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Influence of total hip design on dislocation: a computer model and clinical analysis.

Dislocation following hip arthroplasty remains problematic. While the etiology of dislocation may be multifactorial, implant system design may play a role. Using a computer aided design program, virtual range of motion of several commonly implanted designs was performed with prosthetic interference representing impingement used as an endpoint. Implants with small diameter head size (22 mm) and a larger trunion geometry (type II taper) demonstrated impingement in flexion at less than 90 degrees , suggesting an increased risk for dislocation. To investigate this clinically, we performed a review of a consecutive series of 254 primary hip arthroplasties performed by a single surgeon using an implant with a type II taper (Biomet, Warsaw, IN). At a minimum 2 year followup, 12 patients with 12 hips (4.8%) had at least one episode of dislocation. Stratified by head size, the dislocation rates were 3.6% for 28 mm, 4.8% for 26 mm, and 18.8% for 22 mm bearings. These findings support the notion that computer aided design modeling of implant systems is useful in evaluating range of motion and this technique could be employed during the design of any new implant system.

Arthroplasty, Replacement, Hip↗

Computational de novo design, and characterization of an A(2)B(2) diiron protein.

Diiron proteins are found throughout nature and have a diverse range of functions; proteins in this class include methane monooxygenase, ribonucleotide reductase, Delta(9)-acyl carrier protein desaturase, rubrerythrin, hemerythrin, and the ferritins. Although each of these proteins has a very different overall fold, in every case the diiron active site is situated within a four-helix bundle. Additionally, nearly all of these proteins have a conserved Glu-Xxx-Xxx-His motif on two of the four helices with the Glu and His residues ligating the iron atoms. Intriguingly, subtle differences in the active site can result in a wide variety of functions. To probe the structural basis for this diversity, we designed an A(2)B(2) heterotetrameric four-helix bundle with an active site similar to those found in the naturally occurring diiron proteins. A novel computational approach was developed for the design, which considers the energy of not only the desired fold but also alternatively folded structures. Circular dichroism spectroscopy, analytical ultracentrifugation, and thermal unfolding studies indicate that the A and B peptides specifically associate to form an A(2)B(2) heterotetramer. Further, the protein binds Zn(II) and Co(II) in the expected manner and shows ferroxidase activity under single turnover conditions.

Amino Acid Sequence↗

Design and transient computational fluid dynamics study of a continuous axial flow ventricular assist device.

A ventricular assist device (VAD), which is a miniaturized axial flow pump from the point of view of mechanism, has been designed and studied in this report. It consists of an inducer, an impeller, and a diffuser. The main design objective of this VAD is to produce an axial pump with a streamlined, idealized, and nonobstructing blood flow path. The magnetic bearings are adapted so that the impeller is completely magnetically levitated. The VAD operates under transient conditions because of the spinning movement of the impeller and the pulsatile inlet flow rate. The design method, procedure, and iterations are presented. The VAD's performance under transient conditions is investigated by means of computational fluid dynamics (CFD). Two reference frames, rotational and stationary, are implemented in the CFD simulations. The inlet and outlet surfaces of the impeller, which are connected to the inducer and diffuser respectively, are allowed to rotate and slide during the calculation to simulate the realistic spinning motion of the impeller. The flow head curves are determined, and the variation of pressure distribution during a cardiac cycle (including systole and diastole) is given. The axial oscillation of impeller is also estimated for the magnetic bearing design. The transient CFD simulation, which requires more computer resources and calculation efforts than the steady simulation, provides a range rather than only a point for the VAD's performance. Because of pulsatile flow phenomena and virtual spinning movement of the impeller, the transient simulation, which is realistically correlated with the in vivo implant scenarios of a VAD, is essential to ensure an effective and reliable VAD design.

Blood Flow Velocity↗

Ligand-based computer-aided pesticide design. A review of applications of the CoMFA and CoMSIA methodologies.

An overview is given of the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methodologies that are established ligand-based molecular design tools widely used by medicinal and pesticide chemists. In the absence of a three-dimensional structure of the target biopolymer, CoMFA and CoMSIA often provide a practical solution to an otherwise intractable problem of proper characterization of ligand-receptor interactions. These techniques are especially important in agrochemistry, where the number of known molecular structures of pesticide targets is limited. The use of CoMFA and CoMSIA in the agrochemical field for modelling the interactions of insecticides, fungicides, herbicides and herbicide safeners with their target binding sites is illustrated by using some selected published work. The CoMFA and CoMSIA models developed have been used successfully to map the properties of unknown receptors, construct hypotheses for ligand-receptor interactions, optimize lead structures, design novel active compounds, and predict biological activities. The application of CoMFA by the present authors for deriving a binding site hypothesis for dichloroacetamide-type herbicide safeners is described in somewhat more detail.

Computer-Aided Design↗

SEQPWR and SEQOPR: computer programs for design of maximum information trials based on group sequential logrank tests.

The maximum information trial paradigm for clinical trials with failure time data was recognized and has been investigated. With the maximum information trial paradigm, a study is concluded when a prespecified maximum number of events of interest, thus maximum information, has been accrued if there was no early stopping due to treatment difference or lack thereof. We present two interactive FORTRAN programs for use in designing maximum information trials based on group sequential logrank tests. The program SEQPWR computes the attainable power of group sequential logrank tests given the combinations of the accrual and follow-up durations. The program SEQOPR allows the users to investigate the operating characteristics of the maximum information trial given the information fractions of interim analyses. A clinical trial from the Eastern Cooperative Oncology Group is provided to illustrate the usage and features of the programs.

Algorithms↗

Computer-assisted milling of dental restorations using a new CAD/CAM data acquisition system.

BACKGROUND: Recent technologic innovations have created possibilities for restorative dentistry, such as computer-aided design and computer-aided manufacturing (CAD/CAM). PURPOSE: This article presents a new CAD/CAM process that has been developed for the fabrication of dental restorations. METHODS: This process uses an improved imaging technique, successfully applied in other industries. Imaging is accomplished with 2-dimensional line grids projected onto an object, which allows for a mathematical reproduction of prepared and unprepared tooth surfaces, including those that are outside the direct line of light. The relative position of the sensor to the surface of the object is controlled automatically. CONCLUSIONS: This system, which is undergoing clinical testing, allows the generation of various types of highly accurate dental restorations (inlays, onlays, crown, and fixed partial dentures) from a number of different materials. Acquired digitized data points are directly translated from the sensor to the electronic controls of the milling machine to provide various manufacturing possibilities, including copy milling and accurate reproduction of occlusal tooth surfaces in various materials.

Computer-Aided Design↗

Computer-assisted rational design of immunosuppressive compounds.

We describe the rational design of immunosuppressive peptides without relying on information regarding their receptors or mechanisms of action. The design strategy uses a variety of topological and shape descriptors in combination with an analysis of molecular dynamics trajectories for the identification of potential drug candidates. This strategy was applied to the development of immunosuppressive peptides with enhanced potency. The lead compounds were peptides, derived from the heavy chain of HLA class I, that modulate immune responses in vitro and in vivo. In particular, a peptide derived from HLA-B2702, amino acids 75-84 (2702.75-84) prolonged skin and heart allograft survival in mice. The biological activity of the rationally designed peptides was tested in a heterotopic mouse heart allograft model. The molecule predicted to be most potent displayed an immunosuppressive activity approximately 100 times higher than the lead compound.

Animals↗

An advanced artificial intelligence tool for menu design.

The computer-assisted menu design still remains a difficult task. Usually knowledge that aids in menu design by a computer is hard-coded and because of that a computerised menu planner cannot handle the menu design problem for an unanticipated client. To address this problem we developed a menu design tool, MIKAS (menu construction using incremental knowledge acquisition system), an artificial intelligence system that allows the incremental development of a knowledge-base for menu design. We allow an incremental knowledge acquisition process in which the expert is only required to provide hints to the system in the context of actual problem instances during menu design using menus stored in a so-called Case Base. Our system incorporates Case-Based Reasoning (CBR), an Artificial Intelligence (AI) technique developed to mimic human problem solving behaviour. Ripple Down Rules (RDR) are a proven technique for the acquisition of classification knowledge from expert directly while they are using the system, which complement CBR in a very fruitful way. This combination allows the incremental improvement of the menu design system while it is already in routine use. We believe MIKAS allows better dietary practice by leveraging a dietitian's skills and expertise. As such MIKAS has the potential to be helpful for any institution where dietary advice is practised.

Artificial Intelligence↗

LEA3D: a computer-aided ligand design for structure-based drug design.

We present an improved version of the program LEA developed to design organic molecules. Rational drug design involves finding solutions to large combinatorial problems for which an exhaustive search is impractical. Genetic algorithms provide a tool for the investigation of such problems. New software, called LEA3D, is now able to conceive organic molecules by combining 3D fragments. Fragments were extracted from both biological compounds and known drugs. A fitness function guides the search process in optimizing the molecules toward an optimal value of the properties. The fitness function is build up by combining several independent property evaluations, including the score provided by the FlexX docking program. One application in de novo drug design is described. The example makes use of the structure of Mycobacterium tuberculosis thymidine monophosphate kinase to generate analogues of one of its natural substrates. Among 22 tested compounds, 17 show inhibitory activity in the micromolar range.

Algorithms↗

MProbe: computer aided probe design for oligonucleotide microarrays.

The present work describes a complete probe design software system for oligonucleotide microarrays based on Kane's research on probe sensitivity and specificity (Kane's rule). Combining Kane's rule and traditional criteria for probe design we constructed MProbe, the software system for oligonucleotide microarrays using Java. The general criteria for probe design are: (1) probes may have different lengths that range from 20 to 100 bases; (2) they should have a similar melting temperature (Tm) or GC content; (3) they should not contain stable secondary structures; and (4) they abide by Kane's rule.

Computational Biology↗

Structure-aided drug design: crystallography and computational approaches.

Ideally, a drug that effectively attacks a specific target will be efficacious with few or no side effects. Historically, drug development has relied on a structure-activity sequential (trial-and-error) approach, testing many compounds and observing their pharmacologic effects. More recently, molecular biologists have investigated a new approach to drug design: starting with a specific target, determining what types of molecules would have a desired effect on that target and then constructing molecules that fit those criteria. Structure-aided drug design is a tool used in this new approach, which involves using crystallographic data and computer processing to describe a molecule precisely--in terms of all binding, Van der Waal's and electrostatic interactions--as a computational entity. The goal of this computational approach is to determine whether a molecule will bind to a target molecule and the character of the ligand interaction.

Computer Simulation↗

CAD/CAM subperiosteal implants in Australia. Case report.

This is the first known report of a subperiosteal implant inserted in Australia using computer assisted design (CAD) and computer assisted manufacture (CAM). A case report is presented describing a method of eliminating first stage surgery in treating fully edentulous patients with subperiosteal implants.

Computer-Aided Design↗

Participatory design of computer-supported organizational learning in health care: methods and experiences.

This paper outlines a Computer-Supported Co-operative Work (CSCW) system for primary care and presents from its participatory design process time consumption, costs, and experiences. The system integrates a hypermedia environment, a computerized patient record, and an electronicmessage system. It is developed to coordinate organizational learning in primary care from micro to macro levels by connecting strategic planning to monitoring of patient routines. Summing up design experiences, critical issues for making CSCW systems support cost-effectiveness of health care are discussed.

Community Health Centers↗

Development of a new disposable pulsatile pump for cardiopulmonary bypass: computational fluid-dynamic design and in vitro tests.

A newly conceived blood pump for pulsatile cardiopulmonary bypass (CPB) is presented. The new device's main design features (fully disposable pumping head with ring shaped valves) were intended to overcome the factors that today limit the use of pulsatile blood pumps, i.e., the complexity and costs of devices. The pump was designed and analyzed by means of three-dimensional computational models, including solid computer assisted design of the pumping head and computational fluid-dynamic (CFD) analyses of the fluid domain and of its interaction with deformable components. A prototype of the device, integrated with the venous reservoir, was built to perform hydraulic in vitro tests with aims of both validating CFD results and verifying the new device's pumping behavior. Functional evaluation of the pump was carried out by using the device in a model circuit made with standard CPB components plus a mock hydraulic bench representing an adult patient's systemic circulation. A roller pump used in pulsatile mode (RP-PM) was used for comparison. At a 5 L/min flow rate, the pulsatile hydraulic power ( ) delivered to the patient was approximately 15 mW for the RP-PM. The new pump proved to be able to deliver up to 40 mW, thus providing a more physiological condition, closer to the delivered by the natural heart (90-140 mW).

Cardiopulmonary Bypass↗

Computer-aided treatment design of a distal upper extremity soft tissue tumor with electron beam radiotherapy.

We present here a novel approach for the planning and treatment of a distal upper extremity soft tissue tumor. Utilizing computed tomography (CT) based electron dose calculations, a customized compensating wax bolus was designed in order to deliver sufficient dose coverage to the tumor volume while sparing the draining lymphatics of the patient's hand and digits. A clinical case is presented as well as the design and construction of the compensator. Outcome and clinical implications are discussed.

Adult↗