The effect of the birth hospital and the time of birth on the outcome of Finnish very preterm infants

The purpose of this study was to evaluate the effect of the birth hospital and the time of birth on mortality and the long-term outcome of Finnish very low birth weight (VLBW) or very low gestational age (VLGA) infants. This study included all Finnish VLBW/VLGA infants born at <32 gestational weeks or with a birth weight of ≤1500g, and controls born full-term and healthy. In the first part of the study, the mortality of VLBW/VLGA infants born in 2000–2003 was studied. The second part of the study consisted of a five-year follow-up of VLBW/VLGA infants born in 2001–2002. The study was performed using data from parental questionnaires and several registers. The one-year mortality rate was 11% for live-born VLBW/VLGA infants, 22% for live-born and stillborn VLBW/VLGA infants, and 0% for the controls. In live-born and in all (including stillbirths) VLBW/VLGA infants, the adjusted mortality was lower among those born in level III hospitals compared with level II hospitals. Mortality rates of live-born VLBW/VLGA infants differed according to the university hospital district where the birth hospital was located, but there were no differences in mortality between the districts when stillborn infants were included. There was a trend towards lower mortality rates in VLBW/VLGA infants born during office hours compared with those born outside office hours (night time, weekends, and public holidays). When stillborn infants were included, this difference according to the time of birth was significant. Among five-year-old VLBW/VLGA children, morbidity, use of health care resources, and problems in behaviour and development were more common in comparison with the controls. The health-related quality of life of the surviving VLBW/VLGA children was good but, statistically, it was significantly lower than among the controls. The median and the mean number of quality-adjusted life-years were 4.6 and 3.6 out of a maximum five years for all VLBW/VLGA children. For the controls, the median was 4.8 and the mean was 4.9. Morbidity rates, the use of health care resources, and the mean quality-adjusted life-years differed for VLBW/VLGA children according to the university hospital district of birth. However, the time of birth, the birth hospital level or university hospital district were not associated with the health-related quality of life, nor with behavioural and developmental scores of the survivors at the age of five years. In conclusion, the decreased mortality in level III hospitals was not gained at the expense of long-term problems. The results indicate that VLBW/VLGA deliveries should be centralized to level III hospitals and the regional differences in the treatment practices should further be clarified. A long-term follow-up on the outcome of VLBW/VLGA infants is important in order to recognize the critical periods of care and to optimise the care. In the future, quality-adjusted life-years can be used as a uniform measure for comparing the effectiveness of care between VLBW/VLGA infants and different patient groups

National oral history - Time of change project

Reviews

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.

The Roman Empire as it was in the time of Julius Caesar and it is described in his Commentaries, and in Silius Italicus

Julkaisussa: Geographia classica : the geography of the ancients

“Who is steering the ship and which constellation guides the way? Exploring transparency in the European Central Bank during the time of crisis”

This paper explores transparency in the decision-making of the European Central Bank (ECB). According to ECB´s definition, transparency means that the central bank provides the general public with all relevant information on its strategy, assessments and policy decisions as well as its procedures in an open, clear and timely manner. In this paper, however, the interpretation of transparency is somewhat broader: Information is freely available and directly accessible to those who will be affected by the decisions. Moreover, the individuals shall be able to master this material. ECB´s negative attitude towards publication of documents has demonstrated central bank´s reluctance to strive towards more extensive transparency. By virtue of the definition adopted by the ECB the bank itself is responsible for determining what is considered as relevant information. On the grounds of EU treaties, this paper assesses ECB`s accountability concentrating especially on transparency by employing principal-agent theory and constitutional approach. Traditionally, the definite mandate and the tenet of central bank independence have been used to justify the limited accountability. The de facto competence of the ECB has, however, considerably expanded as the central bank has decisively resorted to non-standard measures in order to combat the economic turbulences facing Europe. It is alleged that non-standard monetary policy constitutes a grey zone occasionally resembling economic policy or fiscal policy. Notwithstanding, the European Court of Justice has repeatedly approved these measures. This dynamic interpretation of the treaties seems to allow temporarily exceptions from the central bank´s primary objective during extraordinary times. Regardless, the paper suggests that the accountability nexus defined in the treaties is not sufficient in order to guarantee the accountability of the ECB after the adoption of the new, more active role. Enhanced transparency would help the ECB to maintain its credibility. Investing in the quality of monetary dialogue between the Parliament and the ECB appears to constitute the most adequate and practicable method to accomplish this intention. As a result of upgraded transparency the legitimacy of the central bank would not solely rest on its policy outputs.

Development of Craniofacial Bone Defect Reconstruction Implant Based on Fibre-Reinforced Composite with Photopolymerisable Resin Systems. Experimental studies in vitro and in vivo.

Reconstruction of defects in the craniomaxillofacial (CMF) area has mainly been based on bone grafts or metallic fixing plates and screws. Particularly in the case of large calvarial and/or craniofacial defects caused by trauma, tumours or congenital malformations, there is a need for reliable reconstruction biomaterials, because bone grafts or metallic fixing systems do not completely fulfill the criteria for the best possible reconstruction methods in these complicated cases. In this series of studies, the usability of fibre-reinforced composite (FRC) was studied as a biostable, nonmetallic alternative material for reconstructing artificially created bone defects in frontal and calvarial areas of rabbits. The experimental part of this work describes the different stages of the product development process from the first in vitro tests with resin-impregnated fibrereinforced composites to the in vivo animal studies, in which this FRC was tested as an implant material for reconstructing different size bone defects in rabbit frontal and calvarial areas. In the first in vitro study, the FRC was polymerised in contact with bone or blood in the laboratory. The polymerised FRC samples were then incubated in water, which was analysed for residual monomer content by using high performance liquid chromatography (HPLC). It was found that this in vitro polymerisation in contact with bone and blood did not markedly increase the residual monomer leaching from the FRC. In the second in vitro study, different adhesive systems were tested in fixing the implant to bone surface. This was done to find an alternative implant fixing system to screws and pins. On the basis of this study, it was found that the surface of the calvarial bone needed both mechanical and chemical treatments before the resinimpregnated FRC could be properly fixed onto it. In three animal studies performed with rabbit frontal bone defects and critical size calvarial bone defect models, biological responses to the FRC implants were evaluated. On the basis of theseevaluations, it can be concluded that the FRC, based on E-glass (electrical glass) fibres forming a porous fibre veil enables the ingrowth of connective tissues to the inner structures of the material, as well as the bone formation and mineralization inside the fibre veil. Bone formation could be enhanced by using bioactive glass granules fixed to the FRC implants. FRC-implanted bone defects healed partly; no total healing of defects was achieved. Biological responses during the follow-up time, at a maximum of 12 weeks, to resin-impregnated composite implant seemed to depend on the polymerization time of the resin matrix of the FRC. Both of the studied resin systems used in the FRC were photopolymerised and the heat-induced postpolymerisation was used additionally.

Development of Special Pumps Repair Process

Tässä diplomityössä käsitellään erikoispumppujen korjausprosessia teollisuuspumppujen korjauksiin erikoistuneessa konepajassa. Työn pääasiallinen tarkoitus on tuotantoprosessin kehittäminen ja tuotantovaiheiden esitteleminen. Tavoitteen taustalla on pyrkimys entisestään parantaa palvelukykyä ja asiakastyytyväisyyttä.Kolme eri keinoa päätavoitteen saavuttamiseksi ovat tuotannon suunnittelun ja ohjauksen kehittäminen, työssä käsiteltyjen pumpputyyppien korjausprosessien läpäisyaikojen lyhentäminen sekä korjausvaiheiden määrittely ja esittely vaihe vaiheelta. Työssä käsiteltyjä erikoispumpputyyppejä ovat imupumput, monijaksopumput sekä pysty/potkuripumput.Tuotannonsuunnittelun ja -ohjauksen kehittämiseksi sekä läpäisyaikojen lyhentämiseksi työssä etsittiin vaihtoehtoisia toimintatapoja. Kolmas tavoite, eli korjausvaiheiden määrittely, toteutettiin esittelemällä korjausprosessin vaiheet käsitellyillä pumpputyypeillä.Tuloksena saatiin keinoja tuotannon suunnittelun ja hallinnan kehittämiseksi. Useimmat keinot koskevat toimintatapojen selkiyttämistä. Myös keinoja läpäisyaikojen lyhentämiseksi löydettiin. Tietyllä imupumpputyypillä ja -koolla läpäisyajan lyheneminen oli 25 % ja osalla monijaksopumpuista jopa 75 %. Tulokset saavutetaan varastoimalla tiettyjä komponentteja, joilla on pitkä valmistus- tai korjausaika. Pysty/potkuripumppujen korjauksen läpäisyaikaa ei saatu lyhennettyä työn rajausten puitteissa Näiden tulosten lisäksi korjausprosessin toimintatavat määriteltiin.

Development a distributed simulation environment on a cluster of workstations

Simulation has traditionally been used for analyzing the behavior of complex real world problems. Even though only some features of the problems are considered, simulation time tends to become quite high even for common simulation problems. Parallel and distributed simulation is a viable technique for accelerating the simulations. The success of parallel simulation depends heavily on the combination of the simulation application, algorithm and message population in the simulation is sufficient, no additional delay is caused by this environment. In this thesis a conservative, parallel simulation algorithm is applied to the simulation of a cellular network application in a distributed workstation environment. This thesis presents a distributed simulation environment, Diworse, which is based on the use of networked workstations. The distributed environment is considered especially hard for conservative simulation algorithms due to the high cost of communication. In this thesis, however, the distributed environment is shown to be a viable alternative if the amount of communication is kept reasonable. Novel ideas of multiple message simulation and channel reduction enable efficient use of this environment for the simulation of a cellular network application. The distribution of the simulation is based on a modification of the well known Chandy-Misra deadlock avoidance algorithm with null messages. The basic Chandy Misra algorithm is modified by using the null message cancellation and multiple message simulation techniques. The modifications reduce the amount of null messages and the time required for their execution, thus reducing the simulation time required. The null message cancellation technique reduces the processing time of null messages as the arriving null message cancels other non processed null messages. The multiple message simulation forms groups of messages as it simulates several messages before it releases the new created messages. If the message population in the simulation is suffiecient, no additional delay is caused by this operation A new technique for considering the simulation application is also presented. The performance is improved by establishing a neighborhood for the simulation elements. The neighborhood concept is based on a channel reduction technique, where the properties of the application exclusively determine which connections are necessary when a certain accuracy for simulation results is required. Distributed simulation is also analyzed in order to find out the effect of the different elements in the implemented simulation environment. This analysis is performed by using critical path analysis. Critical path analysis allows determination of a lower bound for the simulation time. In this thesis critical times are computed for sequential and parallel traces. The analysis based on sequential traces reveals the parallel properties of the application whereas the analysis based on parallel traces reveals the properties of the environment and the distribution.

Novel Functions of ErbB4 and NRG-1 in Development and Cancer

Cells communicate, or signal, with each other constantly to ensure proper functioning of tissues and organs. Cell signaling is often performed by interplay of receptors and ligands that bind these receptors. ErbB receptors (epidermal growth factor receptors, EGFR, HER) bind extracellular growth factors and transduce these signals inside of cells. ErbB dysfunction promotes carcinogenesis, and also results in numerous defects during normal development. This study focused on the functions of one member of the ErbB receptor family, ErbB4, and growth factor, neuregulin-1 (NRG-1), that can bind and activate ErbB4. This study aimed to find novel functions of ErbB4 and NRG-1. Hypoxia, or deficiency of oxygen, is common in cancer and ischemic conditions. One of the key findings of the work was the identification and characterization of a cross-talk between ErbB4 and Hypoxia-inducible factor 1α (HIF-1α), the central mediator of hypoxia signaling. ErbB4 activation by NRG-1 was found to increase HIF-1α activity. Interestingly, this regulation occurred in reciprocal manner as HIF-1α was also able to increase protein levels of NRG-1 and ErbB4. Moreover, expression of NRG-1 and ErbB4 was associated with HIF activity in vivo in human clinical samples and in mice. Reduction of functional ErbB4 in developing zebrafish embryos resulted in defects in development of the skeletal muscles. To study ErbB4 functions in pathological situation in humans, clinical samples of serous ovarian carcinoma were analyzed using tissue microarrays and real-time RT-PCR. A specific isoform of ErbB4, CYT-1, was associated with poor survival in serous ovarian cancer and increased anchorage independent growth of ovarian cancer cells in vitro. These observations demonstrate that ErbB4 and NRG-1 are essential regulators of cellular response to hypoxia, of development, and of ovarian carcinogenesis.

System-level characterization of Th2 cell development and immune cell responses to ZnO and TiO2 nanoparticles

Asthma and allergy are common diseases and their prevalence is increasing. One of the hypotheses that explains this trend is exposure to inhalable chemicals such as traffi c-related air pollution. Epidemiological research supports this theory, as a correlation between environmental chemicals and allergic respiratory diseases has been found. In addition to ambient airborne particles, one may be exposed to engineered nanosized materials that are actively produced due to their favorable physico-chemical properties compared to their bulk size counterparts. On the cellular level, improper activity of T helper (Th) cells has been connected to allergic reactions. Th cells can differentiate into functionally different effector subsets, which are identifi ed according to their characteristic cytokine profi les resulting in specifi c ability to communicate with other cells. Th2 cells activate humoral immunity and stimulate eradication of extracellular pathogens. However, persistent predominance of Th2 cells is involved in a development of number of allergic diseases. The cytokine environment at the time of antigen recognition is the major factor determining the polarization of a naïve Th cell. Th2 cell differentiation is initiated by IL4, which signals via transcription factor STAT6. Although the importance of this pathway has been evaluated in the mouse studies, the signaling components involved have been largely unknown. The aim of this thesis was to identify molecules, which are under the control of IL4 and STAT6 in Th cells. This was done by using system-level analysis of STAT6 target genes at genome, mRNA and protein level resulting in identifi cation of various genes previously not connected to Th2 cell phenotype acquisition. In the study, STAT6-mediated primary and secondary target genes were dissection from each other and a detailed transcriptional kinetics of Th2 cell polarization of naïve human CD4+ T cells was collected. Integration of these data revealed the hierarchy of molecular events that mediates the differentiation towards Th2 cell phenotype. In addition, the results highlighted the importance of exploiting proteomics tools to complement the studies on STAT6 target genes identifi ed through transcriptional profi ling. In the last subproject, the effects of the exposure with ZnO and TiO2 nanoparticles was analyzed in Jurkat T cell line and in primary human monocyte-derived macrophages and dendritic cells to evaluate their toxicity and potential to cause infl ammation. Identifi cation of ZnO-derived gene expression showed that the same nanoparticles may elicit markedly distinctive responses in different cell types, thus underscoring the need for unbiased profi ling of target genes and pathways affected. The results gave additional proof that the cellular response to nanosized ZnO is due to leached Zn2+ ions. The approach used in ZnO and TiO2 nanoparticle study demonstrated the value of assessing nanoparticle responses through a toxicogenomics approach. The increased knowledge of Th2 cell signaling will hopefully reveal new therapeutic nodes and eventually improve our possibilities to prevent and tackle allergic infl ammatory diseases.

Integration of learning supportive applications into the development of the e-portfolio construction process

The portfolio as a means of demonstrating personal skills has lately been gaining prominence among technology students. This is partially due to the introduction of electronic portfolios, or e-portfolios. As platforms for e-portfolio management with different approaches have been introduced, the learning cycle, traditional portfolio pedagogy, and learner centricity have sometimes been forgotten, and as a result, the tools have been used for the most part as data depositories. The purpose of this thesis is to show how the construction of e-portfolios of IT students can be supported by institutions through the usage of different tools that relate to study advising, teaching, and learning. The construction process is presented as a cycle based on learning theories. Actions related to the various phases of the e-portfolio construction process are supported by the implementation of software applications. To maximize learner-centricity and minimize the intervention of the institution, the evaluated and controlled actions for these practices can be separated from the e-portfolios, leaving the construction of the e-portfolio to students. The main contributions of this thesis are the implemented applications, which can be considered to support the e-portfolio construction by assisting in planning, organizing, and reflecting activities. Eventually, this supports the students in their construction of better and more extensive e-portfolios. The implemented tools include 1) JobSkillSearcher to help students’ recognition of the demands of the ICT industry regarding skills, 2) WebTUTOR to support students’ personal study planning, 3) Learning Styles to determine students' learning styles, and 4) MyPeerReview to provide a platform on which to carry out anonymous peer review processes in courses. The most visible outcome concerning the e-portfolio is its representation, meaning that one can use it to demonstrate personal achievements at the time of seeking a job and gaining employment. Testing the tools and the selected open-source e-portfolio application indicates that the degree of richness of e-portfolio content can be increased by using the implemented applications.