Electrolyte measurements differ between point-of-care and reference analysers in dogs with hypoadrenocorticism

Introduction: Dogs treated for hypoadrenocorticism are monitored through analysis of their blood electrolytes. This is routinely performed with point‐of‐care analysers and doses of medications are adjusted based on the results. Objectives: To investigate the performance of two point‐of‐care analysers (IDEXX Catalyst Dx and IDEXX VetStat) against a reference laboratory method for the measurement of blood sodium, potassium and chloride concentrations, as well as sodium: potassium ratios, in dogs diagnosed with and treated for hypoadrenocorticism. Methods: Forty‐eight dogs were enrolled into a prospective cross‐sectional study. Paired blood samples were taken and tested on two point‐of‐care analysers and at a reference laboratory. Statistical analysis was then performed with Bland‐Altman analysis and Passing‐Bablok regression. The clinical effects of inaccurate electrolyte analysis were investigated. Results: In total, 329 samples were tested on the Catalyst analyser, while another 72 samples were tested on the VetStat. Passing‐Bablok regression identified both proportional and constant bias for some analytes. There was poor agreement between sodium and chloride concentrations on both analysers. Both analysers tended to give higher results than the reference method for all analytes, except for potassium when measured on the VetStat. Clinical Significance: There are inherent differences between the electrolyte concentrations measured by these two point‐of‐care analysers and reference laboratory methods in dogs with hypoadrenocorticism

MODELING CYLINDER-TO-CYLINDER COUPLING IN MULTI-CYLINDER HCCI ENGINES INCORPORATING REINDUCTION

ABSTRACT Residual-affected homogeneous charge compression ignition (HCCI) is a promising strategy for decreasing fuel consumption and NOx emissions in internal combustion engines. One practical approach for achieving residual-affected HCCI is by using variable valve actuation to reinduct previously exhausted combustion products. This process inherently couples neighboring engine cylinders as products exhausted by one cylinder may be reinducted by a neighboring one. In order to understand this coupling and its implication for controlling HCCI, this paper outlines a simple physics based model of a multi-cylinder HCCI engine using exhaust reinduction. It is based on a physics based model previously validated for a single cylinder, multi mode HCCI engine. The exhaust manifold model links exhaust gases from one cylinder to those of the other cylinders and also simulates the effect of exhaust reinduction from the previous cycle. Depending on the exhaust manifold geometry and orientation, the heat transfer in the manifold causes a difference in the temperature of the re-inducted product gas across the cylinders. The results show that a subtle difference in the re-inducted exhaust gas temperature results in a dramatic variation in combustion timing (approx. 3 degrees). This model provides a basis for understanding the steady state behavior and also for developing control strategies for multi-cylinder HCCI engines. The paper presents exhaust valve timing induced compression ratio modulation (via flexible valve actuation) as one of the approaches to mitigate the imbalance in combustion timing across cylinders

On Secure Workflow Decentralisation on the Internet

Decentralised workflow management systems are a new research area, where most work to-date has focused on the system's overall architecture. As little attention has been given to the security aspects in such systems, we follow a security driven approach, and consider, from the perspective of available security building blocks, how security can be implemented and what new opportunities are presented when empowering the decentralised environment with modern distributed security protocols. Our research is motivated by a more general question of how to combine the positive enablers that email exchange enjoys, with the general benefits of workflow systems, and more specifically with the benefits that can be introduced in a decentralised environment. This aims to equip email users with a set of tools to manage the semantics of a message exchange, contents, participants and their roles in the exchange in an environment that provides inherent assurances of security and privacy. This work is based on a survey of contemporary distributed security protocols, and considers how these protocols could be used in implementing a distributed workflow management system with decentralised control . We review a set of these protocols, focusing on the required message sequences in reviewing the protocols, and discuss how these security protocols provide the foundations for implementing core control-flow, data, and resource patterns in a distributed workflow environment

Computational social network modeling of terrorist recruitment.

The Seldon terrorist model represents a multi-disciplinary approach to developing organization software for the study of terrorist recruitment and group formation. The need to incorporate aspects of social science added a significant contribution to the vision of the resulting Seldon toolkit. The unique addition of and abstract agent category provided a means for capturing social concepts like cliques, mosque, etc. in a manner that represents their social conceptualization and not simply as a physical or economical institution. This paper provides an overview of the Seldon terrorist model developed to study the formation of cliques, which are used as the major recruitment entity for terrorist organizations

Model-building codes for membrane proteins.

We have developed a novel approach to modeling the transmembrane spanning helical bundles of integral membrane proteins using only a sparse set of distance constraints, such as those derived from MS3-D, dipolar-EPR and FRET experiments. Algorithms have been written for searching the conformational space of membrane protein folds matching the set of distance constraints, which provides initial structures for local conformational searches. Local conformation search is achieved by optimizing these candidates against a custom penalty function that incorporates both measures derived from statistical analysis of solved membrane protein structures and distance constraints obtained from experiments. This results in refined helical bundles to which the interhelical loops and amino acid side-chains are added. Using a set of only 27 distance constraints extracted from the literature, our methods successfully recover the structure of dark-adapted rhodopsin to within 3.2 {angstrom} of the crystal structure

Computational social dynamic modeling of group recruitment.

The Seldon software toolkit combines concepts from agent-based modeling and social science to create a computationally social dynamic model for group recruitment. The underlying recruitment model is based on a unique three-level hybrid agent-based architecture that contains simple agents (level one), abstract agents (level two), and cognitive agents (level three). This uniqueness of this architecture begins with abstract agents that permit the model to include social concepts (gang) or institutional concepts (school) into a typical software simulation environment. The future addition of cognitive agents to the recruitment model will provide a unique entity that does not exist in any agent-based modeling toolkits to date. We use social networks to provide an integrated mesh within and between the different levels. This Java based toolkit is used to analyze different social concepts based on initialization input from the user. The input alters a set of parameters used to influence the values associated with the simple agents, abstract agents, and the interactions (simple agent-simple agent or simple agent-abstract agent) between these entities. The results of phase-1 Seldon toolkit provide insight into how certain social concepts apply to different scenario development for inner city gang recruitment

Bayesian methods for estimating the reliability in complex hierarchical networks (interim report).

Current work on the Integrated Stockpile Evaluation (ISE) project is evidence of Sandia's commitment to maintaining the integrity of the nuclear weapons stockpile. In this report, we undertake a key element in that process: development of an analytical framework for determining the reliability of the stockpile in a realistic environment of time-variance, inherent uncertainty, and sparse available information. This framework is probabilistic in nature and is founded on a novel combination of classical and computational Bayesian analysis, Bayesian networks, and polynomial chaos expansions. We note that, while the focus of the effort is stockpile-related, it is applicable to any reasonably-structured hierarchical system, including systems with feedback

Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation.

BackgroundMucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT.MethodsThis 2-year open-label pilot study of laronidase included ten patients (age 5-13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls.ResultsThe two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients.ConclusionsLaronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made

Acoustic cell washing and raman spectroscopy technologies To address cell therapy bioprocess challenges

Many organizations are confronting the challenges of economically ensuring the manufacture of safe and efficacious cell therapy products. These processes often depend on devices and methods that were developed for only related applications, such as blood cell processing or scientific research. Thus, we are in a window of opportunity to tailor innovative technologies to address the emerging specialized needs of cell therapy manufacturing. The most frequent unit operation is to wash cells between process stages, such as from DMSO containing cryopreservation medium to culture expansion medium. In particular for relatively small-scale autologous cell therapy processing, cell washing is imperfectly performed by closed system blood cell centrifuges or filters. We previously developed an acoustic cell separation device, widely used for over 15 years in CHO cell perfusion cultures. This technology acts as a non-fouling filter for months of operation, by using the forces generated in ultrasonic standing wave fields. These forces separate cells from medium based on differences in density and compressibility. Greater than 99.9% cell washing with 95% washed cell recovery efficiencies have been provided by our device. We also have recently enhanced the acoustic technology to perfuse 100 million cell/mL cultures, maintaining \u3e99% cell separation efficiencies. This provides an alternative high performance closed manufacturing system, to perfuse, concentrate and wash cells, with no physical filter barrier or mechanical moving parts. While many clinical trials have had few adverse events, the great promise of cellular therapies comes with grave risks, such as from potentially oncogenic pluripotent cells present in embryonic stem cell derived populations. There is an urgent need for process analytical technologies to non-invasively monitor mammalian cell populations and improve the reliability of manufactured cell products. This includes to monitor both the expected differentiation as well as to detect unexpected cells in the process. Recently, technological advances have led to an explosive growth in the capabilities of Raman spectroscopy, increasing the potential for novel applications. We are developing the use of this spectroscopic technique to track cell development, by measuring macromolecular changes in cell samples from cultures where stem cells are differentiated towards insulin-producing cells for the treatment of diabetes. Raman spectroscopy has great potential to provide continuous on-line assessment of cell quality during the manufacture of cell-derived therapeutic cells