Multimodal analysis of the effects of dexamethasone on high-altitude cerebral oedema : protocol for a pilot study

Background Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. Methods/design D4H is a double-blind placebo-controlled randomised trial assessing the effect of dexamethasone on hypoxia-induced cerebral oedema. In total, 20 volunteers were randomised in pairs to receive either 8.25 mg dexamethasone or normal saline placebo intravenously after 8 h of hypoxia with an FiO2 of 12%. Serial MRI images of the brain and spinal cord were obtained at hours 0, 7, 11, 22 and 26 of the study along with serum and urinary markers to correlate with the severity of cerebral oedema and the effect of the intervention. Discussion MRI has been used to identify changes in cerebral vasculature in the development of AMS and HACE. Dexamethasone is effective at reducing the symptoms of AMS; however, the mechanism of this effect is unknown. If this study demonstrates a clear objective benefit of dexamethasone in this setting, future studies may be able to demonstrate that dexamethasone is an effective therapy for oedema associated with brain and spinal cord ischaemia beyond AMS

A Very Sensitive 21cm Survey for Galactic High-Velocity HI

Very sensitive HI 21cm observations have been made in 860 directions at dec >= -43deg in search of weak, Galactic, high-velocity HI emission lines at moderate and high Galactic latitudes. One-third of the observations were made toward extragalactic objects. The median 4-sigma detection level is NHI = 8x10^{17} cm^-2 over the 21' telescope beam. High-velocity HI emission is detected in 37% of the directions; about half of the lines could not have been seen in previous surveys. The median FWHM of detected lines is 30.3 km/s. High- velocity HI lines are seen down to the sensitivity limit of the survey implying that there are likely lines at still lower values of NHI. The weakest lines have a kinematics and distribution on the sky similar to that of the strong lines, and thus do not appear to be a new population. Most of the emission originates from objects which are extended over several degrees; few appear to be compact sources. At least 75%, and possibly as many as 90%, of the lines are associated with one of the major high-velocity complexes. The Magellanic Stream extends at least 10 deg to higher Galactic latitude than previously thought and is more extended in longitude as well. Although there are many lines with low column density, their numbers do not increase as rapidly as NHI^-1, so most of the HI mass in the high-velocity cloud phenomenon likely resides in the more prominent clouds. The bright HI features may be mere clumps within larger structures, and not independent objects.Comment: 88 pages includes 22 figures Accepted for Publication in ApJ Suppl. June 200

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Experience in implementing harvest strategies in Australia's south-eastern fisheries

The Southern and Eastern Scalefish and Shark Fishery (SESSF) is a complex multi-species fishery, with 34 stock units under quota management, for which a harvest strategy framework was developed in 2005. The framework involves the application of a set of tier-based harvest control rules (HCR) designed to provide a precautionary approach to management. The harvest strategy framework has been applied from 2005 to 2007, resulting in substantial reductions in quotas across the fishery. The experience in implementing the framework, both positive and negative, is described, and general lessons are drawn. Key lessons include the importance of formally testing such strategies using management strategy evaluation, the impact of external management drivers on implementation of the approach, the need to define strategies for setting "bycatch quotas" in multi-species fisheries, and the need for flexibility and pragmatism in the early stages of implementing such an approach

The Magellanic Stream, High-Velocity Clouds and the Sculptor Group

The Magellanic Stream is a 100\deg x 10\deg filament of gas which lies within the Galactic halo and contains ~ 2 x 10^8 \Msun of neutral hydrogen. We present data from the HI Parkes All Sky Survey (HIPASS) in the first complete survey of the entire Magellanic Stream and its surroundings. We also present a summary of the reprocessing techniques used to recover large-scale structure in the Stream. The Stream properties revealed include: bifurcation along the main Stream filament; dense, isolated clouds which follow the entire length of the Stream; head-tail structures; and a complex filamentary web at the head where gas is being freshly stripped away from the Small Magellanic Cloud and the Bridge. Debris which appears to be of Magellanic origin extends out to 20\deg from the main Stream filaments. The large number of elongated Stream clouds suggests the presence of shearing motions within the Stream, arising from tidal forces or interaction with the tenuous Galactic halo. Clouds along the sightline to the less distant half of the Sculptor Group, show anomalous properties. We argue that these clouds represent halo material, and are not distant Sculptor Group clouds. This result has significant implications for the hypothesis that there might exist distant, massive HVCs within the Local Group. (abridged

Tiny-Scale Molecular Structures in the Magellanic Clouds (Part 1)

We report on the {\small FUSE} detections of the HD and CO molecules {\bf on the lines of sight towards three Large Magellanic stars}: Sk $-$67D05, Sk $-$68D135, and Sk $-$69D246. HD is also detected for the first time {\bf on the lines of sight towards two Small Magellanic Cloud stars}: AV 95 and Sk 159. While the HD and CO abundances are expected to be lower in the Large Magellanic Cloud where molecular fractions are a third of the Galactic value and where the photodissociation flux is up to thousands times larger, we report an average HD/H$_2$ ratio of 1.4$\pm$0.5 ppm and CO/H$_2$ ratio ranging from 0.8 to 2.7 ppm similar to the Galactic ones. We tentatively identify a deuterium reservoir (hereafter D--reservoir) towards the Small Magellanic Cloud, along the light path to AV 95. We derive a D/H ratio ranging from 1. 10$^{-6}$ to 1.1 10$^{-5}$.Comment: 34 pages, 10 tables, 12 figures, accepted for publication in A&

A non-LTE analysis of the spectra of two narrow lined main sequence stars in the SMC

An analysis of high-resolution VLT/UVES spectra of two B-type main sequence stars, NGC 346-11 and AV 304, in the Small Magellanic Cloud (SMC), has been undertaken, using the non-LTE TLUSTY model atmospheres to derive the stellar parameters and chemical compositions of each star. The chemical compositions of the two stars are in reasonable agreement. Moreover, our stellar analysis agrees well with earlier analyses of H II regions. The results derived here should be representative of the current base-line chemical composition of the SMC interstellar medium as derived from B-type stars.Comment: 10 pages, 4 figures, 1 online tabl

Impacts of caring for a child with the CDKL5 disorder on parental wellbeing and family quality of life

Background: Although research in this area remains sparse, raising a child with some genetic disorders has been shown to adversely impact maternal health and family quality of life. The aim of this study was to investigate such impacts in families with a child with the CDKL5 disorder, a newly recognised genetic disorder causing severe neurodevelopmental impairments and refractory epilepsy. Methods: Data were sourced from the International CDKL5 Disorder Database to which 192 families with a child with a pathogenic CDKL5 mutation had provided data by January 2016. The Short Form 12 Health Survey Version 2, yielding a Physical Component Summary and a Mental Component Summary score, was used to measure primary caregiver's wellbeing. The Beach Center Family Quality of Life Scale was used to measure family quality of life. Linear regression analyses were used to investigate relationships between child and family factors and the various subscale scores. Results: The median (range) age of the primary caregivers was 37.0 (24.6-63.7) years and of the children was 5.2 (0.2-34.1) years. The mean (SD) physical and mental component scores were 53.7 (8.6) and 41.9 (11.6), respectively. In mothers aged 25-54 years the mean mental but not the physical component score was lower than population norms. After covariate adjustment, caregivers with a tube-fed child had lower mean physical but higher mean mental component scores than those whose child fed orally (coefficient = -4.80 and 6.79; p = 0.009 and 0.012, respectively). Child sleep disturbances and financial hardship were negatively associated with the mental component score. The mean (SD) Beach Center Family Quality of Life score was 4.06 (0.66) and those who had used respite services had lower scores than those who had not across the subscales. Conclusions: Emotional wellbeing was considerably impaired in this caregiver population, and was particularly associated with increased severity of child sleep problems and family financial difficulties. Family quality of life was generally rated lowest in those using respite care extensively, suggesting that these families may be more burdened by daily caregiving

Subacromial spacer for Tears Affecting Rotator cuff Tendons : a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS)

Background A balloon spacer is a relatively simple addition to an arthroscopic debridement procedure for irreparable rotator cuff tears. Objective To evaluate the clinical and cost-effectiveness of a subacromial balloon spacer for individuals undergoing arthroscopic debridement for irreparable rotator cuff tears. Design A multicentre participant-and assessor-blinded randomised controlled trial comparing arthroscopic debridement with the InSpace® (Stryker, Kalamazoo, MI, USA) balloon to arthroscopic debridement alone, using a novel adaptive design. Pretrial simulations informed stopping boundaries for two interim analyses, using outcome data from early and late time points