Planning for strategic change in the project delivery strategy

For organizations such as state departments of transportation, other public agencies, or private companies, adopting a new approach to procure services for delivery of construction projects requires significant organizational changes; modifications to both their work processes and existing organizational structures may be needed. These adjustments, encompassing many different aspects of the organization's interests, must occur for the change initiative to be successfully put into practice. In this research, the adoption of integrated project delivery methods within the transportation project sector is investigated to better understand the dynamics of this change. In the context of this study, an Owner's project delivery strategy is defined as the set of project delivery methods that are adopted for delivering capital projects. This dissertation presents findings from a study of Public Owner organizations that have implemented the designbuild method for delivering highway projects. Using as a case study the new $1.3 billion SH-130 tolled expressway project in Central Texas, the author analyzed project documentation and conducted many interviews with individuals affiliated with owner, legal, engineering consultants, and contractors. Findings suggest that project representatives institutionalize practices and routines connected to the new approach by adapting to new challenges, rather than "overwriting" previously existing practices. Similarly, the institutionalization of innovative approaches to project delivery happens concurrently with a deinstitutionalization of the previous approaches. Building upon these findings, a conceptual framework is presented for helping Owner organizations implement change in their project delivery strategy. The proposed conceptual framework is based upon both existing published literature and interviews with managers involved in implementing a strategic change in project delivery strategy. This framework was further refined by making a comparative study of four transportation projects in the United States. In addition, a detailed implementation framework was validated and further developed through a Delphi study with representatives from several organizations whose major responsibilities and experiences include the management of change in procurement approach. Findings from these studies, including application to the construction industry and other industries are presented.Civil, Architectural, and Environmental Engineerin

A solution to detect and avoid conflicts for civil remotely piloted aircraft systems into non-segregated airspaces

The capability to ‘‘detect and avoid’’ potential collisions is one of the main technical challenges restricting widespread operations of unmanned aircraft into non-segregated airspaces. In fact, to operate into prescribed environments, an unmanned aircraft needs an onboard technology to replace the capability of the human pilot to ‘‘see and avoid’’ collision hazards. Such a technology is a ‘‘sense and avoid’’ system. This article focuses on the ‘‘avoid function’’ of such a system and proposes a suitable solution. The approach to the problem is to schematize a generic obstacle through a moving ellipsoid that represents the region of space the unmanned aircraft must not violate. The obtained solution enables situations of potential conflict to be detected and avoided through a set of such as speed changes in magnitude and/or direction. Thousands of test cases have been considered to validate this solution. Simulations show that the proposed algorithm is able to detect and avoid situations of potential conflict in the three-dimensional space and in real-time, even without the assistance of a human operator. As such, it can be considered as a fundamental step for the development of a prototype of ‘‘sense and avoid’’ system for promoting the integration of unmanned aircraft into non-segregated airspaces

Rotor blades as curved, twisted and tapered beam-like structures subjected to large deflections

Non-prismatic beam-like structures are widespread in many engineering and science applications. Important examples include the rotor blades of wind turbines and helicopters. Their mechanical behaviour can be simulated using 3D beam models, which are computationally efficient, accurate and explicitly consider such structures’ main geometric features, the large deflection of their reference centre-line and 3D warping of their transverse cross-sections. This paper proposes a mathematical model for such structures. A variational approach and the smallness of the warping and strain fields are exploited to obtain the model. Analytical and numerical results obtained with the proposed modelling approach are presented and compared to those from nonlinear 3DFEM simulations

Demystifying progressive design build: implementation issues and lessons learned through case study analysis

The design–build (DB) project delivery method has been used for several decades in the US construction market. DB contracts are usually awarded on the basis of a multicriteria evaluation, with price as one of the most salient criteria. To ensure the project’s success, an owner usually has to invest enough time and effort during scoping and early design to define a program, scope, and budget, ready for procurement and price generation. However, this process can become a burden for the owner and may lengthen the project development duration. As an alternative to the traditional DB, the progressive design–build (PDB) approach permits the selection of the DB team prior to defining the project program and/ or budget. PDB has the advantage of maintaining a single point of accountability and allowing team selection based mainly on qualifications, with a limited consideration of price. Under PDB, the selected team works with the project stakeholders during the early design stage, while helping the owner balance scope and budget. However, the key to the effectiveness of PDB is its provision for the ongoing and complete involvement of the owner in the early design phase. Due to the differences between PDB and the other project delivery methods (e.g., traditional DB), project teams must carefully consider several factors to ensure its successful implementation. The research team conducted a case study of the University of Washington’s pilot PDB project to complete the West Campus Utility Plant (WCUP). This paper carefully explores and summarizes the project’s entire delivery process (e.g., planning, solicitation, design, and construction), its organizational structures, and the project performance outcomes. The lessons learned from the WCUP project will contribute to best practices for future PDB implementation

The differential effects of bisphosphonates, SERMS (selective estrogen receptor modulators), and parathyroid hormone on bone remodeling in osteoporosis

Osteoporosis is a skeletal metabolic disease characterized by a compromised bone fragility, leading to an increased risk of developing spontaneous and traumatic fractures. Osteoporosis is considered a multifactorial disease and fractures are the results of several different risk factors both extra- and intraskeletal. Thus bone fragility can be the end point of several different causes: a) failure to reach an optimal peak bone mass during growth; b) excessive bone resorption resulting in decreased bone mass and microarchitectural deterioration; c) inadequate formation upon an increased resorption during the process of bone remodeling. The pharmacological therapeutical options, available to date, are directed on prevention of fractures. The aim of this paper is to describe the activities and the mechanisms of action, as known at present, of the most used therapies for osteoporosis and their clinical implications. Improvement of knowledge in this field will allow us to further improve therapeutical choices and pharmacological interventions

Chapter Challenges and New Frontiers in the Paediatric Drug Discovery and Development

Drug discovery and development advances in the last decades allowed to find a treatment for many preventable diseases. However, all too often, children are excluded from these progresses since most of the new medicines have been discovered and developed for the adult population. Even if paediatricians routinely give drugs to children ‘off-label’, researchers have demonstrated that children do not respond to medications in the same way as adults. Furthermore, certain specific disorders are unique to children or occur in children differently than in adults. Besides specifically testing medicines in children in proper clinical studies taking into due account the peculiarity of this population, there is a growing recognition of the need to develop paediatric medicines having in mind the specificities of this vulnerable population. In this chapter, we will provide an overview on the drug discovery and development path for children highlighting challenges and new frontiers of each phase from the discovery to the preclinical and clinical development as well as we will provide a slightest hint about paediatric biomarkers discovery, age-appropriate formulation, pregnancy, and perinatal pharmacology and in silico pharmacology. Finally, pricing and reimbursement policies for medicines and new and existing research initiatives in the field will be discussed

Non-Prismatic Beam-Like Structures with 3D Cross-Sectional Warping

Many complex engineering structures, e.g. blades of wind turbines and helicopters, are beamlike and non-prismatic. They may be tapered, twisted and curved in their unstressed state, undergo large displacements of the centre-line, and cross-sectional warping in and out of plane. For their structural modeling, an approach based on beam elements can be the best compromise between computational efficiency and accuracy, but classical beam models (see, for example, the monumental Love's treatise) may not be sufficient. Better results may be obtained by exploiting geometrically exact and asymptotic approaches. This paper proposes a physical-mathematical model for the aforementioned non-prismatic structures. Analytical results obtained for small warping and strain fields are presented and compared to the results obtainable from nonlinear 3D-FEM analyses

Phenotypic Definition of the Progenitor Cells with Erythroid Differentiation Potential Present in Human Adult Blood

In Human Erythroid Massive Amplification (HEMA) cultures, AB mononuclear cells (MNC) generate 1-log more erythroid cells (EBs) than the corresponding CD34pos cells, suggesting that MNC may also contain CD34neg HPC. To clarify the phenotype of AB HPC which generate EBs in these cultures, flow cytometric profiling for CD34/CD36 expression, followed by isolation and functional characterization (colony-forming-ability in semisolid-media and fold-increase in HEMA) were performed. Four populations with erythroid differentiation potential were identified: CD34posCD36neg (0.1%); CD34posCD36pos (barely detectable-0.1%); CD34negCD36low (2%) and CD34negCD36neg (75%). In semisolid-media, CD34posCD36neg cells generated BFU-E and CFU-GM (in a 1 : 1 ratio), CD34negCD36neg cells mostly BFU-E (87%) and CD34posCD36pos and CD34negCD36low cells were not tested due to low numbers. Under HEMA conditions, CD34posCD36neg, CD34posCD36pos, CD34negCD36low and CD34negCD36neg cells generated EBs with fold-increases of ≈9,000, 100, 60 and 1, respectively, and maturation times (day with >10% CD36highCD235ahigh cells) of 10–7 days. Pyrenocytes were generated only by CD34neg/CD36neg cells by day 15. These results confirm that the majority of HPC in AB express CD34 but identify additional CD34neg populations with erythroid differentiation potential which, based on differences in fold-increase and maturation times, may represent a hierarchy of HPC present in AB

GATA-1 as a Regulator of Mast Cell Differentiation Revealed by the Phenotype of the GATA-1low Mouse Mutant

Here it is shown that the phenotype of adult mice lacking the first enhancer (DNA hypersensitive site I) and the distal promoter of the GATA-1 gene (neoΔHS or GATA-1low mutants) reveals defects in mast cell development. These include the presence of morphologically abnormal alcian blue+ mast cells and apoptotic metachromatic− mast cell precursors in connective tissues and peritoneal lavage and numerous (60–70% of all the progenitors) “unique” trilineage cells committed to erythroid, megakaryocytic, and mast pathways in the bone marrow and spleen. These abnormalities, which were mirrored by impaired mast differentiation in vitro, were reversed by retroviral-mediated expression of GATA-1 cDNA. These data indicate an essential role for GATA-1 in mast cell differentiation