Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia

The macro-economic effects of health co-benefits associated with climate change mitigation strategies

The UK government has specific targets for greenhouse gas (GHG) emission reduction to lower the risk of dangerous climate change. Strategies to reduce GHG emissions are sometimes perceived as expensive and difficult to implement but previous work has demonstrated significant potential health co-benefits from ‘Active Travel and low carbon driving’, ‘Housing Insulation/Ventilation’, and ‘Healthy Diet’ scenarios which may be attractive to policymakers. Here a Computable General Equilibrium model is used to assess the financial effects of such health co-benefits on the wider economy including changes in labour force, social security payments and healthcare costs averted. Results suggest that for all scenarios the financial impacts of the health co-benefits will be positive and increased active travel in particular is likely to make a substantial contribution, largely due to health care costs averted. Strategies to reduce GHG emissions and improve health are likely to result in substantial and increasing positive contributions to the economy which may offset some potential economic costs and thereby be seen more favourably in times of economic austerity

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax

An analysis of consumer protection for gamblers across different online gambling operators in Ireland: a descriptive study

The aim of the present study was to evaluate the responsible gambling tools which are available to online gamblers at Irish online gambling websites. The present study used a similar methodology to a recent study carried out on the world’s most popular websites (Bonello and Griffiths Gaming Law Review and Economics, 21, 278–285, 2017), where 50 of the most advertised online gambling websites were evaluated in relation to their responsible gambling (RG) practices. The present study evaluated 39 gambling websites with either a “.ie” or “.com/ie” domain. Each website was evaluated by checking for a number of RG practices, including presence of a dedicated RG page; age verification; access to gambling account history; the availability of RG tools, such as limit setting facilities and exclusion settings; and links to limit-setting options on the deposit page. Descriptive statistics were then performed on the results from each website. Of the 39 online gambling operators identified, 22 redirected gamblers to a “.com” domain, while 17 operators remained as a “.ie” domain. Thirty-five websites (89.7%) visited had a dedicated RG page. Responsible gambling features were evaluated and demonstrated to be available in an inconsistent manner across online gambling websites. Irish websites were shown to perform poorly in comparison with non-Irish counterparts in the provision of RG tools. The researchers of the present study are not aware of any similar studies conducted to date in Ireland

D3-brane Potentials from Fluxes in AdS/CFT

We give a comprehensive treatment of the scalar potential for a D3-brane in a warped conifold region of a compactification with stabilized moduli. By studying general ultraviolet perturbations in supergravity, we systematically incorporate `compactification effects' sourced by supersymmetry breaking in the compact space. Significant contributions to the D3-brane potential, including the leading term in the infrared, arise from imaginary anti-self-dual (IASD) fluxes. For an arbitrary Calabi-Yau cone, we determine the most general IASD fluxes in terms of scalar harmonics, then compute the resulting D3-brane potential. Specializing to the conifold, we identify the operator dual to each mode of flux, and for chiral operators we confirm that the potential computed in the gauge theory matches the gravity result. The effects of four-dimensional curvature, including the leading D3-brane mass term, arise directly from the ten-dimensional equations of motion. Furthermore, we show that gaugino condensation on D7-branes provides a local source for IASD flux. This flux precisely encodes the nonperturbative contributions to the D3-brane potential, yielding a promising ten-dimensional representation of four-dimensional nonperturbative effects. Our result encompasses all significant contributions to the D3-brane potential discussed in the literature, and does so in the single coherent framework of ten-dimensional supergravity. Moreover, we identify new terms with irrational scaling dimensions that were inaccessible in prior works. By decoupling gravity in a noncompact configuration, then systematically reincorporating compactification effects as ultraviolet perturbations, we have provided an approach in which Planck-suppressed contributions to the D3-brane effective action can be computed.Comment: 70 page

On the use of radon for quantifying the effects of atmospheric stability on urban emissions

Radon is increasingly being used as a tool for quantifying stability influences on urban pollutant concentrations. Bulk radon gradients are ideal for this purpose, since the vertical differencing substantially removes contributions from processes on timescales greater than diurnal and (assuming a constant radon source) gradients are directly related to the intensity of nocturnal mixing. More commonly, however, radon measurements are available only at a single height. In this study we argue that single-height radon observations should not be used quantitatively as an indicator of atmospheric stability without prior conditioning of the time series to remove contributions from larger-scale "non-local" processes. We outline a simple technique to obtain an approximation of the diurnal radon gradient signal from a single-height measurement time series, and use it to derive a four category classification scheme for atmospheric stability on a "whole night" basis. A selection of climatological and pollution observations in the Sydney region are then subdivided according to the radon-based scheme on an annual and seasonal basis. We compare the radon-based scheme against a commonly used Pasquill–Gifford (P–G) type stability classification and reveal that the most stable category in the P–G scheme is less selective of the strongly stable nights than the radon-based scheme; this lead to significant underestimation of pollutant concentrations on the most stable nights by the P–G scheme. Lastly, we applied the radon-based classification scheme to mixing height estimates calculated from the diurnal radon accumulation time series, which provided insight to the range of nocturnal mixing depths expected at the site for each of the stability classes. © 2015, Author(s)

Map of radon flux at the Australian land surface.

A time-dependent map of radon-222 flux density at the Australian land surface has been constructed with a spatial resolution of 0.05° and temporal resolution of one month. Radon flux density was calculated from a simple model utilising data from national gamma-ray aerial surveys, modelled soil moisture, and maps of soil properties. The model was calibrated against a large data set of accumulation-chamber measurements, thereby constraining it with experimental data. A notable application of the map is in atmospheric mixing and transport studies which use radon as a tracer, where it is a clear improvement on the common assumption of uniform radon flux density. © Author(s) 201

Stemming the tide: progress towards resolving the causes of decline and implementing management responses for the disappearing mammal fauna of northern Australia

Introduction: Recent studies at sites in northern Australia have reported severe and rapid decline of several native mammal species, notwithstanding an environmental context (small human population size, limited habitat loss, substantial reservation extent) that should provide relative conservation security. All of the more speciose taxonomic groups of mammals in northern Australia have some species for which their conservation status has been assessed as threatened, with 53 % of dasyurid, 47 % of macropod and potoroid, 33 % of bandicoot and bilby, 33 % of possum, 30 % of rodent, and 24 % of bat species being assessed as extinct, threatened or near threatened. However, the geographical extent and timing of declines, and their causes, remain poorly resolved, limiting the application of remedial management actions.\ud \ud Material and methods: Focusing on the tropical savannas of northern Australia, this paper reviews disparate recent and ongoing studies that provide information on population trends across a broader geographic scope than the previously reported sites, and examines the conservation status and trends for mammal groups (bats, macropods) not well sampled in previous monitoring studies. It describes some diverse approaches of studies seeking to document conservation status and trends, and of the factors that may be contributing to observed patterns of decline.\ud \ud Results and Discussion: Current trends and potential causal factors for declines. The studies reported demonstrate that the extent and timing of impacts and threats have been variable across the region, although there is a general gradational pattern of earlier and more severe decline from inland lower rainfall areas to higher rainfall coastal regions. Some small isolated areas appear to have retained their mammal species, as have many islands which remain critical refuges. There is now some compelling evidence that predation by feral cats is implicated in the observed decline, with those impacts likely to be exacerbated by prevailing fire regimes (frequent, extensive and intense fire), by reduction in ground vegetation cover due to livestock and, in some areas, by 'control' of dingoes. However the impacts of dingoes may be complex, and are not yet well resolved in this area. The relative impacts of these individual factors vary spatially (with most severe impacts in higher rainfall and more rugged areas) and between different mammal species, with some species responding idiosyncratically: the most notable example is the rapid decline of the northern quoll (Dasyurus hallucatus) due to poisoning by the introduced cane toad (Rhinella marina), which continues to spread extensively across northern Australia. The impact of disease, if any, remains unresolved.\ud \ud Conservation Management Responses. Recovery of the native mammal fauna may be impossible in some areas. However, there are now examples of rapid recovery following threat management. Priority conservation actions include: enhanced biosecurity for important islands, establishment of a network of feral predator exclosures, intensive fire management (aimed at increasing the extent of longer-unburnt habitat and in delivering fine scale patch burning), reduction in feral stock in conservation reserves, and acquisition for conservation purposes of some pastoral lands in areas that are significant for mammal conservation