Neural mechanisms underlying perilesional transcranial direct current stimulation in aphasia: A feasibility study

Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS) impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI). We employed a single subject, cross-over, sham-tDCS controlled design, and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI, which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioral stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS effects on brain functions in aphasia.

Iodine Brachytherapy for Large Uveal Melanomas

Uveal melanoma is the most common primary intraocular malignancy in adults. Vision in the affected eye is threatened by both the tumor and side-effects from the treatments currently available. Poor prognosis for saving vision increases with tumor size and, consequently, enucleation has been the treatment of choice for large uveal melanomas in most centers. However, increasing evidence suggests that no survival benefit is gained (nor lost) by enucleation as compared to eye-conserving methods. The Helsinki University Eye Hospital has since 1990 offered episcleral iodine-125 plaque brachytherapy (IBT) for all patients unwilling to undergo enucleation for a large uveal melanoma. The primary aim of this study was to assess survival, local tumor recurrence and preservation of the eye and vision after IBT in a population-based series of 97 patients with uveal melanomas classified as large by the Collaborative Ocular Melanoma Study (COMS) criteria. Further aims included reporting the incidence of side-effects and assessing the role of intraocular dose distribution and clinical risk factors in their development. Finally, means to improve the current treatment were investigated by using computer models to compare existing plaques with collimating ones and by comparing the outcome of a subgroup of 54 IBT patients with very thick tumors with 33 patients with similarly-sized tumors managed with transscleral local resection (TSR) in Liverpool, United Kingdom. Kaplan-Meier estimates of all-cause and melanoma-specific survival at 5 years after IBT were 62% and 65%, respectively, and visually comparable with the survival experience of patients reported after enucleation by the COMS. Local recurrence developed in 6% of eyes and 84% of eyes were conserved at 5 years. Visual prognosis was guarded with 11% avoiding loss of 20/70 vision and 26% avoiding loss of 20/400 vision in the tumor eye at 2 years. Large tumor height and short distance from the posterior pole were independently associated with loss of vision. Using cumulative incidence analysis to account for competing risks, such as enucleation and metastatic death, the 5-year incidence of cataract after IBT was 79%, glaucoma 60%, optic neuropathy 46%, maculopathy 52%, persistent or recurring retinal detachment (RD) 25%, and vitreous hemorrhage 36%. In multivariate competing risks regression models, increasing tumor height was associated with cataract, iris neovascularization and RD. Maculopathy and optic neuropathy were associated with distance from the tumor to the respective structure. Median doses to the tumor apex, macula and optic disc were 81 Gy (range, 40-158), 79 Gy (range, 12-632), and 83 Gy (range, 10-377), respectively. Dose to the optic disc was independently associated with optic neuropathy, and both dose to the optic disc and dose to the macula predicted vision loss after IBT. Simulated treatment using collimating plaques resulted in clinically meaningful reduction in both optic disc (median reduction, 30 Gy) and macular (median reduction, 36 Gy) doses as compared to the actual treatment with standard plaques. In the subgroup of patients with uveal melanomas classified as large because of tumor height, cumulative incidence analysis revealed that while long-term preservation of 20/70 vision was rare after both IBT and TSR, preservation of 20/400 vision was better after TSR (32% vs. 5% at 5 years). In multivariate logistic regression models, TSR was independently associated with better preservation of 20/400 vision (OR 0.03 at 2 years, P=0.005) No cases of secondary glaucoma were observed after TSR and optic neuropathy was rare. However, local tumor recurrence was more common after TSR than it was after IBT (Cumulative incidence 41% vs. 7% at 5 years, respectively). In terms of survival, IBT seems to be a safe alternative to enucleation in managing large uveal melanomas. Local tumor control is no worse than with medium-sized tumors and the chances of avoiding secondary enucleation are good. Unfortunately, side-effects from radiotherapy are frequent, especially in thick tumors, and long-term prognosis of saving vision is consequently guarded. Some complications can be limited by using collimating plaques and by managing uveal melanomas that are large because of tumor height with TSR instead of IBT. However, the patient must be willing to accept a substantial risk of local tumor recurrence after TSR and it is best suited for cases in which the preservation of vision in the tumor eye is critical.

E-book monopolies and the law

This article will examine the legality of the digital rights management (‘DRM’) measures used by the major e-book publishers and device manufacturers in the United States, European Union and Australia not only to enforce their intellectual property rights but also to create monopolistic content silos, restrict interoperability and affect the ability for users to use the content they have bought in the way they wish. The analysis will then proceed to the recent competition investigations in the US and EU over price-fixing in e-book markets, and the current litigation against Amazon in the US for an alleged abuse of its dominant position. A final point will be made on possible responses in Australia to these issues taking into account the jurisprudence on DRM in other scenarios.

Low-frequency resistance fluctuations in metal films under current stressing at low temperature (T<0.3Tmelting)

In this paper, we report a systematic study of low frequency 1∕fα resistance fluctuation in thin metal films (Ag on Si) at different stages of damage process when the film is subjected to high current stressing. The resistance fluctuation (noise) measurement was carried out in situ using a small ac bias that has been mixed with the dc stressing current. The experiment has been carried out as a function of temperature in the range of 150–350 K. The experiment establishes that the current stressed film, as it undergoes damage due to various migration forces, develops an additional low-frequency noise spectral power that does not have the usual 1∕f spectral shape. The magnitude of extra term has an activated temperature dependence (activation energy of ≈0.1 eV) and has a 1∕f1.5 spectral dependence. The activation energy is the same as seen from the temperature dependence of the lifetime of the film. The extra 1∕f1.5 spectral power changes the spectral shape of the noise power as the damage process progress. The extra term likely arising from diffusion starts in the early stage of the migration process during current stressing and is noticeable much before any change can be detected in simultaneous resistance measurements. The experiment carried out over a large temperature range establish a strong correlation between the evolution of the migration process in a current stressed film and the low-frequency noise component that is not a 1∕f noise.

Coping style and ecstasy use motives as predictors of current mood symptoms in ecstasy users

Background Elevated depressive and anxiety symptoms during childhood and adolescence have been associated with greater risk of later ecstasy use. Ecstasy users have reported using ecstasy to reduce depression or worry, or to escape. While these findings suggest that some people use ecstasy as a form of self-medication, limited research has been conducted examining the relationship between affective symptoms, coping styles and drug use motives in ecstasy users. This cross-sectional study aimed to determine if coping style and/or ecstasy use motives are associated with current mood symptoms in ecstasy users. Methods A community sample (n = 184) of 18–35 year olds who had taken ecstasy at least once in the past 12 months completed self-report measures of depression, anxiety, ecstasy use motives and coping styles. Timeline followback methods were used to collect information on lifetime ecstasy, recent drug use and life stress. Trauma exposure was measured using the Composite International Diagnostic Interview—Trauma List. Results Coping motives for ecstasy use and an emotion-focused coping style were significantly associated with current depressive and anxiety symptoms. Emotion-focused coping mediated the relationship between a history of trauma and current anxiety symptoms and moderated the relationship between recent stressful life events and current depressive symptoms. Conclusions These findings highlight the importance of interventions targeting motives for ecstasy use, and providing coping skills training for managing stressful life events among people with co-occurring depressive/anxiety symptoms and ecstasy use.

Rotavirus nonstructural proteins: a structural perspective

Rotavirus is a major cause of acute infantile diarrhoea worldwide. The virus genome consists of 11 segments of double-stranded RNA that codesfor six structural proteins (VP1-6) and six non-structural proteins(NSP1-6). NSPs are proteins expressed from the virus genome in the infected cell, but are not incorporated into the mature virus article. NSPs play an essential role in virus replication, morphogenesis and pathogenesis, and most of them exhibit multifunctional properties. Structure-function analysis of the NSPs is essential for understanding the molecular mechanisms by which the virus circumvents host innate immune responses, inhibits cellular protein synthesis, hijacks the protein synthetic machinery for its own propagation and manifests the disease process. Because of their essential roles in virus biology, NSPs represent potential targets for the development of antiviral agents. Determination of the three-dimensional structure of NSPs has been hindered due to low-level expression and aggregation. To date, the complete three-dimensional structure of only NSP2 has been determined. The structures of the N- and C-terminal domains of NSP3 and the diarrhoea-inducing domain of NSP4 have also been determined. This review primarily covers the structural and biological functions of the NSPs whose three-dimensional structural aspects have been fully or partially understood, but provides a brief account of other NSPs and the structural features of the mature virion as determined by electron cryomicroscopy.

Hybrid Modelling of Titan's Interaction with the Magnetosphere of Saturn

In this dissertation we study the interaction between Saturn's moon Titan and the magnetospheric plasma and magnetic field. The method of research is a three-dimensional computer simulation model, that is used to simulate this interaction. The simulation model used is a hybrid model. Hybrid models enable individual tracking or tracing of ions and also take into account the particle motion in the propagation of the electromagnetic fields. The hybrid model has been developed at the Finnish Meteorological Institute. This thesis gives a general description of the effects that the solar wind has on Earth and other planets of our solar system. Planetary satellites can also have similar interactions with the solar wind but also with the plasma flows of planetary magnetospheres. Titan is clearly the largest among the satellites of Saturn and also the only known satellite with a dense atmosphere. It is the atmosphere that makes Titan's plasma interaction with the magnetosphere of Saturn so unique. Nevertheless, comparisons with the plasma interactions of other solar system bodies are valuable. Detecting charged plasma particles requires in situ measurements obtainable through scientific spacecraft. The Cassini mission has been one of the most remarkable international efforts in space science. Since 2004 the measurements and images obtained from instruments onboard the Cassini spacecraft have increased the scientific knowledge of Saturn as well as its satellites and magnetosphere in a way no one was probably able to predict. The current level of science on Titan is practically unthinkable without the Cassini mission. Many of the observations by Cassini instrument teams have influenced this research both the direct measurements of Titan as well as observations of its plasma environment. The theoretical principles of the hybrid modelling approach are presented in connection to the broader context of plasma simulations. The developed hybrid model is described in detail: e.g. the way the equations of the hybrid model are solved is shown explicitly. Several simulation techniques, such as the grid structure and various boundary conditions, are discussed in detail as well. The testing and monitoring of simulation runs is presented as an essential routine when running sophisticated and complex models. Several significant improvements of the model, that are in preparation, are also discussed. A main part of this dissertation are four scientific articles based on the results of the Titan model. The Titan model developed during the course of the Ph.D. research has been shown to be an important tool to understand Titan's plasma interaction. One reason for this is that the structures of the magnetic field around Titan are very much three-dimensional. The simulation results give a general picture of the magnetic fields in the vicinity of Titan. The magnetic fine structure of Titan's wake as seen in the simulations seems connected to Alfvén waves an important wave mode in space plasmas. The particle escape from Titan is also a major part of these studies. Our simulations show a bending or turning of Titan's ionotail that we have shown to be a direct result of the basic principles in plasma physics. Furthermore, the ion flux from the magnetosphere of Saturn into Titan's upper atmosphere has been studied. The modelled ion flux has asymmetries that would likely have a large impact in the heating in different parts of Titan's upper atmosphere.

Ship collision avoidance and COLREGS compliance using simulation-based control behavior selection with predictive hazard assessment

This paper describes a concept for a collision avoidance system for ships, which is based on model predictive control. A finite set of alternative control behaviors are generated by varying two parameters: offsets to the guidance course angle commanded to the autopilot and changes to the propulsion command ranging from nominal speed to full reverse. Using simulated predictions of the trajectories of the obstacles and ship, compliance with the Convention on the International Regulations for Preventing Collisions at Sea and collision hazards associated with each of the alternative control behaviors are evaluated on a finite prediction horizon, and the optimal control behavior is selected. Robustness to sensing error, predicted obstacle behavior, and environmental conditions can be ensured by evaluating multiple scenarios for each control behavior. The method is conceptually and computationally simple and yet quite versatile as it can account for the dynamics of the ship, the dynamics of the steering and propulsion system, forces due to wind and ocean current, and any number of obstacles. Simulations show that the method is effective and can manage complex scenarios with multiple dynamic obstacles and uncertainty associated with sensors and predictions.

Unfolding studies on soybean agglutinin and concanavalin a tetramers: A comparative account

The unfolding pathway of two very similar tetrameric legume lectins soybean agglutinin (SBA) and Concanavalin A ( ConA) were determined using GdnCl-induced denaturation. Both proteins displayed a reversible two-state unfolding mechanism. The analysis of isothermal denaturation data provided values for conformational stability of the two proteins. It was found that the DeltaG of unfolding of SBA was much higher than ConA at all the temperatures at which the experiments were done. ConA had a T-g 18 degreesC less than SBA. The higher conformational stability of SBA in comparison to ConA is largely due to substantial differences in their degrees of subunit interactions. Ionic interactions at the interface of the two proteins especially at the noncanonical interface seem to play a significant role in the observed stability differences between these two proteins. Furthermore, SBA is a glycoprotein with a GlcNac(2)Man(9) chain attached to Asn-75 of each subunit. The sugar chain in SBA lies at the noncanonical interface of the protein, and it is found to interact with the amino acid residues in the adjacent noncanonical interface. These interactions further stabilize SBA with respect to ConA, which is not glycosylated.

Improved switching frequency variation control of hysteresis controlled voltage source inverter-fed IM drives using current error space vector

A constant switching frequency current error space vector-based hysteresis controller for two-level voltage source inverter-fed induction motor (IM) drives is proposed in this study. The proposed controller is capable of driving the IM in the entire speed range extending to the six-step mode. The proposed controller uses the parabolic boundary, reported earlier, for vector selection in a sector, but uses simple, fast and self-adaptive sector identification logic for sector change detection in the entire modulation range. This new scheme detects the sector change using the change in direction of current error along the axes jA, jB and jC. Most of the previous schemes use an outer boundary for sector change detection. So the current error goes outside the boundary six times during sector change, in one cycle,, introducing additional fifth and seventh harmonic components in phase current. This may cause sixth harmonic torque pulsations in the motor and spread in the harmonic spectrum of phase voltage. The proposed new scheme detects the sector change fast and accurately eliminating the chance of introducing additional fifth and seventh harmonic components in phase current and provides harmonic spectrum of phase voltage, which exactly matches with that of constant switching frequency voltage-controlled space vector pulse width modulation (VC-SVPWM)-based two-level inverter-fed drives.

Current Care Guidelines for Cardiopulmonary Resuscitation : Implementation, skills and attitudes

Background: The national resuscitation guidelines were published in Finland in 2002 and are based on international guidelines published in 2000. The main goal of the national guidelines, available on the Internet free of charge, is early defibrillation by nurses in an institutional setting. Aim: To study possible changes in cardiopulmonary resuscitation (CPR) practices, especially concerning early defibrillation, nurses and students attitudes of guideline implementation and nurses and students ability to implement the guideline recommendations in clinical practices after publication of the Current Care (CC) guidelines for CPR 2002. Material and methods: CPR practices in Finnish health centres; especially concerning rapid defibrillation programmes, as well as the implementation of CC guidelines for CPR was studied in a mail survey to chief physicians of every health centre in Finland (Study I). The CPR skills using an automated external defibrillator (AED) were compared in a study including Objective stuctured clinical examination (OSCE) of resuscitation skills of nurses and nursing students in Finnish and Swedish hospital and institution (Studies II, III). Attitudes towards CPR-D and CPR guidelines among medical and nursing students and secondary hospital nurses were studied in surveys (Studies IV, V). The nurses receiving different CPR training were compared in a randomized trial including OSCE of CPR skills of nurses in Finnish Hospital (Study VI). Results: Two years after the publication, 40.7% of Finnish health centres used national resuscitation guidelines. The proportion of health centres having at least one AED (66%) and principle of nurse-performed defibrillation without the presence of a physician (42%) had increased. The CPR-D training was estimated to be insufficient regarding basic life support and advanced life support in the majority of health centres (Study I). CPR-D skills of nurses and nursing students in two specific Swedish and Finnish hospitals and institutions (Study II and III) were generally inadequate. The nurses performed better than the students and the Swedish nurses surpassed the Finnish ones. Geriatric nurses receiving traditional CPR-D training performed better than those receiving an Internet-based course but both groups failed to defibrillate within 60 s. Thus, the performance was not satisfactory even two weeks after traditional training (Study VI). Unlike the medical students, the nursing students did not feel competent to perform procedures recommended in the cardiopulmonary resuscitation guidelines including the defibrillation. However, the majority of nursing students felt confident about their ability to perform basic life support. The perceived ability to defibrillate correlated significantly with a positive attitude towards nurse-performed defibrillation and negatively with fear of damaging the patient s heart by defibrillation (Study IV). After the educational intervention, the nurses found their level of CPR-D capability more sufficient than before and felt more confident about their ability to perform defibrillation themselves. A negative attitude toward defibrillation correlated with perceived negative organisational attitudes toward cardiopulmonary resuscitation guidelines. After CPR-D education in the hospital, the majority (64%) of nurses hesitated to perform defibrillation because of anxiety and 27 % hesitated because of fear of injuring the patient. Also a negative personal attitude towards guidelines increased markedly after education (Study V). Conclusions: Although a significant change had occurred in resuscitation practices in primary health care after publication of national cardiopulmonary resuscitation guidelines the participants CPR-D skills were not adequate according to the CPR guidelines. The current way of teaching is unlikely to result in participants being able to perform adequate and rapid CPR-D. More information and more frequent training are needed to diminish anxiety concerning defibrillation. Negative beliefs and attitudes toward defibrillation affect the nursing students and nurses attitudes toward cardiopulmonary resuscitation guidelines. CPR-D education increased the participants self-confidence concerning CPR-D skills but it did not reduce their anxiety. AEDs have replaced the manual defibrillators in most institutions, but in spite of the modern devices the anxiety still exists. Basic education does not provide nursing students with adequate CPR-D skills. Thus, frequent training in the workplace has vital importance. This multi-professional program supported by the administration might provide better CPR-D skills. Distance learning alone cannot substitute for traditional small-group learning, tutored hands-on training is needed to learn practical CPR-D skills. Standardized testing would probably help controlling the quality of learning. Training of group-working skills might improve CPR performance.

Knowledge through Discussion : An Interpretation of Epistemology in Plato's Meno

According to Meno s paradox we cannot inquire into what we do not know because we do not know what we are inquiring into. There are many ways to interpret the paradox but the central issue about our ability to reach truth is a profound one. In the dialogue Meno, Plato presents the paradox and an outline of a solution which enables us to reach knowledge (epistēmē) through philosophical discussion. During the last century Meno has often been considered transitional between Socratic thinking and Plato s own philosophy, and thus the dialogue has not been adequately interpreted as an integrated whole. Therefore the distinctive epistemology of the dialogue has not gained due notice. In this thesis the dialogue is analysed as an integrated whole and the philosophical interpretation also takes into account its dramatic features. The thesis emphasises the role of language and definitions in acquiring knowledge. Among the results concerning these subjects is a new interpretation of Socrates s defintion of shape (schēma). The theory of anamnēsis all learning is recollection in the Meno is argued to answer the paradox philosophically although Plato s presentation also contains playful and ironic elements. The background of the way Plato presents his case is that he appreciated the fact that no argument can plausibly demonstrate that argumentation is able to reach truth. In the Meno, Plato makes the earliest explicit distinction between knowledge and true belief in the history of Western philosophy. He also gives a definition of knowledge which is the basis of the so called classical definition of knowledge as justified true belief. In the Meno, true beliefs become knowledge when someone ties them down by reasoning about the explanation. The analysis of the epistemology of the dialogue from this perspective gives an interpretation which integrates the central concepts of the epistemology in the dialogue elenchos, anamnēsis and hypothetical inquiry into a unified whole which contains a plausible argument according to which the ignorant can reach knowledge through discussion. The conception that emerges by such an analysis is interesting both from the point of view of current interests and that of the history of philosophy. The method of knowledge acquisition in the Meno can, for example, be seen as a predecessor of modern scientific methods. The Meno is the earliest Greek mathematical text that has survived in its original form. The analysis presented in the thesis of the geometric passages in the dialogue provides new results both concerning Socrates s geometry lesson with the slave and the example presenting the hypothetical method. Concerning the latter, a new interpretation is presented. Keywords: anamnēsis, epistēmē, knowledge, Meno s paradox, Plato

Muuttoliike ja vetovoimatekijät Helsingissä : - Kyselyaineiston analyysi

This thesis explores migration and the attractiveness of urban living in the Greater Helsinki region. The aim of the thesis is to explore the attractiveness of the city of Helsinki in terms of regional migration and to identify what characterizes migration to Helsinki. The study focuses in particular on housing, which is a key factor influencing migration decisions in the region. Other central themes in the study are housing policy and regional competition among municipalities. This study focuses solely on households moving within Finnish borders excluding international migration. Migration is examined by comparing in- and out-migration in Helsinki, as well as studying migration to the city s inner and outer areas. The primary research material in the study is a questionnaire data collected by the National Consumer Research Centre. In this thesis the data is used for studying migrants aged 25 45. The main research method is analyzing the data statistically using the SPSS software. Methods include frequency analysis, cross tabulation, factor analysis and descriptive analysis. Additionally, statistical data is used to complement the questionnaire data. The research results indicate that Helsinki s in- and out-migration differs both in terms of the type of households that migrate as well as in the reasons why they migrate. Furthermore, differences can also be detected between migration to the inner and outer parts of Helsinki. According to the research results, a household s current phase of life is crucial in determining where and why they move within the Greater Helsinki region. A household s set of values on the other hand, seems to have a lesser impact on migration within the region, even though households moving to Helsinki seem to value a somewhat more urban lifestyle than the ones moving out of the city. The research also shows a direct correlation between the values of migrants and their current phase of life. Decisions of migrating are heavily influenced by wider societal issues. In the Greater Helsinki region the labor and housing market appear to have a great influence on the direction of migration streams. According to the results, households move to and from Helsinki for different reasons. The primary reasons for moving to Helsinki are related to the city s diverse labor market and to the working careers of households. Issues related to urban living and an urban lifestyle seem to be relevant although not the main reason why people move to Helsinki. The research material indicates that Helsinki s urban environment is both a pull and a push factor affecting the decisions of migrants. The city attracts those seeking urban living, but on the contrary does not appeal to households seeking more space and wishing to live closer to nature. According to the research, Helsinki with its densely built urban environment mainly attracts singles and childless couples, whereas the city region s other municipalities are more attractive for families with children. Housing policy is one of the main reasons determining where people move within the Helsinki region. As for the city of Helsinki, improving the city s attractiveness seems to be closely linked to how well the city manages to execute its future housing policies and how well alternative living preferences can be taken into account in planning.