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Biomedical subjects

B M Graham

Publications and source records attributed to B M Graham.

8 recordsLinked to original sources

Objective selection of hyperparameter for EIT.

An algorithm for objectively calculating the hyperparameter for linearized one-step electrical impedance tomography (EIT) image reconstruction algorithms is proposed and compared to existing strategies. EIT is an ill-conditioned problem in which regularization is used to calculate a stable and accurate solution by incorporating some form of prior knowledge into the solution. A hyperparameter is used to control the trade-off between conformance to data and conformance to the prior. A remaining challenge is to develop and validate methods of objectively selecting the hyperparameter. In this paper, we evaluate and compare five different strategies for hyperparameter selection. We propose a calibration-based method of objective hyperparameter selection, called BestRes, that leads to repeatable and stable image reconstructions that are indistinguishable from heuristic selections. Results indicate: (1) heuristic selections of hyperparameter are inconsistent among experts, (2) generalized cross-validation approaches produce under-regularized solutions, (3) L-curve approaches are unreliable for EIT and (4) BestRes produces good solutions comparable to expert selections. Additionally, we show that it is possible to reliably detect an inverse crime based on analysis of these parameters.

Algorithms↗

Cloning, expression and characterization of a single-chain antibody fragment to the herbicide paraquat.

New cost effective methods for the detection and removal of pesticides from water samples are required to meet modern safety standards. The recent development of techniques to produce antibody fragments in bacteria has provided the opportunity to exploit antibodies as specialized chemicals for affinity detection/removal technologies. The variable heavy and light polypeptide chains of the anti-paraquat monoclonal antibody PQXB1/2 have been cloned into the single-chain antibody (ScAb) expression vector pBG1. The construct was expressed in Escherichia coli and 0.4 mg functional antibody produced from 1 dm3 of induced culture. Characterization of ScAb by antigen binding profile and competition ELISA showed it to have a sensitivity one order of magnitude below that of the parent monoclonal. ScAb was purified as a monomer or dimer and analysed by HPLC size exclusion chromatography. When immobilized on polystyrene beads the ScAb could remove 85% of a paraquat-bovine serum albumin conjugate from solution in a single step.

Amino Acid Sequence↗

Expression and purification strategies for the production of single-chain antibody and T-cell receptor fragments in E. coli.

This work describes protocols for the production of single-chain antibody and T-cell receptor fragments in E. coli. A choice of methods is given for the purification of the recombinant fragments that rely on the use of either immunoaffinity or metal chelate affinity chromatography. The TCR fragments may have to be denatured and refolded before the fragments attain their proper conformation.

Chromatography, Affinity↗

Expression of monovalent and bivalent antibody fragments in Escherichia coli.

The technology of humanization of rodent antibodies has opened the way for a broad range of therapeutic antibodies with very low immunogenicity, which are, therefore, suitable for repeated dosing. Such intact antibodies have extended serum half-lives and biodistribution profiles very similar to human antibodies. For some applications, however, the ideal therapeutic should have reduced serum half-life and altered biodistribution patterns typical of antibody fragments, such as Fab or single chain Fv. Bispecific antibody fragments offer exciting additional therapeutic possibilities, but their successful manufacture and purification on a large scale require the development of new methods. Antibody fragments often assemble in Escherichia coli as monovalent fragments with reduced affinities. We describe the spontaneous assembly of bivalent antibody fragments in E. coli and methods of purification that yield either bivalent or monovalent molecules as required.

Animals↗

Signal-averaged electrocardiographic detection of terminal QRS deflection suggesting late potentials.

A terminal QRS deflection on a 12-lead electrocardiogram (previously described as peri-infarction block) most likely represents slowed conduction in a large area of myocardium near the infarct zone. We have described a patient with peri-infarction block, abnormal findings on signal-averaged electrocardiogram, and reentrant ventricular tachyarrhythmias. Our observation underscores the need to recognize the importance of terminal QRS deflections in the appropriate clinical situation.

Adult↗

Effect of hemodialysis on left ventricular systolic function in the presence and absence of beta-blockade: influence of left ventricular mass.

To assess the effect of hemodialysis on the left ventricular (LV) systolic function in the presence and absence of beta blockade, we performed echocardiography just prior to and immediately after 4-hour maintenance hemodialysis in 38 patients with end-stage renal disease. The LV systolic function was assessed in subgroups with normal and increased LV mass in both the beta blockade group (n = 19) and the non-beta blockade group (n = 19). There was a significant negative correlation between LV mass and the dialysis-induced change in the mean velocity of LV circumferential fiber shortening (mean Vcf) in both the beta blockade group (r = -0.93; p less than 0.0005) and in the non-beta blockade group (r = -0.82; p less than 0.0005). The mean dialysis-induced change in mean Vcf in the subgroup with increased LV mass in the beta blockade group (-0.02 +/- 0.11 circumferences/s) was significantly lower than the mean dialysis-induced change in mean Vcf in the non-beta blockade group (+0.12 +/- 0.04 circumferences/s; p less than 0.0005). Thus, the coexistence of increased LV mass and beta blockade significantly impedes the expected improvement of LV systolic function associated with hemodialysis.

Adrenergic beta-Antagonists↗

Left ventricular outflow tract to left atrial communication secondary to rupture of mitral-aortic intervalvular fibrosa in infective endocarditis: diagnosis by transesophageal echocardiography and color flow imaging.

Infection of the mitral-aortic intervalvular fibrosa occurs most commonly in association with infective endocarditis of the aortic valve. Infection of the aortic valve results in a regurgitant jet that presumably strikes this subaortic interannular zone of fibrous tissue and produces a secondary site of infection. Infection of this interannular zone then leads to the formation of subaortic abscess or pseudoaneurysm of the left ventricular outflow tract. This infected zone of mitral-aortic intervalvular fibrosa or subaortic aneurysm can subsequently rupture into the left atrium with systolic ejection of blood from the left ventricular outflow tract to the left atrium. This report describes the echocardiographic findings in three patients with pathologically proved left ventricular outflow tract to left atrial communication. Precise preoperative diagnosis is important, and this lesion should be differentiated from ruptured aneurysm of the sinus of Valsalva and perforation of the anterior mitral leaflet. Transthoracic echocardiography using color flow imaging and conventional Doppler techniques may show an eccentric mitral regurgitation type of signal in the left atrium originating from the region of the left ventricular outflow tract. However, transesophageal echocardiography provides an accurate preoperative diagnosis and should be used intraoperatively during repair of such lesions.

Adult↗