81 research outputs found

    A systematic review of patient and health system characteristics associated with late referral in chronic kidney disease

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    <p>Abstract</p> <p>Background</p> <p>To identify patient and health system characteristics associated with late referral of patients with chronic kidney disease to nephrologists.</p> <p>Methods</p> <p>MEDLINE, CENTRAL, and CINAHL were searched using the appropriate MESH terms in March 2007. Two reviewers individually and in duplicate reviewed the abstracts of 256 articles and selected 18 observational studies for inclusion. The reasons for late referral were categorized into patient or health system characteristics. Data extraction and content appraisal were done using a prespecified protocol.</p> <p>Results</p> <p>Older age, the existence of multiple comorbidities, race other than Caucasian, lack of insurance, lower socioeconomic status and educational levels were patient characteristics associated with late referral of patients with chronic kidney disease. Lack of referring physician knowledge about the appropriate timing of referral, absence of communication between referring physicians and nephrologists, and dialysis care delivered at tertiary medical centers were health system characteristics associated with late referral of patients with chronic kidney disease. Most studies identified multiple factors associated with late referral, although the relative importance and the combined effect of these factors were not systematically evaluated.</p> <p>Conclusion</p> <p>A combination of patient and health system characteristics is associated with late referral of patients with chronic kidney disease. Overall, being older, belonging to a minority group, being less educated, being uninsured, suffering from multiple comorbidities, and the lack of communication between primary care physicians and nephrologists contribute to late referral of patients with chronic kidney disease. Both primary care physicians and nephrologists need to engage in multisectoral collaborative efforts that ensure patient education and enhance physician awareness to improve the care of patients with chronic kidney disease.</p

    Gene expression profiling of primary cultures of ovarian epithelial cells identifies novel molecular classifiers of ovarian cancer

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    In order to elucidate the biological variance between normal ovarian surface epithelial (NOSE) and epithelial ovarian cancer (EOC) cells, and to build a molecular classifier to discover new markers distinguishing these cells, we analysed gene expression patterns of 65 primary cultures of these tissues by oligonucleotide microarray. Unsupervised clustering highlights three subgroups of tumours: low malignant potential tumours, invasive solid tumours and tumour cells derived from ascites. We selected 18 genes with expression profiles that enable the distinction of NOSE from these three groups of EOC with 92% accuracy. Validation using an independent published data set derived from tissues or primary cultures confirmed a high accuracy (87–96%). The distinctive expression pattern of a subset of genes was validated by quantitative reverse transcription–PCR. An ovarian-specific tissue array representing tissues from NOSE and EOC samples of various subtypes and grades was used to further assess the protein expression patterns of two differentially expressed genes (Msln and BMP-2) by immunohistochemistry. This study highlights the relevance of using primary cultures of epithelial ovarian cells as a model system for gene profiling studies and demonstrates that the statistical analysis of gene expression profiling is a useful approach for selecting novel molecular tumour markers

    SPIRITS: Uncovering Unusual Infrared Transients with Spitzer

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    We present an ongoing, five-year systematic search for extragalactic infrared transients, dubbed SPIRITS—SPitzer InfraRed Intensive Transients Survey. In the first year, using Spitzer/IRAC, we searched 190 nearby galaxies with cadence baselines of one month and six months. We discovered over 1958 variables and 43 transients. Here, we describe the survey design and highlight 14 unusual infrared transients with no optical counterparts to deep limits, which we refer to as SPRITEs (eSPecially Red Intermediate-luminosity Transient Events). SPRITEs are in the infrared luminosity gap between novae and supernovae, with [4.5] absolute magnitudes between −11 and −14 (Vega-mag) and [3.6]–[4.5] colors between 0.3 mag and 1.6 mag. The photometric evolution of SPRITEs is diverse, ranging from 7 mag yr−1. SPRITEs occur in star-forming galaxies. We present an in-depth study of one of them, SPIRITS 14ajc in Messier 83, which shows shock-excited molecular hydrogen emission. This shock may have been triggered by the dynamic decay of a non-hierarchical system of massive stars that led to either the formation of a binary or a protostellar merger

    The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

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    We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

    Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

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    The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

    Open Versus Ultrasound Guided Tunneled Central Venous Access in children: A Randomized Controlled Study.

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    BACKGROUND: The purpose of this study was to compare open insertion to ultrasound guided percutaneous insertion of central access catheters performed in a tertiary pediatric hospital in terms of its safety and complication rates. METHODS: This was an ethics approved prospective randomized trial of children under 16 y of age. Procedure was performed by surgeons with varying experience with percutaneous and open insertion. Primary outcome studied was complications-immediate and late. Secondary outcomes were time taken to complete procedure, conversion rates, duration of line use. RESULTS: A total of 108 patients were analyzed. Sixty-four were male. Right internal jugular vein was accessed in 97. Eighty-one lines were double lumen, 23 implantable access devices, and the rest were single lumen catheters. More than one needle puncture was needed in 22% of the cases but there were no conversions in the ultrasound group. Twelve patients needed more than one insertion to achieve optimal position of the tip. Eleven patients had immediate and late complications. Percutaneous lines lasted 45 d longer though this was not statistically significant. Operating time was 20.6% shorter with percutaneous access. Post-removal measurement of vein size by ultrasound demonstrated significant decrease in size in the open group. CONCLUSIONS: Ultrasound guided percutaneous insertion was safe. The study also demonstrated a decrease in operating times, preservation of vein size, and no increase in complication rates in the US group when performed by operators of varying expertise

    Corrigendum to "Open vs Ultrasound Guided Tunneled Central Venous Access in Children: A Randomised Controlled Study": Journal of Surgical Research April 2021 (260) 284-292.

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    The authors regret an error in the manuscript of the article in the results section. Fig. 4 shows comparison of case numbers in the age groups between the study and control groups and not decrease in vein size as mentioned. Decrease in vein size is in table 1. The authors would like to apologise for any inconvenience caused

    Neurocognitive outcomes in children following immersion: A long-term study

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    Objective To investigate long-term neurocognitive outcomes after a near-drowning incident in children who were deemed neurologically intact on discharge from hospital. Design A prospective cohort study of near-drowning children. Setting 95 drowning and near-drowning admissions, 0-16 years of age, from January 2009 to December 2013, to The Children's Hospital at Westmead, Sydney, NSW, Australia. Participants 23 children both met the criteria and had parental consent for the study. Main outcome measures Identification of the long-term deficits in behaviour, executive function, motor skills, communicative skills and well-being over a 5-year period. Assessment was undertaken at 3-6 months, 1 year, 3 years and 5 years after near-drowning at clinic visits. Physical developmental screening and executive function screening were done using Behavior Rating Inventory of Executive Function-Preschool version (BRIEF-P) and BRIEF. Result 95 drowning and near-drowning episodes occurred during the study period. 10 (11%) children died, 28 were admitted to the paediatric intensive care unit and 64 directly to a ward. 3 children died in emergency department, 7 children had severe neurological deficit on discharge from the hospital. 23 were subsequently recruited into the study; 5 (22%) of these children had abnormalities in behaviour and/or executive function at some during their follow-up. Conclusion Children admitted to hospital following a near-drowning event warrant long-term follow-up to identify any subtle sequelae which might be amenable to intervention to ensure optimal patient outcome
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