Cataract, abnormal electroretinogram and visual evoked potentials in a child with SMA-LED2 - extending the phenotype.

This case report describes a girl who presented antenatal arthrogryposis and postnatal hypotonia, generalized and respiratory weakness, joint deformities particularly affecting the lower limbs and poor swallow. By 5 months, cataracts, abnormal electroretinograms, visual evoked potentials and global developmental impairments were recognized. No causative variants were identified on targeted gene panels. After her unexpected death at 11 months, gene-agnostic trio whole exome sequencing revealed a likely pathogenic de novo BICD2 missense variant, NM_001003800.1, c.593T>C, p.(Leu198Pro), confirming the diagnosis of spinal muscular atrophy lower extremity predominant type 2 (SMA-LED2). We propose that cataracts and abnormal electroretinograms are novel features of SMA-LED2

Late Maastrichtian carbon isotope stratigraphy and cyclostratigraphy of the Newfoundland Margin (Site U1403, IODP Expedition 342)

Earth’s climate during the Maastrichtian (latest Cretaceous) was punctuated by brief warming and cooling episodes, accompanied by perturbations of the global carbon cycle. Superimposed on a long-term cooling trend, the middle Maastrichtian is characterized by deep-sea warming and relatively high values of stable carbon-isotope ratios, followed by strong climatic variability towards the end of the Cretaceous. A lack of knowledge on the timing of climatic change inhibits our understanding of underlying causal mechanisms. We present an integrated stratigraphy from Integrated Ocean Drilling Program (IODP) Site U1403, providing an expanded deep ocean record from the North Atlantic (Expedition 342, Newfoundland Margin). Distinct sedimentary cyclicity suggests that orbital forcing played a major role in depositional processes, which is confirmed by statistical analyses of high resolution elemental data obtained by X-ray fluorescence (XRF) core scanning. Astronomical calibration reveals that the investigated interval encompasses seven 405-kyr cycles (Ma4051 to Ma4057) and spans the 2.8 Myr directly preceding the Cretaceous/Paleocene (K/Pg) boundary. A high-resolution carbon-isotope record from bulk carbonates allows us to identify global trends in the late Maastrichtian carbon cycle. Low-amplitude variations (up to 0.4‰) in carbon isotopes at Site U1403 match similar scale variability in records from Tethyan and Pacific open-ocean sites. Comparison between Site U1403 and the hemipelagic restricted basin of the Zumaia section (northern Spain), with its own well-established independent cyclostratigraphic framework, is more complex. Whereas the pre-K/Pg oscillations and the negative values of the Mid-Maastrichtian Event (MME) can be readily discerned in both the Zumaia and U1403 records, patterns diverge during a ~ 1 Myr period in the late Maastrichtian (67.8–66.8 Ma), with Site U1403 more reliably reflecting global carbon cycling. Our new carbon isotope record and cyclostratigraphy offer promise for Site U1403 to serve as a future reference section for high-resolution studies of late Maastrichtian paleoclimatic change

Radiofrequency ablation for Barrett's oesophagus related neoplasia with the 360 Express catheter: initial experience from the United Kingdom and Ireland—preliminary results

BACKGROUND: Radio-frequency ablation (RFA) for Barrett's oesophagus (BE)-related neoplasia is currently used after endoscopic resection of visible neoplasia. The HALO 360 balloon has been used to ablate long segment BE. The Barrx™ 360 Express RFA self-sizing catheter ('RFA Express') may potentially allow quicker ablation times and improved treatment outcomes. The aim of this paper is to present real world data on the use of the 360 Express Device. METHODS: Centres in the UK and Ireland submitted cases where the RFA Express was used. The primary outcome was regression of BE at 3 months. Secondary outcomes were the rate of symptomatic stricture formation and resolution of intestinal metaplasia (CR-IM) and dysplasia (CR-D) at End of Treatment (EoT). RESULTS: 11 centres submitted 123 consecutive patients. 112 had a follow up endoscopy. The median age was 67 years (IQR 62-75). 3 dosimetries were used. The mean reduction in Circumferential (C) length was 78% ± 36 and mean reduction in Maximal length (M) was 55% ± 36. 17 patients (15%) developed strictures requiring dilation. There was a higher rate of stricture formation when the 12 J energy was used (p < 0.05). 47 patients had EoT biopsies, 40 (85%) had CR-D and 34(76%) had CR-IM. CONCLUSIONS: The RFA 360 Express catheter shows reduction in length of baseline BE at 3 months after index treatment, and eradication of intestinal metaplasia and dysplasia at 12 months similar to other studies with earlier devices. It appears that the symptomatic stricture rate is slightly higher than previous series with the HALO 360 catheter. This study was performed as part of the HALO registry and has been approved by the Research Ethics Committee - MREC Number 08/H0714/27 Local project reference 08/0104 Project ID 15,033 IRAS Number 54678 EudraCT 2009-015980-1. Registered on ISRCTN as below: ISRCTN93069556. https://doi.org/10.1186/ISRCTN93069556

On impact and volcanism across the Cretaceous-Paleogene boundary

The cause of the end-Cretaceous mass extinction is vigorously debated, owing to the occurrence of a very large bolide impact and flood basalt volcanism near the boundary. Disentangling their relative importance is complicated by uncertainty regarding kill mechanisms and the relative timing of volcanogenic outgassing, impact, and extinction. We used carbon cycle modeling and paleotemperature records to constrain the timing of volcanogenic outgassing. We found support for major outgassing beginning and ending distinctly before the impact, with only the impact coinciding with mass extinction and biologically amplified carbon cycle change. Our models show that these extinction-related carbon cycle changes would have allowed the ocean to absorb massive amounts of carbon dioxide, thus limiting the global warming otherwise expected from postextinction volcanism

Operationalising a model framework for consumer and community participation in health and medical research

The Consumers' Health Forum of Australia and the National Health and Medical Research Council has recently developed a Model Framework for Consumer and Community Participation in Health and Medical Research in order to better align health and medical research with community need, and improve the impact of research. Model frameworks may have little impact on what goes on in practice unless relevant organisations actively make use of them. Philanthropic and government bodies have reported involving consumers in more meaningful or collaborative ways of late. This paper describes how a large charity organisation, which funds a significant proportion of Australian cancer research, operationalised the model framework using a unique approach demonstrating that it is both possible and reasonable for research to be considerate of public values

Mechanistic insights into a hydrate contribution to the Paleocene-Eocene carbon cycle perturbation from coupled thermohydraulic simulations

During the Paleocene-Eocene Thermal Maximum (PETM), the carbon isotopic signature (δ13C) of surface carbon-bearing phases decreased abruptly by at least 2.5 to 3.0‰. This carbon isotope excursion (CIE) has been attributed to widespread methane hydrate dissociation in response to rapid ocean warming. We ran a thermohydraulic modeling code to simulate hydrate dissociation due to ocean warming for various PETM scenarios. Our results show that hydrate dissociation in response to such warming can be rapid but suggest that methane release to the ocean is modest and delayed by hundreds to thousands of years after the onset of dissociation, limiting the potential for positive feedback from emission-induced warming. In all of our simulations at least half of the dissociated hydrate methane remains beneath the seabed, suggesting that the pre-PETM hydrate inventory needed to account for all of the CIE is at least double that required for isotopic mass balance

Terminal valuations, growth rates and the implied cost of capital

This article is published with open access at Springerlink.comWe develop a model based on the notion that prices lead earnings, allowing for a simultaneous estimation of the implied growth rate and the cost of equity capital for US industrial sectors. The major difference between our approach and that in prior literature is that ours avoids the necessity to make assumptions about terminal values and consequently about future growth rates. In fact, growth rates are an endogenous variable, which is estimated simultaneously with the implied cost of equity capital. Since we require only 1-year-ahead forecasts of earnings and no assumptions about dividend payouts, our methodology allows us to estimate ex ante aggregate growth and risk premia over a larger sample of firms than has previously been possible. Our estimate of the risk premium being between 3.1 and 3.9 % is at the lower end of recent estimates, reflecting the inclusion of these short-lived companies. Our estimate of the long run growth is from 4.2 to 4.7 %

Quantitative Trait Loci Involved in Sex Determination and Body Growth in the Gilthead Sea Bream (Sparus aurata L.) through Targeted Genome Scan

Among vertebrates, teleost fish exhibit a considerably wide range of sex determination patterns that may be influenced by extrinsic parameters. However even for model fish species like the zebrafish Danio rerio the precise mechanisms involved in primary sex determination have not been studied extensively. The zebrafish, a gonochoristic species, is lacking discernible sex chromosomes and the sex of juvenile fish is difficult to determine. Sequential protandrous hermaphrodite species provide distinct determination of the gender and allow studying the sex determination process by looking at the mechanism of sex reversal. This is the first attempt to understand the genetic basis of phenotypic variation for sex determination and body weight in a sequential protandrous hermaphrodite species, the gilthead sea bream (Sparus aurata). This work demonstrates a fast and efficient strategy for Quantitative Trait Loci (QTL) detection in the gilthead sea bream, a non-model but target hermaphrodite fish species. Therefore a comparative mapping approach was performed to query syntenies against two other Perciformes, the European sea bass (Dicentrarchus labrax), a gonochoristic species and the Asian sea bass (Lates calcarifer) a protandrous hermaphrodite. In this manner two significant QTLs, one QTL affecting both body weight and sex and one QTL affecting sex, were detected on the same linkage group. The co-segregation of the two QTLs provides a genomic base to the observed genetic correlation between these two traits in sea bream as well as in other teleosts. The identification of QTLs linked to sex reversal and growth, will contribute significantly to a better understanding of the complex nature of sex determination in S. aurata where most individuals reverse to the female sex at the age of two years through development and maturation of the ovarian portion of the gonad and regression of the testicular area. [Genomic sequences reported in this manuscript have been submitted to GenBank under accession numbers HQ021443–HQ021749.