Hevosen mahahaava - sijainti, vakavuusasteet ja altistavat tekijät

Mahahaava on hyvin yleinen ongelma hevosilla; sen prevalenssi vaihtelee 48-100 % välillä. Mahahaava johtuu epätasapainosta mahalaukkua suojaavien tekijöiden ja mahalaukun limakalvoa ärsyttävien tekijöiden välillä. Tarkkaa syytä mahahaavan syntymiselle ei tunneta ja tietoa altistavista tekijöistä ja niiden merkityksestä on melko vähän. Liikunnan, ruokinnan ja stressin epäillään vaikuttavan mahahaavan syntyyn. Tutkimuksessa tähystettiin 45 Yliopistolliseen Hevossairaalaan mahahaavaan viittaavien oireiden vuoksi tutkittavaksi tullutta hevosta. Hevosilta tutkittiin mahalaukun eri alueet ja mikäli mahdollista, myös duodenum. Haavaumat pisteytettiin niiden syvyyden, laajuuden ja limakalvon ärtyneisyyden perusteella 0-4 asteikolla. Hevosista kerättiin perustiedot ja omistajia haastateltiin kyselykaavakkeen avulla hevosten elintavoista ja olosuhteista. Hevoset olivat iältään 1-22 vuotiaita ja mukana oli tammoja, ruunia ja oreja. Suurin osa hevosista oli puoliverisiä (47%), mutta mukana oli myös suomenhevosia, lämminverisiä ja poneja. Käyttötarkoitukseltaan hevoset olivat ratsuja, ravureita tai levossa olevia hevosia. Hevosista 29% oli kilpahevosia. 31% hevosista oli aiemmin hoidettu mahahaavan vuoksi. Kaikilta hevosilta yhtä lukuunottamatta löytyi mahahaava. Haavaumien vakavuus vaihteli 1. - 3. asteen välillä. Suurin osa haavaumista sijaitsi pyloruksessa ja siellä oli myös eniten vakavia haavaumia. Lievimmät muutokset olivat muulla rauhasalueella; siellä todettiin määrällisesti vähiten haavaumia ja suurin osa todetuista haavaumista oli lieviä. Yllättävän monelta (60%) hevoselta löytyi haavauma duodenumista. Antrumin ja pyloruksen välillä todettiin korrelaatio; mikäli antrumissa oli haavauma, löytyi haavauma todennäköisesti myös pyloruksesta. Samanlainen korrelaatio todettiin muun rauhasalueen ja duodenumin välillä; mikäli muulla rauhasalueella todettiin haavauma, niin myös duodenumista löytyi haavauma. Vakavuusasteen ja altistavien tekijöiden, kuten korsirehumäärän, ruokintakertojen tai ulkoilun välillä ei todettu yhteyttä, Tutkimuksen perusteella ei siis voida arvioida, mitkä tekijät vaikuttavat mahahaavan syntyyn. Myöskään oireiden ja haavaumien välillä ei todettu yhteyttä. Mikään tietty oire ei siis kerro haavauman sijainnista tai vakavuusasteesta. Tutkimuksen aineisto oli hyvin valikoitunutta; kaikilla hevosilla oli indikaatio tulla tähystykseen. Tutkimuksessa ei ollut mukana oireetonta vertailuryhmää. Lisäksi aineisto oli useiden ominaisuuksien suhteen hyvin monimuotoinen. Tarvitaan lisää tutkimuksia, jotta mahahaavaan liitetyistä altistavista tekijöistä tai oireista voitaisiin tehdä tarkempia johtopäätöksiä.

Iatrogeeniset laryngeaalihermovauriot kilpirauhaskirurgiassa Tyksissä vuonna 2011 - insidenssi ja altistavat tekijät

Tämän tutkimuksen tavoitteena on selvittää iatrogeenisten eli hoidon aiheuttamien laryngeaalihermovaurioiden insidenssi kilpirauhaskirurgisilla potilailla Tyksissä vuonna 2011 sekä mahdolliset hermovauriolle altistavat tekijät. Tutkimushypoteesina on, että tutkimusaineistosta on mahdollisesti osoitettavissa laryngeaalihermovaurioille altistava, preoperatiivinen tekijä. Yhtäältä tutkimus toimii laryngeaalihermovaurioiden insidenssiä kartoittavana instrumenttina kilpirauhaskirurgisilla potilailla Tyksissä. Toisaalta tutkimuksessa mahdolliset esille tulevat laryngeaalihermovaurion riskitekijät saattavat vaikuttaa hoitokäytäntöihin ja näin ollen vähentää iatrogeenisia laryngeaalihermovaurioita tulevaisuudessa. Tutkimuksen aineistona on Tyksissä vuonna 2011 kirurgisesti leikatut kilpirauhaspotilaat eli sekä kilpirauhas- että lisäkilpirauhaspotilaat. Tutkimuksessa suoritettiin sähköisen potilastietojärjestelmän tietokantahaku käyttäen kilpirauhaskirurgisia toimenpidekoodeja, jonka tuloksena oli vuonna 2011 Tyksissä leikatut kilpirauhaspotilaat. Jokaiselta potilaalta kirjattiin sähköisestä potilastietojärjestelmästä systemaattisesti mahdollinen laryngeaalihermovaurion aiheuttama äänihuulihalvaus sekä tämän tutkimuksen kannalta oleelliset muuttujat. Tilastollinen analyysi suoritettiin JMP Pro 12 -ohjelmalla. Vuonna 2011 Tyksissä leikattiin 221 kilpirauhaskirurgista potilasta. Laryngeaalihermovaurioiden insidenssi oli 7,4 prosenttia, josta pysyviä oli 4,6 ja ohimeneviä 2,8 prosenttia. Aikaviive leikkauksesta hermovauriodiagnoosin oli pitkä, keskimäärin 102 päivää ja mediaani 51 päivää. Uusintaleikkaus oli merkittävin tilastollisesti merkitsevä hermovaurion riskitekijä. Aineistossa huomiota kiinnitti leikkausten aikainen alhainen recurrens-hermon visualisaatioprosentti – recurrens-hermoista visualisoitiin 71 prosenttia niissä leikkauksissa, joissa kirjallisuudessa visualisaation katsotaan olevan erittäin tärkeää. Kirurgeilla, joiden leikkausten seurauksena aiheutui huomattavasti enemmän hermovaurioita, oli potilasaineiston suhteen hermovauriolle alttiimman iäkkäämmän potilasmateriaalin sekä laajempien leikkausten painottuminen.

Cutaneous porphyrias : Clinical and histopathological study

The prevalence of variegate porphyria (VP) (2.1:100 000, in 2006 n=108) was higher in Finland than elsewhere in European countries due to a founder effect (R152C). The incidence of VP was estimated at 0.2:1 000 000 based on the number of new symptomatic patients yearly. The prevalence of porphyria cutanea tarda (PCT) was 1.2:100 000 (in 2006 n=63), which is only one fourth of the numbers reported from other European countries. The estimated incidence of PCT was 0.5:1 000 000. Based on measurements of the uroporphyrinogen decarboxylase activity in erythrocytes, the proportion of familial PCT was 49% of the cases. The prevalence of erythropoietic protoporphyria (EPP) was at 0.8:100 000 (in 2006 n=39) including asymptomatic carriers of a mutation in the ferrochelatase (FECH) gene. The incidence of EPP was estimated at 0.1:1 000 000. After 1980 the penetrance was 37% among patients with VP. Of the mutation carriers (n=57) 30% manifested with skin symptoms. Frequency of skin symptom as only clinical sign was stable before or after 1980 (22% vs. 21%), but acute attacks became infrequent (29% vs. 7%). Of the symptomatic patients 30% had both acute attacks and skin symptoms and 80% had skin symptoms. Fragility (95%) and blistering (46%) of the skin in the backs of the hands were the most common skin symptoms. Transient correction of porphyrin metabolism using eight haem arginate infusions within five weeks had no effect on the skin symptoms in three of four patients with VP. In one case skin symptoms disappeared transiently. One patient with homozygous VP had severe photosensitivity since birth. Sensory polyneuropathy, glaucoma and renal failure developed during the 25-year follow-up without the presence of acute attacks. The I12T mutation was detected in both of his alleles in the protoporphyrinogen oxidase gene. Lack of skin symptoms and infrequency of acute attacks (1/9) in the patients with I12T mutation at the heterozygous stage indicate a mild phenotype (the penetrance 11%). Four mutations (751delGAGAA, 1122delT, C286T, C343T) in the FECH gene were characterised in four of 15 families with EPP. Burning pain (96%) and swelling (92%) of the sun-exposed skin were the major skin symptoms. Hepatopathy appeared in one of 25 symptomatic patients (4%). Clinical manifestations and associated factors of PCT were similar in the sporadic and familial types of PCT. The majority of the patients with PCT had one to three precipitating factors: alcohol intake (78%), mutations in hemochromatosis associated gene (50%), use of oestrogen (25% of women) and hepatitis B or C infections (25 %). Fatty liver disease (67%) and siderosis (67%) were commonly found in their liver biopsies. The major histopathological change of the sun-exposed skin in the patients with VP (n=20), EPP (n=8) and PCT (n=5) was thickening of the vessel walls of the upper dermis suggesting that the vessel wall is the primary site of the phototoxic reaction in each type of porphyria. The fine structure of the vessel walls was similar in VP, EPP and PCT consisting of the multilayered basement membrane and excess of finely granular substance between the layers which were surrounded by the band of homogenous material. EPP was characterised by amorphous perivascular deposits extending also to the extravascular space. In direct immunofluorescence study homogenous IgG deposits in the vessel walls of the upper dermis of the sun-exposed skin were demonstrated in each type of porphyria. In EPP the excess material around vessel walls consisted of other proteins such as serum amyloid protein, and kappa and lambda light chains in addition to the basement membrane constituents such as collagen IV and laminin. These results suggest that the alterations of the vessel walls are a consequence of the repeated damage and the repairing process in the vessel wall. The microscopic alterations could be demonstrated even in the normal looking but sun-exposed skin of the patients with EPP during the symptom-free phase suggesting that vascular change can be chronic. The stability of vascular changes in the patients with PCT after treatment indicates that circulating porphyrins are not important for the maintenance of the changes.

Early-onset depressive disorders,related mental health disorders and substance use-A prospective : longitudinal study of Finnish twins born 1983-1987

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.

Molecular Genetics of Lactase Deficiencies

Congenital lactase deficiency (CLD) (MIM 223000) is a rare autosomal recessive gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. The CLD locus was previously assigned by linkage and linkage disequilibrium analyses on 2q21 in 19 Finnish families. In this study, the molecular background of this disorder is reported. The CLD locus was refined in 32 CLD patients in 24 families by using microsatellite and single nucleotide polymorphism (SNP) haplotypes. Mutation analyses were performed by direct sequencing. We identified 5 distinct mutations in the lactase (LCT) gene, encoding the enzyme that hydrolyzes lactose in the intestinal lumen. These findings facilitate genetic testing of CLD in clinical practice and enable genetic counseling. The present data also provide the basis for detailed characterization of the molecular pathogenesis of this disorder. Adult-type hypolactasia (MIM 223100) (lactase non-persistence, lactose intolerance) is an autosomal recessive gastrointestinal condition that is a result of a decline in the activity of lactase in the intestinal lumen after weaning. Adult-type hypolactasia is considered to be a normal phenomenon among mammals and symptoms are remarkably milder than experienced in CLD. Recently, a variant C/T-13910 was shown to associate with the adult-type hypolactasia trait, locating 13.9 kb upstream of the LCT gene. In this study, the functional significance of the C/T-13910 variant was determined by studying the LCT mRNA levels in intestinal biopsy samples in children and adults with different genotypes. RT-PCR followed by solid-phase minisequencing was applied to determine the relative expression levels of the LCT alleles using an informative SNP located in exon 1. In children, the C-13910 allele was observed to be downregulated after five years of age in parallel with lactase enzyme activity. The expression of the LCT mRNA in the intestinal mucosa in individuals with the T-13910 A-22018 alleles was 11.5 times higher than that found in individuals with the C-13910, G-22018 alleles. These findings suggest that the C/T-13910 associated with adult-type hypolactasia is associated with the transcriptional regulation of the LCT gene. The presence of the T-13910 A-22018 allele also showed significant elevation lactase activity. Galactose, the hydrolysing product of the milk sugar lactose, has been hypothesized to be poisonous to ovarian epithelial cells. Hence, consumption of dairy products and lactase persistence has been proposed to be a risk factor for ovarian carcinoma. To investigate whether lactase persistence is related to the risk of ovarian carcinoma the C/T-13910 genotype was determined in a cohort of 782 women with ovarian carcinoma 1331 individuals serving as controls. Lactase persistence did not associate significantly with the risk for ovarian carcinoma in the Finnish, in the Polish or in the Swedish populations. The findings do not support the hypothesis that lactase persistence increases the risk for ovarian carcinoma.

Sianlihan tuotantoon vaikuttavat tekijät vuosina 1995-2006

Ennen Suomen EU-jäsenyyttä kansallisen maatalouspolitiikan yksi päätavoitteista oli elintarvikeomavaraisuus. Tavoitteen saavuttamiseksi Suomessa oli maatalouspolitiikan osalta käytössä hintatukijärjestelmä, jossa yksi pääasiallisista tuotannon ohjauskeinoista oli tavoitehinnat, joilla valtiovalta pyrki vaikuttamaan tuottajahintoihin. Tavoitehintojen avulla tuottajat pystyivät ennakoimaan tulevan hintatason ja näin siirtämään tuotantoaan taloudellisesti kannattavimpaan suuntaan. Tästä oli kuitenkin seurauksena kotimaisen elintarvikeomavaraisuuden ylittyminen varsinkin eläinkunnan tuotteiden osalta. Vuonna 1994 lihatuotteiden yhteenlaskettu omavaisuus oli 110 prosenttia. Sianlihan osalta omavaisuus oli hieman tätä suurempi, 114 prosenttia. Suomen liityttyä EU:n jäsenmaaksi vuonna 1995 tavoitehinnoista luovuttiin ja samalla tuottajahinnat putosivat. Korvaukseksi tuottajahintojen pudotuksesta tuottajille alettiin maksaa suoria tulotukia. Tutkimuksen tarkoituksena oli selvittää mitkä tekijät vaikuttivat sianlihan tuotantopäätöksiin maatalouden muuttuneessa toimintaympäristössä ja miten yhteisen maatalouspolitiikan uudistukset vaikuttivat sianlihan tarjontaan. Tutkimuksen tarkasteluaikavälinä olivat vuodet 1995 2006. Tutkimuksen tavoitteena oli myös tuotantoon vaikuttavien tekijöiden pohjalta ennustaa sianlihan tuotantoa vuoteen 2013. Tuotantopäätöksiin vaikuttavia tekijöitä tarkasteltiin regressio-analyysin avulla, jotta saataisiin selville sianlihan tuotantoa parhaiten selittävät tekijät. Tutkimuksen aikasarja-aineisto poimittiin maa- ja metsätalousministeriön tietopalvelukeskuksen (Tike:n) ja tilastokeskuksen julkaisemista ja ylläpitämistä tilastoista. Sianlihan tuotantoon vaikuttavien tekijöiden ennusteisiin tutkimuksessa käytettiin sekä kansainvälisten että kotimaisten taloustutkimuslaitosten ja organisaatioiden ennusteita. Tutkimuksen teoreettinen viitekehys muodostui yrityksen teoriasta, tarjontateoriasta ja aikavälin merkityksestä tarjontaan. Tuotantomallin estimoinnin tuloksena sianlihan tuotantoon vaikuttivat vuosien 1996 2006 aikana sianlihan tuotannon tuottavuuden kasvua kuvaava teknologiamuuttuja, neljällä neljänneksellä viivästetty sianlihan tuottajahinta ja tuotantotuet yhteenlaskettuna, kolmella neljänneksellä viivästetty vehnän tuottajahinta, kahdeksalla neljänneksellä viivästetty sianlihan tuotanto, kahdella neljänneksellä viivästetty porsaan välityshinta ja kuudella neljänneksellä viivästetty investointituet. Sianlihan tuotantomallin selitysasteeksi saatiin 0,91. Estimoidulla tuotantomallilla ennustettiin sianlihan tuotannon kehitystä vuosina 2007 2013. Perusskenaariossa tuotannon ennustettiin muuttuvan vuodesta 2007 eteenpäin samalla tavalla kuin vuosina 1995 2006 keskimäärin. Perusskenaarion lisäksi tuotantomallilla simuloitiin tuotantotukien ja investointitukien dekoplauksen vaikutusta sianlihan tuotantoon. Tuotantotukien dekoplauksen myötä sianlihan tuotanto laskisi 177 milj. kiloon vuonna 2009, mutta nousisi 193 milj. kiloon vuonna 2013. Investointitukien dekoplauksen myötä tuotanto laskisi 176 milj. kiloon vuonna 2009 ja nousisi vuoteen 2013 mennessä 191 milj. kiloon. Suurimman pudotuksen aiheutti kuitenkin vehnän tuottajahinnan nousu vuosien 2006 ja 2007 aikana, jonka seurauksena sianlihan tuotanto laskisi jo vuonna 2008 180 milj. kiloon.

Circadian Rhythm Disruptions and Health

The doctoral thesis defined connections between circadian rhythm disruptions and health problems. Sleep debt, jet-lag, shift work, as well as transitions into and out of the daylight saving time may lead to circadian rhythm disruptions. Disturbed circadian rhythm causes sleep deprivation and decrease of mood and these effects may lead to higher accident rates and trigger mental illnesses. Circadian clock genes are involved in the regulation of the cell cycle and metabolism and thus unstable circadian rhythmicity may also lead to cancer development. In publications I-III it was explored how transitions into and out of the daylight saving time impact the sleep efficiency and the rest-activity cycles of healthy individuals. Also it was explored whether the effect of transition is different in fall as compared to spring, and whether there are subgroup specific differences in the adjustment to transitions into and out of daylight saving time. The healthy participants of studies I-III used actigraphs before and after the transitions and filled in the morningness-eveningness and seasonal pattern assessment questionnaires. In publication IV the incidence of hospital-treated accidents and manic episodes was explored two weeks before and two weeks after the transitions into and out of the daylight saving time in years 1987-2003. In publication V the relationship between circadian rhythm disruption and the prevalence of Non-Hodgkin lymphoma was studied. The study V consisted of all working aged Finns who participated in the national population census in 1970. For our study, all the cancers diagnosed during the years 1971-1995 were extracted from the Finnish Cancer Register and linked with the 1970 census files. In studies I-III it was noticed that transitions into and out of the daylight saving time disturbs the sleep-wake cycle and the sleep efficiency of the healthy participants. We also noticed that short sleepers were more sensitive than long sleepers for sudden changes in the circadian rhythm. Our results also indicated that adaptation to changes in the circadian rhythm is potentially sex, age and chronotype-specific. In study IV no significant increase in the occurrence of hospital treated accidents or manic episodes was noticed. However, interesting observations about the seasonal fluctuation of the occurrence rates of accidents and manic episodes were made. Study V revealed that there might be close relationship between circadian rhythm disruption and cancer. The prevalence of Non-Hodgkin lymphoma was the highest among night workers. The five publications included in this thesis together point out that disturbed circadian rhythms may have adverse effect on health. Disturbed circadian rhythms decrease the quality of sleep and weaken the sleep-wake cycle. A continuous circadian rhythm disruption may also predispose individuals to cancer development. Since circadian rhythm disruptions are common in modern society they might have a remarkable impact on the public health. Thus it is important to continue circadian rhythm research so that better prevention and treatment methods can be developed. Keywords: Circadian rhythm, daylight saving time, manic episodes, accidents, Non-Hodgkin lymphoma 11

Genetic background of bipolar disorder and related cognitive impairments

Bipolar disorder (BP) is a complex psychiatric disorder characterized by episodes of mania and depression. BP affects approximately 1% of the world’s population and shows no difference in lifetime prevalence between males and females. BP arises from complex interactions among genetic, developmental and environmental factors, and it is likely that several predisposing genes are involved in BP. The genetic background of BP is still poorly understood, although intensive and long-lasting research has identified several chromosomal regions and genes involved in susceptibility to BP. This thesis work aims to identify the genetic variants that influence bipolar disorder in the Finnish population by candidate gene and genome-wide linkage analyses in families with many BP cases. In addition to diagnosis-based phenotypes, neuropsychological traits that can be seen as potential endophenotypes or intermediate traits for BP were analyzed. In the first part of the thesis, we examined the role of the allelic variants of the TSNAX/DISC1 gene cluster to psychotic and bipolar spectrum disorders and found association of distinct allelic haplotypes with these two groups of disorders. The haplotype at the 5’ end of the Disrupted-in-Schizophrenia-1 gene (DISC1) was over-transmitted to males with psychotic disorder (p = 0.008; for an extended haplotype p = 0.0007 with both genders), whereas haplotypes at the 3’ end of DISC1 associated with bipolar spectrum disorder (p = 0.0002; for an extended haplotype p = 0.0001). The variants of these haplotypes also showed association with different cognitive traits. The haplotypes at the 5’ end associated with perseverations and auditory attention, while the variants at the 3’ end associated with several cognitive traits including verbal fluency and psychomotor processing speed. Second, in our complete set of BP families with 723 individuals we studied six functional candidate genes from three distinct signalling systems: serotonin-related genes (SLC6A4 and TPH2), BDNF -related genes (BDNF, CREB1 and NTRK2) and one gene related to the inflammation and cytokine system (P2RX7). We replicated association of the functional variant Val66Met of BDNF with BP and better performance in retention. The variants at the 5’ end of SLC6A4 also showed some evidence of association among males (p = 0.004), but the widely studied functional variants did not yield any significant results. A protective four-variant haplotype on P2RX7 showed evidence of association with BP and executive functions: semantic and phonemic fluency (p = 0.006 and p = 0.0003, respectively). Third, we analyzed 23 bipolar families originating from the North-Eastern region of Finland. A genome-wide scan was performed using the 6K single nucleotide polymorphism (SNP) array. We identified susceptibility loci at chromosomes 7q31 with a LOD score of 3.20 and at 9p13.1 with a LOD score of 4.02. We followed up both linkage findings in the complete set of 179 Finnish bipolar families. The finding on chromosome 9p13 was supported (maximum LOD score of 3.02), but the susceptibility gene itself remains unclarified. In the fourth part of the thesis, we wanted to test the role of the allelic variants that have associated with bipolar disorder in recent genome-wide association studies (GWAS). We could confirm findings for the DFNB31, SORCS2, SCL39A3, and DGKH genes. The best signal in this study comes from DFNB31, which remained significant after multiple testing corrections. Two variants of SORCS2 were allelic replications and presented the same signal as the haplotype analysis. However, no association was detected with the PALB2 gene, which was the most significantly associated region in the previous GWAS. Our results indicate that BP is heterogeneous and its genetic background may accordingly vary in different populations. In order to fully understand the allelic heterogeneity that underlies common diseases such as BP, complete genome sequencing for many individuals with and without the disease is required. Identification of the specific risk variants will help us better understand the pathophysiology underlying BP and will lead to the development of treatments with specific biochemical targets. In addition, it will further facilitate the identification of environmental factors that alter risk, which will potentially provide improved occupational, social and psychological advice for individuals with high risk of BP.

Humanitaarisuuden varjossa : Poliittiset tekijät lastensiirroissa Ruotsiin sotiemme aikana ja niiden jälkeen

The evacuation of Finnish children to Sweden during WW II has often been called a small migration . Historical research on this subject is scarce, considering the great number of children involved. The present research has applied, apart from the traditional archive research, the framework of history-culture developed by Rüsen in order to have an all-inclusive approach to the impact of this historical event. The framework has three dimensions: political, aesthetic and cognitive. The collective memory of war children has also been discussed. The research looks for political factors involved in the evacuations during the Winter War and the Continuation War and the post-war period. The approach is wider than a purely humanitarian one. Political factors have had an impact in both Finland and Sweden, beginning from the decision-making process and ending with the discussion of the unexpected consequences of the evacuations in the Finnish Parliament in 1950. The Winter War (30.11.1939 13.3.1940) witnessed the first child transports. These were also the model for future decision making. The transports were begun on the initiative of Swedes Maja Sandler, the wife of the resigned minister of foreign affairs Rickard Sandler, and Hanna Rydh-Munck af Rosenschöld , but this activity was soon accepted by the Swedish government because the humanitarian help in the form of child transports lightened the political burden of Prime Minister Hansson, who was not willing to help Finland militarily. It was help that Finland never asked for and it was rejected at the beginning. The negative response of Minister Juho Koivisto was not taken very seriously. The political forces in Finland supporting child transports were stronger than those rejecting them. The major politicians in support belonged to Finland´s Swedish minority. In addition, close to 1 000 Finnish children remained in Sweden after the Winter War. No analysis was made of the reasons why these children did not return home. A committee set up to help Finland and Norway was established in Sweden in 1941. Its chairman was Torsten Nothin, an influential Swedish politician. In December 1941 he appealed to the Swedish government to provide help to Finnish children under the authority of The International Red Cross. This plea had no results. The delivery of great amounts of food to Finland, which was now at war with Great Britain, had automatically caused reactions among the allies against the Swedish imports through Gothenburg. This included the import of oil, which was essential for the Swedish navy and air force. Oil was later used successfully to force a reduction in commerce between Sweden and Finland. The contradiction between Sweden´s essential political interests and humanitarian help was solved in a way that did not harm the country´s vital political interests. Instead of delivering help to Finland, Finnish children were transported to Sweden through the organisations that had already been created. At the beginning of the Continuation War (25.6.1941 27.4.1945) negative opinion regarding child transports re-emerged in Finland. Karl-August Fagerholm implemented the transports in September 1941. In 1942, members of the conservative parties in the Finnish Parliament expressed their fear of losing the children to the Swedes. They suggested that Finland should withdraw from the inter-Nordic agreement, according to which the adoptions were approved by the court of the country where the child resided. This initiative failed. Paavo Virkkunen, an influential member of the conservative party Kokoomus in Finland, favoured the so-called good-father system, where help was delivered to Finland in the form of money and goods. Virkkunen was concerned about the consequences of a long stay in a Swedish family. The risk of losing the children was clear. The extreme conservative party (IKL, the Patriotic Movement of the Finnish People) wanted to alienate Finland from Sweden and bring Finland closer to Germany. Von Blücher, the German ambassador to Finland, had in his report to Berlin, mentioned the political consequences of the child transports. Among other things, they would bring Finland and Sweden closer to each other. He had also paid attention to the Nordic political orientation in Finland. He did not question or criticize the child transports. His main interest was to increase German political influence in Finland, and the Nordic political orientation was an obstacle. Fagerholm was politically ill-favoured by the Germans, because he had a strong Nordic political disposition and had criticised Germany´s activities in Norway. The criticism of child transports was at the same time criticism of Fagerholm. The official censorship organ of the Finnish government (VTL) denied the criticism of child transports in January 1942. The reasons were political. Statements made by members of the Finnish Parliament were also censored, because it was thought that they would offend the Swedes. In addition, the censorship organ used child transports as a means of active propaganda aimed at improving the relations between the two countries. The Finnish Parliament was informed in 1948 that about 15 000 Finnish children still remained in Sweden. These children would stay there permanently. In 1950 the members of the Agrarian Party in Finland stated that Finland should actively strive to get the children back. The party on the left (SKDL, the Democratic Movement of Finnish People) also focused on the unexpected consequences of the child transports. The Social Democrats, and largely Fagerholm, had been the main force in Finland behind the child transports. Members of the SKDL, controlled by Finland´s Communist Party, stated that the war time authorities were responsible for this war loss. Many of the Finnish parents could not get their children back despite repeated requests. The discussion of the problem became political, for example von Born, a member of the Swedish minority party RKP, related this problem to foreign policy by stating that the request to repatriate the Finnish children would have negative political consequences for the relations between Finland and Sweden. He emphasized expressing feelings of gratitude to the Swedes. After the war a new foreign policy was established by Prime Minister (1944 1946) and later President (1946 1956) Juho Kusti Paasikivi. The main cornerstone of this policy was to establish good relations with the Soviet Union. The other, often forgotten, cornerstone was to simultaneously establish good relations with other Nordic countries, especially Sweden, as a counterbalance. The unexpected results of the child evacuation, a Swedish initiative, had violated the good relations with Sweden. The motives of the Democratic Movement of Finnish People were much the same as those of the Patriotic Movement of Finnish People. Only the ideology was different. The Nordic political orientation was an obstacle to both parties. The position of the Democratic Movement of Finnish People was much better than that of the Patriotic Movement of Finnish People, because now one could clearly see the unexpected results, which included human tragedy for the many families who could not be re-united with their children despite their repeated requests. The Swedes questioned the figure given to the Finnish Parliament regarding the number of children permanently remaining in Sweden. This research agrees with the Swedes. In a calculation based on Swedish population registers, the number of these children is about 7 100. The reliability of this figure is increased by the fact that the child allowance programme began in Sweden in 1948. The prerequisite to have this allowance was that the child be in the Swedish population register. It was not necessary for the child to have Swedish nationality. The Finnish Parliament had false information about the number of Finnish children who remained in Sweden in 1942 and in 1950. There was no parliamentary control in Finland regarding child transports, because the decision was made by one cabinet member and speeches by MPs in the Finnish Parliament were censored, like all criticism regarding child transports to Sweden. In Great Britain parliamentary control worked better throughout the whole war, because the speeches regarding evacuation were not censored. At the beginning of the war certain members of the British Labour Party and the Welsh Nationalists were particularly outspoken about the scheme. Fagerholm does not discuss to any great extent the child transports in his memoirs. He does not evaluate the process and results as a whole. This research provides some possibilities for an evaluation of this sort. The Swedish medical reports give a clear picture of the physical condition of the Finnish children when arriving in Sweden. The transports actually revealed how bad the situation of the poorest children was. According to Titmuss, similar observations were made in Great Britain during the British evacuations. The child transports saved the lives of approximately 2 900 children. Most of these children were removed to Sweden to receive treatment for illnesses, but many among the healthy children were undernourished and some suffered from the effects of tuberculosis. The medical inspection in Finland was not thorough. If you compare the figure of 2 900 children saved and returned with the figure of about 7 100 children who remained permanently in Sweden, you may draw the conclusion that Finland as a country failed to benefit from the child transports, and that the whole operation was a political mistake with far-reaching consequenses. The basic goal of the operation was to save lives and have all the children return to Finland after the war. The difficulties with the repatriation of the children were mainly psychological. The level of child psychology in Finland at that time was low. One may question the report by Professor Martti Kaila regarding the adaptation of children to their families back in Finland. Anna Freud´s warnings concerning the difficulties that arise when child evacuees return are also valid in Finland. Freud viewed the emotional life of children in a way different from Kaila: the physical survival of a small child forces her to create strong emotional ties to the person who is looking after her. This, a characteristic of all small children, occurred with the Finnish children too, and it was something the political decision makers in Finland could not see during and after the war. It is a characteristic of all little children. Yet, such experiences were already evident during the Winter War. The best possible solution had been to limit the child transports only to children in need of medical treatment. Children from large and poor families had been helped by organising meals and by buying food from Denmark with Swedish money. Assisting Finland by all possible means should have been the basic goal of Fagerholm in September 1941, when the offer of child transports came from Sweden. Fagerholm felt gratitude towards the Swedes. The risks became clear to him only in 1943. The war children are today a rather scattered and diffuse group of people. Emotionally, part of these children remained in Sweden after the war. There is no clear collective memory, only individual memories; the collective memory of the war children has partly been shaped later through the activities of the war child associations. The main difference between the children evacuated in Finland (for example from Karelia to safer areas with their families) and the war children, who were sent abroad, is that the war children lack a shared story and experience with their families. They were outsiders . The whole matter is sensitive to many of such mothers and discussing the subject has often been avoided in families. The war-time censorship has continued in families through silence and avoidance and Finnish politicians and Finnish families had to face each other on this issue after the war. The lack of all-inclusive historical research has also prevented the formation of a collective awareness among war children returned to Finland or those remaining permanently abroad.. Knowledge of historical facts will help war-children by providing an opportunity to create an all-inclusive approach to the past. Personal experiences should be regarded as part of a large historical entity shadowed by war and where many political factors were at work in both Finland and Sweden. This means strengthening of the cognitive dimension discussed in Rüsen´s all-inclusive historical approach.

Nuorten mäntyjen ulkoisen laadun kehitykseen vaikuttavat tekijät

Männyn laatuun vaikuttavista tekijöistä tässä tutkimuksessa selvitettiin, mitkä tekijät aiheuttavat nuorissa männyissä oksikkuutta, mutkaisuutta käsittäen myös lenkouden ja haaraisuutta. Jokaiselle laatuvialle laadittiin kolme eritasoista mallia. Eniten keskityttiin tutkimaan oksikkuutta aiheuttavia tekijöitä, koska oksikkuus vaikuttaa männyn sisäiseen oksaisuuteen, joka on yleisin sahatavarakappaleen laatuluokan määräävä ominaisuus. Lisäksi mutkaisuus ja erityisesti haaraisuus osoittautuivat melko sattumanvaraisesti esiintyviksi laatuvioiksi, minkä takia niiden kehittymiseen vaikuttavia tekijöitä on vaikea määritellä. Tutkimuksessa käytettiin Metsäntutkimuslaitoksen taimikoiden inventointikokeiden (TINKA-kokeet) aineiston ensimmäisen ja kolmannen mittauskerran tuloksia. Näiden mittauskertojen väli oli 15 vuotta. Tutkimuksen perustuminen useampaan kuin yhteen mittauskertaan erottaa tämän tutkimuksen monista muista mäntyjen laatua käsittelevistä tutkimuksista, jotka ovat perustuneet yhden mittauskerran poikkileikkausaineistoon. Laadittujen kolmen eritasoisen mallin perusteella voidaan todeta, että oksikkuuden ja mutkaisuuden kehittymistä mäntyihin pystytään arvioimaan kohtalaisesti jo metsikön perustietojen (syntytapa, kasvupaikka, lämpösumma) avulla, jotka metsänomistajalla on tiedossaan jo taimikkoa perustaessaan. Puutason mittauksilla pystytään selvästi tarkentamaan arviota siitä, tuleeko männystä oksikas vai ei. Sitä vastoin puutason mittaukset parantavat vain vähän arviota mutkaisuuden kehittymisestä. Haaraisuuden esiintymistä luotettavasti ennustavaa mallia ei pystytty tekemään. Oksikkuutta lisääviä tekijöitä mallien mukaan olivat mm. männyn suuri läpimitan kasvu, suuri suhteellinen pituus saman metsikön muihin puihin verrattuna, alhainen kasvatustiheys männyntaimikon alkukehitysvaiheessa ja taimikonhoidon tekemättä jättäminen. Mutkaisuutta lisääviä tekijöitä olivat mm. suuri lämpösumma eli männikön sijainti Etelä-Suomessa, männyn suuri läpimitan kasvu, pieni suhteellinen pituus, alhainen kasvatustiheys männyntaimikon alkukehitysvaiheessa ja taimikonhoidon tekemättä jättäminen. Eri uudistamistavoista kylvö osoittautui parhaimmaksi laadun kannalta sekä oksikkuutta että mutkaisuutta tarkasteltaessa. Haaraisuutta lisääviä tekijöitä olivat mm. pieni lämpösumma eli männikön sijainti Pohjois-Suomessa, männyn suuri läpimitan kasvu ja alhainen kasvatustiheys männyntaimikon alkukehitysvaiheessa.

Suomenlinnan Kustaanmiekan ketokasvillisuus ja siihen vaikuttavat tekijät

Suomenlinna on yksi Helsingin suosituimmista matkailu- ja kulttuurinähtävyyksistä. Kustaanmiekan, samoin kuin koko Suomenlinnan luonto on muodostunut perinteisestä suomalaisesta saaristoluonnosta ja vuosisatojen saatossa paikalle tulleista linnoituksien kasvistosta. Saaren vaihtelevien elinympäristöjen johdosta alueen kasvillisuus on hyvin rikasta. Linnoituksien monet kasvilajit ovat tulleet tulokaskasveina eri puolilta Eurooppaa sekä Venäjältä. Suurin osa Suomenlinnan alueesta on kallioketoa ja tämän lisäksi myös valliketoa, joista molemmat kuuluvat suojeltaviin alueisiin. Kustaanmiekan niityillä kasvaa keto- ja paahdelajeja, kuten harvinaista ketonoidanlukkoa (Botrychium lunaria L.) sekä ketoneilikkaa (Dianthus deltoides L.). Tämän tutkimuksen ensisijaisena tarkoituksena oli kartoittaa Kustaanmiekan alueen kesäkauden 2009 ketokasvilajisto ja eri putkilokasvilajien runsaus. Tutkimuksessa selvitettiin myös maaperätekijöiden ja alueen hoitohistorian mahdollista vaikutusta ketokasvilajistoon. Tutkimuksessa kartoitettiin kymmenen eri kedon kasvillisuus Suomenlinnan Kustaanmiekan linnoitusalueella. Kedot sijaitsivat eri puolilla Kustaanmiekkaa, sellaisilla paikoilla, missä ketokasvillisuus oli runsainta. Maastotyöt suoritettiin kesä- ja heinäkuussa laskemalla jokaisen kedon ruutujen putkilokasvien peittävyydet sekä listaamalla ylös myös ruutujen ulkopuoliset kevät- ja loppukesän kukkijat touko- ja elokuussa. Maaperän ominaisuuksien määrittämiseksi otettiin kultakin kedolta pintamaanäytteet elokuussa. Muita tutkittuja muuttujia olivat maapinnan kaltevuus sekä sammalen, karikkeen, paljaan maan, kenttäkasvillisuuden pohjakerros ja kallion osuus tutkimusruuduilla. Ketojen kasvillisuuden keskimääräinen korkeus mitattiin kesä- ja heinäkuussa. Kasvistossa oli selviä eroavaisuuksia ketojen välillä. Kasvilajien määrä vaihteli ketojen kokonaislajimäärän ollessa 40-60 kasvilajia. Yhteensä kedoilta löytyi 120 eri putkilokasvilajia, joista useimmat kukkivat sekä kesä- että heinäkuussa. Ketojen kasvilajimäärä vaihteli yhdellä neliömetrillä 6,3-13,6 kasvilajiin, minkä lisäksi Shannon-Wienerin diversiteetti-indeksi vaihteli 1,4-2,3 arvon välillä. Yleisimpiä lajeja, joita kedoilla tavattiin, olivat muun muassa siankärsämö (Achillea millefolium L.), koiranheinä (Dactylis glomerata L.), juolavehnä (Elymus repens L.) ja hopeahanhikki (Potentilla argentea L.). Alueella kasvoi myös muutamia sotatulokaslajeja kuten harmiota (Berteroa incana L.), ukonpalkoa (Bunias orientalis L.) ja karvahorsmaa (Epilobium hirsutum L.). Maaperätekijöillä, kuten suurella fosforin pitoisuudella ei ollut vaikutusta kasvilajien määrään kedoilla. Vain maan pH ja johtoluku korreloivat positiivisesti ketojen kasvillisuuden korkeuden kanssa. Vaikka tulosten perusteella ketojen hoidolla ei ollut vaikutusta ketojen kasvillisuuden määrään, voidaan kuitenkin olettaa oikeanlaisen hoidon parantavan tyypillisten ketokasvien kilpailukykyä muita niittykasveja kohtaan.

Word-of-mouth -viestintään vaikuttavat tekijät Case: Agronomiliiton suosittelukampanja

Tämän tutkimuksen tavoitteena oli tarkastella laadullisten tutkimuskeinojen avulla keskeisten tekijöiden etenkin palkitsemisen vaikutusta word-of-mouth -viestintään. Teoriakatsauksen perusteella tutkimusaluetta lähestyttiin tarkastelemalla viittä eri aihealuetta, suosittelijan sisäistä motivaatiota, kokemusta tuotteen tai palvelun ominaisuuksista, suhdetta yrityksen kanssa ja suosituksen vastaanottajan kanssa sekä palkitsemista ja suosittelukampanjaa. Tutkimuksen teoreettisessa osuudessa avattiin käsite word-of-mouth -viestintä ja suosittelumarkkinointi sekä selvitettiin word-of-mouth -viestintään vaikuttavia keskeisiä tekijöitä, jotta suosittelupäätökseen liittyviä tekijöitä olemassa olevan tutkimustiedon avulla. Empiirinen tutkimus toteutettiin laadullisena tutkimuksena, jossa tutkimuksen casena oli Agronomiliitto ry:n suosittelukampanja. Tutkimuksessa haastateltiin Helsingin yliopiston maatalous-metsätieteellisen tiedekunnan syksyn 2009 tutoreita koskien heille suunnattua jäsenhankintakampanjaa. Kampanjan tarkoituksena oli saada tutorit suosittelemaan Agronomiliiton jäsenyyttä uusille opiskelijoille. Parhaiten kampanjassa menestyneet tutorit palkittiin. Kahdeksasta haastateltavasta seitsemän oli Agronomiliiton jäseniä. Haastateltavista kolme palkittiin hyvästä menestyksestä kampanjassa. Aineistonkeruumenetelmänä käytettiin puolistrukturoitua ja henkilökohtaista teemahaastattelua. Haastatteluissa pyrittiin ennen kaikkea selvittämään haastateltavien ajatuksia liittyen word-of-mouth -viestintään sekä suosittelusta palkitsemiseen. Tutkimus antaa suuntaa, että sisäisellä motivaatiotekijöillä on suuri merkitys suositteluviestinnän tapahtumiselle. Suosittelijan tulee tunnistaa suositeltavasta tuotteesta tai palvelusta koetut hyödyt. Suosittelua myös edesauttaa jos suosittelija omaa mielipidejohtajan ominaisuuksia. Palkitseminen toimii kannustimena suositella, mutta palkitsemisjärjestelmä tulee miettiä huolellisesti, jotta suosittelija ei koe suosittelun vähentävän omaa tai suositteluviestin uskottavuutta. Tutkimuksen tulokset viittaavat molempien, suosittelijan ja suosittelun vastaanottajan palkitsemisen olevan paras palkitsemisjärjestelmä suosittelukampanjassa.

Ammatillisten opettajien tieto- ja viestintätekniikan opetuskäytön intentionaalisuutta selittävät tekijät

Intention-based models have been one of the main theoretical orientations in the research on the implementation of information and communication technology (ICT). According to these models, actual behavior can be predicted from the intention towards the behavior. If the level of intention to use technology is high, the probability of actual usage of ICT increases. The purpose of this study was to find out which factors explain vocational teachers intention to use ICT in their teaching. In addition, teachers of media and information sciences and teachers of welfare and health were compared. The study also explored how regularly ICT was applied by teachers and how strong their intention to apply the technology was. This Master s thesis is a quantitative study and the data was collected using an Email survey and Eform. The instruments were based on a decomposed theory of planned behavior. The research group consisted of 22 schools of media and information sciences and 20 schools of welfare and health. The data consisted of 231 vocational teachers: 57 teachers worked with media and information sciences and 174 with welfare and health. The data was analyzed using Mann-Whitney U-test, factor analysis and regression analysis. In addition, categorized results were compared with previous study. In this study, the intention to use ICT in teaching was explained by the teachers attitudes and skills and the attitudes of their work community. However, the environment in which ICT was used, i.e., the technical environment, economical resources and time, did not explain the intention. The results did not directly support any of the intention-based models, but they could be interpreted as congruent with the technology acceptance model. The majority of the teachers used ICT at least weekly. They had a strong intention to continue to do that in the future. The study also revealed that there were more teachers who had a critical attitude towards ICT among the teachers of welfare and health. According to the results of this study, it is not possible to state that ICT would not suit any one profession because in every group with teachers with a critical attitude towards ICT there were also teachers with a positive attitude.

Lohjanjärven tilan kehittyminen ja siihen vaikuttaneet tekijät

English summary: The development of lake Lohjanjärvi and the factors affecting it