Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes: A meta-analysis of observational studies

Aims/hypothesis: The aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the published literature and performing a meta-analysis with adjustment for recognised confounders.
Methods: After MEDLINE, Web of Science and EMBASE searches, crude ORs and 95% CIs for type 1 diabetes in children born by Caesarean section were calculated from the data reported in each study. Authors were contacted to facilitate adjustments for potential confounders, either by supplying raw data or calculating adjusted estimates. Meta-analysis techniques were then used to derive combined ORs and to investigate heterogeneity between studies.
Results: Twenty studies were identified. Overall, there was a significant increase in the risk of type 1 diabetes in children born by Caesarean section (OR 1.23, 95% CI 1.15-1.32, p<0.001). There was little evidence of heterogeneity between studies (p=0.54). Seventeen authors provided raw data or adjusted estimates to facilitate adjustments for potential confounders. In these studies, there was evidence of an increase in diabetes risk with greater birthweight, shorter gestation and greater maternal age. The increased risk of type 1 diabetes after Caesarean section was little altered after adjustment for gestational age, birth weight, maternal age, birth order, breast-feeding and maternal diabetes (adjusted OR 1.19, 95% CI 1.04-1.36, p=0.01).
Conclusions/interpretation: This analysis demonstrates a 20% increase in the risk of childhood-onset type 1 diabetes after Caesarean section delivery that cannot be explained by known confounders.

Robust Dynamic Pricing Over Infinite Horizon in The Presence of Model Uncertainty( 2* Journal)

This paper studies a problem of dynamic pricing faced by a retailer with limited inventory, uncertain about the demand rate model, aiming to maximize expected discounted revenue over an infinite time horizon. The retailer doubts his demand model which is generated by historical data and views it as an approximation. Uncertainty in the demand rate model is represented by a notion of generalized relative entropy process, and the robust pricing problem is formulated as a two-player zero-sum stochastic differential game. The pricing policy is obtained through the Hamilton-Jacobi-Isaacs (HJI) equation. The existence and uniqueness of the solution of the HJI equation is shown and a verification theorem is proved to show that the solution of the HJI equation is indeed the value function of the pricing problem. The results are illustrated by an example with exponential nominal demand rate.

Correlating Alpine glaciation with Adriatic sea-level changes through lake and alluvial stratigraphy

We compare lake and alluvial stratigraphy along a frame connecting the southern Alpine foothills and the Adriatic Sea, with the aim of matching the effects of Alpine glaciation and sea-level changes on sedimentation during the last glacial cycle. The palynostratigraphy of Lake Fimon provided proxies for regional vegetation and climate change and was coupled with sediment petrography, loss on ignition and magnetic susceptibility, disentangling alluvial phases from fluvioglacial activity related to culminations of the southeastern Alpine glaciers. The Fimon area was not reached by alluvial fans during the penultimate glacial maximum, nor by the sea transgression during the last interglacial, but a closed lake soon developed at the Eemian onset due to enhanced rainfall. Sea-level fall at glacial inception triggered the entrenchment of the drainage network in the plain reaching the outer Fimon Basin. Slow aggradation, but no sign of fluvioglacial activity, lasted to 38.2 +/- 1.45 cal. ka BP, when a major forest withdrawal took place, coeval to the spread of alluvial fans. By 27.5 perpendicular to 0.5 cal. ka BP the Fimon Basin was dammed by the Brenta outwash system. The main step of of forest recovery commenced at around (15.8) cal. ka BP, when apex trenching of the outwash fans was triggered by the glacier's decay. Copyright (C) 2011 John Wiley & Sons, Ltd.

Mass limits for the progenitor star of supernova 2001du and other Type II-P supernovae

The supernova SN 2001du was discovered in the galaxy NGC 1365 at a distance of 19 +/- 2 Mpc, and is a core-collapse event of Type II-P. Images of this galaxy, of moderate depth, have been taken with the Hubble Space Telescope approximately 6.6 yr before discovery and include the supernova position on the WFPC2 field of view. We have observed the supernova with the WFPC2 to allow accurate differential astrometry of SN 2001du on the pre-explosion frames. As a core-collapse event it is expected that the progenitor was a massive, luminous star. There is a marginal detection (3sigma) of a source close to the supernova position on the pre-discovery V -band frame, but it is not precisely coincident and we do not believe it to be a robust detection of a point source. We conclude that there is no stellar progenitor at the supernova position and derive sensitivity limits of the pre-discovery images that provide an upper mass limit for the progenitor star. We estimate that the progenitor had a mass of less than 15 M-circle dot . We revisit two other nearby Type II-P supernovae that have high-quality pre-explosion images, and refine the upper mass limits for the progenitor stars. Using a new distance determination for SN 1999gi from the expanding photosphere method, we revise the upper mass limit to 12 M-circle dot . We present new HST images of the site of SN 1999em, which validate the use of lower spatial resolution ground-based images in the progenitor studies and use a new Cepheid distance to the galaxy to measure an upper mass limit of 15 M-circle dot for that progenitor. Finally we compile all the direct information available for the progenitors of eight nearby core-collapse supernovae and compare their mass estimates. These are compared with the latest stellar evolutionary models of pre-supernova evolution which have attempted to relate metallicity and mass to the supernovae type. Although this is statistically limited at present, reasonable agreement is already found for the lower-mass events (generally the II-P), but some discrepancies appear at higher masses.

A focused ultrasoft X-ray microbeam for targeting cells individually with submicrometer accuracy

The application of microbeams is providing new insights into the actions of radiation at the cell and tissue levels. So far, this has been achieved exclusively through the use of collimated charged particles. One alternative is to use ultrasoft X rays, focused by X-ray diffractive optics. We have developed a unique facility that uses 0.2-0.8-mm-diameter zone plates to focus ultrasoft X rays to a beam of less than 1 mum diameter. The zone plate images characteristic K-shell X rays of carbon or aluminum, generated by focusing a beam of 5-10 keV electrons onto the appropriate target. By reflecting the X rays off a grazing-incidence mirror, the contaminating bremsstrahlung radiation is reduced to 2%. The focused X rays are then aimed at selected subcellular targets using rapid automated cell-finding and alignment procedures; up to 3000 cells per hour can be irradiated individually using this arrangement. (C) 2001 by Radiation Research Society.

Long-term bone marrow culture profiles in patients with myelodysplastic syndromes are not explicable by defective apoptosis

It has been suggested that increased intramedullary apoptosis may explain the paradox between peripheral blood cytopenias and the hyper- or normo-cellular bone marrow observed in the myelodysplastic syndromes (MDS). We wished to see if culture performance could be related to the presence of apoptotic cells in a group of patients with MDS (12 patients) and other patients with peripheral blood cytopenias (six patients) which caused diagnostic difficulty. There was no correlation between LTBMC or adherent cell growth and the presence of apoptotic cells in the original marrow sample. A variable degree of apoptosis was observed in both groups of patients. LTBMC profiles correlated well with diagnosis but were unrelated to the extent of intramedullary apoptosis. This suggests that apoptosis is a much more ubiquitous process in disease than previously thought. (C) 1998 Elsevier Science Ltd. All rights reserved.

Concrete building blocks made with recycled demolition aggregate

A study undertaken at the University of Liverpool has investigated the potential for using recycled demolition aggregate in the manufacture of precast concrete building blocks. Recycled aggregates derived from construction and demolition waste (C&DW) can be used to replace quarried limestone aggregate, usually used in coarse (6 mm) and fine (4 mm-to-dust) gradings. The manufacturing process used in factories, for large-scale production, involves a “vibro-compaction” casting procedure, using a relatively dry concrete mix with low cement content (˜100 kg/m3). Trials in the laboratory successfully replicated the manufacturing process using a specially modified electric hammer drill to compact the concrete mix into oversize steel moulds to produce blocks of the same physical and mechanical properties as the commercial blocks. This enabled investigations of the effect of partially replacing newly quarried with recycled demolition aggregate on the compressive strength of building blocks to be carried out in the laboratory. Levels of replacement of newly quarried with recycled demolition aggregate have been determined that will not have significant detrimental effect on the mechanical properties. Factory trials showed that there were no practical problems with the use of recycled demolition aggregate in the manufacture of building blocks. The factory strengths obtained confirmed that the replacement levels selected, based on the laboratory work, did not cause any significant strength reduction, i.e. there was no requirement to increase the cement content to maintain the required strength, and therefore there would be no additional cost to the manufacturers if they were to use recycled demolition aggregate for their routine concrete building block production.

Common Themes in Glycoconjugate Assembly Using the Biogenesis of O-Antigen Lipopolysaccharide as a Model System

The biosynthesis of glycoconjugates is remarkably conserved in all types of cells since the biochemical reactions involved exhibit similar characteristics, which can be summarized as follows: (a) the saccharide moiety is formed as a lipid-linked, membrane-associated glycan; (b) the lipid component in most cases is a polyisoprenoid phosphate; (c) the assembly of the lipid-linked saccharide intermediate depends on reactions taking place at both sides of the cell membrane, which requires the obligatory transmembrane movement of amphipathic molecules across the lipid bilayer. These general characteristics are present in the biosynthesis of the O-antigen component of the bacterial lipopolysaccharide, which serves as a model system to investigate the molecular and mechanistic basis of glycoconjugate synthesis, as summarized in this mini-review.

Genome-wide association study of Alzheimer's disease with psychotic symptoms

Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysis of three genome-wide association studies (GWASs) to identify loci that (1) increase susceptibility to an AD and subsequent psychotic symptoms; or (2) modify risk of psychotic symptoms in the presence of neurodegeneration caused by AD. In all, 1299 AD cases with psychosis (AD+P), 735 AD cases without psychosis (AD-P) and 5659 controls were drawn from Genetic and Environmental Risk in AD Consortium 1 (GERAD1), the National Institute on Aging Late-Onset Alzheimer's Disease (NIA-LOAD) family study and the University of Pittsburgh Alzheimer Disease Research Center (ADRC) GWASs. Unobserved genotypes were imputed to provide data on >1.8 million single-nucleotide polymorphisms (SNPs). Analyses in each data set were completed comparing (1) AD+P to AD-P cases, and (2) AD+P cases with controls (GERAD1, ADRC only). Aside from the apolipoprotein E (APOE) locus, the strongest evidence for association was observed in an intergenic region on chromosome 4 (rs753129; 'AD+PvAD-P' P=2.85 × 10(-7); 'AD+PvControls' P=1.11 × 10(-4)). SNPs upstream of SLC2A9 (rs6834555, P=3.0 × 10(-7)) and within VSNL1 (rs4038131, P=5.9 × 10(-7)) showed strongest evidence for association with AD+P when compared with controls. These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterized.Molecular Psychiatry advance online publication, 18 October 2011; doi:10.1038/mp.2011.125.

Interlaboratory ring test of time-resolved fluoroimmunoassays for zeranol and alpha-zearalenol and comparison with zeranol test kits

Many zeranol immunoassay test kits cross-react with toxins formed by naturally occurring Fusarium spp. fungi, leading to false-positive screening results. This paper describes the evaluation and application of recently published, dry reagent time-resolved fluoroimmunoassays (TR-FIA) for zeranol and the toxin alpha-zearalenol. A ring test of bovine urine fortified with zeranol and/or alpha-zearalenol in four European Union National Reference Laboratories demonstrated that the TR-FIA tests were accurate and robust. The alpha-zearalenol TR-FIA satisfactorily quantified alpha-zearalenol in urine fortified at 10-30 ng ml(-1) . The specificity-enhanced zeranol TR-FIA accurately quantified zeranol in the range 2-5 ng ml(-1) and gave no false-positive results in blank urine, even in the presence of 30 ng ml(-1) alpha-zearalenol. Zeranol TR-FIA specificity was demonstrated further by analysing incurred zeranol-free urine samples containing natural Fusarium spp. toxins. The TR-FIA yielded no false-positive results in the presence of up to 22 ng ml(-1) toxins. The performance of four commercially available zeranol immunoassay test kits was more variable. Three kits produced many false-positive results. One kit produced only one potential false-positive using a protocol that was longer than that of the TR-FIA. These TR-FIAs will be valuable tools to develop inspection criteria to distinguish illegal zeranol abuse from contamination arising from in vivo metabolism of Fusarium spp. toxins.