Climate-controlled submarine landslides on the Antarctic continental margin

Antarctica’s continental margins pose an unknown submarine landslidegenerated tsunami risk to Southern Hemisphere populations and infrastructure. Understanding the factors driving slope failure is essential to assessing future geohazards. Here, we present a multidisciplinary study of a major submarine landslide complex along the eastern Ross Sea continental slope (Antarctica) that identifies preconditioning factors and failure mechanisms. Weak layers, identified beneath three submarine landslides, consist of distinct packages of interbedded Miocene- to Pliocene-age diatom oozes and glaciomarine diamicts. The observed lithological differences, which arise from glacial to interglacial variations in biological productivity, ice proximity, and ocean circulation, caused changes in sediment deposition that inherently preconditioned slope failure. These recurrent Antarctic submarine landslides were likely triggered by seismicity associated with glacioisostatic readjustment, leading to failure within the preconditioned weak layers. Ongoing climate warming and ice retreat may increase regional glacioisostatic seismicity, triggering Antarctic submarine landslides

Three-weekly doses of azithromycin for Indigenous infants hospitalized with bronchiolitis: a multicentre, randomized, placebo-controlled trial

Background: Bronchiolitis is a major health burden in infants globally, particularly among Indigenous populations. It is unknown if 3 weeks of azithromycin improve clinical outcomes beyond the hospitalization period. In an international, double-blind randomized controlled trial, we determined if 3 weeks of azithromycin improved clinical outcomes in Indigenous infants hospitalized with bronchiolitis.Methods: Infants aged ≤24 months were enrolled from three centers and randomized to receive three once-weekly doses of either azithromycin (30 mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48 h later. Primary endpoints were hospital length of stay (LOS) and duration of oxygen supplementation monitored every 12 h until judged ready for discharge. Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalizations within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48 h.Results: Two hundred nineteen infants were randomized (n = 106 azithromycin, n = 113 placebo). No significant between-group differences were found for LOS (median 54 h for each group, difference = 0 h, 95% CI: −6, 8; p = 0.8), time receiving oxygen (azithromycin = 40 h, placebo = 35 h, group difference = 5 h, 95% CI: −8, 11; p = 0.7), day-21 symptom/signs, or rehospitalization within 6 months (azithromycin n = 31, placebo n = 25 infants, p = 0.2). Azithromycin reduced nasopharyngeal bacterial carriage (between-group difference 0.4 bacteria/child, 95% CI: 0.2, 0.6; p < 0.001), but had no significant effect upon virus detection rates.Conclusion: Despite reducing nasopharyngeal bacterial carriage, three large once-weekly doses of azithromycin did not confer any benefit over placebo during the bronchiolitis illness or 6 months post hospitalization. Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis.Clinical trial registration: The trial was registered with the Australian and New Zealand Clinical Trials Register: Clinical trials number: ACTRN1261000036099

Genetic and Non-Genetic Influences during Pregnancy on Infant Global and Site Specific DNA Methylation: Role for Folate Gene Variants and Vitamin B12

Inter-individual variation in patterns of DNA methylation at birth can be explained by the influence of environmental, genetic and stochastic factors. This study investigates the genetic and non-genetic determinants of variation in DNA methylation in human infants. Given its central role in provision of methyl groups for DNA methylation, this study focuses on aspects of folate metabolism. Global (LUMA) and gene specific (IGF2, ZNT5, IGFBP3) DNA methylation were quantified in 430 infants by Pyrosequencing®. Seven polymorphisms in 6 genes (MTHFR, MTRR, FOLH1, CβS, RFC1, SHMT) involved in folate absorption and metabolism were analysed in DNA from both infants and mothers. Red blood cell folate and serum vitamin B12 concentrations were measured as indices of vitamin status. Relationships between DNA methylation patterns and several covariates viz. sex, gestation length, maternal and infant red cell folate, maternal and infant serum vitamin B12, maternal age, smoking and genotype were tested. Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p = 0.032) and inversely with ZNT5 methylation (rho = −0.13, p = 0.017). Methylation of the IGFBP3 locus correlated inversely with infant vitamin B12 concentration (rho = −0.16, p = 0.007), whilst global DNA methylation correlated inversely with maternal vitamin B12 concentrations (rho = 0.18, p = 0.044). Analysis of common genetic variants in folate pathway genes highlighted several associations including infant MTRR 66G>A genotype with DNA methylation (χ2 = 8.82, p = 0.003) and maternal MTHFR 677C>T genotype with IGF2 methylation (χ2 = 2.77, p = 0.006). These data support the hypothesis that both environmental and genetic factors involved in one-carbon metabolism influence DNA methylation in infants. Specifically, the findings highlight the importance of vitamin B12 status, infant MTRR genotype and maternal MTHFR genotype, all of which may influence the supply of methyl groups for DNA methylation. In addition, gestational length appears to be an important determinant of infant DNA methylation patterns

Chronostratigraphic Framework for the IODP Expedition 318 Cores from the Wilkes Land Margin: Constraints for Paleoceanographic Reconstruction

[1] The Integrated Ocean Drilling Program Expedition 318 to the Wilkes Land margin of Antarctica recovered a sedimentary succession ranging in age from lower Eocene to the Holocene. Excellent stratigraphic control is key to understanding the timing of paleoceanographic events through critical climate intervals. Drill sites recovered the lower and middle Eocene, nearly the entire Oligocene, the Miocene from about 17 Ma, the entire Pliocene and much of the Pleistocene. The paleomagnetic properties are generally suitable for magnetostratigraphic interpretation, with well‐behaved demagnetization diagrams, uniform distribution of declinations, and a clear separation into two inclination modes. Although the sequences were discontinuously recovered with many gaps due to coring, and there are hiatuses from sedimentary and tectonic processes, the magnetostratigraphic patterns are in general readily interpretable. Our interpretations are integrated with the diatom, radiolarian, calcareous nannofossils and dinoflagellate cyst (dinocyst) biostratigraphy. The magnetostratigraphy significantly improves the resolution of the chronostratigraphy, particularly in intervals with poor biostratigraphic control. However, Southern Ocean records with reliable magnetostratigraphies are notably scarce, and the data reported here provide an opportunity for improved calibration of the biostratigraphic records. In particular, we provide a rare magnetostratigraphic calibration for dinocyst biostratigraphy in the Paleogene and a substantially improved diatom calibration for the Pliocene. This paper presents the stratigraphic framework for future paleoceanographic proxy records which are being developed for the Wilkes Land margin cores. It further provides tight constraints on the duration of regional hiatuses inferred from seismic surveys of the region

Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated

The purple line as a measure of labour progress: a longitudinal study

Background: Vaginal examination (VE) and assessment of the cervix is currently considered to be the gold standard for assessment of labour progress. It is however inherently imprecise with studies indicating an overall accuracy for determining the diameter of the cervix at between 48-56%. Furthermore, VEs can be unpleasant, intrusive and embarrassing for women, and are associated with the risk of introducing infection. In light of increasing concern world wide about the use of routine interventions in labour it may be time to consider alternative, less intrusive means of assessing progress in labour. The presence of a purple line during labour, seen to rise from the anal margin and extend between the buttocks as labour progresses has been reported. The study described in this paper aimed to assess in what percentage of women in labour a purple line was present, clear and measurable and to determine if any relationship existed between the length of the purple line and cervical dilatation and/or station of the fetal head. Methods: This longitudinal study observed 144 women either in spontaneous labour (n=112) or for induction of labour (n=32) from admission through to final VE. Women were examined in the lateral position and midwives recorded the presence or absence of the line throughout labour immediately before each VE. Where present, the length of the line was measured using a disposable tape measure. Within subjects correlation, chi-squared test for independence, and independent samples t-test were used to analyse the data. Results: The purple line was seen at some point in labour for 109 women (76%). There was a medium positive correlation between length of the purple line and cervical dilatation (r=+0.36, n=66, P=0.0001) and station of the fetal head (r=+0.42, n=56, P<0.0001). Conclusions: The purple line does exist and there is a medium positive correlation between its length and both cervical dilatation and station of the fetal head. Where the line is present, it may provide a useful guide for clinicians of labour progress along side other measures. Further research is required to assess whether measurement of the line is acceptable to women in labour and also clinicians

Climate-controlled submarine landslides on the Antarctic continental margin

Antarctica’s continental margins pose an unknown submarine landslide-generated tsunami risk to Southern Hemisphere populations and infrastructure. Understanding the factors driving slope failure is essential to assessing future geohazards. Here, we present a multidisciplinary study of a major submarine landslide complex along the eastern Ross Sea continental slope (Antarctica) that identifies preconditioning factors and failure mechanisms. Weak layers, identified beneath three submarine landslides, consist of distinct packages of interbedded Miocene- to Pliocene-age diatom oozes and glaciomarine diamicts. The observed lithological differences, which arise from glacial to interglacial variations in biological productivity, ice proximity, and ocean circulation, caused changes in sediment deposition that inherently preconditioned slope failure. These recurrent Antarctic submarine landslides were likely triggered by seismicity associated with glacioisostatic readjustment, leading to failure within the preconditioned weak layers. Ongoing climate warming and ice retreat may increase regional glacioisostatic seismicity, triggering Antarctic submarine landslides

Early Emergence of Ethnic Differences in Type 2 Diabetes Precursors in the UK: The Child Heart and Health Study in England (CHASE Study)

Peter Whincup and colleagues carry out a cross-sectional study examining ethnic differences in precursors of of type 2 diabetes among children aged 9–10 living in three UK cities

Novel Anti-Metastatic Action of Cidofovir Mediated by Inhibition of E6/E7, CXCR4 and Rho/ROCK Signaling in HPV+ Tumor Cells

Cervical cancer is frequently associated with HPV infection. The expression of E6 and E7 HPV oncoproteins is a key factor in its carcinogenicity and might also influence its virulence, including metastatic conversion. The cellular mechanisms involved in metastatic spread remain elusive, but pro-adhesive receptors and their ligands, such as SDF-1α and CXCR4 are implicated. In the present study, we assessed the possible relationship between SDF-1α/CXCR4 signaling, E6/E7 status and the metastatic process. We found that SDF-1α stimulated the invasion of E6/E7-positive cancer cell lines (HeLa and TC-1) in Matrigel though CXCR4 and subsequent Rho/ROCK activation. In pulmonary metastatic foci generated by TC-1 cells IV injection a high proportion of cells expressed membrane-associated CXCR4. In both cases models (in vitro and in vivo) cell adhesion and invasion was abrogated by CXCR4 immunological blockade supporting a contribution of SDF-1α/CXCR4 to the metastatic process. E6 and E7 silencing using stable knock-down and the approved anti-viral agent, Cidofovir decreased CXCR4 gene expression as well as both, constitutive and SDF-1α-induced cell invasion. In addition, Cidofovir inhibited lung metastasis (both adhesion and invasion) supporting contribution of E6 and E7 oncoproteins to the metastatic process. Finally, potential signals activated downstream SDF-1α/CXCR4 and involved in lung homing of E6/E7-expressing tumor cells were investigated. The contribution of the Rho/ROCK pathway was suggested by the inhibitory effect triggered by Cidofovir and further confirmed using Y-27632 (a small molecule ROCK inhibitor). These data suggest a novel and highly translatable therapeutic approach to cervix cancer, by inhibition of adhesion and invasion of circulating HPV-positive tumor cells, using Cidofovir and/or ROCK inhibition

KiDS+GAMA:The weak lensing calibrated stellar-to-halo mass relation of central and satellite galaxies

We simultaneously present constraints on the stellar-to-halo mass relation for central and satellite galaxies through a weak lensing analysis of spectroscopically classified galaxies. Using overlapping data from the fourth data release of the Kilo-Degree Survey (KiDS), and the Galaxy And Mass Assembly survey (GAMA), we find that satellite galaxies are hosted by halo masses that are $0.53 \pm 0.39$ dex (68\% confidence, $3\sigma$ detection) smaller than those of central galaxies of the same stellar mass (for a stellar mass of $\log(M_{\star}/M_{\odot}) = 10.6$). This is consistent with galaxy formation models, whereby infalling satellite galaxies are preferentially stripped of their dark matter. We find consistent results with similar uncertainties when comparing constraints from a standard azimuthally averaged galaxy-galaxy lensing analysis and a two-dimensional likelihood analysis of the full shear field. As the latter approach is somewhat biased due to the lens incompleteness and as it does not provide any improvement to the precision when applied to actual data, we conclude that stacked tangential shear measurements are best-suited for studies of the galaxy-halo connection.Comment: 12 pages, 10 figures, accepted for publication in A&