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 and application of a thermo-hydraulic model supporting the design and the deterministic safety analysis in a sodium cooled fast reactor

Il CP-ESFR è un progetto integrato di cooperazione europeo sui reattori a sodio SFR realizzato sotto il programma quadro EURATOM 7, che unisce il contributo di venticinque partner europei. Il CP-ESFR ha l'ambizione di contribuire all'istituzione di una "solida base scientifica e tecnica per il reattore veloce refrigerato a sodio, al fine di accelerare gli sviluppi pratici per la gestione sicura dei rifiuti radioattivi a lunga vita, per migliorare le prestazioni di sicurezza, l'efficienza delle risorse e il costo-efficacia di energia nucleare al fine di garantire un sistema solido e socialmente accettabile di protezione della popolazione e dell'ambiente contro gli effetti delle radiazioni ionizzanti. " La presente tesi di laurea è un contributo allo sviluppo di modelli e metodi, basati sull’uso di codici termo-idraulici di sistema, per l’ analisi di sicurezza di reattori di IV Generazione refrigerati a metallo liquido. L'attività è stata svolta nell'ambito del progetto FP-7 PELGRIMM ed in sinergia con l’Accordo di Programma MSE-ENEA(PAR-2013). Il progetto FP7 PELGRIMM ha come obbiettivo lo sviluppo di combustibili contenenti attinidi minori 1. attraverso lo studio di due diverse forme: pellet (oggetto della presente tesi) e spherepac 2. valutandone l’impatto sul progetto del reattore CP-ESFR. La tesi propone lo sviluppo di un modello termoidraulico di sistema dei circuiti primario e intermedio del reattore con il codice RELAP5-3D© (INL, US). Tale codice, qualificato per il licenziamento dei reattori nucleari ad acqua, è stato utilizzato per valutare come variano i parametri del core del reattore rilevanti per la sicurezza (es. temperatura di camicia e di centro combustibile, temperatura del fluido refrigerante, etc.), quando il combustibile venga impiegato per “bruciare” gli attinidi minori (isotopi radioattivi a lunga vita contenuti nelle scorie nucleari). Questo ha comportato, una fase di training sul codice, sui suoi modelli e sulle sue capacità. Successivamente, lo sviluppo della nodalizzazione dell’impianto CP-ESFR, la sua qualifica, e l’analisi dei risultati ottenuti al variare della configurazione del core, del bruciamento e del tipo di combustibile impiegato (i.e. diverso arricchimento di attinidi minori). Il testo è suddiviso in sei sezioni. La prima fornisce un’introduzione allo sviluppo tecnologico dei reattori veloci, evidenzia l’ambito in cui è stata svolta questa tesi e ne definisce obbiettivi e struttura. Nella seconda sezione, viene descritto l’impianto del CP-ESFR con attenzione alla configurazione del nocciolo e al sistema primario. La terza sezione introduce il codice di sistema termico-idraulico utilizzato per le analisi e il modello sviluppato per riprodurre l’impianto. Nella sezione quattro vengono descritti: i test e le verifiche effettuate per valutare le prestazioni del modello, la qualifica della nodalizzazione, i principali modelli e le correlazioni più rilevanti per la simulazione e le configurazioni del core considerate per l’analisi dei risultati. I risultati ottenuti relativamente ai parametri di sicurezza del nocciolo in condizioni di normale funzionamento e per un transitorio selezionato sono descritti nella quinta sezione. Infine, sono riportate le conclusioni dell’attività.

Design, Synthesis and Development of Transporter Targeting Agents for Image-guided Therapy and Drug Delivery

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with 99mTc and 68Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both 99mTc-N4amG and 99mTc-GP were stable up to 6 hours, whereas 68Ga-GP was stable up to 2 hours. Cell culture studies confirmed radiolabeled N4amG and GP could penetrate the cell membrane through nucleoside transporters and amino acid transporters, respectively. Up to 40% of intracellular 99mTc-N4amG and 99mTc-GP was found within cell nucleus following 2 hours of incubation. Flow cytometry analysis revealed 99mTc-N4amG was a cell cycle S phase-specific agent. There was a significant difference of the uptake of 99mTc-GP between pre- and post- paclitaxel-treated cells, which suggests that 99mTc-GP may be useful in chemotherapy treatment monitoring. Moreover, radiolabeled N4amG and GP were tested in vivo using tumor-bearing animal models. 99mTc-N4amG showed an increase in tumor-to-muscle count density ratios up to 5 at 4 hour imaging. Both 99mTc-labeled agents showed decreased tumor uptake after paclitaxel treatment. Immunohistochemistry analysis demonstrated that the uptake of 99mTc-N4amG was correlated with Ki-67 expression. Both 99mTc-N4amG and 99mTc-GP could differentiate between tumor and inflammation in animal studies. Furthermore, 68Ga-GP was compared to 18F-FDG in rabbit PET imaging studies. 68Ga-GP had lower tumor standardized uptake values (SUV), but similar uptake dynamics, and different biodistribution compared with 18F-FDG. Finally, to demonstrate that GP can be a potential drug carrier for cancer theranostics, several drugs, including doxorubicin, were selected to be conjugated to GP. Imaging studies demonstrated that tumor uptake of GP-drug conjugates was increased as a function of time. GP-doxorubicin (GP-DOX) showed a slow-release pattern in in vitro cytotoxicity assay and exhibited anti-cancer efficacy with reduced toxicity in in vivo tumor growth delay study. In conclusion, both N4amG and GP are transporter-based targeting agents. Radiolabeled N4amG can be used for tumor cell proliferation assessment. GP is a potential agent for image-guided therapy and drug delivery.

Design and evaluation of acceleration strategies for speeding up the development of dialog applications

In this paper, we describe a complete development platform that features different innovative acceleration strategies, not included in any other current platform, that simplify and speed up the definition of the different elements required to design a spoken dialog service. The proposed accelerations are mainly based on using the information from the backend database schema and contents, as well as cumulative information produced throughout the different steps in the design. Thanks to these accelerations, the interaction between the designer and the platform is improved, and in most cases the design is reduced to simple confirmations of the “proposals” that the platform dynamically provides at each step. In addition, the platform provides several other accelerations such as configurable templates that can be used to define the different tasks in the service or the dialogs to obtain or show information to the user, automatic proposals for the best way to request slot contents from the user (i.e. using mixed-initiative forms or directed forms), an assistant that offers the set of more probable actions required to complete the definition of the different tasks in the application, or another assistant for solving specific modality details such as confirmations of user answers or how to present them the lists of retrieved results after querying the backend database. Additionally, the platform also allows the creation of speech grammars and prompts, database access functions, and the possibility of using mixed initiative and over-answering dialogs. In the paper we also describe in detail each assistant in the platform, emphasizing the different kind of methodologies followed to facilitate the design process at each one. Finally, we describe the results obtained in both a subjective and an objective evaluation with different designers that confirm the viability, usefulness, and functionality of the proposed accelerations. Thanks to the accelerations, the design time is reduced in more than 56% and the number of keystrokes by 84%.

Greenfield shopping center development. The integration between environmental features, building design and investment analysis at the decision making stage

The Shopping centre is a long term investment in which Greenfield development decisions are often taken based on risks analysis regarding construction costs, location, competition, market and an expected DCF. Furthermore, integration between the building design, project planning, operational costs and investment analysis is not entirely considered by the investor at the decision making stage. The absence of such information tends to produce certain negative impacts on the future running costs and annual maintenance of the building, especially on energy demand and other occupancy expenses paid by the tenants to the landlord. From the investor´s point of view, this blind spot in strategy development will possibly decrease their profit margin as changes in the occupancy expenses[ ] have a direct outcome on the profit margin. In order to try to reduce some higher operating cost components such as energy use and other utility savings as well as their CO2 emissions, quite a few income properties worldwide have some type of environmental label such as BREEAM and LEED. The drawback identified in this labelling is that usually the investments required to get an ecolabel are high and the investor finds no direct evidence that it increases market value. However there is research on certified commercial properties (especially offices) that shows better performance in terms of occupancy rate and rental cost (Warren-Myers, 2012). Additionally, Sayce (2013) says that the certification only provides a quick reference point i.e. the lack of a certificate does not indicate that a building is not sustainable or efficient. Based on the issues described above, this research compares important components of the development stages such as investments costs, concept/ strategy development as well as the current investor income and property value. The subjects for this analysis are a shopping centre designed with passive cooling/bioclimatic strategies evaluated at the decision making stage, a certified regional shopping centre and a non-certified standard regional shopping centre. Moreover, the proposal intends to provide decision makers with some tools for linking green design features to the investment analysis in order to optimize the decision making process when looking into cost savings and design quality.

Industry Professionals Who Attain Leadership in Energy and Environmental Design (LEED) Accreditation: An Examination of Motivations in Human Resource (HR) Training and Development

Despite the economy, the green building industry continues to grow and drive the demand for environmentally conscious, highly skilled professionals (USGBC 2009). LEED Accredited Professionals (APs) have the knowledge and skills to meet such demand; however, information is limited regarding LEED APs or their motivations and expectations toward prospective employers. The author surveyed a sample of LEED Accredited architects and found a combination of job and personal factors motivated them to attain accreditation. LEED APs value both a competitive salary and commitment to sustainability in prospective employers. To attract, retain, and utilize LEED APs, executives in this industry must reexamine corporate culture, their willingness to pay for credentialing, and the alignment of their reputation with the desires of potential applicants.

Controversy between curriculum design and curriculum development of online "highly specialized" education in the field of construction

Nowadays, on a global level, the Higher Education System has a complex and broad horizon of curricular tools to use in the teaching and learning process. In addition to these new educational instruments, full of possibilities, we face specific socio-economic conditions that affect in a significantly way the Curriculum Development in certain knowledge areas (areas traditionally built on a methodology based on a physical presence of students in the classroom). Some areas such as Restoration, Rehabilitation or Construction Pathologies, and the construction sector in general, require very defined and particular knowledge that only a small number of experts claim as specialized training. All these aspects condition the teaching methodology performed in a physical classroom at a university campus (the only option used until recent years) and made us consider the integration of online teaching in these areas too. The present work shows the teaching methodology used for the development of two online courses, where we offer distance learning for "highly specialized" formation in the Edification area (an area where traditionally there was only classroom training). At the beginning, both courses were designed by classroom training, but got a really small number of applications due to the specialized topic proposed. Later, we proposed a "Curriculum Redesign" of the contents, offering an online modality, which implied a significant demand both within and outside the university area. A notable feature of this educational experience is the great spectrum opened for attendees of both courses in the online version. This situation improved significantly the "Curriculum Development" for the student and implied an interesting new proposal on the offered contents and materials (what would have been really difficult to get in a face to face classroom). In conclusion, the absence of certain types of specialized contents in the academic university curricula makes essential to raise new methodologies to save the gap in this area through additional training courses as those analyzed in this paper. Thus, our experience opens a debate on the appropriateness of implementing online training in relation to the face to face training in constructive content subjects and, especially, presents a new scheme, not without controversy, for the curriculum design.

An investigation of the effectiveness of existing bridge design methodology in providing adequate structural resistance to seismic disturbances : Phase III, Nonlinear soil-structure interaction of skew highway bridges : final report : prepared for Federal Highway Administration, Offices of Research and Development /

Bibliography: p. 46-48.

Automotive tape recorder. Volume 1. Design and preliminary development. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Development of a low-cost truck weighing system design and operator manual. Final report.

Federal Highway Administration, Office of Engineering and Highway Operations Research and Development, McLean, Va.

Development and use of a computer simulation model for the evaluation of design and control alternatives for intersections of minor roads with multi-lane rural highways: field studies and model validation. Interim report.

Federal Highway Administration, Washington, D.C.

Development and use of a computer simulation model for the evaluation of design and control alternatives for intersections of minor roads with multi-lane rural highways: model application. Interim report.

Federal Highway Administration, Washington, D.C.