Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI.

Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue-specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.

Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy

For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases. Copyright © 2014 by Lippincott Williams & Wilkins.

Prevention of recurrences in frequently relapsing herpes labialis with thymopentin a randomized double-blind placebo-controlled multicenter study

The present randomized, placebo-controlled double-blind multicenter study included a population of 36 subjects with frequent recurrences (at least once a month) of herpes labialis. Most of the patients had failed to respond adequately to previous treatment with other therapeutic tools, including acyclovir. Either 50 mg of thymopentin or of placebo was administered 3 times a week, by the subcutaneous route, for 6 weeks. Subsequently, the patients were observed for nearly 6 months on the average. The results achieved with thymopentin for the individual parameters were significantly superior to those obtained with placebo; thus significant improvement was seen in patients on thymopentin in the duration of the longest symptomfree period (prolonged from 2.1 weeks to 20.9 weeks, p = 0.000), in the number of relapses (reduced from 1.6 to 0.4 episodes/month, p = 0.001), and in the total duration of herpes symptoms per month (shortened from 2.0 to 0.3 weeks, p = 0.000). Placebo treatment also resulted in considerable improvement (p < 0.05 or 0.01), but was significantly inferior to the improvement obtained with thymopentin. The longest symptomfree period in the placebo group was prolonged from 2.4 to 11.2 weeks. The number of relapses per month was reduced from 1.4 to 0.8, and the total duration of herpes symptoms per month from 2 to 0.9 weeks. The results of intergroup analyses, in which the observed parameters and the improvement achieved in either group were compared, significantly favored thymopentin treatment. The effect of thymopentin was in all but one parameters superior to that of placebo and highly significant (p < 0.01). © 1985 Humana Press Inc.

Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

Background: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data. Methods. Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications. Results: Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood). Conclusion: Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

Las relaciones pedagógicas entre profesores y alumnos al incorporar el uso de las tecnologías computacionales en el ámbito escolar

El presente trabajo muestra algunas de las experiencias obtenidas en la puesta en práctica del proceso didáctico que propone el programa EMAT –Hidalgo con un grupo de docentes que imparten la asignatura de matemáticas en el nivel de educación secundaria modalidad técnica. La investigación permitió identificar el tipo de relaciones entre profesores y estudiantes al incorporar el uso de las tecnologías computacionales en el ámbito escolar. Para ello, se hicieron entrevistas, encuestas y observaciones en los tres grados de educación secundaria.

Tun Lehrerinnen und Lehrer im Unterricht, was sie als Mitglieder ihrer Profession tun sollten? Zur Diskussion zwischen Wernet und Twardella

Einführung in die Diskussion zwischen Johannes Twardella und Andreas Wernet über Wernets Buch "Pädagogische Permissivität". (DIPF/Autor)

Staggered-mesh computation for aerodynamic sound

For the numerical solution of the linearized Euler equations, an optimized computational scheme is considered. It is based on fully staggered (in space and time) regular meshes and on a simple mirroring procedure at the stepwise solid walls. There is no need to define ghost points into the solid ohjects that reflect the sound waves. Test results demonstrate the accuracy of the method that may be used for aeroacoustic problems with complex geometries.

Aircraft accident statistics and knowledge database: analyzing passenger behavior in aviation accidents

The Aircraft Accident Statistics and Knowledge (AASK) database is a repository of passenger accounts from survivable aviation accidents/incidents compiled from interview data collected by agencies such as the US NTSB. Its main purpose is to store observational and anecdotal data from the actual interviews of the occupants involved in aircraft accidents. The database has wide application to aviation safety analysis, being a source of factual data regarding the evacuation process. It also plays a significant role in the development of the airEXODUS aircraft evacuation model, where insight into how people actually behave during evacuation from survivable aircraft crashes is required. This paper describes the latest version of the database (Version 4.0) and includes some analysis of passenger behavior during actual accidents/incidents.

A study of modelling approaches for rail vehicle collision behaviour

A rigid wall model has been used widely in the numerical simulation of rail vehicle impacts. Finite element impact modelling of rail vehicles is generally based on a half-width and full-length or half-length structure, depending on the symmetry. The structure and components of rail vehicles are normally designed to cope with proof loading to ensure adequate ride performance. In this paper, the authors present a study of a rail vehicle with driving cab focused on improving the modelling approach and exploring the intrinsic structural weaknesses to enhance its crashworthiness. The underpinning research used finite element analysis and compared the behaviour of the rail vehicle in different impact scenarios. It was found that the simulation of a rigid wall impact can mask structural weaknesses; that even a completely symmetrical impact may lead to an asymmetrical result; that downward bending is an intrinsic weakness of conventional rail vehicles and that a rigid part of the vehicle structure, such as the body bolster, may cause uncoordinated deformation and shear fracture between the vehicle sections. These findings have significance for impact simulation, the full-scale testing of rail vehicles and rail vehicle design in general.

Analysis of crush behaviours of a rail cab car and structural modifications for improved crashworthiness

In this paper, the authors present a crashworthiness assessment and suggestions for modification of a conventionally designed rail vehicle with a driving cab (cab car). The analytical approach, based on numerical analysis, consisted of two stages. Firstly, the crashworthiness of the cab car was assessed by simulating a collision between the cab car and a rigid wall. Then, after analysing structural weaknesses, the design of the cab car was modified and simulated again in the same scenario. It was found that downward bending is an intrinsic weakness in conventional rail vehicles and that jackknifing is a main form of failures in conventional rail vehicle components. The cab car, as modified by the authors, overcomes the original weaknesses and shows the desired progressive collapse behaviour in simulation. The conclusions have general relevance for other studies but more importantly, point to the need for a rethink of some aspects of rail vehicle design.

Deriving explanations from partial temporal information

The representation and manipulation of natural human understanding of temporal phenomena is a fundamental field of study in Computer Science, which aims both to emulate human thinking, and to use the methods of human intelligence to underpin engineering solutions. In particular, in the domain of Artificial Intelligence, temporal knowledge may be uncertain and incomplete due to the unavailability of complete and absolute temporal information. This paper introduces an inferential framework for deriving logical explanations from partial temporal information. Based on a graphical representation which allows expression of both absolute and relative temporal knowledge in incomplete forms, the system can deliver a verdict to the question if a given set of statements is temporally consistent or not, and provide understandable logical explanation of analysis by simplified contradiction and rule based reasoning.

An architecture of multiple heterogeneous case-based reasoning employing agent technologies

This paper presents an investigation into applying Case-Based Reasoning to Multiple Heterogeneous Case Bases using agents. The adaptive CBR process and the architecture of the system are presented. A case study is presented to illustrate and evaluate the approach. The process of creating and maintaining the dynamic data structures is discussed. The similarity metrics employed by the system are used to support the process of optimisation of the collaboration between the agents which is based on the use of a blackboard architecture. The blackboard architecture is shown to support the efficient collaboration between the agents to achieve an efficient overall CBR solution, while using case-based reasoning methods to allow the overall system to adapt and “learn” new collaborative strategies for achieving the aims of the overall CBR problem solving process.

Direct measurement of powder flavor adhesion onto crisp surface using a novel adhesion tester

A new experimental procedure has been implemented and a prototype of a novel adhesion tester has been designed and constructed using rapid prototyping technology. A tumbler mixer has been designed and constructed for coating powder material onto a crisp substrate. In the impact separation experiment, the amount of powder detached from one side of a crisp substrate by the effect of impact forces (48g, 77g, 102g) generated by the tester was measured. Salt particles with different size fractions (63-125, 125-180, and 180-250m) and several flavoring powders have been tested extensively. By plotting the detachment versus impact force, the difference obtained between adhesion strength of different flavoring powders (which is a strong function of particle size and surface oil content of the crisp) has been discussed. The detachment rate of salt particles increased (from 1% to 2%) with particle size (from 63 to 250m) in the presence of oil on the surface of the crisp substrate and decreased rapidly with the increase in the amount of oil applied (from 0 to 1%).

Diameter-selective solubilization of carbon nanotubes by lipid micelles

The one-step dispersion of HiPco single-walled carbon nanotubes in aqueous media with the use of a synthetic lyso-phosphatidylcholine was studied. Solubilization occurs through wrapping of lipid molecules around the circumference of the tubes, yielding lipid monolayers on the graphitic sidewalls as evidenced by atomic force microscopy imaging and dynamic light scattering measurements. Raman spectroscopy showed that the dispersion and centrifugation process leads to an effective enrichment of the stable aqueous suspension in carbon nanostructures with smaller diameters.