Fatigue fractures in military conscripts : A study on risk factors, diagnostics and long-term consequences

Fatigue fracture is an overuse injury commonly encountered in military and sports medicine, and known to relate to intensive or recently intensified physical activity. Bone responds to increased stress by enhanced remodeling. If physical stress exceeds bone s capability to remodel, accumulation of microfractures can lead to bone fatigue and stress fracture. Clinical diagnosis of stress fractures is complex and based on patient s anamnesis and radiological imaging. Bone stress fractures are mostly low-risk injuries, healing well after non-operative management, yet, occurring in high-risk areas, stress fractures can progress to displacement, often necessitating surgical treatment and resulting in prolonged morbidity. In the current study, the role of vitamin D as a predisposing factor for fatigue fractures was assessed using serum 25OHD level as the index. The average serum 25OHD concentration was significantly lower in conscripts with fatigue fracture than in controls. Evaluating TRACP-5b bone resorption marker as indicator of fatigue fractures, patients with elevated serum TRACP-5b levels had eight times higher probability of sustaining a stress fracture than controls. Among the 154 patients with exercise induced anterior lower leg pain and no previous findings on plain radiography, MRI revealed a total of 143 bone stress injuries in 86 patients. In 99% of the cases, injuries were in the tibia, 57% in the distal third of the tibial shaft. In patients with injury, forty-nine (57%) patients exhibited bilateral stress injuries. In a 20-year follow-up, the incidence of femoral neck fatigue fractures prior to the Finnish Defence Forces new regimen in 1986 addressing prevention of these fractures was 20.8/100,000, but rose to 53.2/100,000 afterwards, a significant 2.6-fold increase. In nineteen subjects with displaced femoral neck fatigue fractures, ten early local complications (in first postoperative year) were evident, and after the first postoperative year, osteonecrosis of the femoral head in six and osteoarthritis of the hip in thirteen patients were found. It seems likely that low vitamin D levels are related to fatigue fractures, and that an increasing trend exists between TRACP-5b bone resorption marker elevation and fatigue fracture incidence. Though seldom detected by plain radiography, fatigue fractures often underlie unclear lower leg stress-related pain occurring in the distal parts of the tibia. Femoral neck fatigue fractures, when displaced, lead to long-term morbidity in a high percentage of patients, whereas, when non-displaced, they do not predispose patients to subsequent adverse complications. Importantly, an educational intervention can diminish the incidence of fracture displacement by enhancing awareness and providing instructions for earlier diagnosis of fatigue fractures.

Reacting to Complex Threats – the Securitization in the Speeches of Anders Fogh Rasmussen based on NATO´s New Strategic Concept

The purpose of this master´s thesis is to analyze how NATO Secretary General Anders Fogh Rasmussen is trying to justify the existence of the military alliance through the use of security arguments. I am puzzled by the question: why does NATO still exist – what is NATO’s raison d'être. The New Strategic Concept (2010) forms the base for his argumentation. This thesis focuses on the security argumentation of NATO which is examined by analyzing the speeches the Secretary General. The theoretical framework of this study is based on constructivist approach to international security examining the linguistic process of securitization. Issues become securitized after Anders Fogh Rasmussen names them as threats. This thesis focuses on the securitization process relating to NATO and analyses what issues Rasmussen raises to the security agenda. Research data consists of the speeches by Anders Fogh Rasmussen. They are analyzed through J.L. Austin’s speech act taxonomy and Chaïm Perelman’s argumentation theories. The thesis will concentrate on the formulation and articulation of these threats which are considered and coined as “new threats” in contemporary international relations. I am conducting this research through the use of securitization theory. This study illustrates that the threats are constructed by NATO’s member-states in unison, but the resolutions are sounded through Rasmussen’s official speeches and transcripts. . Based on the analysis it can be concluded that Rasmussen is giving reasons for the existence of NATO. This takes place by making use of speech acts and different rhetorical techniques. The results of the analysis indicate that NATO remains an essential organization for the West and the rest of the world according to the Secretary General.

External signal-activated liposomal drug delivery systems

Modern drug discovery gives rise to a great number of potential new therapeutic agents, but in some cases the efficient treatment of patient may not be achieved because the delivery of active compounds to the target site is insufficient. Thus, drug delivery is one of the major challenges in current pharmaceutical research. Numerous nanoparticle-based drug carriers, e.g. liposomes, have been developed for enhanced drug delivery and targeting. Drug targeting may enhance the efficiency of the treatment and, importantly, reduce unwanted side effects by decreasing drug distribution to non-target tissues. Liposomes are biocompatible lipid-based carriers that have been studied for drug delivery during the last 40 years. They can be functionalized with targeting ligands and sensing materials for triggered activation. In this study, various external signal-assisted liposomal delivery systems were developed. Signals can be used to modulate drug permeation or release from the liposome formulation, and they provide accurate control of time, place and rate of activation. The study involved three types of signals that were used to trigger drug permeation and release: electricity, heat and light. Electrical stimulus was utilized to enhance the permeation of liposomal DNA across the skin. Liposome/DNA complex-mediated transfections were performed in tight rat epidermal cell model. Various transfection media and current intensities were tested, and transfection efficiency was evaluated non-invasively by monitoring the concentration of secreted reporter protein in cell culture medium. Liposome/DNA complexes produced gene expression, but electrical stimulus did not enhance the transfection efficiency significantly. Heat-sensitive liposomal drug delivery system was developed by coating liposomes with biodegradable and thermosensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate polymer. Temperature-triggered liposome aggregation and contents release from liposomes were evaluated. The cloud point temperature (CP) of the polymer was set to 42 °C. Polymer-coated liposome aggregation and contents release were observed above CP of the polymer, while non-coated liposomes remained intact. Polymer precipitates above its CP and interacts with liposomal bilayers. It is likely that this induces permeabilization of the liposomal membrane and contents release. Light-sensitivity was introduced to liposomes by incorporation of small (< 5 nm) gold nanoparticles. Hydrophobic and hydrophilic gold nanoparticles were embedded in thermosensitive liposomes, and contents release was investigated upon UV light exposure. UV light-induced lipid phase transitions were examined with small angle X-ray scattering, and light-triggered contents release was shown also in human retinal pigment epithelial cell line. Gold nanoparticles absorb light energy and transfer it into heat, which induces phase transitions in liposomes and triggers the contents release. In conclusion, external signal-activated liposomes offer an advanced platform for numerous applications in drug delivery, particularly in the localized drug delivery. Drug release may be localized to the target site with triggering stimulus that results in better therapeutic response and less adverse effects. Triggering signal and mechanism of activation can be selected according to a specific application.

Il mundus muliebris nelle fonti latine e nei contesti Pompeiani

The subject of the study is the classical Latin concept 'mundus muliebris', usually translated simply as women’s toiletry items. The task of the research is, on one hand, to find a more accurate and comprehensive literary definition for the concept as used in the early Imperial period, and on the other, to examine whether it is possible to find corresponding groupings of material objects among the finds from Pompeian houses destroyed by the eruption of Mount Vesuvius in AD 79. The study is based on two different bodies of evidence, literary and material, and consequently uses two independent methods of research. In the philological part of the study, all occurrences of the concept 'mundus muliebris' in classical Latin texts were identified and analysed in their proper literary context, paying special attention to information about the nature of the objects included (name, owner, quantity, value, location in the house). On the basis of this analysis, mirrors were chosen as the key elements of the archaeological research, being ̶ hypothetically ̶ the most probable objects to be found among any extant 'mundus muliebris' contexts in Pompeian houses. In the archaeological part of the study, all mirrors deposited in the Archaeological Storerooms of Pompeii, mostly unpublished, were examined, together with their original find contexts. For more detailed documentation, classification, as well as quantitative and functional analysis, the fifty-nine best preserved household or shop contexts were chosen. Among these contexts, only a few ‘ideal’ groups closely corresponding to the literary definitions were found. However, in most cases a functional artifact pattern of toiletry items could indeed be found grouped together with the mirror. The arrangement of the contexts in the domestic space also revealed a clear pattern. Firstly, the contexts consistently seem to be found in the place of storage, inside locked boxes, not in the place of use. Secondly, they show that for the storage of such objects small closed rooms flanking the main entrance of the house were preferred. Culturally, 'mundus muliebris' can be described as a very complex multi-layered concept intimately interrelated with the female gender, an instrument of its bodily creation and a symbol of its nature. Concretely, it has at its core mirrors and instruments for the care of skin and hair, and includes, in more technical definitions, washing equipment as well. In the Roman domus, lacking specific women’s quarters, this box containing toiletries and other personal objects could be defined as the true, although mobile, private space of the household’s female members.

Expert Identity in Development of Core-Task-Oriented Working Practices for Mastering Demanding Situations

The point of departure in this dissertation was the practical safety problem of unanticipated, unfamiliar events and unexpected changes in the environment, the demanding situations which the operators should take care of in the complex socio-technical systems. The aim of this thesis was to increase the understanding of demanding situations and of the resources for coping with these situations by presenting a new construct, a conceptual model called Expert Identity (ExId) as a way to open up new solutions to the problem of demanding situations and by testing the model in empirical studies on operator work. The premises of the Core-Task Analysis (CTA) framework were adopted as a starting point: core-task oriented working practices promote the system efficiency (incl. safety, productivity and well-being targets) and that should be supported. The negative effects of stress were summarised and the possible countermeasures related to the operators' personal resources such as experience, expertise, sense of control, conceptions of work and self etc. were considered. ExId was proposed as a way to bring emotional-energetic depth into the work analysis and to supplement CTA-based practical methods to discover development challenges and to contribute to the development of complex socio-technical systems. The potential of ExId to promote understanding of operator work was demonstrated in the context of the six empirical studies on operator work. Each of these studies had its own practical objectives within the corresponding quite broad focuses of the studies. The concluding research questions were: 1) Are the assumptions made in ExId on the basis of the different theories and previous studies supported by the empirical findings? 2) Does the ExId construct promote understanding of the operator work in empirical studies? 3) What are the strengths and weaknesses of the ExId construct? The layers and the assumptions of the development of expert identity appeared to gain evidence. The new conceptual model worked as a part of an analysis of different kinds of data, as a part of different methods used for different purposes, in different work contexts. The results showed that the operators had problems in taking care of the core task resulting from the discrepancy between the demands and resources (either personal or external). The changes of work, the difficulties in reaching the real content of work in the organisation and the limits of the practical means of support had complicated the problem and limited the possibilities of the development actions within the case organisations. Personal resources seemed to be sensitive to the changes, adaptation is taking place, but not deeply or quickly enough. Furthermore, the results showed several characteristics of the studied contexts that complicated the operators' possibilities to grow into or with the demands and to develop practices, expertise and expert identity matching the core task. They were: discontinuation of the work demands, discrepancy between conceptions of work held in the other parts of organisation, visions and the reality faced by the operators, emphasis on the individual efforts and situational solutions. The potential of ExId to open up new paths to solving the problem of the demanding situations and its ability to enable studies on practices in the field was considered in the discussion. The results were interpreted as promising enough to encourage the conduction of further studies on ExId. This dissertation proposes especially contribution to supporting the workers in recognising the changing demands and their possibilities for growing with them when aiming to support human performance in complex socio-technical systems, both in designing the systems and solving the existing problems.

Assessing organizational culture in complex sociotechnical systems : Methodological evidence from studies in nuclear power plant maintenance organizations

Failures in industrial organizations dealing with hazardous technologies can have widespread consequences for the safety of the workers and the general population. Psychology can have a major role in contributing to the safe and reliable operation of these technologies. Most current models of safety management in complex sociotechnical systems such as nuclear power plant maintenance are either non-contextual or based on an overly-rational image of an organization. Thus, they fail to grasp either the actual requirements of the work or the socially-constructed nature of the work in question. The general aim of the present study is to develop and test a methodology for contextual assessment of organizational culture in complex sociotechnical systems. This is done by demonstrating the findings that the application of the emerging methodology produces in the domain of maintenance of a nuclear power plant (NPP). The concepts of organizational culture and organizational core task (OCT) are operationalized and tested in the case studies. We argue that when the complexity of the work, technology and social environment is increased, the significance of the most implicit features of organizational culture as a means of coordinating the work and achieving safety and effectiveness of the activities also increases. For this reason a cultural perspective could provide additional insight into the problem of safety management. The present study aims to determine; (1) the elements of the organizational culture in complex sociotechnical systems; (2) the demands the maintenance task sets for the organizational culture; (3) how the current organizational culture at the case organizations supports the perception and fulfilment of the demands of the maintenance work; (4) the similarities and differences between the maintenance cultures at the case organizations, and (5) the necessary assessment of the organizational culture in complex sociotechnical systems. Three in-depth case studies were carried out at the maintenance units of three Nordic NPPs. The case studies employed an iterative and multimethod research strategy. The following methods were used: interviews, CULTURE-survey, seminars, document analysis and group work. Both cultural analysis and task modelling were carried out. The results indicate that organizational culture in complex sociotechnical systems can be characterised according to three qualitatively different elements: structure, internal integration and conceptions. All three of these elements of culture as well as their interrelations have to be considered in organizational assessments or important aspects of the organizational dynamics will be overlooked. On the basis of OCT modelling, the maintenance core task was defined as balancing between three critical demands: anticipating the condition of the plant and conducting preventive maintenance accordingly, reacting to unexpected technical faults and monitoring and reflecting on the effects of maintenance actions and the condition of the plant. The results indicate that safety was highly valued at all three plants, and in that sense they all had strong safety cultures. In other respects the cultural features were quite different, and thus the culturally-accepted means of maintaining high safety also differed. The handicraft nature of maintenance work was emphasised as a source of identity at the NPPs. Overall, the importance of safety was taken for granted, but the cultural norms concerning the appropriate means to guarantee it were little reflected. A sense of control, personal responsibility and organizational changes emerged as challenging issues at all the plants. The study shows that in complex sociotechnical systems it is both necessary and possible to analyse the safety and effectiveness of the organizational culture. Safety in complex sociotechnical systems cannot be understood or managed without understanding the demands of the organizational core task and managing the dynamics between the three elements of the organizational culture.

Tarinakontekstin vaikutus sanojen muistamiseen kompleksisessa työmuistitehtävässä

Objectives. The sentence span task is a complex working memory span task used for estimating total working memory capacity for both processing (sentence comprehension) and storage (remembering a set of words). Several traditional models of working memory suggest that performance on these tasks relies on phonological short-term storage. However, long-term memory effects as well as the effects of expertise and strategies have challenged this view. This study uses a working memory task that aids the creation of retrieval structures in the form of stories, which have been shown to form integrated structures in longterm memory. The research question is whether sentence and story contexts boost memory performance in a complex working memory task. The hypothesis is that storage of the words in the task takes place in long-term memory. Evidence of this would be better recall for words as parts of sentences than for separate words, and, particularly, a beneficial effect for words as part of an organized story. Methods. Twenty stories consisting of five sentences each were constructed, and the stimuli in all experimental conditions were based on these sentences and sentence-final words, reordered and recombined for the other conditions. Participants read aloud sets of five sentences that either formed a story or not. In one condition they had to report all the last words at the end of the set, in another, they memorised an additional separate word with each sentence. The sentences were presented on the screen one word at a time (500 ms). After the presentation of each sentence, the participant verified a statement about the sentence. After five sentences, the participant repeated back the words in correct positions. Experiment 1 (n=16) used immediate recall, experiment 2 (n=21) both immediate recall and recall after a distraction interval (the operation span task). In experiment 2 a distracting mental arithmetic task was presented instead of recall in half of the trials, and an individual word was added before each sentence in the two experimental conditions when the participants were to memorize the sentence final words. Subjects also performed a listening span task (in exp.1) or an operation span task (exp.2) to allow comparison of the estimated span and performance in the story task. Results were analysed using correlations, repeated measures ANOVA and a chi-square goodness of fit test on the distribution of errors. Results and discussion. Both the relatedness of the sentences (the story condition) and the inclusion of the words into sentences helped memory. An interaction showed that the story condition had a greater effect on last words than separate words. The beneficial effect of the story was shown in all serial positions. The effects remained in delayed recall. When the sentences formed stories, performance in verification of the statements about sentence context was better. This, as well as the differing distributions of errors in different experimental conditions, suggest different levels of representation are in use in the different conditions. In the story condition, the nature of these representations could be in the form of an organized memory structure, a situation model. The other working memory tasks had only few week correlations to the story task. This could indicate that different processes are in use in the tasks. The results do not support short-term phonological storage, but instead are compatible with the words being encoded to LTM during the task.

Matka koulun kestävän kehittämisen maisemassa

A Journey in the Landscape of Sustainable School Development “A Journey in the Landscape of Sustainable School Development” is a story of the Sorrila School development process. This research deals with a school development project as a process, and as a part of international projects on Education for Sustainable Development, with ENSI (Environment and School Initiatives) being the most important. The main purpose of the study was to analyze the change process as a general phenomenon as well as the learning connected to it. The research describes the development period 2001–2008 at the Sorrila Primary school. The research questions are as follows: 1. What did pupils learn during the research and development period? 2. How did the coordinating teacher develop personally? 3. How were the ENSI targets and other closely linked projects reached? 4. What was the feedback from the pupils, their parents and other teachers at the school? 5. How did the developing process proceed in 2001–2008? The method used was integrating action research, which also had ethnographical elements. Narrative was the form of the data as well as the manner of reporting. The method as a whole was integrating, ethnographical action research as a story. The research data consisted mostly of Knowledge Forum notes written by the teacher-researcher. Knowledge Forum is an Internetbased collaborative knowledge-building programme. Pupils’, parents’ and other teachers’ feedback, newspaper articles and students’ writings complied the data, which consists of material from seven years. Sustainable development was the basis of the school improvement. The targets of the United Nations Decade of Education for Sustainable Development (2005–2014) were part of the development projects. According to the research results the school was seen as part of complex systems where manifold and interactive learning took place. The learning of pupils, teachers and the school as a community can be characterised socioculturally. The school was able to reach a level of collaborative transformative learning. As well as several concrete projects, such as Comenius school project, school development consisted of networking at many levels. Along with the projects and networking, the school was able to apply the pedagogy of connection, by carrying out integrative and cross-disciplinary themes and using various learning and teaching methods. International cooperation was a natural part of the work. A figure of Aunt Green, the role model of the teacher researcher, was an innovation which resembled a change agent. The other role of the teacherresearcher as a coordinator, was important for her own professional development. According to the results the change process, which relied on sustainable school development, led the school along a road of positive renewals. It was not a series of projects but an ongoing process. The objectives of the international projects were accomplished to a great extent during the research period. According to the principles of action research, the main results were put forward in order to help others to develop their schools. Frictions and problems as well as positive experiences and rejecting dualities were seen as change forces. Keywords: education for sustainable development (ESD), sustainable school development, teacher professional development, integrating, pedagogy of connection, transformative learning

Noviisiopettajana peruskoulussa : Aloittelevien opettajien autenttisia kokemuksia ensimmäisestä opettajavuodesta

As a Novice Teacher at Comprehensive School: The authentic experiences of the beginning teachers during their first year of teaching The aim of this study is to explicate the novice year of teaching in the light of teachers´ authentic experiences. The subject of this investigation is the teachers´ subjective world of experience during their first academic year of teaching and the sharing of these experiences in collaborative consulting meetings. The themes discussed in the meetings were introduced into the collaborative group by the novice teachers themselves, and the progress of discussion was con-trolled by them. The research data was gathered in a consultative working group where the way a novice teacher starts to interpret, analyze and identify his/her own complex and dynamic teaching situations was observed. The research data gathered in this way illuminates novice teachers´ world of experience and mental picture as well as the unconscious sides of school life. In a theoretical frame of reference, the work of a teacher is identified, according to systemic scientific thought, as a dynamic triangle in which the basic elements are the personality of the teacher, the role of the teacher and the school as an organization. These basic elements form a whole within which the teacher works. The dynamics of this triangle in a teacher’s work are brought to light through the study of the phenomena of groups and group dynamics since a teacher works either as a member of a group (working community), as a leader of a group (teaching situations) or in a network (parent – teacher cooperation). Therefore, tension and force are always present in teaching work. The main research problem was to explain how a novice teacher experiences his/her first working year as a teacher. The participants (n=5) were teaching at five different comprehensive schools in the city of Helsinki. This was their first long-term post as a teacher. The research data consists of seven collaborative consulting meetings, as well as recordings and transcripts of the meetings. A classificatory framework was developed for data analysis which enabled a sys-tematic qualitative content analysis based on theory and material. In addition to the consulting meetings, the teachers were interviewed at the beginning and at the end of the process of collecting the research material. The interviews were used to interpret the meanings of the content analysis based on raw data. The findings show that there is a gap between teacher education and the reality of school life, which causes difficulties for a novice teacher during his/her first teaching year. The gap is rather a global educational problem than a national one, and therefore it is independent of cultural factors. Novice teachers desire a well-structured theory of teacher education and a clear programme where the themes and content delve deeper and deeper into the subject matter during the study years. According to the novice teachers, teacher education frequently consists of sporadic and unconnected study and class situations. An individual content weakness of teacher education is the lack of insufficient initiation into evaluation processes. The novice teachers suggest that a student must be provided good-quality and competent guidance during the study years and during his or her induction. There should be a well-organized, structured and systematic induction program for novice teachers. The induction program should be overseen by an organization so that the requirements of a qualified induction can be met. The findings show that the novice teachers find the first year of teaching at comprehensive school emotionally loaded. The teachers experienced teaching as difficult work and found the workload heavy. Nevertheless, they enjoyed their job because, as they said, there were more pleasant than unpleasant things in their school day. Their main feeling at school was the joy of success in teaching. The novice teachers felt satisfaction with their pupils. The teachers experienced the more serious feelings of anger and disgust when serious violence took place. The most difficult situations arose from teaching pupils who had mental health problems. The toughest thing in the teacher´s work was teaching groups that are too heterogeneous. The most awkward problems in group dynamics happened when new immigrants, who spoke only their own languages, were integrated into the groups in the middle of the school year. Teachers wanted to help children who needed special help with learning but restated at the same time that the groups being taught shouldn’t be too heterogeneous. The teachers wished for help from school assistants so that they could personally concentrate more on teaching. Not all the parents took care of their children according to the comprehensive school law. The teachers found it hard to build a confidential relationship between home and school. In this study, novice teachers found it hard to join the teaching staff at school. Some of the teachers on staff were very strong and impulsive, reacting loudly and emotionally. These teachers provoked disagreement, conflicts, power struggles and competition among the other teachers. Although the novice teachers of the study were all qualified teachers, three of them were not interested in a permanent teaching job. For these teachers teaching at a primary school was just a project, a short period in their working life. They will remain in the teaching profession as long as they are learning new things and enjoying their teaching job. This study is an independent part of the research project on Interplay – Connecting Academic Teacher Education and Work, undertaken by the Department of Applied Sciences of Education at the University of Helsinki. Key words: novice teacher, emotions, groups and group dynamics, authority, co-operation between home and school, teacher community, leadership at school, induction, consulting

Dental health and school-based health education among 15-year-olds in Tehran, Iran

The aim of the present study was to assess dental health and its determinants among 15-year-olds in Tehran, Iran and to evaluate the impact of a school-based educational intervention on their oral cleanliness and gingival health. The total sample comprised 506 students. Data collection was performed through a clinical dental examination and a self-administered structured questionnaire. This questionnaire covered the student s background information, socio-economic status, self-perceived dental health, tooth-brushing, and smoking. The clinical dental examination covered caries experience, gingival status, dental plaque status, and orthodontic treatment needs. Participation was voluntary, and all students responded to the questionnaire. Only three students refused the clinical dental examination. The intervention was based on exposing students to dental health education through a leaflet and a videotape designed for the present study. The outcome examinations took place 12 weeks after the baseline among the three groups of the intervention trial (leaflet, videotape, and control). High participation rates at the baseline and scanty drop-outs (7%) in the intervention speak for reliability of the results. Mean value of the DMFT (D=decayed, M=missing, and F=filled teeth) index of the 15-year-olds was 2.1, which comprised DT=0.9, MT=0.2, and FT=1.0 with no gender differences. Dental plaque existed on at least one index tooth of all students, and healthy periodontium (Community Periodontal Index=0) was found in less than 10% of students. Need for caries treatment existed in 40% of students, for scaling in 24%, for oral hygiene instructions in all, and for orthodontic treatment in 26%. Students with the highest level of parents education had fewer dental caries (36% vs. 48%) and less dental plaque (77% vs. 88%). Of all students, 78% assessed their dental health as good or better. Even more of those with their DMFT=0 (73% vs. 27%) and DT=0 (68% vs. 32%) assessed their dental health as good or better. Smokers comprised 5% of the boys and 2% of the girls. Smoking was common among students of less-educated parents (6% vs. 3%). Of all students, 26% reported twice-daily tooth-brushing; girls (38% vs. 15%) and those of higher socio-economic background (33% vs. 17%) did so more frequently. The best predictors for a good level of oral cleanliness were female gender or twice-daily tooth-brushing. The present study demonstrated that a school-based educational intervention can be effective in the short term in improving the oral cleanliness and gingival health of adolescents. At least 50% reduction in numbers of teeth with dental plaque compared to baseline was achieved by 58% of the students in the leaflet group, by 37% in the videotape group, and by 10% of the controls. Corresponding figures for gingival bleeding were 72%, 64%, and 30%. For improving the oral cleanliness and gingival health of adolescents in countries such as Iran with a developing oral health system, school-based educational intervention should be established with focus on oral self-care and oral health education messages. Emphasizing the immediate gains from good oral hygiene, such as fresh breath, clean teeth, and attractive appearance should be key aspects for motivating these adolescents to learn and maintain good dental health, whilst in planning school-based dental health intervention, special attention should be given to boys and those with lower socio-economic status. Author s address: Reza Yazdani, Department of Oral Public Health, Institute of Dentistry, University of Helsinki, P.O. Box 41, FI-00014 Helsinki, Finland. E-mail: reza.yazdani@helsinki.fi

Evidence-based perspective on CP rehabilitation : Reviews on physiotherapy, physiotherapy-related motor-based interventions and orthotic devices

This thesis utilises an evidence-based approach to critically evaluate and summarize effectiveness research on physiotherapy, physiotherapy-related motor-based interventions and orthotic devices in children and adolescents with cerebral palsy (CP). It aims to assess the methodological challenges of the systematic reviews and trials, to evaluate the effectiveness of interventions in current use, and to make suggestions for future trials Methods: Systematic reviews were searched from computerized bibliographic databases up to August 2007 for physiotherapy and physiotherapy-related interventions, and up to May 2003 for orthotic devices. Two reviewers independently identified, selected, and assessed the quality of the reviews using the Overview Quality Assessment Questionnaire complemented with decision rules. From a sample of 14 randomized controlled trials (RCT) published between January 1990 and June 2003 we analysed the methods of sampling, recruitment, and comparability of groups; defined the components of a complex intervention; identified outcome measures based on the International Classification of Functioning, Disability and Health (ICF); analysed the clinical interpretation of score changes; and analysed trial reporting using a modified 33-item CONSORT (Consolidated Standards of Reporting Trials) checklist. The effectiveness of physiotherapy and physiotherapy-related interventions in children with diagnosed CP was evaluated in a systematic review of randomised controlled trials that were searched from computerized databases from January 1990 up to February 2007. Two reviewers independently assessed the methodological quality, extracted the data, classified the outcomes using the ICF, and considered the level of evidence according to van Tulder et al. (2003). Results: We identified 21 reviews on physiotherapy and physiotherapy-related interventions and five on orthotic devices. These reviews summarized 23 or 5 randomised controlled trials and 104 or 27 observational studies, respectively. Only six reviews were of high quality. These found some evidence supporting strength training, constraint-induced movement therapy or hippotherapy, and insufficient evidence on comprehensive interventions. Based on the original studies included in the reviews on orthotic devices we found some short-term effects of lower limb casting on passive range of movement, and of ankle-foot orthoses on equinus walk. Long term effects of lower limb orthoses have not been studied. Evidence of upper limb casting or orthoses is conflicting. In the sample of 14 RCTs, most trials used simple randomisation, complemented with matching or stratification, but only three specified the concealed allocation. Numerous studies provided sufficient details on the components of a complex intervention, but the overlap of outcome measures across studies was poor and the clinical interpretation of observed score changes was mostly missing. Almost half (48%) of the applicable CONSORT-based items (range 28 32) were reported adequately. Most reporting inadequacies were in outcome measures, sample size determination, details of the sequence generation, allocation concealment and implementation of the randomization, success of assessor blinding, recruitment and follow-up dates, intention-to-treat analysis, precision of the effect size, co-interventions, and adverse events. The systematic review identified 22 trials on eight intervention categories. Four trials were of high quality. Moderate evidence of effectiveness was established for upper extremity treatments on attained goals, active supination and developmental status, and of constraint-induced therapy on the amount and quality of hand use and new emerging behaviours. Moderate evidence of ineffectiveness was found for strength training's effect on walking speed and stride length. Conflicting evidence was found for strength training's effect on gross motor function. For the other intervention categories the evidence was limited due to the low methodological quality and the statistically insignificant results of the studies. Conclusions: The high-quality reviews provide both supportive and insufficient evidence on some physiotherapy interventions. The poor quality of most reviews calls for caution, although most reviews drew no conclusions on effectiveness due to the poor quality of the primary studies. A considerable number of RCTs of good to fair methodological and reporting quality indicate that informative and well-reported RCTs on complex interventions in children and adolescents with CP are feasible. Nevertheless, methodological improvement is needed in certain areas of the trial design and performance, and the trial authors are encouraged to follow the CONSORT criteria. Based on RCTs we established moderate evidence for some effectiveness of upper extremity training. Due to limitations in methodological quality and variations in population, interventions and outcomes, mostly limited evidence on the effectiveness of most physiotherapy interventions is available to guide clinical practice. Well-designed trials are needed, especially for focused physiotherapy interventions.

Statistical analysis of the associations of hereditary factors with the risk of Type 1 diabetes and Diabetic Nephropathy based on the familial data collected through ascertaiment from population-based registers

In genetic epidemiology, population-based disease registries are commonly used to collect genotype or other risk factor information concerning affected subjects and their relatives. This work presents two new approaches for the statistical inference of ascertained data: a conditional and full likelihood approaches for the disease with variable age at onset phenotype using familial data obtained from population-based registry of incident cases. The aim is to obtain statistically reliable estimates of the general population parameters. The statistical analysis of familial data with variable age at onset becomes more complicated when some of the study subjects are non-susceptible, that is to say these subjects never get the disease. A statistical model for a variable age at onset with long-term survivors is proposed for studies of familial aggregation, using latent variable approach, as well as for prospective studies of genetic association studies with candidate genes. In addition, we explore the possibility of a genetic explanation of the observed increase in the incidence of Type 1 diabetes (T1D) in Finland in recent decades and the hypothesis of non-Mendelian transmission of T1D associated genes. Both classical and Bayesian statistical inference were used in the modelling and estimation. Despite the fact that this work contains five studies with different statistical models, they all concern data obtained from nationwide registries of T1D and genetics of T1D. In the analyses of T1D data, non-Mendelian transmission of T1D susceptibility alleles was not observed. In addition, non-Mendelian transmission of T1D susceptibility genes did not make a plausible explanation for the increase in T1D incidence in Finland. Instead, the Human Leucocyte Antigen associations with T1D were confirmed in the population-based analysis, which combines T1D registry information, reference sample of healthy subjects and birth cohort information of the Finnish population. Finally, a substantial familial variation in the susceptibility of T1D nephropathy was observed. The presented studies show the benefits of sophisticated statistical modelling to explore risk factors for complex diseases.

On the functional ordering of biomembranes : Implications for drug binding

Cells are packed with membrane structures, defining the inside and outside, and the different subcellular compartments. These membranes consisting mainly of phospholipids have a variety of functions in addition to providing a permeability barrier for various compounds. These functions involve cellular signaling, where lipids can act as second messengers, or direct regulation of membrane associating proteins. The first part of this study focuses on relating some of the physicochemical properties of membrane lipids to the association of drug compounds to membranes. A fluorescence based method is described allowing for determination of the membrane association of drugs. This method was subsequently applied to a novel drug, siramesine, previously shown to have anti-cancer activity. Siramesine was found to associate with anionic lipids. Especially interesting is its strong affinity for a second messenger lipid phosphatidic acid. This is the first example of a small molecule drug compound specifically interacting with a cellular lipid. Phosphatidic acid in cells is required for the activation of many signaling pathways mediating growth and proliferation. This provides an intriguing possibility for a simple molecular mechanism of the observed anti-cancer activity of siramesine. In the second part the thermal behavior and self assembly of charged and uncharged membrane assemblies was studied. Strong inter-lamellar co-operativity was observed for multilamellar DPPC vesicles using fluorescence techniques together with calorimetry. The commonly used membrane models, large unilamellar vesicles (LUV) and multilamellar vesicles (MLV) were found to possess different biophysical properties as interlamellar interactions of MLVs drive segregation of a pyrene labeled lipid analogue into clusters. The effect of a counter-ion lattice on the self assembly of a cationic gemini surfactant was studied. The presence of NaCl strongly influenced the thermal phase behavior of M-1 vesicles, causing formation of giant vesicles upon exceeding a phase transition temperature, followed by a subsequent transition into a more homogenous dispersion. Understanding the underlying biophysical aspects of cellular membranes is of fundamental importance as the complex picture of the structure and function of cells is evolving. Many of the cellular reactions take place on membranes and membranes are known to regulate the activity of many peripheral and intergral membrane associating proteins. From the point of view of drug design and gene technology, membranes can provide an interesting target for future development of drugs, but also a vehicle sensitive for environmental changes allowing for encapsulating drugs and targeting them to the desired site of action.

Methicillin Resistance In Staphylococci : Horizontal Transfer of Mobile Genetic Element (SCCmec) Between Staphylococcal Species

Regardless of the existence of antibiotics, infectious diseases are the leading causes of death in the world. Staphylococci cause many infections of varying severity, although they can also exist peacefully in many parts of the human body. Most often Staphylococcus aureus colonises the nose, and that colonisation is considered to be a risk factor for spread of this bacterium. S. aureus is considered to be the most important Staphylococcus species. It poses a challenge to the field of medicine, and one of the most problematic aspects is the drastic increase of the methicillin-resistant S. aureus (MRSA) strains in hospitals and community world-wide, including Finland. In addition, most of the clinical coagulase-negative staphylococcus (CNS) isolates express resistance to methicillin. Methicillin-resistance in S. aureus is caused by the mecA gene that encodes an extra penicillin-binding protein (PBP) 2a. The mecA gene is found in a mobile genomic island called staphylococcal chromosome cassette mec (SCCmec). The SCCmec consists of the mec gene and cassette chromosome recombinase (ccr)gene complexes. The areas of the SCCmec element outside the ccr and mec complex are known as the junkyard J regions. So far, eight types of SCCmec(SCCmec I- SCCmec VIII) and a number of variants have been described. The SCCmec island is an acquired element in S. aureus. Lately, it appears that CNS might be the storage place of the SCCmec that aid the S. aureus by providing it with the resistant elements. The SCCmec is known to exist only in the staphylococci. The aim of the present study was to investigate the horizontal transfer of SCCmec between the S. aureus and CNS. One specific aim was to study whether or not some methicillin-sensitive S. aureus (MSSA) strains are more inclined to receive the SCCmec than others. This was done by comparing the genetic background of clinical MSSA isolates in the health care facilities of the Helsinki and Uusimaa Hospital District in 2001 to the representatives of the epidemic MRSA (EMRSA) genotypes, which have been encountered in Finland during 1992-2004. Majority of the clinical MSSA strains were related to the EMRSA strains. This finding suggests that horizontal transfer of SCCmec from unknown donor(s) to several MSSA background genotypes has occurred in Finland. The molecular characteristics of representative clinical methicillin-resistant S. epidermidis (MRSE) isolates recovered in Finnish hospitals between 1990 and 1998 were also studied, examining their genetic relation to each other and to the internationally recognised MRSE clones as well, so as to ascertain the common traits between the SCCmec elements in MRSE and MRSA. The clinical MRSE strains were genetically related to each other; eleven PFGE types were associated with sequence type ST2 that has been identified world-wide. A single MRSE strain may possess two SCCmec types III and IV, which were recognised among the MRSA strains. Moreover, six months after the onset of an outbreak of MRSA possessing a SCCmec type V in a long-term care facility in Northern Finland (LTCF) in 2003, the SCCmec element of nasally carried methicillin-resistant staphylococci was studied. Among the residents of a LTCF, nasal carriage of MR-CNS was common with extreme diversity of SCCmec types. MRSE was the most prevalent CNS species. Horizontal transfer of SCCmec elements is speculated to be based on the sharing of SCCmec type V between MRSA and MRSE in the same person. Additionally, the SCCmec element of the clinical human S. sciuri isolates was studied. Some of the SCCmec regions were present in S. sciuri and the pls gene was common in it. This finding supports the hypothesis of genetic exchange happening between staphylococcal species. Evaluation of the epidemiology of methicillin-resistant staphylococcal colonisation is necessary in order to understand the apparent emergence of these strains and to develop appropriate control strategies. SCCmec typing is essential for understanding the emergence of MRSA strains from CNS, considering that the MR-CNS may represent the gene pool for the continuous creation of new SCCmec types from which MRSA might originate.

Molecular basis of the kidney filtration barrier : Role of the nephrin protein complex

The kidney filtration barrier consists of fenestrated endothelial cell layer, glomerular basement membrane and slit diaphragm (SD), the specialized junction between glomerular viscelar epithelial cells (podocytes). Podocyte injury is associated with the development of proteinuria, and if not reversed the injury will lead to permanent deterioration of the glomerular filter. The early events are characterized by disruption of the integrity of the SD, but the molecular pathways involved are not fully understood. Congenital nephrotic syndrome of the Finnish type (CNF) is caused by mutations in NPHS1, the gene encoding the SD protein nephrin. Lack of nephrin results in loss of the SD and massive proteinuria beginning before birth. Furthermore, nephrin expression is decreased in acquired human kidney diseases including diabetic nephropathy. This highlights the importance of nephrin and consequently SD in regulating the kidney filtration function. However, the precise molecular mechanism of how nephrin is involved in the formation of the SD is unknown. This thesis work aimed at clarifying the role of nephrin and its interaction partners in the formation of the SD. The purpose was to identify novel proteins that associate with nephrin in order to define the essential molecular complex required for the establishment of the SD. The aim was also to decipher the role of novel nephrin interacting proteins in podocytes. Nephrin binds to nephrin-like proteins Neph1 and Neph2, and to adherens junction protein P-cadherin. These interactions have been suggested to play a role in the formation of the SD. In this thesis work, we identified densin as a novel interaction partner for nephrin. Densin was localized to the SD and it was shown to bind to adherens junction protein beta-catenin. Furthermore, densin was shown to behave in a similar fashion as adherens junction proteins in cell-cell contacts. These results indicate that densin may play a role in cell adhesion and, therefore, may contribute to the formation of the SD together with nephrin and adherens junction proteins. Nephrin was also shown to bind to Neph3, which has been previously localized to the SD. Neph3 and Neph1 were shown to induce cell adhesion alone, whereas nephrin needed to trans-interact with Neph1 or Neph3 from the opposite cell surface in order to make cell-cell contacts. This was associated with the decreased tyrosine phosphorylation of nephrin. These data extend the current knowledge of the molecular composition of the nephrin protein complex at the SD and also provide novel insights of how the SD may be formed. This thesis work also showed that densin was up-regulated in the podocytes of CNF patients. Neph3 was up-regulated in nephrin deficient mouse kidneys, which share similar podocyte alterations and lack of the SD as observed in CNF patients podocytes. These data suggest that densin and Neph3 may have a role in the formation of morphological alterations in podocytes detected in CNF patients. Furthermore, this thesis work showed that deletion of beta-catenin specifically from adult mouse podocytes protected the mice from the development of adriamycin-induced podocyte injury and proteinuria compared to wild-type mice. These results show that beta-catenin play a role in the adriamycin induced podocyte injury. Podocyte injury is a hallmark in many kidney diseases and the changes observed in the podocytes of CNF patient share characteristics with injured podocytes observed in chronic kidney diseases. Therefore, the results obtained in this thesis work suggest that densin, Neph3 and beta-catenin participate in the molecular pathways which result in morphological alterations commonly detected in injured podocytes in kidney diseases.