HLA-DQ and HLA-DRB1 alleles associated with Henoch-Schonlein purpura nephritis in Finnish pediatric population : a genome-wide association study

Background The pathophysiology of Henoch-Schonlein purpura (HSP) is still unclear, but several findings suggest that genetic factors may influence disease susceptibility. We aimed to perform a genome-wide association study (GWAS) in pediatric HSP patients with an emphasis on severe HSP nephritis. Methods The study included 46 HSP patients, 42 of whom had undergone kidney biopsy. Forty-nine pediatric patients with an inflammatory bowel disease (IBD) served as an autoimmune disease control group while Finnish bone marrow and blood donors represented the general reference population (n = 18,757). GWAS was performed for HSP and IBD samples in a case-control manner against the reference population. The analysis also included imputation of human leukocyte antigen (HLA) alleles. Results GWAS analysis in HSP revealed several polymorphisms from the HLA region that surpassed the genome-wide significance level. Three HLA class II alleles were also significantly more frequent in HSP than in the reference population: DQA1*01:01, DQB1*05:01, and DRB1*01:01. Haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 occurred in 43.5% of HSP patients, whereas its frequency was 8.2% in IBD patients and 15.0% in the reference population. HSP patients with this haplotype showed similar baseline clinical findings and outcome as HSP patients negative for the haplotype. In IBD patients, no polymorphism or HLA allele appeared significant at the genome-wide level. Conclusions Our results suggest that haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 is associated with susceptibility to HSP, but not with the severity of the kidney involvement. These HLA associations did not occur in IBD patients, suggesting that they are specific to HSP and not related to susceptibility to autoimmune diseases in general.Peer reviewe

Pitkän aikavälin ilmasto- ja energiastrategian ympäristöarviointi

Arvioinnissa tarkasteltiin erityisesti niitä pitkän aikavälin ilmasto- ja energiastrategian ympäristövaikutuksia, jotka voivat syntyä kasvihuonekaasupäästöjen vähentämisen lisäksi. Pääasiassa ilmastonmuutosta hillitsevät toimet, kuten energiansäästö ja uusiutuvan energiantuotannon lisäys, vähentävät myös ilmansaasteiden päästöjä, mutta esimerkiksi puun pienpoltto aiheuttaa pienhiukkaspäästöjä. Kun päästöt tapahtuvat matalalla ja lähellä suuria ihmiskeskittymiä, väestö altistuu suuremmille epäpuhtauksien pitoisuuksille kuin silloin, kun päästöt tulevat korkeista piipuista. Erityisesti on syytä rajoittaa liikenteen ei-pakokaasuperäisiä päästöjä (”katupöly”) kaupungeissa ja puun pienpolton päästöjä tiheästi asutuilla alueilla. Elinkaariarviointiin perustuva skenaarioiden ympäristövaikutusarviointi osoittaa, että polttoaineiden valmistuksen ja käytön yhteenlasketut vaikutukset pienenevät kaikissa tarkastelluissa vaikutusluokissa vuoteen 2005 verrattuna. Tämä johtuu pääasiassa kotimaan käytön vaikutusten vähenemisestä. Polttoaineiden valmistuksen vaikutukset ulkomailla lisääntyvät, mikä johtuu fossiilisten energialähteiden tuonnin kasvusta. Ympäristöanalyysin perusteella typen oksidien ja pienhiukkasten päästöjen rajoittaminen on keskeisin päästövähennystoimenpidealue hiilidioksidipäästöjen rajoittamisen jälkeen. Monet strategian linjaukset ja toimenpiteet pyrkivät viemään kehitystä kohti energiaa säästävää ja vähemmän luonnonvaroja kuluttavaa tuotantoa ja kulutusta, mutta kokonaiskulutuksena mitattuna muutos vuosien 2005 ja 2020 välillä on skenaarioissa verrattain pieni. Merkittävämpi muutos voi toteutua pitkällä aikavälillä, jos ilmasto- ja energiapolitiikka johdonmukaisesti kannustaa säästämään energiaa ja luonnonvaroja niin, että myös absoluuttinen kulutus pienenee. Aikaisempien ilmasto- ja energiastrategioiden toimenpiteiden seuranta osoittaa, että lukuisia erilaisia energiatehokkuutta edistäviä hankkeita on käynnistetty, mutta merkittäviä rakenteellisia muutoksia energiankulutuksessa ei ole vielä tapahtunut. Osana ilmastopolitiikkaa Suomi on kerännyt kokemuksia ns. Kioton mekanismien soveltamisesta. Tarkastelu osoittaa, että näiden mekanismien avulla voidaan edistää myös yleisiä kehityspoliittisia tavoitteita, mutta tämä edellyttää toiminnan aktiivista suuntaamista myös monenkeskisellä tasolla

Phylogeographic separation and formation of sexually discrete lineages in a global population of Yersinia pseudotuberculosis

Yersinia pseudotuberculosis is a Gram-negative intestinal pathogen of humans and has been responsible for several nationwide gastrointestinal outbreaks. Large-scale population genomic studies have been performed on the other human pathogenic species of the genus Yersinia, Yersinia pestis and Yersinia enterocolitica allowing a high-resolution understanding of the ecology, evolution and dissemination of these pathogens. However, to date no purpose-designed large-scale global population genomic analysis of Y. pseudotuberculosis has been performed. Here we present analyses of the genomes of 134 strains of Y. pseudotuberculosis isolated from around the world, from multiple ecosystems since the 1960s. Our data display a phylogeographic split within the population, with an Asian ancestry and subsequent dispersal of successful clonal lineages into Europe and the rest of the world. These lineages can be differentiated by CRISPR cluster arrays, and we show that the lineages are limited with respect to inter-lineage genetic exchange. This restriction of genetic exchange maintains the discrete lineage structure in the population despite co-existence of lineages for thousands of years in multiple countries. Our data highlights how CRISPR can be informative of the evolutionary trajectory of bacterial lineages, and merits further study across bacteria.Peer reviewe

Prediction of renal outcome in Henoch-Schonlein nephritis based on biopsy findings

Background In Henoch-Schonlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable. Methods We evaluated serial renal biopsies from 26 HSN patients. Follow-up biopsy occurred at median 2.1 years after diagnostic biopsy. Patients formed two groups at the follow-up biopsy: patients without proteinuria (group I; n = 11) and with proteinuria (group II; n = 15). Biopsies underwent evaluation according to three classifications: International Study of Kidney Disease in Children (ISKDC), Oxford (MEST-C), and semiquantitative classification (SQC) including an activity and chronicity score. Analysis also included expression of pro-fibrotic (alpha-smooth muscle actin and vimentin) and inflammatory (P-selectin glycoprotein ligand-1) molecules in the diagnostic biopsy specimens. Definition of unfavorable outcome was active renal disease or reduced renal function at last follow-up. Results Between the biopsies, SQC chronicity score increased in 22 (85%) patients, whereas activity score and ISKDC grade decreased in 21 (81%) and 17 (65%), respectively. Of the MEST-C parameters, endocapillary proliferation (from 83 to 13%; p <0.001) and crescents (from 63 to 25%; p = 0.022) showed significant reduction, and segmental glomerulosclerosis (from 38 to 79%; p = 0.006) significant increment. These changes occurred similarly in groups I and II. Expression of the pro-fibrotic and inflammatory molecules showed no clinically significant differences between groups I and II. None in group I and five (33%) patients in group II had unfavorable outcome (p = 0.053). Conclusions Our results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction.Peer reviewe

The ISKDC classification and a new semiquantitative classification for predicting outcomes of Henoch-Schonlein purpura nephritis

Histological findings from primary kidney biopsies were correlated with patient outcomes in a national cohort of paediatric Henoch-Schonlein nephritis (HSN) patients. Primary kidney biopsies from 53 HSN patients were re-evaluated using the ISKDC (International Study of Kidney Disease in Children) classification and a modified semiquantitative classification (SQC) that scores renal findings and also takes into account activity, chronicity and tubulointerstitial indices. The ISKDC and SQC classifications were evaluated comparatively in four outcome groups: no signs of renal disease (outcome A, n = 27), minor urinary abnormalities (outcome B, n = 18), active renal disease (outcome C, n = 3) and renal insufficiency, end-stage renal disease or succumbed due to HSN (outcome D, n = 5). For the receiver operating characteristic and logistic regression analyses, outcomes A and B were considered to be favourable and outcomes C and D to be unfavourable. The median follow-up time was 7.3 years. The patients with an unfavourable outcome (C and D), considered together due to low patient numbers, had significantly higher total biopsy SQC scores and activity indices than those who had a favourable one (groups A and B). The chronicity and tubulointerstitial indices differed significantly only between group C + D and group A. The difference in areas under the curve between the total biopsy SQC scores and ISKDC findings was 0.15 [p = 0.04, normal-based 95% confidence interval (CI) 0.007-0.29, bias-controlled 95% CI -0.004 to 0.28]. Our results suggest that the modified SQC is more sensitive than ISKDC classification for predicting the outcome in HSN cases.Peer reviewe

Itämeren hiekkarantojen ja dyynien hoito - Vård av Östersjöns sandstränder och dyner

Hiekkarannat ja dyynit ovat lajirikkaita elinympäristöjä. Niillä elää lukuisia joukko kovakuoriaisia, luteita, perhosia, hämähäkkieläimiä, kasveja ja lintuja. Monet lajeista ovat nykyisin uhanalaisia. Hiekkarantoja, dyynejä ja niillä eläviä eliöitä uhkaavat muiden muassa Itämeren rehevöityminen, joka näkyy rannoilla levän kertymisenä ja umpeenkasvuna. Myös rakentaminen ja virkistyskäytöstä johtuva kuluminen heikentävät hiekkarantojen lajien elinmahdollisuuksia. Vieraslaji kurtturuusu leviää myös kovaa vauhtia etenkin Suomenlahden rannikolla. Tässä oppaassa kerrotaan hiekkarantojen ja dyynien monimuotoisesta elämästä. Itämeren tilan parantaminen on ensisijaista rantojen eliölajiston hyvinvoinnin kannalta. Meren elpyminen on kuitenkin hidasta ja sitä odotellessa meistä jokainen voi auttaa rantojen erikoistunutta eliölajistoa pienilläkin teoilla

Least-action perihelion precession

The precession of Mercury's perihelion is reinspected by the principle of least action. The anomalous advancement of the apside line that is customarily accounted by the theory of general relativity, is ascribed to the gravitational effect due to the entire Universe. When the least action is written in the Sun's frame of reference, the residual rotation is seen to stem from inertia due to all bodies in the Universe. Since mass corresponds to a bound form of energy, gravity, as any other force, can be described as an energy density difference between a system of bodies and its surrounding energy densities that are dispersed throughout the Universe. According to the principle of least action the Universe is expanding by combustion of mass to radiation in the quest of equilibrating the bound forms of energy with "zero-density surroundings" in least time. Keywords: cosmological principle; energy density; energy dispersal; evolution; gravity; the principle of least actionComment: 7 pages, 3 figure

Renewal of forest based manufacturing towards a sustainable circular bioeconomy

Environmental problems, combined with European Union environmental and energy policies shaped to address them, have created pressures for change. Some of these open significant opportunities to renew industries. This report delivers new understanding of the potential of circular economy for sustainable renewal of manufacturing in bio-based industries. With particular focus on novel value chains, it provides novel insights into the role of innovation policies in facilitating the shift towards sustainable, circular bioeconomy in Finland and Sweden. The textile and multi-storey wood construction sectors, and emergent biorefineries are utilised as case studies that deepen understanding of the circular bioeconomy, its opportunities, barriers, and impacts, and the policies that affect its emergence. Recent developments of bioeconomy and circular economy solutions and governance in the Netherlands are also summarised in order to deliver contrasting context to the Nordic focus countries. In this work, the bioeconomy is conceptualised as an economy where the basic building blocks for materials, chemicals and energy are derived from renewable biological resources, such as plant and animal biomass. The essence of the circular economy, that is used here, lies in maximisation of added value and in making the best use of any extracted raw material. This analysis shows that to date discussions and activities related to the promotion of bioeconomy and circular economy have largely been separate efforts, but there are signs that the discussions may converge. It finds that while the form of developments are similar in Finland and in Sweden in the case areas (i.e. textiles, wood construction and biorefineries), there are also clear differences in the strengths of the countries. Evidence is found that such strengths offer potential to develop world leadership in a circular bioeconomy. The report identifies policy recommendations to support renewal of manufacturing in the wood based industries towards a sustainable circular bioeconomy