Test case based risk predictions using artificial neural network.

INTRODUCTION: The traditional fuzzy-rule-based risk assessment technique has been applied in many industries due to the capability of combining different parameters to obtain an overall risk. However, a drawback occurs as the technique is applied in circumstances where there are multiple parameters to be evaluated that are described by multiple linguistic terms. METHOD: In this study, a risk prediction model incorporating fuzzy set theory and Artificial Neural Network (ANN) capable of resolving the problem encountered is proposed. An algorithm capable of converting the risk-related parameters and the overall risk level from the fuzzy property to the crisp-valued attribute is also developed. Its application is demonstrated by a test case evaluating the navigational safety within port areas. RESULTS: It is concluded that a risk predicting ANN model is capable of generating reliable results as long as the training data takes into account any potential circumstance that may be met. IMPACT ON INDUSTRY: This paper provides safety assessment practitioners with a novel and flexible framework of modelling risks using a fuzzy-rule-base technique. It is especially applicable in circumstances where there are multiple parameters to be considered. The proposed framework also enables the port industry to manage navigational safety in a rational manner.

Stress ventricular function test in conscious, nonthoracotomised dogs to assess cardiac drug efficacy.

The measurement of left ventricular (LV) function is frequently performed in unconscious or thoracotomised animals in the resting state; these conditions may seriously affect the basal haemodynamic state. To assess myocardial function in conscious animals, a technique was developed to place a catheter across the atrial septum into the left ventricle without a thoracotomy. A stress ventricular function test (SVFT) was performed by raising the systemic blood pressure with methoxamine in the conscious dog. In order to demonstrate the effectiveness of the SVFT in the detection of a decrease in ventricular function, a SVFT was performed before and after the acute infusion of verapamil to determine resting and reserve LV function. A slope relating systolic aortic pressure to the LV end-diastolic pressure was obtained in 10 dogs using a low dose (0.005) and in four dogs a high dose (0.01 microgram X kg-1 X min-1) verapamil (V). The mean slope before V was 3.6 +/- 1.2 and after 2.0 +/- 0.92 (p less than 0.001). The day-to-day variability of the SVFT was less than 22% (coefficient of variability). The SVFT is a sensitive, reproducible method to assess resting and increased or decreased myocardial contractility and is useful in selecting appropriate doses of cardiac drugs to determine their effect on the myocardium during acute and chronic infusion studies in the conscious, nonthoracotomised dog.

Structure and organization of the mouse elk1 gene.

In the ets gene family of transcription factors, elk1 belongs to the subfamily of Ternary Complex Factors (TCFs) which bind to the Serum Response Element (SRE) in conjunction with a dimer of Serum Response Factors (SRFs). In this communication we report the isolation of cDNAs from the mouse elk1 gene, containing the full coding sequence homologous (87% identical) to the human gene, and the structure and organization of 22 kb of the mouse elk1 locus. The coding sequence is spread through 5 exons (numbered 1 to 5): exons 1 to 4 range from 102 bp to 447 bp and exon 5 is at least 620 bp. Exon 0 was not found in the 8.5 kb sequence upstream of exon 1. The intron between exons 1 and 2 is 4 kb long and the 3 other introns are less than 500 bp long. This information will be useful to engineer targeted mutations of this gene in mice and to determine the genomic structure of the other TCF genes.

Hemodynamic effects of continuous abdominal binding during cardiac arrest and resuscitation.

Abdominal binding improves arterial pressure and flow during cardiopulmonary resuscitation (CPR). This study was undertaken to assess the mechanisms of improved hemodynamics during cardiac arrest and CPR with continuous abdominal binding in a canine model (n = 8). Carotid and inferior vena caval (IVC) flow probes and cineangiography were used to observe magnitude and direction of blood flow. CPR with binding significantly increased (p less than 0.001) systolic aortic (Ao) (49 +/- 11 vs 34 +/- 12 mm Hg), right atrial (RA) (49 +/- 11 vs 31 +/- 10 mm Hg) and IVC pressure (50 +/- 7 versus 31 +/- 11 mm Hg) and common carotid flow (1.1 +/- 0.4 vs 0.7 +/- 0.4 ml/min/kg, p less than 0.05) compared with CPR without binding. Aortic, RA and IVC diastolic pressures increased similarly. Binding decreased the diastolic Ao-IVC pressure difference by 8 +/- 12 mm Hg and decreased net IVC flow (0.5 +/- 1.4 vs 1.4 +/- 1.2 ml/min/kg, p less than 0.05). Binding also decreased coronary perfusion pressure (Ao-RA) in 5 of 8 dogs. Cineangiograms showed tricuspid incompetence and reflux from the right atrium to the inferior vena cava during chest compression and IVC-to-right heart inflow during relaxation, which was confirmed by the flowmeter data. Abdominal binding during CPR decreased the size of the perfused vascular bed by inhibiting subdiaphragmatic flow and increased intrathoracic pressure for a given chest compression force, leading to preferential cephalad flow. However, coronary perfusion pressure was often adversely affected. Further studies should be undertaken before the widespread clinical application of continuous abdominal binding during CPR.

Shear stress-associated acquired von Willebrand syndrome in patients with mitral regurgitation.

BACKGROUND: Mitral valve regurgitation is associated with an acquired hemostatic defect. OBJECTIVE: We sought to assess the prevalence and severity of acquired von Willebrand syndrome in patients with native valve mitral regurgitation (MR). PATIENTS/METHODS: Fifty-three patients were prospectively observed with bleeding questionnaires and laboratory tests when undergoing an echocardiographic assessment of MR. In patients referred for mitral valve surgery, testing was repeated postoperatively. RESULTS: Echocardiography identified 13 patients with mild MR, 14 with moderate MR, and 26 with severe MR. Among patients with mild, moderate or severe MR, loss of the highest molecular weight von Willebrand factor (VWF) multimers occurred in 8%, 64%, and 85%, respectively, median platelet function analyzer collagen ADP closure times (PFA-CADPs) were 84 s (interquartile range [IQR] 73-96 s), 156 s (IQR 104-181 s), and 190 s (IQR 157-279 s), respectively, and the ratios of VWF latex activity to antigen were 0.92 (IQR 0.83-0.97), 0.85 (IQR 0.76-0.89), and 0.79 (IQR 0.75-0.82), respectively (all P < 0.001). Nine patients reported clinically significant bleeding, and seven had intestinal angiodysplasia and transfusion-dependent gastrointestinal bleeding (Heyde syndrome), with the median number of transfusions required being 20 (IQR 10-33; range 4-50). In patients who underwent mitral valve repair (n = 13) or replacement (n = 7), all measures of VWF function reported above improved significantly. CONCLUSION: The high-shear environment of moderate to severe MR is sufficient to produce prevalent perturbations in VWF activity. Acquired von Willebrand syndrome may occur in this setting, and appears to be reversible with mitral valve surgery.

Analysis of blood flow in the entire coronary arterial tree.

A hemodynamic analysis of coronary blood flow must be based on the measured branching pattern and vascular geometry of the coronary vasculature. We recently developed a computer reconstruction of the entire coronary arterial tree of the porcine heart based on previously measured morphometric data. In the present study, we carried out an analysis of blood flow distribution through a network of millions of vessels that includes the entire coronary arterial tree down to the first capillary branch. The pressure and flow are computed throughout the coronary arterial tree based on conservation of mass and momentum and appropriate pressure boundary conditions. We found a power law relationship between the diameter and flow of each vessel branch. The exponent is approximately 2.2, which deviates from Murray's prediction of 3.0. Furthermore, we found the total arterial equivalent resistance to be 0.93, 0.77, and 1.28 mmHg.ml(-1).s(-1).g(-1) for the right coronary artery, left anterior descending coronary artery, and left circumflex artery, respectively. The significance of the present study is that it yields a predictive model that incorporates some of the factors controlling coronary blood flow. The model of normal hearts will serve as a physiological reference state. Pathological states can then be studied in relation to changes in model parameters that alter coronary perfusion.

A computer reconstruction of the entire coronary arterial tree based on detailed morphometric data.

A rigorous analysis of blood flow must be based on the branching pattern and vascular geometry of the full vascular circuit of interest. It is experimentally difficult to reconstruct the entire vascular circuit of any organ because of the enormity of the vessels. The objective of the present study was to develop a novel method for the reconstruction of the full coronary vascular tree from partial measurements. Our method includes the use of data on those parts of the tree that are measured to extrapolate the data on those parts that are missing. Specifically, a two-step approach was employed in the reconstruction of the entire coronary arterial tree down to the capillary level. Vessels > 40 microm were reconstructed from cast data while vessels < 40 microm were reconstructed from histological data. The cast data were reconstructed one-bifurcation at a time while histological data were reconstructed one-sub-tree at a time by "cutting" and "pasting" of data from measured to missing vessels. The reconstruction algorithm yielded a full arterial tree down to the first capillary bifurcation with 1.9, 2.04 and 1.15 million vessel segments for the right coronary artery (RCA), left anterior descending (LAD) and left circumflex (LCx) trees, respectively. The node-to-node connectivity along with the diameter and length of every vessel segment was determined. Once the full tree was reconstructed, we automated the assignment of order numbers, according to the diameter-defined Strahler system, to every vessel segment in the tree. Consequently, the diameters, lengths, number of vessels, segments-per-element ratio, connectivity and longitudinal matrices were determined for every order number. The present model establishes a morphological foundation for future analysis of blood flow in the coronary circulation.

Involvement of endoplasmic reticulum chaperones in the folding of hepatitis C virus glycoproteins.

The hepatitis C virus (HCV) genome encodes two envelope glycoproteins (E1 and E2) which interact noncovalently to form a heterodimer (E1-E2). During the folding and assembly of HCV glycoproteins, a large portion of these proteins are trapped in aggregates, reducing the efficiency of native E1-E2 complex assembly. To better understand this phenomenon and to try to increase the efficiency of HCV glycoprotein folding, endoplasmic reticulum chaperones potentially interacting with these proteins were studied. Calnexin, calreticulin, and BiP were shown to interact with E1 and E2, whereas no interaction was detected between GRP94 and HCV glycoproteins. The association of HCV glycoproteins with calnexin and calreticulin was faster than with BiP, and the kinetics of interaction with calnexin and calreticulin were very similar. However, calreticulin and BiP interacted preferentially with aggregates whereas calnexin preferentially associated with monomeric forms of HCV glycoproteins or noncovalent complexes. Tunicamycin treatment inhibited the binding of HCV glycoproteins to calnexin and calreticulin, indicating the importance of N-linked oligosaccharides for these interactions. The effect of the co-overexpression of each chaperone on the folding of HCV glycoproteins was also analyzed. However, the levels of native E1-E2 complexes were not increased. Together, our data suggest that calnexin plays a role in the productive folding of HCV glycoproteins whereas calreticulin and BiP are probably involved in a nonproductive pathway of folding.

Coronary perfusion pressure during experimental cardiopulmonary resuscitation.

Systemic blood flow during cardiopulmonary resuscitation may result from alterations in intrapleural pressure (IPP), with the heart serving only as a passive conduit. Chest compression with simultaneous lung inflation (C + SI) or with abdominal binding may also increase vascular pressures and cerebral flow. Our study was done to evaluate the effects of C + SI with and without abdominal binding on coronary perfusion pressure (CPP) during CPR. Micromanometric pressures were recorded in 7 dogs during ventricular fibrillation (VF) and CPR to evaluate CPP (aortic minus right atrial pressure). During chest compression alone, aortic (AoP) and right atrial (RAP) pressures did not differ significantly. During relaxation, AoP (15 +/- 4 mm Hg) was greater than RAP (3 +/- 2 mm Hg; P less than 0.001) and diastolic CPP averaged 12 +/- 4 mm Hg. C + SI significantly increased AoP, RAP, and IPP, but did not improve systolic or diastolic CPP. Tight abdominal binding during chest compression alone or during C + SI also increased AoP and RAP and caused a slight but insignificant decrease in diastolic CPP. Extravascular resistance to coronary flow during VP has been shown to average 28 mm Hg in the in vitro heart. Our study indicates that CPPs calculated during CPR do not reach sufficient values to overcome the resistance offered by the fibrillating myocardium. Interventions which increase IPP, intravascular pressures, and carotid flow do not improve CPP or, by inference, coronary flow.

Characterization of truncated forms of hepatitis C virus glycoproteins.

Hepatitis C virus (HCV) glycoproteins (E1 and E2) both contain a carboxy-terminal hydrophobic region, which presumably serves as a membrane anchor. When they are expressed in animal cell cultures, these glycoproteins, in both mature complexes and misfolded aggregates, are retained in the endoplasmic reticulum. The effect of carboxy-terminal deletions on HCV glycoprotein secretion and folding was examined in this study. Sindbis and/or vaccinia virus recombinants expressing truncated forms of these glycoproteins ending at amino acids 311, 330, 354 and 360 (truncated E1), and 661, 688, 704 and 715 (truncated E2) were constructed. When expressed using Sindbis virus vectors, only truncated forms of E1 and E2 ending at amino acids 311 (E1t311) and 661 (E2t661), respectively, were efficiently secreted. Analysis of secretion of truncated forms of E2 glycoprotein expressed by vaccinia viruses indicated that significant secretion was still observed for a protein as large as E2t715. However, only secreted E2t661 appeared to be properly folded. Secreted HCV glycoprotein complexes were also detected in the supernatant of cell culture when E1t311 and E2t661 were coexpressed. Nevertheless, these secreted complexes, as well as E1t311 expressed alone, were misfolded. The effect of coexpression of E1 and E2 glycoproteins on each other's folding was evaluated with the help of a conformation-sensitive monoclonal antibody (for E2) or by analysing intramolecular disulfide bond formation (for E1). Our data indicate that the folding of E2 is independent of E1, but that E2 is required for the proper folding of E1.