Mapinduzi Daima – Revolution Forever : Using the 1964 Revolution in Nationalistic Political Discourses in Zanzibar

This Master's thesis examines two opposite nationalistic discourses on the revolution of Zanzibar. Chama cha Mapinduzi (CCM), the party in power since the 1964 revolution defends its revolutionary and "African" heritage in the current multi-party system. New nationalists, including among others the main opposition party Civic United Front (CUF), question both the 1964 revolution and the post-revolution period and blame CCM for empty promises, corruption and ethnic discrimination. This study analyzes the role of a significant historical event in the creation of nationalistic ideology and national identity. The 1964 revolution forms the nucleus of various debates related to the history of Zanzibar: slavery, colonialism, racial discrimination and political violence. Representations of these Social constructivist principles form the basis of this study, and central concepts in the theoretical framework are nationalism, national identity, ethnicity and race. I use critical discourse analysis as my research method, lean on the work by Teun A. van Dijk and Norman Fairclough as the most significant researchers in this field. I examine particularly the ways in which linguistic methods, such as stereotypes and metaphors are used to form in- and out-groups ("us" vs. "others"). My material, both in Swahili and English, was collected mainly in Tanzania in the fall of 2007 and from online sources in the spring of 2009. It includes publications by the Zanzibari government between the years of 1964-2000 (12), official speeches for the Revolution Day or the Union Day (12), articles from Tanzanian newspapers from the 1990s until the year of 2009 (15), memoirs and political pamphlets (10), blog posts and opinion pieces from four different websites (8), and interviews or personal communication in Zanzibar, Dar es Salaam and Uppsala (8). Nationalistic rhetoric often creates enemy images by using binary good-bad oppositions. Both discourses in this study build identities on the basis of "otherness" and exclusion, with the intent of emphasizing the particularity of the own group and excluding "evilness" outside the own reference group. These opposite views on the 1964 revolution as the main axis of the history of Zanzibar build different portraits of the nation and Zanzibari-ness (Uzanzibari). CCM still relies on the pre-revolutionary enemy images of Arabs as selfish rulers and cruel slave traders. For CCM, Zanzibar is primarily an "African" nation and a part of Tanzania which is threatened by "Arabs", the outsiders. In contrast, the new nationalists stress the long history of Zanzibar as multi-racial, cosmopolitan and formerly independent country which has its own, separate culture and identity from mainland Tanzanians. Heshima, honour/respect, one of the basic values of Swahili culture, occupies a central role in both discourses: the main party emphasizes that the revolution returned "heshima" to the Zanzibari Africans after centuries of humiliation, whereas the new nationalists claim that ever since the revolution all "non-Africans" have been humiliated and lost their "heshima". According to the new nationalists, true Zanzibari values which include tolerance and harmony between different "races" were lost when the "foreign" revolutionaries arrived from the mainland. Consequently, they see the 1964 revolution as Tanganyikan colonialism which began with the help of Western countries, and maintain that this "colonialism" still continues in the violent multi-party elections.

Principles of Pitch Organization in Béla Bartók's 'Duke Bluebeard's Castle'

The topic of my doctoral thesis is to demonstrate the usefulness of incorporating tonal and modal elements into a pitch-web square analysis of Béla Bartók's (1881-1945) opera, 'A kékszakállú herceg vára' ('Duke Bluebeard's Castle'). My specific goal is to demonstrate that different musical materials, which exist as foreground melodies or long-term key progressions, are unified by the unordered pitch set {0,1,4}, which becomes prominent in different sections of Bartók's opera. In Bluebeard's Castle, the set {0,1,4} is also found as a subset of several tetrachords: {0,1,4,7}, {0,1,4,8}, and {0,3,4,7}. My claim is that {0,1,4} serves to link music materials between themes, between sections, and also between scenes. This study develops an analytical method, drawn from various theoretical perspectives, for conceiving superposed diatonic spaces within a hybrid pitch-space comprised of diatonic and chromatic features. The integrity of diatonic melodic lines is retained, which allows for a non-reductive understanding of diatonic superposition, without appealing to pitch centers or specifying complete diatonic collections. Through combining various theoretical insights of the Hungarian scholar Ernő Lendvai, and the American theorists Elliott Antokoletz, Paul Wilson and Allen Forte, as well as the composer himself, this study gives a detailed analysis of the opera's pitch material in a way that combines, complements, and expands upon the studies of those scholars. The analyzed pitch sets are represented on Aarre Joutsenvirta's note-web square, which adds a new aspect to the field of Bartók analysis. Keywords: Bartók, Duke Bluebeard's Castle (Op. 11), Ernő Lendvai, axis system, Elliott Antokoletz, intervallic cycles, intervallic cells, Allen Forte, set theory, interval classes, interval vectors, Aarre Joutsenvirta, pitch-web square, pitch-web analysis.

Half-occlusion processing in stereoscopic vision

This study investigated questions related to half-occlusion processing in human stereoscopic vision: (1) How does the depth location of a half-occluding figure affect the depth localization of adjacent monocular objects? (2) Is three-dimensional slant around vertical axis (geometric effect) affected by half-occlusion constraints? and (3) How the half-occlusion constraints and surface formation processes are manifested in stereoscopic capture? Our results showed that the depth localization of binocular objects affects the depth localization of discrete monocular objects. We also showed that the visual system has a preference for a frontoparallel surface interpretation if the half-occlusion configuration allows multiple interpretation alternatives. When the surface formation was constrained by textures, our results showed that a process of rematching spreading determines the resulting perception and that the spreading can be limited by illusory contours that support the presence of binocularly unmatched figures. The unmatched figures could be present, if the inducing figures producing the illusory surface contained binocular image differences that provided cues for quantitative da Vinci stereopsis. These findings provide evidence of the significant role of half-occlusions in stereoscopic processing.

Orphan nuclear receptor subfamily NR4A their interplay with other nuclear receptors and functions in osteoblasts

Nurr1, NGFI-B and Nor1 (NR4A2, NR4A1 and NR4A3, respectively) belong to the NR4A subfamily of nuclear receptors. The NR4A receptors are orphan nuclear receptors which means that activating or repressing ligands for these receptors have not been found. NR4A expression is rapidly induced in response to various stimuli including growth factors and the parathyroid hormone (PTH). The studies concerning the NR4A receptors in the central nervous system have demonstrated that they have a major role in the development and function of the dopaminergic neurons of the midbrain and in regulating hypothalamus-pituitary-adrenal-axis. However, the peripheral functions of the NR4A family are largely unknown. Cultured mouse primary osteoblasts, a preosteoblastic cell line and several osteoblastic cell lines were used to investigate the role of NR4A receptors in osteoblasts. NR4A receptors were shown to directly bind to and activate the promoter of the osteopontin gene (OPN) in osteoblastic cells, thus regulating its expression. OPN is a major bone matrix protein expressed throughout the differentiation of preosteoblastic cells into osteoblasts. The activation of the OPN promoter was shown to be dependent on the activation function-1 located in the N-terminal part of Nurr1 and to occur in both monomeric and RXR heterodimeric forms of NR4A receptors. Furthermore, PTH was shown to upregulate OPN expression through the NR4A family. It was also demonstrated that the fibroblast growth factor-8b (FGF-8b) induces the expression of NR4A receptors in osteoblasts as immediate early genes. This induction involved phosphatidylinositol-3 kinase, protein kinase C, and mitogen activated protein kinase, which are all major pathways of FGF signalling. Nurr1 and NGFI-B were shown to induce the proliferation of preosteoblastic cells and to reduce their apoptosis. FGF-8b was shown to stimulate the proliferation of osteoblastic cells through the NR4A receptors. These results suggest that NR4A receptors have a role both in the differentiation of osteoblasts and in the proliferation and apoptosis of preosteoblast. The NR4A receptors were found to bind to the same response element on OPN as the members of the NR3B family of orphan receptors do. Mutual repression was observed between the NR4A receptors and the NR3B receptors. This repression was shown to be dependent on the DNA-binding domains of both receptor families, but to result neither from the competition of DNA binding nor from the competition for coactivators. As the repression was dependent on the relative expression levels of the NR4As and NR3Bs, it seems likely that the ratio of the receptors mediates their activity on their response elements. Rapid induction of the NR4As in response to various stimuli and differential expression of the NR3Bs can effectively control the gene activation by the NR4A receptors. NR4A receptors can bind DNA as monomers, and Nurr1 and NGFI-B can form permissive heterodimers with the retinoid X receptor (RXR). Permissive heterodimers can be activated with RXR agonists, unlike non-permissive heterodimers, which are formed by RXR and retinoic acid receptor or thyroid hormone receptor (RAR and TR, respectively). Non-permissive heterodimers can only be activated by the agonists of the heterodimerizing partner. The mechanisms behind differential response to RXR agonists have remained unresolved. As there are no activating or repressing ligands for the NR4A receptors, it would be important to find out, how they are regulated. Permissiviness of Nurr1/RXR heterodimers was linked to the N-terminal part of Nurr1 ligand-binding domain. This region has previously been shown to mediate the interaction between NRs and corepressors. Non-permissive RAR and TR, permissive Nurr1 and NGFI-B, and RXR were overexpressed with corepressors silencing mediator for retinoic acid and thyroid hormone receptors (SMRT), and with nuclear receptor corepressor in several cell lines. Nurr1 and NGFI-B were found to be repressed by SMRT. The interaction of RXR heterodimers with corepressors was weak in permissive heterodimers and much stronger in non-permissive heterodimers. Non-permissive heterodimers also released corepressors only in response to the agonist of the heterodimeric partner of RXR. In the permissive Nurr1/RXR heterodimer, however, SMRT was released following the treatment with RXR agonists. Corepressor release in response to ligands was found to differentiate permissive heterodimers from non-permissive ones. Corepressors were thus connected to the regulation of NR4A functions. In summary, the studies presented here linked the NR4A family of orphan nuclear receptors to the regulation of osteoblasts. Nurr1 and NGFI-B were found to control the proliferation and apoptosis of preosteoblasts. The studies also demonstrated that cross-talk with the NR3B receptors controls the activity of these orphan receptors. The results clarified the mechanism of permissiviness of RXR-heterodimers. New information was obtained on the regulation and functions of NR4A receptors, for which the ligands are unknown.

Temporomandibular disorders and related psychosocial factors in non-patients : A survey and a clinical follow-up study based on the RDC/TMD

Temporomandibular disorders (TMD) and psychosocial factors reportedly associate. The underlying factors remain partially obscure, however, and further studies are required to clarify the relationships. The aims of this study were thus to assess in a non-patient working population the prevalence of TMD and related symptoms, and to clinically diagnose and follow the natural courses of TMD over a one-year period. In addition, possible comorbidity of temporomandibular and/or neck muscle pain and perceived stress and their impact on work performance were investigated, as well as how various psychosocial aspects relate to TMD. A questionnaire was mailed to all 30- to 55-year-old employees of the Finnish Broadcasting Company Ltd. whose employment in the Helsinki area had lasted at least five years (n = 1784). Of the 1339 subjects, who returned the questionnaire, 241 were examined according to the RDC/TMD and standard neck muscle palpation methods. Clinical signs of temporomandibular and/or neck muscle pain were found in 118 subjects. One-year follow-up TMD examinations were conducted on 211 subjects. The prevalence of frequent painless TMJ-related symptoms was 10%, orofacial pain 7%, neck pain 38%, and headache 15%. TMD diagnoses were: myofascial pain (13%), disc displacements (16%), and arthralgia, osteoarthritis, osteoarthrosis (4%). Chronic myofascial pain was present in 7% and chronic disc displacement with reduction in 11% of the subjects. Symptoms were significantly associated with almost all the studied psychosocial symptoms. Reduced work performance was significantly positively associated with continuous pain, severity of pain, and health stress perception, and according to logistic regression, somatization with the probability of having chronic myofascial pain. It could be concluded based on the results of this study among a non-patient working population that TMD and related symptoms are common and associated with psychosocial factors. Moreover, myofascial pain and disc displacement with reduction are the most common diagnoses of TMD. In addition, self-reported health related stress, and continuous pain in temporomandibular and/or neck muscles are associated with reduced work performance, and somatization is significantly associated with chronic myofascial pain.

Satelliitti-instrumentti IASI ja sen sovellukset sääpalvelulle

IASI on vuodesta 2007 käytössä ollut satelliitti-instrumentti Metop-polaarisatelliitissa. IASI-mittauksista johdettuja lopputuotteita ovat mm. lämpötilan ja kosteuden pystyprofiilit, pilven ylärajan lämpötila ja paine sekä eri hivenkaasujen pitoisuudet. Tämä työ on alkua IASI:n käyttöönotolle Ilmatieteen laitoksella. Työssä selvitetään IASI:n lämpötilaprofiileiden ja pilven ylärajan paineen soveltuvuutta sääpalvelulle vertailemalla niitä jo käytössä oleviin sääpalvelun työkaluihin. IASI-mittauksista johdettuja lämpötilaprofiileita verrataan Ilmatieteen laitoksen operatiivisiin pintaluotauksiin. Lisäksi tarkastellaan IASI:n lämpötilaprofiileiden vaikutusta paikallisen analyysi- ja ennustustyökalu LAPS:in lämpötila-analyysiin. IASI:n pilven ylärajan lämpötiloja verrataan AVHRR-radiometrista johdettuihin pilven ylärajan lämpötiloihin. IASI:sta ja AVHRR:stä johdetut keskimääräiset lämpötilat olivat lähes samat alapilville. Yläpilville ja osittain läpinäkyville cirrus-pilville lämpötilaero oli noin 5 Celsius-astetta. IASI:n lämpötilaluotaukset osoittautuivat käyttökelpoisiksi etenkin keski- ja ylätroposfäärissä (350 - 600 hPa), jossa IASI:n antama lämpötila erosi pintaluotauksen lämpötilasta vain noin +-1 Celsius-astetta. IASI:n lämpötilaluotausten suurin ongelma on mittausten katkeaminen pilven ylärajaan. IASI-luotauksilla oli suuri vaikutus LAPS-lämpötila-analyysiin mallin koko alueella, mutta vertailuaineiston puutteessa ei voida varmasti sanoa onko vaikutus positiivinen vai negatiivinen. Tulokset ovat lupaavia. IASI:n lämpötilaluotaukset ja pilven ylärajan lämpötila vaikuttavat käyttökelpoisilta sääpalvelun tarpeisiin.

Depression, Anxiety, Psychiatric Comorbidity and Dimensions of Temperament and Personality

This study is part of the Mood Disorders Project conducted by the Department of Mental Health and Alcohol Research, National Public Health Institute, and consists of a general population survey sample and a major depressive disorder (MDD) patient cohort from Vantaa Depression Study (VDS). The general population survey study was conducted in 2003 in the cities of Espoo and Vantaa. The VDS is a collaborative depression research project between the Department of Mental Health and Alcohol Research of the National Public Health Institute and the Department of Psychiatry of the Peijas Medical Care District (PMCD) beginning in 1997. It is a prospective, naturalistic cohort study of 269 secondary-level care psychiatric out- and inpatients with a new episode of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) MDD. In the general population survey study, a total of 900 participants (300 from Espoo, 600 from Vantaa) aged 20 70 years were randomly drawn from the Population Register Centre in Finland. A self-report booklet, including the Eysenck Personality Inventory (EPI), the Temperament and Character Inventory Revised (TCI-R), the Beck Depression Inventory and the Beck Anxiety Inventory was mailed to all subjects. Altogether 441 participants responded (94 returned only the shortened version without TCI-R) and gave their informed consent. VDS involved screening all patients aged 20-60 years (n=806) in the PMCD for a possible new episode of DSM-IV MDD. 542 consenting patients were interviewed with a semi-structured interview (the WHO Schedules for Clinical Assessment in Neuropsychiatry, version 2.0). 269 patients with a current DSM-IV MDD were included in the study and further interviewed with semi-structured interviews to assess all other axis I and II psychiatric diagnoses. Exclusion criteria were DSM-IV bipolar I and II, schizoaffective disorder, schizophrenia or another psychosis, organic and substance-induced mood disorders. In the present study are included those 193 (139 females, 54 males) individuals who could be followed up at both 6 and 18 months, and their depression had remained unipolar. Personality was investigated with the EPI. Personality dimensions associated not only to the symptoms of depression, but also to the symptoms of anxiety among general population and in depressive patients, as well as to comorbid disorders in MDD patients, supporting the dimensional view of depression and anxiety. Among the general population High Harm Avoidance and low Self-Directedness associated moderately, whereas low extraversion and high neuroticism strongly with the depressive and anxiety symptoms. The personality dimensions, especially high Harm Avoidance, low Self-Directedness and high neuroticism were also somewhat predictive of self-reported use of health care services for psychiatric reasons, and lifetime mental disorder. Moreover, high Harm Avoidance associated with a family history of mental disorder. In depressive patients, neuroticism scores were found to decline markedly and extraversion scores to increase somewhat with recovery. The predictive value of the changes in symptoms of depression and anxiety in explaining follow-up neuroticism was about 1/3 of that of baseline neuroticism. In contrast to neuroticism, the scores of extraversion showed no dependence on the symptoms of anxiety, and the change in the symptoms of depression explained only 1/20 of the follow-up extraversion compared with baseline extraversion. No evidence was found of the scar effect during a one-year follow-up period. Finally, even after controlling for symptoms of both depression and anxiety, depressive patients had a somewhat higher level of neuroticism (odds ratio 1.11, p=0.001) and a slightly lower level of extraversion (odds ratio 0.92, p=0.003) than subjects in the general population. Among MDD patients, a positive dose-exposure relationship appeared to exist between neuroticism and prevalence and number of comorbid axis I and II disorders. A negative relationship existed between level of extraversion and prevalence of comorbid social phobia and cluster C personality disorders. Personality dimensions are associated with the symptoms of depression and anxiety. Futhermore these findings support the hypothesis that high neuroticism and somewhat low extraversion might be vulnerability factors for MDD, and that high neuroticism and low extraversion predispose to comorbid axis I and II disorders among patients with MDD.

Long-term Outcome of DSM-IV Major Depressive Disorder in Psychiatric Care

Much of what we know regarding the long-term course and outcome of major depressive disorder (MDD) is based on studies of mostly inpatient tertiary level cohorts and samples predating the era of the current antidepressants and the use of maintenance therapies. In addition, there is a lack of studies investigating the comprehensive significance of comorbid axis I and II disorders on the outcome of MDD. The present study forms a part of the Vantaa Depression Study (VDS), a regionally representative prospective and naturalistic cohort study of 269 secondary-level care psychiatric out- and inpatients (aged 20-59) with a new episode of DSM-IV MDD, and followed-up up to five years (n=182) with a life-chart and semistructured interviews. The aim was to investigate the long-term outcome of MDD and risk factors for poor recovery, recurrences, suicidal attempts and diagnostic switch to bipolar disorder, and the association of a family history of different psychiatric disorders on the outcome. The effects of comorbid disorders together with various other predictors from different domains on the outcome were comprehensively investigated. According to this study, the long-term outcome of MDD appears to be more variable when its outcome is investigated among modern, community-treated, secondary-care outpatients compared to previous mostly inpatient studies. MDD was also highly recurrent in these settings, but the recurrent episodes seemed shorter, and the outcome was unlikely to be uniformly chronic. Higher severity of MDD predicted significantly the number of recurrences and longer time spent ill. In addition, longer episode duration, comorbid dysthymic disorder, cluster C personality disorders and social phobia predicted a worse outcome. The incidence rate of suicide attempts varied robustly de¬pending on the level of depression, being 21-fold during major depressive episodes (MDEs), and 4-fold during partial remission compared to periods of full remission. Although a history of previous attempts and poor social support also indicated risk, time spent depressed was the central factor determining overall long-term risk. Switch to bipolar disorder occurred mainly to type II, earlier to type I, and more gradually over time to type II. Higher severity of MDD, comorbid social phobia, obsessive compulsive disorder, and cluster B personality disorder features predicted the diagnostic switch. The majority of patients were also likely to have positive family histories not exclusively of mood, but also of other mental disorders. Having a positive family history of severe mental disorders was likely to be clinically associated with a significantly more adverse outcome.

Opioid dependence: Brain structure and function : a magnetic resonance imaging, neuropsychological, and electromagnetic study

Background: Opiod dependence is a chronic severe brain disorder associated with enormous health and social problems. The relapse back to opioid abuse is very high especially in early abstinence, but neuropsychological and neurophysiological deficits during opioid abuse or soon after cessation of opioids are scarcely investigated. Also the structural brain changes and their correlations with the length of opioid abuse or abuse onset age are not known. In this study the cognitive functions, neural basis of cognitive dysfunction, and brain structural changes was studied in opioid-dependent patients and in age and sex matched healthy controls. Materials and methods: All subjects participating in the study, 23 opioid dependents of whom, 15 were also benzodiazepine and five cannabis co-dependent and 18 healthy age and sex matched controls went through Structured Clinical Interviews (SCID) to obtain DSM-IV axis I and II diagnosis and to exclude psychiatric illness not related to opioid dependence or personality disorders. Simultaneous magnetoencephalography (MEG) and electroencephalography (EEG) measurements were done on 21 opioid-dependent individuals on the day of hospitalization for withdrawal therapy. The neural basis of auditory processing was studied and pre-attentive attention and sensory memory were investigated. During the withdrawal 15 opioid-dependent patients participated in neuropsychological tests, measuring fluid intelligence, attention and working memory, verbal and visual memory, and executive functions. Fifteen healthy subjects served as controls for the MEG-EEG measurements and neuropsychological assessment. The brain magnetic resonance imaging (MRI) was obtained from 17 patients after approximately two weeks abstinence, and from 17 controls. The areas of different brain structures and the absolute and relative volumes of cerebrum, cerebral white and gray matter, and cerebrospinal fluid (CSF) spaces were measured and the Sylvian fissure ratio (SFR) and bifrontal ratio were calculated. Also correlation between the cerebral measures and neuropsychological performance was done. Results: MEG-EEG measurements showed that compared to controls the opioid-dependent patients had delayed mismatch negativity (MMN) response to novel sounds in the EEG and P3am on the contralateral hemisphere to the stimulated ear in MEG. The equivalent current dipole (ECD) of N1m response was stronger in patients with benzodiazepine co-dependence than those without benzodiazepine co-dependence or controls. In early abstinence the opioid dependents performed poorer than the controls in tests measuring attention and working memory, executive function and fluid intelligence. Test results of the Culture Fair Intelligence Test (CFIT), testing fluid intelligence, and Paced Auditory Serial Addition Test (PASAT), measuring attention and working memory correlated positively with the days of abstinence. MRI measurements showed that the relative volume of CSF was significantly larger in opioid dependents, which could also be seen in visual analysis. Also Sylvian fissures, expressed by SFR were wider in patients, which correlated negatively with the age of opioid abuse onset. In controls the relative gray matter volume had a positive correlation with composite cognitive performance, but this correlation was not found in opioid dependents in early abstinence. Conclusions: Opioid dependents had wide Sylvian fissures and CSF spaces indicating frontotemporal atrophy. Dilatation of Sylvian fissures correlated with the abuse onset age. During early withdrawal cognitive performance of opioid dependents was impaired. While intoxicated the pre-attentive attention to novel stimulus was delayed and benzodiazepine co-dependence impaired sound detection. All these changes point to disturbances on frontotemporal areas.

Depressive Disorders in Primary Health Care

The Vantaa Primary Care Depression Study (PC-VDS) is a naturalistic and prospective cohort study concerning primary care patients with depressive disorders. It forms a collaborative research project between the Department of Mental and Alcohol Research of the National Public Health Institute, and the Primary Health Care Organization of the City of Vantaa. The aim is to obtain a comprehensive view on clinically significant depression in primary care, and to compare depressive patients in primary care and in secondary level psychiatric care in terms of clinical characteristics. Consecutive patients (N=1111) in three primary care health centres were screened for depression with the PRIME-MD, and positive cases interviewed by telephone. Cases with current depressive symptoms were diagnosed face-to-face with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P). A cohort of 137 patients with unipolar depressive disorders, comprising all patients with at least two depressive symptoms and clinically significant distress or disability, was recruited. The Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), medical records, rating scales, interview and a retrospective life-chart were used to obtain comprehensive cross-sectional and retrospective longitudinal information. For investigation of suicidal behaviour the Scale for Suicidal Ideation (SSI), patient records and the interview were used. The methodology was designed to be comparable to The Vantaa Depression Study (VDS) conducted in secondary level psychiatric care. Comparison of major depressive disorder (MDD) patients aged 20-59 from primary care in PC-VDS (N=79) was conducted with new psychiatric outpatients (N =223) and inpatients (N =46) in VDS. The PC-VDS cohort was prospectively followed up at 3, 6 and 18 months. Altogether 123 patients (90%) completed the follow-up. Duration of the index episode and the timing of relapses or recurrences were examined using a life-chart. The retrospective investigation revealed current MDD in most (66%), and lifetime MDD in nearly all (90%) cases of clinically significant depressive syndromes. Two thirds of the “subsyndromal” cases had a history of major depressive episode (MDE), although they were currently either in partial remission or a potential prodromal phase. Recurrences and chronicity were common. The picture of depression was complicated by Axis I co-morbidity in 59%, Axis II in 52% and chronic Axis III disorders in 47%; only 12% had no co-morbidity. Within their lifetimes, one third (37%) had seriously considered suicide, and one sixth (17%) had attempted it. Suicidal behaviour clustered in patients with moderate to severe MDD, co-morbidity with personality disorders, and a history of treatment in psychiatric care. The majority had received treatment for depression, but suicidal ideation had mostly remained unrecognised. The comparison of patients with MDD in primary care to those in psychiatric care revealed that the majority of suicidal or psychotic patients were receiving psychiatric treatment, and the patients with the most severe symptoms and functional limitations were hospitalized. In other clinical aspects, patients with MDD in primary care were surprisingly similar to psychiatric outpatients. Mental health contacts earlier in the current MDE were common among primary care patients. The 18-month prospective investigation with a life-chart methodology verified the chronic and recurrent nature of depression in primary care. Only one-quarter of patients with MDD achieved and maintained full remission during the follow-up, while another quarter failed to remit at all. The remaining patients suffered either from residual symptoms or recurrences. While severity of depression was the strongest predictor of recovery, presence of co-morbid substance use disorders, chronic medical illness and cluster C personality disorders all contributed to an adverse outcome. In clinical decision making, beside severity of depression and co-morbidity, history of previous MDD should not be ignored by primary care doctors while depression there is usually severe enough to indicate at least follow-up, and concerning those with residual symptoms, evaluation of their current treatment. Moreover, recognition of suicidal behaviour among depressed patients should also be improved. In order to improve outcome of depression in primary care, the often chronic and recurrent nature of depression should be taken into account in organizing the care. According to literature management programs of a chronic disease, with enhancement of the role of case managers and greater integration of primary and specialist care, have been successful. Optimum ways of allocating resources between treatment providers as well as within health centres should be found.

Cardiac function before and after treatment for various types of loading conditions and in myocardial restriction : A prospective study on pediatric patients with two- and three-dimensional echocardiography and measurement of serum natriuretic peptides

Background: The incidence of all forms of congenital heart defects is 0.75%. For patients with congenital heart defects, life-expectancy has improved with new treatment modalities. Structural heart defects may require surgical or catheter treatment which may be corrective or palliative. Even those with corrective therapy need regular follow-up due to residual lesions, late sequelae, and possible complications after interventions. Aims: The aim of this thesis was to evaluate cardiac function before and after treatment for volume overload of the right ventricle (RV) caused by atrial septal defect (ASD), volume overload of the left ventricle (LV) caused by patent ductus arteriosus (PDA), and pressure overload of the LV caused by coarctation of the aorta (CoA), and to evaluate cardiac function in patients with Mulibrey nanism. Methods: In Study I, of the 24 children with ASD, 7 underwent surgical correction and 17 percutaneous occlusion of ASD. Study II had 33 patients with PDA undergoing percutaneous occlusion. In Study III, 28 patients with CoA underwent either surgical correction or percutaneous balloon dilatation of CoA. Study IV comprised 26 children with Mulibrey nanism. A total of 76 healthy voluntary children were examined as a control group. In each study, controls were matched to patients. All patients and controls underwent clinical cardiovascular examinations, two-dimensional (2D) and three-dimensional (3D) echocardiographic examinations, and blood sampling for measurement of natriuretic peptides prior to the intervention and twice or three times thereafter. Control children were examined once by 2D and 3D echocardiography. M-mode echocardiography was performed from the parasternal long axis view directed by 2D echocardiography. The left atrium-to-aorta (LA/Ao) ratio was calculated as an index of LA size. The end-diastolic and end-systolic dimensions of LV as well as the end-diastolic thicknesses of the interventricular septum and LV posterior wall were measured. LV volumes, and the fractional shortening (FS) and ejection fraction (EF) as indices of contractility were then calculated, and the z scores of LV dimensions determined. Diastolic function of LV was estimated from the mitral inflow signal obtained by Doppler echocardiography. In three-dimensional echocardiography, time-volume curves were used to determine end-diastolic and end-systolic volumes, stroke volume, and EF. Diastolic and systolic function of LV was estimated from the calculated first derivatives of these curves. Results: (I): In all children with ASD, during the one-year follow-up, the z score of the RV end-diastolic diameter decreased and that of LV increased. However, dilatation of RV did not resolve entirely during the follow-up in either treatment group. In addition, the size of LV increased more slowly in the surgical subgroup but reached control levels in both groups. Concentrations of natriuretic peptides in patients treated percutaneously increased during the first month after ASD closure and normalized thereafter, but in patients treated surgically, they remained higher than in controls. (II): In the PDA group, at baseline, the end-diastolic diameter of LV measured over 2SD in 5 of 33 patients. The median N-terminal pro-brain natriuretic peptide (proBNP) concentration before closure measured 72 ng/l in the control group and 141 ng/l in the PDA group (P = 0.001) and 6 months after closure measured 78.5 ng/l (P = NS). Patients differed from control subjects in indices of LV diastolic and systolic function at baseline, but by the end of follow-up, all these differences had disappeared. Even in the subgroup of patients with normal-sized LV at baseline, the LV end-diastolic volume decreased significantly during follow-up. (III): Before repair, the size and wall thickness of LV were higher in patients with CoA than in controls. Systolic blood pressure measured a median 123 mm Hg in patients before repair (P < 0.001) and 103 mm Hg one year thereafter, and 101 mm Hg in controls. The diameter of the coarctation segment measured a median 3.0 mm at baseline, and 7.9 at the 12-month (P = 0.006) follow-up. Thicknesses of the interventricular septum and posterior wall of the LV decreased after repair but increased to the initial level one year thereafter. The velocity time integrals of mitral inflow increased, but no changes were evident in LV dimensions or contractility. During follow-up, serum levels of natriuretic peptides decreased correlating with diastolic and systolic indices of LV function in 2D and 3D echocardiography. (IV): In 2D echocardiography, the interventricular septum and LV posterior wall were thicker, and velocity time integrals of mitral inflow shorter in patients with Mulibrey nanism than in controls. In 3D echocardiography, LV end-diastolic volume measured a median 51.9 (range 33.3 to 73.4) ml/m² in patients and 59.7 (range 37.6 to 87.6) ml/m² in controls (P = 0.040), and serum levels of ANPN and proBNP a median 0.54 (range 0.04 to 4.7) nmol/l and 289 (range 18 to 9170) ng/l, in patients and 0.28 (range 0.09 to 0.72) nmol/l (P < 0.001) and 54 (range 26 to 139) ng/l (P < 0.001) in controls. They correlated with several indices of diastolic LV function. Conclusions (I): During the one-year follow-up after the ASD closure, RV size decreased but did not normalize in all patients. The size of the LV normalized after ASD closure but the increase in LV size was slower in patients treated surgically than in those treated with the percutaneous technique. Serum levels of ANPN and proBNP were elevated prior to ASD closure but decreased thereafter to control levels in patients treated with the percutaneous technique but not in those treated surgically. (II): Changes in LV volume and function caused by PDA disappeared by 6 months after percutaneous closure. Even the children with normal-sized LV benefited from the procedure. (III): After repair of CoA, the RV size and the velocity time integrals of mitral inflow increased, and serum levels of natriuretic peptides decreased. Patients need close follow-up, despite cessation of LV pressure overload, since LV hypertrophy persisted even in normotensive patients with normal growth of the coarctation segment. (IV): In children with Mulibrey nanism, the LV wall was hypertrophied, with myocardial restriction and impairment of LV function. Significant correlations appeared between indices of LV function, size of the left atrium, and levels of natriuretic peptides, indicating that measurement of serum levels of natriuretic peptides can be used in the clinical follow-up of this patient group despite its dependence on loading conditions.

Testicular function in adolescent boys with Klinefelter syndrome

Klinefelter syndrome (KS) is the most frequent karyotype disorder of male reproductive function. Since its original clinical description in 1942 and the identification of its chromosomal basis 47,XXY in 1959, the typical KS phenotype has become well recognized, but the mechanisms behind the testicular degeneration process have remained unrevealed. This prospective study was undertaken to increase knowledge about testicular function in adolescent KS boys. It comprised a longitudinal follow-up of growth, pubertal development, and serum reproductive hormone levels in 14 prepubertal and pubertal KS boys. Each boy had a testicular biopsy that was analyzed with histomorphometric and immunohistochemical methods. The KS boys had sufficient testosterone levels to allow normal onset and progression of puberty. Their serum testosterone levels remained within the low-normal range throughout puberty, but from midpuberty onwards, findings like a leveling-off in testosterone and insulin-like factor 3 (INSL3) concentrations, high gonadotropin levels, and exaggerated responses to gonadotropin-releasing hormone stimulation suggest diminished testosterone secretion. We also showed that the Leydig cell differentiation marker INSL3 may serve as a novel marker for onset and normal progression of puberty in boys. In the KS boys the number of germ cells was already markedly lower at the onset of puberty. The pubertal activation of the pituitary-testicular axis accelerated germ cell depletion, and germ cell differentiation was at least partly blocked at the spermatogonium or early primary spermatocyte stages. The presence of germ cells correlated with serum reproductive hormone levels. The immature Sertoli cells were incapable of transforming to the adult type, and during puberty the degeneration of Sertoli cells increased markedly. The older KS boys displayed an evident Leydig cell hyperplasia, as well as fibrosis and hyalinization of the interstitium and peritubular connective tissue. Altered immunoexpression of the androgen receptor (AR) suggested that in KS boys during puberty a relative androgen deficiency develops at testicular level. The impact of genetic features of the supernumerary X chromosome on the KS phenotype was also studied. The present study suggests that parental origin of the supernumerary X chromosome and the length of the CAG repeat of the AR gene influence pubertal development and testicular degeneration. The current study characterized by several means the testicular degeneration process in the testes of adolescent KS boys and confirmed that this process accelerates at the onset of puberty. Although serum reproductive hormone levels indicated no hypogonadism during early puberty, the histological analyses showed an already markedly reduced fertility potential in prepubertal KS boys. Genetic features of the X chromosome affect the KS phenotype.

Developmental origins of physiological stress reactivity

The model of developmental origins of health and disease proposes that organisms during fetal period utilize cues that enable their adaptation in the postnatal environment they are likely to live, having short-term advantages when trying to survive in environment but simultaneously in the long run have costs for health. A large body of epidemiological research has found that low birth weight, a marker of intrauterine conditions, is associated with cardiovascular (CV) disease. Since the reported associations of birth weight with normal variation in the resting blood pressure (BP), a major predictor of CV disease risk, have been modest, a key candidate mediating the link has been CV and hypothalamus-pituitary-adrenal axes (HPAA) reactivity to stress. In addition, not only weight at birth but also gestational age and early postnatal growth may have independent associations to stress reactivity. The aim of this thesis was to investigate whether pre- and postnatal growth and gestational age are associated with CV and HPAA activity before, during and after stress in childhood and in late adulthood. Altogether 287 men and women aged 60-70 and 299 boys and girls aged 7-9 underwent Trier Social Stress Test. Several indices of HPAA and CV were measured and birth size and gestational age were obtained from birth records. Results showed that low birth weight was associated with low HPAA activity during psychosocial stress, and rapid gain in BMI during years 7-11 was related to heightened stress reactivity to psychosocial stress. Size at birth in children and gestational age and early postnatal (0-2 years) gain in height in adults were associated with CV stress responses; however, in a sex-specific manner. Given that CV stress responses and HPAA activity are markers of CV disease vulnerability, our results may partly explain the associations between early environment and later CV disease.

Measurement of the kT Distribution of Particles in Jets Produced in pp̅ Collisions at √s=1.96 TeV

We present a measurement of the transverse momentum with respect to the jet axis (kt) of particles in jets produced in pp̅ collisions at √s=1.96  TeV. Results are obtained for charged particles in a cone of 0.5 radians around the jet axis in events with dijet invariant masses between 66 and 737  GeV/c2. The experimental data are compared to theoretical predictions obtained for fragmentation partons within the framework of resummed perturbative QCD using the modified leading log and next-to-modified leading log approximations. The comparison shows that trends in data are successfully described by the theoretical predictions, indicating that the perturbative QCD stage of jet fragmentation is dominant in shaping basic jet characteristics.

Measurement of the kT Distribution of Particles in Jets Produced in pp̅ Collisions at √s=1.96 TeV

We present a measurement of the transverse momentum with respect to the jet axis ($k_{T}$) of particles in jets produced in $p\bar p$ collisions at $\sqrt{s}=1.96$ TeV. Results are obtained for charged particles within a cone of opening angle 0.5 radians around the jet axis in events with dijet invariant masses between 66 and 737 GeV/c$^{2}$. The experimental data are compared to theoretical predictions obtained for fragmentation partons within the framework of resummed perturbative QCD using the modified leading log and next-to-modified leading log approximations. The comparison shows that trends in data are successfully described by the theoretical predictions, indicating that the perturbative QCD stage of jet fragmentation is dominant in shaping basic jet characteristics.