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  • Mohebbi, Simin Z. (Helsingfors universitet, 2008)
    The present study assessed the prevalence of and risk factors for Early Childhood Caries (ECC) in children 12- to 36- month-old and evaluated the impacts of an educational intervention on ECC prevention in the 12- to 15-month-old cohort. The target population included 12- to 36-month-olds (n = 504) and their mothers attending the vaccination offices of 18 randomly selected public health centers of Tehran city. The mother was first interviewed by a structured questionnaire covering background factors, feeding habits, daytime sugar intake, mother’s and child’s oral cleaning habits, and mother’s perception toward her ability to maintain the child’s oral hygiene; then the child’s clinical dental examination was carried out covering caries experience and dental plaque status. In addition, the 12- to 15-month-olds (n = 242) were assigned to a six-month interventional study. The 18 health centers were randomly allocated into two groups for intervention and one for control. The mothers in the intervention groups received education on caries prevention from the vaccination staff with extra motivation as reminder phone calls in one of the intervention groups. The outcome was measured as differences in increments of enamel and dentinal caries. The results showed that the prevalence of ECC was rather high (3%-26%) in the three age groups, and almost all dmft was due to untreated caries. The majority of the children showed visible plaque on central upper incisors. Oral cleaning on a daily basis was reported for just 68% of mothers and 39% of children. The frequency of oral cleaning and good oral hygiene of the child were directly proportional to the mother’s own toothbrushing frequency. Of the children, 98% were solely or partly breastfed. ECC was more likely to occur among those for whom the burden of milk-bottle feeding at night existed (OR = 4.9), while breastfeeding per se, its duration, and its nighttime burden were not related to ECC. The indicator of daytime sugar intake also did not show a clear relationship with ECC. The educational intervention applying a pamphlet with some extra motivation and implemented by non-dental staff of public health centers appeared to be successful in preventing caries increments. To improve oral health status among the young children in countries with a developing oral health system, community-based oral health educational programs should be established by involving non-dental staff of health settings who are more frequently in contact with these children. Parents should be encouraged to realize that they play the dominant role in the oral health care of their children. Parents’ own oral health behaviors should be emphasized in dental and general health settings.
  • Toljamo, Tuula (Helsingin yliopisto, 2012)
    Chronic obstructive pulmonary disease (COPD) is an under-diagnosed and life-threatening progressive disease. Early symptoms of COPD include excessive sputum production and chronic cough. The primary risk factor of this disease in the western world is smoking. COPD is confirmed by spirometry, which does not totally reveal reversible airway obstruction. This study, conducted mainly in the Northern Finland, aimed to assess 1) smoking habits and smoking cessation in healthy middle-aged and young adults, 2) the prevalence of COPD and role of spirometry and prolonged respiratory symptoms in the diagnosis of COPD of smoking middle-aged adults, 3) the association of symptoms of chronic bronchitis with smoking habits in young adult males, and 4) to seek and to identify new potential biomarkers related to early COPD using non-hypothesis driven non-biased proteomics. A two-year prospective study included two visits to evaluate symptoms in healthy cigarette smokers, to screen new COPD cases and to assess the success of smoking cessation using motivational counselling and pharmacological therapies. In addition, a quantitative cross-sectional questionnaire survey was conducted in 1163 male conscripts during their military service in Northern Finland. A lung tissue proteomic approach was used to identify new COPD biomarkers. Spirometry revealed COPD by GOLD criteria in 11,0% and by national criteria in 15.3 % of originally asymptomatic chronic smokers. Further, chronic cough or sputum production was detected in 62.0% of the participants. After two years, 23.3% of adults had succeeded in quitting smoking. In young adults, 46.5% were daily smokers. The prevalence of self-reported chronic cough and sputum production was high in daily smokers (40.7%). The majority (60.2%) of the daily young smokers had made quit attempts and 46.9% of them had used nicotine replacement therapy (NRT). Based on the lung tissue proteomics, surfactant protein A (SP-A) was one of the most highly elevated spots in the COPD lung. The plasma SP-A concentration was higher both in chronic smokers and in COPD as compared to the non-smokers, and declined significantly during 2-year follow-up in those who succeeded to quit smoking compared to those who continued to smoke. To conclude there is remarkable burden of chronic bronchitis and COPD in the groups of chronic smokers who considered themselves as healthy. Motivational counselling seems to be successful, since over 23% of the adult smokers succeeded in stopping smoking. SP-A is a potential new biomarker for COPD although it needs further evaluation.
  • Gao, Weiguo (Helsingin yliopisto, 2010)
    Objectives of this study were to determine secular trends of diabetes prevalence in China and develop simple risk assessment algorithms for screening individuals with high-risk for diabetes or with undiagnosed diabetes in Chinese and Indian adults. Two consecutive population based surveys in Chinese and a prospective study in Mauritian Indians were involved in this study. The Chinese surveys were conducted in randomly selected populations aged 20-74 years in 2001-2002 (n=14 592) and 35-74 years in 2006 (n=4416). A two-step screening strategy using fasting capillary plasma glucose (FCG) as first-line screening test followed by standard 2-hour 75g oral glucose tolerance tests (OGTTs) was applied to 12 436 individuals in 2001, while OGTTs were administrated to all participants together with FCG in 2006 and to 2156 subjects in 2002. In Mauritius, two consecutive population based surveys were conducted in Mauritian Indians aged 20-65 years in 1987 and 1992; 3094 Indians (1141 men), who were not diagnosed as diabetes at baseline, were reexamined with OGTTs in 1992 and/or 1998. Diabetes and pre-diabetes was defined following 2006 World Health Organization/ International Diabetes Federation Criteria. Age-standardized, as well as age- and sex-specific, prevalence of diabetes and pre-diabetes in adult Chinese was significantly increased from 12.2% and 15.4% in 2001 to 16.0% and 21.2% in 2006, respectively. A simple Chinese diabetes risk score was developed based on the data of Chinese survey 2001-2002 and validated in the population of survey 2006. The risk scores based on β coefficients derived from the final Logistic regression model ranged from 3 – 32. When the score was applied to the population of survey 2006, the area under operating characteristic curve (AUC) of the score for screening undiagnosed diabetes was 0.67 (95% CI, 0.65-0.70), which was lower than the AUC of FCG (0.76 [0.74-0.79]), but similar to that of HbA1c (0.68 [0.65-0.71]). At a cut-off point of 14, the sensitivity and specificity of the risk score in screening undiagnosed diabetes was 0.84 (0.81-0.88) and 0.40 (0.38-0.41). In Mauritian Indian, body mass index (BMI), waist girth, family history of diabetes (FH), and glucose was confirmed to be independent risk predictors for developing diabetes. Predicted probabilities for developing diabetes derived from a simple Cox regression model fitted with sex, FH, BMI and waist girth ranged from 0.05 to 0.64 in men and 0.03 to 0.49 in women. To predict the onset of diabetes, the AUC of the predicted probabilities was 0.62 (95% CI, 0.56-0.68) in men and 0.64(0.59-0.69) in women. At a cut-off point of 0.12, the sensitivity and specificity was 0.72(0.71-0.74) and 0.47(0.45-0.49) in men; and 0.77(0.75-0.78) and 0.50(0.48-0.52) in women, respectively. In conclusion, there was a rapid increase in prevalence of diabetes in Chinese adults from 2001 to 2006. The simple risk assessment algorithms based on age, obesity and family history of diabetes showed a moderate discrimination of diabetes from non-diabetes, which may be used as first line screening tool for diabetes and pre-diabetes, and for health promotion purpose in Chinese and Indians.
  • Hukkinen, Katja (Helsingin yliopisto, 2007)
    The greatest effect on reducing mortality in breast cancer comes from the detection and treatment of invasive cancer when it is as small as possible. Although mammography screening is known to be effective, observer errors are frequent and false-negative cancers can be found in retrospective studies of prior mammograms. In the year 2001, 67 women with 69 surgically proven cancers detected at screening in the Mammography Centre of Helsinki University Hospital had previous mammograms as well. These mammograms were analyzed by an experienced screening radiologist, who found that 36 lesions were already visible in previous screening rounds. CAD (Second Look v. 4.01) detected 23 of these missed lesions. Eight readers with different kinds of experience with mammography screening read the films of 200 women with and without CAD. These films included 35 of those missed lesions and 16 screen-detected cancers. CAD sensitivity was 70.6% and specificity 15.8%. Use of CAD lengthened the mean time spent for readings but did not significantly affect readers sensitivities or specificities. Therefore the use of applied version of CAD (Second Look v. 4.01) is questionable. Because none of those eight readers found exactly same cancers, two reading methods were compared: summarized independent reading (at least a single cancer-positive opinion within the group considered decisive) and conference consensus reading (the cancer-positive opinion of the reader majority was considered decisive). The greatest sensitivity of 74.5% was achieved when the independent readings of 4 best-performing readers were summarized. Overall the summarized independent readings were more sensitive than conference consensus readings (64.7% vs. 43.1%) while there was far less difference in mean specificities (92.4% vs. 97.7%). After detecting suspicious lesion, the radiologist has to decide what is the most accurate, fast, and cost-effective means of further work-up. The feasibility of FNAC and CNB in the diagnosis of breast lesions was compared in non-randomised, retrospective study of 580 (503 malignant) breast lesions of 572 patients. The absolute sensitivity for CNB was better than for FNAC, 96% (206/214) vs. 67% (194/289) (p < 0.0001). An additional needle biopsy or surgical biopsy was performed for 93 and 62 patients with FNAC, but for only 2 and 33 patients with CNB. The frequent need of supplement biopsies and unnecessary axillary operations due to false-positive findings made FNAC (294 ) more expensive than CNB (223 ), and because the advantage of quick analysis vanishes during the overall diagnostic and referral process, it is recommendable to use CNB as initial biopsy method.
  • Ylihärsilä, Hilkka (Helsingin yliopisto, 2008)
    Theory of developmental origins of adult health and disease proposes that experiences during critical periods of early development may have consequences on health throughout a lifespan. Thesis studies aimed to characterize associations between early growth and some components of the metabolic syndrome cluster. Participants belong to two epidemiological cohorts with data on birth measurements and, for the younger cohort, on serial recordings of weight and height during childhood. They were born as singletons between 1924-33 and 1934-44 in the Helsinki University Central Hospital, and 500 and 2003 of them, respectively, attended clinical studies at the age of 65-75 and 56-70 years, respectively. In the 65-75 year old men and women, the well-known inverse relationship between birth weight and systolic blood pressure (SBP) was confined to people who had established hypertension. Among them a 1-kg increase in birth weight was associated with a 6.4-mmHg (95% CI: 1.0 to 11.9) decrease in SBP. This relationship was further confined to people with the prevailing Pro12Pro polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene. People with low birth weight were more likely to receive angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB, p=0.03), and, again, this relationship was confined to the carriers of the Pro12Pro (p=0.01 for interaction). These results suggest that the inverse association between birth weight and systolic BP becomes focused in hypertensive people because pathological features of BP regulation, associated with slow fetal growth, become self-perpetuating in adult life. Insulin resistance of the Pro12Pro carriers with low birth weight may interact with the renin-angiotensin system leading to raised BP levels. Habitual physical activity protected men and women who were small at birth, and thus at increased risk for the development of type 2 diabetes, against glucose intolerance more strongly. Among subjects with birth weight ≤3000 g, the odds ratio (OR) for glucose intolerance was 5.2 (95% CI: 2.1 to 13) in those who exercised less than 3 times per week compared to regular exercisers; in those who scored their exercise light compared with moderate exercisers (defined as comparable to brisk walking) the OR was 3.5 (1.5 to 8.2). In the 56-70 year old men a 1 kg increase in birth weight corresponded to a 4.1 kg (95% CI: 3.1 to 5.1) and in women to a 2.9 kg (2.1 to 3.6) increase in adult lean mass. Rapid gain in body mass index (BMI), i.e. crossing from an original BMI percentile to a higher one, before the age of 2 years increased adult lean mass index (LMI, lean mass/height squared) without excess fat accumulation whereas rapid gain in BMI during later childhood, despite the concurrent rise in LMI, resulted in a relatively higher increase in adult body fat mass. These findings illustrate how genes, the environment and their interactions, early growth patterns, and adult lifestyle modify adult health risks which originate from early life.
  • Perälä, Mia-Maria (Helsingin yliopisto, 2014)
    Epidemiological studies have shown that low birth weight and slow growth during infancy predict an increased risk of metabolic diseases, including type 2 diabetes and cardiovascular disease, in adult life. Unhealthy dietary habits are also closely linked with these diseases. However, few results are available on whether dietary habits play a role in the association between birth size and disease risk in later life. The aim of this thesis was to determine whether body size at birth is associated with food and nutrient intake later in life and whether birth weight modifies the relationship between salt intake and blood pressure. In addition, the impact of early growth on postprandial metabolism was examined. These studies included 2003 men and women born in Helsinki between 1934 and 1944 with detailed information of their birth weight and childhood growth. They participated in a clinical examination between 2001 and 2004. In the clinic, their weight, height and blood pressure were measured and they filled a validated food-frequency questionnaire. Of those who attended the clinical study, 12 obese individuals with a slow increase in body mass index (BMI) during the first year of life and 12 BMI- and age-matched controls were recruited to participate in the postprandial studies. Each participant consumed six different test meals in random order. Body size at birth was positively associated with consumption of fruits and berries and intake of carbohydrates, sugars and fibre, and inversely associated with intake of fat. Salt intake was related to systolic blood pressure among low birth weight participants (birth weight ≤ 3050 g) but not among participants whose birth weight was > 3050 g. Salt intake was not significantly associated with diastolic blood pressure, either in the low birth weight or high birth weight groups. Early growth affected the postprandial responses, and insulin and triglyceride responses were significantly higher in the group that grew slowly during early life than in the controls. Individuals with slow early growth also showed higher appetite regulatory hormone peptide YY responses than did the controls. This study showed that individuals born with small body size may be programmed towards unhealthy dietary habits. In addition, they are sensitive to the blood pressure-raising effect of salt and therefore, may especially benefit from a reduction in salt intake. Slow growth during early life adversely affects postprandial insulin and triglyceride responses. Unhealthy dietary habits and elevated postprandial responses may be one underlying mechanism explaining the increased risk of metabolic diseases associated with nonoptimal early growth. Early growth may also alter appetite regulatory hormone secretion, which could be one explanation why individuals born small or who grow slowly during infancy are unlikely to become obese in later life.
  • Salonen, Minna (Helsingin yliopisto, 2011)
    The Developmental Origins of Health and Disease Hypothesis proposes that adverse health outcomes in adult life are in part programmed during fetal life and infancy. This means that e.g. restricted nutrition during pregnancy programmes the offspring to store fat more effectively, to develop faster and to reach puberty earlier. These adaptations are beneficial in terms of short term survival. However, in developed countries these adaptations often lead to an increased risk of obesity and metabolic disturbances in later life, due to a mismatch between the prenatal and postnatal environment. This thesis aimed to study the role of early growth in people who are obese as adults, but metabolically healthy as well as in those who are normal in weight but metabolically obese. Other study aims were to assess whether physical activity and cardiorespiratory fitness are programmed early in life. The role of socioeconomic status in the development of obesity from a life course setting was also studied. These studies included 2003 men and women born in Helsinki between 1934 and 1944 with detailed information of their prenatal and childhood growth as well as living conditions. They participated in the detailed clinical examination during the years 2001-2004. A sub-group of the subjects participated in the UKK Institute 2-kilometre walk test. Metabolic syndrome was defined according to the 2005 criteria of the International Diabetes Federation. Among the obese men and women 20 % were metabolically healthy. Those with metabolic syndrome did not differ in birth size compared to the healthy ones, but by two years of age, they were lighter and thinner, and remained so up to 11 years. The period when changes in BMIs were predictive of the metabolic syndrome was from birth to 7 years. Of the normal weight individuals 17 % were metabolically obese. Again, there were no differences in birth size. However, by the age 7 years, those men who later developed metabolic syndrome were thinner. Gains in BMI during the first two years of life were protective of the syndrome. Children who were heavier, and especially taller, were more physically active, exercised with higher intensity and had higher cardiorespiratory fitness in their adult life than those who were shorter and thinner as children. Lower educational attainment and lower adult social class were associated with obesity in both men and women. Childhood social class was inversely associated with body mass index only in men while lower household income was associated with higher BMI in women. These results support the role of early life factors in the development of metabolic syndrome and adult life style. Early detection of risk factors predisposing to these conditions is highly relevant from a public health point of view.
  • Pesonen, Maria (Helsingin yliopisto, 2008)
    Atopy-related allergic diseases, i.e. allergic rhinoconjunctivitis, atopic dermatitis and asthma, have increased in frequency in the industrialized countries. In order to reverse this trend, effective preventive strategies need to be developed. This requires a better understanding of the early-life events leading to the expression of the atopic phenotype. The present study has aimed at defining early-life factors and markers associated with the subsequent development of allergic diseases in a cohort of 200 healthy, unselected Finnish newborns prospectively followed up from birth to age 20 years. Their mothers were encouraged to start and maintain exclusive breastfeeding as long as it was nutritionally sufficient for the infant. Consequently, all the infants received some duration of exclusive breastfeeding, 58% of the infants were on exclusive breastfeeding for the first 6 months of life, and 18% received this feeding at least for the first 9 months. Of the infants, 42% had a family history of allergy. After the first year of follow-up, the children were re-assessed at ages 5, 11 and 20 years with clinical examination, skin prick testing, and parental and personal interviews. Exclusive breastfeeding for over 9 months was associated with atopic dermatitis and symptoms of food hypersensitivity at age 5 years, and with symptoms of food hypersensitivity at age 11 years in the children with a familial allergy. Subjects with allergic symptoms or a positive skin prick test in childhood or adolescence had lower retinol concentrations during their infancy and childhood than others. An elevated cord serum immunoglobulin E concentration predicted subsequent atopic manifestations though with modest sensitivity. Children and adolescents with allergic symptoms, skin prick test positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the nonatopic subjects. In conclusion, prolonging strictly exclusive breastfeeding for over 9 months of age was not of help in prevention of allergic symptoms; instead, it was associated with increased atopic dermatitis and food hypersensitivity symptoms in childhood. Due to the modest sensitivity, cord serum IgE is not an effective screening method for atopic predisposition in the general population. Retinol and cholesterol concentrations in infancy were inversely associated with the subsequent development of allergic symptoms. Based on these findings, it is proposed that there may be differences in the inborn regulation of retinol and cholesterol levels in children with and without a genetic susceptibility to atopy, and these may play a role in the development of atopic sensitization and allergic diseases.
  • Lahti, Marius (Helsingin yliopisto, 2012)
    Previous studies suggest that a suboptimal early life environment may predict an increased risk of adult personality disorders. However, most of this evidence is based on studies with retrospective accounts of early adversity. This retrospective design may induce a bias and hinder interpretation of the direction of causality. This thesis examines, in a longitudinal study setting, the developmental origins of personality disorders severe enough to justify hospitalisation. The focus is on pre- and postnatal growth and on parental separation in childhood due to temporary evacuations from Finland during World War II in the etiology of both any and dramatic personality disorders requiring hospitalisation. The study cohort is the Helsinki Birth Cohort Study, which comprises 13,345 individuals born 1934-1944. Data on early life growth, on childhood evacuations, and on the diagnoses of personality disorders were drawn from birth- and child welfare records and national registers. These objective record- and register-based data enabled the longitudinal design of the studies. In the current study cohort, there were 1,781 individuals who had been separated from their parents in childhood. There were 202 subjects who had been hospitalised for personality disorders, and 77 individuals with dramatic personality disorders. The results showed that a small head circumference and a small head-to-length ratio at birth predicted an increased risk of any severe personality disorder among men and a small placental surface area at birth predicted dramatic personality disorders among women. Slower gain in BMI between birth and six months of age, faster gains in weight and in BMI between six months and one year, and slower gains in weight and in BMI between seven and 11 years of age also predicted personality disorders among men. Slower height growth between two and seven years of age predicted an increased risk of personality disorders among women. The associations between infancy and childhood growth and severe personality disorders among men were especially characteristic of dramatic personality disorders, and were independent of comorbid mood disorders. Temporary separation from parents, particularly in the first five years of life, predicted an increased risk of severe personality disorders, and among men, of dramatic personality disorders. The effects of early parental separation were specific to personality disorders, since they emerged in comparisons to both healthy control participants and to individuals with other mental disorders. These longitudinal study findings strongly support an etiological role for early life, both pre- and postnatal, environmental adversity in the development of severe personality disorders, especially dramatic personality disorders. Vulnerability to severe personality disorders is developmentally programmed in early life.
  • Alastalo, Hanna (Helsingin yliopisto, 2013)
    Experienced stress in childhood might have been so severe that it has effects throughout the life course. It has been suggested that early life stress may extend consequences on psychological and physical well-being. Previous findings focusing upon consequences of early life stress are however limited and mostly based upon retrospective studies. Still little is known about the consequences of early life stress, such as war separation on physical health from a longitudinal aspect. This thesis aimed to study cardiovascular mortality and morbidity in late adulthood among people who experienced separation without their parents to temporary foster care during World War II (WWII). Other study aims were to examine cardiovascular health, blood pressure levels and physical and psychosocial functioning in the separated participants. People who were not separated served as controls. Participants in this study belong to the Helsinki Birth Cohort Study (HBCS) which includes 13,345 people born in Helsinki between 1934 and 1944 and visited child welfare clinics in the city. Of these 13.5% had experienced evacuation abroad. Data on parental separation was obtained from National Archives, and information on use of medication or events on coronary heart disease (CHD), hypertension, stroke and cardiovascular deaths are obtained from national registers during a follow-up period from 1971-2002. Clinical study cohort included 2003 men and women who participated in the detailed clinical examination during the years 2001-2004. All these participants are included the cardiovascular health sub-study and of them 16.0% were separated participants. The blood pressure sub-study consist of 1361 non-obese subjects whose body mass index (BMI) were <30 kg/m2, of whom 14.1% had experienced evacuation abroad. The sub-study of physical and psychosocial functioning included 1803 people and of these separated participants were 14.8%. In all sub-studies the participants who did not experience war separation in childhood served as controls. Among the separated participants over one-third were separated in toddlerhood and approximately duration of separation was two years. The separated group were older and they have lower socioeconomic status in childhood and adulthood than among the non-separated controls. War separation was associated with higher CHD morbidity, the prevalence of cardiovascular disease (CVD) and diabetes. The separation in early childhood and the duration of separation were associated with higher CHD morbidity. Duration of separation over three years showed higher prevalence of CVD in later life. Despite this the evidence of higher hospitalizations and mortality was not found. In addition war separation predicted higher blood pressure levels in late adulthood and moreover increases in the risk of impaired physical functioning. The separation in early childhood was associated with higher blood pressure levels likewise duration in less than a year and over three years. The separation in school age and duration for over two years were associated with the later life lower physical functioning. The effects of separation in overall health were more pronounced among the separated men than women. These studies suggest that early life stress experience such as temporary parental separation may have consequences on cardiovascular health and general well-being through the lifespan. The war separation and its timing and duration are stressors, which could have long-term influence on critical development phases and thereby increases the risk of chronic non-communicable diseases in later life.
  • Mononen, Riikka (Helsingin yliopisto, 2014)
    The purpose of this thesis was to investigate the effectiveness of early mathematics interventions for young children with low performance in mathematics. Previous research has indicated that early mathematics skills are a strong predictor of later mathematics performance. The goal of early mathematics support by means of interventions is to improve mathematics performance, and consequently, to diminish the possibility of mathematics learning disability emerging later on. This thesis sought to complement and extend previous research in the field of early mathematics interventions, by reviewing early mathematics interventions, and investigating the effectiveness of two early mathematics intervention programmes. Study I reviewed mathematics interventions (N = 19) aimed at 4–7-year-old children with low performance in mathematics. For each intervention, effect sizes were calculated for mathematics outcome measures, and the pedagogical implementation was described. The effectiveness of the RightStart Mathematics (RS) (Cotter, 2001) instruction was investigated in Studies II and III. In Study II, the instruction was provided for Finnish kindergartners (RS group: n = 38, comparison group: n = 32) in general education classrooms, with focus on low-performing children. In Study III, the RS instruction was provided in special education classrooms for children with a specific language impairment (SLI group: n = 9, comparison group: n = 32). In Study IV, a mathematics intervention programme Improving Mathematics Skills in the Second Grade (IMS-2) (Mononen & Aunio, 2012) was developed, and its effectiveness for second graders performing low in mathematics was examined (IMS-2 group: n = 11, low-performing controls: n = 13 and typically performing controls: n = 64). In Studies II-IV, quantitative methods were used for analysing the interventions’ effects. According to the results of the review, in the majority of the interventions, the mathematics skills of the participating children improved more than the skills of the children in control groups, with effect sizes varying from small to large. Progress in mathematics learning was evident when instruction included one or more of the following instructional features: explicit instruction, peer-assisted instruction, applying a concrete-representational-abstract sequence, computer assisted instruction, or games. Study II showed that the RS instruction was as effective as the typical Finnish kindergarten mathematics instruction. The counting skills of the initially low-performing children improved to the level of their typically performing peers. Follow-up in the first grade revealed performance differences between the initially low- and typically performing children, highlighting the importance of continuously monitoring progress, and providing intensified support. In Study III, children with a SLI receiving RS instruction improved their counting skills to the level of their peers. In the first grade follow-up, the children with SLI performed similarly to their peers in addition and subtraction skills (accuracy) and multi-digit number comparison. In Study IV, the mathematics skills of the second graders participating in the IMS-2 intervention did not improve more than the skills of the children in control groups. However, the study provided valuable information about the functionality of the IMS-2 programme’s intensity and content. To conclude, in general, the results indicate that rather than waiting for children to fail, mathematics interventions can be used successfully to promote the early mathematics skills of children with low performance in mathematics, already before the onset of formal schooling and in the early grades. Therefore, identifying low performance in mathematics and providing sufficient support should be emphasised already in early childhood education, in accordance with the Finnish three-tiered educational support system. Keywords: early mathematics skills, low performance in mathematics, mathematics learning disability, mathematics intervention, review, specific language impairment, educational support
  • Tegelberg, Saara (Helsingin yliopisto, 2013)
    Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited neurodegenerative disorder caused by mutations in the cystatin B (CSTB) gene. Although the gene behind the disease has long been known, the exact physiological function of CSTB and the molecular pathogenesis in EPM are largely unknown. In my thesis, I have characterized the developmental and degenerative processes in the brains of young, pre-symptomatic and fully symptomatic Cstb-deficient mice. This mouse is an excellent model for EPM1, as its phenotype closely resembles the human disease. To study the spatiotemporal disease progression, we conducted systematic analyses of changes in neurons and glia in Cstb-deficient brains. We saw significant microgliosis already in two-week-old Cstb-deficient animals, before the appearance of myoclonus at 1 month of age. Early microgliosis was followed by astroglial activation along with progressive neuron loss and brain atrophy. The phenotype of activated microglial cells changed during disease progression. To characterize molecular alterations in Cstb-deficient mouse brains, we performed a gene expression profiling. As the cerebellum shows the earliest and most prominent pathological changes, we focused the gene expression analyses on cerebellum of young Cstb-deficient animals. The results implied disturbances in pathways related to synaptic development, structure and function. Immunohisto¬chemical, electrophysiological and ligand binding studies suggested the involvement of especially GABAergic synapses. Data also showed alterations in genes related to the cytoskeleton and intracellular transport, along with pathways implying activation of immune defence. To shed light on the neuron death seen in the brain of Cstb-deficient mouse, we studied the effect of oxidative stress on Cstb-deficient neurons. As CSTB is an inhibitor of cysteine cathepsins and thus is proposed to protect cells from adverse cathepsin functions, we studied also the role of cathepsins in oxidative stress. The results show that oxidative insult increases the expression of both CSTB and cathepsin B. Cstb-deficient cells are sensitized to oxidative stress-induced damage and cell death, which is at least partially mediated through increased cathepsin B activity. These findings in Cstb-deficient mouse suggest that CSTB has an important role in protecting normal cellular integrity and functions along with affecting the development and function of synaptic connections. Our results also imply that microglia have a central role in nervous system damage already before the appearance of symptoms of EPM1. The results of my thesis study have guided the research of our group into new fields by revealing the importance of microglia in the early stages of EPM1. This study also shows that CSTB-deficiency leads not only to neurodegeneration per se, but also results in developmental defects whose consequences manifest later in EPM1 disease progression.
  • Sihvola, Elina (Helsingin yliopisto, 2010)
    Early-onset psychiatric illnesses effects scatter to academic achievements as well as functioning in familial and social environments. From a public health point of view, depressive disorders are the most significant mental health disorders that begin in adolescence. Using prospective and longitudinal design, this study aimed to increase the understanding of early-onset depressive disorders, related mental health disorders and developing substance use in a large population-derived sample of adolescent Finnish twins. The participants of this study, FinnTwin12, an ongoing longitudinal population-based study, came from Finnish families with twins born in 1983-87 (exhaustive of five birth cohorts, identified from Finland s Central Population Register). With follow-up ongoing at age 20-24, this thesis assessed adolescent mental health in the first three waves, starting from baseline age 11-12 to follow-ups at age 14 and 17½. Some 5600 twins participated in questionnaire assessments of a wide range of health related behaviors. Mental health was further assessed among an intensively studied subsample of 1852 adolescents, who completed also professionally administered interviews at age 14, which provided data for full DSM-IV/III-R (Diagnostic and Statistical Manual for Mental Health disorders, 4th and 3rd editions) diagnoses. The participation rates of the study were 87-92%. The results of the study suggest, that the diagnostic criteria for major depressive disorder (MDD) may not capture youth with clinically significant early-onset depressive conditions outside clinical settings. Milder cases of depression, namely adolescents fulfilling the diagnostic criteria for minor depressive disorder, a qualitatively similar condition to MDD with fewer symptoms are also associated with marked suicidal thoughts, plans and attempts, recurrences and a high degree of comorbidity. Prospectively and longitudinally, early-onset depressive disorders were of substantial importance in the context of other mental health disorders and substance use behaviors: These data from a large population-derived sample established a substantial overlap between early-onset depressive disorders and attention deficit hyperactivity disorder in adolescent females, both of them significantly predictive for development of substance use among girls. Only in females baseline DSM-IV ADHD symptoms were strong predictors of alcohol abuse and dependence and illicit drug use at age 14 and frequent alcohol use and illicit drug use at age 17.½ when conduct disorder and previous substance use were controlled for. Early-onset depressive disorders were also prospectively and longitudinally associated to daily smoking behavior, smokeless tobacco use, frequent alcohol use and illicit drug use and eating disorders. Analysis of discordant twins suggested that these predictive associations were independent of familial confounds, such as family income, structure and parental models. In sum, early-onset depressive disorders predict subsequent involvement of substance use and psychiatric morbidity. A heightened risk for substance use is substantial also among those depressed below categorical diagnosis of MDD. Whether early recognition and interventions among these young people hold potential for substance use prevention further in their lives has potential public health significance and calls for more research. Data from this population-derived sample with balanced representation of boys and girls, suggested that boys and girls with ADHD behaviors may differ from each other in their vulnerability to substance use and depressive disorders: the data suggest more adverse substance use outcome for girls that was not attenuated by conduct disorder or previous substance use. Further, the prospective associations of early-onset depressive disorders and future elevated levels of addictive substance use is not explained by familial factors supporting future substance use, which could have important implications for substance use prevention.
  • Bingham, Clarissa (Helsingin yliopisto, 2012)
    Men at the age of military service are in a transition phase between childhood home and independent adulthood. They are starting to make own decisions about their future and ways of life including also eating habits. In Finland, all men are liable to military service and a majority (nearly 80%) complete service. The increasing prevalence of overweight and obesity also among soldiers has raised concerns about conscripts eating habits. This doctoral dissertation studied eating habits of young men before and during military service, determinants of eating habits and associations between diet and health risk factors, and effects of an intervention promoting healthy eating in military conditions. Two datasets were used. In the first, data on conscripts food use and nutrient intake was collected in garrison, encampment and leave conditions. The second belonged to the VARU intervention study in which the supply of healthy food was increased in military eating environments i.e. garrison canteens and soldier s homes. Study questionnaires were collected before military service and during it at the 8th week and 6th month of service. Conscripts health status was also followed during service through 13 anthropometric and clinical risk factors. Main dietary outcomes were food indexes which were formed specifically for studying young men and to suit military conditions. Prior to military service, the diet was mainly healthy although fruit and vegetable consumption was clearly low. Upper secondary school and healthy behaviour predicted healthy eating. During military service, nutrient intake was adequate although salt intake was high and fibre intake low. Food at garrison met nutrition recommendations most and especially fibre-containing foods belonged to it. At fee-time, nutrient intake was less favourable and sugar consumption high. Nutrient-poor foods, such as soft drinks and pizza, were frequently used. Conscripts health risk factor levels were low. During service, overweight decreased and body composition improved. Blood pressure improved but lipid and glucose levels deteriorated. The intervention succeeded in improving conscripts eating habits. In intervention group, cereal foods were consumed more and several fat- and sugar-containing foods less than in control group. The intervention did not increase fruit and vegetable consumption. Positively, young men s everyday diet contained several healthy foods which consumption increased during military service. On the other hand, consumption of some unhealthy foods increased especially at free-time. Already in early adulthood, young men s eating habits, other health behaviours and health risk factors accumulate. Conscripts healthy eating habits can be supported by promoting the food supply in garrison canteens and soldier s homes. Effective intervening on individual choices, as low fruit and vegetable consumption, remains more challenging.
  • Drakou, Aleksandros (2005)
    Title: Exchange rate dynamics with pricing-to-market (PTM). This study aims to demonstrate how the presence of sticky prices and pricing-to-market practices of firms affect the exchange rate volatility as well as international macroeconomic transmission and welfare. The model utilized is a simple exchange rate framework which combines international market segmentation by competitive firms as well as local currency price setting. The main reference of the study is Betts and Devereux (2000), "Exchange rate dynamics in a model of pricing-to-market". Section 2 presents the determinants of the model, section 3 the impact of PTM to exchange rate variability, section 4 the impacts of monetary government spending shocks under PTM, and finally section 5 examines the welfare aspects. Main results are the following. PTM is important for the determination of the exchange rate as well as for international macroeconomic fluctuations. It decreases the pass-through from exchange rate changes to prices, as well as the expenditure switching effect of exchange rate variations. The presence of PTM also increases exchange rate variability. Furthermore since it causes departures from purchasing power parity, it also lessens the comovement in consumption across economies. Finally PTM influences the transmission of monetary policy shocks, thus causing vital welfare repercussions. More specifically, domestic monetary expansions raise domestic welfare while reducing foreign one. Thus monetary policy becomes a beggar thy neighbor instrument under the influence of pricing to market policies.
  • Ruokolainen, Lasse (Helsingin yliopisto, 2009)
    While environmental variation is an ubiquitous phenomenon in the natural world which has for long been appreciated by the scientific community recent changes in global climatic conditions have begun to raise consciousness about the economical, political and sociological ramifications of global climate change. Climate warming has already resulted in documented changes in ecosystem functioning, with direct repercussions on ecosystem services. While predicting the influence of ecosystem changes on vital ecosystem services can be extremely difficult, knowledge of the organisation of ecological interactions within natural communities can help us better understand climate driven changes in ecosystems. The role of environmental variation as an agent mediating population extinctions is likely to become increasingly important in the future. In previous studies population extinction risk in stochastic environmental conditions has been tied to an interaction between population density dependence and the temporal autocorrelation of environmental fluctuations. When populations interact with each other, forming ecological communities, the response of such species assemblages to environmental stochasticity can depend, e.g., on trophic structure in the food web and the similarity in species-specific responses to environmental conditions. The results presented in this thesis indicate that variation in the correlation structure between species-specific environmental responses (environmental correlation) can have important qualitative and quantitative effects on community persistence and biomass stability in autocorrelated (coloured) environments. In addition, reddened environmental stochasticity and ecological drift processes (such as demographic stochasticity and dispersal limitation) have important implications for patterns in species relative abundances and community dynamics over time and space. Our understanding of patterns in biodiversity at local and global scale can be enhanced by considering the relevance of different drift processes for community organisation and dynamics. Although the results laid out in this thesis are based on mathematical simulation models, they can be valuable in planning effective empirical studies as well as in interpreting existing empirical results. Most of the metrics considered here are directly applicable to empirical data.
  • Valosaari, Kata-Riina (Helsingin yliopisto, 2008)
    Biological invasions are considered as one of the greatest threats to biodiversity, as they may lead to disruption and homogenization of natural communities, and in the worst case, to native species extinctions. The introduction of gene modified organisms (GMOs) to agricultural, fisheries and forestry practices brings them into contact with natural populations. GMOs may appear as new invasive species if they are able to (1) invade into natural habitats or (2) hybridize with their wild relatives. The benefits of GMOs, such as increased yield or decreased use of insecticides or herbicides in cultivation, may thus be reduced due the potential risks they may cause. A careful ecological risk analysis therefore has to precede any responsible GMO introduction. In this thesis I study ecological invasion in relation to GMOs, and what kind of consequences invasion may have in natural populations. A set of theoretical models that combine life-history evolution, population dynamics, and population genetics were developed for the hazard identification part of ecological risks assessment of GMOs. In addition, the potential benefits of GMOs in management of an invasive pest were analyzed. In the first study I showed that a population that is fluctuating due to scramble-type density dependence (due to, e.g., nutrient competition in plants) may be invaded by a population that is relatively more limited by a resource (e.g., light in plants) that is a cause of contest-type density dependence. This result emphasises the higher risk of invasion in unstable environments. The next two studies focused on escape of a growth hormone (GH) transgenic fish into a natural population. The results showed that previous models may have given too pessimistic a view of the so called Trojan gene -effect, where the invading genotype is harmful for the population as a whole. The previously suggested population extinctions did not occur in my studies, since the changes in mating preferences caused by the GH-fish were be ameliorated by decreased level of competition. The GH-invaders may also have to exceed a threshold density before invasion can be successful. I also showed that the prevalence of mature parr (aka. sneaker) strategy among GH-fish may have clear effect on invasion outcome. The fourth study assessed the risks and developed methods against the invasion of the Colorado Potato Beetle (CPB, Leptinotarsa decemlineata). I showed that the eradication of CPB is most important for the prevention of their establishment, but the cultivation of transgenic Bt-potato could also be effective. In general, my results emphasise that invasion of transgenic species or genotypes to be possible under certain realistic conditions and resulting in competitive exclusion, population decline through outbreeding depression and genotypic displacement of native species. Ecological risk assessment should regard the decline and displacement of the wild genotype by an introduced one as a consequence that is as serious as the population extinction. It will also be crucial to take into account different kinds of behavioural differences among species when assessing the possible hazards that GMOs may cause if escaped. The benefits found of GMO crops effectiveness in pest management may also be too optimistic since CPB may evolve resistance to Bt-toxin. The models in this thesis could be further applied in case specific risk assessment of GMOs by supplementing them with detailed data of the species biology, the effect of the transgene introduced to the species, and also the characteristics of the populations or the environments in the risk of being invaded.
  • Magnusson, Roland Lars Johannes (2006)
    Over the last fifteen years, the connection between free trade and the environment has been the subject of considerable debate. Among other things, it has been proposed that freer trade may harm the environment if it induces national governments to compete by undercutting each others’ environmental standards. We assess this proposition in a federal economy with free movement of capital and goods, but labour that is immobile. Our analysis shows that if the member states are small, firms perfectly competitive and pollution non-transboundary, the national governments’ choice of environmental standards coincide with that of the federal government’s. However, if the third assumption is relaxed, without cooperation, all states choose less strict standards than the federal government, even if pollution is only partially transboundary. If we assume monopolistically instead of perfectly competitive firms, the result that non-cooperative regulations are federally efficient when pollution is non-transboundary holds no longer. Nonetheless, there is nothing to suggest that environmental policy is less strict under non-cooperation than under cooperation. Intuitively, this is because the choice of emission tax by one country imposes a number externalities on the other. These externalities are partly positive and partly negative. Without assigning values to at least one of the model’s parameters, we are not able to say whether the negative or the positive externalities dominate, that is, whether the non-cooperative equilibrium is characterised ecological dumping or not-in-my-back-yard. In the special case of perfectly transboundary pollution, we find that ecological dumping occurs regardless of the choice of values for the model’s other parameters. We contribute to the literature in three ways. First, we show that the existence of pollution that spills from one country into another works in favour of ecological dumping both in perfect and in monopolistic product market competition. Second, we show that for ecological dumping to occur, a priori, pollution must be perfectly transboundary if firms are monopolistically competitive, whereas it suffices that pollution is partially transboundary if firms are perfectly competitive. Third, we show that perfect competition, and the standard results associated with it are obtained as a special case of monopolistic competition when the monopolistically competitive firms’ market power is eliminated.