Predictors of care-giver stress in families of preschool-aged children with developmental disabilities

Background This study examined the predictors, mediators and moderators of parent stress in families of preschool-aged children with developmental disability. Method One hundred and five mothers of preschool-aged children with developmental disability completed assessment measures addressing the key variables. Results Analyses demonstrated that the difficulty parents experienced in completing specific caregiving tasks, behaviour problems during these caregiving tasks, and level of child disability, respectively, were significant predictors of level of parent stress. In addition, parents’ cognitive appraisal of care-giving responsibilities had a mediating effect on the relationship between the child’s level of disability and parent stress. Mothers’ level of social support had a moderating effect on the relationship between key independent variables and level of parent stress. Conclusions Difficulty of care-giving tasks, difficult child behaviour during care-giving tasks, and level of child disability are the primary factors which contribute to parent stress. Implications of these findings for future research and clinical practice are outlined

ELEVATED PHENYLACETIC ACID LEVELS DO NOT CORRELATE WITH ADVERSE EVENTS IN PATIENTS WITH UREA CYCLE DISORDERS OR HEPATIC ENCEPHALOPATHY AND CAN BE PREDICTED BASED ON THE PLASMA PAA TO PAGN RATIO

Background Phenylacetic acid (PAA) is the active moiety in sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB, HPN-100), both are approved for treatment of urea cycle disorders (UCDs) - rare genetic disorders characterized by hyperammonemia. PAA is conjugated with glutamine in the liver to form phenylacetyleglutamine (PAGN), which is excreted in urine. PAA plasma levels ≥500 μg/dL have been reported to be associated with reversible neurological adverse events (AEs) in cancer patients receiving PAA intravenously. Therefore, we have investigated the relationship between PAA levels and neurological AEs in patients treated with these PAA pro-drugs as well as approaches to identifying patients most likely to experience high PAA levels. Methods The relationship between nervous system AEs, PAA levels and the ratio of plasma PAA to PAGN were examined in 4683 blood samples taken serially from: [1] healthy adults [2], UCD patients ≥2 months of age, and [3] patients with cirrhosis and hepatic encephalopathy (HE). The plasma ratio of PAA to PAGN was analyzed with respect to its utility in identifying patients at risk of high PAA values. Results Only 0.2% (11) of 4683 samples exceeded 500 ug/ml. There was no relationship between neurological AEs and PAA levels in UCD or HE patients, but transient AEs including headache and nausea that correlated with PAA levels were observed in healthy adults. Irrespective of population, a curvilinear relationship was observed between PAA levels and the plasma PAA:PAGN ratio, and a ratio > 2.5 (both in μg/mL) in a random blood draw identified patients at risk for PAA levels > 500 μg/ml. Conclusions The presence of a relationship between PAA levels and reversible AEs in healthy adults but not in UCD or HE patients may reflect intrinsic differences among the populations and/or metabolic adaptation with continued dosing. The plasma PAA:PAGN ratio is a functional measure of the rate of PAA metabolism and represents a useful dosing biomarker

Rationale and design of the IRON-AF study: a double-blind, randomised, placebo-controlled study to assess the effect of intravenous ferric carboxymaltose in patients with atrial fibrillation and iron deficiency

Introduction: Atrial fibrillation (AF) is associated with significantly impaired quality-of-life. Iron deficiency (ID) is prevalent in patients with AF. Correction of ID in other patient populations with intravenous iron supplementation has been shown to be a safe, convenient and effective way of improving exercise tolerance, fatigue and quality-of-life. The IRON-AF (Effect of Iron Repletion in Atrial Fibrillation) study is designed to assess the effect of iron repletion with intravenous ferric carboxymaltose in patients with AF and ID. Methods and Analysis: The IRON-AF study is a double-blind, randomised controlled trial that will recruit at least 84 patients with AF and ID. Patients will be randomised to receive infusions of either ferric carboxymaltose or placebo, given in repletion and then maintenance doses. The study will have follow-up visits at weeks 4, 8 and 12. The primary endpoint is change in peak oxygen uptake from baseline to week 12, as measured by cardiopulmonary exercise testing (CPET) on a cycle ergometer. Secondary endpoints include changes in quality-of-life and AF disease burden scores, blood parameters, other CPET parameters, transthoracic echocardiogram parameters, 6-minute walk test distance, 7-day Holter/Event monitor burden of AF, health resource utilisation and mortality. Ethics and dissemination: The study protocol has been approved by the Central Adelaide Local Health Network Human Research Ethics Committee, Australia. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations.Samuel J Tu, Adrian D Elliott, Nicole Hanna-Rivero, Celine Gallagher, Ricardo S Mishima, Ellen Lyrtzis, Danielle Wlochowicz, Nicholas AR Clarke, Kurt C Roberts-Thomson, Michael B Stokes, Mehrdad Emami, Dennis H Lau, Prashanthan Sanders, Christopher X Won

TOPoS: III. An ultra iron-poor CEMP multiple system

Aims. One of the primary objectives of the TOPoS survey is to search for the most metal-poor stars. Our search has led to the discovery of one of the most iron-poor objects known, SDSS J092912.32+023817.0. This object is a multiple system, in which two components are clearly detected in the spectrum. Methods. We have analysed 16 high-resolution spectra obtained using the UVES spectrograph at the ESO 8.2 m VLT telescope to measure radial velocities and determine the chemical composition of the system. Results. Cross correlation of the spectra with a synthetic template yields a double-peaked cross-correlation function (CCF) for eight spectra, and in one case there is evidence for the presence of a third peak. Chemical analysis of the spectrum obtained by averaging all the spectra for which the CCF showed a single peak found that the iron abundance is [Fe/H]=–4.97. The system is also carbon enhanced with [C/Fe]=+3.91 (A(C) = 7.44). From the permitted oxygen triplet we determined an upper limit for oxygen of [O/Fe] 1.3. We are also able to provide more stringent upper limits on the Sr and Ba abundances ([Sr/Fe] < +0.70, and [Ba/Fe] < +1.46, respectively)

Implementing subtype-specific pre-clinical models of breast cancer to study pre-treatment aspirin effects

YesBackgorund Prior data suggest pre-diagnostic aspirin use impacts breast tumour biology and patient outcome. Here, we employed faithful surgical resection models of HER2+ and triple-negative breast cancer (TNBC), to study outcome and response mechanisms across breast cancer subtypes. Method NOD/SCID mice were implanted with HER2+ MDA-MB-231/LN/2-4/H2N, trastuzumab-resistant HER2+ HCC1954 or a TNBC patient-derived xenograft (PDX). A daily low-dose aspirin regimen commenced until primary tumours reached ~250 mm3 and subsequently resected. MDA-MB-231/LN/2-4/H2N mice were monitored for metastasis utilising imaging. To interrogate the survival benefit of pre-treatment aspirin, 3 weeks post-resection, HCC1954/TNBC animals received standard-of-care (SOC) chemotherapy for 6 weeks. Primary tumour response to aspirin was interrogated using immunohistochemistry. Results Aspirin delayed time to metastasis in MDA-MB-231/LN/2-4/H2N xenografts and decreased growth of HER2+/TNBC primary tumours. Lymphangiogenic factors and lymph vessels number were decreased in HER2+ tumours. However, no survival benefit was seen in aspirin pre-treated animals (HCC1954/TNBC) that further received adjuvant SOC, compared with animals treated with SOC alone. In an effort to study mechanisms responsible for the observed reduction in lymphangiogenesis in HER2+ BC we utilised an in vitro co-culture system of HCC1954 tumour cells and mesenchymal stromal cells (MSC). Aspirin abrogated the secretion of VEGF-C in MSCs and also decreased the lymph/angiogenic potential of the MSCs and HCC1954 by tubule formation assay. Furthermore, aspirin decreased the secretion of uPA in HCC1954 cells potentially diminishing its metastatic capability. Conclusion Our data employing clinically relevant models demonstrate that aspirin alters breast tumour biology. However, aspirin may not represent a robust chemo-preventative agent in the HER2+ or TNBC setting.Funding is acknowledged from the Irish Cancer Society Collaborative Cancer Research Centre under BREAST- PREDICT grant CCRC13GAL (www.breas tpred ict.com). I.S.M, E.M and A.T.B, are members of the EurOPDX Consortium, and receive funding from the European Union's Horizon 2020 research and innovation programme, grant agreement no. #731105 (EurOPDX Research Infrastructure, www.europ dx.eu)

An overview of the MHONGOOSE survey: Observing nearby galaxies with MeerKAT

MHONGOOSE is a deep survey of the neutral hydrogen distribution in a representative sample of 30 nearby disk and dwarf galaxies with HI masses from 10^6 to ~10^{11} M_sun, and luminosities from M_R ~ -12 to M_R ~ -22. The sample is selected to uniformly cover the available range in log(M_HI). Our extremely deep observations, down to HI column density limits of well below 10^{18} cm^{-2} - or a few hundred times fainter than the typical HI disks in galaxies - will directly detect the effects of cold accretion from the intergalactic medium and the links with the cosmic web. These observations will be the first ever to probe the very low-column density neutral gas in galaxies at these high resolutions. Combination with data at other wavelengths, most of it already available, will enable accurate modelling of the properties and evolution of the mass components in these galaxies and link these with the effects of environment, dark matter distribution, and other fundamental properties such as halo mass and angular momentum. MHONGOOSE can already start addressing some of the SKA-1 science goals and will provide a comprehensive inventory of the processes driving the transformation and evolution of galaxies in the nearby universe at high resolution and over 5 orders of magnitude in column density. It will be a Nearby Galaxies Legacy Survey that will be unsurpassed until the advent of the SKA, and can serve as a highly visible, lasting statement of MeerKAT's capabilities

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements