1,180 research outputs found

    Multi-format Notifications for Multi-tasking

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    Abstract. We studied people's perception of and response to a set of visual and auditory notifications issued in a multi-task environment. Primary findings show that participants' reactive preference ratings of notifications delivered in various contexts during experimentation appear to contradict their reflective, overall ratings of the notification formats when elicited independently of contextual information, indicating a potential difficulty in people's abilities to articulate their preferences in the absence of context. We also found people to vary considerably in their preferences for different notification formats delivered in different contexts, such taht simple approaches to selecting notification delivery formats will be dissatisfying to users a substantial portion of the time. These findings can inform the designs of future systems: rather than target the general user alone, they should strive to better understand each user individually

    Reassessing the association: Evaluation of a polyalanine deletion variant of RUNX2 in non‐syndromic sagittal and metopic craniosynostosis

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    The RUNT‐related transcription factor RUNX2 plays a critical role in osteoblast differentiation, and alterations to gene dosage cause distinct craniofacial anomalies. Uniquely amongst the RUNT‐related family, vertebrate RUNX2 encodes a polyglutamine/polyalanine repeat (Gln23‐Glu‐Ala17 in humans), with the length of the polyalanine component completely conserved in great apes. Surprisingly, a frequent 6‐amino acid deletion polymorphism, p.(Ala84_Ala89)del, occurs in humans (termed 11A allele), and a previous association study (Cuellar et al. Bone 137:115395;2020) reported that the 11A variant was significantly more frequent in non‐syndromic sagittal craniosynostosis (nsSag; allele frequency [AF] = 0.156; 95% confidence interval [CI] 0.126–0.189) compared to non‐syndromic metopic craniosynostosis (nsMet; AF = 0.068; 95% CI 0.045–0.098). However, the gnomAD v.2.1.1 control population used by Cuellar et al. did not display Hardy–Weinberg equilibrium, hampering interpretation. To re‐examine this association, we genotyped the RUNX2 11A polymorphism in 225 individuals with sporadic nsSag as parent–child trios and 164 singletons with sporadic nsMet, restricting our analysis to individuals of European ancestry. We compared observed allele frequencies to the non‐transmitted alleles in the parent–child trios, and to the genome sequencing data from gnomAD v.4, which display Hardy–Weinberg equilibrium. Observed AFs (and 95% CI) were 0.076 (0.053–0.104) in nsSag and 0.082 (0.055–0.118) in nsMet, compared with 0.062 (0.042–0.089) in non‐transmitted parental alleles and 0.065 (0.063–0.067) in gnomAD v.4.0.0 non‐Finnish European control genomes. In summary, we observed a non‐significant excess, compared to gnomAD data, of 11A alleles in both nsSag (relative risk 1.18, 95% CI 0.83–1.67) and nsMet (relative risk 1.29, 95% CI 0.87–1.92), but we did not replicate the much higher excess of RUNX2 11A alleles in nsSag previously reported (p = 0.0001)

    Unexpected Widespread Hypophosphatemia and Bone Disease Associated with Elemental Formula Use in Infants and Children

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    OBJECTIVE: Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. METHODS: A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. RESULTS: Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed NeocateÂź formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. CONCLUSION: The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop

    The role of ICT in supporting disruptive innovation: a multi-site qualitative study of nurse practitioners in emergency departments

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    <p>Abstract</p> <p>Background</p> <p>The disruptive potential of the Nurse Practitioner (NP) is evident in their ability to offer services traditionally provided by primary care practitioners and their provision of a health promotion model of care in response to changing health trends. No study has qualitatively investigated the role of the Emergency NP in Australia, nor the impact of Information and Communication Technology (ICT) on this disruptive workforce innovation. This study aimed to investigate ways in which Nurse Practitioners (NP) have incorporated the use of ICT as a mechanism to support their new clinical role within Emergency Departments.</p> <p>Methods</p> <p>A cross-sectional qualitative study was undertaken in the Emergency Departments (EDs) of two large Australian metropolitan public teaching hospitals. Semi-structured, in-depth interviews were conducted with five nurse practitioners, four senior physicians and five senior nurses. Transcribed interviews were analysed using a grounded theory approach to develop themes in relation to the conceptualisation of the ED nurse practitioner role and the influences of ICT upon the role. Member checking of results was achieved by revisiting the sites to clarify findings with participants and further explore emergent themes.</p> <p>Results</p> <p>The role of the ENP was distinguished from those of Emergency nurses and physicians by two elements: advanced practice and holistic care, respectively. ICT supported the advanced practice dimension of the NP role in two ways: availability and completeness of electronic patient information enhanced timeliness and quality of diagnostic and therapeutic decision-making, expediting patient access to appropriate care. The ubiquity of patient data sourced from a central database supported and improved quality of communication between health professionals within and across sites, with wider diffusion of the Electronic Medical Record holding the potential to further facilitate team-based, holistic care.</p> <p>Conclusions</p> <p>ICT is a facilitator through which the disruptive impact of NPs can be extended. However, integration of ICT into work practices without detracting from provider-patient interaction is crucial to ensure utilisation of such interventions and realisation of potential benefits.</p

    Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

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    Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression
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