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    Evaluating targets for diagnostic methods in multiple sclerosis, progressive multifocal leukoencephalopathy and diseases of cerebral small blood vessels

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    The inadequacy of validated fluid biomarkers in neurological diseases associated with a risk of progressive neurodegeneration underscores the crucial need for precise methods in early detection. Consequently, early diagnosis is required for efficient treatment and effective monitoring. This thesis focuses on various neurological conditions primarily impacting the brain's white matter in magnetic resonance imaging (MRI), unfolding through four studies. These studies provide essential insights into clinical characteristics, diagnosis, and disease management. The primary objective is to evaluate biomarkers for their potential to advance the diagnosis, assess disease activity or progression, measure treatment effects, and identify rare treatment side-effects in multiple sclerosis (MS). The research starts with an exploration into the pathogenesis of MS, shedding light on the role of oxidative stress (OS). Subsequently, the study investigates progressive multifocal leukoencephalopathy (PML), an exceptionally severe treatment side-effect associated with a few MS treatments, and examines the utility of JC polyomavirus (JCPyV) antibody assays in clinical practice. In the final research phase, the thesis delves into the differential diagnosis of MS, examining conditions that show similar cerebral white matter changes as observed in MRI scans of individuals with MS. The first study uncovers plasma antioxidant capacity in MS patients, revealing influences from sex, specific disease-modifying therapies (DMTs), and disability levels. While plasma total radical-trapping antioxidant parameter (TRAP) may not reliably indicate oxidative injury in MS disease, it remains a useful tool for studying physiological responses to OS. The recommendation for future research involves expanding cohorts and investigating cerebrospinal fluid (CSF) antioxidant capacity for a more profound understanding. The second study delves into PML, identifying high-risk groups and emphasizing early diagnosis, particularly in immunosuppressed patients. Among the common underlying diseases, hematologic malignancies, B cell lymphoma, and HIV infection stand out. Notably, several cytostatics, some immunomodulating and monoclonal antibody (mAb) treatments, including MS treatments, also present a heightened risk for PML. Supportive care has proven to be instrumental in enhancing survival rates, especially in cases of PML associated with MS treatment and HIV-associated PML. The third study explores the diagnostic utility of JCPyV DNA testing in various samples, highlighting the importance of CSF polymerase chain reaction (PCR) and, in some cases, brain biopsy in confirming PML or granule cell neuronopathy (GCN). However, JCPyV findings in urine, especially in kidney transplant recipients, lack specificity, making urine less suitable for diagnosis or monitoring. Plasma samples in asymptomatic transplant patients did not correlate with JCPyV-related disease symptoms. The fourth study scrutinizes the relationship between neurofilament light chain (NfL) protein levels and clinical factors in cerebral small vessel disease (CSVD) patients. NfL emerges as a sensitive biomarker of neuroaxonal damage, often associated with deterioration of motor performance and cognitive function. Collectively, these studies offer valuable insights into the clinical presentation, and management of neurological diseases causing white matter injury, contributing to enhanced patient care and outcomes. In conclusion, the pressing need for validated biomarkers in clinical neurology is underscored, aiming to improve diagnosis, progression monitoring, and overall patient care. The identification and validation of reliable biomarkers has the potential to greatly improve how we monitor neurological diseases, keep track of their progression, and provide better care and treatment for patients.Etenevän hermosolukadon riskiä lisäävien sairauksien varhaista taudinmääritystä ja seurantaa varten tarvittaisiin lisää luotettavaksi osoitettuja, laboratorionäytteistä mitattavia biomerkkiaineita. Tautien etenemisen estämiseksi pyritään mahdollisimman varhaiseen taudinmääritykseen ja varhain aloitettuun hoitoon. Neurologisten sairauksien alkuvaiheen oireet voivat olla epäspesifisiä ja monimuotoisia, minkä vuoksi taudinmäärityksissä tarvitaan kliinisten tutkimusten lisäksi usein laaja-alaisempaa eri tutkimusmenetelmistä koostuvia tutkimuspaketteja. Väitöskirjassa käsitellään aivojen valkean aineen vaurioina visualisoituvista neurologisista sairauksista multippeliskleroosia (MS), progressiivista multifokaalista leukoenkefalopatiaa (PML) ja aivojen pienten suonten tautia (CSVD) neljässä erillisessä tutkimuksessa, tarjoten uusia näkemyksiä näiden sairauksien kliinisen kuvan, diagnostisen prosessin ja hoidon osalta. Ensimmäisessä osatyössä tarkastellaan MS-tautia sairastavien potilaiden plasman antioksidanttipitoisuutta total radical-trapping antioxidant parameter eli TRAP menetelmällä. Tutkimuksemme tulokset osoittivat, että plasman antioksidanttikapasiteetti on yhteydessä potilaiden sukupuoleen, tautia muokkaaviin hoitoihin (DMT) ja potilaiden toimintakyvyn laskuun. Plasman antioksidanttikapasiteetin määritys yksinään ei ole riittävä arvioimaan elimistön oksidatiivista stressiä eli hapetusstressiä, mutta se voisi olla hyödyllinen työkalu muiden biomarkkerien kanssa arvioimaan MS taudin tai lääkehoitojen aiheuttamia muutoksia antioksidatiivisessa puolustusjärjestelmässä. Tulevaisuudessa olisi tärkeä tutkia suurempia potilasryhmiä ja selvittää aivo-selkäydinnesteen antioksidanttikykyä lisätäksemme ymmärrystämme oksidatiivisen stressin osuudesta MS taudin syntymekanismeissa. Toinen tutkimus käsitteli progressiivista multifokaalista leukoenkefalopatiaa (PML) eli etenevää monipesäkkeistä aivojen valkean aineen tautia. Tutkimme taudin kliinistä kuvaa, diagnostisia prosesseja ja potilaiden selviytymistuloksia. Selvitimme millä potilasryhmillä on suurin riski sairastua PML-tautiin. Tutkimuksessa korostui varhaisen diagnoosin tärkeys erityisesti immuunipuutteisilla potilailla. Taustasairauksista yleisimmät olivat erilaiset hematologiset maligniteetit, B-solu lymfooma ja HIV-infektio. Lisäksi monet sytostaatit, tietyt immunomoduloivat lääkkeet ja monoklonaaliset vasta-aineet, mukaan lukien MS-taudin hoidossa käytetyt lääkkeet, voivat harvinaisena sivuvaikutuksena lisätä riskiä sairastua PML:ään. Suurin osa PML-tautiin sairastuneista potilaista oli saanut edeltävästi immuniteettiin vaikuttavaa lääkitystä. Vaikka PML on vakava sairaus, nykyhoidon ansiosta selviytymisennuste on parantunut erityisesti MS taudin hoitoon liittyvissä ja HIV-PML tapauksissa. Kolmannessa osatyössä selvitettiin JC-polyomaviruksen (JCPyV) DNA-määrityksen diagnostista hyödyllisyyttä eri näytetyypeissä ja potilasryhmissä. Tulokset osoittavat, että aivoselkäydinnesteestä tehtävä PCR-tutkimus ja joissain tapauksissa aivobiopsia ovat olennaisia PML:n ja jyvässolujen neuronopatian (GCN) diagnosoinnissa. JCPyV:n erittyminen virtsaan on yleistä, erityisesti munuaisensiirron saaneilla potilailla, ja positiiviset löydökset virtsasta ovat usein epäspesifisiä. Näin ollen JCPyV:n määrittäminen virtsanäytteestä ei ole hyödyllistä viruksen aiheuttamien sairauksien monitoroinnissa tai diagnosoinnissa. JCPyV:n nukleiinihappolöydökset plasmanäytteistä elinsiirron saaneilla potilailla eivät myöskään olleet yhteydessä JCPyV:n liittyviin sairauksiin. Neljännessä osatyössä tutkittiin neurofilamentin kevytketjun (NfL) pitoisuuksia aivojen pienten verisuonten tautia (CSVD) sairastavilla potilailla. NfL on hermostovaurion merkkiaine, joka kuvastaa hermosolun viejähaarakkeiden eli aksoneiden vauriota. Ikään ja painoon suhteutettu NfL:n pitoisuuden nousu liittyy eri aivoalueiden eri syistä johtuvaan aivosurkastumaan. Lisäksi korkeat NfL:n pitoisuudet korreloivat motorisen suorituskyvyn ja kognitiivisen toimintakyvyn heikkenemiseen. Tutkimusten tulokset tuovat uusia näkökulmia tutkittujen neurologisten sairauksien kliinisistä ilmenemismuodoista ja hoidosta. Tulokset korostavat tarvetta uusille validoiduille biomarkkereille kliinisessä neurologiassa. Tehokkaat ja validoidut biomarkkerit auttavat tarkentamaan diagnooseja sekä selvittämään myös sairauksien syntysyitä. Sairauksien syntymekanismien tarkempi ymmärtäminen puolestaan avaa mahdollisuuksia uusien hoitomenetelmien kehittämiseen.ei saavutettav

    Laulu isänmaallisena retoriikkana ja taiteena : Tutkimus isänmaallisista ja kansallisuusaatteellisista lauluista Ranskan vallankumouksessa (1789–1800), Espanjan itsenäisyyssodassa (1808–1814) ja Suomen suuriruhtinaskunnassa (1846–1876)

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    This musical semiotic research analyses and comments on the ways in which patriotic and nationalistic messages have been encoded in the studied song material. The song material is approached as both artistic and rhetorical texts. The historical song material of this study is from the French Revolution (1789–1800), the Spanish War of Independence (1808–1814), and the period of the autonomous Grand Duchy of Finland (c. 1846–1876). Encoding is in this study defined as the representation of private ideas in a communicable and public form. This study’s definition of patriotic and nationalistic song is based on Josiah Royce’s philosophy of loyalty. The patriotic song is defined as a message encoded in verbal form with the intention of upholding or arousing love towards one’s Patria or fatherland. The nationalistic song has the same aim, but the object of love is the nation instead of the fatherland. Naturally, these two categories often overlap in the actual texts. In order to categorise the song material the study applies the Greimassian semiotic square, which has been used to create a model of four species of crisis song, or crisis attitudes: incitation, lament, celebrative, and comical. Each song has been categorised into one of these species according to their primary crisis attitude. The central analytical perspective of this study is the existential semiotica z/emic-model, first formulated by Eero Tarasti. It is the basis for the study’s analytical method, which has four stages. The analytical method is applied to the analysis of both the verbal and musical dimensions of the song material. The musical tone gives the song an emotional quality, while the words specify the object signified, the cause of the emotion, and whether it is intended to incite to action, lament about suffering, arouse a celebrative mood, or represent an opponent in a comical light. With respect to their musical encoding, the patriotic and nationalistic songs are not a distinct species. They do not necessarily use a national style in music, even if they do make use of national musical styles and previously existing popular tunes. Rather, it is characteristic of these songs to use habitual musical styles and symbolism in order to communicate and spread the verbally expressed message. Unsurprisingly, the military march is a popular way to encode patriotic and nationalistic verbal messages, but musical tones belonging to the funeral march, sturm und drang, pastoral, and religious music are also used. In the French and Spanish material the most prominent form of musical encoding are marches which are associated with the military. They are often found in the Finnish material as well. However, despite the fact that the central poetic base text for the Finnish song material is from the poet Johan Ludvig Runeberg’s The Tales of Ensign Stål (I part 1848, II part 1860), which has the Finnish War (1808–1809) as its subject, the military tones are not as central as in the French and Spanish material. The Finnish patriotic song material rather represents a typical classical romantic style containing ballades and romances as well as marches. The French Revolution’s Invocation (1791) is a work in sonata form for orchestra, choir, and soloists that most closely resembles the orchestral church music of the time. Likewise, August Engelbert’s composition of Runeberg’s “Vårt land” (1846) ends in a pious and ecclesiastical tone. The sonata form is also found in the funeral march of the Hymne funèbre sur la mort du Général Hoche (1797). Its allegro finale is in a zealous sturm und drang style. The French songs celebrating agriculture make use of pastoral music. In the case of Spain, beside the marches one can find, for instance, the Cantos del trovador, a troubadourish lament about Fernando VII’s captivity, with music by Mariano de Ledesma.Tämän musiikin semioottisen tutkimuksen aiheena on poliittinen musiikki isänmaallisten ja kansallisuusaatteellisten laulujen muodossa Ranskan vallankumouksessa (1789–1800), Espanjan itsenäisyyssodassa (1808–1814) ja Suomen suuriruhtinaskunnassa (1846–1876). Josiah Roycen lojaliteetti-filosofiaa hyödyntäen isänmaallisuus määritellään rakkaudeksi isänmaata kohtaan ja kansallisuusaate rakkaudeksi kansaa kohtaan. Tutkimus jaottelee isänmaalliset ja kansallisuusaatteelliset laulut lähtökohtaisesti neljään eri lajiin laulun kriisi-asenteen mukaan: 1) yllyttävään, 2) valittavaan, 3) juhlistavaan ja 4) koomiseen. Näitä kaikkia lajeja käytetään kommunikoimaan musiikillisesti kansalliseen ja isänmaalliseen kriisitilanteeseen liittyviä viestejä. Yllyttävät laulut yllättävät toimintaan koettua uhkaa vastaan. Valittavat laulut valittavat kärsittyä menetystä. Juhlistavat laulut juhlistavat saavutettua voittoa tai tilannetta. Koomiset laulut pääsääntöisesti tekevät pilkkaa vastustajasta. Musiikillisessa mielessä isänmaalliset ja kansallisuusaatteelliset laulut eivät muodosta omaa lajiaan. Ne erottuvat isänmaallisiksi tai kansallisuusaatteellisiksi sanojensa perusteella. Ne eivät myöskään edellytä kansallisten musiikkityylien käyttöä. Musiikillisen symboliikan suhteen sävellykset noudattavat aikansa musiikillisia yleisiä käytäntöjä. Marssi on suosittu tapa tutkimuksen viestien musiikillisen välittämiseen. Sen lisäksi kuitenkin käytössä ovat esimerkiksi sturm und drangin, pastoraalin ja uskonnollisen musiikin sävyt. Kaikissa aineistoissa poliittisten laulujen säveltäjät ovat oman kontekstinsa keskeisiä säveltäjiä. Tutkimuksessa analysoidaan ja kommentoidaan esimerkiksi Luigi Cherubinin ”Suruhymniä kenraali Hochelle” (1797), August Engelbergin säveltämää ”Maamme-laulua” (1846) ja lukuisia espanjalaisia marsseja, jotka on sepitetty yllyttämään Napoleonin joukkojen vastaiseen taisteluun.ei saavutettav

    CUL3-related neurodevelopmental disorder : Clinical phenotype of 20 new individuals and identification of a potential phenotype-associated episignature

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    Neurodevelopmental disorder with or without autism or seizures (NEDAUS) is a neurodevelopmental disorder characterized by global developmental delay, speech delay, seizures, autistic features, and/or behavior abnormalities. It is caused by CUL3 (Cullin-3 ubiquitin ligase) haploinsufficiency. We collected clinical and molecular data from 26 individuals carrying pathogenic variants and variants of uncertain significance (VUS) in the CUL3 gene, including 20 previously unreported cases. By comparing their DNA methylation (DNAm) classifiers with those of healthy controls and other neurodevelopmental disorders characterized by established episignatures, we aimed to create a diagnostic biomarker (episignature) and gain more knowledge of the molecular pathophysiology. We discovered a sensitive and specific DNAm episignature for patients with pathogenic variants in CUL3 and utilized it to reclassify patients carrying a VUS in the CUL3 gene. Comparative epigenomic analysis revealed similarities between NEDAUS and several other rare genetic neurodevelopmental disorders with previously identified episignatures, highlighting the broader implication of our findings. In addition, we performed genotype-phenotype correlation studies to explain the variety in clinical presentation between the cases. We discovered a highly accurate DNAm episignature serving as a robust diagnostic biomarker for NEDAUS. Furthermore, we broadened the phenotypic spectrum by identifying 20 new individuals and confirming five previously reported cases of NEDAUS.Peer reviewe

    Assessing climate impacts of agroforestry system in LCA : case study in Zambia

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    Purpose: Agroforestry systems have the potential to reduce the carbon footprint (CF) of food production. One of the advantages of these systems is carbon removal from the atmosphere to biogenic carbon of trees. Nevertheless, there is not a common agreement on the method to include the climatic benefits of agroforestry systems in life cycle assessment (LCA). This study aims to evaluate methods for including biogenic carbon in the LCA of agroforestry systems. Methods: We studied three different maize production systems in Zambia: Low-input, High-input, and Agroforestry scenario. In the Agroforestry scenario, we studied a maize–Faidherbia albida system by investigating three methodological approaches with a functional unit (FU) of 1 ha. In Methodological Approach 1, biogenic carbon in the above- and below-ground biomass of trees in the agroforestry system was considered as a temporary carbon dioxide (CO2) storage via correction flow. In Methodological Approach 2, the biomass of trees was used as an energy source. In Methodological Approach 3, the mass balance principle was employed. The system expansion method was utilized to make each production system comparable. Three sensitivity analyses with a FU of 1000 kg of dry matter maize grain were also conducted following the methodological approaches. Results and discussion: The Agroforestry scenario had the lowest CF in all methodological approaches and in all sensitivity analyses when the maize grain yield level was the same as reported in the literature. Yet, uncertainty levels were high, as an IPCC tier 1 method was used. It was found that the biogenic carbon of the trees in agroforestry systems can be included in LCA by the currently available methods. The mass balance principle was a practical method for including the biogenic carbon of the trees in LCA. System expansion was another feasible method, wherein processes are added to the compared systems until they include the provision of the same functions. Conclusions: Biogenic carbon in the biomass of trees in agroforestry systems can greatly contribute to decreasing the CF if it is considered in LCA. If the FU and allocation methods are selected accordingly, the biogenic carbon can be effectively included in LCA. Based on the results of this case study, the maize–F. albida agroforestry system has the potential for decreasing the CF of maize production in Zambia.Peer reviewe

    Estimation of carrier frequencies of autosomal and X-linked recessive genetic conditions based on gnomAD v4.0 data in different ancestries

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    Purpose: Monogenic rare diseases contribute significantly to infant deaths and pediatric hospitalizations and cause burden to the patients and their families. The American College of Medical Genetics and Genomics recommended in 2021 that carrier screening of autosomal recessive and X-linked conditions with a carrier frequency of >= 1/200 and a severe or moderate phenotype should be offered when planning or during pregnancy. In November 2023 gnomAD v4.0 was released. It contains in total 807,162 individuals, being nearly 5x larger than previous versions, which have been used to estimate gene carrier frequencies (GCF). Methods: We utilized gnomAD v4.0 (GRCh38) to calculate the GCFs for available genetic ancestry groups for variants having pathogenic or likely pathogenic classification (>80% of submissions) in ClinVar. We calculated GCF separately for exomes and genomes, combined data, and at-risk couple frequencies (ACF) per genetic ancestry group. Results: In total, 324 genes had a GCF >= 1/200 in at least 1 ancestry subgroup. The number of genes with GCF >= 1/200 varied greatly between subgroups. ACFs were more similar, Ashkenazi Jewish having the highest ACF of 6.11%. Conclusion: Improved understanding of carrier risks and updated carrier screening content would allow patients to make more informed reproductive decisions. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

    Impaired Gait, Postural Instability, and Rigidity in Relation to CB1 Receptor Availability in Parkinson's Disease

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    Background: In Parkinson's disease (PD), postural instability and gait disorder (PIGD) symptoms are associated with a worse prognosis for an unknown reason. Objective: The objective was to explore the relationship between cannabinoid receptor type 1 (CB1R) availability and motor symptoms in PD with [18F]FMPEP-d2 positron emission tomography (PET). Methods: Fifteen individuals with PD underwent [18F]FMPEP-d2 PET to measure cerebral CB1R availability. The Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) was used to evaluate the motor symptoms. Results: A negative correlation was observed between [18F]FMPEP-d2 VT and PIGD score (P = 0.002) as well as rigidity subscore (P < 0.001). Both clusters covered widespread areas of both hemispheres. In contrast, tremor or bradykinesia did not correlate to [18F]FMPEP-d2 VT. Conclusions: Gait, postural instability, and rigidity in PD are associated with decreased CB1R availability, unlike tremor or bradykinesia, suggesting that the endocannabinoid system has a role in the pathophysiology of different motor symptoms in PD. (c) 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Peer reviewe

    CVOT summit report 2024: new cardiovascular, kidney, and metabolic outcomes

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    Abstract The 10th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on December 5–6, 2024. This year, discussions about cardiovascular (CV) and kidney outcome trials centered on the recent findings from studies involving empagliflozin (EMPACT-MI), semaglutide (STEP-HFpEF-DM and FLOW), tirzepatide (SURMOUNT-OSA and SUMMIT), and finerenone (FINEARTS-HF). These studies represent significant advances in reducing the risk of major adverse cardiovascular events (MACE) and improving metabolic outcomes in heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD), and obstructive sleep apnea (OSA). The congress also comprised sessions on novel and established therapies for managing HFpEF, CKD, and obesity; guidelines for managing CKD and metabolic dysfunction-associated steatotic liver disease (MASLD); organ crosstalk and the development of cardio-kidney-metabolic (CKM) syndrome; precision medicine and person-centered management of diabetes, obesity, cardiovascular disease (CVD) and CKD; early detection of type 1 diabetes (T1D) and strategies to delay its onset; continuous glucose monitoring (CGM) and automated insulin delivery (AID); cardiovascular autonomic neuropathy (CAN) and the diabetic heart; and the role of primary care in the early detection, prevention and management of CKM diseases. The contribution of environmental plastic pollution to CVD risk, the increasing understanding of the efficacy and safety of incretin therapies in the treatment of CKM diseases, and the latest updates on nutrition strategies for CKM management under incretin-based therapies were also topics of interest for a vast audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians, who actively engaged in online discussions. The 11th CVOT Summit will be held virtually on November 20–21, 2025 ( http://www.cvot.org )

    Europe Beyond the Courts : Constitutionalism, Pluralism and Integration in the Nordic Countries

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    The study examines the question of the contested boundaries between EU law and national constitutional law in the Nordic EU member states, Denmark, Sweden, and Finland, in the context of their distinctive and evolving forms of constitutional review and as part of the recent major shifts in Nordic constitutionalism. The rise of powerful judicial institutions in Europe was accelerated by two institutional responses to the events of the Second World War. Constitutional courts were established in various countries, shifting the dominance from parliamentary supremacy to judicial review based on a centralised model. Simultaneously, the enforcement of international norms within states gained prominence, with the project of European economic integration leading the way. The powerful European Court of Justice, with its transformative jurisprudence, played a crucial role in establishing the supremacy of European law. The third step in this development was the meeting of these two institutional models. The fact that the boundaries between the two legal orders remain contested was made clear by the first ‘Solange’ judgment of the German Constitutional Court in 1974, which initiated a critical questioning of the constitutional claim of the European Court of Justice and laid down conditions for its application on the basis of national constitutional frameworks. Rulings such as these created a grey area within this new architecture, which was now shaping the limits and conditions of legal integration, especially in its most difficult area: its relationship with national constitutions. The response of both legal and political science to this problem has been the development of a number of approaches and theories, including ‘judicial dialogues’ and inter-court competition, which aim to explain the evolving relationships between European and national legal orders in this setting. These approaches develop their proposals based on the same institutional structures and generally emphasise the shaping of the European legal space through interactions between courts. They also seek to draw generalisable conclusions about the changes in national constitutionalism and the role of the courts that result from these patterns of interaction, such as the weakening of national constitutionalism and constitutional courts and the strengthening of the role of the lower courts due to their special role in the enforcement of EU law and their relationship with the European Court of Justice. One of the turning points in this development was the Maastricht phase in the mid-1990s, when several European top courts renewed their challenge to the European Court of Justice. This also led to the turn to ‘constitutional pluralism’, which focuses on the problem of constitutional conflict and dialogue between courts without a fixed hierarchy, originally initiated by Neil MacCormick and later developed by several scholars. The study explores the evolution and implications of this constitutional dilemma in the Nordic internally pluralist and majoritarian institutional frameworks of constitutional review. It calls into question the generalisability of the court-based assumptions of the European debates and aims to create space for Nordic law in the current discussion. While the Nordic countries had long kept their courts on the fringes of constitutionalism and to some extent had reservations about European integration, all three countries eventually joined the EU at an important moment. While Finland and Sweden joined the EU in the midst of the constitutional turmoil of the Maastricht turn in 1995, Denmark’s story began before its accession in 1973 and has long run parallel to the more familiar European developments, without its specific characteristics being taken into account. In fact, the first Danish constitutional evaluation of the European Court of Justice’s foundational jurisprudence preceded the German ‘Solange I’ decision, and the Nordic reactions to the Court’s Maastricht decision also constitute the first, often forgotten and largely misunderstood act of migration of the German Court’s jurisprudence. However, the encounter between national constitutionalism and EU law also took place in a different way and at a different time than in continental Europe, and the Maastricht turn marked not only a turn to pluralism and a new intensification of debates on European constitutional tensions, but also a period of ‘Europeanisation’ and ‘constitutionalisation’, including the late breakthrough of rights-based constitutionalism. Although the shared traits in Nordic constitutional law are often a matter of how close or distant one looks at events, behind the very different national solutions there also emerges a common Nordic story of the upheavals of the 1990s and the question of constitutional boundaries as part of it. Over the past 30 years, the three Nordic countries have moved from very similar starting points to similar destinations, and the main factors underlying constitutional change have also been the same. Ultimately, the shared legal cultural heritage of majoritarian constitutionalism, together with different models of constitutional review, has meant that developments concerning the limits of the constitution have also emerged as variations on the same themes: the prominence of the legislature, the strengthening of the role of the courts, and the renewal of the traditional legal culture, which has undergone a process of transformation during the period of membership of the EU and the ECHR. By holding up a mirror to many of the assumptions of contemporary discourse, the study shows that the practices we think we know in fact take on different forms when viewed through institutional frameworks that differ from the constitutional court model, exposing current approaches as constrained by their original institutional inspirations and country-specific national contexts. With a special focus on the turning point of the Maastricht era, the study covers for the first time the development of all three Nordic countries throughout the period of their EU membership, thus also seeking to refine the understanding of the process of Europeanisation of Nordic law. It provides a contextual account of key events and traces the issues, actors, evolution of the constitutional question and development of constitutional review through the constitutional turn in Nordic law.Väitöskirja käsittelee EU:n ja sen jäsenvaltioiden välisessä suhteessa ilmenevää konstitutionaalisen konfliktin ongelmaa Pohjoismaiden valtiosääntöoikeudessa ja niiden perustuslakikontrollin institutionaalisessa ympäristössä. Kysymys konstitutionaalisen konfliktin mahdollisuudesta on klassiseksi muodostunut kysymys, jossa on kyse toisaalta siitä, että kukin jäsenvaltio kansallisen valtiosääntönsä nojalla valtuuttaa perustavat toimivallansiirrot kansallisilta lainsäädäntöelimiltä Euroopan Unionille, jolloin sen omat ylimmät perustuslainvalvontaa harjoittavat elimet viime kädessä valvovat näiden toimivallansiirtojen ja Unionin lainsäädännön perustuslainmukaisuutta. Toisaalta myös EU:n tuomioistuimella on sen omaan oikeuskäytäntöön perustuen toimivalta päättää Unionin toimivallan rajoista ja asettaa myös muita rajoitteita jäsenvaltioille, niiden perustuslaista kumpuavat velvoitteet mukaan lukien. 1990-luvulta lähtien oikeudellista keskustelua pitkälti hallinneen, alun perin Neil MacCormickin kehittämän valtiosääntöisen pluralismin teorian mukaan tilanne voidaan ymmärtää siten, että kyseessä on kaksi valtiosääntöä, joilla kummallakin on oikeutettu perustansa, mutta jotka kuitenkin katsovat viime kädessä samaa tilannetta kahdesta erilaisesta, mutta omasta näkökulmastaan viimesijaisesta ja ylimmästä näkökulmasta, mikä johtaa myös konfliktin mahdollisuuteen. Kuten tutkimus osoittaa, laajentuessaan nykyistä eurooppalaista oikeutta kuvaavaksi yleiseksi teoriaksi siitä miten harmoniaa ja legitimiteettiä kansallisen tason ja Unionitason välillä voidaan ylläpitää, se säilyttää aina institutionaalisen perusoletuksensa, jossa ylintä tulkintavaltaa käyttävät EU:n tuomioistuin ja vahvat kansalliset perustuslakituomioistuimet, tyypillisesti Saksan valtiosääntötuomioistuin. Samalla teoria myös perustuu monille sellaisille kansallista valtiosääntöoikeutta koskeville oletuksille, jotka poikkeavat merkittävästi Pohjoismaisesta ympäristöstä. Tällä on lukuisia erilaisia vaikutuksia siihen, miten teoriaa voidaan soveltaa ja miten nykyistä oikeudellista maailmaa voidaan sen avulla hahmottaa. Tutkimus kattaa EU:n kolmen pohjoismaisen jäsenvaltion, Tanskan, Ruotsin ja Suomen, kehityksen niiden koko jäsenyyden ajalta ja asettaa tapahtumat alkuperäisten asiakirjojen valossa osaksi pohjoismaisten valtiosääntöjen merkityksen samanaikaista vahvistumista ja oikeuden laajempaa eurooppalaistumiskehitystä. Se tarjoaa uuden kattavan luennan erityisesti tuomioistuinten ja lainsäätäjän muuttuvista suhteista ja oikeustieteen roolista tässä kehityksessä, Pohjoismaiden oikeuden ja EU-oikeuden vuorovaikutuksesta sekä kritiikin ja konfliktin välttämisen keinoista.ei saavutettav

    Molecular characterization of exopolysaccharide from Periweissella beninensis LMG 25373T and technological properties in plant-based food production

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    Periweissella beninensis LMG 25373T, belonging to the recently established Periweissella genus, exhibits unique motility and high adhesion capabilities, indicating significant probiotic potential, including resilience under simulated gastrointestinal conditions. This study demonstrates for the first time that P. beninensis LMG 25373T produces a dextran-type exopolysaccharide (EPS) with a distinctive high degree of branching (approximately 71 % of alpha-(1-* 6)-linkages and 29 % alpha-(1-* 3)-linkages). Growth performance, acidification, and proteolytic activity were investigated in various plant-based substrates (lentil, chickpea, and rice flours water soluble extracts and semi-liquid mixtures), in comparison with the well-characterized lactic acid bacteria strains Leuconostoc pseudomesenteroides DSM 20193 (EPS-producing) and Lacticaseibacillus rhamnosus GG (probiotic). The strain displayed effective pro-technological properties, especially in gelatinized and non-gelatinized legume-based substrates, achieving EPS synthesis levels of up to 1.3 g/100 g and 2.7 +/- 0.2 g/100 g, respectively. When used as a starter for a plant-based yogurt-type ("gurt") prototype, compared to the control, P. beninensis LMG 25373T produced a substantial increase in viscosity which remained stable during refrigerated storage, confirming the role of its unique structure pattern as a hydrocolloid. Furthermore, the strain demonstrated high viability throughout storage, an essential trait for probiotic food applications.Peer reviewe

    Helsingfors universitets principer för öppen publicering 2025

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    Detta dokument ersätter Helsingfors universitets tidigare principer för öppen publicering som godkändes 2017.Helsingin yliopiston avoimen julkaisemisen periaatteet 2025 saatavilla osoitteesta http://hdl.handle.net/10138/591218. University of Helsinki, Principles of open publishing 2025 available at http://hdl.handle.net/10138/591240.ei saavutettav

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