Pre-eclampsia : The role of soluble VEGF receptor-1 and related anti-angiogenic factors beyond

Pre-eclampsia is a pregnancy complication that affects about 5% of all pregnancies. It is known to be associated with alterations in angiogenesis -related factors, such as vascular endothelial growth factor (VEGF). An excess of antiangiogenic substances, especially the soluble receptor-1 of VEGF (sVEGFR-1), has been observed in maternal circulation after the onset of the disease, probably reflecting their increased placental production. Smoking reduces circulating concentrations of sVEGFR-1 in non-pregnant women, and in pregnant women it reduces the risk of pre-eclampsia. Soluble VEGFR-1 acts as a natural antagonist of VEGF and placental growth factor (PlGF) in human circulation, holding a promise for potential therapeutic use. In fact, it has been used as a model to generate a fusion protein, VEGF Trap , which has been found effective in anti-angiogenic treatment of certain tumors and ocular diseases. In the present study, we evaluated the potential use of maternal serum sVEGFR-1, Angiopoietin-2 (Ang-2) and endostatin, three central anti-angiogenic markers, in early prediction of subsequent pre-eclampsia. We also studied whether smoking affects circulating sVEGFR-1 concentrations in pregnant women or their first trimester placental secretion and expression in vitro. Last, in order to allow future discussion on the potential therapy based on sVEGFR-1, we determined the biological half-life of endogenous sVEGFR-1 in human circulation, and measured the concomitant changes in free VEGF concentrations. Blood or placental samples were collected from a total of 268 pregnant women between the years 2001 2007 in Helsinki University Central Hospital for the purposes above. The biomarkers were measured using commercially available enzyme-linked immunosorbent assays (ELISA). For the analyses of sVEGFR-1, Ang-2 and endostatin, a total of 3 240 pregnant women in the Helsinki area were admitted to blood sample collection during two routine ultrasoundscreening visits at 13.7 ± 0.5 (mean ± SD) and 19.2 ± 0.6 weeks of gestation. Of them, 49 women later developing pre-eclampsia were included in the study. Their disease was further classified as mild in 29 and severe in 20 patients. Isolated early-onset intrauterine growth retardation (IUGR) was diagnosed in 16 women with otherwise normal medical histories and uncomplicated pregnancies. Fifty-nine women remaining normotensive, non-proteinuric and finally giving birth to normal-weight infants were picked to serve as the control population of the study. Maternal serum concentrations of Ang-2, endostatin and sVEGFR-1, were increased already at 16 20 weeks of pregnancy, about 13 weeks before the clinical manifestation of preeclampsia. In addition, these biomarkers could be used to identify women at risk with a moderate precision. However, larger patient series are needed to determine whether these markers could be applied for clinical use to predict preeclampsia. Intrauterine growth retardation (IUGR), especially if noted at early stages of pregnancy and not secondary to any other pregnancy complication, has been suggested to be a form of preeclampsia compromising only the placental sufficiency and the fetus, but not affecting the maternal endothelium. In fact, IUGR and preeclampsia have been proposed to share a common vascular etiology in which factors regulating early placental angiogenesis are likely to play a central role. Thus, these factors have been suggested to be involved in the pathogenesis of IUGR. However, circulating sVEGFR-1, Ang-2 and endostatin concentrations were unaffected by subsequent IUGR at early second trimester. Furthermore, smoking was not associated with alterations in maternal circulating sVEGFR-1 or its placental production. The elimination of endogenous sVEGFR-1 after pregnancy was calculated from serial samples of eight pregnant women undergoing elective Caesarean section. As typical for proteins in human compartments, the elimination of sVEGFR-1 was biphasic, containing a rapid halflife of 3.4 h and a slow one of 29 h. The decline in sVEGFR-1 concentrations after mid-trimester legal termination of pregnancy was accompanied with a simultaneous increase in the serum levels of free VEGF so that within a few days after pregnancy VEGF dominated in the maternal circulation. Our study provides novel information on the kinetics of endogenous sVEGFR-1, which serves as a potential tool in the development of new strategies against diseases associated with angiogenic imbalance and alterations in VEGF signaling.

Elämää suuremmat sankarittaret : Suomalaisen teatterin elämäkerralliset taiteilijahahmot vuosina 2000 - 2010

In the first decade of the 21st century, national notables were a significant theme in the Finnish theatre. The lives of artists, in particular, inspired the performances that combined historical and fictional elements. In this study, I focus on the characters of female artists in 18 Finnish plays or performances from the first decade of the 21st century. The study pertains to the field of performance analysis. I approach the characters from three points of view. Firstly, I examine them through the action of performances at the thematic level. Secondly, I concentrate on the forms of relationships between the audience and the half-historical character. Thirdly, I examine the representations of characters and their relationships to the audience using myth as a tool. I approach characters from the frame of feminist phenomenological theatre study but also combine the points of view of other traditions. As a model, I adapt the approach of the theatre researcher Bert O. States, which concentrates on the relation between a play s text and an actor, and between an actor and the public. Furthermore, I use the analysing tools of performance art in an examination of performances counted among the contemporary performance genre. The biographical plays about these artists are concentrated in the domestic sphere and take part in the conversation about the position of women in both the community and private life. They represent the heroines work, love, temptations and hardships. The artists do not carry out heroic acts, being more like everyday heroines whose lives and art were shared with the audience in an aphoristic atmosphere. In the examined performances, criticism of the heterosexual matrix was mainly conservative and the myths of female and male artists differed from each other: the woman artist was presented as a super heroine whose strength often meant sacrifices; the male artist was a weaker figure primarily pursuing his individualistic objectives. The performances proved to be a kind of documentary theatre, a hybrid of truth and fiction. Nonetheless, the constructions of subject and identity mainly represented the characters of the mythical stories and only secondarily gave a faithful rendition of the artists lives. Although these performances were addressed to the general and heterogeneous public, their audience proved to be a strictly predefined group, for which the national myths and the experience of a collective identity emerged as an important theme. The heroine characters offered the audience "safe" idols who ensured the solidity of the community. These performances contained common, shared values and gave the audience an opportunity to feel empathy and to be charmed by the confessions of well-known national characters.

Dietary aspects of cow's milk allergy in young children

Cow s milk allergy (CMA) affects about 2-6% of infants and young children. Environmental factors during early life are suggested to play a role in the development of allergic diseases. One of these factors is likely to be maternal diet during pregnancy and lactation. The association between maternal diet and development of CMA in offspring is not well known, but diet could contain factors that facilitate development of tolerance. After an established food allergy, another issue is gaining tolerance towards an antigen that causes symptoms. The strictness of the elimination depends on the individual level of tolerance. This study aimed at validating a questionnaire used to inquire about food allergies in children, at researching associations between maternal diet during pregnancy and lactation and subsequent development of cow s milk allergy in the offspring, and at evaluating the degree of adherence to a therapeutic elimination diet of children with CMA and factors associated with the adherence and age of recovery. These research questions were addressed in a prospective birth cohort born between 1997 and 2004 at the Tampere and Oulu University Hospitals. Altogether 6753 children of the Diabetes Prediction and Prevention (DIPP) Nutrition cohort were investigated. Questionnaires regarding allergic diseases are often used in studies without validation. High-quality valid tools are therefore needed. Two validation studies were conducted here: one by comparing parentally reported food allergies with information gathered from patient records of 1122 children, and the other one by comparing parentally reported CMA with information in the reimbursement records of special infant formulae in the registers of the Social Insurance Institution for 6753 children. Both of these studies showed that the questionnaire works well and is a valid tool for measuring food allergies in children. In the first validation study, Cohen s kappa values were within 0.71-0.88 for CMA, 0.74-0.82 for cereal allergy, and 0.66-0.86 for any reported food allergy. In the second validation study, the kappa value was 0.79, sensitivity 0.958, and specificity 0.965 for reported and diagnosed CMA. To investigate the associations between maternal diet during pregnancy and lactation and CMA in offspring, 6288 children were studied. Maternal diet during pregnancy (8th month) and lactation (3rd month) was assessed by a validated, 181-item semi-quantitative food frequency questionnaire (FFQ), and as an endpoint register-based information on diagnosed CMA was obtained from the Social Insurance Institution and complemented with parental reports of CMA in their children. The associations between maternal food consumption and CMA in offspring were analyzed by logistic regression comparing the highest and lowest quarters with two middle quarters of consumption and adjusted for several potential confounding factors. High maternal intake of milk products (OR 0.56, 95% CI 0.37-0.86 p = 0.002) was associated with a lower risk of CMA in offspring. When stratified according to maternal allergic rhinitis or asthma, a protective association of high use of milk products with CMA was seen in children of allergy-free mothers (OR 0.30, 95% CI 0.13 - 0.69, p < 0.001), but not in children of allergic mothers. Moreover, low maternal consumption of fish during pregnancy was associated with a higher risk of CMA in children of mothers with allergic rhinitis or asthma (OR 1.47, 95% CI 0.96 - 2.27 for the lowest quarter, p = 0.043). In children of nonallergic mothers, this association was not seen. Maternal diet during lactation was not associated with CMA in offspring, apart from an inverse association between citrus and kiwi fruit consumption and CMA. These results imply that maternal diet during pregnancy may contain factors protective against CMA in offspring, more so than maternal diet during lactation. These results need to be confirmed in other studies before giving recommendations to the public. To evaluate the degree of adherence to a therapeutic elimination diet in children with diagnosed CMA, food records of 267 children were studied. Subsequent food records were examined to assess the age at reintroduction of milk products to the child s diet. Nine of ten families adhered to the elimination diet of the child with extreme accuracy. Older and monosensitized children had more often small amounts of cow s milk protein in their diet (p < 0.001 for both). Adherence to the diet was not related to any other sociodemographic factor studied or to the age at reintroduction of milk products to the diet. Low intakes of vitamin D, calcium, and riboflavin are of concern in children following a cow s milk-free diet. In summary, we found that the questionnaires used in the DIPP study are valid in investigating CMA in young children; that there are associations between maternal diet during pregnancy and lactation and the development of CMA in offspring; and that the therapeutic elimination diet in children with diagnosed CMA is rigorously adhered to.

The Enlightenment Idea of History as a Legitimation Tool of Kemalism in Turkey

The study analyzes the effort to build political legitimacy in the Republic of Turkey by ex-ploring a group of influential texts produced by Kemalist writers. The study explores how the Kemalist regime reproduced certain long-lasting enlightenment meta-narrative in its effort to build political legitimacy. Central in this process was a hegemonic representation of history, namely the interpretation of the Anatolian Resistance Struggle of 1919 1922 as a Turkish Revolution executing the enlightenment in the Turkish nation-state. The method employed in the study is contextualizing narratological analysis. The Kemalist texts are analyzed with a repertoire of concepts originally developed in the theory of narra-tive. By bringing these concepts together with epistemological foundations of historical sciences, the study creates a theoretical frame inside of which it is possible to highlight how initially very controversial historical representations in the end manage to construct long-lasting, emotionally and intellectually convincing bases of national identity for the secular middle classes in Turkey. The two most important explanatory concepts in this sense are di-egesis and implied reader. The diegesis refers to the ability of narrative representation to create an inherently credible story-world that works as the basis of national community. The implied reader refers to the process where a certain hegemonic narrative creates a formula of identification and a position through which any individual real-world reader of a story can step inside the narrative story-world and identify oneself as one of us of the national narra-tive. The study demonstrates that the Kemalist enlightenment meta-narrative created a group of narrative accruals which enabled generations of secular middle classes to internalize Kemalist ideology. In this sense, the narrative in question has not only worked as a tool utilized by the so-called Kemalist state-elite to justify its leadership, but has been internalized by various groups in Turkey, working as their genuine world-view. It is shown in the study that secular-ism must be seen as the core ingredient of these groups national identity. The study proposes that the enlightenment narrative reproduced in the Kemalist ideology had its origin in a simi-lar totalizing cultural narrative created in and for Europe. Currently this enlightenment project is challenged in Turkey by those who are in an attempt to give religion a greater role in Turkish society. The study argues that the enduring practice of legitimizing political power through the enlightenment meta-narrative has not only become a major factor contributing to social polarization in Turkey, but has also, in contradiction to the very real potentials for crit-ical approaches inherent in the Enlightenment tradition, crucially restricted the development of critical and rational modes of thinking in the Republic of Turkey.

Light scattering in random media with wavelength-scale structures : astronomical and industrial applications

Light scattering, or scattering and absorption of electromagnetic waves, is an important tool in all remote-sensing observations. In astronomy, the light scattered or absorbed by a distant object can be the only source of information. In Solar-system studies, the light-scattering methods are employed when interpreting observations of atmosphereless bodies such as asteroids, atmospheres of planets, and cometary or interplanetary dust. Our Earth is constantly monitored from artificial satellites at different wavelengths. With remote sensing of Earth the light-scattering methods are not the only source of information: there is always the possibility to make in situ measurements. The satellite-based remote sensing is, however, superior in the sense of speed and coverage if only the scattered signal can be reliably interpreted. The optical properties of many industrial products play a key role in their quality. Especially for products such as paint and paper, the ability to obscure the background and to reflect light is of utmost importance. High-grade papers are evaluated based on their brightness, opacity, color, and gloss. In product development, there is a need for computer-based simulation methods that could predict the optical properties and, therefore, could be used in optimizing the quality while reducing the material costs. With paper, for instance, pilot experiments with an actual paper machine can be very time- and resource-consuming. The light-scattering methods presented in this thesis solve rigorously the interaction of light and material with wavelength-scale structures. These methods are computationally demanding, thus the speed and accuracy of the methods play a key role. Different implementations of the discrete-dipole approximation are compared in the thesis and the results provide practical guidelines in choosing a suitable code. In addition, a novel method is presented for the numerical computations of orientation-averaged light-scattering properties of a particle, and the method is compared against existing techniques. Simulation of light scattering for various targets and the possible problems arising from the finite size of the model target are discussed in the thesis. Scattering by single particles and small clusters is considered, as well as scattering in particulate media, and scattering in continuous media with porosity or surface roughness. Various techniques for modeling the scattering media are presented and the results are applied to optimizing the structure of paper. However, the same methods can be applied in light-scattering studies of Solar-system regoliths or cometary dust, or in any remote-sensing problem involving light scattering in random media with wavelength-scale structures.

Dokumentation och beskrivning som språkplanering : perspektiv från arbete med tre tecknade minoritetsspråk

Language Documentation and Description as Language Planning Working with Three Signed Minority Languages Sign languages are minority languages that typically have a low status in society. Language planning has traditionally been controlled from outside the sign-language community. Even though signed languages lack a written form, dictionaries have played an important role in language description and as tools in foreign language learning. The background to the present study on sign language documentation and description as language planning is empirical research in three dictionary projects in Finland-Swedish Sign Language, Albanian Sign Language, and Kosovar Sign Language. The study consists of an introductory article and five detailed studies which address language planning from different perspectives. The theoretical basis of the study is sociocultural linguistics. The research methods used were participant observation, interviews, focus group discussions, and document analysis. The primary research questions are the following: (1) What is the role of dictionary and lexicographic work in language planning, in research on undocumented signed language, and in relation to the language community as such? (2) What factors are particular challenges in the documentation of a sign language and should therefore be given special attention during lexicographic work? (3) Is a conventional dictionary a valid tool for describing an undocumented sign language? The results indicate that lexicographic work has a central part to play in language documentation, both as part of basic research on undocumented sign languages and for status planning. Existing dictionary work has contributed new knowledge about the languages and the language communities. The lexicographic work adds to the linguistic advocacy work done by the community itself with the aim of vitalizing the language, empowering the community, receiving governmental recognition for the language, and improving the linguistic (human) rights of the language users. The history of signed languages as low status languages has consequences for language planning and lexicography. One challenge that the study discusses is the relationship between the sign-language community and the hearing sign linguist. In order to make it possible for the community itself to take the lead in a language planning process, raising linguistic awareness within the community is crucial. The results give rise to questions of whether lexicographic work is of more importance for status planning than for corpus planning. A conventional dictionary as a tool for describing an undocumented sign language is criticised. The study discusses differences between signed and spoken/written languages that are challenging for lexicographic presentations. Alternative electronic lexicographic approaches including both lexicon and grammar are also discussed. Keywords: sign language, Finland-Swedish Sign Language, Albanian Sign Language, Kosovar Sign Language, language documentation and description, language planning, lexicography