Skin barrier function and Staphylococcus aureus colonization in vestibulum nasi and fauces in healthy infants and infants with eczema: A population-based cohort study

Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants

Identification of putative pathogenic single nucleotide variants (SNVs) in genes associated with heart disease in 290 cases of stillbirth

The incidence of stillbirth in Sweden has essentially remained constant since the 1980s, and despite thorough investigation, many cases remain unexplained. It has been suggested that a proportion of stillbirth cases is caused by heart disease, mainly channelopathies. The aim of this study was to analyze DNA from 290 stillbirth cases without chromosomal abnormalities for pathogenic single nucleotide variants (SNVs) in 70 genes associated with cardiac channelopathies and cardiomyopathies. The HaloPlex Target Enrichment System (Agilent Technologies) was utilized to prepare sequencing libraries which were sequenced on the Illumina NextSeq platform. We found that 12.1% of the 290 investigated stillbirth cases had one (n = 31) or two (n = 4) variants with evidence supporting pathogenicity, i.e. loss-of-function variants (nonsense, frameshift, splice site substitutions), evidence from functional studies, or previous identification of the variants in affected individuals. Regarding identified putative pathogenic variants in genes associated with channelopathies, the prevalence was significantly higher in the stillbirth cohort (n = 23, 7.93%) than the corresponding prevalence of the same variants in the non-Finnish European population of the Exome Aggregation Consortium (2.70%, pamp;lt;0.001) and SweGen, (2.30%, pamp;lt;0.001). Our results give further support to the hypothesis that cardiac channelopathies might contribute to stillbirth. Screening for pathogenic SNVs in genes associated with heart disease might be a valuable complement for stillbirth cases where todays conventional investigation does not reveal the underlying cause of fetal demise.Funding Agencies|FORSS, Forskningsradet i sydostra Sverige (the Medical Research Council of Southeast Sweden) [FORSS-307961]; Stockholms Ians landsting (Stockholm County Council) [SLL20160339]</p

Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization

Clustered copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) are often reported as germline chromothripsis. However, such cases might need further investigations by massive parallel whole genome sequencing (WGS) in order to accurately define the underlying complex rearrangement, predict the occurrence mechanisms and identify additional complexities. Here, we utilized WGS to delineate the rearrangement structure of 21 clustered CNV carriers first investigated by CMA and identified a total of 83 breakpoint junctions (BPJs). The rearrangements were further sub-classified depending on the patterns observed: I) Cases with only deletions (n = 8) often had additional structural rearrangements, such as insertions and inversions typical to chromothripsis; II) cases with only duplications (n = 7) or III) combinations of deletions and duplications (n = 6) demonstrated mostly interspersed duplications and BPJs enriched with microhomology. In two cases the rearrangement mutational signatures indicated both a breakage-fusion-bridge cycle process and haltered formation of a ring chromosome. Finally, we observed two cases with Alu- and LINE-mediated rearrangements as well as two unrelated individuals with seemingly identical clustered CNVs on 2p25.3, possibly a rare European founder rearrangement. In conclusion, through detailed characterization of the derivative chromosomes we show that multiple mechanisms are likely involved in the formation of clustered CNVs and add further evidence for chromoanagenesis mechanisms in both "simple" and highly complex chromosomal rearrangements. Finally, WGS characterization adds positional information, important for a correct clinical interpretation and deciphering mechanisms involved in the formation of these rearrangements.Peer reviewe

Regulatory convergence in EU securities regulation

The aim of the thesis is to map out and critically discuss the very recent phenomenon of 'regulatory convergence' in EU securities regulation. 'Regulatory convergence' is a new development in EU governance in financial services and markets regulation following the Financial Services Action Plan 1999 and the Lamfalussy Report of 2001. Regulatory convergence has 2 aspects, Le. 'regulatory' and 'convergence'. The thesis suggests that the 'regulatory' aspect may be looked at in 4 parts, namely the source ofregulation, the administration ofregulation, the supervision ofregulation, and the enforcement of the regulation. The thesis maps out and critically discusses each area ofregulatory convergence in EU securities regulation, and the methodologies employed by policy and law-makers in securing convergence, which include EU legislation, Commission legislation and 'soft law' produced by the Committee of European Securities Regulators. In particular, a cybernetic model ofanalysis is applied to discuss each aspect of regulation, and the methodologies used in securing 'convergence'. The application ofthe cybernetic model of analysis to the 4 aspects of regulatory convergence allows the drawing of some conclusions about the prospects of regulatory convergence. The thesis also examines whether and to what extent, there is an EU level regulatory system for ED securities regulation, and in the absence of such an ED level system for securities regulation, what forces or incentives would induce Member States to adopt divergent national regulation. The final chapter of the thesis explores theoretical frameworks in organisation theory to suggest how creating an EU agency for securities regulation may address the deficits in the current framework for securing regulatory convergence and lead the way forward to a cybernetically sufficient system for regulatory convergence in EU securities regulation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Characteristics.

<p>Characteristics of 240 infants, recruited from the general population in Oslo and Fredrikstad, Norway, of whom 167 were included and 73 excluded from the analyses. Exclusions were done due to crying during the measuring transepidermal water loss (n = 7) and/or measuring conditions not fulfilling strict environmental criteria for humidity and/or temperature (n = 66). All values are given as number (percentage), unless otherwise stated.</p><p>Characteristics.</p

Transepidermal waterloss and <i>filaggrin</i> mutation.

<p>Boxplot showing <i>filaggrin</i> (<i>FLG</i>) mutation identified in 14 (8%) of 167 infants recruited from the general population and transepidermal water loss (TEWL; g/m²h^-1) on the lateral upper arm. <i>FLG</i> mutations were associated with increased TEWL (p = 0.006).</p

Characteristics.

<p>Characteristics of 240 infants, recruited from the general population in Oslo and Fredrikstad, Norway, of whom 167 were included and 73 excluded from the analyses. Exclusions were done due to crying during the measuring transepidermal water loss (n = 7) and/or measuring conditions not fulfilling strict environmental criteria for humidity and/or temperature (n = 66). All values are given as number (percentage), unless otherwise stated.</p><p>Characteristics.</p