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"Roberts, Ian"
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The wonders of language : or How to make noises and influence people
\"Ian Roberts offers a stimulating introduction to our greatest gift as a species: our capacity for articulate language. We are mostly as blissfully unaware of the intricacies of the structure of language as fish are of the water they swim in. We live in a mental ocean of nouns, verbs, quantifiers, morphemes, vowels and other rich, strange and deeply fascinating linguistic objects. This book introduces the reader to this amazing world. Offering a thought-provoking and accessible introduction to the main discoveries and theories about language, the book is aimed at general readers and undergraduates who are curious about linguistics and language. Written in a lively and direct style, technical terms are carefully introduced and explained and the book includes a full glossary. The book covers all the central areas of linguistics, including phonetics, phonology, morphology, syntax, semantics and pragmatics, as well as historical linguistics, sociolinguistics and psycholinguistics\"-- Provided by publisher.
Book
Post-mortem imaging as an alternative to autopsy in the diagnosis of adult deaths: a validation study
Public objection to autopsy has led to a search for minimally invasive alternatives. Imaging has potential, but its accuracy is unknown. We aimed to identify the accuracy of post-mortem CT and MRI compared with full autopsy in a large series of adult deaths.
This study was undertaken at two UK centres in Manchester and Oxford between April, 2006, and November, 2008. We used whole-body CT and MRI followed by full autopsy to investigate a series of adult deaths that were reported to the coroner. CT and MRI scans were reported independently, each by two radiologists who were masked to the autopsy findings. All four radiologists then produced a consensus report based on both techniques, recorded their confidence in cause of death, and identified whether autopsy was needed.
We assessed 182 unselected cases. The major discrepancy rate between cause of death identified by radiology and autopsy was 32% (95% CI 26–40) for CT, 43% (36–50) for MRI, and 30% (24–37) for the consensus radiology report; 10% (3–17) lower for CT than for MRI. Radiologists indicated that autopsy was not needed in 62 (34%; 95% CI 28–41) of 182 cases for CT reports, 76 (42%; 35–49) of 182 cases for MRI reports, and 88 (48%; 41–56) of 182 cases for consensus reports. Of these cases, the major discrepancy rate compared with autopsy was 16% (95% CI 9–27), 21% (13–32), and 16% (10–25), respectively, which is significantly lower (p<0·0001) than for cases with no definite cause of death. The most common imaging errors in identification of cause of death were ischaemic heart disease (n=27), pulmonary embolism (11), pneumonia (13), and intra-abdominal lesions (16).
We found that, compared with traditional autopsy, CT was a more accurate imaging technique than MRI for providing a cause of death. The error rate when radiologists provided a confident cause of death was similar to that for clinical death certificates, and could therefore be acceptable for medicolegal purposes. However, common causes of sudden death are frequently missed on CT and MRI, and, unless these weaknesses are addressed, systematic errors in mortality statistics would result if imaging were to replace conventional autopsy.
Policy Research Programme, Department of Health, UK.
Journal Article
Pathology of IgA nephropathy
Key Points
IgA nephropathy is defined by the presence of IgA-dominant or co-dominant glomerular deposits
Glomerular changes under light microscopy are diverse, ranging from minimal abnormality to crescentic glomerulonephritis, or an appearance resembling primary focal segmental glomerulosclerosis
Mesangial hypercellularity, segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis are of prognostic value and predict renal outcomes independent of clinical variables
Evidence from retrospective clinicopathological studies indicates that endocapillary hypercellularity and cellular crescents are responsive to steroid and/or immunosuppressive therapy
Prospective data from randomized control trials are required to determine how histopathology should be used to guide therapy
In this Review, Ian Roberts provides a detailed description of the immunohistology and light microscopical features of IgA nephropathy, and highlights the importance of accurate recognition of the various histological lesions for reproducible classification of the disease. The different schemas used for classifying IgA nephropathy are compared, with particular focus on the Oxford classification.
IgA nephropathy is defined by the presence of IgA-dominant or co-dominant immune deposits within glomeruli. Biopsy specimens meeting these diagnostic criteria have a range of histological changes that are reflected in the variable clinical course of IgA nephropathy. The impact of histology on outcomes in IgA nephropathy has been clarified in a number of large retrospective clinicopathological studies. These studies have consistently demonstrated that the stage of disease at presentation, as indicated by the extent of interstitial fibrosis and tubular atrophy in the biopsy, is the strongest histological predictor of renal survival. The effect of active proliferative lesions on the disease course is less clear cut, owing in part to considerable treatment bias in most published retrospective studies. There is evidence that endocapillary hypercellularity and cellular crescents are responsive to immunosuppressive therapy, but this observation requires confirmation in prospective randomized controlled trials. Future challenges include improving the reproducibility of histological scoring, particularly for the presence and extent of endocapillary lesions, and to improve prognostic modelling by combining histological data with clinical variables and biomarker data.
Journal Article
The origins, prevention and treatment of infant crying and sleeping problems : an evidence-based guide for healthcare professionals and the families they support
\"Babies who cry a lot, or are unsettled in the night, are common sources of concern for parents and, consequently, costly problems for health services. In this book, Ian St James-Roberts summarises new evidence concerning infant crying and sleeping problems to provide an evidence-based approach to the subject. The book begins by distinguishing between infant and parental parts of the problems and provides guidelines for assessing each issue. Topics covered include: - the pros and cons of 'infant-demand' versus 'limit-setting' - causes of infant 'colicky' crying and night waking - effects of night-time separations on infant attachments - interventions such as swaddling and herbal remedies. Since there is now firm evidence that parents' vulnerabilities and cultural backgrounds affect how problems are defined and guidance is acted upon, and that parents who wish to do so can reduce infant crying and unsettled night waking, social factors are considered alongside medical issues. Translating research evidence into practical tools and guidance, The Origins, Prevention and Treatment of Infant Crying and Sleeping Problems will therefore be essential reading for a wide range of professionals including mental health staff, social workers, midwives and health visitors\"-- Provided by publisher.
Book
Next-Generation Morphometry for pathomics-data mining in histopathology
Pathology diagnostics relies on the assessment of morphology by trained experts, which remains subjective and qualitative. Here we developed a framework for large-scale histomorphometry (FLASH) performing deep learning-based semantic segmentation and subsequent large-scale extraction of interpretable, quantitative, morphometric features in non-tumour kidney histology. We use two internal and three external, multi-centre cohorts to analyse over 1000 kidney biopsies and nephrectomies. By associating morphometric features with clinical parameters, we confirm previous concepts and reveal unexpected relations. We show that the extracted features are independent predictors of long-term clinical outcomes in IgA-nephropathy. We introduce single-structure morphometric analysis by applying techniques from single-cell transcriptomics, identifying distinct glomerular populations and morphometric phenotypes along a trajectory of disease progression. Our study provides a concept for Next-generation Morphometry (NGM), enabling comprehensive quantitative pathology data mining, i.e., pathomics.
Pathology diagnostics still rely on tissue morphology assessment by trained experts. Here, the authors perform deep-learning-based segmentation followed by large-scale feature extraction of histological images, i.e., next-generation morphometry, to enable outcome-relevant and disease-specific pathomics analysis of non-tumor kidney pathology.
Journal Article
Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis
Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment.
Journal Article
Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis
Background
Tranexamic acid (TXA) reduces surgical bleeding and reduces death from bleeding after trauma and childbirth. However, its effects on thrombotic events and seizures are less clear. We conducted a systematic review and meta-analysis to examine the safety of TXA in bleeding patients.
Methods
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials from inception until June 1, 2020. We included randomized trials comparing intravenous tranexamic acid and placebo or no intervention in bleeding patients. The primary outcomes were thrombotic events, venous thromboembolism, acute coronary syndrome, stroke and seizures. A meta-analysis was performed using a random effects model and meta-regression analysis was performed to evaluate how effects vary by dose. We assessed the certainty of evidence using the grading of recommendations, assessment, development and evaluations (GRADE) approach.
Results
A total of 234 studies with 102,681 patients were included in the meta-analysis. In bleeding patients, there was no evidence that TXA increased the risk of thrombotic events (RR = 1.00 [95% CI 0.93–1.08]), seizures (1.18 [0.91–1.53]), venous thromboembolism (1.04 [0.92–1.17]), acute coronary syndrome (0.88 [0.78–1.00]) or stroke (1.12 [0.98–1.27]). In a dose-by-dose sensitivity analysis, seizures were increased in patients receiving more than 2 g/day of TXA (3.05 [1.01–9.20]). Meta-regression showed an increased risk of seizures with increased dose of TXA (
p
= 0.011).
Conclusion
Tranexamic acid did not appear to increase the risk of thrombotic events in bleeding patients. However, because there may be dose-dependent increase in the risk of seizures, very high doses should be avoided.
Journal Article