APOE status modulates the changes in network connectivity induced by brain stimulation in non-demented elders.

Behavioral consequences of a brain insult represent an interaction between the injury and the capacity of the rest of the brain to adapt to it. We provide experimental support for the notion that genetic factors play a critical role in such adaptation. We induced a controlled brain disruption using repetitive transcranial magnetic stimulation (rTMS) and show that APOE status determines its impact on distributed brain networks as assessed by functional MRI (fMRI).Twenty non-demented elders exhibiting mild memory dysfunction underwent two fMRI studies during face-name encoding tasks (before and after rTMS). Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas. APOE ε4 bearers exhibited this pattern in two separate independent components, whereas ε4-non carriers presented a single partially overlapping network. Following rTMS all subjects showed slight ameliorations in memory performance, regardless of APOE status. However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation. Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS. Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Kiinteistön palautetiedon analysointi

Diplomityö käsittelee kiinteistön palautetiedon analysointia. Tässä diplomityössä palautetiedolla tarkoitetaan kiinteistön talotekniikkaan liittyviä teknisiä ja inhimillisiä tietoja, joiden perusteella rakennuksen ja sen tekniikan toimivuudesta voidaan tehdä päätelmiä. Tiedot kerätään järjestelmistä mittauspisteiden kautta etävalvomoon, josta niitä voidaan tarkastella ja edelleen analysoida. Valvomosta saatavan tiedon rinnalle pyritään suunnitteluvaiheessa kokoamaan valvottavasta kohteesta laskennallisia energiankulutusmalleja. Myös kiinteistön asukkaat, rakennuksen ominaisuudet ja ympäristö muodostavat osan palautetiedosta. Kiinteistön palautetieto voidaankin jakaa tekniseen ja inhimilliseen tietoon, ja edelleen analysoinnin kannalta staattiseen tai dynaamiseen tietoon. Tässä diplomityössä selvitettiin palautetiedon keruuta etävalvomolla yhdistämällä tähän rakentamisen laadunvalvonnan työkaluja ja sumeaa logiikkaa. Työn käytännön osio koostuu kiinteistön ja siihen yhdistetyn etävalvomon välillä kulkevan tiedon käsittelystä, mittauspisteiden määrittämisestä ja tietojen analysoinnista. Työssä esitellään kolme esimerkkikohdetta Helsingin seudulta. Työssä laadittiin arviointimalli, joka sisältää kaiken kiinteistön palautetietoon liittyvän aineiston ja sen analysointitavat, sekä erityisesti uutena asiana myös sumeaa logiikkaa. Tiedon analysointi etenee oletusarvojen muodostamisesta, simuloinnin laatimisesta ja sen vertaamisesta todellisiin tietoihin ja edelleen näistä tehtäviin päätelmiin. Tavanomaisten teknisten tietojen lisäksi sumean logiikan avulla tuotiin esille poikkeamia selittäviä tekijöitä mm. kiinteistön asukkaiden ominaisuuksista.

Population pharmacokinetic study to evaluate dosing strategies of imipenem in neonates and infants

Objective: Imipenem is a broad spectrum antibiotic used to treat severe infections in critically ill patients. Imipenem pharmacokinetics (PK) was evaluated in a cohort of neonates treated in the Neonatal Intensive Care Unit of the Lausanne University Hospital. The objective of our study was to identify key demographic and clinical factors influencing imipenem exposure in this population. Method: PK data from neonates and infants with at least one imipenem concentration measured between 2002 and 2013 were analyzed applying population PK modeling methods. Measurement of plasma concentrations were performed upon the decision of the physician within the frame of a therapeutic drug monitoring (TDM) programme. Effects of demographic (sex, body weight, gestational age, postnatal age) and clinical factors (serum creatinine as a measure of kidney function; co-administration of furosemide, spironolactone, hydrochlorothiazide, vancomycin, metronidazole and erythromycin) on imipenem PK were explored. Model-based simulations were performed (with a median creatinine value of 46 μmol/l) to compare various dosing regimens with respect to their ability to maintain drug levels above predefined minimum inhibitory concentrations (MIC) for at least 40 % of the dosing interval. Results: A total of 144 plasma samples was collected in 68 neonates and infants, predominantly preterm newborns, with median gestational age of 27 weeks (24 - 41 weeks) and postnatal age of 21 days (2 - 153 days). A two-compartment model best characterized imipenem disposition. Actual body weight exhibited the greatest impact on PK parameters, followed by age (gestational age and postnatal age) and serum creatinine on clearance. They explain 19%, 9%, 14% and 9% of the interindividual variability in clearance respectively. Model-based simulations suggested that 15 mg/kg every 12 hours maintain drug concentrations over a MIC of 2 mg/l for at least 40% of the dosing interval during the first days of life, whereas neonates older than 14 days of life required a dose of 20 mg/kg every 12 hours. Conclusion: Dosing strategies based on body weight and post-natal age are recommended for imipenem in all critically ill neonates and infants. Most current guidelines seem adequate for newborns and TDM should be restricted to some particular clinical situations.

Järjestelmäintegroinnin vaatimukset dokumenttien hallinnan sovelluspalvelussa ja palvelualustan suunnittelu

Työssä on selvitetty soveltuvatko maailman johtavien ECM (Enterprise Content Management)-toimittajien järjestelmät palvelualustaksi dokumenttien hallinnan sovelluspalvelulle. Sovelluspalvelulla tarkoitetaan palvelutoimittajan (Application Service Provider, ASP) tiloissa toimivia sovelluksia, joita tarjotaan palveluna asiakkaille tietoverkon yli. Selvitystä varten työssä on kerätty tärkeimmät palvelualustaan kohdistuvat vaatimukset. Integrointivaatimusten tunnistaminen oli työn tärkein tavoite. Integroitavuuden lisäksi työssä on tutkittu sovelluspalvelumallista syntyviä erityisvaatimuksia. Vaatimusten keruu ja vaatimusten pohjalta tehty ominaisuuskartoitus ovat osa palvelualustan suunnittelua. Ominaisuuskartoituksessa vaatimuksista on laadittu laaja kyselylomake ja pyydetty valituilta toimittajilta siihen vastaukset. Saatuja vastauksia on peilattu asetettuihin vaatimuksiin. Tehtyjen havaintojen pohjalta on esitetty soveltuvuusarvio tutkittujen järjestelmien soveltuvuudesta tarpeita vastaavaksi sovelluspalvelualustaksi. Lopputuloksena on todettu, että useimpien järjestelmien soveltuvuus perustasolla on hyvä. Yksittäisiä selkeitä puutteita kuitenkin tunnistettiin. Integrointivaatimukset täyttyvät pääosin hyvin, mutta erityisesti tietoturvassa havaittiin puutteita.

Transcriptome diversity among rice root types during asymbiosis and interaction with arbuscular mycorrhizal fungi.

Root systems consist of different root types (RTs) with distinct developmental and functional characteristics. RTs may be individually reprogrammed in response to their microenvironment to maximize adaptive plasticity. Molecular understanding of such specific remodeling-although crucial for crop improvement-is limited. Here, RT-specific transcriptomes of adult rice crown, large and fine lateral roots were assessed, revealing molecular evidence for functional diversity among individual RTs. Of the three rice RTs, crown roots displayed a significant enrichment of transcripts associated with phytohormones and secondary cell wall (SCW) metabolism, whereas lateral RTs showed a greater accumulation of transcripts related to mineral transport. In nature, arbuscular mycorrhizal (AM) symbiosis represents the default state of most root systems and is known to modify root system architecture. Rice RTs become heterogeneously colonized by AM fungi, with large laterals preferentially entering into the association. However, RT-specific transcriptional responses to AM symbiosis were quantitatively most pronounced for crown roots despite their modest physical engagement in the interaction. Furthermore, colonized crown roots adopted an expression profile more related to mycorrhizal large lateral than to noncolonized crown roots, suggesting a fundamental reprogramming of crown root character. Among these changes, a significant reduction in SCW transcripts was observed that was correlated with an alteration of SCW composition as determined by mass spectrometry. The combined change in SCW, hormone- and transport-related transcript profiles across the RTs indicates a previously overlooked switch of functional relationships among RTs during AM symbiosis, with a potential impact on root system architecture and functioning.

Impact of model complexity on cross-temporal transferability in Maxent species distribution models: An assessment using paleobotanical data

Maximum entropy modeling (Maxent) is a widely used algorithm for predicting species distributions across space and time. Properly assessing the uncertainty in such predictions is non-trivial and requires validation with independent datasets. Notably, model complexity (number of model parameters) remains a major concern in relation to overfitting and, hence, transferability of Maxent models. An emerging approach is to validate the cross-temporal transferability of model predictions using paleoecological data. In this study, we assess the effect of model complexity on the performance of Maxent projections across time using two European plant species (Alnus giutinosa (L.) Gaertn. and Corylus avellana L) with an extensive late Quaternary fossil record in Spain as a study case. We fit 110 models with different levels of complexity under present time and tested model performance using AUC (area under the receiver operating characteristic curve) and AlCc (corrected Akaike Information Criterion) through the standard procedure of randomly partitioning current occurrence data. We then compared these results to an independent validation by projecting the models to mid-Holocene (6000 years before present) climatic conditions in Spain to assess their ability to predict fossil pollen presence-absence and abundance. We find that calibrating Maxent models with default settings result in the generation of overly complex models. While model performance increased with model complexity when predicting current distributions, it was higher with intermediate complexity when predicting mid-Holocene distributions. Hence, models of intermediate complexity resulted in the best trade-off to predict species distributions across time. Reliable temporal model transferability is especially relevant for forecasting species distributions under future climate change. Consequently, species-specific model tuning should be used to find the best modeling settings to control for complexity, notably with paleoecological data to independently validate model projections. For cross-temporal projections of species distributions for which paleoecological data is not available, models of intermediate complexity should be selected.

Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state

Background: The rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness. Methods fMRI was used to investigate cortical responses to passive language stimulation as well as task-induced deactivations related to the default-mode network. DTI was used to assess the integrity of the global white matter and the arcuate fasciculus. We also performed a neuropsychological assessment at the time of the second MRI examination in order to characterize the profile of cognitive deficits. Results: fMRI analysis revealed anatomically appropriate activation to speech in both the first and the second scans but a reduced pattern of task-induced deactivations in the first scan. In the second scan, following the recovery of consciousness, this pattern became more similar to that classically described for the default-mode network. DTI analysis revealed relative preservation of the arcuate fasciculus and of the global normal-appearing white matter at both time points. The neuropsychological assessment revealed recovery of receptive linguistic functioning by 12-months post-ictus. Conclusions: These results suggest that the combination of different structural and functional imaging modalities may provide a powerful means for assessing the mechanisms involved in the recovery from the VS.

Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state

Background: The rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness. Methods fMRI was used to investigate cortical responses to passive language stimulation as well as task-induced deactivations related to the default-mode network. DTI was used to assess the integrity of the global white matter and the arcuate fasciculus. We also performed a neuropsychological assessment at the time of the second MRI examination in order to characterize the profile of cognitive deficits. Results: fMRI analysis revealed anatomically appropriate activation to speech in both the first and the second scans but a reduced pattern of task-induced deactivations in the first scan. In the second scan, following the recovery of consciousness, this pattern became more similar to that classically described for the default-mode network. DTI analysis revealed relative preservation of the arcuate fasciculus and of the global normal-appearing white matter at both time points. The neuropsychological assessment revealed recovery of receptive linguistic functioning by 12-months post-ictus. Conclusions: These results suggest that the combination of different structural and functional imaging modalities may provide a powerful means for assessing the mechanisms involved in the recovery from the VS.

Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state

Background: The rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness. Methods fMRI was used to investigate cortical responses to passive language stimulation as well as task-induced deactivations related to the default-mode network. DTI was used to assess the integrity of the global white matter and the arcuate fasciculus. We also performed a neuropsychological assessment at the time of the second MRI examination in order to characterize the profile of cognitive deficits. Results: fMRI analysis revealed anatomically appropriate activation to speech in both the first and the second scans but a reduced pattern of task-induced deactivations in the first scan. In the second scan, following the recovery of consciousness, this pattern became more similar to that classically described for the default-mode network. DTI analysis revealed relative preservation of the arcuate fasciculus and of the global normal-appearing white matter at both time points. The neuropsychological assessment revealed recovery of receptive linguistic functioning by 12-months post-ictus. Conclusions: These results suggest that the combination of different structural and functional imaging modalities may provide a powerful means for assessing the mechanisms involved in the recovery from the VS.

Zins-Spreads als Einnahmequelle für Kantone : Die Abhängigkeit des Passivzinssatzes von den Bruttoschulden und damit einhergehende Renditemöglichkeiten am Kapitalmarkt

Über eine längere Zeitdauer betrachtet, weisen staatliche Schulden tendenziell tiefere Zinssätze respektive Renditen auf als andere auf dem Markt gehandelte papiere, was teilweise durch das geringere Risiko erklärt werden kann (Mehra & Prescott, 2003: S.892). Indem die Abhängigkeit der Schuldzinssätze von den Schuldenquoten der Schweizer Kantone modelliert und in Beziehung zu einer adäquaten Marktrendite gebracht wird, zeigt diese Arbeit, welches Einnahmepotential sich aus diesem Zins-Spread für die Schweizer Kantone ergibt. Zur Schätzung der Zinskurve wird vom Marktgleichgewicht ausgegangen, bei welchem die investoren mit einem Default Premium für einen möglichen Ausfall des Kantons als Schuldner, im Vergleich zu einer risikolosen Anlage, abgegolten werden müssen (Bayoumi, Goldstein und Woglom, 1995: S. 1048-1051). Dazu werden die für den Schweizer Kontext spezifischen Determinanten für die Ausfallswahrscheinlichkeit identifiziert (Daldoss und Foraita, 2003: S. 87). Empirisch überprüft wird dieses Modell anhand eines quantitativen Ansatzes, wobei in erster Linie die Generalisierte Momenten-Methode (GMM) angewandt wird. Als Datenbasis dient hauptsächlich die Finanzstatistik der Eidgenössischen Finanzverwaltung (EFV), wobei alle 26 Schweizer Kantone im Zeitraum von 1981 bis 2011 betrachtet werden. Als Marktrendite wird die durchschnittliche Rendite der Schweizer Pensionskassen verwendet. Mit den verwendeten Daten und Modellen kann die Form der Zinskurve jedoch nicht eindeutig bestimmt werden, was grösstenteils auf die Endogenitätsproblematik zurückzuführen ist. Diese kann aufgrund ungenügender und mangelhafter Instrumente ohne zusätzliche Daten nicht überwunden werden. Folglich kann auch keine optimale Schuldenquote bestimmt werden. Die quantitativen Resultate deuten dennoch auf ein gewisses Einnahmepotential hin. Wie das Fallbeispiel Kanton Aargau zeigt, kann dieses punktuell auch gebraucht werden und findet in der Praxis Anwendung (Anonymer Interviewpartner, 2013).

Jatkuvan säästämisen kohdentuminen ja sijoitustuotteiden kustannusrakenteista. Case: Etelä-Karjalan Osuuspankki

Tutkimuksen tavoitteena on selvittää Etelä-Karjalan Osuuspankin asiakkaiden jatkuvan säästämisen kohdentumista tulevaisuudessa ja samalla analysoida sijoitustuotteiden kustannusrakenteita pankin näkökulmasta. Lisaksi tutkitaan sijoittajien käyttäytymiseen vaikuttavia tekijöitä, vertaillaan eri tuotteiden arvoketjuissa kustannuksia aiheuttavia tekijöitä ja tuottojen muodostumista toisiinsa pyrkien saamaan tuotteille edullisuusjärjestys sekä selvitetään asiakkaiden ja pankin mieltymyksien kohtaamista. Tutkielman teoriaosassa määritellään käsitteet ja perehdytään aikaisempiin tutkimuksiin sijoittajakäyttäytymisestä. Teoriaosan pohjalta muodostetaan oletushypoteeseja, joita käytetään empiirisen osan jatkuvan säästämisen kyselytutkimuksen analysoinnissa. Kustannusrakenteita käsittelevässä empiirisessä osassa teoriaosaa hyödynnetään haastattelututkimuksen pohjana. Tutkimuksessa käytetään lähinnä toiminta-analyyttista tutkimusotetta. Tutkimustulosten mukaan sijoittajakäyttäytyminen tulee muuttumaan ja jatkuva säästäminen tulee kohdistumaan tileistä enemmän muihin sijoitustuotteisiin, erityisesti sijoitusrahastoihin. Sijoitustuotteiden kustannusrakenteissa ATK- ja henkilöstökulut aiheuttavat kannattavuuseroja tuotteiden välille.