Whose ETSIP? National and local ownership of Namibia's education and training sector improvement programme

Tämä työ tarkastelee kansallista ja paikallista omistajuutta Namibian opetussektorin kehittämisohjelmassa. Opetussektorin kehittämisohjelma ETSIP on 15-vuotinen sektoriohjelma vuosille 2005-2015 ja sen tavoitteena on edesauttaa Namibian kehittymistä tietoyhteiskunnaksi. Tutkimuksen tarkoituksena on selvittää miten kansallinen ja paikallinen omistajuus on toteutunut ETSIP prosessin aikana. Erityisesti pyritään selvittämään paikallistason opetussektorin virkamiesten näkemyksiä ETSIP prosessista, heidän roolistaan siinä ja siitä millaisia vaikuttamisen ja hallinnan mahdollisuuksia heillä on ollut prosessin aikana. Tutkimuksen lähtökohta on laadullinen ja lähestymistapa konstruktionistinen: tutkimus tarkastelee todellisuutta ihmisten kokemusten, näkemysten ja toiminnan kautta. Tutkimusaineisto koostuu haastatteluista, epävirallisista keskusteluista, lehtiartikkeleista ja ETSIP dokumenteista. Tutkimus osoittaa että kansallinen omistajuus on epämääräinen käsite sillä kansallisia toimijoita ja näkemyksiä on useita. Tutkimus vahvistaa Castel-Brancon huomion siitä, että omistajuutta on tarkasteltava kontekstissaan: muuttuvana ja kilpailtuna. ETSIPin rinnalle ollaan valmistelemassa uutta strategista ohjelmaa opetusministeriölle mikä saattaa muuttaa omistajuutta ETSIPiin. ETSIP dokumenttien omistajuusretoriikka myötäilee kansainvälisiä sitoumuksia avun vaikuttavuuden parantamiseksi mutta niistä puuttuu syvällisempi analyysi siitä, miten kansallinen ja paikallinen omistajuus toteutuisi käytännössä. Avunantajien näkemys omistajuudesta on suppea: omistajuus nähdään lähinnä sitoutumisena ennalta määrättyyn politiikkaohjelmaan. Haastatteluaineistosta nousee esiin Whitfieldin ja Frazerin jaottelu suppeista ja laajoista omistajuuskäsityksistä. Sitoutumista ETSIP ohjelmaan pidetään tärkeänä mutta riittämättömänä määritteenä omistajuudelle. Paikallisella tasolla sitoutuminen ETSIP ohjelman periaatteisiin ja tavoitteisiin on toteutunut melko hyvin mutta jos omistajuutta tarkastellaan laajemmin vaikutusvallan ja hallinnan käsitteiden kautta voidaan todeta että omistajuus on ollut heikkoa. Paikallisella tasolla ei ole ollut juurikaan vaikutusvaltaa ETSIP ohjelman sisältöön eikä mahdollisuutta hallita ohjelman toteutusta ja päättää siitä mitä hankkeita ohjelman kautta rahoitetaan. Tujanin demokraattisen omistajuuden käsite kuvaa tarvetta muuttaa ja laajentaa omistajuusajattelua huomioiden paikallisen tason paremmin. Tämä tutkimus viittaa siihen että omistajuuden toteutuminen paikallisella tasolla edellyttäisi institutionaalisen kulttuurin muutosta ja institutionaalisen legitimiteetin vahvistamista. Omistajuuden mahdollistamiseksi paikallisella tasolla tarvittaisiin poliittista johtajuutta, luottamusta, vastuullisuuden kulttuurin kehittämistä, tehokkaampaa tiedonjakoa, laajaa osallistumista, vuoropuhelua ja yhteistyötä. Ennen kaikkea tarvittaisiin paikallisen tason vaikutusvaltaa päätöksenteossa ja kontrollia resurssien käytöstä. Tälle muutokselle on selvä tarve ja tilaus.

Confucian education and enlightenment for the masses in the manner of Guwen guanzhi

The topic of this study is the most renowned anthology of essays written in Literary Chinese, Guwen guanzhi, compiled and edited by Wu Chengquan (Chucai) and Wu Dazhi (Diaohou), and first published during the Qing dynasty, in 1695. Because of the low social standing of the compilers, their anthology remained outside the recommended study materials produced by members of the established literati and used for preparing students in the imperial civil-service examinations. However, since the end of the imperial era, Guwen guanzhi has risen to a position as the classical anthology par excellence. Today it is widely used as required or supplementary reading material of Literary Chinese in middle-schools both in Mainland China and on Taiwan. The goal of this study is to explain the persistent longevity of the anthology. So far, Guwen guanzhi has not been a topic of any published academic study, and the opinions expressed on it in various sources are widely discrepant. Through a comparative study with a dozen classical Chinese anthologies in use during the early Qing dynasty, this study reveals the extent to which the compilers of Guwen guanzhi modelled their work after other selections. Altogether 86 % of the texts in Guwen guanzhi originate from another Qing era anthology, Guwen xiyi, often copied character by character. However, the notes and commentaries are all different. Concentrating on the special characteristics unique to Guwen guanzhi—the commentaries and certain peculiarities in the selection of texts—this study then discusses the possible reasons for the popularity of Guwen guanzhi over the competing readers during the Qing era. Most remarkably, Guwen guanzhi put in practise the equalitarian, educational ideals of the Ming philosopher Wang Shouren (Yangming). Thus Guwen guanzhi suited the self-enlightenment needs of the ”subordinate classes”, in particular the rising middle-class comprised mainly of merchants. The lack of moral teleology, together with the compact size, relative comprehensiveness of the selection and good notes and comments, have made Guwen guanzhi well suited for the new society since the abolition of the imperial examination system. Through a content analysis, based on a sample of the texts, this study measures the relative emphasis on centralism and localism (both in concrete and spiritual terms) expressed in the texts of Guwen guanzhi. The analysis shows that the texts manifest some bias towards emphasising innate virtue on the expense of state-defined moral. This may reflect hidden critique towards intellectual oppression by the centralised imperial rule. During the early decades of the Qing era, such critique was often linked to Ming-loyalism. Finally, this study concludes that the kind of ”spiritual localism” that Guwen guanzhi manifests gives it the potential to undermine monolithic orthodoxy even in today’s Chinese societies. This study has progressed hand in hand with the translation of a selection of texts from Guwen guanzhi into Finnish, published by Gaudeamus Helsinki University Press: Jadekasvot – Valittuja tarinoita Kiinan muinaisajoilta (2005), Jadelähde – Valittuja kirjoituksia Kiinan keskiajalta (2007) and Jadepeili – Valittuja kirjoituksia keisarillisen Kiinan kulta-ajoilta (2008). All translations are critical editions, complete with extensive notation. The trilogy is the first comprehensive translation based on Guwen guanzhi in a European language.

Pharmacogenetic Variation at CYP2D6, CYP2C9, and CYP2C19: Population Genetic and Forensic Aspects

Pharmacogenetics deals with genetically determined variation in drug response. In this context, three phase I drug-metabolizing enzymes, CYP2D6, CYP2C9, and CYP2C19, have a central role, affecting the metabolism of about 20-30% of clinically used drugs. Since genes coding for these enzymes in human populations exhibit high genetic polymorphism, they are of major pharmacogenetic importance. The aims of this study were to develop new genotyping methods for CYP2D6, CYP2C9, and CYP2C19 that would cover the most important genetic variants altering the enzyme activity, and, for the first time, to describe the distribution of genetic variation at these loci on global and microgeographic scales. In addition, pharmacogenetics was applied to a postmortem forensic setting to elucidate the role of genetic variation in drug intoxications, focusing mainly on cases related to tricyclic antidepressants, which are commonly involved in fatal drug poisonings in Finland. Genetic variability data were obtained by genotyping new population samples by the methods developed based on PCR and multiplex single-nucleotide primer extension reaction, as well as by collecting data from the literature. Data consisted of 138, 129, and 146 population samples for CYP2D6, CYP2C9, and CYP2C19, respectively. In addition, over 200 postmortem forensic cases were examined with respect to drug and metabolite concentrations and genotypic variation at CYP2D6 and CYP2C19. The distribution of genetic variation within and among human populations was analyzed by descriptive statistics and variance analysis and by correlating the genetic and geographic distances using Mantel tests and spatial autocorrelation. The correlation between phenotypic and genotypic variation in drug metabolism observed in postmortem cases was also analyzed statistically. The genotyping methods developed proved to be informative, technically feasible, and cost-effective. Detailed molecular analysis of CYP2D6 genetic variation in a global survey of human populations revealed that the pattern of variation was similar to those of neutral genomic markers. Most of the CYP2D6 diversity was observed within populations, and the spatial pattern of variation was best described as clinal. On the other hand, genetic variants of CYP2D6, CYP2C9, and CYP2C19 associated with altered enzymatic activity could reach extremely high frequencies in certain geographic regions. Pharmacogenetic variation may also be significantly affected by population-specific demographic histories, as seen within the Finnish population. When pharmacogenetics was applied to a postmortem forensic setting, a correlation between amitriptyline metabolic ratios and genetic variation at CYP2D6 and CYP2C19 was observed in the sample material, even in the presence of confounding factors typical for these cases. In addition, a case of doxepin-related fatal poisoning was shown to be associated with a genetic defect at CYP2D6. Each of the genes studied showed a distinct variation pattern in human populations and high frequencies of altered activity variants, which may reflect the neutral evolution and/or selective pressures caused by dietary or environmental exposure. The results are relevant also from the clinical point of view since the genetic variation at CYP2D6, CYP2C9, and CYP2C19 already has a range of clinical applications, e.g. in cancer treatment and oral anticoagulation therapy. This study revealed that pharmacogenetics may also contribute valuable information to the medicolegal investigation of sudden, unexpected deaths.

Noise sensitivity medical, psychological and genetic aspects

Noise can be defined as unwanted sound. It may adversely affect the health and well-being of individuals. Noise sensitivity is a personality trait covering attitudes towards noise in general and a predictor of noise annoyance. Noise sensitive individuals are more affected by noise than less sensitive individuals. The determinants and characteristics related to noise sensitivity are rather poorly known. The risk of health effects caused by noise can be hypothesized to be higher for noise sensitive individuals compared to those who are not noise sensitive. A cardiovascular disease may be an example of outcomes. The general aim of the present study was to investigate the association of noise sensitivity with specific somatic and psychological factors, including the genetic component of noise sensitivity, and the association of noise sensitivity with mortality. The study was based on the Finnish Twin Cohort of same-sex twin pairs born before 1958. In 1988 a questionnaire was sent to twin pairs discordant for hypertension. 1495 individuals (688 men, 807 women) aged 31 88 years replied, including 573 twin pairs. 218 of the subjects lived in the Helsinki Metropolitan Area. Self-reported noise sensitivity, lifetime noise exposure and hypertension were obtained from the questionnaire study in 1988 and other somatic and psychological factors from the questionnaire study in 1981 for the same individuals. In addition, noise map information (1988 1992) from the Helsinki Metropolitan Area and mortality follow-up 1989 2003 were used. To evaluate the stability and validity of noise sensitivity, a new questionnaire was sent in 2002 to a sample of the subjects who had replied to the 1988 questionnaire. Of all subjects who had answered the question on noise sensitivity, 38 % were noise sensitive. Noise sensitivity was independent of noise exposure levels indicated in noise maps. Subjects with high noise sensitivity reported more transportation noise exposure than subjects with low noise sensitivity. Noise sensitive subjects reported transportation noise exposure outside the environmental noise map areas almost twice as often as non-sensitive subjects. Noise sensitivity was associated with hypertension, emphysema, use of psychotropic drugs, smoking, stress and hostility, even when lifetime noise exposure was adjusted for. Monozygotic twin pairs were more similar with regards noise sensitivity than dizygotic twin pairs, and quantitative genetic modelling indicated significant familiality. The best fitting genetic model provided an estimate of heritability of 36 %. Follow-up of subjects in the case-control study showed that cardiovascular mortality was significantly increased among noise sensitive women, but not among men. For coronary heart mortality the interaction of noise sensitivity and lifetime noise exposure was statistically significant in women. In conclusion, noise sensitivity has both somatic and psychological components. It does aggregate in families and probably has a genetic component. Noise sensitivity may be a risk factor for cardiovascular mortality in women.

Molecular and epidemiological aspects of Streptococcus pyogenes disease in Finland: Severe infections and bacterial, non-necrotizing cellulitis

Streptococcus pyogenes (group A streptococcus) is an important human pathogen, causing a wide array of infections ranging in severity. The majority of S. pyogenes infections are mild upper respiratory tract or skin infections. Severe, invasive infections, such as bacteraemia, are relatively rare, but constitute a major global burden with a high mortality. Certain streptococcal types are associated with a more severe disease and higher mortality. Bacterial, non-necrotizing cellulitis and erysipelas are localised infections of the skin, and although they are usually not life-threatening, they have a tendency to recur and therefore cause substantial morbidity. Despite several efforts aimed at developing an effective and safe vaccine against S. pyogenes infections, no vaccine is yet available. In this study, the epidemiology of invasive S. pyogenes infections in Finland was described over a decade of national, population-based surveillance. Recent trends in incidence, outcome and bacterial types were investigated. The beta-haemolytic streptococci causing cellulitis and erysipelas infections in Finland were studied in a case-control study. Bacterial isolates were characterised using both conventional and molecular typing methods, such as the emm typing, which is the most widely used typing method for beta-haemolytic streptococci. The incidence of invasive S. pyogenes disease has had an increasing trend during the past ten years in Finland, especially from 2006 onwards. Age- and sex-specific differences in the incidence rate were identified, with men having a higher incidence than women, especially among persons aged 45-64 years. In contrast, more infections occurred in women aged 25-34 years than men. Seasonal patterns with occasional peaks during the midsummer and midwinter were observed. Differences in the predisposing factors and underlying conditions of patients may contribute to these distinctions. Case fatality associated with invasive S. pyogenes infections peaked in 2005 (12%) but remained at a reasonably low level (8% overall during 2004-2007) compared to that of other developed countries (mostly exceeding 10%). Changes in the prevalent emm types were associated with the observed increases in incidence and case fatality. In the case-control study, acute bacterial non-necrotizing cellulitis was caused predominantly by Streptococcus dysgalactiae subsp. equisimilis, instead of S. pyogenes. The recurrent nature of cellulitis became evident. This study adds to our understanding of S. pyogenes infections in Finland and provides a basis for comparison to other countries and future trends. emm type surveillance and outcome analyses remain important for detecting such changes in type distribution that might lead to increases in incidence and case fatality. Bacterial characterisation serves as a basis for disease pathogenesis studies and vaccine development.

Obstetric and gynaecological aspects of HIV infection

The purpose of the present study was to examine the outcome of pregnancies among HIV-infected women in Helsinki, use of the levonorgestrel-releasing intrauterine system (LNG-IUS) among HIV-infected women and the prevalence and risk factors of cytological and histologically proven cervical lesions in this population. Between 1993 and 2003 a total of 45 HIV-infected women delivered 52 singleton infants. HIV infection was diagnosed during pregnancy in 40% of the mothers. Seventeen of the mothers received antiretroviral (ARV) medication prior to pregnancy and in 34 cases, the medication was started during pregnancy. A good virological response (i.e. HIV RNA load <1000/mL during the last trimester) to ARV medication was achieved in 36/40 (90%) of the patients in whom HI viral load measurements were performed. Of the infants, 92% were born at term, and their mean (±SD) birth weight was 3350±395 g. The Caesarean section rate was low, 25%. All newborns received ARV medication and none of the infants born to mothers with pre-delivery diagnosis of maternal HIV infection were infected. The safety and advantages of the LNG-IUS were studied prospectively (n=12) and retrospectively (n=6). The LNG-IUS was well tolerated and no cases of PID or pregnancy were noted. Menstrual bleeding was reduced significantly during use of the LNG-IUS; this was associated with a slight increase in haemoglobin levels. Serum oestradiol concentrations remained in the follicular range in all subjects. The key finding was that genital shedding of HIV RNA did not change after the insertion of the LNG-IUS. The mean annual prevalence of low-grade squamous intraepithelial lesions (SIL) was 15% and that of high-grade SIL was 5% among 108 systematically followed HIV-infected women during 1989 2003. A reduced CD4 lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection, use of ARV medication and HI viral load were not. The cumulative risk of any type of SIL was 17% after one year and 48% after five years among patients with initially normal Pap smears. The risk of developing SIL was associated with young age and a high initial HI viral load. During the follow-up 51 subjects (n=153) displayed cervical intraepithelial neoplasia (CIN), (16% CIN1 and 18% CIN 2-3). Only one case of cancer of the uterine cervix was detected. Pap smears were reliable in screening for CIN. Both nulliparity (p<0.01) and bacterial vaginosis (p<0.04) emerged as significant risk factors of CIN. In conclusion, a combination of universal antenatal screening and multidisciplinary management allows individualized treatment and prevents vertical transmission of HIV. Use of the LNG-IUS is safe among HIV-infected women and cervicovaginal shedding of HIV RNA is not affected by use of the LNG-IUS. The risk of cervical pre-malignant lesions is high among HIV-infected women despite systematic follow-up.

Atrial remodeling in atrial fibrillation : Epidemiological, clinical and magnetocardiographic aspects

Atrial fibrillation is the most common arrhythmia requiring treatment. This Thesis investigated atrial fibrillation (AF) with a specific emphasis on atrial remodeling which was analysed from epidemiological, clinical and magnetocardiographic (MCG) perspectives. In the first study we evaluated in real-life clinical practice a population-based cohort of AF patients referred for their first elective cardioversion (CV). 183 consecutive patients were included of whom in 153 (84%) sinus rhythm (SR) was restored. Only 39 (25%) of those maintained SR for one year. Shorter duration of AF and the use of sotalol were the only characteristics associated with better restoration and maintenance of SR. During the one-year follow-up 40% of the patients ended up in permanent AF. Female gender and older age were associated with the acceptance of permanent AF. The LIFE-trial was a prospective, randomised, double-blinded study that evaluated losartan and atenolol in patients with hypertension and left ventricular hypertrophy (LVH). Of the 8,851 patients with SR at baseline and without a history of AF 371 patients developed new-onset AF during the study. Patients with new-onset AF had an increased risk of cardiac events, stroke, and increased rate of hospitalisation for heart failure. Younger age, female gender, lower systolic blood pressure, lesser LVH in ECG and randomisation to losartan therapy were independently associated with lower frequency of new-onset AF. The impact of AF on morbidity and mortality was evaluated in a post-hoc analysis of the OPTIMAAL trial that compared losartan with captopril in patients with acute myocardial infarction (AMI) and evidence of LV dysfunction. Of the 5,477 randomised patients 655 had AF at baseline, and 345 patients developed new AF during the follow-up period, median 3.0 years. Older patients and patients with signs of more serious heart disease had and developed AF more often. Patients with AF at baseline had an increased risk of mortality (hazard ratio (HR) of 1.32) and stroke (HR 1.77). New-onset AF was associated with increased mortality (HR 1.82) and stroke (HR of 2.29). In the fourth study we assessed the reproducibility of our MCG method. This method was used in the fifth study where 26 patients with persistent AF had immediately after the CV longer P-wave duration and higher energy of the last portion of atrial signal (RMS40) in MCG, increased P-wave dispersion in SAECG and decreased pump function of the atria as well as enlarged atrial diameter in echocardiography compared to age- and disease-matched controls. After one month in SR, P-wave duration in MCG still remained longer and left atrial (LA) diameter greater compared to the controls, while the other measurements had returned to the same level as in the control group. In conclusion is not a rare condition in either general population or patients with hypertension or AMI, and it is associated with increased risk of morbidity and mortality. Therefore, atrial remodeling that increases the likelihood of AF and also seems to be relatively stable has to be identified and prevented. MCG was found to be an encouraging new method to study electrical atrial remodeling and reverse remodeling. RAAS-suppressing medications appear to be the most promising method to prevent atrial remodeling and AF.

Microbiological, environmental and proteolytic aspects in chronic rhinosinusitis with nasal polyposis

Chronic rhinosinusitis is one of the most common chronic respiratory tract diseases affecting up to 15% of the adult population in the Western world. It may be perpetuated by factors predisposing to sinus ostial obstruction together with inflammatory changes in the sinus mucosa. Chronic rhinosinusitis is associated with asthma, and it may represent the same disease process. Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma share also the characteristic inflammatory features and histopathologic feature of airway remodelling. Remodelling is considered as a key event in the pathogenesis of asthma. It is controlled by a delicate balance between the matrix metalloproteinases (MMPs) and their regulators. The purpose of the present study was to evaluate the microbiological findings, inflammatory features and MMP and tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in CRSwNP. The results were related to the patient history, exposure to moisture and clinical outcome in order to find out possible explanations for the etiology and chronicity of CRSwNP. Bacterial culture results were similar in patients and in controls and do not explain the chronic course of CRSwNP. The presence of fungi seems to be more common in CRSwNP than chronic rhinosinusitis in general, and they should be actively searched for using microbiological as well as histological methods. Typical outdoor fungal species were found in nasal lavage samples taken from controls in the autumn but not in the winter, reflecting environmental exposure. Exposure to moisture was reported by 46% of the CRSwNP patients, which is in accordance to the Finnish general population. Exposed patients did not differ significantly from non-exposed subjects with regards to microbiological findings, tissue eosinophilia and clinical outcome. Significantly elevated levels of collagenase-2 (MMP-8) and interleukin (IL)-8 but not tumour necrosis factor-α were found in CRSwNP patients. In particular, the activation of mesenchymal-type MMP-8 but not polymorphonuclear-type MMP-8 was associated with elevated IL-8 levels. IL-8 and MMP-8 may form an inductive cytokine-proteinase cascade in CRSwNP pathogenesis and provide a target for novel therapies and a diagnostic tool for monitoring CRSwNP treatment. The proteolytic spectrum is different in eosinophilic and non-eosinophilic CRSwNP with the up-regulation of MMP-8 and MMP-9 in non-eosinophilic CRSwNP, suggesting different pathophysiology in these subgroups. The lack of MMP up-regulation was associated with a poor prognostic factor and worse clinical outcome, representing a possible synergic anti-inflammatory function of MMP-8 and MMP-9 in CRSwNP. This study provides new information about possible immunologic mechanisms in the pathogenesis of CRSwNP. The recently discovered anti-inflammatory/ defensive properties of MMP-8 and MMP-9 in animal models are reported for the first time in a clinical setting in human inflammatory diseases.