Portacaval Transposition in the Rat: A New Model for Investigation of Portal-Systemic Encephalopathy

The object of this work was to establish an experimental model in the rat to examine the relative roles of portal-systemic diversion and of impaired liver function in the pathogenesis of chronic portal-systemic encephalopathy (PSE). The problem with conventional end-to-side portacaval shunting, both clinically and in the experimental animal, is that in addition to producing total shunting of portal blood into the systemic circulation, the procedure itself leads to hepatocellular atrophy and impaired hepatic function. For this reason the new model of portacaval transposition (PCT) was developed in the rat. In this preparation total portal shunting takes place, but blood flow through the portal tracts of the liver is replaced by systemic blood from the inferior vena cava. Comparison of this model with the conventional portacaval shunt (PCS) should allow separation of the two phenomena of shunting and liver dysfunction. This is of some clinical importance, since it has been proposed that selection of patients or "tailoring" of portal diversion procedures on the basis of haemodynamic characteristics should lead to a lower incidence of chronic post-shunt encephalopathy, which remains the major clinical disadvantage of such operations. It was first established (Chapter III) that PCT is attended by retention of a normal body growth pattern, little reduction in relative liver weight, and maintenance of normal hepatic morphology. This contrasts with PCS, following which there is impaired body growth and specific atrophy of the liver with marked histological changes. Since PCS rats were shown to have reduced food intake, the specific nature of these findings was confirmed by using PCT and control animals which were pair-fed against PCS rats. It was also demonstrated that biochemical parameters of liver function were better conserved in the PCT preparation. It was further confirmed by use of radio-labelled Rose Bengal clearance that liver blood flow was in fact reduced in PCS rats and normal after PCT. Sections prepared from the rapidly perfused brains of these animals were examined microscopically (Chapter IV). In both groups (and in a small number of control animals) it was possible to identify changes in the astroglial cells similar to those described by Alzheimer and characteristic of the brain in PSE in man and in experimental animals. However, these changes were significantly greater in the PCS rats than in the PCT rats, and in one experiment the abnormal cell count in PCT rats did not differ from control values. These results were also validated in a small group of pair-fed animals. This finding confirms the importance of hepatic dysfunction in the pathogenesis of central nervous system damage in these models, and suggests that maintenance of total hepatic blood flow even in the absence of direct perfusion by portal blood might confer protection against the development of PSE. A characteristic pattern of plasma amino acids was seen following PCS, with reduction in the branched-chain amino acids valine, leucine and isoleucine, and elevation of the aromatic amino acids tyrosine and phenylalanine. This pattern, which characterizes chronic liver failure and PSE in man and experimental animals, was not seen after PCT (Chapter V). SUMMARY Similar results were found in the pair-feeding experiment. Plasma insulin and glucagon levels were elevated to a similar degree after PCS and PCT. These results suggest that the hormone elevation seen as a result of portal-systemic diversion cannot entirely explain the amino acid imbalance, which appears to depend largely upon hepatic dysfunction in the PCS rats. Changes in levels of glutamine, glutamate and tryptophan, substances known to be associated with central nervous system neurotransmission and possibly with glial function, were also examined (Chapter V). The differences observed did not achieve statistical significance, although the patterns seen amongst the groups were consistent with small but biologically important changes masked by metabolic compartmentation within the brain. We conclude that the PCT model has proved valuable in separating the effects of portal diversion from those of hepatic dysfunction. The results confirm the vital role of normal liver function in protecting the brain against damage resulting from portal-systemic diversion, and suggest that liver function may be maintained close to normal even in the absence of direct portal perfusion if total liver blood flow is maintained. These findings are in keeping with the observation in man that a substantial compensatory increase in arterial flow following total portal diversion results in a lesser degree of encephalopathy. The establishment of the PCS/PCT model permits a further degree of refinement in future studies of the fundamental biochemical and cellular mechanisms of hepatic coma

Inverse Problems in a Bayesian Setting

In a Bayesian setting, inverse problems and uncertainty quantification (UQ) --- the propagation of uncertainty through a computational (forward) model --- are strongly connected. In the form of conditional expectation the Bayesian update becomes computationally attractive. We give a detailed account of this approach via conditional approximation, various approximations, and the construction of filters. Together with a functional or spectral approach for the forward UQ there is no need for time-consuming and slowly convergent Monte Carlo sampling. The developed sampling-free non-linear Bayesian update in form of a filter is derived from the variational problem associated with conditional expectation. This formulation in general calls for further discretisation to make the computation possible, and we choose a polynomial approximation. After giving details on the actual computation in the framework of functional or spectral approximations, we demonstrate the workings of the algorithm on a number of examples of increasing complexity. At last, we compare the linear and nonlinear Bayesian update in form of a filter on some examples.Comment: arXiv admin note: substantial text overlap with arXiv:1312.504

Patients' perception of radiation safety of radiological investigations in urology

Background: This study analyses patients’ knowledge of common radiological investigations. Methods: At a university teaching hospital, 100 patients attending urological clinics, who had had a plain X-ray of the kidney, ureter and bladder, magnetic resonance imaging (MRI), computed tomography (CT) or ultrasound scan (USS), completed a 14-item Likert scale questionnaire assessing patients’ perception of safety (both qualitatively and quantitatively) and the hazards of radiological investigations. Results: Using a radiation risk score, patients perceived the following investigations to be in rank order of increasing radiation risk: USS (0.84), MRI (1.4), CT (1.5) and plain X-ray (1.6). On the same scale (0–5), only 17% of patients correctly attributed a risk score of 3 or 4 for a CT scan, and 49% were able to identify a plain X-ray’s risk score correctly as 1 or 2. In addition, more patients identified CT (34%) as having a lower risk of 0 than an X-ray (24%). The mean (1.35 vs. 1.60), median (1 vs. 1) and mode (0 vs. 1) for the CT risk scores are less than those for a plain X-ray, demonstrating that patients perceived CT scans to be safer. Further, the majority of patients understood USS to have no radiation exposure (56%) but thought that MRI posed a radiation risk (62%). Patients were unable to quantify radiation exposure correctly: USS (37% correctly attributed – 0 mSv), MRI (22% – 0 mSv), X-ray (47% – 1 mSv) and CT scan (28% – 10 mSv). Conclusion: This demonstration of suboptimal patient awareness of radiation exposure of common radiological investigations highlights the need to educate patients in order to improve patient autonomy and possibly reduce the demand for unnecessary radiological investigations such as CT. Level of evidence: Level 2

An events based algorithm for distributing concurrent tasks on multi-core architectures

In this paper, a programming model is presented which enables scalable parallel performance on multi-core shared memory architectures. The model has been developed for application to a wide range of numerical simulation problems. Such problems involve time stepping or iteration algorithms where synchronization of multiple threads of execution is required. It is shown that traditional approaches to parallelism including message passing and scatter-gather can be improved upon in terms of speed-up and memory management. Using spatial decomposition to create orthogonal computational tasks, a new task management algorithm called H-Dispatch is developed. This algorithm makes efficient use of memory resources by limiting the need for garbage collection and takes optimal advantage of multiple cores by employing a “hungry” pull strategy. The technique is demonstrated on a simple finite difference solver and results are compared to traditional MPI and scatter-gather approaches. The H-Dispatch approach achieves near linear speed-up with results for efficiency of 85% on a 24-core machine. It is noted that the H-Dispatch algorithm is quite general and can be applied to a wide class of computational tasks on heterogeneous architectures involving multi-core and GPGPU hardware.Schlumberger-Doll Research CenterSaudi Aramc

Evidence for a kilometre-scale seismically slow layer atop the core-mantle boundary from normal modes

Geodynamic modelling and seismic studies have highlighted the possibility that a thin layer of low seismic velocities, potentially molten, may sit atop the core-mantle boundary but has thus far eluded detection. In this study we employ normal modes, an independent data type to body waves, to assess the visibility of a seismically slow layer atop the core-mantle boundary to normal mode centre frequencies. Using forward modelling and a dataset of 353 normal mode observations we find that some centre frequencies are sensitive to one-dimensional kilometre-scale structure at the core-mantle boundary. Furthermore, a global slow and dense layer 1 - 3 km thick is better-fitting than no layer. The well-fitting parameter space is broad with a wide range of possible seismic parameters, which precludes inferring a possible composition or phase. Our methodology cannot uniquely detect a layer in the Earth but one should be considered possible and accounted for in future studies

Bringing 'place' back in: regional clusters, project governance, and new product outcomes

We examine new product outcomes in the context of regional clusters. Based on past research on marketing relationships, clusters, and social networks, we propose that the overall configuration of a cluster helps promote particular governance practices among its members. These practices have distinct value-creating properties, and when they are brought to bear on a specific new product development project within a cluster, they promote performance outcomes like product novelty and speed to market. Ultimately, these performance effects are reinforced by the configuration of the cluster itself. In general, we propose that new product outcomes follow from complex interactions between a cluster's macro-level configuration and its micro-level governance processes. More broadly, our framework points to the importance of geographical variables and to the role of “place” in marketing decision-making

Thermal cracking of ethane and ethylene in a stock tube

The rates of decomposition of ethane and ethylene were measured at temperatures between 1,250° and 2,800°K. and pressures between 0.25 and 2.0 atm. by exposing the gases to high temperature during the interval between the arrival of a compression wave and a reflected rarefaction wave in a shock tube. As contrasted with cracking at lower temperatures the ethane apparently reacted to hydrogen, ethylene, and acetylene and the ethylere to hydrogen and acetylene with negligible side reactions or polymerization. The over-all decomposition rates at high temperature fall off sharply from those extrapolated from low temperature, indicating a change in mechanism. Additions of air, oxygen, carbon monoxide, and chlorine in amounts up to 17% did not effect the rate constants significantly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37324/1/690080214_ftp.pd