Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Model for injury to the foreleg of the Thoroughbred racehorse

A discussion is presented of contributing factors to the injury to the foreleg of the Thoroughbred racehorse. The critical part of the step is taken to be the first 10-20 ms after ground contact as the hoof slides forward and stops. Large nonaxial loads associated with the deceleration of the hoof are shown to arise. Results of accelerometer measurements on the hoof of a horse running at racing speed are presented as well as mechanical properties of the racing surface. The mechanical properties of the track surface, the type of shoe, and the degree of fatigue of the horse all work together to determine the level of risk.     

Modelling biological processes under anaerobic conditions through integrating titrimetric and off-gas measurements-applied to EBPR systems.

An innovative method for modelling biological processes under anaerobic conditions is presented and discussed. The method is based on titrimetric and off-gas measurements. Titrimetric data is recorded as the addition rate of hydroxyl ions or protons that is required to maintain pH in a bioreactor at a constant level. An off-gas analysis arrangement measures, among other things, the transfer rate of carbon dioxide. The integration of these signals results in a continuous signal which is solely related to the biological reactions. When coupled with a mathematical model of the biological reactions, the signal allows a detailed characterisation of these reactions, which would otherwise be difficult to achieve. Two applications of the method to the enhanced biological phosphorus removal processes are presented and discussed to demonstrate the principle and effectiveness of the method.     

Mining data from intensive care patients

In this paper we describe the application of data mining methods for predicting the evolution of patients in an intensive care unit. We discuss the importance of such methods for health care and other application domains of engineering. We argue that this problem is an important but challenging one for the current state of the art data mining methods and explain what improvements on current methods would be useful. We present a promising study on a preliminary data set that demonstrates some of the possibilities in this area.     

Symbolic control of visual attention: The role of working memory and attentional control settings.

This study examined how 1 symbol is selected to control the allocation of attention when several symbols appear in the visual field. In Experiments 1-3, the critical target feature was color, and it was found that uninformative central arrows that matched the color of the target were selected and produced unintentional shifts of attention (i.e., involuntary, initiated slowly, producing long-lasting facilitatory effects). Experiment 4 tested whether such selection is the result of an attentional filter or of a competition bias due to a match of incoming information against integrated object representations stored in working memory. Here, the critical feature was shape and color was irrelevant, but matching color arrows were still selected. Thus, features of objects in working memory will bias the selection of symbols in the visual field, and such selected symbols are capable of producing unintentional shifts of attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Allowables-Based Flow Curves for Nonlinear Finite-Element Analysis

A methodology for developing allowables-based stress versus strain relationships for metal alloys is presented. The approach incorporates Federal Aviation Administration/Department of Defense (FAA/DoD) Metallic Materials Property Development and Standardization (MMPDS) statistically derived material properties for tensile yield and ultimate strengths to derive flow curves at room or elevated temperature with an A-, B-, or S-Basis probability. The resulting flow curves may be used for new designs to comply with Federal Air Regulations as well as for forensic investigations and failure analysis.     

Robustness of VS-MRAC with respect to unmodelled dynamics and external disturbances

A variable structure model reference adaptive controller (VS-MRAC) using only input and output measurements was recently proposed and shown to be globally asymptotically stable with superior transient behaviour and disturbance rejection properties. In this paper a singular perturbation approach is used in order to establish the robustness of the controller in the presence of unmodelled dynamics (parasitics) and disturbances. We develop a new Lyapunov-based technique to analyse the overall system and show that for sufficiently small parasitics the system remains stable and the output error is small in some sense.     

The role of DnaJ-like proteins in glucocorticoid receptor.hsp90 heterocomplex assembly by the reconstituted hsp90.p60.hsp70 foldosome complex

The glucocorticoid receptor (GR) is recovered from hormone-free cells in a heterocomplex with the molecular chaperone hsp90, which is required to produce the proper folding state for steroid binding. GR.hsp90 heterocomplexes are formed by a multiprotein system that appears to exist in all eukaryotic cells. Recently, we have reconstituted a receptor.hsp90 heterocomplex assembly system with purified rabbit hsp90 and hsp70 and bacterially expressed human p23 and p60. We have shown that hsp90, p60, and hsp70 form an hsp90.p60. hsp70 complex that converts the GR from a non-steroid binding to a steroid binding form (Dittmar, K. D., and Pratt, W. B. (1997) J. Biol. Chem. 272, 13047-13054). The resulting GR.hsp90 heterocomplex rapidly disassembles unless p23 is present to bind to the ATP-dependent conformation of hsp90 and stabilize its association with the receptor (Dittmar, K. D., Demady, D. R., Stancato, L. F., Krishna, P., and Pratt, W. B. (1997) J. Biol. Chem. 272, 21213-21220). In the current work, we show that the purified rabbit hsp70 utilized in prior studies is contaminated with a small amount of the rabbit DnaJ homolog hsp40. Elimination of the hsp40 from the purified GR.hsp90 assembly system reduces assembly activity, and the activity is restored by addition of the purified yeast DnaJ homolog YDJ-1. hsp40 is a component of the hsp90.p60.hsp70 foldosome complex isolated from reticulocyte lysate with antibody against p60. Under conditions that promote binding of p23 to hsp90 (elevated temperature, ATP, Nonidet P-40, molybdate), a five-membered (p23. hsp90.p60.hsp70.hsp40) complex of chaperone proteins is formed in reticulocyte lysate or from purified proteins. The hsp40-free, purified assembly system has a modest level of assembly activity that is maximally potentiated by YDJ-1 when it is present at about one-twentieth the concentration of hsp70. Although hsp40 is not in the final GR.hsp90 heterocomplex isolated from L cell cytosol, it is in the GR.hsp90 heterocomplex assembled in reticulocyte lysate. We conclude that hsp40 is a component of the multiprotein hsp90-based chaperone system where it potentiates GR.hsp90 heterocomplex assembly.