Health-related quality of life in the Cambridge City over-75s Cohort (CC75C): development of a dementia-specific scale and descriptive analyses.

BACKGROUND: The assessment of Health Related Quality of Life (HRQL) is important in people with dementia as it could influence their care and support plan. Many studies on dementia do not specifically set out to measure dementia-specific HRQL but do include related items. The aim of this study is to explore the distribution of HRQL by functional and socio-demographic variables in a population-based setting. METHODS: Domains of DEMQOL's conceptual framework were mapped in the Cambridge City over 75's Cohort (CC75C) Study. HRQL was estimated in 110 participants aged 80+ years with a confirmed diagnosis of dementia with mild/moderate severity. Acceptability (missing values and normality of the total score), internal consistency (Cronbach's alpha), convergent, discriminant and known group differences validity (Spearman correlations, Wilcoxon Mann-Whitney and Kruskal-Wallis tests) were assessed. The distribution of HRQL by socio-demographic and functional descriptors was explored. RESULTS: The HRQL score ranged from 0 to 16 and showed an internal consistency Alpha of 0.74. Validity of the instrument was found to be acceptable. Men had higher HRQL than women. Marital status had a greater effect on HRQL for men than it did for women. The HRQL of those with good self-reported health was higher than those with fair/poor self-reported health. HRQL was not associated with dementia severity. CONCLUSIONS: To our knowledge this is the first study to examine the distribution of dementia-specific HRQL in a population sample of the very old. We have mapped an existing conceptual framework of dementia specific HRQL onto an existing study and demonstrated the feasibility of this approach. Findings in this study suggest that whereas there is big emphasis in dementia severity, characteristics such as gender should be taken into account when assessing and implementing programmes to improve HRQL.

Strategic Development of Electricity Distribution Networks – Concept and Methods

Strategic development of distribution networks plays a key role in the asset management in electricity distribution companies. Owing to the capital-intensive nature of the field and longspan operations of companies, the significance of a strategy is emphasised. A well-devised strategy combines awareness of challenges posed by the operating environment and the future targets of the distribution company. Economic regulation, ageing infrastructure, scarcity of resources and tightening supply requirements with challenges created by the climate change put a pressure on the strategy work. On the other hand, technology development related to network automation and underground cabling assists in answering these challenges. This dissertation aims at developing process knowledge and establishing a methodological framework by which key issues related to network development can be addressed. Moreover, the work develops tools by which the effects of changes in the operating environment on the distribution business can be analysed in the strategy work. To this end, the work discusses certain characteristics of the distribution business and describes the strategy process at a principle level. Further, the work defines the subtasks in the strategy process and presents the key elements in the strategy work and long-term network planning. The work delineates the factors having either a direct or indirect effect on strategic planning and development needs in the networks; in particular, outage costs constitute an important part of the economic regulation of the distribution business, reliability being thus a key driver in network planning. The dissertation describes the methodology and tools applied to cost and reliability analyses in the strategy work. The work focuses on determination of the techno-economic feasibility of different network development technologies; these feasibility surveys are linked to the economic regulation model of the distribution business, in particular from the viewpoint of reliability of electricity supply and allowed return. The work introduces the asset management system developed for research purposes and to support the strategy work, the calculation elements of the system and initial data used in the network analysis. The key elements of this asset management system are utilised in the dissertation. Finally, the study addresses the stages of strategic decision-making and compilation of investment strategies. Further, the work illustrates implementation of strategic planning in an actual distribution company environment.

Development of an instrument to measure the degree of critical patient's satisfaction with nursing care: research protocol

Aim: To investigate and understand patient's satisfaction with nursing care in the intensive care unit to identify the dimensions of the concept of"satisfaction" from the patient's point of view. To design and validate a questionnaire that measures satisfaction levels in critical patients. Background: There are many instruments capable of measuring satisfaction with nursing care; however, they do not address the reality for critical patients nor are they applicable in our context. Design: A dual approach study comprising: a qualitative phase employing Grounded Theory and a quantitative and descriptive phase to prepare and validate the questionnaire. Methods: Data collection in the qualitative phase will consist of: in-depth interview after theoretical sampling, on-site diary and expert discussion group. The sample size will depend on the expected theoretical saturation n = 27-36. Analysis will be based on Grounded Theory. For the quantitative phase, the sampling will be based on convenience (n = 200). A questionnaire will be designed on the basis of qualitative data. Descriptive and inferential statistics will be used. The validation will be developed on the basis of the validity of the content, the criteria of the construct and reliability of the instrument by the Cronbach's alpha and test-retest approach. Approval date for this protocol was November 2010. Discussion: Self-perceptions, beliefs, experiences, demographic, socio-cultural epistemological and political factors are determinants for satisfaction, and these should be taken into account when compiling a questionnaire on satisfaction with nursing care among critical patients.

Farmacología y toxicología en I+D+i: adquisición de competencias a través de un ejemplo de desarrollo de un fármaco

The implementation of the subject Pharmacology and Toxicology in R+D+i in the Pharmacy Degree, has led to the launch of a new methodological approach and teaching performance with the aim of developing the generic skills of the University of Barcelona (e.g., self-learning, team-working). An additional objective was students' integration of knowledge from different subjects in the degree which form the basis of the preclinical and clinical development of a drug. For this purpose, the teaching strategy used in the development of the subject was based on: 1) re-developing the content that students had been taught previously or were being taught in the same semester as a part of other subjects, and framing them in the environment of the pharmaceutical industry, 2) introducing new and previously unseen contents to do with drug development and toxicology, 3) developing a battery of activities to be undertaken by teams of students relating to the R+D+i of a particular drug. During the development of these activities, students have to acquire generic skills in addition to the subject-specific skills. The results obtained from the student survey give us grounds for satisfaction and allow us to consider that we have reached the goal of improving students' learning in Pharmacology and Toxicology applied to drug development in the pharmaceutical world today.

Role of ErbB2 and ErbB4 in Cancer Growth, Prognosis and as Targets for Immunotherapy

ErbB receptors (EGFR, ErbB2, ErbB3 and ErbB4) are growth factor receptors that regulate signals of cell differentiation, proliferation, migration and survival. Inappropriate activation of these receptors is associated with the development and severity of many cancers and has prognostic and predictive value in cancer therapy. Drugs, such as therapeutic antibodies, targeted against EGFR and ErbB2, are currently used in therapy of breast, colorectal and head and neck cancers. The role of ErbB4 in tumorigenesis has remained relatively poorly understood. Alternative splicing produces four different isoforms of one ErbB4 gene. These isoforms (JM-a, JM-b, CYT-1 and CYT-2) are functionally dissimilar and proposed to have different roles in carcinogenesis. The juxtamembrane form JM-a undergoes regulated intramembrane proteolysis producing a soluble receptor ectodomain and an intracellular domain that translocates into the nucleus and regulates transcription. Nuclear signaling via JM-a isoform stimulates cancer cell proliferation. This study aimed to develop antibodies targeting the proposed oncogenic ErbB4 JM-a isoform that show potential in inhibiting ErbB4 dependent tumorigenesis. Also, the clinical relevance of ErbB4 shedding in cancer was studied. The currently used monoclonal antibody trastuzumab, targeting ErbB2, has shown efficacy in breast cancer therapy. In this study novel tissues with ErbB2 amplification and trastuzumab sensitivity were analyzed. The results of this study indicated that a subpopulation of breast cancer patients demonstrate increased shedding and cleavage of ErbB4. A JM-a isoform-specific antibody that inhibited ErbB4 shedding and consequent activation of ErbB4 had anti-tumor activity both in vitro and in vivo. Thus, ErbB4 shedding associates with tumor growth and specific targeting of the cleavable JM-a isoform could be considered as a strategy for developing novel ErbB-based cancer drugs. In addition, it was demonstrated that ErbB2 amplification is common in intestinal type gastric cancers with poor clinical outcome. Trastuzumab inhibited growth of gastric and breast cancer cells with equal efficacy. Thus, ErbB2 may be a useful target in gastric cancer.

Platform as a Service - new opportunities for software development companies

Today cloud computing is the next stage in development information-oriented society in field of information technologies. Great attention is paid to cloud computing in general, but the lack of scientific consideration to components brings to the problem, that not all aspects are well examined. This thesis is an attempt to consider Platform as a Service (a technology of providing development environment through the Internet) from divergent angles. Technical characteristics, costs, time, estimation of effectiveness, risks, strategies that can be applied, migration process, advantages and disadvantages and the future of the approach are examined to get the overall picture of cloud platforms. During the work literature study was used to examine Platform as a Service, characteristics of existent cloud platforms were explored and a model of a typical software development company was developed to create a scenario of migration to cloud technologies. The research showed that besides all virtues in reducing costs and time, cloud platforms have some significant obstacles in adoption. Privacy, security and insufficient legislation impede the concept to be widespread.

Reducing Manufacturing Costs of the Screen Dryer’s Hot Section by Design

In this thesis, the purpose was to find the cost distribution of the screen dryer and the largest cost factors. The hot section of the screen dryer was revealed as the biggest cost factor, so composing new cost efficient solutions were directed to it. DFMA (Design for Manufacture and Assembly) was chosen to help the design process. DFMA is a product design strategy developed for taking manufacturing and assembly costs into account at the early stages of the design process. In the theory part of the thesis, other methods of economical design and tools needed for estimating manufacturing costs are introduced. In the empirical part, the hot section of the screen dryer was divided into sub-assemblies and their manufacturing costs were estimated. The design propositions were directed to the self-manufactured assemblies and parts. The new manufacturing costs were calculated for the developed propositions. Lastly, the most cost efficient solutions were summarized. The savings on the self-manufactured assemblies were about 40 %, which was about 13 % of the combined total costs of the hot section.

Analysis of electricity distribution network operation business models and capitalization of control room functions with DMS

Electricity distribution network operation (NO) models are challenged as they are expected to continue to undergo changes during the coming decades in the fairly developed and regulated Nordic electricity market. Network asset managers are to adapt to competitive technoeconomical business models regarding the operation of increasingly intelligent distribution networks. Factors driving the changes for new business models within network operation include: increased investments in distributed automation (DA), regulative frameworks for annual profit limits and quality through outage cost, increasing end-customer demands, climatic changes and increasing use of data system tools, such as Distribution Management System (DMS). The doctoral thesis addresses the questions a) whether there exist conditions and qualifications for competitive markets within electricity distribution network operation and b) if so, identification of limitations and required business mechanisms. This doctoral thesis aims to provide an analytical business framework, primarily for electric utilities, for evaluation and development purposes of dedicated network operation models to meet future market dynamics within network operation. In the thesis, the generic build-up of a business model has been addressed through the use of the strategicbusiness hierarchy levels of mission, vision and strategy for definition of the strategic direction of the business followed by the planning, management and process execution levels of enterprisestrategy execution. Research questions within electricity distribution network operation are addressed at the specified hierarchy levels. The results of the research represent interdisciplinary findings in the areas of electrical engineering and production economics. The main scientific contributions include further development of the extended transaction cost economics (TCE) for government decisions within electricity networks and validation of the usability of the methodology for the electricity distribution industry. Moreover, DMS benefit evaluations in the thesis based on the outage cost calculations propose theoretical maximum benefits of DMS applications equalling roughly 25% of the annual outage costs and 10% of the respective operative costs in the case electric utility. Hence, the annual measurable theoretical benefits from the use of DMS applications are considerable. The theoretical results in the thesis are generally validated by surveys and questionnaires.

A Development and Application of a Three-Dimensional Model for a CFB Gasifier

The developing energy markets and rising energy system costs have sparked the need to find new forms of energy production and increase the self-sufficiency of energy production. One alternative is gasification, whose principles have been known for decades, but it is only recently when the technology has become a true alternative. However, in order to meet the requirements of modern energy production methods, it is necessary to study the phenomenon thoroughly. In order to understand the gasification process better and optimize it from the viewpoint of ecology and energy efficiency, it is necessary to develop effective and reliable modeling tools for gasifiers. The main aims of this work have been to understand gasification as a process and furthermore to develop an existing three-dimensional circulating fluidized bed modeling tool for modeling of gasification. The model is applied to two gasification processes of 12 and 50 MWth. The results of modeling and measurements have been compared and subsequently reviewed. The work was done in co-operation with Lappeenranta University of Technology and Foster Wheeler Energia Oy.

Factors Regulating Chondrogenic Differentiation

Chondrogenesis is a co-ordinated differentiation process in which mesenchymal cells condensate, differentiate into chondrocytes and begin to secrete molecules that form the extracellular matrix. It is regulated in a spatio-temporal manner by cellular interactions and growth and differentiation factors that modulate cellular signalling pathways and transcription of specific genes. Moreover, post-transcriptional regulation by microRNAs (miRNAs) has appeared to play a central role in diverse biological processes, but their role in skeletal development is not fully understood. Mesenchymal stromal cells (MSCs) are multipotent cells present in a variety of adult tissues, including bone marrow and adipose tissue. They can be isolated, expanded and, under defined conditions, induced to differentiate into multiple cell lineages including chondrocytes, osteoblasts and adipocytes in vitro and in vivo. Owing to their intrinsic capability to self-renew and differentiate into functional cell types, MSCs provide a promising source for cell-based therapeutic strategies for various degenerative diseases, such as osteoarthritis (OA). Due to the potential therapeutic applications, it is of importance to better understand the MSC biology and the regulatory mechanisms of their differentiation. In this study, an in vitro assay for chondrogenic differentiation of mouse MSCs (mMSCs) was developed for the screening of various factors for their chondrogenic potential. Conditions were optimized for pellet cultures by inducing mMSC with different bone morphogenetic proteins (BMPs) that were selected based on their known chondrogenic relevance. Characterization of the surface epitope profile, differentiation capacity and molecular signature of mMSCs illustrated the importance of cell population composition and the interaction between different populations in the cell fate determination and differentiation of MSCs. Regulation of Wnt signalling activity by Wnt antagonist sFRP-1 was elucidated as a potential modulator of lineage commitment. Delta-like 1 (dlk1), a factor regulating adipogenesis and osteogenesis, was shown to exhibit stage-specific expression during embryonic chondrogenesis and identified as a novel regulator of chondrogenesis, possibly through mediating the effect of TGF-beta1. Moreover, miRNA profiling demonstrated that MSCs differentiating into a certain lineage exhibit a specific miRNA expression profile. The complex regulatory network between miRNAs and transcription factors is suggested to play a crucial role in fine-tuning the differentiation of MSCs. These results demonstrate that commitment of mesenchymal stromal cells and further differentiation into specific lineages is regulated by interactions between MSCs, various growth and transcription factors, and miRNA-mediated translational repression of lineage-specific genes.

Integrating eco-innovation principles into regional strategy and policy: case of Päijät-Häme region, Finland

This study focuses on the integration of eco-innovation principles into strategy and policy at the regional level. The importance of regions as a level for integrating eco-innovative programs and activities served as the point of interest for this study. Eco-innovative activities and technologies are seen as means to meet sustainable development objective of improving regions’ quality of life. This study is conducted to get an in-depth understanding and learning about eco-innovation at regional level, and to know the basic concepts that are important in integrating eco-innovation principles into regional policy. Other specific objectives of this study are to know how eco-innovation are developed and practiced in the regions of the EU, and to analyze the main characteristic features of an eco-innovation model that is specifically developed at Päijät-Häme Region in Finland. Paijät-Häme Region is noted for its successful eco-innovation strategies and programs, hence, taken as casework in this study. Both primary (interviews) and secondary data (publicly available documents) are utilized in this study. The study shows that eco-innovation plays an important role in regional strategy as reviewed based on the experience of other regions in the EU. This is because of its localized nature which makes it easier to facilitate in a regional setting. Since regional authorities and policy-makers are normally focused on solving its localized environmental problems, eco-innovation principles can easily be integrated into regional strategy. The case study highlights Päijät-Häme Region’s eco-innovation strategies and projects which are characterized by strong connection of knowledge-producing institutions. Policy instruments supporting eco-innovation (e.g. environmental technologies) are very much focused on clean technologies, hence, justifying the formation of cleantech clusters and business parks in Päijät-Häme Region. A newly conceptualized SAMPO model of eco-innovation has been developed in Päijät-Häme Region to better capture the region’s characteristics and to eventually replace the current model employed by the Päijät-Häme Regional Authority. The SAMPO model is still under construction, however, review of its principles points to some of its three important spearheads – practice-based innovation, design (eco-design) and clean technology or environmental technology (environment).

Complexity Optimization in Product Development with Modularization

A company’s competence to manage its product portfolio complexity is becoming critically important in the rapidly changing business environment. The continuous evolvement of customer needs, the competitive market environment and internal product development lead to increasing complexity in product portfolios. The companies that manage the complexity in product development are more profitable in the long run. The complexity derives from product development and management processes where the new product variant development is not managed efficiently. Complexity is managed with modularization which is a method that divides the product structure into modules. In modularization, it is essential to take into account the trade-off between the perceived customer value and the module or component commonality across the products. Another goal is to enable the product configuration to be more flexible. The benefits are achieved through optimizing complexity in module offering and deriving the new product variants more flexibly and accurately. The developed modularization process includes the process steps for preparation, mapping the current situation, the creation of a modular strategy and implementing the strategy. Also the organization and support systems have to be adapted to follow-up targets and to execute modularization in practice.

Methods for construction and analysis of computational models in systems biology : applications to the modelling of the heat shock response and the self-assembly of intermediate filaments

Systems biology is a new, emerging and rapidly developing, multidisciplinary research field that aims to study biochemical and biological systems from a holistic perspective, with the goal of providing a comprehensive, system- level understanding of cellular behaviour. In this way, it addresses one of the greatest challenges faced by contemporary biology, which is to compre- hend the function of complex biological systems. Systems biology combines various methods that originate from scientific disciplines such as molecu- lar biology, chemistry, engineering sciences, mathematics, computer science and systems theory. Systems biology, unlike “traditional” biology, focuses on high-level concepts such as: network, component, robustness, efficiency, control, regulation, hierarchical design, synchronization, concurrency, and many others. The very terminology of systems biology is “foreign” to “tra- ditional” biology, marks its drastic shift in the research paradigm and it indicates close linkage of systems biology to computer science. One of the basic tools utilized in systems biology is the mathematical modelling of life processes tightly linked to experimental practice. The stud- ies contained in this thesis revolve around a number of challenges commonly encountered in the computational modelling in systems biology. The re- search comprises of the development and application of a broad range of methods originating in the fields of computer science and mathematics for construction and analysis of computational models in systems biology. In particular, the performed research is setup in the context of two biolog- ical phenomena chosen as modelling case studies: 1) the eukaryotic heat shock response and 2) the in vitro self-assembly of intermediate filaments, one of the main constituents of the cytoskeleton. The range of presented approaches spans from heuristic, through numerical and statistical to ana- lytical methods applied in the effort to formally describe and analyse the two biological processes. We notice however, that although applied to cer- tain case studies, the presented methods are not limited to them and can be utilized in the analysis of other biological mechanisms as well as com- plex systems in general. The full range of developed and applied modelling techniques as well as model analysis methodologies constitutes a rich mod- elling framework. Moreover, the presentation of the developed methods, their application to the two case studies and the discussions concerning their potentials and limitations point to the difficulties and challenges one encounters in computational modelling of biological systems. The problems of model identifiability, model comparison, model refinement, model inte- gration and extension, choice of the proper modelling framework and level of abstraction, or the choice of the proper scope of the model run through this thesis.

Software Test Process Development

In this thesis, the components important for testing work and organisational test process are identified and analysed. This work focuses on the testing activities in reallife software organisations, identifying the important test process components, observing testing work in practice, and analysing how the organisational test process could be developed. Software professionals from 14 different software organisations were interviewed to collect data on organisational test process and testing‐related factors. Moreover, additional data on organisational aspects was collected with a survey conducted on 31 organisations. This data was further analysed with the Grounded Theory method to identify the important test process components, and to observe how real‐life test organisations develop their testing activities. The results indicate that the test management at the project level is an important factor; the organisations do have sufficient test resources available, but they are not necessarily applied efficiently. In addition, organisations in general are reactive; they develop their process mainly to correct problems, not to enhance their efficiency or output quality. The results of this study allows organisations to have a better understanding of the test processes, and develop towards better practices and a culture of preventing problems, not reacting to them.

On the impact of rigorous approaches on the quality of development

Software systems are expanding and becoming increasingly present in everyday activities. The constantly evolving society demands that they deliver more functionality, are easy to use and work as expected. All these challenges increase the size and complexity of a system. People may not be aware of a presence of a software system, until it malfunctions or even fails to perform. The concept of being able to depend on the software is particularly significant when it comes to the critical systems. At this point quality of a system is regarded as an essential issue, since any deficiencies may lead to considerable money loss or life endangerment. Traditional development methods may not ensure a sufficiently high level of quality. Formal methods, on the other hand, allow us to achieve a high level of rigour and can be applied to develop a complete system or only a critical part of it. Such techniques, applied during system development starting at early design stages, increase the likelihood of obtaining a system that works as required. However, formal methods are sometimes considered difficult to utilise in traditional developments. Therefore, it is important to make them more accessible and reduce the gap between the formal and traditional development methods. This thesis explores the usability of rigorous approaches by giving an insight into formal designs with the use of graphical notation. The understandability of formal modelling is increased due to a compact representation of the development and related design decisions. The central objective of the thesis is to investigate the impact that rigorous approaches have on quality of developments. This means that it is necessary to establish certain techniques for evaluation of rigorous developments. Since we are studying various development settings and methods, specific measurement plans and a set of metrics need to be created for each setting. Our goal is to provide methods for collecting data and record evidence of the applicability of rigorous approaches. This would support the organisations in making decisions about integration of formal methods into their development processes. It is important to control the software development, especially in its initial stages. Therefore, we focus on the specification and modelling phases, as well as related artefacts, e.g. models. These have significant influence on the quality of a final system. Since application of formal methods may increase the complexity of a system, it may impact its maintainability, and thus quality. Our goal is to leverage quality of a system via metrics and measurements, as well as generic refinement patterns, which are applied to a model and a specification. We argue that they can facilitate the process of creating software systems, by e.g. controlling complexity and providing the modelling guidelines. Moreover, we find them as additional mechanisms for quality control and improvement, also for rigorous approaches. The main contribution of this thesis is to provide the metrics and measurements that help in assessing the impact of rigorous approaches on developments. We establish the techniques for the evaluation of certain aspects of quality, which are based on structural, syntactical and process related characteristics of an early-stage development artefacts, i.e. specifications and models. The presented approaches are applied to various case studies. The results of the investigation are juxtaposed with the perception of domain experts. It is our aspiration to promote measurements as an indispensable part of quality control process and a strategy towards the quality improvement.