Towards Optimal Testing of Auditory Memory : Methodological development of recording of the mismatch negativity (MMN) of the auditory event-related potential (ERP)

The overlapping sound pressure waves that enter our brain via the ears and auditory nerves must be organized into a coherent percept. Modelling the regularities of the auditory environment and detecting unexpected changes in these regularities, even in the absence of attention, is a necessary prerequisite for orientating towards significant information as well as speech perception and communication, for instance. The processing of auditory information, in particular the detection of changes in the regularities of the auditory input, gives rise to neural activity in the brain that is seen as a mismatch negativity (MMN) response of the event-related potential (ERP) recorded by electroencephalography (EEG). --- As the recording of MMN requires neither a subject s behavioural response nor attention towards the sounds, it can be done even with subjects with problems in communicating or difficulties in performing a discrimination task, for example, from aphasic and comatose patients, newborns, and even fetuses. Thus with MMN one can follow the evolution of central auditory processing from the very early, often critical stages of development, and also in subjects who cannot be examined with the more traditional behavioural measures of auditory discrimination. Indeed, recent studies show that central auditory processing, as indicated by MMN, is affected in different clinical populations, such as schizophrenics, as well as during normal aging and abnormal childhood development. Moreover, the processing of auditory information can be selectively impaired for certain auditory attributes (e.g., sound duration, frequency) and can also depend on the context of the sound changes (e.g., speech or non-speech). Although its advantages over behavioral measures are undeniable, a major obstacle to the larger-scale routine use of the MMN method, especially in clinical settings, is the relatively long duration of its measurement. Typically, approximately 15 minutes of recording time is needed for measuring the MMN for a single auditory attribute. Recording a complete central auditory processing profile consisting of several auditory attributes would thus require from one hour to several hours. In this research, I have contributed to the development of new fast multi-attribute MMN recording paradigms in which several types and magnitudes of sound changes are presented in both speech and non-speech contexts in order to obtain a comprehensive profile of auditory sensory memory and discrimination accuracy in a short measurement time (altogether approximately 15 min for 5 auditory attributes). The speed of the paradigms makes them highly attractive for clinical research, their reliability brings fidelity to longitudinal studies, and the language context is especially suitable for studies on language impairments such as dyslexia and aphasia. In addition I have presented an even more ecological paradigm, and more importantly, an interesting result in view of the theory of MMN where the MMN responses are recorded entirely without a repetitive standard tone. All in all, these paradigms contribute to the development of the theory of auditory perception, and increase the feasibility of MMN recordings in both basic and clinical research. Moreover, they have already proven useful in studying for instance dyslexia, Asperger syndrome and schizophrenia.

Studies of solar and stellar flares using multi-instrument data

Solar flares were first observed by plain eye in white light by William Carrington in England in 1859. Since then these eruptions in the solar corona have intrigued scientists. It is known that flares influence the space weather experienced by the planets in a multitude of ways, for example by causing aurora borealis. Understanding flares is at the epicentre of human survival in space, as astronauts cannot survive the highly energetic particles associated with large flares in high doses without contracting serious radiation disease symptoms, unless they shield themselves effectively during space missions. Flares may be at the epicentre of man s survival in the past as well: it has been suggested that giant flares might have played a role in exterminating many of the large species on Earth, including dinosaurs. Having said that prebiotic synthesis studies have shown lightning to be a decisive requirement for amino acid synthesis on the primordial Earth. Increased lightning activity could be attributed to space weather, and flares. This thesis studies flares in two ways: in the spectral and the spatial domain. We have extracted solar spectra using three different instruments, namely GOES (Geostationary Operational Environmental Satellite), RHESSI (Reuven Ramaty High Energy Solar Spectroscopic Imager) and XSM (X-ray Solar Monitor) for the same flares. The GOES spectra are low resolution obtained with a gas proportional counter, the RHESSI spectra are higher resolution obtained with Germanium detectors and the XSM spectra are very high resolution observed with a silicon detector. It turns out that the detector technology and response influence the spectra we see substantially, and are important to understanding what conclusions to draw from the data. With imaging data, there was not such a luxury of choice available. We used RHESSI imaging data to observe the spatial size of solar flares. In the present work the focus was primarily on current solar flares. However, we did make use of our improved understanding of solar flares to observe young suns in NGC 2547. The same techniques used with solar monitors were applied with XMM-Newton, a stellar X-ray monitor, and coupled with ground based Halpha observations these techniques yielded estimates for flare parameters in young suns. The material in this thesis is therefore structured from technology to application, covering the full processing path from raw data and detector responses to concrete physical parameter results, such as the first measurement of the length of plasma flare loops in young suns.

Change detection and controlling forest information using multi-temporal Landsat TM imagery.

A method was developed for relative radiometric calibration of single multitemporal Landsat TM image, several multitemporal images covering each others, and several multitemporal images covering different geographic locations. The radiometricly calibrated difference images were used for detecting rapid changes on forest stands. The nonparametric Kernel method was applied for change detection. The accuracy of the change detection was estimated by inspecting the image analysis results in field. The change classification was applied for controlling the quality of the continuously updated forest stand information. The aim was to ensure that all the manmade changes and any forest damages were correctly updated including the attribute and stand delineation information. The image analysis results were compared with the registered treatments and the stand information base. The stands with discrepancies between these two information sources were recommended to be field inspected.

Il mundus muliebris nelle fonti latine e nei contesti Pompeiani

The subject of the study is the classical Latin concept 'mundus muliebris', usually translated simply as women’s toiletry items. The task of the research is, on one hand, to find a more accurate and comprehensive literary definition for the concept as used in the early Imperial period, and on the other, to examine whether it is possible to find corresponding groupings of material objects among the finds from Pompeian houses destroyed by the eruption of Mount Vesuvius in AD 79. The study is based on two different bodies of evidence, literary and material, and consequently uses two independent methods of research. In the philological part of the study, all occurrences of the concept 'mundus muliebris' in classical Latin texts were identified and analysed in their proper literary context, paying special attention to information about the nature of the objects included (name, owner, quantity, value, location in the house). On the basis of this analysis, mirrors were chosen as the key elements of the archaeological research, being ̶ hypothetically ̶ the most probable objects to be found among any extant 'mundus muliebris' contexts in Pompeian houses. In the archaeological part of the study, all mirrors deposited in the Archaeological Storerooms of Pompeii, mostly unpublished, were examined, together with their original find contexts. For more detailed documentation, classification, as well as quantitative and functional analysis, the fifty-nine best preserved household or shop contexts were chosen. Among these contexts, only a few ‘ideal’ groups closely corresponding to the literary definitions were found. However, in most cases a functional artifact pattern of toiletry items could indeed be found grouped together with the mirror. The arrangement of the contexts in the domestic space also revealed a clear pattern. Firstly, the contexts consistently seem to be found in the place of storage, inside locked boxes, not in the place of use. Secondly, they show that for the storage of such objects small closed rooms flanking the main entrance of the house were preferred. Culturally, 'mundus muliebris' can be described as a very complex multi-layered concept intimately interrelated with the female gender, an instrument of its bodily creation and a symbol of its nature. Concretely, it has at its core mirrors and instruments for the care of skin and hair, and includes, in more technical definitions, washing equipment as well. In the Roman domus, lacking specific women’s quarters, this box containing toiletries and other personal objects could be defined as the true, although mobile, private space of the household’s female members.

Kaukainen rakkaus : Saavuttamattomuuden semantiikka Kaija Saariahon oopperassa

L Amour de loin: The semantics of the unattainable in Kaija Saariaho s opera Kaija Saariaho (born 1952) is one of the most internationally successful Finnish composers there has ever been. Her first opera L Amour de loin (Love from afar, 1999-2000) has been staged all over the world and has won a number of important prizes. The libretto written for L Amour de loin by Amin Malouf (born 1949) sets the work firmly in the culture of courtly love and the troubadours, which flourished in Occitania in the South of France during the Middle Ages. The male lead in the opera is the troubadour Jaufré Rudel, who lived in the twelfth century and is known to have taken part in the Second Crusade in 1147-1148. This doctoral thesis L Amour de loin: The semantics of the unattainable in Kaija Saariaho s opera, which comes within the field of musicology and opera research, examines the dimensions of meaning contained in Kaija Saariaho s opera L Amour de loin. This hermeneutic-semiotic study is the first doctoral thesis dealing with Saariaho to be completed at the University of Helsinki. It is also the first thesis-level study of Saariaho s opera to be completed anywhere in the world. The study focuses on the libretto and music of the opera, that is to say the dramatic text (L Amour de loin 1980), and examines on the one hand the dimensions of meaning produced by the dramatic text and on the other, the way in which they fix the dramatic text in a historical and cultural context. Thus the study helps to answer questions about the dimensions of meaning contained in the dramatic text of the opera and how they can be interpreted. The most important procedural viewpoint is Lawrence Kramer s hermeneutic window (1990), supplemented by Raymond Monelle s semiotic theory of musical topics (2000, 2006) and the philosophical concept of Emmanuel Levinas (1996, 2002) in which the latter acts as an instrument for semantic interpretation to build up an analysis. The analytical section of the study is built around the three characters in the opera, Jaufré Rudel, Clémence the Countess of Tripoli, and the Pilgrim. The study shows that the music of Saariaho, who belongs to the third generation of Finnish modernists, has become distanced from the post-serial aesthetic towards a more diatonic form of expression. There is diatonicity, for instance, in the sonorous individuality of the male lead, which is based on the actual melodies of the historical Jaufré Rudel. The use of outside material in this context is exceptional in the work of Saariaho. At the same time, Saariaho s opera contains a wealth of expressive devices she has used in her earlier work. It became apparent during the study that, as a piece of music, L Amour de loin is a many layered and multi-dimensional work that does not unambiguously represent any single stylistic trend or aesthetic. Despite the composer s post-serial background and its abrasive relationship with opera, L Amour de loin is firmly attached to the tradition of western opera. The analysis based on the theory of musical topics that was carried out in the study, shows that topics referring to death and resurrection, used in opera since the seventeenth century, appear in L Amour de loin. The troubadour topic, mainly identified with the harp, also emerges in the work. The study also shows that the work is firmly attached to the tradition of western opera in other aspects, too, such as the travesti or trouser role played by the Pilgrim, and the idea of deus ex machina derived from Ancient Greek theatre. The study shows that the concept of love based on the medieval practices of courtly love, and the associated longing for another defined by almost 1,000 years of western culture, are both manifested in the semantics of Kaija Saariaho s opera which takes its place in the contemporary music genre.

Routine Measurement of Health-Related Quality of Life in Assessing Cost-Effectiveness in Secondary Health Care

Aims: The aims of this study were 1) to identify and describe health economic studies that have used quality-adjusted life years (QALYs) based on actual measurements of patients' health-related quality of life (HRQoL); 2) to test the feasibility of routine collection of health-related quality of life (HRQoL) data as an indicator of effectiveness of secondary health care; and 3) to establish and compare the cost-utility of three large-volume surgical procedures in a real-world setting in the Helsinki University Central Hospital, a large referral hospital providing secondary and tertiary health-care services for a population of approximately 1.4 million. Patients and methods: So as to identify studies that have used QALYs as an outcome measure, a systematic search of the literature was performed using the Medline, Embase, CINAHL, SCI and Cochrane Library electronic databases. Initial screening of the identified articles involved two reviewers independently reading the abstracts; the full-text articles were also evaluated independently by two reviewers, with a third reviewer used in cases where the two reviewers could not agree a consensus on which articles should be included. The feasibility of routinely evaluating the cost-effectiveness of secondary health care was tested by setting up a system for collecting HRQoL data on approximately 4 900 patients' HRQoL before and after operative treatments performed in the hospital. The HRQoL data used as an indicator of treatment effectiveness was combined with diagnostic and financial indicators routinely collected in the hospital. To compare the cost-effectiveness of three surgical interventions, 712 patients admitted for routine operative treatment completed the 15D HRQoL questionnaire before and also 3-12 months after the operation. QALYs were calculated using the obtained utility data and expected remaining life years of the patients. Direct hospital costs were obtained from the clinical patient administration database of the hospital and a cost-utility analysis was performed from the perspective of the provider of secondary health care services. Main results: The systematic review (Study I) showed that although QALYs gained are considered an important measure of the effectiveness of health care, the number of studies in which QALYs are based on actual measurements of patients' HRQoL is still fairly limited. Of the reviewed full-text articles, only 70 reported QALYs based on actual before after measurements using a valid HRQoL instrument. Collection of simple cost-effectiveness data in secondary health care is feasible and could easily be expanded and performed on a routine basis (Study II). It allows meaningful comparisons between various treatments and provides a means for allocating limited health care resources. The cost per QALY gained was 2 770 for cervical operations and 1 740 for lumbar operations. In cases where surgery was delayed the cost per QALY was doubled (Study III). The cost per QALY ranges between subgroups in cataract surgery (Study IV). The cost per QALY gained was 5 130 for patients having both eyes operated on and 8 210 for patients with only one eye operated on during the 6-month follow-up. In patients whose first eye had been operated on previous to the study period, the mean HRQoL deteriorated after surgery, thus precluding the establishment of the cost per QALY. In arthroplasty patients (Study V) the mean cost per QALY gained in a one-year period was 6 710 for primary hip replacement, 52 270 for revision hip replacement, and 14 000 for primary knee replacement. Conclusions: Although the importance of cost-utility analyses has during recent years been stressed, there are only a limited number of studies in which the evaluation is based on patients own assessment of the treatment effectiveness. Most of the cost-effectiveness and cost-utility analyses are based on modeling that employs expert opinion regarding the outcome of treatment, not on patient-derived assessments. Routine collection of effectiveness information from patients entering treatment in secondary health care turned out to be easy enough and did not, for instance, require additional personnel on the wards in which the study was executed. The mean patient response rate was more than 70 %, suggesting that patients were happy to participate and appreciated the fact that the hospital showed an interest in their well-being even after the actual treatment episode had ended. Spinal surgery leads to a statistically significant and clinically important improvement in HRQoL. The cost per QALY gained was reasonable, at less than half of that observed for instance for hip replacement surgery. However, prolonged waiting for an operation approximately doubled the cost per QALY gained from the surgical intervention. The mean utility gain following routine cataract surgery in a real world setting was relatively small and confined mostly to patients who had had both eyes operated on. The cost of cataract surgery per QALY gained was higher than previously reported and was associated with considerable degree of uncertainty. Hip and knee replacement both improve HRQoL. The cost per QALY gained from knee replacement is two-fold compared to hip replacement. Cost-utility results from the three studied specialties showed that there is great variation in the cost-utility of surgical interventions performed in a real-world setting even when only common, widely accepted interventions are considered. However, the cost per QALY of all the studied interventions, except for revision hip arthroplasty, was well below 50 000, this figure being sometimes cited in the literature as a threshold level for the cost-effectiveness of an intervention. Based on the present study it may be concluded that routine evaluation of the cost-utility of secondary health care is feasible and produces information essential for a rational and balanced allocation of scarce health care resources.

Effect of waiting time on health outcomes and service utilization : A prospective randomized study on patients admitted to hospital for hip or knee replacement

Although the principle of equal access to medically justified treatment has been promoted by official health policies in many Western health care systems, practices do not completely meet policy targets. Waiting times for elective surgery vary between patient groups and regions, and growing problems in the availability of services threaten equal access to treatment. Waiting times have come to the attention of decision-makers, and several policy initiatives have been introduced to ensure the availability of care within a reasonable time. In Finland, for example, the treatment guarantee came into force in 2005. However, no consensus exists on optimal waiting time for different patient groups. The purpose of this multi-centre randomized controlled trial was to analyse health-related quality of life, pain and physical function in total hip or knee replacement patients during the waiting time and to evaluate whether the waiting time is associated with patients health outcomes at admission. This study also assessed whether the length of waiting time is associated with social and health services utilization in patients awaiting total hip or knee replacement. In addition, patients health-related quality of life was compared with that of the general population. Consecutive patients with a need for a primary total hip or knee replacement due to osteoarthritis were placed on the waiting list between August 2002 and November 2003. Patients were randomly assigned to a short waiting time (maximum 3 months) or a non-fixed waiting time (waiting time not fixed in advance, instead the patient followed the hospitals routine practice). Patients health-related quality of life was measured upon being placed on the waiting list and again at hospital admission using the generic 15D instrument. Pain and physical function were evaluated using the self-report Harris Hip Score for hip patients and a scale modified from the Knee Society Clinical Rating System for knee patients. Utilization measures were the use of home health care, rehabilitation and social services, physician visits and inpatient care. Health and social services use was low in both waiting time groups. The most common services used while waiting were rehabilitation services and informal care, including unpaid care provided by relatives, neighbours and volunteers. Although patients suffered from clear restrictions in usual activities and physical functioning, they seemed primarily to lean on informal care and personal networks instead of professional care. While longer waiting time did not result in poorer health-related quality of life at admission and use of services during the waiting time was similar to that at the time of placement on the list, there is likely to be higher costs of waiting by people who wait longer simply because they are using services for a longer period. In economic terms, this would represent a negative impact of waiting. Only a few reports have been published of the health-related quality of life of patients awaiting total hip or knee replacement. These findings demonstrate that, in addition to physical dimensions of health, patients suffered from restrictions in psychological well-being such as depression, distress and reduced vitality. This raises the question of how to support patients who suffer from psychological distress during the waiting time and how to develop strategies to improve patients initiatives to reduce symptoms and the burden of waiting. Key words: waiting time, total hip replacement, total knee replacement, health-related quality of life, randomized controlled trial, outcome assessment, social service, utilization of health services

Management of multi-scale forest resource data over time

During the last decades there has been a global shift in forest management from a focus solely on timber management to ecosystem management that endorses all aspects of forest functions: ecological, economic and social. This has resulted in a shift in paradigm from sustained yield to sustained diversity of values, goods and benefits obtained at the same time, introducing new temporal and spatial scales into forest resource management. The purpose of the present dissertation was to develop methods that would enable spatial and temporal scales to be introduced into the storage, processing, access and utilization of forest resource data. The methods developed are based on a conceptual view of a forest as a hierarchically nested collection of objects that can have a dynamically changing set of attributes. The temporal aspect of the methods consists of lifetime management for the objects and their attributes and of a temporal succession linking the objects together. Development of the forest resource data processing method concentrated on the extensibility and configurability of the data content and model calculations, allowing for a diverse set of processing operations to be executed using the same framework. The contribution of this dissertation to the utilisation of multi-scale forest resource data lies in the development of a reference data generation method to support forest inventory methods in approaching single-tree resolution.

NMR Spectroscopy of Multi-domain Proteins : Immunoglobulin-like Domains of Human Filamin A

Proteins are complex biomacromolecules playing fundamental roles in the physiological processes of all living organisms. They function as structural units, enzymes, transporters, process regulators, and signal transducers. Defects in protein functions often derive from genetic mutations altering the protein structure, and impairment of essential protein functions manifests itself as pathological conditions. Proteins operate through interactions, and all protein functions depend on protein structure. In order to understand biological mechanisms at the molecular level, one has to know the structures of the proteins involved. This thesis covers structural and functional characterization of human filamins. Filamins are actin-binding and -bundling proteins that have numerous interaction partners. In addition to their actin-organizing functions, filamins are also known to have roles in cell adhesion and locomotion, and to participate in the logistics of cell membrane receptors, and in the coordination of intracellular signaling pathways. Filamin mutations in humans induce severe pathological conditions affecting the brain, bones, limbs, and the cardiovascular system. Filamins are large modular proteins composed of an N-terminal actin-binding domain and 24 consecutive immunoglobulin-like domains (IgFLNs). Nuclear magnetic resonance (NMR) spectroscopy is a versatile method of gaining insight into protein structure, dynamics and interactions. NMR spectroscopy was employed in this thesis to study the atomic structure and interaction mechanisms of C-terminal IgFLNs, which are known to house the majority of the filamin interaction sites. The structures of IgFLN single-domains 17 and 23 and IgFLN domain pairs 16-17 and 18-19 were determined using NMR spectroscopy. The structures of domain pairs 16 17 and 18 19 both revealed novel domain domain interaction modes of IgFLNs. NMR titrations were employed to characterize the interactions of filamins with glycoprotein Ibα, FilGAP, integrin β7 and dopamine receptors. Domain packing of IgFLN domain sextet 16 21 was further characterized using residual dipolar couplings and NMR relaxation analysis. This thesis demonstrates the versatility and potential of NMR spectroscopy in structural and functional studies of multi-domain proteins.

Multi-user resource-sharing problem for the Internet

In this thesis we study a series of multi-user resource-sharing problems for the Internet, which involve distribution of a common resource among participants of multi-user systems (servers or networks). We study concurrently accessible resources, which for end-users may be exclusively accessible or non-exclusively. For all kinds we suggest a separate algorithm or a modification of common reputation scheme. Every algorithm or method is studied from different perspectives: optimality of protocols, selfishness of end users, fairness of the protocol for end users. On the one hand the multifaceted analysis allows us to select the most suited protocols among a set of various available ones based on trade-offs of optima criteria. On the other hand, the future Internet predictions dictate new rules for the optimality we should take into account and new properties of the networks that cannot be neglected anymore. In this thesis we have studied new protocols for such resource-sharing problems as the backoff protocol, defense mechanisms against Denial-of-Service, fairness and confidentiality for users in overlay networks. For backoff protocol we present analysis of a general backoff scheme, where an optimization is applied to a general-view backoff function. It leads to an optimality condition for backoff protocols in both slot times and continuous time models. Additionally we present an extension for the backoff scheme in order to achieve fairness for the participants in an unfair environment, such as wireless signal strengths. Finally, for the backoff algorithm we suggest a reputation scheme that deals with misbehaving nodes. For the next problem -- denial-of-service attacks, we suggest two schemes that deal with the malicious behavior for two conditions: forged identities and unspoofed identities. For the first one we suggest a novel most-knocked-first-served algorithm, while for the latter we apply a reputation mechanism in order to restrict resource access for misbehaving nodes. Finally, we study the reputation scheme for the overlays and peer-to-peer networks, where resource is not placed on a common station, but spread across the network. The theoretical analysis suggests what behavior will be selected by the end station under such a reputation mechanism.

EU Multi-level Governance in the Making - The Community Initiative LEADER+ in Finland and Germany

In order to fully understand the process of European integration it is of paramount importance to consider developments at the sub-national and local level. EU integration scholars shifted their attention to the local level only at the beginning of the 1990s with the concept of multi-level governance (MLG). While MLG is the first concept to scrutinise the position of local levels of public administration and other actors within the EU polity, I perceive it as too optimistic in the degree of influence it ascribes to local levels. Thus, learning from and combining MLG with other concepts, such as structural constructivism, helps to reveal some of the hidden aspects of EU integration and paint a more realistic picture of multi-level interaction. This thesis also answers the call for more case studies in order to conceptualise MLG further. After a critical study of theories and concepts of European integration, above all, MLG, I will analyse sub-national and local government in Finland and Germany. I show how the sub-national level and local governments are embedded in the EU s multi-level structure of governance and how, through EU integration, those levels have been empowered but also how their scope of action has partially decreased. After theoretical and institutional contextualisation, I present the results of my empirical study of the EU s Community Initiative LEADER+. LEADER stands for Liaison Entre Actions de Développement de l'Économie Rurale , and aims at improving the economic conditions in Europe s rural areas. I was interested in how different actors construct and shape EU financed rural development, especially in how local actors organised in so-called local action groups (LAGs) cooperate with other administrative units within the LEADER+ administrative chain. I also examined intra-institutional relations within those groups, in order to find out who are the most influential and powerful actors within them. Empirical data on the Finnish and German LAGs was first gathered through a survey, which was then supplemented and completed by interviewing LAG members, LAG-managers, several civil servants from Finnish and German decision-making and managing authorities and a civil servant from the EU Commission. My main argument is that in both Germany and Finland, the Community Initiative LEADER+ offered a space for multi-level interaction and local-level involvement, a space that on the one hand consists of highly motivated people actively contributing to the improvement of the quality of life and economy in Europe s countryside but which is dependent and also restricted by national administrative practices, implementation approaches and cultures on the other. In Finland, the principle of tri-partition (kolmikantaperiaatte) in organising the executive committees of LAGs is very noticeable. In comparison to Germany, for instance, the representation of public administration in those committees is much more limited due to this principle. Furthermore, the mobilisation of local residents and the bringing together of actors from the local area with different social and institutional backgrounds to become an active part of LEADER+ was more successful in Finland than in Germany. Tri-partition as applied in Finland should serve as a model for similar policies in other EU member states. EU integration changed the formal and informal inter-institutional relations linking the different levels of government. The third sector including non-governmental institutions and interest groups gained access to policy-making processes and increasingly interact with government institutions at all levels of public administration. These developments do not necessarily result in the empowering of the local level.