Biomedical subjects

Christopher Sewell

Publications and source records attributed to Christopher Sewell.

6 recordsLinked to original sources

PubMed2006

Achieving proper exposure in surgical simulation.

One important technique common throughout surgery is achieving proper exposure of critical anatomic structures so that their shapes, which may vary somewhat among patients, can be confidently established and avoided. In this paper, we present an algorithm for determining which regions of selected structures are properly exposed in the context of a mastoidectomy simulation. Furthermore, our algorithm then finds and displays all other points along the surface of the structure that lie along a sufficiently short and straight path from an exposed portion such that their locations can be safely inferred. Finally, we present an algorithm for providing realistic visual cues about underlying structures with view-dependent shading of the bone.

Algorithms↗

PubMed2005

Quantifying risky behavior in surgical simulation.

Evaluating a trainee's performance on a simulated procedure involves determining whether a specified objective was met while avoiding certain "injurious" actions that damage vulnerable structures. However, it is also important to teach the stylistic behaviors that minimize overall risk to the patient, even though these criteria may be more difficult to explicitly specify and detect. In this paper, we address the development of metrics that evaluate the risk in a trainee's behavior while performing a simulated mastoidectomy. Specifically, we measure the trainee's ability to maintain an appropriate field of view so as to avoid drilling bone that is hidden from view, as well as to consistently apply appropriate forces and velocities. Models of the maximum safe force and velocity magnitudes as functions of distances from key vulnerable structures are learned from model procedures performed by an expert surgeon on the simulator. In addition to quantitatively scoring the trainee's performance, these metrics allow for interactive 3D visualization of the performance by distinctive coloring of regions in which excessive forces or velocities were applied or insufficient visibility was maintained, enabling the trainee to pinpoint his/her mistakes and how to correct them. Although these risky behaviors relate to a mastoidectomy simulator, the objectives of maintaining visibility and applying safe forces and velocities are common in surgery, so it may be possible to extend much of this methodology to other procedures.

Computer Simulation↗

PubMed2003

Reduction and methyl transfer kinetics of the alpha subunit from acetyl coenzyme a synthase.

Stopped-flow was used to evaluate the methylation and reduction kinetics of the isolated alpha subunit of acetyl-Coenzyme A synthase from Moorella thermoacetica. This catalytically active subunit contains a novel Ni-X-Fe4S4 cluster and a putative unidentified n = 2 redox site called D. The D-site must be reduced for a methyl group to transfer from a corrinoid-iron-sulfur protein, a key step in the catalytic synthesis of acetyl-CoA. The Fe4S4 component of this cluster is also redox active, raising the possibility that it is the D-site or a portion thereof. Results presented demonstrate that the D-site reduces far faster than the Fe4S4 component, effectively eliminating this possibility. Rather, this component may alter catalytically important properties of the Ni center. The D-site is reduced through a pathway that probably does not involve the Fe4S4 component of this active-site cluster.

Acetate-CoA Ligase↗

PubMed2002

Stopped-Flow Kinetics of Methyl Group Transfer between the Corrinoid-Iron-Sulfur Protein and Acetyl-Coenzyme A Synthase from Clostridium thermoaceticum.

Kinetics of methyl group transfer between the Ni-Fe-S-containing acetyl-CoA synthase (ACS) and the corrinoid protein (CoFeSP) from Clostridium thermoaceticum were investigated using the stopped-flow method at 390 nm. Rates of the reaction CH(3)-Co(3+)FeSP + ACS(red) <==> Co(1+)FeSP + CH(3)-ACS(ox) in both forward and reverse directions were determined using various protein and reductant concentrations. Ti(3+)citrate, dithionite, and CO were used to reductively activate ACS (forming ACS(red)). The simplest mechanism that adequately fit the data involved formation of a [CH(3)-Co(3+)FeSP]:[ACS(red)] complex, methyl group transfer (forming [Co(1+)FeSP]:[CH(3)-ACS(ox)]), product dissociation (forming Co(1+)FeSP + CH(3)-ACS(ox)), and CO binding yielding a nonproductive enzyme state (ACS(red) + CO <==> ACS(red)-CO). Best-fit rate constants were obtained. CO inhibited methyl group transfer by binding ACS(red) in accordance with K(D) = 180 +/- 90 microM. Fits were unimproved when >1 CO was assumed to bind. Ti(3+)citrate and dithionite inhibited the reverse methyl group transfer reaction, probably by reducing the D-site of CH(3)-ACS(ox). This redox site is oxidized by 2e(-) when the methyl cation is transferred from CH(3)-Co(3+)FeSP to ACS(red), and is reduced during the reverse reaction. Best-fit K(D) values for pre- and post-methyl-transfer complexes were 0.12 +/- 0.06 and 0.3 +/- 0.2 microM, respectively. Intracomplex methyl group transfer was reversible with K(eq) = 2.3 +/- 0.9 (k(f)/k(r) = 6.9 s(-1)/3.0 s(-1)). The nucleophilicity of the [Ni(2+)D(red)] unit appears comparable to that of Co(1+) cobalamins. Reduction of the D-site may cause the Ni(2+) of the A-cluster to behave like the Ni of an organometallic Ni(0) complex.

Acetate-CoA Ligase↗

PubMed2002

Analysis of protein homeostatic regulatory mechanisms in perturbed environments at steady state.

Nine different protein homeostatic regulatory mechanisms were analysed for their ability to maintain a generic protein P within a specified range of a set-point steady-state concentration while perturbed by external processes that altered the rates at which P was produced and/or consumed. Steady state regulatory effectiveness was defined by the area within a rectangular region of "perturbation space", where axes correspond to rates of positive and negative perturbations. The size of this region differed in accordance with the regulatory elements composing the homeostatic mechanism. Such elements included basic negative feedback control of transcription (in which P, at some high concentration relative to its set-point value, binds to the gene G that encodes it, thereby inhibiting transcription), multiple sequential binding of a feedback effector (two P's bind sequentially to G), and dimerization of a feedback effector (a P(2) dimer binds to G). Two homeostatic mechanisms included a cascade structure, one with and one without translational feedback control. Another mechanism included feedback control of P degradation. Finally, two mechanisms illustrated the limits of regulatory systems. One lacked all regulatory elements (and included only an invariant rate of P synthesis and degradation) while the other assumed perfect (Boolean) regulation, in which transcription is completely inhibited at [P]>[P](sp) and is fully active at [P]<[P](sp). All of the systems evaluated are known, but the analytical expressions developed here allow quantitative comparisons between them. These expressions were evaluated at values typical of the average protein in Escherichia coli. A method for building regulatory networks by linking semi-independent regulatory modules is discussed.

Animals↗

PubMedDate not supplied

Visuohaptic simulation of bone surgery for training and evaluation.

Visual and haptic simulation of bone surgery can support and extend current surgical training techniques. The authors present a system for simulating surgeries involving bone manipulation, such as temporal bone surgery and mandibular surgery, and discuss the automatic computation of surgical performance metrics. Experimental results confirm the system's construct validity.

Bone and Bones↗