Mother-Infant Antibodies to Pneumococcal Polysaccharides and Proteins : Transfer and Persistence of Maternal Antibodies and Development of Vaccine-Induced and Naturally Acquired Antibodies in Infants

Symptomless nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) is very common in young children. Occasionally the carriage proceeds into mild mucosal diseases, such as sinusitis or acute otitis media, or into serious life-threatening diseases, such as pneumonia, sepsis or meningitis. Each year, up to one million children less than five years of age worldwide die of invasive pneumococcal diseases (IPD). Especially in the low-income countries IPD is a leading health problem in infants; 75% of all IPD cases occur before one year of age. This stresses the need of increased protection against pneumococcus in infancy. Anti-pneumococcal antibodies form an important component in the defence against pneumococcal infection. Maternal immunisation and early infant immunisation are two possible ways by which potentially protective antibody concentrations against pneumococci could be achieved in early infancy. The aim of this thesis is to increase the knowledge of antibody mediated protection against pneumococcal disease in infants and young children. We investigated the transfer of maternal anti-pneumococcal antibodies from Filipino mothers to their infants, the persistence of the transferred antibodies in the infants, the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine (PPV) in infants and the response of the children to a second dose of PPV at three years of age. We also investigated the development of antibodies to pneumococcal protein antigens in relation to culture-confirmed pneumococcal carriage in infants. Serum samples were collected from the mothers, the umbilical cords and from the infants at young age as well as at three years of age. The samples were used to determine the antibody concentrations to pneumococcal serotypes 1, 5, 6B, 14, 18C and 19F, as well as to the pneumococcal proteins PspA, PsaA, Ply, PspC, PhtD, PhtDC and LytC by the enzyme immunoassay. The findings of the present study confirm previously obtained results and add to the global knowledge of responses to PPV in young children. Immunising pregnant women with PPV provides the infants with increased concentrations of pneumococcal polysaccharide antibodies. Of the six serotypes examined, serotypes 1 and 5 were immunogenic already in infants. At three years of age, the children responded well to the second dose of PPV suggesting that maternal and early infant immunisations might not induce hyporesponsiveness to polysaccharide antigens after subsequent immunisations. The anti-protein antibody findings provide useful information for the development of pneumococcal protein vaccines. All six proteins studied were immunogenic in infancy and the development of anti-protein antibodies started early in life in relation to pneumococcal carriage.

Diabetesassocierade autoantikroppar hos barn med nydiagnostiserad typ 1 diabetes i relation till demografiska och kliniska faktorer

Syftet med studien var att undersöka sambanden mellan de diabetesassocierade autoantikropparna ICA, IAA, GADA, IA-2A och klinisk manifestation, HLA-genotyp, släktanamnes samt demografiska faktorer såsom ålder och kön hos finländska barn under 15 år med nydiagnostiserad typ 1 diabetes. Analyserna baserades på ett utdrag ur det finländska pediatriska diabetesregistret (2257 barn). Antikroppsfrekvenserna fastställdes utgående från halterna i serum. Alla barn HLA-genotypades och indelades i DR3- och DR4-positiva. Småbarnen (?5 år) hade ofta 3-4 positiva antikroppar. Äldre barn hade färre autoantikroppar men en allvarligare metabolisk dekompensering vid diagnostillfället. Diabetisk ketoacidos var vanligare hos flickor. I gruppen med endast en positiv autoantikropp var IA-2A-barnen oftare acidotiska, i övrigt påverkade inte antikroppsprofilen den kliniska bilden. Högriskgenotypen DR4/non-DR3 var associerad med IA-2A, som verkar fungera som en markör för betacelldestruktion. Det omfattande patientmaterialet gav stöd åt tidigare rapporter om samband mellan autoantikroppar och ålder, kön samt genotyp. Den allvarligare metaboliska dekompenseringen hos äldre barn tyder på att de inte diagnostiseras lika snabbt som småbarn.

Betydelser i barnfamiljsbroschyrer : Systemisk-funktionell analys av den tänkta läsaren och institutionen

This thesis concerns Swedish and Finland-Swedish brochures to families with children, presenting family allowances from the social insurance institutions in the two countries. The aim of the study is to analyse what meanings are conveyed with reference to the conceivable reader and the institution in the brochures. The material consists of information brochures in Swedish from Kela, the social insurance institution of Finland, and Försäkringskassan, the Swedish social insurance agency, issued during 2003–2006. The general theoretical framework is systemic-functional linguistics (SFL) as presented by Halliday & Matthiessen (2004) and Holmberg & Karlsson (2006). The study consists of a quantitative study of the lexical choices of the social insurance brochures. Furthermore, a qualitative process and participant analysis is annotated with the UAM Corpus tool and the results are quantified. Speech functions and modal auxiliaries are analysed qualitatively. The analysis shows that material and relational processes are most common. The relational and verbal processes are used more in the Sweden-Swedish brochures, while the material processes are more common in the Finland-Swedish brochures. The participants in the brochures are the institution, mentioned by its name, and the conceivable reader, directly addressed with “you” (du). In addition, the referent “child” is often mentioned. The participants assigned for the reader are Actor, Receiver, Carrier and Speaker. In the Finland-Swedish texts, the reader is often an Actor, while the reader in the Sweden-Swedish texts is a Carrier. Thus, the conceivable reader is an active participant who takes care of his or her own matters using the internet, communicates actively to the institution and has legal rights and obligations. The institution is visible in the texts but does not have an active role as the name of the institution is mostly used in circumstances. The institution is not often a participant, but when it is, it is Actor, Receiver, Listener and Carrier, expecting the clients to address it. Speech functions are performed in different ways. For instance, questions structure the reading process and commands are realised by modal auxiliaries, not by imperatives. The most common modal auxiliary is kan (can, may), and another common auxiliary is ska (shall, must). Statements are surrounded by subordinate clauses and adverbs that describe situations and criteria. The results of the study suggest that the brochures in the two countries are similar, in particular when produced in similar ways, that is, when the Finland-Swedish texts are not translated. Existing differences reflect the differences in the institutions, the social insurance systems and the cultural contexts. KEYWORDS: Finland-Swedish, Swedish, comparative analysis, SFL, discourse analysis, administrative language, institutional discourse, institutional communication

Lagöversättning som process och produkt : Revideringar och institutioner vid lagöversättning till svenska i Finland

The thesis studies the translation process for the laws of Finland as they are translated from Finnish into Swedish. The focus is on revision practices, norms and workplace procedures. The translation process studied covers three institutions and four revisions. In three separate studies the translation process is analyzed from the perspective of the translations, the institutions and the actors. The general theoretical framework is Descriptive Translation Studies. For the analysis of revisions made in versions of the Swedish translation of Finnish laws, a model is developed covering five grammatical categories (textual revisions, syntactic revisions, lexical revisions, morphological revisions and content revisions) and four norms (legal adequacy, correct translation, correct language and readability). A separate questionnaire-based study was carried out with translators and revisers at the three institutions. The results show that the number of revisions does not decrease during the translation process, and no division of labour can be seen at the different stages. This is somewhat surprising if the revision process is regarded as one of quality control. Instead, all revisers make revisions on every level of the text. Further, the revisions do not necessarily imply errors in the translations but are often the result of revisers following different norms for legal translation. The informal structure of the institutions and its impact on communication, visibility and workplace practices was studied from the perspective of organization theory. The results show weaknesses in the communicative situation, which affect the co-operation both between institutions and individuals. Individual attitudes towards norms and their relative authority also vary, in the sense that revisers largely prioritize legal adequacy whereas translators give linguistic norms a higher value. Further, multi-professional teamwork in the institutions studied shows a kind of teamwork based on individuals and institutions doing specific tasks with only little contact with others. This shows that the established definitions of teamwork, with people co-working in close contact with each other, cannot directly be applied to the workplace procedures in the translation process studied. Three new concepts are introduced: flerstegsrevidering (multi-stage revision), revideringskedja (revision chain) and normsyn (norm attitude). The study seeks to make a contribution to our knowledge of legal translation, translation processes, institutional translation, revision practices and translation norms for legal translation. Keywords: legal translation, translation of laws, institutional translation, revision, revision practices, norms, teamwork, organizational informal structure, translation process, translation sociology, multilingual.

Det pedagogiska självet : en narrativ studie av direktvalda svensklärarstudenters berättelser

The Pedagogical Self: a narrative study of stories by prospective subject teachers of Swedish The aim of this study is to examine how prospective subject teachers of Swedish experience themselves, their lives and their studies in university context. By answering this question I try to shed light on the pedagogical self of the students, i.e. to reach a deeper understanding of the narrative construction of their teacher identity. My material consists of stories written by one group of students and of transcribed interviews with another group of students at Nordica. All these students have entered both the teacher education programme and studies in their major subject simultaneously, through the so called direct admission. My study focuses on the students first year at the university. I define teacher identity, the pedagogical self, as the part of an individual s self-concept where he/she makes an assessment of himself/herself as a teacher(-to-be). The frame of reference of this interdisciplinary narrative study is founded on phenomenology, hermeneutics, social constructionism and dialogism. The main analysis of the stories is thematic, with the addition of linguistic and metaphorical analysis. With reference to the theories of Paul Ricoeur and Katharine Young, I regard the textual world of the stories as a world of its own. This implies that the researcher can feel free to concentrate on the texts, thus being able to leave the mental processes of the writers disregarded. The theoretician that has influenced my research the most is Max van Manen. He combines a pedagogical attitude with a phenomenological-hermeneutic philosophy. My research results imply that most of these students are drawn to studying Swedish by the clear professional orientation of the studies; their identity as teachers seems to be stronger than their identity as language teachers. The image of a teacher is relatively traditional: a teacher is seen as a self-evident authority, but at the same time as a fostering educator. The students see their studies in a larger perspective: studies as well as the future profession are only one part of life, albeit an important one. Keywords: narrativity, teacher identity

Genus i östra Nyland : från dialektutjämning till dialektmarkör

Gender in eastern Nyland – from dialect levelling to identity marking The study of dialect leveling in eastern Nyland focuses on variation and change in the Swedish dialects of Nyland (Fi. Uusimaa) on the south coast of Finland. During the last century the grammatical gender system of the dialects in the area has been reduced from a three-gender system to a two-gender system (cf. Corbett 1991). The present study is based on five linguistic variables in the gender system: the anaphoric pronouns (han, hon, den) when used for inanimates; the neuter pronouns he(t) and de(t) – when used anaphorically or as expletives; and three different types of morphological postposed definite articles. For all these variables, both dialect variants and standard variants are used in the dialects. Within the study of processes of variation and change, the work focuses on the mechanisms of leveling, simplification and reallocation; cf. Trudgill (1986) and Hinskens, Auer Kerswill (2005). With regard to the reductions of the gender system, the possibility that some of these variables might have turned into becoming dialect markers (Labov 1972) in the modern varieties of eastern Nyland is given special attention. The primary data consist of tape recordings with 25 informants done in the 1960s and 1970s. The informants were born in 1881–1913. In addition, recent changes were investigated in detail in tape recordings from 2005–2008 with 15 informants, who were born in the period 1927–1947 or 1976–1988. The study combines quantitative and qualitative methods in the systematic analysis of the data. Theoretically and methodologically the study relies on methods and results from variation studies and socio-dialectology, as well as on methods and results from traditional dialectology; cf. Ahlbäck (1946) and the dictionary of Swedish dialects, Ordbok över Finlands svenska folkmål, (1976–). The results show that there are different strategies among the informants in their use of the features studied. In the modern varieties of the dialects, most of the informants use only two genders, uter and neuter. Of the variables, the masculine pronoun for inanimates, the traditional neuter pronoun he(t) and some variants of the traditional definite articles have received a new function as dialect markers in my data. These changes first affect the gender distinctions, and the function of marking gender is lost; gradually the features then get new functions as dialect markers through processes of dialect leveling and reallocation. These processes are connected to changes taking place in the communities in eastern Nyland because of urbanization. When the dialect speakers experience that the traditional values of both the dialects and the culture are threatened, they begin to mark their dialectal identity by using dialect markers in their speech.

Konstteoretikern och livet : Mikael Lybecks Breven till Cecilia i nietzscheansk belysning

I avhandlingen analyseras den finlandssvenska författaren Mikael Lybecks (1864-1925) verk Breven till Cecilia. Denna brevroman hör till Lybecks senare produktion och utkom 1920. Verket har kommit att betraktas som en klassiker inom den finlandssvenska litteraturen. Av författarensövriga produktion är det strängt taget endast Tomas Indal (1911) som haft en jämförbar genomslagskraft. Trots detta har romanen inte varit föremål för en enda mer omfattande studie. l sin Lybeckbiografi relaterar Erik Kihlman i första hand verket till det biografiska och till samhällssituationen vid tiden för romanens tillkomst. Vetenskapen, konsten och livet bildar tillsammans den triangel som utgör romanens stomme. Antiken är starkt närvarande i romanen och med begrepp som härrör från denna era kan man tala om det sokratiska, det apollinska och det dionysiska. Detta är begrepp som Friedrich Nietzsche utgår i från i sitt ungdomsverk Tragedins födelse (Die Geburt der Tragödie aus dem Geiste der Musik) från 1872. Nietzsches vetenskapskritik och hans syn på den högsta konsten som ett brödraförbund mellan Dionysos och Apollon står i förvånansvärt hög grad i samklang med den övergripande tematiken i Lybecks verk. När Nietzsche därtill framhäver musiken som grunden förall konst får många inslag i romanen sin förklaring. l Breven till Cecilia skildras en vändpunkt i huvudpersonen Sven Ingelets liv. Därför ligger tyngdpunkten i den tematiska analysen vid det som gör att verket kan betraktas som en utvecklingsroman. Även om romanen skildrar en tidsperiod på endast ett och ett halvt år så hinnerhuvudpersonen ändå undergå en betydande personlighetsförändring. Nietzsches Tragedinsfödelse med dess ovannämnda grundläggande begrepp lämpar sig ypperligt som referensram för en analys av denna förändring. Avhandlingen har också strukturerats utgående från de nietzscheanska begreppen sokratiskt, dionysiskt och apollinskt vilka alltså återspeglar huvudpersonens utvecklingsfaser. Från att ha varit en renodlad förnuftsmänniska väcks Sven Ingelet genom ett kortvarigt kärleksförhållande till det dionysiska med allt vad det innebär av känslorus och lidande. Att Ingelet nästan helt uppgått i sin roll som konstteoretiker har medfört att hans förhållningssätt till omvärlden utmärks av intresselös betraktelse. Till följd av sin viljesvaghet och bristande handlingskraft måstehan försöka behålla sin älskades gunst genom magiska pseudohandlingar. Detta leder in Ingelet i myternas värld. Hans verklighetsuppfattning får andra dimensioner än den vetenskapliga. Det dionysiska uppvaknandet medför tillsammans med det efterföljande brevskrivandet att Ingeletnår fram till en självkännedom och upphör att vara en främling i tillvaron. Ingelet utvecklar ocksåen ny konstsyn som förutsätter ett samband mellan konsten och livet. Detta apollinska utvecklingsstadium kännetecknas också av sanningsförmedlande drömmar, och av en tilltagande resignation som till slut utmynnar i ett självmord. Nyckelord: brevroman, Dionysos, Apollon, främlingskap, verklighetsflykt

"Han är en trollkarl. Alla skriver laudatur som går på hans lektioner" : en studie om elevernas uppfattningar om orsakerna till toppresultat i svenska i tre finska gymnasier

Tämä pro gradu -tutkielma on tehty osana Svenska i toppen -projektia, joka alkoi syksyllä 2008 Pohjoismaisten kielten ja pohjoismaisen kirjallisuuden laitoksella. Tutkimuksen tavoitteena on selvittää, mitkä tekijät vaikuttavat lukiolaisten näkökulmasta hyvien tulosten saavuttamiseen ruotsin ylioppilaskirjoituksissa kolmessa suomenkielisessä lukiossa, jotka sijaitsevat Turun, Tampereen ja Joensuun seuduilla. Lisäksi tavoitteena on selvittää, miten maantieteelliset tekijät vaikuttavat opiskelijoiden ruotsin kielen osaamiseen sekä mitä eroja on keskipitkän ja pitkän ruotsin oppimäärän opiskelijoiden asenteissa kieltä kohtaan. Tutkielman aineistona on kolme ryhmähaastattelua, joihin on osallistunut 14 lukiolaista, 11 tyttöä ja 3 poikaa. Haastattelut on tehty joulukuussa 2008 sekä tammi- ja maaliskuussa 2009. Haastatteluissa on käytetty strukturoitua kyselylomaketta, jossa kysytään opiskelijoiden näkemyksiä ruotsin opiskelusta. Tutkimusmenetelmänä on kvalitatiivinen tutkimusote, jossa on piirteitä kolmesta eri menetelmästä: tapaustutkimuksesta, etnografisesta tutkimuksesta sekä temaattisesta analyysistä. Tärkeimpänä teoriataustana on ruotsi toisena kielenä -tutkimus, oppiminen sosiokonstruktivistisena ilmiönä sekä motivaatiotutkimus. Tarkastelen kielenoppijaa luokkahuoneessa sosiaalisena osallistujana omassa oppimisprosessissaan. Oppiminen nähdään kokonaisuutena, johon kuuluu eri osa-alueita, esimerkiksi koulujen käytännöt, yhteisön vaikutus oppimiseen sekä opiskelijan identiteetin muokkautuminen kouluyhteisössä. Motivaatiota tarkastelen kielenoppimisen näkökulmasta, ja se koostuu erilaisista dynaamisista vaiheista, esimerkiksi tavoitteiden asettamisesta oppimisprosessin alussa, valintojen tekemisestä sekä motivaation ylläpitämisestä oppimisprosessin kuluessa. Tutkimuksen tulokset osoittavat, että suurin yksittäinen syy menestykseen opiskelijoiden näkökulmasta on opettaja, joka omalla toiminnallaan voi merkittävästi parantaa opiskelijoiden oppimisedellytyksiä. Työhön panostaminen, opiskelijoiden yksilöllinen kohtaaminen myös luokkahuoneen ulkopuolella ja esimerkiksi omien oppimateriaalien valmistaminen ovat opettajaan liittyviä tekijöitä, jotka voivat nostaa opiskelijoiden motivaatiota huomattavasti. Myös lukion maantieteellisellä sijainnilla on vaikutusta. Paikkakunnilla, joilla ruotsin kieltä käytetään vähän, korostuu opettajan rooli kielellisen oppimisympäristön luomisessa. Keskipitkän ja pitkän ruotsin opiskelijoiden välillä ei tutkimuksessa ilmene eroja asenteissa kieltä kohtaan.

Tidigt fullständigt svenskt språkbad i Esbo

Avhandlingen behandlar tidigt fullständigt svenskt språkbad i Esbo. Arbetet utreder vad tidigt fullständigt språkbad innebär samt vad språkbadsföräldrars och språkbadslärares åsikter om språkbadet i Esbo är. Undersökningen omfattar 60 familjer samt samtliga lärare (14 st) som arbetar med språkbad i Esbo. Undersökningen består av två enkäter; en till språkbadsföräldrar och en tillspråkbadslärare. Av de 60 enkäter som sändes ut till språkbadsföräldrarna besvarades 45, dvs. 75%. 12 lärare av 14, dvs. 86%, besvarade den andra enkäten. Det är viktigt att känna till centrala begrepp i anslutning till tvåspråkighet, då man talar om andraspråkstillägnandet i språkbad. I detta arbete presenteras en modell (Sahi, 1999) som åskådliggör centrala begrepp i anslutning till tvåspråkighet. Tidigtfullständigt språkbad är ett program som är planerat att omfatta hela grundskolan. Språkbad är ämnat för enspråkiga majoritetsbarn i ett tvåspråkigt land. Dessa barn tillägnar sig minoritetsspråket i skolan. Språkbadet är inte enbart ett program, utan även en metod. Skillnaden mellan språkbad och traditionell undervisning i språk är att man i språkbadet betonar kommunikation framom grammatik. Målet medspråkbadet är funktionell tvåspråkighet. Många faktorer inverkar på andraspråkstillägnandet i språkbadet. I detta arbete betonas attitydernas och motivationens betydelse. Språkbad kräver en medveten och aktiv insats av föräldrarna. Vidare betonar litteraturen som behandlar språkbad undervisningsmetodernas betydelse samt språkbadslärarens viktiga roll. Föräldrarna är nöjda med språkbadsprogrammet, eftersom det givit goda resultat och motsvarat förväntningarna. Enligt föräldrarna är språkbad ett mjukt, modernt och effektivt program. Föräldrarna anser att barnen lär sig badspråket på ett naturligt sätt och även får en öppnare inställning till språk och kulturer. Föräldrarna betonar lärarnas viktiga insatser samt kontinuitetens betydelse. Vidare tycker föräldrarna att språkbadet borde inledas i ett tidigare skede och att eleverna borde ha mera kontakt med badspråket utanför skolan. Målet med att barnen går i språkbad är, enligt föräldrarna, att barnen ska förstå och tala språket flytande samtkänna kulturen som hör ihop med språket. Både föräldrarna och lärarna tycker att språkbadsklasserna är för stora och att det är brist på material. Lärarna anser att man mer än tidigare borde informera allmänheten, beslutsfattare samt föräldrar om verksamheten. Därtill tycker lärarna att samarbetet mellan daghem och skola samt specialundervisningen borde utvecklas. Lärarna betonar att språkbad inte lämpar sig för alla barn. Lärarna anser sig främst behöva praktiska råd av andra som arbetar med språkbad samt teoretisk kunskap. Både föräldrarna och lärarna tycker att språkbadsverksamheten i Esbo borde koordineras och att språkbadselevernas prestationer noggrant borde följas upp. Nyckelord: Tvåspråkighet, Språkbad, Andraspråkstillägnande Keywords: Bilingualism, Immersion, Second Language Aquisition.

Adult-type hypolactasia: Genotype-phenotype correlation

Adult-type hypolactasia (primary lactose malabsorption, lactase non-persistence) is the most common enzyme deficiency worldwide, and manifests with symptoms of lactose intolerance such as abdominal pain, gas formation and diarrhea. In humans with adult-type hypolactasia, lactase activity is high at birth, but declines during childhood to about one-tenth of the activity at birth. In 2002, a one base polymorphism C/T-13910, located 14 kilobases from the starting codon of the lactase-phlorizin hydrolase (LPH) gene was observed to be associated with the persistence of lactase activity. The T-13910 allele (C/T-13910 and T/T-13910 genotypes) associates with persistence of lactase activity throughout life, whereas the C/C-13910 genotype associates with adult-type hypolactasia. In this thesis work, the timing and mechanism of decline of lactase enzyme activity during development was studied using the C/T-13910 polymorphism as a molecular marker. We observed an excellent correlation between low lactase activity and the C/C-13910 genotype in all subjects > 12 years of age, irrespective their ethnicity. In children of African origin, the lactase activity declined somewhat earlier than among Finnish children. Furthermore, we observed an increasing imbalance in the relative lactase mRNA expression from the C-13910 and T-13910 alleles in Finnish children beginning from five years of age. The genetic test for adult-type hypolactasia showed a sensitivity of 93% and a specificity of 100% in the Finnish children and adolescents > 12 years of age. The relation of milk consumption and the milk-related abdominal complaints to the C/T-13910 genotypes associated with lactase persistence/non-persistence was studied by a questionnaire-based approach in > 2100 Finns. Both Finnish children and adults with the C/C-13910 genotype consumed significantly less dairy products compared to those with the C/T-13910 and T/T-13910 genotypes. Flatulence was the only of the abdominal symptoms of lactose intolerance that subjects with the C/C-13910 genotype reported significantly more often than those with the C/T-13910 and T/T-13910 genotypes. A minor proportion (<10%) of subjects with the C/C-13910 genotype, nevertheless, reported drinking milk without any symptoms afterwards. There was no association between cow's milk allergy starting as a newborn and adult-type hypolactasia. In an association study an increased risk of colorectal cancer was observed among those with molecular diagnosis of adult-type hypolactasia. It warrants further studies to clarify whether the increased risk observed in the Finnish population is associated with lactose or decreased intake of dairy products in these subjects.

Molecular pathogenesis of human parechovirus 1 infection

The Parechoviruses (HPEV) belong to the family Picornaviridae of positive-stranded RNA viruses. Although the parechovirus genome shares the general properties of other picornaviruses, the genus has several unique features when compared to other family members. We found that HPEV1 attaches to αv integrins on the cell surface and is internalized through the clathrin-mediated endocytic pathway. During he course of the infection, the Golgi was found to disintegrate and the ER membranes to swell and loose their ribosomes. The replication of HPEV1 was found to take place on small clusters of vesicles which contained the trans-Golgi marker GalT as well as the viral non-structural 2C protein. 2C was additionally found on stretches of modified ER-membranes, seemingly not involved in RNA replication. The viral non-structural 2A and 2C proteins were studied in further detail and were found to display several interesting features. The 2A protein was found to be a RNA-binding protein that preferably binds to positive sense 3 UTR RNA. It was found to bind also duplex RNA containing 3 UTR(+)-3 UTR(-), but not other dsRNA molecules studied. Mutagenesis revealed that the N-terminal basic-rich region as well as the C-terminus, are important for RNA-binding. The 2C protein on the other hand, was found to have both ATP-diphosphohydrolase and AMP kinase activities. Neither dATP nor other NTP:s were suitable substrates. Furthermore, we found that as a result of theses activities the protein is autophosphorylated. The intracellular changes brought about by the individual HPEV1 non-structural proteins were studied through the expression of fusion proteins. None of the proteins expressed were able to induce membrane changes similar to those seen during HPEV1 infection. However, the 2C protein, which could be found on the surface of lipid droplets but also on diverse intracellular membranes, was partly relocated to viral replication complexes in transfected, superinfected cells. Although Golgi to ER traffic was arrested in HPEV1-infected cells, none of the individually expressed non-structural proteins had any visible effect on the anterograde membrane traffic. Our results suggest that the HPEV1 replication strategy is different from that of many other picornaviruses. Furthermore, this study shows how relatively small differences in genome sequence result in very different intracellular pathology.

Campylobacter Infections of Domestic Origin in Finland

Campylobacter jejuni and C. coli are the leading causes of human bacterial gastroenteritis in developed countries. Most human Campylobacter infections are sporadic and a seasonal peak in the distribution of infections can be seen in the summer months in several countries, including Finland. A variety of risk factors for Campylobacter infections have been identified; handling and eating poultry, drinking unpasteurized milk, contact with domestic animals, and travelling abroad. However, the relative importance of the different risk factors in sporadic cases of Campylobacter infection remains unknown. In most cases, the infection is self-limiting and no specific treatment is required. Campylobacter enteritis can cause a wide range of complications, including reactive arthritis (ReA) that is reported in 1-5% of the cases. Seven clinical microbiology laboratories serving different geographical areas of Finland, participated in this multi-centre study, conducted during a seasonal peak in 2002. In a matched case-control study, domestically-acquired sporadic Campylobacter infections from three geographical areas were collected. The final study comprised 100 cases and 137 controls. Risk factors for sporadic domestically-acquired Campylobacter infections were identified on the basis of a questionnaire; swimming in natural waters was found to be a novel risk factor for Campylobacter infection. Other independent risk factors were tasting or eating raw or undercooked meat and drinking untreated water from a dug well. The role of bacterial strain and host characteristics are not fully understood in Campylobacter infections. Exposure factors, demographical characteristics, and the serotype of the Campylobacter isolate may affect the severity of the enteritis. This cross-sectional study comprised 114 patients with C. jejuni enteritis, diagnosed in three clinical microbiology laboratories; most of the patients had participated in the previous case-control study. Swimming was associated with age ≤ 5 years and serotype Pen 6,7 was found significantly more often among patients reporting swimming. The geographical distribution among serotypes varied; serotype Pen 4-complex appeared more often in patients from urban areas and serotype Pen 21 among patients from more rural areas. Thus, risk factors and sources of infection for C. jejuni infection may vary among individuals depending on age and geographical location. The in vitro susceptibilities of C. jejuni and C. coli strains isolated from patients infected abroad (85 strains) or domestically (393 strains) revealed that susceptibility to erythromycin is still high, even among isolates of foreign origin. However, the novel antimicrobial agent telithromycin did not offer any advantage over erythromycin; isolates with high minimal inhibitory concentrations (MICs) for erythromycin also showed reduced susceptibility to telithromycin. Reduced susceptibility to fluoroquinolones was detected almost exclusively among isolates of foreign origin and half of these isolates with high MICs for fluoroquinolones also showed elevated MICs for doxycycline. Questionnaires concerning complications associated with C. jejuni enteritis were sent to patients two months after becoming ill; 201 patients from seven different geographical areas were included in the study. Musculoskeletal complications after C. jejuni infection were commonly reported by patients (39%). The incidence of classical ReA was 4% and that of Achilles enthesopathy and/or heel pain 9%. Other C. jejuni-associated reactive joint symptoms were commonly reported, however, due to their milder nature seldom seen and diagnosed by a physician. The severity of the enteritis may predict further complications; stomach ache during enteritis was connected to the development of later joint pain. Early antimicrobial treatment, within two days from the start of symptoms, shortened the duration of diarrhoea by two days but did not prevent later musculoskeletal complications. Campylobacter is an important human enteropathogen and causes a significant burden of illness. As the incidence of Campylobacter infections is high, the importance of the infection and the occurrence of complications will increase. This stresses the importance of understanding the risk factors for acquiring Campylobacter infection and how bacterial strain and host characteristics may affect the risk for infection. The role of antimicrobial treatment for acute Campylobacter enteritis seems to be marginal and should be used restrictively.

Viljan visar vägen till identiteten : Berättelsetyper och teman i livsberättelser av kvinnliga teologer i Svenskfinland

Forskningens utgångspunkt var att tillföra information om kvinnliga teologers liv i Svenskfinland under en period då kyrkan hade omdefinierat sin syn på kvinnor som präster. Till forskningens intresseområden hörde frågan om hur situationen hade påverkat kvinnors motivation att välja teologiska studier och yrken samt hur situationen hade inverkat på kvinnliga teologer i arbetslivet. Forskningens uppgift är att ur ett identitetsperspektiv undersöka målgruppens egna skildringar av livet som kvinnlig teolog i Svenskfinland. Forskningsfrågan delades in i två delfrågor: 1)Hur har kvinnliga teologer kommit att välja studier, yrken och arbetsplats? 2)Vad har kvinnliga teologer upplevt i sina studier och arbetsliv? Forskningens material samlades in hösten 2003 genom en förfrågan per brev och genom en tidningsnotis i tidningen Kyrkpressen. Materialet bestod av livsberättelser som kvinnliga teologer i olika yrkesgrupper hade skrivit utgående ifrån rubriken ”Mitt liv som kvinnlig teolog i Svenskfinland”. Cirka 250 kvinnor hade avlagt teologisk examen på svenska i Finland. Antalet personer som deltog i undersökningen med sin livsberättelse var 27. Materialet analyserades kvalitativt och induktivt med en narrativ analys som tog fasta på teman och berättelsetyper i olika livsskeden: val av studier, studietid, val av karriär och erfarenheter från arbetslivet. Analysresultatet var att studievalets beskrivning kunde tolkas som en valsituation där egenskaper jämfördes med yrkesrollen, som en socialisationsprocess, som ett alternativ till tidigare studieinriktning eller som en process där kvinnoprästdiskussioner, intresse för teologi och teologuppgifter fick informanten att välja teologin. Teman från studietiden handlade om studiers fördröjning, om yrkesinriktning, om studier som förberedelse för arbetslivet och om kvinnoprästdiskussionens inverkan på yrkesinriktningen. Val av arbetsplatser och yrken beskrevs utgående ifrån kvinnliga teologers förändrade position, moderskapets inverkan på karriären, en strävan att hitta en arbetsplats som passade informanten, erfarenheter från en enda arbetsplats och karriärsbyte. Lektorer tog fasta på välsignelseaktens betydelse, kyrkoherdens stora inflytande på arbetets karaktär samt hur situationen förändrades då kvinnor tilläts bli präster. För en del präster innebar prästrollen att andra människor betonade att de var kvinnor. Några informanter hade behov av stöd både från Borgå stifts ledning och från andra kvinnliga präster under den första tiden med kvinnliga präster. Till en början upplevdes ledningens stöd inte alltid som tillräckligt men det förbättrades med tiden. Informanterna berättade inte så mycket om läraryrket. Inom forskning verkade teologtiteln vara naturlig, medan informanter med erfarenhet av annat än teologyrken ibland hade stött på reaktioner på sitt yrkesval eller sin arbetsroll. Finlandssvenskheten upplevdes av olika informanter både som tryggt och inskränkt. Eventuella kontakter till finska stift upplevdes positivt även om det egna sammanhanget upplevdes som viktigt. Trivsel på arbetsplatsen orsakades av subjektiva belöningar och i en del fall av att arbetet motsvarade informantens yrkesinriktning. Att vara kvinnlig teolog innebar ibland att informantens yrkesval tolkades av andra som ett ställningstagande för någon ideologi i kvinnoprästfrågan.

Long-term clinical outcome after liver transplantation

With transplant rejection rendered a minor concern and survival rates after liver transplantation (LT) steadily improving, long-term complications are attracting more attention. Current immunosuppressive therapies, together with other factors, are accompanied by considerable long-term toxicity, which clinically manifests as renal dysfunction, high risk for cardiovascular disease, and cancer. This thesis investigates the incidence, causes, and risk factors for such renal dysfunction, cardiovascular risk, and cancer after LT. Long-term effects of LT are further addressed by surveying the quality of life and employment status of LT recipients. The consecutive patients included had undergone LT at Helsinki University Hospital from 1982 onwards. Data regarding renal function – creatinine and estimated glomerular filtration rate (GFR) – were recorded before and repeatedly after LT in 396 patients. The presence of hypertension, dyslipidemia, diabetes, impaired fasting glucose, and overweight/obesity before and 5 years after LT was determined among 77 patients transplanted for acute liver failure. The entire cohort of LT patients (540 patients), including both children and adults, was linked with the Finnish Cancer Registry, and numbers of cancers observed were compared to site-specific expected numbers based on national cancer incidence rates stratified by age, gender, and calendar time. Health-related quality of life (HRQoL), measured by the 15D instrument, and employment status were surveyed among all adult patients alive in 2007 (401 patients). The response rate was 89%. Posttransplant cardiovascular risk factor prevalence and HRQoL were compared with that in the age- and gender-matched Finnish general population. The cumulative risk for chronic kidney disease increased from 10% at 5 years to 16% at 10 years following LT. GFR up to 10 years after LT could be predicted by the GFR at 1 year. In patients transplanted for chronic liver disease, a moderate correlation of pretransplant GFR with later GFR was also evident, whereas in acute liver failure patients after LT, even severe pretransplant renal dysfunction often recovered. By 5 years after LT, 71% of acute liver failure patients were receiving antihypertensive medications, 61% were exhibiting dyslipidemia, 10% were diabetic, 32% were overweight, and 13% obese. Compared with the general population, only hypertension displayed a significantly elevated prevalence among patients – 2.7-fold – whereas patients exhibited 30% less dyslipidemia and 71% less impaired fasting glucose. The cumulative incidence of cancer was 5% at 5 years and 13% at 10. Compared with the general population, patients were subject to a 2.6-fold cancer risk, with non-melanoma skin cancer (standardized incidence ratio, SIR, 38.5) and non-Hodgkin lymphoma (SIR 13.9) being the predominant malignancies. Non-Hodgkin lymphoma was associated with male gender, young age, and the immediate posttransplant period, whereas old age and antibody induction therapy raised skin-cancer risk. HRQoL deviated clinically unimportantly from the values in the general population, but significant deficits among patients were evident in some physical domains. HRQoL did not seem to decrease with longer follow-up. Although 87% of patients reported improved working capacity, data on return to working life showed marked age-dependency: Among patients aged less than 40 at LT, 70 to 80% returned to work, among those aged 40 to 50, 55%, and among those above 50, 15% to 28%. The most common cause for unemployment was early retirement before LT. Those patients employed exhibited better HRQoL than those unemployed. In conclusion, although renal impairment, hypertension, and cancer are evidently common after LT and increase with time, patients’ quality of life remains comparable with that of the general population.

Invasive pneumococcal infections in Finland before routine use of conjugate vaccines : opportunities for prevention

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis and bacteremia worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for adults less than 65 years old with certain chronic medical conditions and for all elderly persons because of high rates of invasive pneumococcal infections (IPI) and increased risk of death. This study provides a comprehensive picture of the epidemiology of pneumococcal infections in Finland before the introduction of childhood pneumococcal conjugate vaccines, focusing on disease rates, risk factors, clinical outcome, and healthcare associated infections. This study was based on national, population-based laboratory surveillance for IPI. Information on all episodes of IPI was collected from the primary diagnostic laboratory. A case with IPI was defined as the isolation of S. pneumoniae from blood or cerebrospinal fluid during 1995-2002. Information on comorbidities and underlying conditions for IPI patients was obtained by linking the IPI surveillance database to other national, population-based health registries using each patient’s unique national identity code. In total, 4357 cases of IPI were identified. The overall annualized IPI incidence increased by 35% during the study period and was 10.6 per 100 000 population. The temporal increase in disease rates was associated with higher blood culturing rates over time. In working age adults, two-thirds of severe infections and one half of fatal cases occurred in persons with no recognized PPV23 indication. Persons with asthma were at increased risk for IPI and this new risk factor accounted for 5% of the overall disease burden. One tenth of pneumococcal bacteremias were healthcare-associated, and mortality among these patients was over twice as high as among patients with community-associated bacteremia. Most patients with nosocomial infections had underlying conditions for which PPV23 is recommended. The incidence of IPI in Finland has increased and the overall disease burden is higher than previously reported. The findings of this study underscore the urgent need for improved prevention efforts against pneumococcal infections in Finland through increased use of PPV23 in adult risk groups and introduction of childhood immunization with pneumococcal conjugate vaccine.