PCIM:a project control and inhibiting‐factors management model

In construction projects, the aim of project control is to ensure projects finish on time, within budget, and achieve other project objectives. During the last few decades, numerous project control methods have been developed and adopted by project managers in practice. However, many existing methods focus on describing what the processes and tasks of project control are; not on how these tasks should be conducted. There is also a potential gap between principles that underly these methods and project control practice. As a result, time and cost overruns are still common in construction projects, partly attributable to deficiencies of existing project control methods and difficulties in implementing them. This paper describes a new project cost and time control model, the project control and inhibiting factors management (PCIM) model, developed through a study involving extensive interaction with construction practitioners in the UK, which better reflects the real needs of project managers. A set of good practice checklist is also developed to facilitate implementation of the model. © 2013 American Society of Civil Engineers.

Development of a multicellular co-culture model of normal and cystic fibrosis human airways in vitro

Cystic fibrosis (CF) is the most common lethal inherited disease among Caucasians and arises due to mutations in a chloride channel, called cystic fibrosis transmembrane conductance regulator. A hallmark of this disease is the chronic bacterial infection of the airways, which is usually, associated with pathogens such as Pseudomonas aeruginosa, S. aureus and recently becoming more prominent, B. cepacia. The excessive inflammatory response, which leads to irreversible lung damage, will in the long term lead to mortality of the patient at around the age of 40 years. Understanding the pathogenesis of CF currently relies on animal models, such as those employing genetically-modified mice, and on single cell culture models, which are grown either as polarised or non-polarised epithelium in vitro. Whilst these approaches partially enable the study of disease progression in CF, both types of models have inherent limitations. The overall aim of this thesis was to establish a multicellular co-culture model of normal and CF human airways in vitro, which helps to partially overcome these limitations and permits analysis of cell-to-cell communication in the airways. These models could then be used to examine the co-ordinated response of the airways to infection with relevant pathogens in order to validate this approach over animals/single cell models. Therefore epithelial cell lines of non-CF and CF background were employed in a co-culture model together with human pulmonary fibroblasts. Co-cultures were grown on collagen-coated permeable supports at air-liquid interface to promote epithelial cell differentiation. The models were characterised and essential features for investigating CF infections and inflammatory responses were investigated and analysed. A pseudostratified like epithelial cell layer was established at air liquid interface (ALI) of mono-and co-cultures and cell layer integrity was verified by tight junction (TJ) staining and transepithelial resistance measurements (TER). Mono- and co-cultures were also found to secrete the airway mucin MUC5AC. Influence of bacterial infections was found to be most challenging when intact S. aureus, B. cepacia and P. aeruginosa were used. CF mono- and co-cultures were found to mimic the hyperinflammatory state found in CF, which was confirmed by analysing IL-8 secretions of these models. These co-culture models will help to elucidate the role fibroblasts play in the inflammatory response to bacteria and will provide a useful testing platform to further investigate the dysregulated airway responses seen in CF.

Development of a co-culture model of the human lungs for toxicity testing and identification of biomarkers of inhalation toxicity

The airway epithelium is the first point of contact in the lung for inhaled material, including infectious pathogens and particulate matter, and protects against toxicity from these substances by trapping and clearance via the mucociliary escalator, presence of a protective barrier with tight junctions and initiation of a local inflammatory response. The inflammatory response involves recruitment of phagocytic cells to neutralise and remove and invading materials and is oftern modelled using rodents. However, development of valid in vitro airway epithelial models is of great importance due to the restrictions on animal studies for cosmetic compound testing implicit in the 7th amendment to the European Union Cosmetics Directive. Further, rodent innate immune responses have fundamental differences to human. Pulmonary endothelial cells and leukocytes are also involved in the innate response initiated during pulmonary inflammation. Co-culture models of the airways, in particular where epithelial cells are cultured at air liquid interface with the presence of tight junctions and differentiated mucociliary cells, offer a solution to this problem. Ideally validated models will allow for detection of early biomarkers of response to exposure and investigation into inflammatory response during exposure. This thesis describes the approaches taken towards developing an in vitro epithelial/endothelial cell model of the human airways and identification biomarkers of response to exposure to xenobiotics. The model comprised normal human primary microvascular endothelial cells and the bronchial epithelial cell line BEAS-2B or normal human bronchial epithelial cells. BEAS-2B were chosen as their characterisation at air liquid interface is limited but they are robust in culture, thereby predicted to provide a more reliable test system. Proteomics analysis was undertaken on challenged cells to investigate biomarkers of exposure. BEAS-2B morphology was characterised at air liquid interface compared with normal human bronchial epithelial cells. The results indicate that BEAS-2B cells at an air liquid interface form tight junctions as shown by expression of the tight junction protein zonula occludens-1. To this author’s knowledge this is the first time this result has been reported. The inflammatory response of BEAS-2B (measured as secretion of the inflammatory mediators interleukin-8 and -6) air liquid interface mono-cultures to Escherichia coli lipopolysaccharide or particulate matter (fine and ultrafine titanium dioxide) was comparable to published data for epithelial cells. Cells were also exposed to polymers of “commercial interest” which were in the nanoparticle range (and referred to particles hereafter). BEAS-2B mono-cultures showed an increased secretion of inflammatory mediators after challenge. Inclusion of microvascular endothelial cells resulted in protection against LPS- and particle- induced epithelial toxicity, measured as cell viability and inflammatory response, indicating the importance of co-cultures for investigations into toxicity. Two-dimensional proteomic analysis of lysates from particle-challenged cells failed to identify biomarkers of toxicity due to assay interference and experimental variability. Separately, decreased plasma concentrations of serine protease inhibitors, and the negative acute phase proteins transthyretin, histidine-rich glycoprotein and alpha2-HS glycoprotein were identified as potential biomarkers of methyl methacrylate/ethyl methacrylate/butylacrylate treatment in rats.

Integrated approach to healthcare quality management:a case study

Purpose - The purpose of the paper is to develop an integrated quality management model, which identifies problems, suggests solutions, develops a framework for implementation and helps evaluate performance of health care services dynamically. Design/methodology/approach - This paper uses logical framework analysis (LFA), a matrix approach to project planning for managing quality. This has been applied to three acute healthcare services (Operating room utilization, Accident and emergency, and Intensive care) in order to demonstrate its effectiveness. Findings - The paper finds that LFA is an effective method of quality management of hospital-based healthcare services. Research limitations/implications - This paper shows LFA application in three service processes in one hospital. However, ideally this is required to be tested in several hospitals and other services as well. Practical implications - In the paper the proposed model can be practised in hospital-based healthcare services for improving performance. Originality/value - The paper shows that quality improvement in healthcare services is a complex and multi-dimensional task. Although various quality management tools are routinely deployed for identifying quality issues in health care delivery and corrective measures are taken for superior performance, there is an absence of an integrated approach, which can identify and analyze issues, provide solutions to resolve those issues, develop a project management framework (planning, monitoring, and evaluating) to implement those solutions in order to improve process performance. This study introduces an integrated and uniform quality management tool. It integrates operations with organizational strategies. © Emerald Group Publishing Limited.

Delivering optometric care in the UK

Optometrists play an important part in delivering eye care in the United Kingdom; however opportunities for practitioners to extend their role through co-management of patients with ophthalmologists vary across the country. Devolution in Scotland and Wales has led to greater emphasis on community based care in these regions. This thesis reviews the current situation and, by examining ophthalmic outpatient clinic data, discusses further opportunities to reduce demands on secondary care and the cost savings that can be made. To assess whether the profession is currently in a position to adopt an extended clinical role, changes in the availability of optometric instrumentation are assessed over a two year period. An increased prevalence of fundus cameras and contact tonometers places optometrists in a good position to take on further responsibilities in glaucoma management, however future investment could be impacted by the current economic climate as value for money became increasingly important to practitioners looking to purchase equipment. Methods of training optometrists in the necessary skills to utilise new technology to extend their role are evaluated in terms of both learning and cost effectiveness. Interactive distance learning is proposed as a convenient and effective method to deliver continuing professional development. Any changes to optometric practice must take account of the need for a sustainable business and the importance of attracting and retaining patients. The views of patients are assessed through a validated service quality questionnaire, SERVQUAL. The questionnaire is found to be valid for use in an optometry setting. Patients have a generally positive view of the service quality they receive from their optical practice and consider the intangible aspects, in particular responsiveness and empathy, most important. Optometrists are well placed to increase their role in patient management; however a viable business model must exist to enable investment in instrumentation and training.

Project risk management using multiple criteria decision-making technique and decision tree analysis:a case study of Indian oil refinery

This study proposes an integrated analytical framework for effective management of project risks using combined multiple criteria decision-making technique and decision tree analysis. First, a conceptual risk management model was developed through thorough literature review. The model was then applied through action research on a petroleum oil refinery construction project in the Central part of India in order to demonstrate its effectiveness. Oil refinery construction projects are risky because of technical complexity, resource unavailability, involvement of many stakeholders and strict environmental requirements. Although project risk management has been researched extensively, practical and easily adoptable framework is missing. In the proposed framework, risks are identified using cause and effect diagram, analysed using the analytic hierarchy process and responses are developed using the risk map. Additionally, decision tree analysis allows modelling various options for risk response development and optimises selection of risk mitigating strategy. The proposed risk management framework could be easily adopted and applied in any project and integrated with other project management knowledge areas.

Integrated project management in Indian petroleum industry

The Indian Petroleum Industry is passing through a very dynamic business environment due to liberalization. Effective project management for developing new infrastructures and maintaining the existing facilities has been considered as one of the means for remaining competitive but these practices suffer from many shortcomings, as time, cost and quality non-achievements are part and parcel of almost every project. This study focuses on identifying the specific causes of project failure by demonstrating first the characteristics of projects in Indian Petroleum industry and suggests some remedial measures for resolving these issues. The suggested project management model is integrated through information management system and demonstrated through a case study.

A value-oriented model for managing service supply chains

Service supply chain (SSC) has attracted more and more attention from academia and industry. Although there exists extensive product-based supply chain management models and methods, they are not applicable to the SSC as the differences between service and product. Besides, the existing supply chain management models and methods possess some common deficiencies. Because of the above reasons, this paper develops a novel value-oriented model for the management of SSC using the modeling methods of E3-value and Use Case Maps (UCMs). This model can not only resolve the problems of applicability and effectiveness of the existing supply chain management models and methods, but also answer the questions of ‘why the management model is this?’ and ‘how to quantify the potential profitability of the supply chains?’. Meanwhile, the service business processes of SSC system can be established using its logic procedure. In addition, the model can also determine the value and benefits distribution of the entire service value chain and optimize the operations management performance of the service supply.

Managing healthcare quality using logical framework analysis

Purpose - The purpose of this paper is to develop an integrated quality management model that identifies problems, suggests solutions, develops a framework for implementation and helps to evaluate dynamically healthcare service performance. Design/methodology/approach - This study used the logical framework analysis (LFA) to improve the performance of healthcare service processes. LFA has three major steps - problems identification, solution derivation, and formation of a planning matrix for implementation. LFA has been applied in a case-study environment to three acute healthcare services (Operating Room utilisation, Accident and Emergency, and Intensive Care) in order to demonstrate its effectiveness. Findings - The paper finds that LFA is an effective method of quality management of hospital-based healthcare services. Research limitations/implications - This study shows LFA application in three service processes in one hospital. This very limited population sample needs to be extended. Practical implications - The proposed model can be implemented in hospital-based healthcare services in order to improve performance. It may also be applied to other services. Originality/value - Quality improvement in healthcare services is a complex and multi-dimensional task. Although various quality management tools are routinely deployed for identifying quality issues in healthcare delivery, they are not without flaws. There is an absence of an integrated approach, which can identify and analyse issues, provide solutions to resolve those issues, develop a project management framework to implement those solutions. This study introduces an integrated and uniform quality management tool for healthcare services. © Emerald Group Publishing Limited.

Single-cell ELISA and flow cytometry as methods for highlighting potential neuronal and astrocytic toxicant specificity

The timeline imposed by recent worldwide chemical legislation is not amenable to conventional in vivo toxicity testing, requiring the development of rapid, economical in vitro screening strategies which have acceptable predictive capacities. When acquiring regulatory neurotoxicity data, distinction on whether a toxic agent affects neurons and/or astrocytes is essential. This study evaluated neurofilament (NF) and glial fibrillary acidic protein (GFAP) directed single-cell (S-C) ELISA and flow cytometry as methods for distinguishing cell-specific cytoskeletal responses, using the established human NT2 neuronal/astrocytic (NT2.N/A) co-culture model and a range of neurotoxic (acrylamide, atropine, caffeine, chloroquine, nicotine) and non-neurotoxic (chloramphenicol, rifampicin, verapamil) test chemicals. NF and GFAP directed flow cytometry was able to identify several of the test chemicals as being specifically neurotoxic (chloroquine, nicotine) or astrocytoxic (atropine, chloramphenicol) via quantification of cell death in the NT2.N/A model at cytotoxic concentrations using the resazurin cytotoxicity assay. Those neurotoxicants with low associated cytotoxicity are the most significant in terms of potential hazard to the human nervous system. The NF and GFAP directed S-C ELISA data predominantly demonstrated the known neurotoxicants only to affect the neuronal and/or astrocytic cytoskeleton in the NT2.N/A cell model at concentrations below those affecting cell viability. This report concluded that NF and GFAP directed S-C ELISA and flow cytometric methods may prove to be valuable additions to an in vitro screening strategy for differentiating cytotoxicity from specific neuronal and/or astrocytic toxicity. Further work using the NT2.N/A model and a broader array of toxicants is appropriate in order to confirm the applicability of these methods.

Energy conservation in the steel industry

The last few years have witnessed an unprecedented increase in the price of energy available to industry in the United Kingdom and worldwide. The steel industry, as a major consumer of energy delivered in U.K. (8% of national total and nearly 25% of industrial total) and whose energy costs currently form some 28% of the total manufacturing cost, is very much aware of the need to conserve energy. Because of the complexities of steelmaking processes it is imperative that a full understanding of each process and its interlinking role in an integrated steelworks is understood. An analysis of energy distribution shows that as much as 70% of heat input is dissipated to the environment in a variety of forms. Of these, waste gases offer the best potential for energy conservation. The study identifies areas for and discusses novel methods of energy conservation in each process. Application of these schemes in BSC works is developed and their economic incentives highlighted. A major part of this thesis describes design, development and testing of a novel ceramic rotary regenerator for heat recovery from high temperature waste gases, where no such system is available. The regenerator is a compact, efficient heat exchanger. Application of such a system to a reheating furnace provides a fuel saving of up to 40%. A mathematical model developed is verified on the pilot plant. The results obtained confirm the success of the concept and material selection and outlines the work needed to develop an industrial unit. Last, but not least, the key position of an energy manager in an energy conservation programme is identified and a new Energy Management Model for the BSC is developed.

A novel extracellular role for tissue transglutaminase in matrix-bound VEGF-mediated angiogenesis

The importance of tissue transglutaminase (TG2) in angiogenesis is unclear and contradictory. Here we show that inhibition of extracellular TG2 protein crosslinking or downregulation of TG2 expression leads to inhibition of angiogenesis in cell culture, the aorta ring assay and in vivo models. In a human umbilical vein endothelial cell (HUVEC) co-culture model, inhibition of extracellular TG2 activity can halt the progression of angiogenesis, even when introduced after tubule formation has commenced and after addition of excess vascular endothelial growth factor (VEGF). In both cases, this leads to a significant reduction in tubule branching. Knockdown of TG2 by short hairpin (shRNA) results in inhibition of HUVEC migration and tubule formation, which can be restored by add back of wt TG2, but not by the transamidation-defective but GTP-binding mutant W241A. TG2 inhibition results in inhibition of fibronectin deposition in HUVEC monocultures with a parallel reduction in matrix-bound VEGFA, leading to a reduction in phosphorylated VEGF receptor 2 (VEGFR2) at Tyr1214 and its downstream effectors Akt and ERK1/2, and importantly its association with b1 integrin. We propose a mechanism for the involvement of matrix-bound VEGFA in angiogenesis that is dependent on extracellular TG2-related activity. © 2013 Macmillan Publishers Limited. All rights reserved.

Functional astrocyte-neuron lactate shuttle in a human stem cell derived neuronal network

The development of stem cell-derived neuronal networks will promote experimental system development for drug screening, toxicological testing and disease modelling, providing that they mirror closely the functional competencies of their in vivo counterparts. The NT2 cell line is one of the best documented embryocarcinoma cell lines, and can be differentiated into neurons and astrocytes. Great focus has also been placed on defining the electrophysiological properties of these cells, and more recently we have investigated the functional properties of their associated astrocytes. We now show for the first time in a human stem cell derived co-culture model that these cultures are also metabolically competent and demonstrate a functional astrocyte neuron lactate shuttle (ANLS). The ANLS hypothesis proposes that during neuronal activity, glutamate released into the synaptic cleft is taken up by astrocytes and triggers glucose uptake which is converted into lactate and released via monocarboxylate transporters for neuronal use. Using mixed cultures of NT2 derived neurons and astrocytes we have shown that these cells modulate their glucose uptake in response to glutamate, an effect that was blocked by cytochalasin B and ouabain. Additionally we demonstrate that in response to increased neuronal activity and under hypoglycaemic conditions, co-cultures modulate glycogen turnover and increase lactate production. Similar results were also shown following treatment with glutamate, potassium, Isoproterenol and dbcAMP. Together these results demonstrate for the first time a functional ANLS in a human stem cell derived co-culture.