The John Radcliffe Hospital

Oxford, United Kingdom

The John Radcliffe Hospital

Oxford, United Kingdom
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Gajewska-Knapik K.,The John Radcliffe Hospital | Impey L.,The John Radcliffe Hospital
Seminars in Pediatric Surgery | Year: 2015

Congenital lung lesions are common sonographic findings in pregnancy, usually detected at the routine 20 weeks scan. The most common is cystic adenomatous malformation of the lung (CCAM). This usually causes few prenatal problems; however, fetal hydrops occurs in about 5%. Prenatal intervention for these is possible in many to allow survival to birth. Bronchoplumonary sequestration (BPS), with an aberrant "feeder" vessel arising from the aorta may co-exist but is detectable as a separate entity by visualization of this vessel. Symptomatic or curative prenatal intervention is again possible in the few severe cases where hydrops or pleural effusions develop. Pleural effusions may be due to a primary leak usually of chylous fluid: prenatal thoracoamniotic shunting may prevent pulmonary hyoplasia or cure the consequent fetal hydrops. More often, however, effusions are a consequence of an underlying abnormality, including many structural or chromosomal abnormalities that may also cause co-existing fetal hydrops. Congenital high airway obstruction (CHAOS) is commonly fatal but cases potentially amenable to prenatal intervention or to immediate perinatal management may be identified using ultrasound or MRI. © 2015 Elsevier Inc.


Li J.,University of Toronto | Rohailla S.,University of Toronto | Gelber N.,University of Toronto | Rutka J.,The Hospital for Sick Children | And 6 more authors.
Basic Research in Cardiology | Year: 2014

Remote ischemic preconditioning (rIPC) induced by cycles of transient limb ischemia and reperfusion is a powerful cardioprotective strategy with additional pleiotropic effects. However, our understanding of its underlying mediators and mechanisms remains incomplete. We examined the role of miR-144 in the cardioprotection induced by rIPC. Microarray studies first established that rIPC increases, and IR injury decreases miR-144 levels in mouse myocardium, the latter being rescued by both rIPC and intravenous administration of miR-144. Going along with this systemic treatment with miR-144 increased P-Akt, P-GSK3β and P-p44/42 MAPK, decreased p-mTOR level and induced autophagy signaling, and induced early and delayed cardioprotection with improved functional recovery and reduction in infarct size similar to that achieved by rIPC. Conversely, systemic administration of a specific antisense oligonucleotide reduced myocardial levels of miR-144 and abrogated cardioprotection by rIPC. We then showed that rIPC increases plasma miR-144 levels in mice and humans, but there was no change in plasma microparticle (50-400 nM) numbers or their miR-144 content. However, there was an almost fourfold increase in miR-144 precursor in the exosome pellet, and a significant increase in miR-144 levels in exosome-poor serum which, in turn, was associated with increased levels of the miR carriage protein Argonaute-2. Systemic release of microRNA 144 plays a pivotal role in the cardioprotection induced by rIPC. Future studies should assess the potential for plasma miR-144 as a biomarker of the effectiveness of rIPC induced by limb ischemia, and whether miR-144 itself may represent a novel therapy to reduce clinical ischemia-reperfusion injury. © 2014 Springer-Verlag Berlin Heidelberg.


De Silva R.J.,The John Radcliffe Hospital | Gallo A.,The John Radcliffe Hospital | Westaby S.,The John Radcliffe Hospital
European Journal of Cardio-thoracic Surgery | Year: 2012

End-stage cardiac failure where appropriate is best treated with cardiac transplantation. With improvements in medical therapy, the emergence of primary percutaneous coronary intervention, and an increasingly ageing population, patients with right, left or biventricular failure, who are not suitable for cardiac transplantation or long-term ventricular assist device therapy, present for cardiac surgery. The modern cardiac surgeon needs to have a safe strategy for dealing with these complex cases. We report two cases that illustrate simple and safe cannulation techniques for temporary left and right ventricular failure. © The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.


Collins S.L.,The John Radcliffe Hospital | Impey L.,The John Radcliffe Hospital
Early Human Development | Year: 2012

Up to 3% of UK pregnancies will be affected by congenital abnormality. Prenatal diagnosis allows the parents to make informed decisions about their pregnancy, healthcare professionals to optimise the antenatal care and families prepare for the birth of the baby. There are many techniques employed which range from the non-invasive ultrasonography to the highly invasive amniocentesis. This review explores the methods currently available in the UK as well as considering the newer minimally-invasive technologies available including cell-free fetal DNA and pre-implantation genetic diagnosis. © 2011 Elsevier Ireland Ltd.


Royston D.J.,The John Radcliffe Hospital | Warren B.F.,The John Radcliffe Hospital
Colorectal Disease | Year: 2011

Aim The accuracy of ileo-anal pouch biopsy reporting was assessed. Method The pathology reports of 100 consecutive pouch biopsies were reviewed to assess the accuracy and consistency with which the St Mark's histological scoring criteria were applied. The quality of pouch biopsy sampling and provision of clinical and endoscopic information on pathology request forms was also assessed. Results In 27% of cases no relevant endoscopic or clinical information was provided with the pathology request form. Separately labelled biopsies from the prepouch ileum, pouch and columnar cuff were submitted in only 4% of cases. In 32% of pathology reports, no acute or chronic St Mark's score was included. In 2% of cases the St Mark's scoring criteria were applied inappropriately. Twenty per cent of cases histologically diagnosed as pouchitis did not include a numerical score. In 30% of cases diagnosed histologically as pouchitis, an acute inflammatory score of <4 (i.e. insufficient for this diagnosis) was included in the report. Conclusion Pouchitis is a combined clinical, endoscopic and histological diagnosis. The correct interpretation and application of the St Mark's histological scoring criteria for pouch biopsies is an important part of this diagnostic process. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.


Jarrett M.E.,The John Radcliffe Hospital
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland | Year: 2010

The aim was to evaluate the relationship between the presence of an enterocoele and grade of rectal prolapse (RP). Defaecating proctograms of consecutive patients presenting to the Oxford Pelvic Floor Clinic between January 2004 and November 2008 were analysed. Patients were included if they had full thickness internal (grades 1-4 prolapse) or external RP (grade 5 prolapse). All those included were analysed with regards to the presence of an enterocoele. Three hundred and seventy-one patients [322 (87%) women and 49 (23%) men] were found to have a degree of RP. One out of eight (12.5%) patients with grade 1 RP, 10/42 (18.5%) with grade 2 RP, 34/125 (27%) with grade 3 RP, 62/135 (46%) with grade 4 RP and 23/49 (47%) with grade 5 full thickness external RP had an enterocoele present. This was a statistically significant trend (Pearson chi(2) test P < 0.0002). There was a significantly higher proportion of enterocoeles in women [125/322 (39%) than in men (5/49 (10%)] (P < 0.0001) and a higher likelihood of having an enterocoele with advancing age (P < 0.0001). Within the study, there was no significant difference in the proportion of nulliparous and parous women with enterocoeles (P = 0.8); there were a significantly higher proportion of enterocoeles in hysterectomized women (P = 0.015). Enterocoele is increasingly seen with advancing RP severity. This suggests that the two findings are part of the same pelvic floor process. These data support the hypothesis that enterocoele is a marker of severe pelvic floor weakness. Enterocoele is seen more frequently in females particularly after hysterectomy.


Watkinson P.J.,The John Radcliffe Hospital | Barber V.S.,The John Radcliffe Hospital | Amira E.,The John Radcliffe Hospital | James T.,The John Radcliffe Hospital | And 2 more authors.
Annals of Clinical Biochemistry | Year: 2012

Background: Critical care glycaemic control protocols commonly have treatment adjustment (target) ranges spanning ≤2 mmol/L. These require precise point-of-care glucose measurement, unaffected by other variables, to avoid measurement errors increasing glycaemic variability and hypoglycaemic episodes (both strongly associated with mortality in critically ill patients). Methods: A prospective 206 intensive care patient study was carried out. Arterial glucose concentrations were measured in duplicate using three point-of-care instruments (MediSense Precision PCχ, HemoCue DM and Radiometer 700), a central laboratory instrument (Siemens ADVIA), and in whole blood and plasma using the Yellow Springs Instruments 2300 instrument. Results: Coefficients of variation for the MediSense, HemoCue, Radiometer and Siemens instruments were 5.1%, 2.5%, 2.1% and 2.3%, respectively. Compared with the Siemens instrument, the bias (95% limits of agreement) for the MediSense, HemoCue and Radiometer instruments were 0.0 (-1.4 to 1.4), 0.0 (-1.2 to 1.1) and -0.2 (-0.9 to 0.6) mmol/L, respectively. The whole blood-plasma glucose concentration differencewas significantly affected by the haematocrit. MediSense and HemoCue instrument performances were substantially affected by haematocrit. MediSense instrument performance was also affected by pH and PaO2. Radiometer instrument performance was not affected by haematocrit, pH or PaO2. Conclusions: The MediSense instrument was too imprecise for use in critically ill patients. The haematocrit range seen is too great to allow fixed-factor conversion between whole blood and plasma values, substantially affecting the accuracy of both glucose meters. However, the Radiometer instrument was unaffected by the haematocrit, pH or pO2, resulting in a performance equivalent to the laboratory method. Instrument performance differences may therefore partially explain the differing results of tight glycaemic control therapy trials.


Herrington W.G.,The John Radcliffe Hospital | Nye H.J.,The John Radcliffe Hospital | Hammersley M.S.,The John Radcliffe Hospital | Watkinson P.J.,The John Radcliffe Hospital
Diabetic Medicine | Year: 2012

Aims To assess the comparability of venous and arterial samples for pH, bicarbonate and potassium measurements in critically ill patients. Methods Simultaneous arterial and venous samples from 206 critically ill patients were analysed in duplicate. Coefficients of variation and 95% limits of agreement were calculated for arterial and venous samples. Bland-Altman plots were constructed to assess agreement between sampling sites. Results The median (range) of arterial pH, bicarbonate concentrations, potassium concentrations and glucose concentrations were 7.40 (7.01-7.56), 25 (9-41) mmol/l, 4.2 (3.1-6.8) mmol/l and 7.4 (3.0-13.5) mmol/l, respectively. Coefficients of variation for arterial and venous pH were both 0.1%, with bias (95% limits of agreement) of -0.01 (-0.03 to 0.01) for arterial and -0.01 (-0.02 to 0.01) for venous samples. The bias (95% limits of agreement) between arterial and venous samples was 0.03 (-0.02 to 0.08). Coefficients of variation for arterial and venous bicarbonate results were 0.8 and 0.7%, respectively, with bias (95% limits of agreement) of 0 (-0.5 to 0.5) mmol/l for both sample types. The bias (95% limits of agreement) between venous and arterial samples was 0 (-1.3 to 1.3) mmol/l. Coefficients of variation for arterial and venous potassium samples were 0.8 and 1.1%, respectively, with bias (95% limits of agreement) of 0 (-0.1 to 0.1) for both sample types. The bias (95% limits of agreement) between venous and arterial samples was 0.1 (-0.4 to 0.6) mmol/l. Conclusions A venous blood sample, analysed on a blood gas machine, is sufficiently reliable to assess pH, bicarbonate and potassium concentrations in critically ill patients, suggesting that venous sampling alone is appropriate in the management of diabetic ketoacidosis. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.


Friston K.,University College London | Schwartenbeck P.,University College London | FitzGerald T.,University College London | Moutoussis M.,University College London | And 3 more authors.
Frontiers in Human Neuroscience | Year: 2013

This paper considers agency in the setting of embodied or active inference. In brief, we associate a sense of agency with prior beliefs about action and ask what sorts of beliefs underlie optimal behavior. In particular, we consider prior beliefs that action minimizes the Kullback-Leibler (KL) divergence between desired states and attainable states in the future. This allows one to formulate bounded rationality as approximate Bayesian inference that optimizes a free energy bound on model evidence. We show that constructs like expected utility, exploration bonuses, soft max choice rules and optimism bias emerge as natural consequences of this formulation. Previous accounts of active inference have focused on predictive coding and Bayesian filtering schemes for minimizing free energy. Here, we consider variational Bayes as an alternative scheme that provides formal constraints on the computational anatomy of inference and action-constraints that are remarkably consistent with neuroanatomy. Furthermore, this scheme contextualizes optimal decision theory and economic (utilitarian) formulations as pure inference problems. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (of soft max functions and quantal response equilibria) has a unique and Bayes-optimal solution-that minimizes free energy. This sensitivity corresponds to the precision of beliefs about behavior, such that attainable goals are afforded a higher precision or confidence. In turn, this means that optimal behavior entails a representation of confidence about outcomes that are under an agent's control. © 2013 Friston, Schwartenbeck, FitzGerald, Moutoussis, Behrens and Dolan.


Friston K.,University College London | Schwartenbeck P.,University College London | FitzGerald T.,University College London | Moutoussis M.,University College London | And 3 more authors.
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

This paper considers goal-directed decision-making in terms of embodied or active inference. We associate bounded rationality with approximate Bayesian inference that optimizes a free energy bound on model evidence. Several constructs such as expected utility, exploration or novelty bonuses, softmax choice rules and optimism bias emerge as natural consequences of free energy minimization. Previous accounts of active inference have focused on predictive coding. In this paper, we consider variational Bayes as a scheme that the brain might use for approximate Bayesian inference. This scheme provides formal constraints on the computational anatomy of inference and action, which appear to be remarkably consistent with neuroanatomy. Active inference contextualizes optimal decision theory within embodied inference, where goals become prior beliefs. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (associated with softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution. Crucially, this sensitivity corresponds to the precision of beliefs about behaviour. The changes in precision during variational updates are remarkably reminiscent of empirical dopaminergic responses—and they may provide a new perspective on the role of dopamine in assimilating reward prediction errors to optimize decision-making. ©2014 The Authors.

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