and provides accurate characterization. Despite, its accuracy in diagnosis of cardiac masses (CM) remains challenging and, up to date, no validated diagnostic algorithm is validated. Purpose The aim of our study was to evaluate the diagnostic accuracy of echocardiography, to identify the echocardiographic predictors of malignancy and to develop and then validate a multiparametric echocardiographic score that could be used to estimate the likelihood of the histological nature of a CM. Materials and methods The final sample consisted of 273 consecutive patients who had a 2D-echocardiographic evaluation and a histologic diagnosis. Logistic regression was performed to evaluate the ability of echocardiographic findings to discriminate benign versus malignant masses, then a scoring system was developed and validated in a separate test cohort. Results Of the 322 patients initially included in the Bologna Cardiac Masses Registry, 13 with a poor acoustic window, 27 with no histological examination patients and 9 extra-cardiac masses were excluded. In the remaining 273 patients, classical 2-D echocardiogram identified 249 masses with a diagnostic accuracy of 88%. A weighted score [Diagnostic Echocardiographic Mass (DEM) Score] ranging from 0 to 9 was obtained from 6 variables: infiltration, polylobate mass, moderate-severe pericardial effusion. The AUC for the score was 0.965 (95% CI [0.938-0.993]). In a logistic regression analysis using the DEM score as a predictor, the likelihood of malignant CM increased more than 4 times for a 1-unit increase in the score (OR=4.468; 95% CI 2.733-7.304). A score < 3 denoted a high probability of a benign diagnosis, and a score ≥ 5 points corresponded to a higher risk of malignancy. Conclusion 2D-Echocardiography provides a high diagnostic accuracy in identifying cardiac masses and our multiparametric echocardiographic score could be useful to predict the histological nature of cardiac masses.

Development of musculoskeletal models for the design and the pre-clinical validation of hip resurfacing prosthesis

Background. The surgical treatment of dysfunctional hips is a severe condition for the patient and a costly therapy for the public health. Hip resurfacing techniques seem to hold the promise of various advantages over traditional THR, with particular attention to young and active patients. Although the lesson provided in the past by many branches of engineering is that success in designing competitive products can be achieved only by predicting the possible scenario of failure, to date the understanding of the implant quality is poorly pre-clinically addressed. Thus revision is the only delayed and reliable end point for assessment. The aim of the present work was to model the musculoskeletal system so as to develop a protocol for predicting failure of hip resurfacing prosthesis. Methods. Preliminary studies validated the technique for the generation of subject specific finite element (FE) models of long bones from Computed Thomography data. The proposed protocol consisted in the numerical analysis of the prosthesis biomechanics by deterministic and statistic studies so as to assess the risk of biomechanical failure on the different operative conditions the implant might face in a population of interest during various activities of daily living. Physiological conditions were defined including the variability of the anatomy, bone densitometry, surgery uncertainties and published boundary conditions at the hip. The protocol was tested by analysing a successful design on the market and a new prototype of a resurfacing prosthesis. Results. The intrinsic accuracy of models on bone stress predictions (RMSE < 10%) was aligned to the current state of the art in this field. The accuracy of prediction on the bone-prosthesis contact mechanics was also excellent (< 0.001 mm). The sensitivity of models prediction to uncertainties on modelling parameter was found below 8.4%. The analysis of the successful design resulted in a very good agreement with published retrospective studies. The geometry optimisation of the new prototype lead to a final design with a low risk of failure. The statistical analysis confirmed the minimal risk of the optimised design over the entire population of interest. The performances of the optimised design showed a significant improvement with respect to the first prototype (+35%). Limitations. On the authors opinion the major limitation of this study is on boundary conditions. The muscular forces and the hip joint reaction were derived from the few data available in the literature, which can be considered significant but hardly representative of the entire variability of boundary conditions the implant might face over the patients population. This moved the focus of the research on modelling the musculoskeletal system; the ongoing activity is to develop subject-specific musculoskeletal models of the lower limb from medical images. Conclusions. The developed protocol was able to accurately predict known clinical outcomes when applied to a well-established device and, to support the design optimisation phase providing important information on critical characteristics of the patients when applied to a new prosthesis. The presented approach does have a relevant generality that would allow the extension of the protocol to a large set of orthopaedic scenarios with minor changes. Hence, a failure mode analysis criterion can be considered a suitable tool in developing new orthopaedic devices.

Development of the optimal estimation method for inversion of stratospheric emission spectra and validation of HNO3 profiles

This doctoral thesis focuses on ground-based measurements of stratospheric nitric acid (HNO3)concentrations obtained by means of the Ground-Based Millimeter-wave Spectrometer (GBMS). Pressure broadened HNO3 emission spectra are analyzed using a new inversion algorithm developed as part of this thesis work and the retrieved vertical profiles are extensively compared to satellite-based data. This comparison effort I carried out has a key role in establishing a long-term (1991-2010), global data record of stratospheric HNO3, with an expected impact on studies concerning ozone decline and recovery. The first part of this work is focused on the development of an ad hoc version of the Optimal Estimation Method (Rodgers, 2000) in order to retrieve HNO3 spectra observed by means of GBMS. I also performed a comparison between HNO3 vertical profiles retrieved with the OEM and those obtained with the old iterative Matrix Inversion method. Results show no significant differences in retrieved profiles and error estimates, with the OEM providing however additional information needed to better characterize the retrievals. A final section of this first part of the work is dedicated to a brief review on the application of the OEM to other trace gases observed by GBMS, namely O3 and N2O. The second part of this study deals with the validation of HNO3 profiles obtained with the new inversion method. The first step has been the validation of GBMS measurements of tropospheric opacity, which is a necessary tool in the calibration of any GBMS spectra. This was achieved by means of comparisons among correlative measurements of water vapor column content (or Precipitable Water Vapor, PWV) since, in the spectral region observed by GBMS, the tropospheric opacity is almost entirely due to water vapor absorption. In particular, I compared GBMS PWV measurements collected during the primary field campaign of the ECOWAR project (Bhawar et al., 2008) with simultaneous PWV observations obtained with Vaisala RS92k radiosondes, a Raman lidar, and an IR Fourier transform spectrometer. I found that GBMS PWV measurements are in good agreement with the other three data sets exhibiting a mean difference between observations of ~9%. After this initial validation, GBMS HNO3 retrievals have been compared to two sets of satellite data produced by the two NASA/JPL Microwave Limb Sounder (MLS) experiments (aboard the Upper Atmosphere Research Satellite (UARS) from 1991 to 1999, and on the Earth Observing System (EOS) Aura mission from 2004 to date). This part of my thesis is inserted in GOZCARDS (Global Ozone Chemistry and Related Trace gas Data Records for the Stratosphere), a multi-year project, aimed at developing a long-term data record of stratospheric constituents relevant to the issues of ozone decline and expected recovery. This data record will be based mainly on satellite-derived measurements but ground-based observations will be pivotal for assessing offsets between satellite data sets. Since the GBMS has been operated for more than 15 years, its nitric acid data record offers a unique opportunity for cross-calibrating HNO3 measurements from the two MLS experiments. I compare GBMS HNO3 measurements obtained from the Italian Alpine station of Testa Grigia (45.9° N, 7.7° E, elev. 3500 m), during the period February 2004 - March 2007, and from Thule Air Base, Greenland (76.5°N 68.8°W), during polar winter 2008/09, and Aura MLS observations. A similar intercomparison is made between UARS MLS HNO3 measurements with those carried out from the GBMS at South Pole, Antarctica (90°S), during the most part of 1993 and 1995. I assess systematic differences between GBMS and both UARS and Aura HNO3 data sets at seven potential temperature levels. Results show that, except for measurements carried out at Thule, ground based and satellite data sets are consistent within the errors, at all potential temperature levels.

Validation of the CFD code NEPTUNE for a full scale simulator for decay heat removal systems with in-pool heat exchangers

In the present work, a multi physics simulation of an innovative safety system for light water nuclear reactor is performed, with the aim to increase the reliability of its main decay heat removal system. The system studied, denoted by the acronym PERSEO (in Pool Energy Removal System for Emergency Operation) is able to remove the decay power from the primary side of the light water nuclear reactor through a heat suppression pool. The experimental facility, located at SIET laboratories (PIACENZA), is an evolution of the Thermal Valve concept where the triggering valve is installed liquid side, on a line connecting two pools at the bottom. During the normal operation, the valve is closed, while in emergency conditions it opens, the heat exchanger is flooded with consequent heat transfer from the primary side to the pool side. In order to verify the correct system behavior during long term accidental transient, two main experimental PERSEO tests are analyzed. For this purpose, a coupling between the mono dimensional system code CATHARE, which reproduces the system scale behavior, with a three-dimensional CFD code NEPTUNE CFD, allowing a full investigation of the pools and the injector, is implemented. The coupling between the two codes is realized through the boundary conditions. In a first analysis, the facility is simulated by the system code CATHARE V2.5 to validate the results with the experimental data. The comparison of the numerical results obtained shows a different void distribution during the boiling conditions inside the heat suppression pool for the two cases of single nodalization and three volume nodalization scheme of the pool. Finaly, to improve the investigation capability of the void distribution inside the pool and the temperature stratification phenomena below the injector, a two and three dimensional CFD models with a simplified geometry of the system are adopted.

Validation of a new method to assess the long-term Hypothalamic-Pituitary-Adrenal Activity using hair glucocorticoids as biomarkers. - Studies on pigs and laboratory Sprague-Dawley Rats

The evaluation of chronic activity of the hypothalamic-pituitary-adrenal (HPA) axis is critical for determining the impact of chronic stressful situations. The potential use of hair glucocorticoids as a non-invasive, retrospective, biomarker of long term HPA activity is of great interest, and it is gaining acceptance in humans and animals. However, there are still no studies in literature examining hair cortisol concentration in pigs and corticosterone concentration in laboratory rodents. Therefore, we developed and validated, for the first time, a method for measuring hair glucocorticoids concentration in commercial sows and in Sprague-Dawley rats. Our preliminary data demonstrated: 1) a validated and specific washing protocol and extraction assay method with a good sensitivity in both species; 2) the effect of the reproductive phase, housing conditions and seasonality on hair cortisol concentration in sows; 3) similar hair corticosterone concentration in male and female rats; 4) elevated hair corticosterone concentration in response to chronic stress manipulations and chronic ACTH administration, demonstrating that hair provides a good direct index of HPA activity over long periods than other indirect parameters, such adrenal or thymus weight. From these results we believe that this new non-invasive tool needs to be applied to better characterize the overall impact in livestock animals and in laboratory rodents of chronic stressful situations that negatively affect animals welfare. Nevertheless, further studies are needed to improve this methodology and maybe to develop animal models for chronic stress of high interest and translational value in human medicine.

Development and experimental validation of a knock induced damage model and real-time implementation of model-based strategies to control knock intensity in boosted gasoline engines

This PhD thesis reports the main activities carried out during the 3 years long “Mechanics and advanced engineering sciences” course, at the Department of Industrial Engineering of the University of Bologna. The research project title is “Development and analysis of high efficiency combustion systems for internal combustion engines” and the main topic is knock, one of the main challenges for boosted gasoline engines. Through experimental campaigns, modelling activity and test bench validation, 4 different aspects have been addressed to tackle the issue. The main path goes towards the definition and calibration of a knock-induced damage model, to be implemented in the on-board control strategy, but also usable for the engine calibration and potentially during the engine design. Ionization current signal capabilities have been investigated to fully replace the pressure sensor, to develop a robust on-board close-loop combustion control strategy, both in knock-free and knock-limited conditions. Water injection is a powerful solution to mitigate knock intensity and exhaust temperature, improving fuel consumption; its capabilities have been modelled and validated at the test bench. Finally, an empiric model is proposed to predict the engine knock response, depending on several operating condition and control parameters, including injected water quantity.

Numerical modeling and experimental validation of the recrystallization behaviour in the extrusion of 6XXX aluminum alloys

The microstructure of 6XXX aluminum alloys deeply affects mechanical, crash, corrosion and aesthetic properties of extruded profiles. Unfortunately, grain structure evolution during manufacturing processes is a complex phenomenon because several process and material parameters such as alloy chemical composition, temperature, extrusion speed, tools geometries, quenching and thermal treatment parameters affect the grain evolution during the manufacturing process. The aim of the present PhD thesis was the analysis of the recrystallization kinetics during the hot extrusion of 6XXX aluminum alloys and the development of reliable recrystallization models to be used in FEM codes for the microstructure prediction at a die design stage. Experimental activities have been carried out in order to acquire data for the recrystallization models development, validation and also to investigate the effect of process parameters and die design on the microstructure of the final component. The experimental campaign reported in this thesis involved the extrusion of AA6063, AA6060 and AA6082 profiles with different process parameters in order to provide a reliable amount of data for the models validation. A particular focus was made to investigate the PCG defect evolution during the extrusion of medium-strength alloys such as AA6082. Several die designs and process conditions were analysed in order to understand the influence of each of them on the recrystallization behaviour of the investigated alloy. From the numerical point of view, innovative models for the microstructure prediction were developed and validated over the extrusion of industrial-scale profiles with complex geometries, showing a good matching in terms of the grain size and surface recrystallization prediction. The achieved results suggest the reliability of the developed models and their application in the industrial field for process and material properties optimization at a die-design stage.

Development of JADE, a new software for the verification and validation of nuclear data libraries

Nuclear cross sections are the pillars onto which the transport simulation of particles and radiations is built on. Since the nuclear data libraries production chain is extremely complex and made of different steps, it is mandatory to foresee stringent verification and validation procedures to be applied to it. The work here presented has been focused on the development of a new python based software called JADE, whose objective is to give a significant help in increasing the level of automation and standardization of these procedures in order to reduce the time passing between new libraries releases and, at the same time, increasing their quality. After an introduction to nuclear fusion (which is the field where the majority of the V\&V action was concentrated for the time being) and to the simulation of particles and radiations transport, the motivations leading to JADE development are discussed. Subsequently, the code general architecture and the implemented benchmarks (both experimental and computational) are described. After that, the results coming from the major application of JADE during the research years are presented. At last, after a final discussion on the objective reached by JADE, the possible brief, mid and long time developments for the project are discussed.