Literaturnaja skazka A.M. Remizova (1900-1920-e gody)

Literary tale of A.M. Remizov (1900’s – 1920’s) The thesis is devoted to a detailed historical-literary description of a tale as a genre tradition in the creative work of Alexei Mikhailovich Remizov (1877-1957), one of the major Russian prose writers of the 20’s century. This very approach allows to specify the place and functional meaning of this genre in literary practice of the writer and to appeal to one of the key problems of the 20-21 century literature history – a specific of modernistic literature composition principle and a role of montage techniques in its formation. Remizov was working on tales during his whole life, though the most productive years of folklore studies fell to 1900’s – 1910’s. During this period he intensively studied folklore materials, narrated several hundreds of folk tales and in 1900’s – 1920’s published eight tale collections which played a significant role in the formation of stylistic and compositional principles of his prose of the 1910’s – 1920’s, especially montage techniques, which in its turn influenced the development of the narrative forms in the Russian post-revolutionary literature. At the same time a tale has specified not only poetics but also problematics of Remizov’s creative work, as when choosing folklore sources the writer always alluded to modern themes and relevant intellectual trends. The current research work, based on various archive materials and a wide spectrum of modern historical-literary data, complies four chapters with a consistent description of creation history, publication and critics’ reviews of Remizov’s tale collections and single tales contributing to his creative evolution characteristic. Furthermore, the work refers to composition and subject of the particular collections. On the whole it enables to follow up genre dynamics. The first chapter of the work is devoted to Posolon’ (Sunwise), the earliest tale collection of Remizov. The main feature of the collection is that its composition is oriented on the agrarian calendar and the subject – on the system of mythological views reflected in the Russian folklore. This very collection to a large extent corresponds to the writer’s views on the myth represented in Pis’mo v redaktsiyu (Letter to the Editor). The history of this manifesto appearing is analyzed in the second chapter. The incident which caused its forthcoming contributed to ‘legitimization’ of Remizov’s narrations as a relevant genre of modern literature and to upgrading the writer in professional hierarchy. The third chapter analyzes Remizov’s collections of 1900’s – early 1920’s, a result of Remizov’s scrupulous work with a specific tale material. He is acting here as a tale repertory researcher and in some cases as a collector as well. The means of such collections’ topical organization is not the myth but the hero of the tale. According to this principle single pieces are grouped into cycles, which then form complicated montage constructs. Texts themselves can be viewed as a sort of hyper-quotations, as they in fact entirely coincide with their original sources. Besides, collections usually have their own ideal patterns. In the fourth chapter a connection of Remizov’s creative work with folk fun culture and a tradition of the folklore noel story is being demonstrated on Zavetnyie skazy (Secret Tales) material. A consistent collections’ history creation analysis convinces us that the tale was a sort of laboratory in which main writer’s prose methods were being worked out.

The Letter Collections of Anselm of Canterbury

Anselm of Canterbury (1033–1109) was a prolific letter writer. The modern edition of his letter collection comprises more than 600 folio-size pages in print and includes 472 letters, the vast majority of which were sent by him. Our knowledge of Anselm’s letters is derived from collections of his letters, for none of his correspondence survives in its original form of individual letters. There was no one canonical version of the collection, and the extant manuscripts generally differ substantially: the largest medieval manuscript witnesses include over 400 letters, while the smallest contain only a few. We know 38 manuscript witnesses, but no authorial manuscript survives. Certain references in Anselm’s letters reveal, however, that he collected his correspondence on at least two occasions while he was still abbot of Bec, and this study proposes that a third collection was possibly made under his supervision in Christ Church. The third collection also covered Anselm’s Canterbury period. Whether the third collection was authorial or posthumous is unclear. Certain contextual evidence and references in letters would suggest that the collection was authorial. If so, the collection was probably a register book, which was started in c. 1101 at the earliest. There is no positive proof that any of the three surviving minor collections may be authorial. Each of these collections was circulating at a very early stage, however, some probably in Anselm’s lifetime. Moreover, the minor collections seem to have been put together from smaller source units, which possibly originated at Bec. The contents of these units suggest very early and possibly authorial origins: the letters are mainly from Anselm’s years as prior of Bec. The critical edition by F. S. Schmitt represents the current phase in the textual tradition of Anselm’s letter collection. This study demonstrates that the value of the edition is weakened in particular by the way in which Schmitt selected manuscripts for collation, doubtless influenced by the fact that he had not established the structure of the tradition properly. Ultimately it is impossible to undertake systematic research on the letter collection on the basis of Schmitt’s edition.

Feature integration in human vision

The earliest stages of human cortical visual processing can be conceived as extraction of local stimulus features. However, more complex visual functions, such as object recognition, require integration of multiple features. Recently, neural processes underlying feature integration in the visual system have been under intensive study. A specialized mid-level stage preceding the object recognition stage has been proposed to account for the processing of contours, surfaces and shapes as well as configuration. This thesis consists of four experimental, psychophysical studies on human visual feature integration. In two studies, classification image a recently developed psychophysical reverse correlation method was used. In this method visual noise is added to near-threshold stimuli. By investigating the relationship between random features in the noise and observer s perceptual decision in each trial, it is possible to estimate what features of the stimuli are critical for the task. The method allows visualizing the critical features that are used in a psychophysical task directly as a spatial correlation map, yielding an effective "behavioral receptive field". Visual context is known to modulate the perception of stimulus features. Some of these interactions are quite complex, and it is not known whether they reflect early or late stages of perceptual processing. The first study investigated the mechanisms of collinear facilitation, where nearby collinear Gabor flankers increase the detectability of a central Gabor. The behavioral receptive field of the mechanism mediating the detection of the central Gabor stimulus was measured by the classification image method. The results show that collinear flankers increase the extent of the behavioral receptive field for the central Gabor, in the direction of the flankers. The increased sensitivity at the ends of the receptive field suggests a low-level explanation for the facilitation. The second study investigated how visual features are integrated into percepts of surface brightness. A novel variant of the classification image method with brightness matching task was used. Many theories assume that perceived brightness is based on the analysis of luminance border features. Here, for the first time this assumption was directly tested. The classification images show that the perceived brightness of both an illusory Craik-O Brien-Cornsweet stimulus and a real uniform step stimulus depends solely on the border. Moreover, the spatial tuning of the features remains almost constant when the stimulus size is changed, suggesting that brightness perception is based on the output of a single spatial frequency channel. The third and fourth studies investigated global form integration in random-dot Glass patterns. In these patterns, a global form can be immediately perceived, if even a small proportion of random dots are paired to dipoles according to a geometrical rule. In the third study the discrimination of orientation structure in highly coherent concentric and Cartesian (straight) Glass patterns was measured. The results showed that the global form was more efficiently discriminated in concentric patterns. The fourth study investigated how form detectability depends on the global regularity of the Glass pattern. The local structure was either Cartesian or curved. It was shown that randomizing the local orientation deteriorated the performance only with the curved pattern. The results give support for the idea that curved and Cartesian patterns are processed in at least partially separate neural systems.

Development of regulatory T cells in the human thymus

The role of the immune system is to protect an organism against pathogens while maintaining tolerance against self. T cells are an essential component of the immune system and they develop in the thymus. The AIRE (autoimmune regulator) gene product plays an important role in T cell development, as it promotes expression of peripheral tissue antigens in the thymus. Developing T cells, thymocytes, which recognize self-antigens with high affinity are deleted. However, this deletion process is not perfect and not all autoreactive T cells are destroyed. When the distinction between self and non-self fails, tolerance breaks and the immune system attacks the host s own tissues. This results in autoimmunity. Regulatory T cells contribute to the maintenance of self-tolerance. They can actively suppress the function of autoreactive cells. Several populations of cells with regulatory properties have been described, but the best characterized population is the natural regulatory T cells (Treg cells), which develop in the thymus and express the transcription factor FOXP3. The thymic development of Treg cells in humans is the subject of this thesis. Thymocytes at different developmental stages were analyzed using flow cytometry. The CD4-CD8- double-negative (DN) thymocytes are the earliest T cell precursors in the T cell lineage. My results show that the Treg cell marker FOXP3 is up-regulated already in a subset of these DN thymocytes. FOXP3+ cells were also found among the more mature CD4+CD8+ double-positive (DP) cells and among the CD4+ and CD8+ single-positive (SP) thymocytes. The different developmental stages of the FOXP3+ thymocytes were isolated and their gene expression examined by quantitative PCR. T cell receptor (TCR) repertoire analysis was used to compare these different thymocyte populations. My data show that in humans commitment to the Treg cell lineage is an early event and suggest that the development of Treg cells follows a linear developmental pathway, FOXP3+ DN precursors evolving through the DP stage to become mature CD4+ Treg cells. Most T cells have only one kind of TCR on their cell surface, but a small fraction of cells expresses two different TCRs. My results show that the expression of two different TCRs is enriched among Treg cells. Furthermore, both receptors were capable of transmitting signals when bound by a ligand. By extrapolating flow cytometric data, it was estimated that the majority of peripheral blood Treg cells are indeed dual-specific. The high frequency of dual-specific cells among human Treg cells suggests that dual-specificity has a role in directing these cells to the Treg cell lineage. It is known that both genetic predisposition and environmental factors influence the development of autoimmunity. It is also known that the dysfunction or absence of Treg cells leads to the development of autoimmune manifestations. APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) is a rare monogenic autoimmune disease, caused by mutations in the AIRE gene. In the absence of AIRE gene product, deletion of self-specific T cells is presumably disturbed and autoreactive T cells escape to the periphery. I examined whether Treg cells are also affected in APECED. I found that the frequency of FOXP3+ Treg cells and the level of FOXP3 expression were significantly lower in APECED patients than in controls. Additionally, when studied in cell cultures, the suppressive capacity of the patients' Treg cells was impaired. Additionally, repertoire analysis showed that the TCR repertoire of Treg cells was altered. These results suggest that AIRE contributes to the development of Treg cells in humans and the selection of Treg cells is impaired in APECED patients. In conclusion, my thesis elucidates the developmental pathway of Treg cells in humans. The differentiation of Tregs begins early during thymic development and both the cells dual-specificity and AIRE probably affect the final commitment of Treg cells.

Postglacial climate changes and vegetation responses in northern Europe

Postglacial climate changes and vegetation responses were studied using a combination of biological and physical indicators preserved in lake sediments. Low-frequency trends, high-frequency events and rapid shifts in temperature and moisture balance were probed using pollen-based quantitative temperature reconstructions and oxygen-isotopes from authigenic carbonate and aquatic cellulose, respectively. Pollen and plant macrofossils were employed to shed light on the presence and response rates of plant populations in response to climate changes, particularly focusing on common boreal and temperate tree species. Additional geochemical and isotopic tracers facilitated the interpretation of pollen- and oxygen-isotope data. The results show that the common boreal trees were present in the Baltic region (~55°N) during the Lateglacial, which contrasts with the traditional view of species refuge locations in the south-European peninsulas during the glacial/interglacial cycles. The findings of this work are in agreement with recent paleoecological and genetic evidence suggesting that scattered populations of tree species persisted at higher latitudes, and that these taxa were likely limited to boreal trees. Moreover, the results demonstrate that stepwise changes in plant communities took place in concert with major climate fluctuations of the glacial/interglacial transition. Postglacial climate trends in northern Europe were characterized by rise, maxima and fall in temperatures and related changes in moisture balance. Following the deglaciation of the Northern Hemisphere and the early Holocene reorganization of the ice-ocean-atmosphere system, the long-term temperature trends followed gradually decreasing summer insolation. The early Holocene (~11,700-8000 cal yr BP) was overall cool, moist and oceanic, although the earliest Holocene effective humidity may have been low particularly in the eastern part of northern Europe. The gradual warming trend was interrupted by a cold event ~8200 cal yr BP. The maximum temperatures, ~1.5-3.0°C above modern values, were attained ~8000-4000 cal yr BP. This mid-Holocene peak warmth was coupled with low lake levels, low effective humidity and summertime drought. The late Holocene (~4000 cal yr BP-present) was characterized by gradually decreasing temperatures, higher lake levels and higher effective humidity. Moreover, the gradual trends of the late Holocene were probably superimposed by higher-frequency variability. The spatial variability of the Holocene temperature and moisture balance patterns were tentatively attributed to the differing heat capacities of continents and oceans, changes in atmospheric circulation modes and position of sites and subregions with respect to large water bodies and topographic barriers. The combination of physical and biological proxy archives is a pivotal aspect of this work, because non-climatic factors, such as postglacial migration, disturbances and competitive interactions, can influence reshuffling of vegetation and hence, pollen-based climate reconstructions. The oxygen-isotope records and other physical proxies presented in this work manifest that postglacial climate changes were the main driver of the establishment and expansion of temperate and boreal tree populations, and hence, large-scale and long-term vegetation patterns were in dynamic equilibrium with climate. A notable exception to this pattern may be the postglacial invasion of Norway spruce and the related suppression of mid-Holocene temperate forest. This salient step in north-European vegetation history, the development of the modern boreal ecosystem, cannot be unambiguously explained by current evidence of postglacial climate changes. The results of this work highlight that plant populations, including long-lived trees, may be able to respond strikingly rapidly to changes in climate. Moreover, interannual and seasonal variation and extreme events can exert an important influence on vegetation reshuffling. Importantly, the studies imply that the presence of diffuse refuge populations or local stands among the prevailing vegetation may have provided the means for extraordinarily rapid vegetation responses. Hence, if scattered populations are not provided and tree populations are to migrate long distances, their capacity to keep up with predicted rates of future climate change may be lower than previously thought.

Power Aware Real Time Scheduling in Constrained Devices

Real-time scheduling algorithms, such as Rate Monotonic and Earliest Deadline First, guarantee that calculations are performed within a pre-defined time. As many real-time systems operate on limited battery power, these algorithms have been enhanced with power-aware properties. In this thesis, 13 power-aware real-time scheduling algorithms for processor, device and system-level use are explored.

Paradise Reconsidered : A Study of the Ophite Myth and Ritual and their Relationship to Sethianism

This thesis examines the mythology in and social reality behind a group of texts from the Nag Hammadi and related literature, to which certain leaders of the early church attached the label, Ophite, i.e., snake people. In the mythology, which essentially draws upon and rewrites the Genesis paradise story, the snake's advice to eat from the tree of knowledge is positive, the creator and his angels are demonic beasts and the true godhead is depicted as an androgynous heavenly projection of Adam and Eve. It will be argued that this unique mythology is attested in certain Coptic texts from the Nag Hammadi and Berlin 8502 Codices (On the Origin of the World, Hypostasis of the Archons, Apocryphon of John, Eugnostos, Sophia of Jesus Christ), as well as in reports by Irenaeus (Adversus Haereses 1.30), Origen (Contra Celsum 6.24-38) and Epiphanius (Panarion 26). It will also be argued that this so-called Ophite evidence is essential for a proper understanding of Sethian Gnosticism, often today considered one of the earliest forms of Gnosticism; there seems to have occurred a Sethianization of Ophite mythology. I propose that we replace the current Sethian Gnostic category by a new one that not only adds texts that draw upon the Ophite mythology alongside these Sethian texts, but also arranges the material in smaller typological units. I also propose we rename this remodelled and expanded Sethian corpus "Classic Gnostic." I have divided the thesis into four parts: (I) Introduction; (II) Myth and Innovation; (III) Ritual; and (IV) Conclusion. In Part I, the sources and previous research on Ophites and Sethians will be examined, and the new Classic Gnostic category will be introduced to provide a framework for the study of the Ophite evidence. Chapters in Part II explore key themes in the mythology of our texts, first by text comparison (to show that certain texts represent the Ophite mythology and that this mythology is different from Sethianism), and then by attempting to unveil social circumstances that may have given rise to such myths. Part III assesses heresiological claims of Ophite rituals, and Part IV is the conclusion.

Yhteisöllisyys juutalaisessa kansallisuusajattelussa ja Israelin valtion itsenäisyysjulistuksessa

The Idea of Community in the Jewish National Thinking and in the Proclamation of Independence The aim of this study is to clarify the idea of community in the Jewish national thinking and in the Proclamation of Independence of the State of Israel in 1948. The method is the community analysis. The values of the culture are studied by two- and threefold dimensions on the arena. On the field of that arena one can find the society of order, the society of pressure, the societies made by mosaics and the societies that are breaking apart. The community way of behaving means, that the individuals voluntarily follow common values. The earliest Jewish ideals elevated the concept of unity among the people. The reality in the society was different especially in Roman times when the religious and national thinking was fragmented into four different main views. During the Diaspora the religious tradition mostly warned against pursuing a Jewish state, but many forms of Anti-Judaism and the new national thinking in the nineteenth century created the Zionist movement. The religious Jewish people did not rely on the earthy nationalism and when some of them later chose Zionism, they stressed the religious aspects in governing the state. The cultural Zionists preferred a slower and more low key spiritual way of change. The Revisionists saw no alternatives but to use military force. Many in the majority, the Labour movement, hoped that the progress brought to the region by Zionism would change the minds of opponents. The general appearance of the proclamation is optimistic. It characterizes national and political unity gathering people who think differently and who come from different factions of the Jewish political and cultural orientation. These people can be placed on different corners in the community analysis. The proclamation concentrates on state and administrative points of view. It aims at a state for the Jews, and the Jewishness of the state is more clearly seen in later legislation. The hope for co-operation from all sides was clearly articulated. The central aim was the security of the Jews. The proclamation has a community quotation because it aimed to build up a net of cooperation. The vision of building a nation of their own is balanced by the collaboration with the Arabs and the international community. In the same roclamation the individual civil rights are side by side with the Prophets thoughts about peace and justice. The Proclamation describes a society of a good order which aims at uniting the people. In the midst of grave difficulties a noble proclamation of national and international co-operation was created. It was not taken for granted that the ideals would be realized. The care of the national homeland could become egocentric nationalism and the attention to the Prophets heritage could turn to emphasizing strict religious rules or to isolation from others. The emphasis of civil rights could turn to assimilation or in other words to other kinds of values in their own country.

The Restless Love of Thinking : The Concept Liebe in Hegel's Philosophy

The German philosopher G.W.F.Hegel (1770–1831) is best known for his idealistic system philosophy, his concept of spirit [Geist] and for his dictum that the existing and the rational overlap. This thesis offers a new perspective: it examines the working of the concept ‘love’ in Hegel’s philosophy by looking at the contexts and function he puts it to, from his earliest writings to the very last lectures he gave. The starting point of the inquiry is that he applied the concept Liebe to different contexts for different purposes, but each time to provide an answer to a specific philosophical problem. His formulation, reformulation and use of ‘love’ give possible solutions to problems the solving of which was crucial to the development of his thought as a whole. The study is divided into three parts, each analysing the different problems and solutions to which Hegel applied the concept of love. The first part, "Love, morality and ethical life", examines these interconnected themes in Hegel’s early work. The main questions he addressed during this period concerned how to unite Kant’s philosophy and the Greek ideal of the good life. In this context, the concept ‘love’ did three things. First, it served to formulate his grounding idea of the relation between unity and difference, or the manifold. Secondly, it was the key to his attempt to base an ideal folk religion on Christianity interpreted as a religion of love. Finally, it provided the means to criticise Kant’s moral philosophy. The question of the moral value of love helped Hegel to break away from Kant’s thought and develop his own theory about love and ethical life. The second part of the study, "Love and the political realm", considers the way 'Liebe' functions in connection with questions concerning the community and political life in Hegel’s work. In addition to questioning the universal applicability of the concept of recognition as a key to his theory of social relations, the chapters focus on gender politics and the way he conceptualised the gender category ‘woman’ through the concept ‘love’. Another line of inquiry is the way the figure of Antigone was used to conceptualise the differentiated spheres of action for men and women, and the part ‘love’ played in Hegel’s description of Antigone’s motives. Thirdly, Hegel’s analogy of the family and the state and the way ‘love’ functions in an attempt to promote understanding of the relation between citizens and the state are examined. The third and final part of the study, "Love as absolute spirit", focuses on ‘love’ within Hegel’s systemic thought and the way he continued to characterise Geist through the language of Liebe up until and including his very last works. It is shown how Liebe functions in his hierarchical organisation of the domains of art, religion and philosophy, and how both art and religion end up in similar structural positions with regard to philosophy. One recurrent theme in the third part is Hegel’s complex relation to Romantic thought. Another line of investigation is how he reconstructed Christianity as a religion of love in his mature work. In striking contrast to his early thought, in his last works Hegel introduced a new concept of love that incorporated negativity, and that could also function as the root of political action.

The family Herbertaceae and its novel systematic position within liverworts

Taxonomic relationships of the liverwort genus Herbertus in Asia were examined. In addition, the phylogeny of the family Herbertaceae and its close relatives was investigated and analyses conducted of higher level relationships within the entire liverwort phylum. Species of Herbertus show great plasticity in various morphological characters, resulted in a large number of described species. This study was the first comprehensive revision of Asian Herbertus, with 12 species recognized for the continent. Eleven names were reduced to synonymy under earlier described species, and one species was excluded from the genus. Herbertus buchii Juslén was described as a new species. Phylogenetic analyses based on both molecular and morphological characters resolved the families Vetaformaceae, Lepicoleaceae, and Herbertaceae (including Mastigophoraceae) as a monophyletic entity. This clade is among the most derived groups within the leafy liverworts and comprises mostly isophyllous plants, all of which have bracteolar antheridia. The relationships of Mastigophoraceae have formerly been controversial. My results confirm the view that this family is closely related to Herbertaceae, Lepicoleaceae, and Vetaformaceae. In the proposed new classification Mastigophoraceae is included in Herbertaceae. Phylogenetic relationships within the liverworts were reconstructed using both chloroplast and nuclear sequences as well as morphological characters. These analyses were the most comprehensive to date at the time of publication. Previously it was believed that liverworts had a common ancestor with an erect, radial gametophyte and a tetrahedral apical cell. The leafy liverworts were arranged based on the assumption that similar structures had repeatedly developed in many different suborders, with evolution proceeding from erect and isophyllous to creeping and anisophyllous plants. The complex thalloid liverworts were assumed to be the most derived group. By contrast, our studies resolved a clade comprising Treubia and Haplomitrium as the earliest extant liverwort lineage. According to our results the complex thalloids are also an early diverging lineage, and the simple thalloids, traditionally classified together, are a paraphyletic group. Within leafy liverworts, the hypothesis of repeated evolution from isophyllous to anisophyllous plants based on the assumption of a basal unresolved polytomy was rejected. Fundamentally, the leafy liverworts can be divided into three groups. In conflict with the earlier hypotheses, the isophyllous liverworts, including Herbertaceae, were resolved as derived lineages within the liverworts.

Neuromagnetic studies on cortical somatosensory functions in infants and children : Normal development and effect of early brain lesions

Until recently, objective investigation of the functional development of the human brain in vivo was challenged by the lack of noninvasive research methods. Consequently, fairly little is known about cortical processing of sensory information even in healthy infants and children. Furthermore, mechanisms by which early brain insults affect brain development and function are poorly understood. In this thesis, we used magnetoencephalography (MEG) to investigate development of cortical somatosensory functions in healthy infants, very premature infants at risk for neurological disorders, and adolescents with hemiplegic cerebral palsy (CP). In newborns, stimulation of the hand activated both the contralateral primary (SIc) and secondary somatosensory cortices (SIIc). The activation patterns differed from those of adults, however. Some of the earliest SIc responses, constantly present in adults, were completely lacking in newborns and the effect of sleep stage on SIIc responses differed. These discrepancies between newborns and adults reflect the still developmental stage of the newborns’ somatosensory system. Its further maturation was demonstrated by a systematic transformation of the SIc response pattern with age. The main early adult­like components were present by age two. In very preterm infants, at term age, the SIc and SIIc were activated at similar latencies as in healthy fullterm newborns, but the SIc activity was weaker in the preterm group. The SIIc response was absent in four out of the six infants with brain lesions of the underlying hemisphere. Determining the prognostic value of this finding remains a subject for future studies, however. In the CP adolescents with pure subcortical lesions, contrasting their unilateral symptoms, the SIc responses of both hemispheres differed from those of controls: For example the distance between SIc representation areas for digits II and V was shorter bilaterally. In four of the five CP patients with cortico­subcortical brain lesions, no normal early SIc responses were evoked by stimulation of the palsied hand. The varying differences in neuronal functions, underlying the common clinical symptoms, call for investigation of more precisely designed rehabilitation strategies resting on knowledge about individual functional alterations in the sensorimotor networks.

Health-Related Quality of Life, Costs and Treatment of Inflammatory Rheumatic Diseases in Routine Practice : With special emphasis on biological drugs

Rheumatoid arthritis (RA) and other chronic inflammatory joint diseases already begin to affect patients health-related quality of life (HRQoL) in the earliest phases of these diseases. In treatment of inflammatory joint diseases, the last two decades have seen new strategies and treatment options introduced. Treatment is started at an earlier phase; combinations of disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroids are used; and in refractory cases new drugs such as tumour necrosis factor (TNF) inhibitors or other biologicals can be started. In patients with new referrals to the Department of Rheumatology of the Helsinki University Central Hospital, we evaluated the 15D and the Stanford Health Assessment Questionnaire (HAQ) results at baseline and approximately 8 months after their first visit. Altogether the analysis included 295 patients with various rheumatic diseases. The mean baseline 15D score (0.822, SD 0.114) was significantly lower than for the age-matched general population (0.903, SD 0.098). Patients with osteoarthritis (OA) and spondyloarthropathies (SPA) reported the poorest HRQoL. In patients with RA and reactive arthritis (ReA) the HRQoL improved in a statistically significant manner during the 8-month follow-up. In addition, a clinically important change appeared in patients with systemic rheumatic diseases. HAQ score improved significantly in patients with RA, arthralgia and fibromyalgia, and ReA. In a study of 97 RA patients treated either with etanercept or adalimumab, we assessed their HRQoL with the RAND 36-Item Health Survey 1.0 (RAND-36) questionnaire. We also analysed changes in clinical parameters and the HAQ. With etanercept and adalimumab, the values of all domains in the RAND-36 questionnaire increased during the first 3 months. The efficacy of each in improving HRQoL was statistically significant, and the drug effects were comparable. Compared to Finnish age- and sex-matched general population values, the HRQoL of the RA patients was significantly lower at baseline and, despite the improvement, remained lower also at follow-up. Our RA patients had long-standing and severe disease that can explain the low HRQoL also at follow-up. In a pharmacoeconomic study of patients treated with infliximab we evaluated medical and work disability costs for patients with chronic inflammatory joint disease during one year before and one year after institution of infliximab treatment. Clinical and economic data for 96 patients with different arthritis diagnoses showed, in all patients, significantly improved clinical and laboratory variables. However, the medical costs increased significantly during the second period by 12 015 (95% confidence interval, 6 496 to 18 076). Only a minimal decrease in work disability costs occurred mean decrease 130 (-1 268 to 1 072). In a study involving a switch from infliximab to etanercept, we investigated the clinical outcome in 49 patients with RA. Reasons for switching were in 42% failure to respond by American College of Rheumatology (ACR) 50% criteria; in 12% adverse event; and in 46% non-medical reasons although the patients had responded to infliximab. The Disease Activity Score with 28 joints examined (DAS28) allowed us to measure patients disease activity and compare outcome between groups based on the reason for switching. In the patients in whom infliximab was switched to etanercept for nonmedical reasons, etanercept continued to suppress disease activity effectively, and 1-year drug survival for etanercept was 77% (95% CI, 62 to 97). In patients in the infliximab failure and adverse event groups, DAS28 values improved significantly during etanercept therapy. However, the 1-year drug survival of etanercept was only 43% (95% CI, 26 to 70) and 50% (95% CI, 33 to 100), respectively. Although the HRQoL of patients with inflammatory joint diseases is significantly lower than that of the general population, use of early and aggressive treatment strategies including TNF-inhibitors can improve patients HRQoL effectively. Further research is needed in finding new treatment strategies for those patients who fail to respond or lose their response to TNF-inhibitors.

Atrial Electric Signal During Sinus Rhythm in Lone Paroxysmal Atrial Fibrillation

Atrial fibrillation (AF) is the most common tachyarrhythmia and is associated with substantial morbidity, increased mortality and cost. The treatment modalities of AF have increased, but results are still far from optimal. More individualized therapy may be beneficial. Aiming for this calls improved diagnostics. Aim of this study was to find non-invasive parameters obtained during sinus rhythm reflecting electrophysiological patterns related to propensity to AF and particularly to AF occurring without any associated heart disease, lone AF. Overall 240 subjects were enrolled, 136 patients with paroxysmal lone AF and 104 controls (mean age 45 years, 75% males). Signal measurements were performed by non-invasive magnetocardiography (MCG) and by invasive electroanatomic mapping (EAM). High-pass filtering techniques and a new method based on a surface gradient technique were adapted to analyze atrial MCG signal. The EAM was used to elucidate atrial activation in patients and as a reference for MCG. The results showed that MCG mapping is an accurate method to detect atrial electrophysiologic properties. In lone paroxysmal AF, duration of the atrial depolarization complex was marginally prolonged. The difference was more obvious in women and was also related to interatrial conduction patterns. In the focal type of AF (75%), the root mean square (RMS) amplitudes of the atrial signal were normal, but in AF without demonstrable triggers the late atrial RMS amplitudes were reduced. In addition, the atrial characteristics tended to remain similar even when examined several years after the first AF episodes. The intra-atrial recordings confirmed the occurrence of three distinct sites of electrical connection from right to left atrium (LA): the Bachmann bundle (BB), the margin of the fossa ovalis (FO), and the coronary sinus ostial area (CS). The propagation of atrial signal could also be evaluated non-invasively. Three MCG atrial wave types were identified, each of which represented a distinct interatrial activation pattern. In conclusion, in paroxysmal lone AF, active focal triggers are common, atrial depolarization is slightly prolonged, but with a normal amplitude, and the arrhythmia does not necessarily lead to electrical or mechanical dysfunction of the atria. In women the prolongation of atrial depolarization is more obvious. This may be related to gender differences in presentation of AF. A significant minority of patients with lone AF lack frequent focal triggers, and in them, the late atrial signal amplitude is reduced, possibly signifying a wider degenerative process in the LA. In lone AF, natural impulse propagation to LA during sinus rhythm goes through one or more of the principal pathways described. The BB is the most common route, but in one-third, the earliest LA activation occurs outside the BB. Susceptibility to paroxysmal lone AF is associated with propagation of the atrial signal via the margin of the FO or via multiple pathways. When conduction occurs via the BB, it is related with prolonged atrial activation. Thus, altered and alternative conduction pathways may contribute to pathogenesis of lone AF. There is growing evidence of variability in genesis of AF also within lone paroxysmal AF. Present study suggests that this variation may be reflected in cardiac signal pattern. Recognizing the distinct signal profiles may assist in understanding the pathogenesis of AF and identifying subgroups for patient-tailored therapy.

Language learning in infancy

Although immensely complex, speech is also a very efficient means of communication between humans. Understanding how we acquire the skills necessary for perceiving and producing speech remains an intriguing goal for research. However, while learning is likely to begin as soon as we start hearing speech, the tools for studying the language acquisition strategies in the earliest stages of development remain scarce. One prospective strategy is statistical learning. In order to investigate its role in language development, we designed a new research method. The method was tested in adults using magnetoencephalography (MEG) as a measure of cortical activity. Neonatal brain activity was measured with electroencephalography (EEG). Additionally, we developed a method for assessing the integration of seen and heard syllables in the developing brain as well as a method for assessing the role of visual speech when learning phoneme categories. The MEG study showed that adults learn statistical properties of speech during passive listening of syllables. The amplitude of the N400m component of the event-related magnetic fields (ERFs) reflected the location of syllables within pseudowords. The amplitude was also enhanced for syllables in a statistically unexpected position. The results suggest a role for the N400m component in statistical learning studies in adults. Using the same research design with sleeping newborn infants, the auditory event-related potentials (ERPs) measured with EEG reflected the location of syllables within pseudowords. The results were successfully replicated in another group of infants. The results show that even newborn infants have a powerful mechanism for automatic extraction of statistical characteristics from speech. We also found that 5-month-old infants integrate some auditory and visual syllables into a fused percept, whereas other syllable combinations are not fully integrated. Auditory syllables were paired with visual syllables possessing a different phonetic identity, and the ERPs for these artificial syllable combinations were compared with the ERPs for normal syllables. For congruent auditory-visual syllable combinations, the ERPs did not differ from those for normal syllables. However, for incongruent auditory-visual syllable combinations, we observed a mismatch response in the ERPs. The results show an early ability to perceive speech cross-modally. Finally, we exposed two groups of 6-month-old infants to artificially created auditory syllables located between two stereotypical English syllables in the formant space. The auditory syllables followed, equally for both groups, a unimodal statistical distribution, suggestive of a single phoneme category. The visual syllables combined with the auditory syllables, however, were different for the two groups, one group receiving visual stimuli suggestive of two separate phoneme categories, the other receiving visual stimuli suggestive of only one phoneme category. After a short exposure, we observed different learning outcomes for the two groups of infants. The results thus show that visual speech can influence learning of phoneme categories. Altogether, the results demonstrate that complex language learning skills exist from birth. They also suggest a role for the visual component of speech in the learning of phoneme categories.