A pitfall in the interpretation of plain abdnominal radiographs in neonatal intestinal perforation: a case report

<p>Abstract</p> <p>Introduction</p> <p>The recognition of neonatal intestinal perforation relies on identification of free gas in the peritoneum on plain abdominal radiographs and the associated clinical signs. The neonatal bowel takes several hours to fill with gas, potentially obscuring one of the radiological signs of bowel perforation in the neonate.</p> <p>Case presentation</p> <p>We describe the case of a male, Caucasian neonate, born prematurely at 35⁺²weeks of gestation, who was suspected before birth to be at risk of intestinal perforation, based on antenatal ultrasound signs of bowel obstruction. However, the diagnosis of intestinal perforation after birth was initially delayed because the first abdominal radiograph, requested by the neonatal team, was taken too early in the clinical progression of the neonate's condition. As a consequence, this delayed referral to the paediatric surgical team and definitive management.</p> <p>Conclusion</p> <p>This case illustrates how consideration of the timing of abdominal radiographs in suspected intestinal perforation in the neonate may avoid misinterpretation of radiographic signs, thereby avoiding delays in referral and treatment in the crucial first few hours of life.</p

The Campbells: lordship, literature and liminality

The Campbells have the potential to offer much to the theme of literature and borders, given that the kindred’s astonishing political success in the late medieval and early modern period depended heavily upon the ability to negotiate multiple frontiers: between Highlands and Lowlands; between Gaelic Scotland and Ireland, and, especially after the Reformation, with England and the matter of Britain. This paper will explore the literary dimension to Campbell expansionism, from the Book of the Dean of Lismore in the earlier sixteenth century, to poetry addressed to dukes of Argyll in the earlier eighteenth century. Particular attention will be paid to the literary proclivities of the household of the Campbells of Glenorchy on either side of what appears to be a major watershed in 1550; and to the agenda of the Campbell protégé John Carswell, first post-Reformation bishop of the Isles, and author of the first printed book in Gaelic in either Scotland or Ireland, Foirm na n-Urrnuidheadh (‘The Form of Prayers’), published at Edinburgh in 1567

A mathematical model of tumour & blood pHe regulation: The HCO-3/CO2 buffering system

Malignant tumours are characterised by a low, acidic extracellular pH (pHe) which facilitates invasion and metastasis. Previous research has proposed the potential benefits of manipulating systemic pHe, and recent experiments have highlighted the potential for buffer therapy to raise tumour pHe, prevent metastases, and prolong survival in laboratory mice. To examine the physiological regulation of tumour buffering and investigate how perturbations of the buffering system (via metabolic/respiratory disorders or changes in parameters) can alter tumour and blood pHe, we develop a simple compartmentalised ordinary differential equation model of pHe regulation by the View the MathML source buffering system. An approximate analytical solution is constructed and used to carry out a sensitivity analysis, where we identify key parameters that regulate tumour pHe in both humans and mice. From this analysis, we suggest promising alternative and combination therapies, and identify specific patient groups which may show an enhanced response to buffer therapy. In addition, numerical simulations are performed, validating the model against well-known metabolic/respiratory disorders and predicting how these disorders could change tumour pHe

Predicting the safety and efficacy of butter therapy to raise tumour pHe: an integrative modelling study

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts.\ud \ud Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies.\ud \ud Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2.\ud \ud Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising

Dorsal Anterior Cingulate Cortices Differentially Lateralize Prediction Errors and Outcome Valence in a Decision-Making Task.

The dorsal anterior cingulate cortex (dACC) is proposed to facilitate learning by signaling mismatches between the expected outcome of decisions and the actual outcomes in the form of prediction errors. The dACC is also proposed to discriminate outcome valence—whether a result has positive (either expected or desirable) or negative (either unexpected or undesirable) value. However, direct electrophysiological recordings from human dACC to validate these separate, but integrated, dimensions have not been previously performed. We hypothesized that local field potentials (LFPs) would reveal changes in the dACC related to prediction error and valence and used the unique opportunity offered by deep brain stimulation (DBS) surgery in the dACC of three human subjects to test this hypothesis. We used a cognitive task that involved the presentation of object pairs, a motor response, and audiovisual feedback to guide future object selection choices. The dACC displayed distinctly lateralized theta frequency (3–8 Hz) event-related potential responses—the left hemisphere dACC signaled outcome valence and prediction errors while the right hemisphere dACC was involved in prediction formation. Multivariate analyses provided evidence that the human dACC response to decision outcomes reflects two spatiotemporally distinct early and late systems that are consistent with both our lateralized electrophysiological results and the involvement of the theta frequency oscillatory activity in dACC cognitive processing. Further findings suggested that dACC does not respond to other phases of action-outcome-feedback tasks such as the motor response which supports the notion that dACC primarily signals information that is crucial for behavioral monitoring and not for motor control

Dairy herd mastitis and reproduction: using simulation to aid interpretation of results from discrete time survival analysis

Probabilistic sensitivity analysis (PSA) is a simulation-based technique for evaluating the relative importance of different inputs to a complex process model. It is commonly employed in decision analysis and for evaluation of the potential impact of uncertainty in research findings on clinical practice, but has a wide variety of other possible applications. In this example, it was used to evaluate the association between herd-level udder health and reproductive performance in dairy herds. Although several recent studies have found relatively large associations between mastitis and fertility at the level of individual inseminations or lactations, the current study demonstrated that herd-level intramammary infection status is highly unlikely to have a clinically significant impact on the overall reproductive performance of a dairy herd under typical conditions. For example, a large increase in incidence rate of clinical mastitis (from 92 to 131 cases per 100 cows per year) would be expected to increase a herd's modified FERTEX score (a cost-based measure of overall reproductive performance) by just £4.501 per cow per year. The herd's background level of submission rate (proportion of eligible cows served every 21 days) and pregnancy risk (proportion of inseminations leading to a pregnancy) correlated strongly with overall reproductive performance and explained a large proportion of the between-herd variation in performance. PSA proved to be a highly useful technique to aid understanding of results from a complex statistical model, and has great potential for a wide variety of applications within the field of veterinary science

The impact of Cochrane Systematic Reviews : a mixed method evaluation of outputs from Cochrane Review Groups supported by the UK National Institute for Health Research

© 2014 Bunn et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: There has been a growing emphasis on evidence-informed decision making in health care. Systematic reviews, such as those produced by the Cochrane Collaboration, have been a key component of this movement. The UK National Institute for Health Research (NIHR) Systematic Review Programme currently supports 20 Cochrane Review Groups (CRGs). The aim of this study was to identify the impacts of Cochrane reviews published by NIHR funded CRGs during the years 2007-11. Methods: We sent questionnaires to CRGs and review authors, interviewed guideline developers and used bibliometrics and documentary review to get an overview of CRG impact and to evaluate the impact of a sample of 60 Cochrane reviews. We used a framework with four categories (knowledge production, research targeting, informing policy development, and impact on practice/services). Results: A total of 1502 new and updated reviews were produced by the 20 NIHR funded CRGs between 2007-11. The clearest impacts were on policy with a total of 483 systematic reviews cited in 247 sets of guidance; 62 were international, 175 national (87 from the UK) and 10 local. Review authors and CRGs provided some examples of impact on practice or services, for example safer use of medication, the identification of new effective drugs or treatments and potential economic benefits through the reduction in the use of unproven or unnecessary procedures. However, such impacts are difficult to objectively document and the majority of reviewers were unsure if their review had produced specific impacts. Qualitative data suggested that Cochrane reviews often play an instrumental role in informing guidance although a poor fit with guideline scope or methods, reviews being out of date and a lack of communication between CRGs and guideline developers were barriers to their use. Conclusions: Health and economic impacts of research are generally difficult to measure. We found that to be the case with this evaluation. Impacts on knowledge production and clinical guidance were easier to identify and substantiate than those on clinical practice. Questions remain about how we define and measure impact and more work is needed to develop suitable methods for impact analysis.Peer reviewe

Reduction of metastasis using a non-volatile buffer

The tumor microenvironment is acidic as a consequence of upregulated glycolysis and poor perfusion and this acidity, in turn, promotes invasion and metastasis. We have recently demonstrated that chronic consumption of sodium bicarbonate increased tumor pH and reduced spontaneous and experimental metastases. This occurred without affecting systemic pH, which was compensated. Additionally, these prior data did not rule out the possibility that bicarbonate was working though effects on carbonic anhydrase, and not as a buffer per se. Here, we present evidence that chronic ingestion of a non-volatile buffer, 2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA) with a pKa of 6.9 also reduced metastasis in an experimental PC3M prostate cancer mouse model. Animals (n = 30) were injected with luciferase expressing PC3M prostate cancer cells either subcutaneously (s.c., n = 10) or intravenously (i.v., n = 20). Four days prior to inoculations, half of the animals for each experiment were provided drinking water containing 200 mM IEPA buffer. Animals were imaged weekly to follow metastasis, and these data showed that animals treated with IEPA had significantly fewer experimental lung metastasis compared to control groups (P < 0.04). Consistent with prior work, the pH of treated tumors was elevated compared to controls. IEPA is observable by in vivo magnetic resonance spectroscopy and this was used to measure the presence of IEPA in the bladder, confirming that it was orally available. The results of this study indicate that metastasis can be reduced by non-volatile buffers as well as bicarbonate and thus the effect appears to be due to pH buffering per se