The Quality of Life scale for Children (QoL-C)

This is the author's version of the article, which has been published in final form at http://dx.doi.org/10.1108/JCS-05-2013-0019Purpose – There is a lack of valid and reliable generic measures of Health-Related Quality of Life (HRQoL) for children under eight. The purpose of this paper is to assess the psychometric properties of the newly formulated Quality of Life Scale for Children (QoL-C), which uses a pictorial response format. Design/methodology/approach – In total, 335 primary school children completed the QoL-C on two occasions, two weeks apart. Children aged four to seven were interviewed one-to-one while children aged eight to nine completed the measure as a class activity. Test-re-test reliability, convergent validity and child-parent concordance were assessed. Findings – Only one child refused to complete the QoL-C, which suggests the measure is user-friendly. Test-re-test reliability was moderate for the measure's total score (intraclass correlation coefficient =0.48, 95 percent CI 0.39, 0.57) but low to fair for individual items (K from 0.13 to 0.37). Internal consistency was moderate (α=0.42 time one, 0.53 time two). A small significant correlation was found between the QoL-C and Child Health Meter in the expected direction (r=−0.32), suggesting convergent validity. There was low concordance between the children's QoL-C responses and parent's responses (r=0.19) to a parallel measure. Research limitations/implications – The results suggest that further development of this measure is needed. However, the findings indicate that one-to-one support increases the reliability of very young children's responses. The use of pictures, emoticons and minimal text used in the QoL-C should be investigated further. Originality/value – Low parent-child concordance underscores the importance of younger children getting the opportunity to share their views about their HRQoL

Sodium bicarbonate and high-intensity-cycling capacity: variability in responses

Purpose: The aim of this study was to determine whether gastrointestinal (GI) distress affects the ergogenicity of sodium bicarbonate and whether the degree of alkalaemia or other metabolic responses are different between individuals who improve exercise capacity and those who do not. Methods: Twenty-one males completed two cycling capacity tests at 110% of maximum power output. Participants were supplemented with 0.3 g∙kg-1BM of either placebo (maltodextrin) or sodium bicarbonate (SB). Blood pH, bicarbonate, base excess and lactate were determined at baseline, pre-exercise, immediately post-exercise and 5 minutes post-exercise. Results: SB supplementation did not significantly increase total work done (TWD) (P = 0.16, 46.8 ± 9.1 vs. 45.6 ± 8.4 kJ, d = 0.14), although magnitude based inferences suggested a 63% likelihood of a positive effect. When data were analysed without four participants who experienced GI discomfort, TWD (P = 0.01) was significantly improved with SB. Immediately post-exercise blood lactate was higher in SB for the individuals who improved but not for those who didn’t. There were also differences in the pre to post-exercise change in blood pH, bicarbonate and base excess between individuals who improved and individuals who did not. Conclusions: SB improved high intensity cycling capacity, but only with the exclusion of participants experiencing GI discomfort. Differences in blood responses suggest that sodium bicarbonate may not be beneficial to all individuals. Magnitude based inferences suggested that the exercise effects are unlikely to be negative; therefore individuals should determine whether they respond well to sodium bicarbonate supplementation prior to competition

Interdisciplinary Perspectives on Restraint Use in Aged Care.

Restraint use in Australian residential aged care has been highlighted by the media, and investigated by researchers, government and advocacy bodies. In 2018, the Royal Commission into Aged Care selected 'Restraint' as a key focus of inquiry. Subsequently, Federal legislation was passed to ensure restraint is only used in residential aged care services as the 'last resort'. To inform and develop Government educational resources, we conducted qualitative research to gain greater understanding of the experiences and attitudes of aged care stakeholders around restraint practice. Semi-structured interviews were held with 28 participants, comprising nurses, care staff, physicians, physiotherapists, pharmacists and relatives. Two focus groups were also conducted to ascertain the views of residential and community aged care senior management staff. Data were thematically analyzed using a pragmatic approach of inductive and deductive coding and theme development. Five themes were identified during the study: 1. Understanding of restraint; 2. Support for legislation; 3. Restraint-free environments are not possible; 4. Low-level restraint; 5. Restraint in the community is uncharted. Although most staff, health practitioners and relatives have a basic understanding of restraint, more education is needed at a conceptual level to enable them to identify and avoid restraint practice, particularly 'low-level' forms and chemical restraint. There was strong support for the new restraint regulations, but most interviewees admitted they were unsure what the legislation entailed. With regards to resources, stakeholders wanted recognition that there were times when restraint was necessary and advice on what to do in these situations, as opposed to unrealistic aspirations for restraint-free care. Stakeholders reported greater oversight of restraint in residential aged care but specified that community restraint use was largely unknown. Research is needed to investigate the extent and types of restraint practice in community aged care

T1 Mapping Detects Pharmacological Retardation of Diffuse Cardiac Fibrosis in Mouse Pressure-Overload Hypertrophy

Background: Diffuse interstitial fibrosis is present in diverse cardiomyopathies and associated with poor prognosis. We investigated whether magnetic resonance imaging-based T1 mapping could quantify the induction and pharmacological suppression of diffuse cardiac fibrosis in murine pressure-overload hypertrophy. / Methods and Results: Mice were subjected to transverse aortic constriction or sham surgery. The angiotensin receptor blocker losartan was given to half the animals. Cine-magnetic resonance imaging performed at 7 and 28 days showed hypertrophy and remodeling and systolic and diastolic dysfunction in transverse aortic constriction groups as expected. Late gadolinium-enhanced magnetic resonance imaging revealed focal signal enhancement at the inferior right ventricular insertion point of transverse aortic constriction mice concordant with the foci of fibrosis in histology. The extracellular volume fraction, calculated from pre- and postcontrast T1 measurements, was elevated by transverse aortic constriction and showed direct linear correlation with picrosirius red collagen volume fraction, thus confirming the suitability of extracellular volume fraction as an in vivo measure of diffuse fibrosis. Treatment with losartan reduced left ventricular dysfunction and prevented increased extracellular volume fraction, indicating that T1 mapping is sensitive to pharmacological prevention of fibrosis. / Conclusions: Magnetic resonance imaging can detect diffuse and focal cardiac fibrosis in a clinically relevant animal model of pressure overload and is sensitive to pharmacological reduction of fibrosis by angiotensin receptor blockade. Thus, T1 mapping can be used to assess antifibrotic therapeutic strategies

A 12-month phase 3 study of pasireotide in cushing's disease

BACKGROUND: Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. METHODS: In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 ??g (82 patients) or 900 ??g (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 ??g twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. RESULTS: Twelve of the 82 patients in the 600-??g group and 21 of the 80 patients in the 900-??g group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose-lowering medication was initiated in 74 of 162 patients. CONCLUSIONS: The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.) Copyright © 2012 Massachusetts Medical Society

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

Kerr-AdS and its Near-horizon Geometry: Perturbations and the Kerr/CFT Correspondence

We investigate linear perturbations of spin-s fields in the Kerr-AdS black hole and in its near-horizon geometry (NHEK-AdS), using the Teukolsky master equation and the Hertz potential. In the NHEK-AdS geometry we solve the associated angular equation numerically and the radial equation exactly. Having these explicit solutions at hand, we search for linear mode instabilities. We do not find any (non-)axisymmetric instabilities with outgoing boundary conditions. This is in agreement with a recent conjecture relating the linearized stability properties of the full geometry with those of its near-horizon geometry. Moreover, we find that the asymptotic behaviour of the metric perturbations in NHEK-AdS violates the fall-off conditions imposed in the formulation of the Kerr/CFT correspondence (the only exception being the axisymmetric sector of perturbations).Comment: 26 pages. 4 figures. v2: references added. matches published versio

Intermediate behavior of Kerr tails

The numerical investigation of wave propagation in the asymptotic domain of Kerr spacetime has only recently been possible thanks to the construction of suitable hyperboloidal coordinates. The asymptotics revealed an apparent puzzle in the decay rates of scalar fields: the late-time rates seemed to depend on whether finite distance observers are in the strong field domain or far away from the rotating black hole, an apparent phenomenon dubbed "splitting". We discuss far-field "splitting" in the full field and near-horizon "splitting" in certain projected modes using horizon-penetrating, hyperboloidal coordinates. For either case we propose an explanation to the cause of the "splitting" behavior, and we determine uniquely decay rates that previous studies found to be ambiguous or immeasurable. The far-field "splitting" is explained by competition between projected modes. The near-horizon "splitting" is due to excitation of lower multipole modes that back excite the multipole mode for which "splitting" is observed. In both cases "splitting" is an intermediate effect, such that asymptotically in time strong field rates are valid at all finite distances. At any finite time, however, there are three domains with different decay rates whose boundaries move outwards during evolution. We then propose a formula for the decay rate of tails that takes into account the inter--mode excitation effect that we study.Comment: 16 page

Role of thrombin receptor in breast cancer invasiveness

Invasion, the ability of an epithelial cancer cell to detach from and move through a basement membrane, is a central process in tumour metastasis. Two components of invasion are proteolysis of extracellular matrix and cellular movement through it. A potential promoter of these two processes is thrombin, the serine proteinase derived from the ubiquitous plasma protein prothrombin. Thrombin promotes the invasion of MDA-MB231 breast tumour cells (a highly aggressive cell line) in an in vitro assay. Invasion by MDA-MB436 and MCF-7 cells, less aggressive cell lines, is not promoted by thrombin. Thrombin, added to the cells, is a stimulator of cellular movement; fibroblast-conditioned medium is the chemotaxin. Thrombin-promoted invasion is inhibited by hirudin. Stimulation of invasion is a receptor-mediated process that is mimicked by a thrombin receptor-activating peptide. Thrombin has no effect on chemotaxis in vitro. Thrombin receptor is detectable on the surface of MDA-MB231 cells, but not on the other two cell lines. Introduction of oestrogen receptors into MDA-MB231 cells by transfection with pHEO had no effect on thrombin receptor expression, in the presence or absence of oestradiol. This paper demonstrates that thrombin increases invasion by the aggressive breast cancer cell line MDA-MB231 by a thrombin receptor-dependent mechanism. © 1999 Cancer Research Campaig

Molecular basis of FIR-mediated c-myc transcriptional control

The far upstream element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream of the c-myc promoter. Then, FBP recruits its specific repressor (FIR), which acts as an on/off transcriptional switch. Here we describe the molecular basis of FIR recruitment, showing that the tandem RNA recognition motifs of FIR provide a platform for independent FUSE DNA and FBP protein binding and explaining the structural basis of the reversibility of the FBP-FIR interaction. We also show that the physical coupling between FBP and FIR is modulated by a flexible linker positioned sequentially to the recruiting element. Our data explain how the FUSE system precisely regulates c-myc transcription and suggest that a small change in FBP-FIR affinity leads to a substantial effect on c-Myc concentration.MRC Grant-in-aid U11757455