303 research outputs found

    ‘Being the bridge and the beacon’: a qualitative study of the characteristics and functions of the liaison role in child and family health services in Australia

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    © 2016 John Wiley & Sons Ltd Aims and objectives: This article explores the characteristics and functions of the liaison role in child and family health services in Australia. Background: Liaison roles are increasingly being used to improve communication between health services and professionals and to facilitate access to support for individuals and families in need. Nurses are commonly, although not always, the professionals who undertake these roles. Research on the role and outcomes of liaison positions in child and family health services is limited in Australia and internationally. Design: A qualitative interpretive design informed this study. Interviews and focus groups were conducted with 40 liaison and other health professionals, primarily nurses, working with families with newborn and young children in two Australian States. Data were analysed thematically. Results: Three major themes were identified reflecting the importance of defining the role and tasks which included building bridges between services and professionals, supporting families during transition between services and supporting clinicians. Several facilitators and barriers were identified, including concerns about sustainability of the roles. Conclusions: Professionals working in a liaison role in child and family health services emphasise that these positions have the potential to link services and professionals, thereby providing more effective care pathways for children and families especially for those with complex and multiple vulnerabilities. While a few children and family health services in Australia provide liaison services, the extent of liaison support and the outcomes for families in Australia is unknown. Relevance to clinical practice: Nurses working with children and families are the most likely health professionals to undertake a liaison role. In many nursing contexts, liaison roles are relatively new and those in the role have the responsibility to define the key purpose of their role. Liaison roles are multifaceted requiring the nurse to have excellent communication and negotiation skills to effectively link diverse professionals and services, while simultaneously engaging with and supporting vulnerable families and children. Nurses in these roles also support and educate clinical colleagues

    Gastro-oesophageal reflux: A mixed methods study of infants admitted to hospital in the first 12months following birth in NSW (2000-2011)

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    © 2018 The Author(s). Background: Gastro-oesophageal reflux (GOR) is common in infants. When the condition causes pathological symptoms and/or complications it is considered gastro-oesophageal reflux disease (GORD). It appears to be increasingly diagnosed and causes great distress in the first year of infancy. In New South Wales (NSW), residential parenting services support families with early parenting difficulties. These services report a large number of babies admitted with a label of GOR/GORD. The aim of this study was to explore the maternal and infant characteristics, obstetric interventions, and reasons for clinical reporting of GOR/GORD in NSW in the first 12months following birth (2000-2011). Methods: A three phase, mixed method sequential design was used. Phase 1 included a linked data population based study (n=869,188 admitted babies). Phase 2 included a random audit of 326 medical records from admissions to residential parenting centres in NSW (2013). Phase 3 included eight focus groups undertaken with 45 nurses and doctors working in residential parenting centres in NSW. Results: There were a total of 1,156,020 admissions recorded of babies in the first year following birth, with 11,513 containing a diagnostic code for GOR/GORD (1% of infants admitted to hospitals in the first 12months following birth). Babies with GOR/GORD were also more likely to be admitted with other disorders such as feeding difficulties, sleep problems, and excessive crying. The mothers of babies admitted with a diagnostic code of GOR/GORD were more likely to be primiparous, Australian born, give birth in a private hospital and have: a psychiatric condition; a preterm or early term infant (37-or-38weeks); a caesarean section; an admission of the baby to SCN/NICU; and a male infant. Thirty six percent of infants admitted to residential parenting centres in NSW had been given a diagnosis of GOR/GORD. Focus group data revealed two themes: "It is over diagnosed" and "A medical label is a quick fix, but what else could be going on?" Conclusions: Mothers with a mental health disorder are nearly five times as likely to have a baby admitted with GOR/GORD in the first year after birth. We propose a new way of approaching the GOR/GORD issue that considers the impact of early birth (immaturity), disturbance of the microbiome (caesarean section) and mental health (maternal anxiety in particular)

    Ultrafast laser inscribed Yb:KGd(WO4)2 and Yb:KY(WO4)2 channel waveguide lasers

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    We demonstrate laser action in diode-pumped microchip monolithic cavity channel waveguides of Yb:KGd(WO4)2 and Yb:KY(WO4)2 that were fabricated by ultrafast laser writing. The maximum output power achieved was 18.6 mW with a threshold of approximately 100 mW from an Yb:KGd(WO4)2waveguide laser operating at 1023 nm. The propagation losses for this waveguide structure were measured to be 1.9 dBcm−1

    Flow-based pipeline for systematic modulation and analysis of 3D tumor microenvironments

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    The cancer microenvironment, which incorporates interactions with stromal cells, extracellular matrix (ECM), and other tumor cells in a 3-dimensional (3D) context, has been implicated in every stage of cancer development, including growth of the primary tumor, metastatic spread, and response to treatment. Our understanding of the tumor microenvironment and our ability to develop new therapies would greatly benefit from tools that allow us to systematically probe microenvironmental cues within a 3D context. Here, we leveraged recent advances in microfluidic technology to develop a platform for high-throughput fabrication of tunable cellular microniches (“microtissues”) that allow us to probe tumor cell response to a range of microenvironmental cues, including ECM, soluble factors, and stromal cells, all in 3D. We further combine this tunable microniche platform with rapid, flow-based population level analysis (n > 500), which permits analysis and sorting of microtissue populations both pre- and post-culture by a range of parameters, including proliferation and homotypic or heterotypic cell density. We used this platform to demonstrate differential responses of lung adenocarcinoma cells to a selection of ECM molecules and soluble factors. The cells exhibited enhanced or reduced proliferation when encapsulated in fibronectin- or collagen-1-containing microtissues, respectively, and they showed reduced proliferation in the presence of TGF-β, an effect that we did not observe in monolayer culture. We also measured tumor cell response to a panel of drug targets and found, in contrast to monolayer culture, specific sensitivity of tumor cells to TGFβR2 inhibitors, implying that TGF-β has an anti-proliferative affect that is unique to the 3D context and that this effect is mediated by TGFβR2. These findings highlight the importance of the microenvironmental context in therapeutic development and that the platform we present here allows the high-throughput study of tumor response to drugs as well as basic tumor biology in well-defined microenvironmental niches.American Association for Cancer Research (Stand Up to Cancer Charitable Initiative)National Institute for Biomedical Imaging and Bioengineering (U.S.) (National Research Service Award Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship Program Grant 1122374)Howard Hughes Medical Institut

    Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies

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    A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, and hematopoietic lineages. These 3D structures capture key features of human bone marrow— stroma, lumen-forming sinusoids, and myeloid cells including proplatelet-forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGFβ stimulation and engraftment with myelofibrosis but not healthy donor–derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow–like milieu. This enabling technology is likely to accelerate the discovery and prioritization of novel targets for bone marrow disorders and blood cancers. SIGNIFICANCE: We present a human bone marrow organoid that supports the growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment and provides a much-needed ex vivo tool for the prioritization of new therapeutics.</p

    Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A

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    Chromothripsis, the process of catastrophic shattering and haphazard repair of chromosomes, is a common event in cancer. Whether chromothripsis might constitute an actionable molecular event amenable to therapeutic targeting remains an open question. We describe recurrent chromothripsis of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ∼25% of patients (‘chr21amp’). We report that chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. The chr21amp event is highly clonal and present throughout the hematopoietic hierarchy. DYRK1A, a serine threonine kinase and transcription factor, is the only gene in the 2.7Mb minimally amplified region which showed both increased expression and chromatin accessibility compared to non-chr21amp BP-MPN controls. We demonstrate that DYRK1A is a central node at the nexus of multiple cellular functions critical for BP-MPN development, including DNA repair, STAT signalling and BCL2 overexpression. DYRK1A is essential for BP-MPN cell proliferation in vitro and in vivo, and DYRK1A inhibition synergises with BCL2 targeting to induce BP-MPN cell apoptosis. Collectively, these findings define the chr21amp event as a prognostic biomarker in BP-MPN and link chromothripsis to a druggable target
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