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  • Editorial 
    Näre, Lena Margareta; Bendixsen, Synnöve (Versita, 2017)
  • Hankonen, Nelli; Heino, Matti T. J.; Hynynen, Sini-Tuuli; Laine, Hanna; Araujo-Soares, Vera; Sniehotta, Falko F.; Vasankari, Tommi; Sund, Reijo; Haukkala, Ari (BioMed Central Ltd, 2017)
    BACKGROUND: No school-based physical activity (PA) interventions among older adolescents have demonstrated long-term effectiveness, and few of them so far have addressed sedentary behaviour (SB). Based on behavioural theories and evidence, we designed a multi-level intervention to increase PA and decrease SB among vocational school students. This study investigates feasibility and acceptability of two main intervention components and research procedures. We also examine uptake of behaviour change techniques (BCTs) by the participants. METHODS: Design was an outcome assessor blinded, cluster-randomised controlled trial. Four classes of students (matched pairs) were randomised into one intervention and one control arm. The intervention consisted of (1) a 6-h group-based intervention for students, (2) two 2-h training workshops to reduce their students' sitting in class for teachers, and (3) provision of light PA equipment in classrooms. At baseline (T1), mid-intervention (T2) at 3 weeks, post-intervention (T3) and 6 months after baseline (T4) we measured hypothesised psychosocial mediators and self-reported PA and sitting. Objective assessment of PA and SB (7-day accelerometry) was conducted at T1, T3 and T4. Body composition (bioimpedance) was measured at T1 and T4. Students and teachers in the intervention arm filled in acceptability questionnaires at T3. RESULTS: Recruitment rate was 64% (students) and 88.9% (teachers), and at T3, all post-intervention measurements were completed by 33 students (retention 76.7%) and 15 teachers (retention 93.8%). Acceptability ratings of sessions were high (students M = 6.29, scale 1-7), and data collection procedures were feasible. Intervention arm students reported increased use of BCTs, but uptake of some key BCTs was suboptimal. BCT use correlated highly with objective measures of PA. Based on both self-report and student evaluation, teachers in the intervention arm increased the use of sitting reduction strategies at post-intervention and T4 follow-up (p < .05). CONCLUSIONS: We detected willingness of the target groups to participate, good response rates to questionnaires, adequate retention, as well as acceptability of the trial protocol. Investigation of BCT use among students helped further enhance intervention procedures to promote BCT use. After making necessary modifications identified, intervention effectiveness can next be tested in a definitive trial. TRIAL REGISTRATION: ISRCTN34534846 . Registered 23 May 2014. Retrospectively registered.
  • Patel, Kishan; Kouvonen, Anne Maria; Close, Ciara; Väänänen, Ari; O'Reilly, Dermot; Donnelly, Michael (BioMed Central, 2017)
  • Laaksonen, Maija; Sajanti, Eeva; Sormunen, Jani J.; Penttinen, Ritva; Hanninen, Jari; Ruohomaki, Kai; Saaksjarvi, Ilari; Vesterinen, Eero J.; Vuorinen, Ilppo; Hytonen, Jukka; Klemola, Tero (Nature Publishing Group, 2017)
    A national crowdsourcing-based tick collection campaign was organized in 2015 with the objective of producing novel data on tick distribution and tick-borne pathogens in Finland. Nearly 20 000 Ixodes ticks were collected. The collected material revealed the nationwide distribution of I. persulcatus for the first time and a shift northwards in the distribution of I. ricinus in Finland. A subset of 2038 tick samples containing both species was screened for Borrelia burgdorferi sensu lato (the prevalence was 14.2% for I. ricinus and 19.8% for I. persulcatus), B. miyamotoi (0.2% and 0.4%, respectively) and tick-borne encephalitis virus (TBEV; 0.2% and 3.0%, respectively). We also report new risk areas for TBEV in Finland and, for the first time, the presence of B. miyamotoi in ticks from mainland Finland. Most importantly, our study demonstrates the overwhelming power of citizen science in accomplishing a collection effort that would have been impossible with the scientific community alone.
  • Tahko, Tuomas E. (Springer, 2017)
    Synthese Library
    In this chapter, it is suggested that our epistemic access to metaphysical modality generally involves rationalist, a priori elements. However, these a priori elements are much more subtle than ‘traditional’ modal rationalism assumes. In fact, some might even question the ‘apriority’ of these elements, but I should stress that I consider a priori and a posteriori elements especially in our modal inquiry to be so deeply intertwined that it is not easy to tell them apart. Supposed metaphysically necessary identity statements involving natural kind terms are a good example: the fact that empirical input is crucial in establishing their necessity has clouded the role and content of the a priori input, as I have previously argued (Tahko forthcoming). For instance, the supposed metaphysically necessary identity statement involving water and its microstructure can only be established with the help of a controversial a priori principle concerning the determination of chemical properties by microstructure. The Kripke-Putnam framework of modal epistemology fails precisely because it is unclear whether the required a priori element is present. My positive proposal builds on E. J. Lowe’s work. Lowe holds that our knowledge of metaphysical modality is based on our knowledge of essence. Lowe’s account strives to offer a uniform picture of modal epistemology: essence is the basis of all our modal knowledge. This is the basis of Lowe’s modal rationalism. I believe that Lowe’s proposal is on the right lines in the case of abstract objects, but I doubt that it can be successfully applied to the case of natural kinds. Accordingly, the case of natural kinds will be my main focus and I will suggest that modal rationalism, at least as it is traditionally understood, falls short of explaining modal knowledge concerning natural kinds. Yet, I think that Lowe has identified something of crucial importance for modal epistemology, namely the essentialist, a priori elements present in our modal inquiry. The upshot is that rather than moving all the way from modal rationalism to modal empiricism, a type of hybrid approach, ‘empirically-informed modal rationalism’, can be developed.
  • Roinila, Markku (2010)
    Filosofisia tutkimuksia Helsingin yliopistosta
    Julkaisematta jääneessä muistiossaan Mietteitä oikeuden yleiskäsitteestä (1702-1703?) G. W. Leibniz muotoilee uudelleen Platonin Euthyfron-dialogissa esitetyn kuuluisan kysymyksen. Hän kirjoittaa: ”Myönnetään, että kaikki mitä Jumala tahtoo, on hyvää ja oikein. Sen sijaan kysytään, onko se hyvää ja oikein siksi että Jumala niin tahtoo, vai tahtooko Jumala sitä koska se on hyvää ja oikein. Eli kysytään, onko hyvyys tai oikeus jotakin mielivaltaista, vai koostuvatko ne asioiden luonnetta koskevista välttämättömistä ja ikuisista totuuksista, kuten luvut ja suhteet.” Universaaleja, ikuisia totuuksia puolustava filosofi ei voi hyväksyä ensin mainittua vaihtoehtoa. Hänen mukaansa ”Se toden totta tuhoaisi Jumalan oikeudenmukaisuuden. Sillä miksi ylistäisimme häntä oikeudenmukaisista teoista, jos oikeudenmukaisuuden käsite ei hänen tapauksessaan lisää mitään teon käsitteeseen? Ja sanonta stat pro ratione voluntas, minun tahtoni käyköön perusteesta, on todella tyrannin motto.” Leibnizin kritiikki on suunnattu erityisesti hänen aikalaisiaan René Descartesia, Thomas Hobbesia ja Samuel Pufendorfia vastaan. Hän ei voi hyväksyä näkemystä, jonka mukaan oikeudenmukaisuuden mitta on vain Jumalan tahto. Perustan on löydyttävä ikuisista totuuksista, jotka ovat myös Jumalan oikeudenmukaisuuden standardi. Erityisen kuuluisaksi tuli Leibnizin kritiikki Pufendorfin näkemyksiä kohtaan, sillä Pufendorfin laajalle levinneen teoksen De officio hominis et civis ranskalaisen laitoksen neljännen painoksen toimittaja Barbeyrac liitti siihen Leibnizin kiistakirjoituksen, joka tunnetaan lyhyellä nimellä Monita (Epistola viri excellentissimi ad amicum qua monita quaedam ad principia Pufendorfiani operis de officio hominis et civis continentur, 1706) ja puolusti Pufendorfia Leibnizia vastaan. Leibnizin onnistui kuitenkin ilmeisesti osoittaa eräs heikkous Pufendorfin näkemyksissä, jota Barbeyrac ei pystynyt sivuuttamaan: tämän mukaan Jumala on saman aikaan sekä ylin tuomari että lakien laatija. Siten Leibnizin näkökulmasta Jumala on tyranni – hänen tahtonsa on oikeuden ja etiikan mitta ja koska hän on kaikkivaltias, hän voi pakottaa ihmiset noudattamaan sellaista oikeudenmukaisuutta, joka on hänen mieleistään. Koska Jumalan yläpuolella ei ole Pufendorfin mukaan mitään, hän voi toimia aivan mielivaltaisesti. Leibnizin kritiikki kiteytyy Pufendorfin epäselvään erotteluun ulkoisen ja sisäisen velvollisuuden välillä, joka jättää hänen näkemyksensä arvoitukselliseksi. Tutkiskelen tässä esitelmässä oliko Leibnzin kritiikki johdonmukainen ja oikeutettu. Onko Pufendorfin näkemyksissä heikkous, jota hän ei itse huomannut? Vertailen myös asiaa koskevia eri kommentaareja (mm. Kari Saastamoinen, Petter Korkman, Fiametta Palladini) ja arvioin Leibnizin kritiikin reseptiota Pufendorf-tutkimuksessa.
  • Harris, Vanessa C.; Armah, George; Fuentes, Susana; Korpela, Katri E.; Parashar, Umesh; Victor, John C.; Tate, Jacqueline; de Weerth, Carolina; Giaquinto, Carlo; Wiersinga, Willem Joost; Lewis, Kristen D. C.; de Vos, Willem M. (Oxford University Press, 2017)
    Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. Methods. We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip. Results. We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P =.002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009). Conclusions. The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries.
  • Nordenstedt, Noora; Marcenaro, Delfia; Chilagane, Daudi; Mwaipopo, Beatrice; Rajamaki, Minna-Liisa; Nchimbi-Msolla, Susan; Njau, Paul J. R.; Mbanzibwa, Deusdedith R.; Valkonen, Jari P. T. (PUBLIC LIBRARY OF SCIENCE, 2017)
    Common bean (Phaseolus vulgaris) is an annual grain legume that was domesticated in Mesoamerica (Central America) and the Andes. It is currently grown widely also on other continents including Africa. We surveyed seedborne viruses in new common bean varieties introduced to Nicaragua (Central America) and in landraces and improved varieties grown in Tanzania (eastern Africa). Bean seeds, harvested from Nicaragua and Tanzania, were grown in insect-controlled greenhouse or screenhouse, respectively, to obtain leaf material for virus testing. Equal amounts of total RNA from different samples were pooled (30-36 samples per pool), and small RNAs were deep-sequenced (Illumina). Assembly of the reads (21-24 nt) to contiguous sequences and searches for homologous viral sequences in data-bases revealed Phaseolus vulgaris endornavirus 1 (PvEV-1) and PvEV-2 in the bean varieties in Nicaragua and Tanzania. These viruses are not known to cause symptoms in common bean and are considered non-pathogenic. The small-RNA reads from each pool of samples were mapped to the previously characterized complete PvEV-1 and PvEV-2 sequences (genome lengths ca. 14 kb and 15 kb, respectively). Coverage of the viral genomes was 87.9-99.9%, depending on the pool. Coverage per nucleotide ranged from 5 to 471, confirming virus identification. PvEV-1 and PvEV-2 are known to occur in Phaseolus spp. in Central America, but there is little previous information about their occurrence in Nicaragua, and no information about occurrence in Africa. Aside from Cowpea mild mosaic virus detected in bean plants grown from been seeds harvested from one region in Tanzania, no other pathogenic seedborne viruses were detected. The low incidence of infections caused by pathogenic viruses transmitted via bean seeds may be attributable to new, virus-resistant CB varieties released by breeding programs in Nicaragua and Tanzania.
  • Lokki, A. Inkeri; Kaartokallio, Tea; Holmberg, Ville; Onkamo, Paivi; Koskinen, Lotta; Saavalainen, Paivi; Heinonen, Seppo Tapani; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Villa, Pia M.; Hiltunen, Leena; Laivuori, Hannele; Meri, Seppo (Frontiers Media S.A., 2017)
    Preeclampsia (PE) is a common vascular disease of pregnancy with genetic predisposition. Dysregulation of the complement system has been implicated, but molecular mechanisms are incompletely understood. In this study, we determined the potential linkage of severe PE to the most central complement gene, C3. Three cohorts of Finnish patients and controls were recruited for a genetic case-control study. Participants were genotyped using Sequenom genotyping and Sanger sequencing. Initially, we studied 259 Finnish patients with severe PE and 426 controls from the Southern Finland PE and the Finnish population-based PE cohorts. We used a custom-made single nucleotide polymorphism (SNP) genotyping assay consisting of 98 SNPs in 18 genes that encode components of the complement system. Following the primary screening, C3 was selected as the candidate gene and consequently Sanger sequenced. Fourteen SNPs from C3 were also genotyped by a Sequenom panel in 960 patients with severe PE and 705 controls, including already sequenced individuals. Three of the 43 SNPs observed within C3 were associated with severe PE: rs2287845 (p = 0.038, OR = 1.158), rs366510 (p = 0.039, OR = 1.158), and rs2287848 (p = 0.041, OR = 1.155). We also discovered 16 SNP haplotypes with extreme linkage disequilibrium in the middle of the gene with a protective (p = 0.044, OR = 0.628) or a predisposing (p = 0.011, OR = 2.110) effect to severe PE depending on the allele combination. Genetic variants associated with PE are located in key domains of C3 and could thereby influence the function of C3. This is, as far as we are aware, the first candidate gene in the complement system with an association to a clinically relevant PE subphenotype, severe PE. The result highlights a potential role for the complement system in the pathogenesis of PE and may help in defining prognostic and therapeutic subgroups of preeclamptic women.
  • Neittaanmäki, Noora; Karppinen, Toni T.; Tani, Taneli T.; Snellman, Erna; Gronroos, Mari (Acta Dermato-Venereologica, 2017)
  • Laitinen, Anne; Sannino, Annalisa; Engeström, Yrjö (Pontifícia Universidade Católica do Rio Grande do Sul, Faculdade de Educação, 2016)
  • Karppinen, Toni; Ala-Houhala, Meri; Ylianttila, Lasse; Kautiainen, Hannu; Lakkala, Kaisa; Hannula, Henna-Reetta; Turunen, Esa; Viljakainen, Heli; Reunala, Timo; Snellman, Erna (TAYLOR & FRANCIS LTD, 2017)
    Humans obtain vitamin D from conversion of 7-dehydrocholesterol in the skin by ultraviolet B (UVB) radiation or from dietary sources. As the radiation level is insufficient in winter, vitamin D deficiency is common at higher latitudes. We assessed whether vernal solar UVB radiation at latitudes 61 degrees N and 67 degrees N in Finland has an impact on serum 25-hydroxyvitamin D [S-25(OH) D] concentrations. Twenty-seven healthy volunteers participated in outdoor activities in snow-covered terrain for 4-10 days in March or April, with their face and hands sun-exposed. The personal UVB doses and S-25(OH) D levels were monitored. A mean UVB dose of 11.8 standard erythema doses (SED) was received during an average of 12.3 outdoor hours. The mean S-25(OH) D concentration in subjects with a baseline concentration below 90.0 nmol/L (n=13) increased significantly, by 6.0 nmol/L from an initial mean of 62.4 nmol/L (p
  • Nagaraj, Ashwini S.; Lahtela, Jenni; Hemmes, Annabrita; Pellinen, Teijo; Blom, Sami; Devlin, Jennifer R.; Salmenkivi, Kaisa; Kallioniemi, Olli; Mäyränpää, Mikko; Narhi, Katja; Verschuren, Emmy W. (Cell Press, 2017)
    Lung cancers exhibit pronounced functional heterogeneity, confounding precision medicine. We studied how the cell of origin contributes to phenotypic heterogeneity following conditional expression of Kras(G12D) and loss of Lkb1 (Kras; Lkb1). Using progenitor cell-type-restricted adenoviral Cre to target cells expressing surfactant protein C (SPC) or club cell antigen 10 (CC10), we show that Ad5-CC10-Cre-infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts. We further demonstrate that CC10(+) cells are the predominant progenitors of adenosquamous carcinoma (ASC) tumors and give rise to a wider spectrum of histotypes that includes mucinous and acinar adenocarcinomas. Transcriptome analysis shows ASC histotype-specific upregulation of pro-inflammatory and immunomodulatory genes. This is accompanied by an ASC-specific immunosuppressive environment, consisting of downregulated MHC genes, recruitment of CD11b(+) Gr-1(+) tumor-associated neutrophils (TANs), and decreased T cell numbers. We conclude that progenitor cell-specific etiology influences the Kras; Lkb1-driven tumor histopathology spectrum and histotype-specific immune microenvironment.
  • Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B.; Haanpää, Maija; Hansson, Per; Huellemann, Philipp; Jensen, Troels S.; Freynhagen, Rainer; Kennedy, Jeffrey D.; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S. C.; Segerdahl, Marta; Serra, Jordi; Sindrup, Soren; Sommer, Claudia; Toelle, Thomas; Vollert, Jan; Treede, Rolf-Detlef; German Neuropathic Pain Res Networ; EUROPAIN; NEUROPAIN Consortia (LIPPINCOTT WILLIAMS & WILKINS, 2017)
    Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of painrelated sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profilesmight respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroupswith characteristic sensory profileswere identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combinationwith pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.
  • Sedmak, Goran; Jovanov-Milošević, Natasa; Puskarjov, Martin; Ulamec, Monica; Krušlin, B; Kaila, Kai Kalervo; Judas, Milos (Oxford University Press, 2016)