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Sökning: WFRF:(Lehtonen K. K.)

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1.
  • Sliz, E., et al. (författare)
  • Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
  • 2023
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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  • Tabassum, R, et al. (författare)
  • Genetic architecture of human plasma lipidome and its link to cardiovascular disease
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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  • Kaasinen, E, et al. (författare)
  • Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1252-
  • Tidskriftsartikel (refereegranskat)abstract
    • Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.
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  • Pietila, EA, et al. (författare)
  • Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3904-
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to its dynamic nature, the evolution of cancer cell-extracellular matrix (ECM) crosstalk, critically affecting metastasis and treatment resistance, remains elusive. Our results show that platinum-chemotherapy itself enhances resistance by progressively changing the cancer cell-intrinsic adhesion signaling and cell-surrounding ECM. Examining ovarian high-grade serous carcinoma (HGSC) transcriptome and histology, we describe the fibrotic ECM heterogeneity at primary tumors and distinct metastatic sites, prior and after chemotherapy. Using cell models from systematic ECM screen to collagen-based 2D and 3D cultures, we demonstrate that both specific ECM substrates and stiffness increase resistance to platinum-mediated, apoptosis-inducing DNA damage via FAK and β1 integrin-pMLC-YAP signaling. Among such substrates around metastatic HGSCs, COL6 was upregulated by chemotherapy and enhanced the resistance of relapse, but not treatment-naïve, HGSC organoids. These results identify matrix adhesion as an adaptive response, driving HGSC aggressiveness via co-evolving ECM composition and sensing, suggesting stromal and tumor strategies for ECM pathway targeting.
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  • van der Plas, F., et al. (författare)
  • Continental mapping of forest ecosystem functions reveals a high but unrealised potential for forest multifunctionality
  • 2018
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 21:1, s. 31-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Humans require multiple services from ecosystems, but it is largely unknown whether trade-offs between ecosystem functions prevent the realisation of high ecosystem multifunctionality across spatial scales. Here, we combined a comprehensive dataset (28 ecosystem functions measured on 209 forest plots) with a forest inventory dataset (105,316 plots) to extrapolate and map relationships between various ecosystem multifunctionality measures across Europe. These multifunctionality measures reflected different management objectives, related to timber production, climate regulation and biodiversity conservation/recreation. We found that trade-offs among them were rare across Europe, at both local and continental scales. This suggests a high potential for win-win' forest management strategies, where overall multifunctionality is maximised. However, across sites, multifunctionality was on average 45.8-49.8% below maximum levels and not necessarily highest in protected areas. Therefore, using one of the most comprehensive assessments so far, our study suggests a high but largely unrealised potential for management to promote multifunctional forests.
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  • Artigas, J., et al. (författare)
  • Towards a renewed research agenda in ecotoxicology
  • 2012
  • Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 160, s. 201-206
  • Tidskriftsartikel (refereegranskat)abstract
    • New concerns about biodiversity, ecosystem services and human health triggered several new regulations increasing the need for sound ecotoxicological risk assessment. The PEER network aims to share its view on the research issues that this challenges. PEER scientists call for an improved biologically relevant exposure assessment. They promote comprehensive effect assessment at several biological levels. Biological traits should be used for Environmental risk assessment (ERA) as promising tools to better understand relationships between structure and functioning of ecosystems. The use of modern high throughput methods could also enhance the amount of data for a better risk assessment. Improved models coping with multiple stressors or biological levels are necessary to answer for a more scientifically based risk assessment. Those methods must be embedded within life cycle analysis or economical models for efficient regulations. Joint research programmes involving humanities with ecological sciences should be developed for a sound risk management. (C) 2011 Elsevier Ltd. All rights reserved.
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  • Darlow, Brian A, et al. (författare)
  • International variations and trends in the treatment for retinopathy of prematurity
  • 2017
  • Ingår i: British Journal of Ophthalmology. - : BMJ Publishing Group Ltd. - 0007-1161 .- 1468-2079. ; 101:10, s. 1399-1404
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To compare the rates of retinopathy of prematurity (ROP) and treatment of ROP by laser or intravitreal anti-vascular endothelial growth factor among preterm neonates from high-income countries participating in the International Network for Evaluating Outcomes (iNeo) of neonates.METHODS: weeks' gestation who were admitted to neonatal units in Australia/New Zealand, Canada, Finland, Israel, Japan, Spain, Sweden, Switzerland, Tuscany (Italy) and the UK between 2007 and 2013. Pairwise comparisons of ROP treatment in survivors between countries were evaluated by Poisson and multivariable logistic regression analyses after adjustment for confounders. A composite outcome of death or ROP treatment was compared between countries using logistic regression and standardised ratios.RESULTS: Of 48 087 infants included in the analysis, 81.8% survived to 32 weeks postmenstrual age, and 95% of survivors were screened for ROP. Rates of any ROP ranged from 25.2% to 91.0% in Switzerland and Japan, respectively, among those examined. The overall rate of those receiving treatment was 24.9%, which varied from 4.3% to 30.4%. Adjusted risk ratios for ROP treatment were lower for Switzerland in all pairwise comparisons, whereas Japan displayed significantly higher ratios. Comparisons of the composite outcome between countries revealed similar, but less marked differences.CONCLUSIONS: Rates of any ROP and ROP treatment varied significantly between iNeo members, while an overall decline in ROP treatment was observed during the study period. It is unclear whether these variations represent differences in care practices, diagnosis and/or treatment thresholds.
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  • Jaaskelainen, T, et al. (författare)
  • A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants
  • 2018
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 14616-
  • Tidskriftsartikel (refereegranskat)abstract
    • Preeclampsia (PE) is a complex pregnancy disorder. It is not extensively known how the metabolic alterations of PE women contribute to the metabolism of newborn. We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of plasma from umbilical cord differs between infants born to PE and non-PE pregnancies in the FINNPEC study. Cord plasma was available from 42 newborns born from PE and 53 from non-PE pregnancies. 133 molecular features differed between PE and non-PE newborns after correction for multiple testing. Decreased levels of 4-pyridoxic acid were observed in the cord plasma samples of PE newborns when compared to non-PE newborns. Compounds representing following areas of metabolism were increased in the cord plasma of PE newborns: urea and creatine metabolism; carnitine biosynthesis and acylcarnitines; putrescine metabolites; tryptophan metabolism and phosphatidylcholines. To our knowledge, this study is the first one to apply LC-MS based metabolomics in cord plasma of PE newborns. We demonstrate that this strategy provides a global picture of the widespread metabolic alterations associated with PE and particularly the elevated levels of carnitine precursors and trimethylated compounds appear to be associated with PE at birth.
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  • Kelly, L E, et al. (författare)
  • Perinatal health services organization for preterm births : a multinational comparison
  • 2017
  • Ingår i: Journal of Perinatology. - : Nature Publishing Group. - 0743-8346 .- 1476-5543. ; 37:7, s. 762-768
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To explore population characteristics, organization of health services and comparability of available information for very low birth weight or very preterm neonates born before 32 weeks' gestation in 11 high-income countries contributing data to the International Network for Evaluating Outcomes of Neonates (iNeo).STUDY DESIGN: We obtained population characteristics from public domain sources, conducted a survey of organization of maternal and neonatal health services and evaluated the comparability of data contributed to the iNeo collaboration from Australia, Canada, Finland, Israel, Italy, Japan, New Zealand, Spain, Sweden, Switzerland and UK.RESULTS: All countries have nationally funded maternal/neonatal health care with >90% of women receiving prenatal care. Preterm birth rate, maternal age, and neonatal and infant mortality rates were relatively similar across countries. Most (50 to >95%) between-hospital transports of neonates born at non-tertiary units were conducted by designated transport teams; 72% (8/11 countries) had designated transfer and 63% (7/11 countries) mandate the presence of a physician. The capacity of 'step-down' units varied between countries, with capacity for respiratory care available in <10% to >75% of units. Heterogeneity in data collection processes for benchmarking and quality improvement activities were identified.CONCLUSIONS: Comparability of healthcare outcomes for very preterm low birth weight neonates between countries requires an evaluation of differences in population coverage, healthcare services and meta-data.
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  • Lehtonen, K. K., et al. (författare)
  • The BEEP project in the Baltic Sea: Overview of results and outline for a regional biological effects monitoring strategy
  • 2006
  • Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X. ; 53:8-9, s. 523-537
  • Tidskriftsartikel (refereegranskat)abstract
    • Field studies in the framework of the EU funded BEEP project (Biological Effects of Environmental Pollution in Marine Coastal Ecosystems, 2001-2004) aimed at validating and intercalibrating a battery of biomarkers of contaminant exposure and effects in selected indicator species in the Mediterranean, the North Atlantic and the Baltic Seas. Major strategic goals of the BEEP project were the development of a sensitive and cost-efficient biological effects monitoring approach, delivery of information and advice to end-user groups, and the implementation of a network of biomarker researchers around Europe. Based on the main results obtained in the Baltic Sea component of the BEEP the present paper summarises and assesses the applicability of biomarkers for different regions and species in this sea area. Moreover, a general strategy and some practical considerations for the monitoring of biological effects in the Baltic Sea are outlined. (c) 2006 Elsevier Ltd. All rights reserved.
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  • Pulkka, OP, et al. (författare)
  • Anagrelide for Gastrointestinal Stromal Tumor
  • 2019
  • Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 25:5, s. 1676-1687
  • Tidskriftsartikel (refereegranskat)
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  • Turja, R., et al. (författare)
  • A multibiomarker approach to the assessment of pollution impacts in two Baltic Sea coastal areas in Sweden using caged mussels (Mytilus trossulus)
  • 2014
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 473, s. 398-409
  • Tidskriftsartikel (refereegranskat)abstract
    • Blue mussels (Mytilus trossulus) were transplanted in cages for three months in two Swedish coastal areas in the Bothnian Sea (northern Baltic Sea) to investigate the interactions between analysed environmental chemicals and biological responses. A wide array of biological parameters (biomarkers) including antioxidant and biotransformation activity, geno-, cyto- and neurotoxic effects, phagocytosis, bioenergetic status and heart rate were measured to detect the possible effects of contaminants. Integrated Biomarker Response index and Principal Component Analysis performed on the individual biological response data were able to discriminate between the two study areas as well as the contaminated sites from their respective local reference sites. The two contaminated sites outside the cities of Sundsvall (station 51) and Gavle (station G1) were characterised by different biomarker response patterns. Mussels at station S1 showed a low condition index, increased heart rate recovery time and phagocytosis activity coinciding with the highest tissue concentrations of some trace metals, polycyclic aromatic hydrocarbons and organotins. At station G1 the highest organochlorine pesticide concentration was recorded as well as elevations in glutathione S-transferase activity, thiamine content and low lysosomal membrane stability. Significant variability in the geno- and cytotoxic responses and bioenergetic status was also observed at the different caging stations. The results obtained suggest that different chemical mixtures present in the study areas cause variable biological response patterns in organisms.
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  • Adams, M, et al. (författare)
  • Preventive strategies and factors associated with surgically treated necrotising enterocolitis in extremely preterm infants: an international unit survey linked with retrospective cohort data analysis
  • 2019
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:10, s. e031086-
  • Tidskriftsartikel (refereegranskat)abstract
    • To compare necrotising enterocolitis (NEC) prevention practices and NEC associated factors between units from eight countries of the International Network for Evaluation of Outcomes of Neonates, and to assess their association with surgical NEC rates.DesignProspective unit-level survey combined with retrospective cohort study.SettingNeonatal intensive care units in Australia/New Zealand, Canada, Finland, Israel, Spain, Sweden, Switzerland and Tuscany (Italy).PatientsExtremely preterm infants born between 240to 286weeks’ gestation, with birth weights<1500 g, and admitted between 2014–2015.ExposuresNEC prevention practices (probiotics, feeding, donor milk) using responses of an on-line pre-piloted questionnaire containing 10 questions and factors associated with NEC in literature (antenatal steroids, c-section, indomethacin treated patent ductus arteriosus and sepsis) using cohort data.Outcome measuresSurgical NEC rates and death following NEC using cohort data.ResultsThe survey response rate was 91% (153 units). Both probiotic provision and donor milk availability varied between 0%–100% among networks whereas feeding initiation and advancement rates were similar in most networks. The 9792 infants included in the cohort study to link survey results and cohort outcomes, revealed similar baseline characteristics but considerable differences in factors associated with NEC between networks. 397 (4.1%) neonates underwent NEC surgery, ranging from 2.4%–8.4% between networks. Standardised ratios for surgical NEC were lower for Australia/New Zealand, higher for Spain, and comparable for the remaining six networks.ConclusionsThe variation in implementation of NEC prevention practices and in factors associated with NEC in literature could not be associated with the variation in surgical NEC incidence. This corroborates the current lack of consensus surrounding the use of preventive strategies for NEC and emphasises the need for research.
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  • Ahola, Virpi, et al. (författare)
  • The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
  • 2014
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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  • Beltempo, Marc, et al. (författare)
  • Respiratory Management of Extremely Preterm Infants : An International Survey
  • 2018
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 114:1, s. 28-36
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There are significant international variations in chronic lung disease rates among very preterm infants yet there is little data on international variations in respiratory strategies.OBJECTIVE: To evaluate practice variations in the respiratory management of extremely preterm infants born at < 29 weeks' gestational age (GA) among 10 neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of Neonates collaboration.METHODS: A web-based survey was sent to the representatives of 390 neonatal intensive care units from Australia/New Zealand, Canada, Finland, Illinois (USA), Israel, Japan, Spain, Sweden, Switzerland, and Tuscany (Italy). Responses were based on practices in 2015.RESULTS: Overall, 321 of the 390 units responded (82%). The majority of units within networks (40-92%) mechanically ventilate infants born at 23-24 weeks' GA on continuous positive airway pressure (CPAP) with 30-39% oxygen in respiratory distress within 48 h after birth, but the proportion of units that offer mechanical ventilation for infants born at 25-26 weeks' GA at similar settings varied significantly (20-85% of units within networks). The most common respiratory strategy for infants born at 27-28 weeks' GA on CPAP with 30-39% oxygen with respiratory distress within 48 h after birth used by units also varied significantly among networks: mechanical ventilation (0-60%), CPAP (3-82%), intubation and surfactant administration with immediate extubation (0-75%), and less invasive surfactant administration (0-68%).CONCLUSIONS: There are marked variations but also similarities in respiratory management of extremely preterm infants between networks. Further collaboration and exploration is needed to better understand the association of these variations in practice with pulmonary outcomes.
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  • Brommer, Jon E., et al. (författare)
  • Passerine Extrapair Mating Dynamics : A Bayesian Modeling Approach Comparing Four Species
  • 2010
  • Ingår i: American Naturalist. - : University of Chicago Press. - 0003-0147 .- 1537-5323. ; 176:2, s. 178-187
  • Tidskriftsartikel (refereegranskat)abstract
    • In many socially monogamous animals, females engage in extrapair copulation (EPC), causing some broods to contain both within-pair and extrapair young (EPY). The proportion of all young that are EPY varies across populations and species. Because an EPC that does not result in EPY leaves no forensic trace, this variation in the proportion of EPY reflects both variation in the tendency to engage in EPC and variation in the extrapair fertilization (EPF) process across populations and species. We analyzed data on the distribution of EPY in broods of four passerines (blue tit, great tit, collared flycatcher, and pied flycatcher), with 18,564 genotyped nestlings from 2,346 broods in two to nine populations per species. Our Bayesian modeling approach estimated the underlying probability function of EPC (assumed to be a Poisson function) and conditional binomial EPF probability. We used an information theoretical approach to show that the expected distribution of EPC per female varies across populations but that EPF probabilities vary on the above-species level (tits vs. flycatchers). Hence, for these four passerines, our model suggests that the probability of an EPC mainly is determined by ecological (population-specific) conditions, whereas EPF probabilities reflect processes that are fixed above the species level.
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  • Gagliardi, L, et al. (författare)
  • Neonatal outcomes of extremely preterm twins by sex pairing: an international cohort study
  • 2021
  • Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 106:1, s. F17-F24
  • Tidskriftsartikel (refereegranskat)abstract
    • Infant boys have worse outcomes than girls. In twins, the ‘male disadvantage’ has been reported to extend to female co-twins via a ‘masculinising’ effect. We studied the association between sex pairing and neonatal outcomes in extremely preterm twins.DesignRetrospective cohort studySettingEleven countries participating in the International Network for Evaluating Outcomes of Neonates.PatientsLiveborn twins admitted at 23–29 weeks’ gestation in 2007–2015.Main outcome measuresWe examined in-hospital mortality, grades 3/4 intraventricular haemorrhage or cystic periventricular leukomalacia (IVH/PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity requiring treatment and a composite outcome (mortality or any of the outcomes above).ResultsAmong 20 924 twins, 38% were from male-male pairs, 32% were from female-female pairs and 30% were sex discordant. We had no information on chorionicity. Girls with a male co-twin had lower odds of mortality, IVH/PVL and the composite outcome than girl-girl pairs (reference group): adjusted OR (aOR) (95% CI) 0.79 (0.68 to 0.92), 0.83 (0.72 to 0.96) and 0.88 (0.79 to 0.98), respectively. Boys with a female co-twin also had lower odds of mortality: aOR 0.86 (0.74 to 0.99). Boys from male-male pairs had highest odds of BPD and composite outcome: aOR 1.38 (1.24 to 1.52) and 1.27 (1.16 to 1.39), respectively.ConclusionsSex-related disparities in outcomes exist in extremely preterm twins, with girls having lower risks than boys and opposite-sex pairs having lower risks than same-sex pairs. Our results may help clinicians in assessing risk in this large segment of extremely preterm infants.
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  • Helenius, Kjell, et al. (författare)
  • Survival in very preterm infants : an international comparison of 10 national neonatal networks
  • 2017
  • Ingår i: Pediatrics. - : The American Academy of Pediatrics. - 0031-4005 .- 1098-4275. ; 140:6
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To compare survival rates and age at death among very preterm infants in 10 national and regional neonatal networks.METHODS: A cohort study of very preterm infants, born between 24 and 29 weeks' gestation and weighing <1500 g, admitted to participating neonatal units between 2007 and 2013 in the International Network for Evaluating Outcomes of Neonates. Survival was compared by using standardized ratios (SRs) comparing survival in each network to the survival estimate of the whole population.RESULTS: Network populations differed with respect to rates of cesarean birth, exposure to antenatal steroids and birth in nontertiary hospitals. Network SRs for survival were highest in Japan (SR: 1.10; 99% confidence interval: 1.08-1.13) and lowest in Spain (SR: 0.88; 99% confidence interval: 0.85-0.90). The overall survival differed from 78% to 93% among networks, the difference being highest at 24 weeks' gestation (range 35%-84%). Survival rates increased and differences between networks diminished with increasing gestational age (GA) (range 92%-98% at 29 weeks' gestation); yet, relative differences in survival followed a similar pattern at all GAs. The median age at death varied from 4 days to 13 days across networks.CONCLUSIONS: The network ranking of survival rates for very preterm infants remained largely unchanged as GA increased; however, survival rates showed marked variations at lower GAs. The median age at death also varied among networks. These findings warrant further assessment of the representativeness of the study populations, organization of perinatal services, national guidelines, philosophy of care at extreme GAs, and resources used for decision-making.
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34.
  • Hines, Delaney, et al. (författare)
  • Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus
  • 2017
  • Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 106:3, s. 366-374
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We searched papers published in English from 2010 and 2015 reporting BPD as an outcome, together with studies that compared BPD definitions between 1978 and 2015. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long-term pulmonary and/or neurosensory outcomes reported moderate-to-low predictive values regardless of the BPD criteria.CONCLUSION: A comprehensive and evidence-based definition for BPD needs to be developed for benchmarking and prognostic use.
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36.
  • Huhtala, V, et al. (författare)
  • Low plasma cholecystokinin levels in colicky infants
  • 2003
  • Ingår i: Journal of pediatric gastroenterology and nutrition. - : Ovid Technologies (Wolters Kluwer Health). - 0277-2116. ; 37:1, s. 42-46
  • Tidskriftsartikel (refereegranskat)
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37.
  • Isayama, Tetsuya, et al. (författare)
  • International Variation in the Management of Patent Ductus Arteriosus and Its Association with Infant Outcomes : A Survey and Linked Cohort Study
  • 2022
  • Ingår i: The Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 244, s. 24-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess whether treating patients with a presymptomatic patent ductus arteriosus (PDA), based on early routine echocardiography, performed regardless of clinical signs, improved outcomes. Study design: This multicenter, survey-linked retrospective cohort study used an institutional-level questionnaire and individual patient-level data and included infants of <29 weeks of gestation born in 2014-2016 and admitted to tertiary neonatal intensive care units (NICUs) of 9 population-based national or regional neonatal networks. Infants in NICUs receiving treatment of presymptomatic PDA identified by routine echocardiography and those not were compared for the primary composite outcome (early death [≤7 days after birth] or severe intraventricular hemorrhage) and secondary outcomes (any in-hospital mortality and major morbidities). Results: The unit survey (response rates of 86%) revealed a wide variation among networks in the treatment of presymptomatic PDA (7%-86%). Among 246 NICUs with 17 936 infants (mean gestational age of 26 weeks), 126 NICUs (51%) with 7785 infants treated presymptomatic PDA. The primary outcome of early death or severe intraventricular hemorrhage was not significantly different between the NICUs treating presymptomatic PDA and those who did not (17% vs 21%; aOR 1.00, 95% CI 0.85-1.18). The NICUs treating presymptomatic PDA had greater odds of retinopathy of prematurity treatment (13% vs 7%; aOR 1.47, 95% CI 1.01-2.12); however, it was not significant in a sensitivity analysis excluding Japanese data. Conclusions: Treating presymptomatic PDA detected by routine echocardiography was commonplace but associated with no significant benefits. Well-designed trials are needed to assess the efficacy and safety of early targeted PDA treatment.
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  • Isayama, Tetsuya, et al. (författare)
  • Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm
  • 2020
  • Ingår i: Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 220, s. 34-39.e05
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To assess associations between neonatal intensive care unit (NICU)- level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes.Study design: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for >= 100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio.Results: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis.Conclusions: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.
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39.
  • Kambach, S., et al. (författare)
  • How do trees respond to species mixing in experimental compared to observational studies?
  • 2019
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 9:19, s. 11254-11265
  • Tidskriftsartikel (refereegranskat)abstract
    • For decades, ecologists have investigated the effects of tree species diversity on tree productivity at different scales and with different approaches ranging from observational to experimental study designs. Using data from five European national forest inventories (16,773 plots), six tree species diversity experiments (584 plots), and six networks of comparative plots (169 plots), we tested whether tree species growth responses to species mixing are consistent and therefore transferrable between those different research approaches. Our results confirm the general positive effect of tree species mixing on species growth (16% on average) but we found no consistency in species-specific responses to mixing between any of the three approaches, even after restricting comparisons to only those plots that shared similar mixtures compositions and forest types. These findings highlight the necessity to consider results from different research approaches when selecting species mixtures that should maximize positive forest biodiversity and functioning relationships.
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40.
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41.
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42.
  • Kooij, J. J. S., et al. (författare)
  • Updated European Consensus Statement on diagnosis and treatment of adult ADHD
  • 2019
  • Ingår i: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 56, s. 14-34
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAttention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.MethodsThe European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.ResultsBesides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?ConclusionsADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
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43.
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44.
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45.
  • Kuprijanov, Ivan, et al. (författare)
  • A case study on microlitter and chemical contaminants : Assessing biological effects in the southern coast of the Gulf of Finland (Baltic sea) using the mussel Mytilus trossulus as a bioindicator
  • 2024
  • Ingår i: Marine Environmental Research. - : Elsevier. - 0141-1136 .- 1879-0291. ; 199
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemical and microlitter (ML) pollution in three Estonian coastal areas (Baltic Sea) was investigated using mussels (Mytilus trossulus). Polycyclic aromatic hydrocarbons (PAH) in mussel tissues were observed in moderate levels with high bioaccumulation factors for the more hydrophilic and low molecular weight PAH (LMW PAH), namely anthracene and fluorene. Tissue concentrations of polybrominated diphenyl ethers (PBDE) and cadmium within mussel populations exceeded the Good Environmental Status thresholds by more than 200% and 60%, respectively. Multiple contamination at the Muuga Harbour site by tributyltin, high molecular weight PAH, including the highly toxic benzo[c]fluorene and PBDE, coincided with the inhibition of acetylcholinesterase activity and a lower condition index of the mussels. The metabolization and removal of bioaccumulated LMW PAH, reflected in the dominance of oxy-PAH such as anthracene-9,10-dione, is likely associated with the increased activity of glutathione S-transferase in caged mussels. Only a few microplastic particles were observed among the ML in mussel tissues, with coloured cellulose-based microfibers being the most prevalent. The average concentration of ML in mussels was significantly higher at the harbour area than at other sites. The integrated biomarker response index values allowed for the differentiation of pollution levels across studied locations representing high, intermediate, and low pollution levels within the studied area.
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46.
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47.
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48.
  • Lehtonen, Kari K., et al. (författare)
  • Development of Tools for Integrated Monitoring and Assessment of Hazardous Substances and Their Biological Effects in the Baltic Sea
  • 2014
  • Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 43:1, s. 69-81
  • Tidskriftsartikel (refereegranskat)abstract
    • The need to develop biological effects monitoring to facilitate a reliable assessment of hazardous substances has been emphasized in the Baltic Sea Action Plan of the Helsinki Commission. An integrated chemical-biological approach is vitally important for the understanding and proper assessment of anthropogenic pressures and their effects on the Baltic Sea. Such an approach is also necessary for prudent management aiming at safeguarding the sustainable use of ecosystem goods and Services. The BEAST project (Biological Effects of Anthropogenic Chemical Stress: Tools for the Assessment of Ecosystem Health) set out to address this topic within the BONUS Programme. BEAST generated a large amount of quality-assured data on several biological effects parameters (biomarkers) in various marine species in different sub-regions of the Baltic Sea. New indicators (biological response measurement methods) and management tools (integrated indices) with regard to the integrated monitoring approach were suggested.
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49.
  • Lehtonen, Liisa, et al. (författare)
  • Family Rooms in Neonatal Intensive Care Units and Neonatal Outcomes : An International Survey and Linked Cohort Study
  • 2020
  • Ingår i: The Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 226, s. 112-117
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the proportion of neonatal intensive care units with facilities supporting parental presence in their infants’ rooms throughout the 24-hour day (ie, infant-parent rooms) in high-income countries and to analyze the association of this with outcomes of extremely preterm infants.Study design: In this survey and linked cohort study, we analyzed unit design and facilities for parents in 10 neonatal networks of 11 countries. We compared the composite outcome of mortality or major morbidity, length of stay, and individual morbidities between neonates admitted to units with and without infant-parent rooms by linking survey responses to patient data from 2015 for neonates of less than 29 weeks of gestation.Results: Of 331 units, 13.3% (44/331) provided infant-parent rooms. Patient-level data were available for 4662 infants admitted to 159 units in 7 networks; 28% of the infants were cared for in units with infant-parent rooms. Neonates from units with infant-parent rooms had lower odds of mortality or major morbidity (aOR, 0.76; 95% CI, 0.64-0.89), including lower odds of sepsis and bronchopulmonary dysplasia, than those from units without infant-parent rooms. The adjusted mean length of stay was 3.4 days shorter (95%, CI –4.7 to −3.1) in the units with infant-parent rooms.Conclusions: The majority of units in high-income countries lack facilities to support parents' presence in their infants' rooms 24 hours per day. The availability vs absence of infant-parent rooms was associated with lower odds of composite outcome of mortality or major morbidity and a shorter length of stay.
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50.
  • Lehtonen, Paula K., et al. (författare)
  • Geographic patterns of genetic differentiation and plumage colour variation are different in the pied flycatcher (Ficedula hypoleuca)
  • 2009
  • Ingår i: Molecular Ecology. - 0962-1083. ; 18:21, s. 4463-4476
  • Tidskriftsartikel (refereegranskat)abstract
    • The pied flycatcher is one of the most phenotypically variable bird species in Europe. The geographic variation in phenotypes has often been attributed to spatial variation in selection regimes that is associated with the presence or absence of the congeneric collared flycatcher. Spatial variation in phenotypes could however also be generated by spatially restricted gene flow and genetic drift. We examined the genetic population structure of pied flycatchers across the breeding range and applied the phenotypic Q(ST) (P(ST))-F(ST) approach to detect indirect signals of divergent selection on dorsal plumage colouration in pied flycatcher males. Allelic frequencies at neutral markers were found to significantly differ among populations breeding in central and southern Europe whereas northerly breeding pied flycatchers were found to be one apparently panmictic group of individuals. Pairwise differences between phenotypic (P(ST)) and neutral genetic distances (F(ST)) were positively correlated after removing the most differentiated Spanish and Swiss populations from the analysis, suggesting that genetic drift may have contributed to the observed phenotypic differentiation in some parts of the pied flycatcher breeding range. Differentiation in dorsal plumage colouration however greatly exceeded that observed at neutral genetic markers, which indicates that the observed pattern of phenotypic differentiation is unlikely to be solely maintained by restricted gene flow and genetic drift.
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