Non-reductive Physicalism, Irreducibility of the Mental and the Problem of Mental Causation : A study of Donald Davidson's and Georg Henrik von Wright's positions in the philosophy of mind

In this study I consider what kind of perspective on the mind body problem is taken and can be taken by a philosophical position called non-reductive physicalism. Many positions fall under this label. The form of non-reductive physicalism which I discuss is in essential respects the position taken by Donald Davidson (1917-2003) and Georg Henrik von Wright (1916-2003). I defend their positions and discuss the unrecognized similarities between their views. Non-reductive physicalism combines two theses: (a) Everything that exists is physical; (b) Mental phenomena cannot be reduced to the states of the brain. This means that according to non-reductive physicalism the mental aspect of humans (be it a soul, mind, or spirit) is an irreducible part of the human condition. Also Davidson and von Wright claim that, in some important sense, the mental aspect of a human being does not reduce to the physical aspect, that there is a gap between these aspects that cannot be closed. I claim that their arguments for this conclusion are convincing. I also argue that whereas von Wright and Davidson give interesting arguments for the irreducibility of the mental, their physicalism is unwarranted. These philosophers do not give good reasons for believing that reality is thoroughly physical. Notwithstanding the materialistic consensus in the contemporary philosophy of mind the ontology of mind is still an uncharted territory where real breakthroughs are not to be expected until a radically new ontological position is developed. The third main claim of this work is that the problem of mental causation cannot be solved from the Davidsonian - von Wrightian perspective. The problem of mental causation is the problem of how mental phenomena like beliefs can cause physical movements of the body. As I see it, the essential point of non-reductive physicalism - the irreducibility of the mental - and the problem of mental causation are closely related. If mental phenomena do not reduce to causally effective states of the brain, then what justifies the belief that mental phenomena have causal powers? If mental causes do not reduce to physical causes, then how to tell when - or whether - the mental causes in terms of which human actions are explained are actually effective? I argue that this - how to decide when mental causes really are effective - is the real problem of mental causation. The motivation to explore and defend a non-reductive position stems from the belief that reductive physicalism leads to serious ethical problems. My claim is that Davidson's and von Wright's ultimate reason to defend a non-reductive view comes back to their belief that a reductive understanding of human nature would be a narrow and possibly harmful perspective. The final conclusion of my thesis is that von Wright's and Davidson's positions provide a starting point from which the current scientistic philosophy of mind can be critically further explored in the future.

John Searlen teoria tietoisuudesta

Tutkielmassa esitellään ja arvioidaan John Searlen teoriaa tietoisuudesta. Tietoisuus (consciousness) on Searlen mukaan tärkein mielenfilosofinen käsite. Searle ei määrittele käsitettä tarkasti, vaan tyytyy esittämään sitä kuvaavia esimerkkejä ja analogioita. Tietoisuuden keskeisimmiksi ominaisuuksiksi Searlen teoriassa näyttävät muodostuvan intentionaalisuus (intentionality), subjektiivisuus (subjectivity) ja kausaalinen vaikutus käyttäytymiseen (mental causation). Näihin ominaisuuksiin liittyvät myös Searlen painavimmat tietoisuudesta esittämät argumentit. Argumenttien analysointi on tutkielman tärkein tavoite. Searlen yhteysperiaatteen (Connection Principle) mukaan intentionaalisia tiloja voi olla vain olennolla, jolla voi olla tietoisia intentionaalisia tiloja, ja jokainen alitajuinen intentionaalinen tila on ainakin potentiaalisesti tietoinen. Toisin sanoen intentionaalisuuden ja tietoisuuden välillä vallitsee välttämätön yhteys seuraavasti: on loogisesti välttämätöntä, että jokainen intentionaalinen tila voi ainakin periaattessa päästä tietoisuuteen.Tutkielmassa kuitenkin osoitetaan, että yhteysperiaateeseen on syytä suhtautua epäillen. Searlen yhteysperiaatteen puolesta esittämä argumentti näyttää nimittäin sisältävän dilemman. Jos erottelu intrinsiseen ja näennäiseen intentionaalisuuteen tulkitaan Searlen tavoin, syyllistytään sen olettamiseen, mikä pitäisi todistaa; jos taas erottelu tulkitaan toisin kuin Searle, argumentti ei tue yhteysperiaatetta. Searlen mukaan mentaaliset tilat ovat aina jonkun mentaalisia tiloja. Tästä väitteestä Searle pyrkii johtamaan toisen, paljon radikaalimman väitteen: mielen ilmiöt kuuluvat omaan ontologiseen kategoriaansa, subjektiivisten mentaalisten tilojen kategoriaan. Searlen käsitystä tukee Thomas Nagelin esittämä, hyvin samansisältöinen argumentti. Yksimielisyys ei kuitenkaan ole erehtymättömyyden tae, sillä Paul Churchlandin kritiikki näyttää pahasti horjuttavan Searlen subjektiivisuusargumentin uskottavuutta. Churchland väittää Searlen syyllistyvän intensionaaliseen virhepäätelmään. Yksittäisen henkilön episteemisen pääsyn rajoittuneisuudesta ei Churchlandin mukaan voida tehdä mitään ontologisia johtopäätöksiä, koska tiedetyksi tuleminen ei ole objektin aito ominaisuus. Vastaväite näyttää olevan kohtalokas Searlen subjektiivisuusargumentille. Subjektiivisuuden ongelma näyttää olevan perustava metafyysinen vedenjakaja, joka jakaa mielenfilosofiset teoriat toisaalta materialistisiin, toisaalta dualistisiin. Searle uskoo, että mieli-ruumis -ongelma (mind-body problem) on ratkaistavissa ilman, että tarvitsee valita kumpaakaan. Ratkaisu sisältyy kahteen Searlen näennäisesti yhteensopimattomaan teesiin. Ensimmäisen teesin mukaan mentaaliset tilat ovat todellisia ilmiöitä, eikä niitä voida redusoida mihinkään muuhun tai eliminoida määrittelemällä ne uudestaan. Toisen teesin mukaan aivojen operaatiot aiheuttavat mentaaliset tilat ja mentaaliset tilat ovat aivojen piirteitä. Teeseistä jälkimmäinen osoittautuu ongelmalliseksi syistä, jotka Jaegwon Kim on esittänyt. Jos mentaaliset tilat olisivat aivojen ominaisuuksia, ei mielen ja aivojen välinen suhde voisi olla kausaalinen, koska kausaatiossa (causation) on aina kyse kahden erillisen entiteetin tai tapahtuman välisestä relaatiosta, jossa suhteen osapuolien välillä on oltava ajallista etäisyyttä. Toiseksi Searlen vertaus tietoisuuden ja aivojen suhteesta kappaleen kiinteyden ja sen mikrorakenteen suhteeseen epäonnistuu, koska tietoisuus ja kiinteys kuuluvat Searlen teoriassa eri ontologisiin kategorioihin, eikä niitä siten voi ongelmattomasti rinnastaa. Searlen analogia kiinteyteen murtuu myös siksi, että kappaleen mikrorakenne ei yksinkertaisesti aiheuta sen kiinteyttä. Tietoisuus ei siis voi olla samanaikaisesti aivojen ominaisuus ja aivojen kausaalisen toiminnan seuraus. Tutkielmassa päädytään puolustamaan kantaa, että Searlen argumentit eivät ole vakuuttavia ja että Searle ei ole onnistunut eksplikoimaan teoriaa, joka välttäisi dualismiin ja materialismiin liittyvät tunnetut ongelmat. Kysymys mikä on mielen suhde ruumiiseen, jää siten avoimeksi. Avainsanat: intentionaalisuus, mentaalinen, mieli-ruumis -ongelma, Searle, subjektiivisuus, tietoisuus

Prevention of type 2 diabetes with lifestyle intervention - emphasis on dietary composition and identification of high-risk individuals

Type 2 diabetes is an increasing, serious, and costly public health problem. The increase in the prevalence of the disease can mainly be attributed to changing lifestyles leading to physical inactivity, overweight, and obesity. These lifestyle-related risk factors offer also a possibility for preventive interventions. Until recently, proper evidence regarding the prevention of type 2 diabetes has been virtually missing. To be cost-effective, intensive interventions to prevent type 2 diabetes should be directed to people at an increased risk of the disease. The aim of this series of studies was to investigate whether type 2 diabetes can be prevented by lifestyle intervention in high-risk individuals, and to develop a practical method to identify individuals who are at high risk of type 2 diabetes and would benefit from such an intervention. To study the effect of lifestyle intervention on diabetes risk, we recruited 522 volunteer, middle-aged (aged 40 - 64 at baseline), overweight (body mass index > 25 kg/m2) men (n = 172) and women (n = 350) with impaired glucose tolerance to the Diabetes Prevention Study (DPS). The participants were randomly allocated either to the intensive lifestyle intervention group or the control group. The control group received general dietary and exercise advice at baseline, and had annual physician's examination. The participants in the intervention group received, in addition, individualised dietary counselling by a nutritionist. They were also offered circuit-type resistance training sessions and were advised to increase overall physical activity. The intervention goals were to reduce body weight (5% or more reduction from baseline weight), limit dietary fat (< 30% of total energy consumed) and saturated fat (< 10% of total energy consumed), and to increase dietary fibre intake (15 g / 1000 kcal or more) and physical activity (≥ 30 minutes/day). Diabetes status was assessed annually by a repeated 75 g oral glucose tolerance testing. First analysis on end-points was completed after a mean follow-up of 3.2 years, and the intervention phase was terminated after a mean duration of 3.9 years. After that, the study participants continued to visit the study clinics for the annual examinations, for a mean of 3 years. The intervention group showed significantly greater improvement in each intervention goal. After 1 and 3 years, mean weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 kg and 0.9 kg in the control group. Cardiovascular risk factors improved more in the intervention group. After a mean follow-up of 3.2 years, the risk of diabetes was reduced by 58% in the intervention group compared with the control group. The reduction in the incidence of diabetes was directly associated with achieved lifestyle goals. Furthermore, those who consumed moderate-fat, high-fibre diet achieved the largest weight reduction and, even after adjustment for weight reduction, the lowest diabetes risk during the intervention period. After discontinuation of the counselling, the differences in lifestyle variables between the groups still remained favourable for the intervention group. During the post-intervention follow-up period of 3 years, the risk of diabetes was still 36% lower among the former intervention group participants, compared with the former control group participants. To develop a simple screening tool to identify individuals who are at high risk of type 2 diabetes, follow-up data of two population-based cohorts of 35-64 year old men and women was used. The National FINRISK Study 1987 cohort (model development data) included 4435 subjects, with 182 new drug-treated cases of diabetes identified during ten years, and the FINRISK Study 1992 cohort (model validation data) included 4615 subjects, with 67 new cases of drug-treated diabetes during five years, ascertained using the Social Insurance Institution's Drug register. Baseline age, body mass index, waist circumference, history of antihypertensive drug treatment and high blood glucose, physical activity and daily consumption of fruits, berries or vegetables were selected into the risk score as categorical variables. In the 1987 cohort the optimal cut-off point of the risk score identified 78% of those who got diabetes during the follow-up (= sensitivity of the test) and 77% of those who remained free of diabetes (= specificity of the test). In the 1992 cohort the risk score performed equally well. The final Finnish Diabetes Risk Score (FINDRISC) form includes, in addition to the predictors of the model, a question about family history of diabetes and the age category of over 64 years. When applied to the DPS population, the baseline FINDRISC value was associated with diabetes risk among the control group participants only, indicating that the intensive lifestyle intervention given to the intervention group participants abolished the diabetes risk associated with baseline risk factors. In conclusion, the intensive lifestyle intervention produced long-term beneficial changes in diet, physical activity, body weight, and cardiovascular risk factors, and reduced diabetes risk. Furthermore, the effects of the intervention were sustained after the intervention was discontinued. The FINDRISC proved to be a simple, fast, inexpensive, non-invasive, and reliable tool to identify individuals at high risk of type 2 diabetes. The use of FINDRISC to identify high-risk subjects, followed by lifestyle intervention, provides a feasible scheme in preventing type 2 diabetes, which could be implemented in the primary health care system.

A local 2-approximation algorithm for the vertex cover problem

We present a distributed 2-approximation algorithm for the minimum vertex cover problem. The algorithm is deterministic, and it runs in (Δ + 1)2 synchronous communication rounds, where Δ is the maximum degree of the graph. For Δ = 3, we give a 2-approximation algorithm also for the weighted version of the problem.

A local 2-approximation algorithm for the vertex cover problem

We present a distributed 2-approximation algorithm for the minimum vertex cover problem. The algorithm is deterministic, and it runs in (Δ + 1)2 synchronous communication rounds, where Δ is the maximum degree of the graph. For Δ = 3, we give a 2-approximation algorithm also for the weighted version of the problem.

Coffee and risk of type 2 diabetes

Type 2 diabetes is one of the diseases that largely determined by lifestyle factors. Coffee is one of the most consumed beverages in the world and recently released data suggest the effects of coffee consumption on type 2 diabetes. The objective of the present study was to evaluate the effects of habitual coffee consumption on various aspects of type 2 diabetes and its most common complications. This study is part of the national FINRISK studies. Baseline surveys were carried out between 1972 and 1997. The surveys covered two eastern regions in 1972 and 1977, but were expanded to include a third region in southwestern Finland in 1982, 1987, 1992, and 1997. The Helsinki capital area was included in the survey in 1992 and 1997 and the Oulu province, in northern Finland, in 1997. Each survey was drawn from an independent random sample of the national register of subjects aged 25-64. In 1997, an additional sample of subjects aged 65-74 was conducted. The blood pressure, weight, and height of subjects were measured. By using self-administered questionnaires data were collected on medical history, socioeconomic factors, physical activity, smoking habits, and alcohol, coffee, and tea consumption. Higher coffee consumption was associated with higher body mass index, occupational physical activity and cigarette smoking, and lower blood pressure, education level, leisure time physical activity, tea consumption and alcohol use. Age, body mass index, systolic blood pressure and current smoking were positively associated with the risk of type 2 diabetes, however, education, and occupational, commuting and leisure time physical activity were inversely associated. The significant inverse association between coffee consumption and the risk of type 2 diabetes was found in both sexes but the association was stronger in women. Coffee consumption was significantly and inversely associated with fasting glucose, 2-hour plasma glucose, fasting insulin, impaired fasting glucose, impaired glucose regulation, and hyperinsulinemia among both men and women and with isolated impaired glucose tolerance among women. Serum gamma-glutamyltransferase modified the association between coffee consumption and incident diabetes. Among subjects with high serum -glutamyltransferase (>75th percentile), coffee consumption showed an inverse association for women, as well as men and women combined. An inverse association also occurred between coffee consumption and the risk of total, cardiovascular disease, and coronary heart disease mortality among patients with type 2 diabetes. The results of this study showed that habitual coffee consumption may be associated with a reduced risk of type 2 diabetes. Coffee consumption may have some effects on several markers of glycemia, and may lower the incident of type 2 diabetes in high normal serum -glutamyltransferase levels. Total, cardiovascular disease, and coronary heart disease mortality rate among subjects with type 2 diabetes may also be reduced by coffee consumption.

Early detection of type 2 diabetes mellitus in Chinese and Indian adult population

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.

Early growth and adult health: focus on blood pressure, glucose tolerance status and body composition

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.

Anthropometric measures of obesity-their association with type 2 diabetes and hypertension across ethnic groups

Clinical trials have shown that weight reduction with lifestyles can delay or prevent diabetes and reduce blood pressure. An appropriate definition of obesity using anthropometric measures is useful in predicting diabetes and hypertension at the population level. However, there is debate on which of the measures of obesity is best or most strongly associated with diabetes and hypertension and on what are the optimal cut-off values for body mass index (BMI) and waist circumference (WC) in this regard. The aims of the study were 1) to compare the strength of the association for undiagnosed or newly diagnosed diabetes (or hypertension) with anthropometric measures of obesity in people of Asian origin, 2) to detect ethnic differences in the association of undiagnosed diabetes with obesity, 3) to identify ethnic- and sex-specific change point values of BMI and WC for changes in the prevalence of diabetes and 4) to evaluate the ethnic-specific WC cutoff values proposed by the International Diabetes Federation (IDF) in 2005 for central obesity. The study population comprised 28 435 men and 35 198 women, ≥ 25 years of age, from 39 cohorts participating in the DECODA and DECODE studies, including 5 Asian Indian (n = 13 537), 3 Mauritian Indian (n = 4505) and Mauritian Creole (n = 1075), 8 Chinese (n =10 801), 1 Filipino (n = 3841), 7 Japanese (n = 7934), 1 Mongolian (n = 1991), and 14 European (n = 20 979) studies. The prevalence of diabetes, hypertension and central obesity was estimated, using descriptive statistics, and the differences were determined with the χ2 test. The odds ratios (ORs) or  coefficients (from the logistic model) and hazard ratios (HRs, from the Cox model to interval censored data) for BMI, WC, waist-to-hip ratio (WHR), and waist-to-stature ratio (WSR) were estimated for diabetes and hypertension. The differences between BMI and WC, WHR or WSR were compared, applying paired homogeneity tests (Wald statistics with 1 df). Hierarchical three-level Bayesian change point analysis, adjusting for age, was applied to identify the most likely cut-off/change point values for BMI and WC in association with previously undiagnosed diabetes. The ORs for diabetes in men (women) with BMI, WC, WHR and WSR were 1.52 (1.59), 1.54 (1.70), 1.53 (1.50) and 1.62 (1.70), respectively and the corresponding ORs for hypertension were 1.68 (1.55), 1.66 (1.51), 1.45 (1.28) and 1.63 (1.50). For diabetes the OR for BMI did not differ from that for WC or WHR, but was lower than that for WSR (p = 0.001) in men while in women the ORs were higher for WC and WSR than for BMI (both p < 0.05). Hypertension was more strongly associated with BMI than with WHR in men (p < 0.001) and most strongly with BMI than with WHR (p < 0.001), WSR (p < 0.01) and WC (p < 0.05) in women. The HRs for incidence of diabetes and hypertension did not differ between BMI and the other three central obesity measures in Mauritian Indians and Mauritian Creoles during follow-ups of 5, 6 and 11 years. The prevalence of diabetes was highest in Asian Indians, lowest in Europeans and intermediate in others, given the same BMI or WC category. The  coefficients for diabetes in BMI (kg/m2) were (men/women): 0.34/0.28, 0.41/0.43, 0.42/0.61, 0.36/0.59 and 0.33/0.49 for Asian Indian, Chinese, Japanese, Mauritian Indian and European (overall homogeneity test: p > 0.05 in men and p < 0.001 in women). Similar results were obtained in WC (cm). Asian Indian women had lower  coefficients than women of other ethnicities. The change points for BMI were 29.5, 25.6, 24.0, 24.0 and 21.5 in men and 29.4, 25.2, 24.9, 25.3 and 22.5 (kg/m2) in women of European, Chinese, Mauritian Indian, Japanese, and Asian Indian descent. The change points for WC were 100, 85, 79 and 82 cm in men and 91, 82, 82 and 76 cm in women of European, Chinese, Mauritian Indian, and Asian Indian. The prevalence of central obesity using the 2005 IDF definition was higher in Japanese men but lower in Japanese women than in their Asian counterparts. The prevalence of central obesity was 52 times higher in Japanese men but 0.8 times lower in Japanese women compared to the National Cholesterol Education Programme definition. The findings suggest that both BMI and WC predicted diabetes and hypertension equally well in all ethnic groups. At the same BMI or WC level, the prevalence of diabetes was highest in Asian Indians, lowest in Europeans and intermediate in others. Ethnic- and sex-specific change points of BMI and WC should be considered in setting diagnostic criteria for obesity to detect undiagnosed or newly diagnosed diabetes.

Type 1 and type 2 diabetes among young adults in Finland : Incidence and perinatal exposures

This study aimed to examine the incidence of young adult-onset T1DM and T2DM among Finns, and to explore the possible risk factors for young adult-onset T1DM and T2DM that occur during the perinatal period and childhood. In the studies I-II, the incidence of diabetes was examined among 15-39-year-old Finns during the years 1992-2001. Information on the new diagnoses of diabetes was collected from four sources: standardized national reports filled in by diabetes nurses, the Hospital Discharge Register, the Drug Reimbursement Register, and the Drug Prescription Register. The type of diabetes was assigned using information obtained from these four data sources. The incidence of T1DM was 18 per 100,000/year, and there was a clear male predominance in the incidence of T1DM. The incidence of T1DM increased on average 3.9% per year during 1992-2001. The incidence of T2DM was 13 per 100,000/year, and it displayed an increase of 4.3% per year. In the studies III-V, the effects of perinatal exposures and childhood growth on the risk for young adult-onset T1DM and T2DM were explored in a case-control setting. Individuals diagnosed with T1DM (n=1,388) and T2DM (n=1,121) during the period 1992-1996 were chosen as the diabetes cases for the study, and two controls were chosen for each case from the National Population Register. Data on the study subjects parents and siblings was obtained from the National Population Register. The study subjects original birth records and child welfare clinic records were traced nationwide. The risk for young adult-onset T2DM was the lowest among the offspring of mothers aged about 30 years, whereas the risk for T2DM increased towards younger and older maternal ages. Birth orders second to fourth were found protective of T2DM. In addition, the risk for T2DM was observed to decrease with increasing birth weight until 4.2 kg, after which the risk began to increase. A high body mass index (BMI) at the BMI rebound between ages 3-11 years substantially increased the risk for T2DM, and the excess weight gain in individuals diagnosed with T2DM began in early childhood. Maternal age, birth order, or body size at birth had no effect on the risk for young adult-onset T1DM. Instead, individuals with T1DM were observed to have a higher maximum BMI before the age of 3 than their control subjects. In conclusion, the increasing trend in the development of both T1DM and T2DM among young Finnish adults is alarming. The high risk for T1DM among the Finnish population extends to at least 40 years of age, and at least 200-300 young Finnish adults are diagnosed with T2DM every year. Growth during the fetal period and childhood notably affects the risk for T2DM. T2DM prevention should also target childhood obesity. Rapid growth during the first years of life may be a risk factor for late-onset T1DM.

Complement system and alcoholic liver disease

Alcoholic liver disease (ALD) is a well recognized and growing health problem worldwide. ALD advances from fatty liver to inflammation, necrosis, fibrosis and cirrhosis. There is accumulating evidence that the innate immune system is involved in alcoholic liver injury. Within the innate and acquired immune systems, the complement system participates in inflammatory reactions and in the elimination of invading foreign, as well as endogenous apoptotic or injured cells. The present study aimed at evaluating the role of the complement system in the development of alcoholic liver injury. First, in order to study the effects of chronic ethanol intake on the complement system, the deposition of complement components in liver and the expression of liver genes associated with complement in animals with alcohol-induced liver injury were examined. It was demonstrated that chronic alcohol exposure leads to hepatic deposition of the complement components C1, C3, C8 and C9 in the livers of rats. Liver gene expression analysis showed that ethanol up-regulated the expression of transcripts for complement factors B, C1qA, C2, C3 and clusterin. In contrast, ethanol down-regulated the expression of the complement regulators factor H, C4bp and factor D and the terminal complement components C6, C8α and C9. Secondly, the role of the terminal complement pathway in the development of ALD was evaluated by using rats genetically deficient in the complement component C6 (C6-/-). It was found that chronic ethanol feeding induced more liver pathology (steatosis and inflammatory changes) in C6-/- rats than in wild type rats. The hepatic triacylglyceride content and plasma alanine aminotransferase activity increased in C6-/- rats, supporting the histopathological findings and elevation of the plasma pro-/anti-inflammatory TNF-/IL-10 ratio was also more marked in C6-/- rats. Third, the role of the alternative pathway in the development of alcoholic liver steatosis was characterized by using C3-/- mice. In C3-/- mice ethanol feeding tended to reduce steatosis and had no further effect on liver triacylglyceride, liver/body weight ratio nor on liver malondialdehyde level and serum alanine aminotransferase activity. In C3-/- mice alcohol-induced liver steatosis was reduced also after an acute alcohol challenge. In both wild type and C3-/- mice ethanol markedly reduced serum cholesterol and ApoA-I levels, phospholipid transfer protein activity and hepatic mRNA levels of fatty acid binding proteins and fatty acid -oxidation enzymes. In contrast, exclusively in C3-/- mice, ethanol treatment increased serum and liver adiponectin levels but down-regulated the expression of transcripts of lipogenic enzymes, adiponectin receptor 2 and adipose differentiation-related protein and up-regulated phospholipase D1. In conclusion, this study has demonstrated that the complement system is involved in the development of alcohol-induced liver injury. Chronic alcohol exposure causes local complement activation and induction of mRNA expression of classical and alternative pathway components in the liver. In contrast expression of the terminal pathway components and soluble regulators were decreased. A deficient terminal complement pathway predisposes to alcoholic liver damage and promotes a pro-inflammatory cytokine response. Complement component C3 contributes to the development of alcohol-induced fatty liver and its consequences by affecting regulatory and specific transcription factors of lipid homeostasis.

Individuals on the Move : Body Condition Dependent Dispersal and Quasi-Local Competition in Metapopulations

Individual movement is very versatile and inevitable in ecology. In this thesis, I investigate two kinds of movement body condition dependent dispersal and small-range foraging movements resulting in quasi-local competition and their causes and consequences on the individual, population and metapopulation level. Body condition dependent dispersal is a widely evident but barely understood phenomenon. In nature, diverse relationships between body condition and dispersal are observed. I develop the first models that study the evolution of dispersal strategies that depend on individual body condition. In a patchy environment where patches differ in environmental conditions, individuals born in rich (e.g. nutritious) patches are on average stronger than their conspecifics that are born in poorer patches. Body condition (strength) determines competitive ability such that stronger individuals win competition with higher probability than weak individuals. Individuals compete for patches such that kin competition selects for dispersal. I determine the evolutionarily stable strategy (ESS) for different ecological scenarios. My models offer explanations for both dispersal of strong individuals and dispersal of weak individuals. Moreover, I find that within-family dispersal behaviour is not always reflected on the population level. This supports the fact that no consistent pattern is detected in data on body condition dependent dispersal. It also encourages the refining of empirical investigations. Quasi-local competition defines interactions between adjacent populations where one population negatively affects the growth of the other population. I model a metapopulation in a homogeneous environment where adults of different subpopulations compete for resources by spending part of their foraging time in the neighbouring patches, while their juveniles only feed on the resource in their natal patch. I show that spatial patterns (different population densities in the patches) are stable only if one age class depletes the resource very much but mainly the other age group depends on it.

Dirichlet problem at infinity for p-harmonic functions on negatively curved spaces

The object of this dissertation is to study globally defined bounded p-harmonic functions on Cartan-Hadamard manifolds and Gromov hyperbolic metric measure spaces. Such functions are constructed by solving the so called Dirichlet problem at infinity. This problem is to find a p-harmonic function on the space that extends continuously to the boundary at inifinity and obtains given boundary values there. The dissertation consists of an overview and three published research articles. In the first article the Dirichlet problem at infinity is considered for more general A-harmonic functions on Cartan-Hadamard manifolds. In the special case of two dimensions the Dirichlet problem at infinity is solved by only assuming that the sectional curvature has a certain upper bound. A sharpness result is proved for this upper bound. In the second article the Dirichlet problem at infinity is solved for p-harmonic functions on Cartan-Hadamard manifolds under the assumption that the sectional curvature is bounded outside a compact set from above and from below by functions that depend on the distance to a fixed point. The curvature bounds allow examples of quadratic decay and examples of exponential growth. In the final article a generalization of the Dirichlet problem at infinity for p-harmonic functions is considered on Gromov hyperbolic metric measure spaces. Existence and uniqueness results are proved and Cartan-Hadamard manifolds are considered as an application.

4QMMT - The Problem of the Epilogue

The main focus of this study is the epilogue of 4QMMT (4QMiqsat Ma aseh ha-Torah), a text of obscure genre containing a halakhic section found in cave 4 at Qumran. In the official edition published in the series Discoveries of the Judaean Desert (DJD X), the extant document was divided by its editors, Elisha Qimron and John Strugnell, into three literary divisions: Section A) the calendar section representing a 364-day solar calendar, Section B) the halakhot, and Section C) an epilogue. The work begins with text critical inspection of the manuscripts containing text from the epilogue (mss 4Q397, 4Q398, and 4Q399). However, since the relationship of the epilogue to the other sections of the whole document 4QMMT is under investigation, the calendrical fragments (4Q327 and 4Q394 3-7, lines 1-3) and the halakhic section also receive some attention, albeit more limited and purpose oriented. In Ch. 2, after a transcription of the fragments of the epilogue, a synopsis is presented in order to evaluate the composite text of the DJD X edition in light of the evidence provided by the individual manuscripts. As a result, several critical comments are offered, and finally, an alternative arrangement of the fragments of the epilogue with an English translation. In the following chapter (Ch. 3), the diversity of the two main literary divisions, the halakhic section and the epilogue, is discussed, and it is demonstrated that the author(s) of 4QMMT adopted and adjusted the covenantal pattern known from biblical law collections, more specifically Deuteronomy. The question of the genre of 4QMMT is investigated in Ch. 4. The final chapter (Ch. 5) contains an analysis of the use of Scripture in the epilogue. In a close reading, both the explicit citations and the more subtle allusions are investigated in an attempt to trace the theology of the epilogue. The main emphases of the epilogue are covenantal faithfulness, repentance and return. The contents of the document reflect a grave concern for the purity of the cult in Jerusalem, and in the epilogue Deuteronomic language and expressions are used to convince the readers of the necessity of a reformation. The large number of late copies found in cave 4 at Qumran witness the significance of 4QMMT and the continuous importance of the Jerusalem Temple for the Qumran community.

One Word, One Body, One Voice : Studies in Apophatic Theology and Christocentric Anthropology in Gregory of Nyssa

The thesis consists of five international congress papers and a summary with an introduction. The overarching aim of the studies and the summary is to examine the inner coherency of the theological and anthropological thinking of Gregory of Nyssa (331-395). To the issue is applied an "apophatic approach" with a "Christological focus". It is suggested that the coherency is to be found from the Christological concept of unity between "true God" and "true man" in the one person of Jesus Christ. Gregory is among the first to make a full recognition of two natures of Christ, and to use this recognition systematically in his writings. The aim of the studies is pursued by the method of "identification", a combination of the modern critical "problematic method" and Gregory's own aphairetic method of "following" (akolouthia). The preoccupation with issues relating to the so-called Hellenization of Christianity in the patristic era was strong in the twentieth-century Gregory scholarship. The most discussed questions have been the Greek influence in his thought and his philosophical sources. In the five articles of the thesis it is examined how Gregory's thinking stands in its own right. The manifestly apophatic character of his theological thinking is made a part of the method of examining his thought according to the principles of his own method of following. The basic issue concerning the relation of theology and anthropology is discussed in the contexts of his central Trinitarian, anhtropological, Christological and eschatological sources. In the summary the Christocentric integration of Gregory's thinking is discussed also in relation to the issue of the alledged Hellenization. The main conclusion of the thesis concerns the concept of theology in Gregory. It is not indebted to the classical concept of theology as metaphysics or human speculation of God. Instead, it is founded to the traditional Judeo-Christian idea of God who speaks with his people face to face. In Gregory, theologia connotes the oikonomia of God's self-revelation. It may be regarded as the state of constant expression of love between the Creator and his created image. In theology, the human person becomes an image of the Word by which the Father expresses his love to "man" whom he loves as his own Son. Eventually the whole humankind, as one, gives the divine Word a physical - audible and sensible - Body. Humankind then becomes what theology is. The whole humanity expresses divine love by manifesting Christ in words and deeds, singing in one voice to the glory of the Father, the Son and the Holy Spirit.