Effects of group size and space allocation on physiological, behavioural and production-related welfare parameters in farmed silver fox cubs

Selostus: Ryhmäkoon ja käytössä olevan tilan vaikutus tarhattujen hopeakettupentujen hyvinvointiin

Interactions between genes and alcohol on aggressive behavior and anger related traits : the oxytocin receptor gene as a candidate

Alkoholberusning är en av de starkaste riskfaktorerna för aggressivt beteende. Alla individer blir dock inte aggressiva under alkoholberusning. I sin doktorsavhandling undersökte Johansson ifall individens genetiska uppsättning kan förklara skillnader i vem som reagerar på alkohol med ökat aggressivt beteende och ilska och vem som inte gör det. Resultaten visade att individer som är bärare av en viss variant av genen som kodar för oxytocinets receptorer är i högre grad benägna att uppvisa aggressivt beteende än andra när de är alkoholberusade. Sambandet mellan alkohol och ilska påverkades även av individens genetiska uppsättning av två oxytocinreceptorgenvarianter, vilket antyder att dessa genvarianter även påverkar benägenheten att känna ilska under alkoholberusning. Oxytocinet, som fungerar både som ett hormon och en neurotransmittor, har i tidigare studier visats ha breda effekter på sociala förmågor hos människan, såsom förmåga till igenkännande av andras känslouttryck. Resultaten är de första att hos människan experimentellt påvisa att vissa individer beter sig mer aggressivt än andra när de är berusade, beroende på individens genetiska uppsättning. ”Det är viktigt att komma ihåg att genens effekt i det här fallet inte är av en sådan natur att den direkt och ofrånkomligen orsakar aggressivt beteende. Med andra ord är det orimligt i detta fall att tänka att en individ skulle tillmätas ansvarsfrihet i exempelvis ett våldsbrottmål om hon bär på en viss variant av denna gen”, påpekar Johansson. Oxytocinreceptorgenens effekter analyserades i två olika urval. I ett experimentellt upplägg indelades 116 män slumpässigt i två grupper: en grupp som tilldelades alkoholhaltiga drycker, och en kontrollgrupp som tilldelades alkoholfria drycker. Aggressivt beteende mättes med ett laboratorietest där försökspersonerna fick bestraffa en fiktiv motspelare genom att spela upp motbjudande ljud för denne. Resultaten replikerades i ett populationsbaserat urval av män och kvinnor (n = 3755) vilka besvarat frågor om deras aggressiva beteenden, ilska, och alkoholanvändning.

Free Prostate-specific Antigen Forms and Kallikrein-related Peptidase 2: Tools for Prostate Cancer Diagnostics

Prostate-specific antigen (PSA) is a marker that is commonly used in estimating prostate cancer risk. Prostate cancer is usually a slowly progressing disease, which might not cause any symptoms whatsoever. Nevertheless, some cases of cancer are aggressive and need to be treated before they become life-threatening. However, the blood PSA concentration may rise also in benign prostate diseases and using a single total PSA (tPSA) measurement to guide the decision on further examinations leads to many unnecessary biopsies, over-detection, and overtreatment of indolent cancers which would not require treatment. Therefore, there is a need for markers that would better separate cancer from benign disorders, and would also predict cancer aggressiveness. The aim of this study was to evaluate whether intact and nicked forms of free PSA (fPSA-I and fPSA-N) or human kallikrein-related peptidase 2 (hK2) could serve as new tools in estimating prostate cancer risk. First, the immunoassays for fPSA-I and free and total hK2 were optimized so that they would be less prone to assay interference caused by interfering factors present in some blood samples. The optimized assays were shown to work well and were used to study the marker concentrations in the clinical sample panels. The marker levels were measured from preoperative blood samples of prostate cancer patients scheduled for radical prostatectomy. The association of the markers with the cancer stage and grade was studied. It was found that among all tested markers and their combinations especially the ratio of fPSA-N to tPSA and ratio of free PSA (fPSA) to tPSA were associated with both cancer stage and grade. They might be useful in predicting the cancer aggressiveness, but further follow-up studies are necessary to fully evaluate the significance of the markers in this clinical setting. The markers tPSA, fPSA, fPSA-I and hK2 were combined in a statistical model which was previously shown to be able to reduce unnecessary biopsies when applied to large screening cohorts of men with elevated tPSA. The discriminative accuracy of this model was compared to models based on established clinical predictors in reference to biopsy outcome. The kallikrein model and the calculated fPSA-N concentrations (fPSA minus fPSA-I) correlated with the prostate volume and the model, when compared to the clinical models, predicted prostate cancer in biopsy equally well. Hence, the measurement of kallikreins in a blood sample could be used to replace the volume measurement which is time-consuming, needs instrumentation and skilled personnel and is an uncomfortable procedure. Overall, the model could simplify the estimation of prostate cancer risk. Finally, as the fPSA-N seems to be an interesting new marker, a direct immunoassay for measuring fPSA-N concentrations was developed. The analytical performance was acceptable, but the rather complicated assay protocol needs to be improved until it can be used for measuring large sample panels.

Family-based dietary intervention in the STRIP study – influences on diet and diet-related attitudes

The focus of this dissertation was to investigate the effects of family-based dietary intervention during childhood and adolescence. The participants comprised of children and parents who participated in a longitudinal, randomised atherosclerosis prevention trial (STRIP study). The intervention families (n=540) took part in a dietary intervention since the child’s age of 8- months. The control group (n=522) did not receive any tailored dietary intervention. The main focus of the intervention was to improve the quality of dietary fat. The diet of children and parents was evaluated by daily food records and dietrelated attitudes by a questionnaire. The dietary intervention influenced, favourably, the dietary fat quality in children and parents. Fat quality improved mainly by the decrease of saturated fat intake. Some minor effects of the intervention were also observed in children’s fruit and vegetable (F&V) consumption although the F&V consumption was very low. The intervention increased parental interest in healthy eating, but there was no difference in interest in natural products or in attitudes towards hedonic eating attitudes between the intervention and control parents. Parents’ interest in healthy eating associated with parents’ and children’s high fruit and vegetable consumption but not with their fat quality ratio. On the other hand, dietary fat quality improved at every level of interest in healthy eating. It seems that the main target of the intervention, the dietary fat quality of the children, was promoted effectively. In the future, more emphasis should be given on increasing unsaturated fat intake and on elevating F&V consumption in children. Children’s diet, especially F&V consumption, associated with diet-related attitudes of the parents. Therefore, co-operation with parents and family-based premises for working should be capitalized upon when promoting healthy eating in children and adolescents.

JNK regulation of neurogenesis, neuroplasticity and anxiety-related behaviors in mice

I vår moderna värld har förekomsten av ångeststörningar drastiskt ökat, vilket påverkar välfärden i våra samhällen. Eftersom de molekylära mekanismerna bakom ångest är relativt okända, är möjligheterna till behandling av ångeststörningar begränsade. I och med utvecklingen av genetiska manipuleringmetoder och avbildningstekniker har strukturella förändringar associerade med ångeststörningar kunnat konstateras. Neuroanatomiska studier har påvisat störningar i dendritarkitektur, dendrittaggar och i neurogenesen hos vuxna individer. Särskilt neurogenesen i hippocampus anses viktig i detta sammanhang. Neurogenes i hippocampus har föreslagits spela en viktig roll i ångeststörningarnas patofysiologi och för hur vissa antidepressiva läkemedel förmedlar sin effekt. Under senare år har MAP-kinaser (MAPK) föreslagits vara involverade både i uppkomsten av affektiva störningar och i neurogenes i hippocampus. JNK är en grupp kinaser inom MAPK-familjen som aktiveras av olika externa stressfaktorer. I normala celler är aktiviteten hos JNK låg. Cell-stress ökar aktiviteten hos JNK vilket leder till bl.a. apoptos. JNK kinaser anses vara potentiella terapeutiska mål för behandling av neurodegenerativa sjukdomar men deras potential som mål för behandling av affektiva sjukdomar har tillsvidare inte utretts. Den här avhandlingen behandlar betydelsen av JNK för ångestrelaterat beteende hos möss. Med hjälp av Jnk1-knockout möss och farmakologisk inhibering av JNK-signalering, demonstreras att JNK reglerar neurogenes i hippocampus, vilket i sin tur ligger bakom mössens ångestrelaterade beteende. Jnk1-knockout möss var mindre ängsliga och uppvisade ökad neurogenes i hippcampus jämfört med kontrollmöss. Inhibering av JNK-signalering i hjärnan hos möss gjorde dem också mindre ängsliga och ökade neurogenesen i hippocampus på samma sätt som vissa antidepressiva läkemedel. Inhibering av JNK-aktivitet ledde inte bara till ökad neurogenes i hippocampus, utan främjade också mognandet av nybildade nervceller hos vuxna möss. Resultaten visar också att dendritarkitekturen och fördelningen av dendrittaggar hos CA3 neuroner i hippocampus är förändrad hos Jnk1-knockout möss. Genom screening av substratmolekyler för JNK hittades två JNKeffektormolekyler, MARCKSL1 (ett aktin-associerat protein) och MAP2 (ett mikrotubulus-associerat protein), som reglerade neuronernas sttruktur. Det här tyder på att JNK-signalering kan kontrollera ångeststörningsrelaterade förändringar hor dendriter och dendrittaggar. Sammanfattningsvis ger resultaten som presenteras i avhandlingen en ökad insikt i molekylära mekanismer som kan leda till ångeststörningsrelaterade förändringar i neurogenes och dendritstruktur. Därtill föreslås att JNKsignalbanan har potential som terapeutiskt mål för behandling av ångeststörningar.

Evaluation of Teacher Education Programs by Students and Graduates

The purpose of this research was to do a repeated cross-sectional research on class teachers who study in the 4th year and also graduated at the Faculty of Education, University of Turku between the years of 2000 through 2004. Specifically, seven research questions were addressed to target the main purpose of the study: How do class teacher education masters’ degree senior students and graduates rate “importance; effectiveness; and quality” of training they have received at the Faculty of Education? Are there significant differences between overall ratings of importance; effectiveness and quality of training by year of graduation, sex, and age (for graduates) and sex and age (for senior students)? Is there significant relationship between respondents’ overall ratings of importance; effectiveness and their overall ratings of the quality of training and preparation they have received? Are there significant differences between graduates and senior students about importance, effectiveness, and quality of teacher education programs? And what do teachers’ [Graduates] believe about how increasing work experience has changed their opinions of their preservice training? Moreover the following concepts related to the instructional activities were studied: critical thinking skills, communication skills, attention to ethics, curriculum and instruction (planning), role of teacher and teaching knowledge, assessment skills, attention to continuous professional development, subject matters knowledge, knowledge of learning environment, and using educational technology. Researcher also tried to find influence of some moderator variables e.g. year of graduation, sex, and age on the dependent and independent variables. This study consisted of two questionnaires (a structured likert-scale and an open ended questionnaire). The population in study 1 was all senior students and 2000-2004 class teacher education masters’ degree from the departments of Teacher Education Faculty of Education at University of Turku. Of the 1020 students and graduates the researcher was able to find current addresses of 675 of the subjects and of the 675 graduates contacted, 439 or 66.2 percent responded to the survey. The population in study 2 was all class teachers who graduated from Turku University and now work in the few basic schools (59 Schools) in South- West Finland. 257 teachers answered to the open ended web-based questions. SPSS was used to produce standard deviations; Analysis of Variance; Pearson Product Moment Correlation (r); T-test; ANOVA, Bonferroni post-hoc test; and Polynomial Contrast tests meant to analyze linear trend. An alpha level of .05 was used to determine statistical significance. The results of the study showed that: A majority of the respondents (graduates and students) rated the overall importance, effectiveness and quality of the teacher education programs as important, effective and good. Generally speaking there were only a few significant differences between the cohorts and groups related to the background variables (gender, age). The different cohorts were rating the quality of the programs very similarly but some differences between the cohorts were found in the importance and effectiveness ratings. Graduates of 2001 and 2002 rated the importance of the program significantly higher than 2000 graduates. The effectiveness of the programs was rated significantly higher by 2001 and 2003 graduates than other groups. In spite of these individual differences between cohorts there were no linear trends among the year cohorts in any measure. In respondents’ ratings of the effectiveness of teacher education programs there was significant difference between males and females; females rated it higher than males. There were no significant differences between males’ and females’ ratings of the importance and quality of programs. In the ratings there was only one difference between age groups. Older graduates (35 years or older) rated the importance of the teacher training significantly higher that 25-35 years old graduates. In graduates’ ratings there were positive but relatively low correlations between all variables related to importance, effectiveness and quality of Teacher Education Programs. Generally speaking students’ ratings about importance, effectiveness and quality of teacher education program were very positive. There was only one significant difference related to the background variables. Females rated higher the effectiveness of the program. The comparison of students’ and graduates’ perception about importance, effectiveness, and quality of teacher education programs showed that there were no significant differences between graduates and students in the overall ratings. However there were differences in some individual variables. Students rated higher in importance of “Continuous Professional Development”, effectiveness of “Critical Thinking Skills” and “Using Educational Technology” and quality of “Advice received from the advisor”. Graduates rated higher in importance of “Knowledge of Learning Environment” and effectiveness of “Continuous Professional Development”. According to the qualitative data of study 2 some graduates expressed that their perceptions have not changed about the importance, effectiveness, and quality of training that they received during their study time. They pointed out that teacher education programs have provided them the basic theoretical/formal knowledge and some training of practical routines. However, a majority of the teachers seems to have somewhat critical opinions about the teacher education. These teachers were not satisfied with teacher education programs because they argued that the programs failed to meet their practical demands in different everyday situations of the classroom e.g. in coping with students’ learning difficulties, multiprofessional communication with parents and other professional groups (psychologists and social workers), and classroom management problems. Participants also emphasized more practice oriented knowledge of subject matter, evaluation methods and teachers’ rights and responsibilities. Therefore, they (54.1% of participants) suggested that teacher education departments should provide more practice-based courses and programs as well as closer collaboration between regular schools and teacher education departments in order to fill gap between theory and practice.

Biotransformation and endocrine disruptive effects of contaminants in ringed seals - implications for monitoring and risk assessment

Marine mammals are exposed to persistent organic pollutants (POPs), which may be biotransformed to metabolites some of which are highly toxic. Both POPs and their metabolites may lead to adverse health effects, which have been studied using various biomarkers. Changes in endocrine homeostasis have been suggested to be sensitive biomarkers for contaminant-related effects. The overall objective of this doctoral thesis was to investigate biotransformation capacity of POPs and their potential endocrine disruptive effects in two contrasting ringed seal populations from the low contaminated Svalbard area and from the highly contaminated Baltic Sea. Biotransformation capacity was studied by determining the relationships between congener-specific patterns and concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and their hydroxyl (OH)- and/or methylsulfonyl (MeSO₂)-metabolites, and catalytic activities of hepatic xenobiotic-metabolizing phase I and II enzymes. The results suggest that the biotransformation of PCBs, PBDEs and toxaphenes in ringed seals depends on the congener-specific halogen-substitution pattern. Biotransformation products detected in the seals included OH-PCBs, MeSO₂-PCBs and –DDE, pentachlorophenol, 4-OHheptachlorostyrene, and to a minor extent OH-PBDEs. The effects of life history state (moulting and fasting) on contaminant status and potential biomarkers for endocrine disruption, including hormone and vitamin homeostasis, were investigated in the low contaminated ringed seal population from Svalbard. Moulting/fasting status strongly affected thyroid, vitamin A and calcitriol homeostasis, body condition and concentrations of POPs and their OH-metabolites. In contrast, moulting/fasting status was not associated with variations in vitamin E levels. Endocrine disruptive effects on multiple endpoints were investigated in the two contrasting ringed seal populations. The results suggest that thyroid, vitamin A and calcitriol homeostasis may be affected by the exposure of contaminants and/or their metabolites in the Baltic ringed seals. Complex and non-linear relationships were observed between the contaminant levels and the endocrine variables. Positive relationships between circulating free and total thyroid hormone concentration ratios and OH-PCBs suggest that OH-PCBs may mediate the disruption of thyroid hormone transport in plasma. Species differences in thyroid and bone-related effects of contaminants were studied in ringed and grey seals from low contaminated references areas and from the highly contaminated Baltic Sea. The results indicate that these two species living at the same environment approximately at the same trophic level respond in a very different way to contaminant exposure. The results of this thesis suggest that the health status of the Baltic ringed seals has still improved during the last decade. PCB and DDE levels have decreased in these seals and the contaminant-related effects are different today than a decade ago. The health of the Baltic ringed seals is still suggested to be affected by the contaminant exposure. At the present level of the contaminant exposure the Baltic ringed seals seem to be at a zone where their body is able to compensate for the contaminant-mediated endocrine disruption. Based on the results of this thesis, several recommendations that could be applied on monitoring and assessing risk for contaminant effects are provided. Circulating OH-metabolites should be included in monitoring and risk assessment programs due to their high toxic potential. It should be noted that endogenous variables may have complex and highly variable responses to contaminant exposure including non-linear responses. These relationships may be further confounded by life history status. Therefore, it is highly recommended that when using variables related to endocrine homeostasis to investigate/monitor or assess the risk of contaminant effects in seals, the life history status of the animal should be carefully taken into consideration. This applies especially when using thyroid, vitamin A or calcitriolrelated parameters during moulting/fasting period. Extrapolations between species for assessing risk for contaminant effects in phocid seals should be avoided.

Very preterm infants in Finland - Use of health care services and economic consequences during the first five years of life

The aim of this thesis was to study the health, the hospitalisations, and the use of communal health care services in very preterm children during the first five years of life. In addition, the effect of very preterm birth and prematurity-related morbidities on the costs of hospitalisations, other health care services and the cost per quality adjusted life years (QALY) were studied. This population-based study included all very preterm children (gestational age (GA) <32 weeks or birth weight<1501g, N=2 064) and full-term controls (GA 37+0−41+6, N=200 609) born in Finland during 2000-2003. The data sources included national register data, costing data from the participating hospitals and parental questionnaires. This study showed that most very preterm infants born in Finland survived without prematurity-related morbidities diagnosed during the first years of life. They required relatively little hospital care after the initial discharge, which accounted for the vast majority of the total four-year hospitalisation costs. However, a minority of children born very preterm later developing morbidities had a long initial length of stay and more re-admissions and outpatient visits during the five-year follow-up period. In particular, the number and costs of non-emergency outpatient visits were considerable in individuals with prematurity-related morbidities. The need and costs of hospitalisations decreased clearly with each follow-up year, even in individuals with morbidities. The health-care related costs during the fifth year of life in children born very preterm without prematurity-related morbidities were close to the costs in infants born healthy at term. The cost per QALY of 19,245 € was at an acceptable level already by four years of age in the very preterm population as a whole. Prematurity-related later morbidities and decreasing GA increased the costs per QALY. As the initial hospital stay accounted for a great majority of the total four-year costs, and the costs of hospitalisation decreased with each follow-up year, the cost per QALY is likely to decrease with age. In conclusion, the majority of costs arising after the initial hospitalisation were associated with morbidities related to prematurity. Therefore offering high-quality neonatal care to prevent later morbidities in very preterm survivors has a long-term impact on the cost per QALY. In addition, this study indicates that when estimating the costs of prematurity after the first year of life, one should calculate not only the hospitalisation costs, but also other costs for social welfare services, primary care, and therapies, as these exceed the hospitalisation costs in very preterm infants during the fifth year of life.

PET Imaging of Osteomyelitis. Feasibility of 18F-FDG, 68Ga-Chloride and 68Ga-DOTAVAP-P1 Tracers in Staphylococcal Bone Infections

Due to technical restrictions of the database system the title of the thesis does not show corretly on this page. Numbers in the title are in superscript. Please see the PDF-file for correct title. ---- Osteomyelitis is a progressive inflammatory disease of bone and bone marrow that results in bone destruction due to an infective microorganism, most frequently Staphylococcus aureus. Orthopaedic concern relates to the need for reconstructive and trauma-related surgical procedures in the fast grow¬ing population of fragile, aged patients, who have an increased susceptibility to surgical site infections. Depending on the type of osteomyelitis, infection may be acute or a slowly progressing, low-grade infection. Peri-implant infections lead to implant loosening. The emerging antibiotic resistance of com¬mon pathogens further complicates the situation. With current imaging methods, significant limitations exist in the diagnosing of osteomyelitis and implant-related infections. Positron emission tomography (PET) with a glucose analogue, 18F-fluoro¬deoxyglucose (18F-FDG), seems to facilitate a more accurate diagnosis of chronic osteomyelitis. The method is based on the increased glucose consumption of activated inflammatory cells. Unfortunately, 18F-FDG accumulates also in sterile inflammation regions and causes false-positive findings, for exam¬ple, due to post-operative healing processes. Therefore, there is a clinical need for new, more infection-specific tracers. In addition, it is still unknown why 18F-FDG PET imaging is less accurate in the detec¬tion of periprosthetic joint infections, most frequently due to Staphylococcus epidermidis. This doctoral thesis focused on testing novel PET tracers (68Ga-chloride and 68Ga-DOTAVAP-P1) for early detections of bone infections and evaluated the role of pathogen-related factors in the appli¬cations of 18F-FDG PET in the diagnostics of bone infections. For preclinical models of S. epidermidis and S. aureus bone/implant infections, the significance of the causative pathogen was studied with respect to 18F-FDG uptake. In a retrospective analysis of patients with confirmed bone infections, the significance of the presence or absence of positive bacterial cultures on 18F-FDG uptake was evalu¬ated. 18F-FDG and 68Ga-chloride resulted in a similar uptake in S. aureus osteomyelitic bones. However, 68Ga-chloride did not show uptake in healing bones, and therefore it may be a more-specific tracer in the early post-operative or post-traumatic phase. 68Ga-DOTAVAP-P1, a novel synthetic peptide bind¬ing to vascular adhesion protein 1 (VAP-1), was able to detect the phase of inflammation in healing bones, but the uptake of the tracer was elevated also in osteomyelitis. Low-grade peri-implant infec¬tions due to S. epidermidis were characterized by a low uptake of 18F-FDG, which reflects the virulence of the causative pathogen and the degree of leukocyte infiltration. In the clinical study, no relationship was found between the level of 18F-FDG uptake and the presence of positive or negative bacterial cul¬tures. Thus 18F-FDG PET may help to confirm metabolically active infection process in patients with culture-negative, histologically confirmed, low-grade osteomyelitis.

Beauty for Sale - An Empirical Study of Appearance-Related Consumption in Finland

This study examines appearance-related consumption in Finland. The theoretical portion discusses appearance-related consumption, on one hand from a consumer culture perspective, as both a possibility and responsibility for everyone; and on the other hand, from the point of view of behaviour and attitudes associated with sociodemographic and lifestyle-related factors. The empirical part of the study concentrates on the following aspects: 1) Finns’ appearance-related consumption patterns, attitudes towards appearance-related consumption and attending to one’s looks through consumption, as well as general changes in consumption patterns and attitudes; 2) gender differences in attitudes and consumption patterns, and their possible changes over time, and; 3) other differences among population groups in attitudes and consumption patterns, and their possible changes over time. The following dissertation utilises data from seven different nationally representative surveys. Data include Finnish Household Budget surveys from 1998 (N=4 359), 2001 (N=5 495) and 2006 (N=4 007), as well as, The Everyday Life and Well-being Survey (N=908) collected in 2011, and Finland 1999 (N=2 417), Finland 2004 (N=3 574) and Finland 2009 (N=1 202) surveys. The study indicates that Finns’ relationship to appearance-related consumption is, generally, somewhat inconsistent. In Finland, a significant share of a household’s total spending, around the EU average, is allocated to products and services related to appearance. In addition, at an attitudinal level, physical appearance is important to most Finnish consumers. However, in many respects, these attitudes reflect a certain reservation towards appearance-related consumption practices. The number of those consumers who see themselves as truly dedicated to attending to their looks through consumption is quite small, whereas the amount of those willing to take a reserved or even negative attitude towards appearance-related consumption is clearly higher. Attitudes towards attending to one’s looks and the importance of appearance-related consumption had not changed during the past decade. Study shows that at present, appearance-related consumption is a form of consumption that is particularly important to women, younger consumers, people with middle or higher income, and those with normal weight. Gender is in the key role when explaining appearance-related consumption and contrary to common belief, gender differences seem to have stayed quite stable. The results also indicate that, to some extent, differences between younger and older age groups might be diminishing.

Benzodiazepines and Cognitive Functioning in Older Adults. With Emphasis on Long-Term Use and Withdrawal

Benzodiazepines (BZD) and benzodiazepine related drugs (RD) are the most commonly used psychotropics among the aged. The use of other psychotropics taken concomitantly with BZD/ RD or their cognitive effects with BZD/RD have not been studied frequently. The aim of this academic thesis was to describe and analyse relationships between the use of BZD/RD alone or concomitantly with antipsychotics, antidepressants, opioids, antiepileptics, opioids and anticholinergics in the aged and their health. Especially, the relationships between long-term use of BZD/RD and cognitive decline were studied. Additionally, the effect of melatonin on BZD/RD withdrawal and the cognitive effects of BZD/RD withdrawal were studied. This study used multiple data sets: the first study (I) was based on clinical data containing aged patients (≥65 years; N=164) admitted to Pori City Hospital due to acute disease. The second data set (Studies II and III) was based on population-based data from the Lieto Study, a clinico-epidemiological longitudinal study carried out among the aged (≥65 years) in the municipality of Lieto. Follow-up data was formed by combining the cohort data collected in 1990-1991 (N=1283) and in 1998-1999 (N=1596) from those who participated in both cohorts (N=617). The third data set (Studies IV and V) was based on the Satauni Study’s data. This study was performed in the City of Pori in 2009-2010. In the RCT part of the Satauni Study, ninety-two long-term users of BZD/RD were withdrawn from their drugs using melatonin against placebo. The change of their cognitive abilities was measured during and after BZD/ RD withdrawal. BZD/RD use was related to worse cognitive and functional abilities, and their use may predict worse cognitive outcomes compared with BZD/RD non-users. Hypnotic use of BZD/RD could be withdrawn with psychosocial support in motivated participants, but melatonin did not improve the withdrawal results compared to those with placebo. Cognitive abilities in psychomotor tests did not show, or showed only modest, improvements for up to six months after BZD/RD withdrawal. This suggests that the cognitive effects of BZD/RD may be longlasting or permanent.

Determinants of Bone Strength and Predictors of Hip Fracture among Finnish Adults. Results from the Health 2000 Survey and the Mini-Finland Health Survey

The objective of this thesis was to identify the determinants of bone strength and predictors of hip fracture in representative samples of Finnish adults. A secondary objective was to construct a simple multifactorial model for hip fracture prediction over a 10-year follow-up period. The study was based on the Health 2000 Survey conducted during 2000 to 2001 (men and women aged 30 years or over, n=6 035) and the Mini-Finland Health Survey conducted during 1978 to 1980 (women aged 45 years or over, n=2 039). Study subjects participated in health interviews and comprehensive health examination. In the Health 2000 Survey, bone strength was assessed by means of calcaneal quantitative ultrasound (QUS). The follow-up information about hip fractures was drawn from the National Hospital Discharge Register. In this study, age, weight, height, serum 25-hydroxyvitamin D (S-25(OH)D), physical activity, smoking and alcohol consumption as well as menopause and eventual HRT in women were found to be associated with calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS). Parity was associated with a decreased risk of hip fracture in postmenopausal women. Age, height, weight or waist circumference, quantitative ultrasound index (QUI), S-25(OH)D and fall-related factors, such as maximal walking speed, Parkinson’s disease, and the number of prescribed CNS active medication were significant independent predictors of hip fracture. At the population level, the incremental value of QUS appeared to be minor in hip fracture prediction when the fall-related risk factors were taken into account. A simple multifactorial model for hip fracture prediction presented in this study was based on readily available factors (age, gender, height, waist circumference, and fallrelated factors). Prospective studies are needed to test this model in patient-based study populations.