523 resultados para Level of underwriting
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This chapter argues that evolutionary economics should be founded upon complex systems theory rather than neo-Darwinian analogies concerning natural selection, which focus on supply side considerations and competition amongst firms and technologies. It suggests that conceptions such as production and consumption functions should be replaced by network representations, in which the preferences or, more correctly, the aspirations of consumers are fundamental and, as such, the primary drivers of economic growth. Technological innovation is viewed as a process that is intermediate between these aspirational networks, and the organizational networks in which goods and services are produced. Consumer knowledge becomes at least as important as producer knowledge in determining how economic value is generated. It becomes clear that the stability afforded by connective systems of rules is essential for economic flexibility to exist, but that too many rules result in inert and structurally unstable states. In contrast, too few rules result in a more stable state, but at a low level of ordered complexity. Economic evolution from this perspective is explored using random and scale free network representations of complex systems.
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Historically, determining the country of origin of a published work presented few challenges, because works were generally published physically – whether in print or otherwise – in a distinct location or few locations. However, publishing opportunities presented by new technologies mean that we now live in a world of simultaneous publication – works that are first published online are published simultaneously to every country in world in which there is Internet connectivity. While this is certainly advantageous for the dissemination and impact of information and creative works, it creates potential complications under the Berne Convention for the Protection of Literary and Artistic Works (“Berne Convention”), an international intellectual property agreement to which most countries in the world now subscribe. Under the Berne Convention’s national treatment provisions, rights accorded to foreign copyright works may not be subject to any formality, such as registration requirements (although member countries are free to impose formalities in relation to domestic copyright works). In Kernel Records Oy v. Timothy Mosley p/k/a Timbaland, et al. however, the Florida Southern District Court of the United States ruled that first publication of a work on the Internet via an Australian website constituted “simultaneous publication all over the world,” and therefore rendered the work a “United States work” under the definition in section 101 of the U.S. Copyright Act, subjecting the work to registration formality under section 411. This ruling is in sharp contrast with an earlier decision delivered by the Delaware District Court in Håkan Moberg v. 33T LLC, et al. which arrived at an opposite conclusion. The conflicting rulings of the U.S. courts reveal the problems posed by new forms of publishing online and demonstrate a compelling need for further harmonization between the Berne Convention, domestic laws and the practical realities of digital publishing. In this article, we argue that even if a work first published online can be considered to be simultaneously published all over the world it does not follow that any country can assert itself as the “country of origin” of the work for the purpose of imposing domestic copyright formalities. More specifically, we argue that the meaning of “United States work” under the U.S. Copyright Act should be interpreted in line with the presumption against extraterritorial application of domestic law to limit its application to only those works with a real and substantial connection to the United States. There are gaps in the Berne Convention’s articulation of “country of origin” which provide scope for judicial interpretation, at a national level, of the most pragmatic way forward in reconciling the goals of the Berne Convention with the practical requirements of domestic law. We believe that the uncertainties arising under the Berne Convention created by new forms of online publishing can be resolved at a national level by the sensible application of principles of statutory interpretation by the courts. While at the international level we may need a clearer consensus on what amounts to “simultaneous publication” in the digital age, state practice may mean that we do not yet need to explore textual changes to the Berne Convention.
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Currently, well established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, their application, however, is associated with disadvantages. These include limited access and availability, donor site morbidity and haemorrhage, increased risk of infection, and insufficient transplant integration. As a result, recent research focuses on the development of complementary therapeutic concepts. The field of tissue engineering has emerged as an important alternative approach to bone regeneration. Tissue engineering unites aspects of cellular biology, biomechanical engineering, biomaterial sciences and trauma and orthopaedic surgery. To obtain approval by regulatory bodies for these novel therapeutic concepts the level of therapeutic benefit must be demonstrated rigorously in well characterized, clinically relevant animal models. Therefore, in this PhD project, a reproducible and clinically relevant, ovine, critically sized, high load bearing, tibial defect model was established and characterized as a prerequisite to assess the regenerative potential of a novel treatment concept in vivo involving a medical grade polycaprolactone and tricalciumphosphate based composite scaffold and recombinant human bone morphogenetic proteins.
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DeLone and McLean (1992, p. 16) argue that the concept of “system use” has suffered from a “too simplistic definition.” Despite decades of substantial research on system use, the concept is yet to receive strong theoretical scrutiny. Many measures of system use and the development of measures have been often idiosyncratic and lack credibility or comparability. This paper reviews various attempts at conceptualization and measurement of system use and then proposes a re-conceptualization of it as “the level of incorporation of an information system within a user’s processes.” The definition is supported with the theory of work systems, system, and Key-User-Group considerations. We then go on to develop the concept of a Functional- Interface-Point (FIP) and four dimensions of system usage: extent, the proportion of the FIPs used by the business process; frequency, the rate at which FIPs are used by the participants in the process; thoroughness, the level of use of information/functionality provided by the system at an FIP; and attitude towards use, a set of measures that assess the level of comfort, degree of respect and the challenges set forth by the system. The paper argues that the automation level, the proportion of the business process encoded by the information system has a mediating impact on system use. The article concludes with a discussion of some implications of this re-conceptualization and areas for follow on research.
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Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.
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Despite promising benefits and advantages, there are reports of failures and low realisation of benefits in Enterprise System (ES) initiatives. Among the research on the factors that influence ES success, there is a dearth of studies on the knowledge implications of multiple end-user groups using the same ES application. An ES facilitates the work of several user groups, ranging from strategic management, management, to operational staff, all using the same system for multiple objectives. Given the fundamental characteristics of ES – integration of modules, business process views, and aspects of information transparency – it is necessary that all frequent end-users share a reasonable amount of common knowledge and integrate their knowledge to yield new knowledge. Recent literature on ES implementation highlights the importance of Knowledge Integration (KI) for implementation success. Unfortunately, the importance of KI is often overlooked and little about the role of KI in ES success is known. Many organisations do not achieve the potential benefits from their ES investment because they do not consider the need or their ability to integrate their employees’ knowledge. This study is designed to improve our understanding of the influence of KI among ES end-users on operational ES success. The three objectives of the study are: (I) to identify and validate the antecedents of KI effectiveness, (II) to investigate the impact of KI effectiveness on the goodness of individuals’ ES-knowledge base, and (III) to examine the impact of the goodness of individuals’ ES-knowledge base on the operational ES success. For this purpose, we employ the KI factors identified by Grant (1996) and an IS-impact measurement model from the work of Gable et al. (2008) to examine ES success. The study derives its findings from data gathered from six Malaysian companies in order to obtain the three-fold goal of this thesis as outlined above. The relationships between the antecedents of KI effectiveness and its consequences are tested using 188 responses to a survey representing the views of management and operational employment cohorts. Using statistical methods, we confirm three antecedents of KI effectiveness and the consequences of the antecedents on ES success are validated. The findings demonstrate a statistically positive impact of KI effectiveness of ES success, with KI effectiveness contributing to almost one-third of ES success. This research makes a number of contributions to the understanding of the influence of KI on ES success. First, based on the empirical work using a complete nomological net model, the role of KI effectiveness on ES success is evidenced. Second, the model provides a theoretical lens for a more comprehensive understanding of the impact of KI on the level of ES success. Third, restructuring the dimensions of the knowledge-based theory to fit the context of ES extends its applicability and generalisability to contemporary Information Systems. Fourth, the study develops and validates measures for the antecedents of KI effectiveness. Fifth, the study demonstrates the statistically significant positive influence of the goodness of KI on ES success. From a practical viewpoint, this study emphasises the importance of KI effectiveness as a direct antecedent of ES success. Practical lessons can be drawn from the work done in this study to empirically identify the critical factors among the antecedents of KI effectiveness that should be given attention.
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The rapid economic development and social changes in Malaysia recently have led to many psychosocial problems in young people, such as drug addiction, child sexual abuse and mental illness. The Malaysian government is beginning to focus more attention on its social welfare and human service needs in order to alleviate these psychosocial problems. Although counselling is accepted and widespread in Malaysia, the practice of family therapy is not as accepted as it is still a widely held belief that family problems need to be kept within the family. However, changes are imminent and thus the theoretical basis of family therapy needs to be culturally relevant. Bowen‟s Family Systems Theory (BFST) is already one of the major theories taught to tertiary counselling students in Malaysian universities. The main tenet of Bowen‟s theory is that the family as a system may be unstable unless each member of the family is well differentiated. High differentiation levels in the family allow a person to both leave the family‟s boundaries in search of uniqueness and to continually return to the family fold in order to establish a more mature sense of belonging. The difficulty, however, is that while Bowen has claimed that his theory is universal nearly all of the research confirming the theory has been conducted in the United States of America. The only known study outside America, however, did show that Bowen‟s theory applied to a Filipino population but, one of the theory‟s propositions that differentiation is intergenerational was not supported in this non-American sample. The American sample that was compared to the Malay sample was taken from Skowron and Friedlander‟s (1998) study. One hundred and twenty-seven faculty staff in an American university completed the Differentiation of Self Inventory (DSI) to measure level of differentiation of self. This thesis therefore, set out to determine whether Bowen‟s theory applied to another non-American sample, the Malaysian community. The research also investigated if the intergenerational effect was present in the Malaysian sample as well as explored the role of socio-economic status on Bowen‟s theory of differentiation and gender effect. Three hundred and seventy-four families completed four measures to examine these research questions: the Differentiation of Self Inventory (DSI), the Family Inventory of Life Event (FILE), the Depression Anxiety and Stress Scale (DASS) and the Connor-Davidson Resilience Scale (CD-RISC). The results of the study showed that differentiation of self is a valid construct for the Malay population. However, all four subscales of the Differentiation of Self Inventory (DSI); emotional reactivity (ER), emotional cut-off (EC), fusion with other (FO) and I position (IP), showed significant differences compared to the American sample from Skowron and Friedlander‟s (1998) study. The Malay sample scored higher in emotional reaction (ER), fusion with other (FO), but lower on emotional cut-off (EC) and I position (IP) than the American sample. The intergenerational effect was found in the Malay population as the parent‟s level of differentiation correlated with their children‟s level of differentiation. It was found that stress as measured by the Family Inventory of Life Event (FILE) and as measured by the Depression Anxiety and Stress Scale (DASS) were not correlated with the level of differentiation of self in parents. However, gender had a significant effect in predicting the level of differentiation among parents in Malay population with females scores higher on emotional reactivity (ER) and fusion with other (FO) than males. An additional finding was that resilience can be predicted from the level of differentiation of self in children in the Malay sample. There was also a positive correlation between the level of differentiation of self in parents and resilience in their children. Findings from this study indicate that the concept of differentiation of self is applicable to a Malay sample; however, the implementation of the theory should be applied with cultural sensitivity.
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The Request For Proposal (RFP) with the design‐build (DB) procurement arrangement is a document in which an owner develops his requirements and conveys the project scope to DB contractors. Owners should provide an appropriate level of design in DB RFPs to adequately describe their requirements without compromising the prospects for innovation. This paper examines and compares the different levels of owner‐provided design in DB RFPs by the content analysis of 84 requests for RFPs for public DB projects advertised between 2000 and 2010 with an aggregate contract value of over $5.4 billion. A statistical analysis was also conducted in order to explore the relationship between the proportion of owner‐provided design and other project information, including project type, advertisement time, project size, contractor selection method, procurement process and contract type. The results show that the majority (64.8%) of the RFPs provide less than 10% of the owner‐provided design. The owner‐provided design proportion has a significant association with project type, project size, contractor selection method and contract type. In addition, owners are generally providing less design in recent years than hitherto. The research findings also provide owners with perspectives to determine the appropriate level of owner‐provided design in DB RFPs.
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To assess and improve their practices, and thus ensure the future excellence of the Texas highway system, the Texas Department of Transportation (TxDOT) sought a forum in which experts from other State Departments of Transportation could evaluate the TxDOT maintenance program and practices based on their expertise. To meet this need, a Peer State Review of TxDOT Maintenance Practices project was organized and conducted by the Center for Transportation Research (CTR) at The University of Texas at Austin. CTR researchers, along with TxDOT staff, conducted a workshop to present TxDOT’s maintenance practices to the visiting peer reviewers and invite their feedback. Directors of maintenance from six different states—California, Kansas, Georgia, Missouri, North Carolina, and Washington—participated in the workshop. CTR and TxDOT worked together to design a questionnaire with 15 key questions to capture the peers’ opinions on maintenance program and practices. This paper compiles and summarizes this information. The examination results suggested that TxDOT should use a more state-wide approach to funding and planning, in addition to funding and planning for each district separately. Additionally, the peers recommended that criteria such as condition and level of service of the roadways be given greater weight in the funding allocation than lane miles or vehicle miles traveled (VMT). The Peer Reviewers also determined that TxDOT maintenance employee experience and communications were strong assets. Additional strengths included the willingness of TxDOT to invite peer reviews of their practices and a willingness to consider opportunities for improvement.
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Sustainability Declarations were introduced by the Queensland State Government on 1 January 2010 as a mandatory disclosure measure for all dwelling sales in the State. The purpose of this paper is to assess the impact this policy decision has had in the homebuyer decision-making process in the first year since its introduction and to consider the effectiveness of the legislation in meeting its policy objectives. This quantitative research comprised a two-part process: the first stage surveyed the level of compliance by the real estate industry with the legislative requirements. Stage two comprised an online survey of Real Estate Institute of Queensland members to determine what impact the Sustainability Declaration has had on home buyer decision making and how effective the legislative mechanisms have been in achieving the policy objectives. This paper assesses the initial impact of this initiative over its first year in operation. These preliminary findings indicate a high level of compliance from the real estate industry, however results confirm that sustainability is yet to become a criterion of relevance to the majority of homebuyers in Queensland. These quantitative findings support anecdotal evidence that the objectives of the legislation to increase homebuyer awareness and relevance of sustainability issues in the home are not being achieved. Sustainability Declarations are a first step in raising homebuyer awareness of the importance of sustainability in housing. Further monitoring of this impact will be carried out over time. This is the first research undertaken to assess the impact of this new mandatory disclosure legislation in Queensland, Australia. The findings will inform policy makers and assist them to assess the effectiveness of the current legislation in achieving its policy objectives.
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Given the substantial investment in information technology (IT), and the significant impact IT has on organizational success, organizations consume considerable resources to manage acquisition and use of their IT resources. While various arguments proposed suggest which IT governance arrangements may work best, our understanding of the effectiveness of such initiatives is limited. We examine the relationship between the effectiveness of IT steering committee driven IT governance initiatives and firm's IT management and IT infrastructure related capabilities. We further propose that firm's ITrelated capabilities generated through IT governance initiatives should improve its business processes and firm-level performance. We test these relationships empirically by a field survey. Results suggest that firms' effectiveness of IT steering committee driven IT governance initiatives positively relates to the level of their IT-related capabilities. We also found positive relationships between IT-related capabilities and internal process-level performance. Our results also support that improvement in internal process-level performance positively relates to improvement in customer service and firm-level performance.
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The purpose of this paper is to explore the trend of Purpose Built Office (PBO) supply and occupancy in Malaysia. In achieving this, the number of PBO supply by the private sector in the market is compared with the government sector to gain an understanding of the current emerging market for the PBO. There have been limited studies in Malaysia comparing the trend supply and occupancy of PBOs by both sectors. This paper outcome will illustrate the needs for public sector asset management in Malaysia, particularly for PBOs. An analytical framework is developed using time series to measure the level of supply and occupancy of PBO by both sectors, indicating the percentage of government’s PBO compared to the total numbers of PBOs in the market from 2004 to 2010
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The purpose of this paper is to study the profiling of property, plant and equipment (PPE) contributions in Australia and Malaysia construction companies. A company’s worth is usually based on the listed share price on the stock exchange. In arriving at the net profit, the contribution of PPE in the company’s assets is somehow being neglected. This paper will investigate the followings; firstly the level of PPE contribution in the construction firms by comparing the PPE contributions to the company’s asset as a whole which includes fixed (non-current) assets and current assets. This will determine the true strength of the companies, rather than relying on the share prices alone. Secondly, the paper will determine the trend of company’s asset ownership to show the company’s performance of the PPE ownership during the period of study. The data is based on the selected construction companies listed on the Australian Stock Exchange (ASX) and Malaysian Stock Exchange, known as Bursa Malaysia. The profiling will help to determine the strength of the construction firms based on the PPE holding, and the level of PPE ownerships in the two countries construction firms during the period of study.
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Under pressure from both the ever increasing level of market competition and the global financial crisis, clients in consumer electronics (CE) industry are keen to understand how to choose the most appropriate procurement method and hence to improve their competitiveness. Four rounds of Delphi questionnaire survey were conducted with 12 experts in order to identify the most appropriate procurement method in the Hong Kong CE industry. Five key selection criteria in the CE industry are highlighted, including product quality, capability, price competition, flexibility and speed. This study also revealed that product quality was found to be the most important criteria for the “First type used commercially” and “Major functional improvements” projects. As for “Minor functional improvements” projects, price competition was the most crucial factor to be considered during the PP selection. These research findings provide owners with useful insights to select the procurement strategies.
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This article describes the rationale, developmental process, and content of a resilience-building program that has been implemented with new recruits to a police academy. The process of extensive consultation with the police service (consistent with community-based participatory research principles) has helped to provide a sustainable and pragmatic program framework. The Promoting Resilient Officers (PRO) program is a seven-session strength-based program that integrates CBT and interpersonal perspectives within a salutogenic paradigm. PRO also includes two “refresher” sessions delivered online up to 18 months post the initial face-to-face sessions. PRO was delivered with high fidelity as an integral part of police recruit training and made sustainable by using psychologists within the police service to deliver the intervention. Implementation incorporated a Randomized Controlled design by which a rigorous evaluation of program effectiveness is being conducted. Initial data presented indicates a high level of engagement and acceptability of the PRO program.