971 research outputs found

    UK Renal Registry 18th Annual Report: Chapter 11 2014 Multisite Dialysis Access Audit in England, Northern Ireland and Wales and 2013 PD One Year Follow-up: National and Centre-specific Analyses

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    Data are presented from the third combined vascular and peritoneal dialysis access audit. In 2014, 53 centres in England, Wales and Northern Ireland (out of 62) returned data on first access from 4,339 incident haemodialysis (HD) patients and 1,090 incident peritoneal dialysis (PD) patients. Of the 5,429 incident patients, 20.1% started dialysis on PD, 27.8% started with an arteriovenous fistula (AVF), 1.0% with an arteriovenous graft (AVG), 27.1% on a tunnelled line (TL) and 24.0% on a non-tunnelled line (NTL). Older patients (565 years) were more likely to start haemodialysis using AVF compared to their younger counterparts (36.2% vs. 32.8%). Thirteen of the nineteen centres (68%) using the physician led percutaneous insertion technique had over 20% of their incident patients starting on PD when compared to only seven out of fourteen centres (50%) which used single technique (open surgical or laparoscopic) for their PD catheter insertion. Wide variations were apparent between centres for use of AVF as the first haemodialysis access ranging from 10-54%. Eight of the 49 centres were achieving close to the 65% target for AV fistula in their incident patients. Length of time known to nephrology services and likelihood of commencing dialysis using either an AVF or a PD catheter are strongly associated. Patients who were known to a nephrologist for over one year were more likely to start dialysis with AVF, as compared to those who were referred between 90-365 days (39.2% vs. 24.6%). Similarly, patients who were known to a nephrologist between 90 days and one year were more likely to start on PD when compared to patients who were referred ,90 days prior to dialysis start (26.9% vs. 9.1%). By comparison, amongst the late presenters, only 3.5% had first access documented as an AVF and 87.3% started dialysis on either a tunnelled line or a nontunnelled line. Initial surgical assessment was a key determinant of the likelihood of AVF formation. Of the incident patients known to renal services for longer than three months and in those assessed by a surgeon at least three months prior to starting dialysis, 71.4% started dialysis with an AVF whereas of those who were not seen by a surgeon only 10.8% did. Thirty one of the 38 centres were 2 or 3 standard deviations below the 85% target for prevalent haemodialysis patients with an AV fistula. For centres returning data on one-year peritoneal dialysis outcomes, the majority of centres (28/32) maintained 550% of patients on PD at one year, having censored for transplantation. This report demonstrates wide variations in practice between centres across several domains in the provision of dialysis access and further work will be required to understand the underlying reasons

    Immunophenotyping without antibodies: New perspectives for lymphoma characterization

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    Aims: Accurate classification of haematological malignancies is a prerequisite for their correct diagnosis, prognosis and therapy. Clear classification of lymphomas is often hindered by the limited number of available cell surface protein markers that are suitable for immunophenotyping. A systematic and quantitative analysis of cell surface proteins is thus required to identify new protein markers on lymphoma subtypes in an unbiased and discovery-driven approach. Methods: Nine Hodgkin and non-Hodgkin B cell lines of diffuse large cell type and mediastinal type were investigated by cell surface capture (CSC) technology, a mass spectrometry-based method to identify cell surface glycoproteins. Selected proteins are verified by antibody-based methods, including flow cytometry and immunohistochemistry on cell line arrays. Results: A total of 747 predicted transmembrane proteins were identified from all cell lines, including 142 CD (cluster of differentiation) annotated proteins. A group of differentially expressed cell surface glycoproteins between Hodgkin and non-Hodgkin B cell lines was revealed via quantitative CSC technology. In addition to classical and expected CD molecules such as CD20 and CD30, less frequently expressed molecules such as CD2 on Hodgkin lymphoma (HL) cell lines were identified by CSC and verified by immunohistochemistry in cell lines and primary lymphoma tissue. A panel of CSC-identified differentiation glycoprotein candidates is currently under investigation on tissue microarrays (TMAs) from patient sample

    Structural insights on TRPV5 gating by endogenous modulators.

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    TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery

    Focusing on ICT in Rural and Regional Education in Australia

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    National priorities set by an Australian ministerial taskforce provide clear guidelines to develop pedagogy that integrates ICT. Although these guidelines do not specifically address rural and regional schools needs, the two priorities: promoting pedagogic leadership and creating new learning environments, are of particular interest. But how are these priorities reflected in the realities of rural and regional schools? Focus group interviews were conducted at a selection of rural and regional schools in each state and territory across Australia. These provided teachers, parents and students with the opportunity to identify key issues in relation to ICT in their schools. Issues identified by the focus groups were; the state of equipment in schools, comparability between home and school ICT experiences for students, pedagogical approaches, leadership, professional development and availability of ICT specialist teachers
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