• Childhood cancer survival in Europe 1999-2007: results of EUROCARE-5--a population-based study.

      Gatta, Gemma; Botta, Laura; Rossi, Silvia; Aareleid, Tiiu; Bielska-Lasota, Magdalena; Clavel, Jacqueline; Dimitrova, Nadya; Jakab, Zsuzsanna; Kaatsch, Peter; Lacour, Brigitte; et al. (Elsevier Science Inc, 2014-01)
      Survival and cure rates for childhood cancers in Europe have greatly improved over the past 40 years and are mostly good, although not in all European countries. The EUROCARE-5 survival study estimates survival of children diagnosed with cancer between 2000 and 2007, assesses whether survival differences among European countries have changed, and investigates changes from 1999 to 2007.
    • Clozapine treatment and discontinuation in Iceland: A national longitudinal study using electronic patient records.

      Ingimarsson, Oddur; MacCabe, James H; Haraldsson, Magnús; Jónsdóttir, Halldóra; Sigurdsson, Engilbert; [ 1 ] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland [ 2 ] Landspitali Univ Hosp, Mental Hlth Serv, IS-101 Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 3 ] Kings Coll London, London WC2R 2LS, England [ 4 ] South London & Maudsley NHS Fdn Trust, Bethlem Royal Hosp, Natl Psychosis Unit, London, England (Taylor & Francis Ltd, 2016-08)
      Clozapine is the only drug approved for treatment-resistant schizophrenia. There is evidence that clozapine is underutilized.
    • CNVs conferring risk of autism or schizophrenia affect cognition in controls.

      Stefansson, Hreinn; Meyer-Lindenberg, Andreas; Steinberg, Stacy; Magnusdottir, Brynja; Morgen, Katrin; Arnarsdottir, Sunna; Bjornsdottir, Gyda; Walters, G Bragi; Jonsdottir, Gudrun A; Doyle, Orla M; et al. (NPG, 2014)
      In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.
    • Common variant at 16p11.2 conferring risk of psychosis.

      Steinberg, S; de Jong, S; Mattheisen, M; Costas, J; Demontis, D; Jamain, S; Pietiläinen, O P H; Lin, K; Papiol, S; Huttenlocher, J; et al. (Nature Publishing Group, 2014-01)
      Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).
    • A common variant at 8q24.21 is associated with renal cell cancer.

      Gudmundsson, Julius; Sulem, Patrick; Gudbjartsson, Daniel F; Masson, Gisli; Petursdottir, Vigdis; Hardarson, Sverrir; Gudjonsson, Sigurjon A; Johannsdottir, Hrefna; Helgadottir, Hafdis Th; Stacey, Simon N; et al. (Nature Publishing Group, 2013)
      Renal cell carcinoma (RCC) represents between 80 and 90% of kidney cancers. Previous genome-wide association studies of RCC have identified five variants conferring risk of the disease. Here we report the results from a discovery RCC genome-wide association study and replication analysis, including a total of 2,411 patients and 71,497 controls. One variant, rs35252396[CG] located at 8q24.21, is significantly associated with RCC after combining discovery and replication results (OR=1.27, P(combined)=5.4 × 10(-11)) and has an average risk allele frequency in controls of 46%. rs35252396[CG] does not have any strongly correlated variants in the genome and is located within a region predicted to have regulatory functions in several cell lines, including six originating from the kidney. This is the first RCC variant reported at 8q24.21 and it is largely independent (r(2)≤0.02) of the numerous previously reported cancer risk variants at this locus.
    • Common variants at VRK2 and TCF4 conferring risk of schizophrenia.

      Steinberg, Stacy; de Jong, Simone; Andreassen, Ole A; Werge, Thomas; Børglum, Anders D; Mors, Ole; Mortensen, Preben B; Gustafsson, Omar; Costas, Javier; Pietiläinen, Olli P H; et al. (Oxford University Press, 2011-10-15)
      Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10(-9)] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10(-9)).
    • Common variants conferring risk of schizophrenia.

      Stefansson, Hreinn; Ophoff, Roel A; Steinberg, Stacy; Andreassen, Ole A; Cichon, Sven; Rujescu, Dan; Werge, Thomas; Pietiläinen, Olli P H; Mors, Ole; Mortensen, Preben B; et al. (Nature Publishing Group, 2009-08-06)
      Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
    • A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2.

      Thiele, Ines; Hyduke, Daniel R; Steeb, Benjamin; Fankam, Guy; Allen, Douglas K; Bazzani, Susanna; Charusanti, Pep; Chen, Feng-Chi; Fleming, Ronan M T; Hsiung, Chao A; et al. (BioMed Central Ltd, 2011)
      Metabolic reconstructions (MRs) are common denominators in systems biology and represent biochemical, genetic, and genomic (BiGG) knowledge-bases for target organisms by capturing currently available information in a consistent, structured manner. Salmonella enterica subspecies I serovar Typhimurium is a human pathogen, causes various diseases and its increasing antibiotic resistance poses a public health problem.
    • A community-driven global reconstruction of human metabolism.

      Thiele, Ines; Swainston, Neil; Fleming, Ronan M T; Hoppe, Andreas; Sahoo, Swagatika; Aurich, Maike K; Haraldsdottir, Hulda; Mo, Monica L; Rolfsson, Ottar; Stobbe, Miranda D; et al. (Nature Publishing Group, 2013-05)
      Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including ∼2× more reactions and ∼1.7× more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
    • A compendium of inborn errors of metabolism mapped onto the human metabolic network.

      Sahoo, Swagatika; Franzson, Leifur; Jonsson, Jon J; Thiele, Ines; Center for Systems Biology, University of Iceland, Iceland. (RSC publishing, 2012)
      Inborn errors of metabolism (IEMs) are hereditary metabolic defects, which are encountered in almost all major metabolic pathways occurring in man. Many IEMs are screened for in neonates through metabolomic analysis of dried blood spot samples. To enable the mapping of these metabolomic data onto the published human metabolic reconstruction, we added missing reactions and pathways involved in acylcarnitine (AC) and fatty acid oxidation (FAO) metabolism. Using literary data, we reconstructed an AC/FAO module consisting of 352 reactions and 139 metabolites. When this module was combined with the human metabolic reconstruction, the synthesis of 39 acylcarnitines and 22 amino acids, which are routinely measured, was captured and 235 distinct IEMs could be mapped. We collected phenotypic and clinical features for each IEM enabling comprehensive classification. We found that carbohydrate, amino acid, and lipid metabolism were most affected by the IEMs, while the brain was the most commonly affected organ. Furthermore, we analyzed the IEMs in the context of metabolic network topology to gain insight into common features between metabolically connected IEMs. While many known examples were identified, we discovered some surprising IEM pairs that shared reactions as well as clinical features but not necessarily causal genes. Moreover, we could also re-confirm that acetyl-CoA acts as a central metabolite. This network based analysis leads to further insight of hot spots in human metabolism with respect to IEMs. The presented comprehensive knowledge base of IEMs will provide a valuable tool in studying metabolic changes involved in inherited metabolic diseases.
    • Consensus and conflict cards for metabolic pathway databases.

      Stobbe, Miranda D; Swertz, Morris A; Thiele, Ines; Rengaw, Trebor; van Kampen, Antoine H C; Moerland, Perry D; [ 1 ] Univ Amsterdam, Acad Med Ctr, Bioinformat Lab, NL-1100 DE Amsterdam, Netherlands [ 2 ] Univ Amsterdam, Swammerdam Inst Life Sci, NL-1098 XH Amsterdam, Netherlands [ 3 ] Univ Luxembourg, Luxembourg Ctr Syst Biomed, L-4362 Esch Sur Alzette, Luxembourg [ 4 ] Univ Med Ctr Groningen, Genom Coordinat Ctr, NL-9700 RB Groningen, Netherlands [ 5 ] Univ Groningen, NL-9700 RB Groningen, Netherlands [ 6 ] Netherlands Bioinformat Ctr, NL-6525 GA Nijmegen, Netherlands [ 7 ] Univ Amsterdam, Netherlands Consortium Syst Biol, NL-1090 GE Amsterdam, Netherlands (BioMed Central, 2013)
      The metabolic network of H. sapiens and many other organisms is described in multiple pathway databases. The level of agreement between these descriptions, however, has proven to be low. We can use these different descriptions to our advantage by identifying conflicting information and combining their knowledge into a single, more accurate, and more complete description. This task is, however, far from trivial.
    • Contextualization procedure and modeling of monocyte specific TLR signaling.

      Aurich, Maike K; Thiele, Ines; [ 1 ] Univ Iceland, Ctr Syst Biol, Reykjavik, Iceland, Univ Iceland, Fac Ind Engn Mech Engn & Comp Sci, Reykjavik, Iceland (Public Library Science, 2012)
      Innate immunity is the first line of defense against invasion of pathogens. Toll-like receptor (TLR) signaling is involved in a variety of human diseases extending far beyond immune system-related diseases, affecting a number of different tissues and cell-types. Computational models often do not account for cell-type specific differences in signaling networks. Investigation of these differences and its phenotypic implications could increase understanding of cell signaling and processes such as inflammation. The wealth of knowledge for TLR signaling has been recently summarized in a stoichiometric signaling network applicable for constraint-based modeling and analysis (COBRA). COBRA methods have been applied to investigate tissue-specific metabolism using omics data integration. Comparable approaches have not been conducted using signaling networks. In this study, we present ihsTLRv2, an updated TLR signaling network accounting for the association of 314 genes with 558 network reactions. We present a mapping procedure for transcriptomic data onto signaling networks and demonstrate the generation of a monocyte-specific TLR network. The generated monocyte network is characterized through expression of a specific set of isozymes rather than reduction of pathway contents. While further tailoring the network to a specific stimulation condition, we observed that the quantitative changes in gene expression due to LPS stimulation affected the tightly connected set of genes. Differential expression influenced about one third of the entire TLR signaling network, in particular, NF-κB activation. Thus, a cell-type and condition-specific signaling network can provide functional insight into signaling cascades. Furthermore, we demonstrate the energy dependence of TLR signaling pathways in monocytes.
    • Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene.

      Luo, X-J; Li, M; Huang, L; Steinberg, S; Mattheisen, M; Liang, G; Donohoe, G; Shi, Y; Chen, C; Yue, W; et al. (Nature Publishing Group, 2014-07)
      Genes that are differentially expressed between schizophrenia patients and healthy controls may have key roles in the pathogenesis of schizophrenia. We analyzed two large-scale genome-wide expression studies, which examined changes in gene expression in schizophrenia patients and their matched controls. We found calcium/calmodulin (CAM)-dependent protein kinase kinase 2 (CAMKK2) is significantly downregulated in individuals with schizophrenia in both studies. To seek the potential genetic variants that may regulate the expression of CAMKK2, we investigated the association between single-nucleotide polymorphisms (SNPs) within CAMKK2 and the expression level of CAMKK2. We found one SNP, rs1063843, which is located in intron 17 of CAMKK2, is strongly associated with the expression level of CAMKK2 in human brains (P=1.1 × 10(-6)) and lymphoblastoid cell lines (the lowest P=8.4 × 10(-6)). We further investigated the association between rs1063843 and schizophrenia in multiple independent populations (a total of 130 623 subjects) and found rs1063843 is significantly associated with schizophrenia (P=5.17 × 10(-5)). Interestingly, we found the T allele of rs1063843, which is associated with lower expression level of CAMKK2, has a higher frequency in individuals with schizophrenia in all of the tested samples, suggesting rs1063843 may be a causal variant. We also found that rs1063843 is associated with cognitive function and personality in humans. In addition, protein-protein interaction (PPI) analysis revealed that CAMKK2 participates in a highly interconnected PPI network formed by top schizophrenia genes, which further supports the potential role of CAMKK2 in the pathogenesis of schizophrenia. Taken together, these converging lines of evidence strongly suggest that CAMKK2 may have pivotal roles in schizophrenia susceptibility.
    • Convergent validity of the interRAI-HC for societal costs estimates in comparison with the RUD Lite instrument in community dwelling older adults.

      van Lier, Lisanne I; van der Roest, Henriëtte G; van Hout, Hein P J; van Eenoo, Liza; Declercq, Anja; Garms-Homolová, Vjenka; Onder, Graziano; Finne-Soveri, Harriet; Jónsson, Pálmi V; Hertogh, Cees M P M; et al. (BioMed Central, 2016)
      The interRAI-Home Care (interRAI-HC) instrument is commonly used in routine care to assess care and service needs, resource utilisation and health outcomes of community dwelling home care clients. Potentially, the interRAI-HC can also be used to calculate societal costs in economic evaluations. The purpose of this study was to assess the convergent validity of the interRAI-HC instrument in comparison with the RUD Lite instrument for the calculation of societal costs among care-dependent community dwelling older adults.
    • Decoding the jargon of bottom-up metabolic systems biology.

      Rolfsson, Óttar; Palsson, Bernhard O; Univ Iceland, Ctr Syst Biol, Reykjavik, Iceland, Univ Iceland, Biomed Ctr, Reykjavik, Iceland (Wiley-Blackwell, 2015-06)
    • Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.

      Liu, Jimmy Z; Hov, Johannes Roksund; Folseraas, Trine; Ellinghaus, Eva; Rushbrook, Simon M; Doncheva, Nadezhda T; Andreassen, Ole A; Weersma, Rinse K; Weismüller, Tobias J; Eksteen, Bertus; et al. (Nature Publishing Group, 2013-06)
      Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
    • A detailed genome-wide reconstruction of mouse metabolism based on human Recon 1

      Sigurdsson, Martin I; Jamshidi, Neema; Steingrimsson, Eirikur; Thiele, Ines; Palsson, Bernhard Ø; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (BioMed Central Ltd., 2010-10)
      BACKGROUND: Well-curated and validated network reconstructions are extremely valuable tools in systems biology. Detailed metabolic reconstructions of mammals have recently emerged, including human reconstructions. They raise the question if the various successful applications of microbial reconstructions can be replicated in complex organisms. RESULTS: We mapped the published, detailed reconstruction of human metabolism (Recon 1) to other mammals. By searching for genes homologous to Recon 1 genes within mammalian genomes, we were able to create draft metabolic reconstructions of five mammals, including the mouse. Each draft reconstruction was created in compartmentalized and non-compartmentalized version via two different approaches. Using gap-filling algorithms, we were able to produce all cellular components with three out of four versions of the mouse metabolic reconstruction. We finalized a functional model by iterative testing until it passed a predefined set of 260 validation tests. The reconstruction is the largest, most comprehensive mouse reconstruction to-date, accounting for 1,415 genes coding for 2,212 gene-associated reactions and 1,514 non-gene-associated reactions.We tested the mouse model for phenotype prediction capabilities. The majority of predicted essential genes were also essential in vivo. However, our non-tissue specific model was unable to predict gene essentiality for many of the metabolic genes shown to be essential in vivo. Our knockout simulation of the lipoprotein lipase gene correlated well with experimental results, suggesting that softer phenotypes can also be simulated. CONCLUSIONS: We have created a high-quality mouse genome-scale metabolic reconstruction, iMM1415 (Mus Musculus, 1415 genes). We demonstrate that the mouse model can be used to perform phenotype simulations, similar to models of microbe metabolism. Since the mouse is an important experimental organism, this model should become an essential tool for studying metabolic phenotypes in mice, including outcomes from drug screening.
    • Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy.

      Zuidmeer-Jongejan, Laurian; Huber, Hans; Swoboda, Ines; Rigby, Neil; Versteeg, Serge A; Jensen, Bettina M; Quaak, Suzanne; Akkerdaas, Jaap H; Blom, Lars; Asturias, Juan; et al. (Karger, 2015)
      The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1.
    • DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

      Osorio, Ana; Milne, Roger L; Kuchenbaecker, Karoline; Vaclová, Tereza; Pita, Guillermo; Alonso, Rosario; Peterlongo, Paolo; Blanco, Ignacio; de la Hoya, Miguel; Duran, Mercedes; et al. (Public Library Science, 2014-04)
      Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
    • The effect of fontanel on scalp EEG potentials in the neonate.

      Gargiulo, P; Belfiore, P; Friðgeirsson, E A; Vanhatalo, S; Ramon, C; [ 1 ] Reykjavik Univ, Inst Biomed & Neural Engn, Reykjavik, Iceland [ 2 ] Landspitali Univ Hosp, Dept Sci, Reykjavik, Iceland [ 3 ] Univ Naples Federico II, Dept Biomed Elect & Telecommun Engn, Naples, Italy [ 4 ] Landspitali Univ Hosp, Dept Dev CE & IT, Reykjavik, Iceland [ 5 ] Univ Helsinki, Cent Hosp, HUS Med Imaging Ctr, Dept Childrens Clin Neurophysiol, Helsinki, Finland [ 6 ] Univ Helsinki, Cent Hosp, Childrens Hosp, Helsinki, Finland [ 7 ] Univ Helsinki, Helsinki, Finland [ 8 ] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA (Elsevier, 2015-09)
      To define how fontanels affect scalp EEG potentials in neonates.