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The computer as a stereotactic surgical instrument.

We have developed methodology and stereotactic software for an operating room computer and imaging system. Patients undergo preoperative CT, MR and DSA imaging with their heads fixed in a stereotactic headholder. Localization systems attach to the headholder during the studies to create reference marks for computer transformation of points and volumes into three-dimensional stereotactic space. At the operating room computer console, the surgeon selects target points, avascular trajectories and tumour boundaries for volume reconstruction. Surgical approaches are simulated and target coordinates calculated. During surgery, the computer interactively monitors the position of stereotactically directed surgical instruments in relationship to the resident database along any viewing angle and conveniently superimposes the multiple data sources. We have found this system useful to provide rapid data acquisition and retrieval, accurate target point calculations, lesion volume reconstructions, and a convenient ability to reformat data from multiple sources in a manner useful to the surgeon and beneficial to the patient.

Angiography↗

Finite element modeling of trabecular bone damage.

This paper presents a finite element-based, computational model for analysis of structural damage to trabecular bone tissues. A modulus reduction method was formulated from elasto-plasticity theory, and was used to account for site-specific trabecular bone tissue damage. Trabecular bone tissue damage is illustrated using a large-scale, anatomically accurate, two-dimensional, microstructural finite element model of a human thoracic vertebral body. Four models with varying specifications for damage accumulation were subjected to compressive loading and unloading cycles. The numerical results and experimental validation demonstrated that the modulus reduction method reproduced the non-linear mechanical behaviour of vertebal trabecular bone. The iterative computational approach presented provides a methodology to study trabecular bone damage, and should provide researchers with a computational approach to study bone fracture and repair and to predict vertebral fragility.

Aged↗

Estimation of ACL forces by reproducing knee kinematics between sets of knees: A novel non-invasive methodology.

In situ force in the anterior cruciate ligament (ACL) has been quantified both in vitro in response to relatively simple loads by means of robotic technology, as well as in vivo in response to more complex loads by means of force transducers and computational models. However, a methodology has been suggested to indirectly estimate the in situ forces in the ACL in a non-invasive, non-contact manner by reproducing six-degree of freedom (six-DOF) in vivo kinematics on cadaveric knees using a robotic/UFS testing system. Therefore, the objective of this study was to determine the feasibility of this approach. Kinematics from eight porcine knees (source knees) were collected at 30 degrees , 60 degrees , and 90 degrees of flexion in response to: (1) an anterior load of 100 N and (2) a valgus load of 5 N m. The average of each kinematic data set was reproduced on a separate set of eight knees (target knees). The in situ forces in the ACL were determined for both sets of knees and compared. Significant differences (rho<0.05) were found between the source knees and the target knees for all flexion angles in response to an anterior load. However, in response to valgus loads, there was no significant difference between the source knees and the target knees at 30 degrees and 90 degrees of flexion. It was noted that there was a correlation between anterior knee laxity (the distance along the displacement axis from the origin to the beginning of the linear region of the load-displacement curve) and internal-external rotation. These data suggest that in order to obtain reproducible results one needs to first match knees to knees with comparable anterior knee laxity. Thus, an estimate of the in situ forces in the ACL during in vivo activities might be obtainable using this novel methodology.

Animals↗

From Jabberwocky to genome: Lewis Carroll and computational biology.

In addition to his literary output, Lewis Carroll created a vast range of games and puzzles that depend upon wordplay of various kinds, especially the manipulation of alphabetic symbols in diverse contexts. Such wordplay reveals a turn of mind well suited to methodologies used in modern computational biology.

Computational Biology↗

Bayesian estimation of doxorubicin pharmacokinetic parameters.

Doxorubicin was given by brief i.v. infusion (doses ranging from 25 to 72 mg/m2) to 28 patients for 2-7 successive courses of chemotherapy (68 courses studied in all). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of doxorubicin. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 19 patients and a total of 30 courses, which, when combined with 4 individual plasma concentrations of drug, led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 38 courses. The estimated parameters for the elimination phase (A3/V1 and t1/2 elimination) and the residual plasma level at 48 h as computed by Bayesian estimation on this reduced sub-optimal sampling protocol were compared with a maximal likelihood estimation of these parameters. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean errors were -0.0315 x 10(-4) l-1 for A3/V1, 0.0839 h for t1/2 elimination, and -0.22 ng/ml for c(48 h). The precision of the prediction of these three parameters (0.304 x 10(-5) l-1, 3.34 h, and 0.659 ng/ml, respectively) remained lower than the interindividual standard deviation (1.42 x 10(-4) l-1, 14.9 h, and 4.54 ng/ml, respectively). This procedure enables the estimation of individual pharmacokinetic parameters for doxorubicin at minimal cost and minimal disturbance of the patient.

Bayes Theorem↗

Toward objective quantification of perfusion-weighted computed tomography in subarachnoid hemorrhage: quantification of symmetry and automated delineation of vascular territories.

RATIONALE AND OBJECTIVES: Perfusion-weighted computed tomography (CTP) is a relatively recent innovation that estimates a value for cerebral blood flow (CBF) using a series of axial head CT images tracking the time course of a signal from an intravenous contrast bolus. MATERIALS AND METHODS: CTP images were obtained using a standard imaging protocol and were analyzed using commercially available software. A novel computer-based method was used for objective quantification of side-to-side asymmetries of CBF values calculated from CTP images. RESULTS: Our method corrects for the inherent variability of the CTP methodology seen in the subarachnoid hemorrhage (SAH) patient population to potentially aid in the diagnosis of cerebral vasospasm (CVS). This method analyzes and quantifies side-to-side asymmetry of CBF and presents relative differences in a construct termed a Relative Difference Map (RDM). To further automate this process, we have developed a unique methodology that enables a computer to delineate vascular territories within a brain image, regardless of the size and shape of the brain. CONCLUSIONS: While both the quantification of image symmetry using RDMs and the automated assignment of vascular territories were initially designed for the analysis of CTP images, it is likely that they will be useful in a variety of applications.

Adult↗

Interest of image processing in cell biology and immunology.

Microscopy is a basic tool for cell biologists. Recent progress of electronics and computer science made powerful methodologies for digital processing of microscopic images easily available. These methods allowed impressive increase of the power of conventional microscopy. Dramatic image enhancement may be achieved by combination of filtering techniques, computer-based deblurring and contrast enhancement. Quantitative treatment of digitized images allows absolute determination of the density of different components of the observed sample, including antigens, intracellular calcium and pH. Morphometric studies are also greatly facilitated by image processing techniques. The capture of fast phenomena may be performed by transfer of small portion of microscopic images into computer memory as well as particular use of confocal microscopy. Finally, improved display of experimental data through coded colors or other procedures may enhance the amount of information that can be conveyed by visual examination of microscopical images. The purpose of the present review is to describe the basic principles of image processing and exemplify the power of this approach with a variety of illustrated applications to conventional, fluorescence or electron microscopy as well as confocal microscopy.

Image Processing, Computer-Assisted↗

HLA and ophthalmic disease associations: a critical review and improved method for statistical analysis.

A critical review of published ophthalmic histocompatibility antigen association studies found numerous conflicting or ambiguous reports. Methodologic errors that could account for these discrepancies were categorized into 3 groups (1) arbitrary application of statistical methods to determine significance, (2) poor sampling design, and (3) variable disease definition. Multivariate analysis, not previously applied in this area provides a more powerful tool for assessing statistical significance. A computer program using this methodology for large studies is now available.

Computers↗

[The computer in nursing education--analysis of the attitudes of students of university schools].

This study aims at identifying and analyzing the attitudes by students from different institutions regarding the use of the computer in Nursing teaching. Methodology consisted in the elaboration, application and analysis of Likert scales distributed among students of the eighth semester in higher education institutions at the cities of Ribeirão Preto and Bauru. Results indicated the computer as one of the main resources for nursing teaching and the simulation as an excellent bridge between theory and practice as well as the educational softwares useful and interesting. Authors verified the high level of interest and positive attitudes regarding the employment of computer resources in nursing teaching.

Attitude of Health Personnel↗

[The role of the biostatistician in biomedical research].

Medical research projects that involve any aspect of the collection, summarization, analysis and/or interpretation of clinical quantitative information require statistical support. This input may be provided by the clinicians themselves if properly trained, but is most appropriately and commonly achieved by a relationship with a biostatistician. The biostatistician can be an assistant, a consultant, or a colleague co-investigator. The role of the biostatistician in the research endeavor is one that is partially dictated by the nature of this relationship, but also is one that has evolved considerably in the recent past. This paper reviews the role of the biostatistician in terms of the potential contribution to the research, with special attention to the evolution of this role in light of the fast changes in computation and in statistical methodology. Finally, a method for biostatistical critical appraisal of the biomedical literature is proposed.

Biometry↗

A molecular thermodynamic view of DNA-drug interactions: a case study of 25 minor-groove binders.

Developing a molecular view of the thermodynamics of DNA recognition is essential to the design of ligands for regulating gene expression. In a first comprehensive attempt at sketching an atlas of DNA-drug energetics, we present here a detailed thermodynamic view of minor-groove recognition by small molecules via a computational study on 25 DNA-drug complexes. The studies are configured in the MMGBSA (Molecular Mechanics-Generalized Born-Solvent Accessibility) framework at the current state of the art and facilitate a structure-energy component correlation. Analyses were conducted on both energy minimized structures of DNA-drug complexes and molecular dynamics trajectories developed for the purpose of this study. While highlighting the favorable role of packing, shape complementarity, and van der Waals and hydrophobic interactions of the drugs in the minor groove in conformity with experiment, the studies reveal an interesting annihilation of favorable electrostatics by desolvation. Structural modifications attempted on the ligands point to the requisite physico-chemical factors for obtaining improved binding energies. Hydrogen bonds predicted to be important for specificity based on structural considerations do not always turn out to be significant to binding in post facto analyses of molecular dynamics trajectories, which treat thermal averaging, solvent, and counterion effects rigorously. The strength of the hydrogen bonds retained between the DNA and drug during the molecular dynamics simulations is approximately 1kcal/mol. Overall, the study reveals the compensatory nature of the diverse binding free energy components, possible threshold limits for some of these properties, and the availability of a computationally viable free energy methodology which could be of value in drug-design endeavors.

Binding Sites↗

[Biomedical imaging in pharmacology with nuclear medical imaging methodologies: positron emission tomography (PET) and single photon emission computed tomography (SPECT)].

The nuclear imaging technologies, positron emission tomography (PET) and single photon emission computed tomography (SPECT), have the power to non-invasively obtain dynamic and real-time information on the in vivo behaviors of radiolabeled molecules not only in humans but also in experimental animals. Thus, PET and SPECT can image molecular interactions of biological processes in vivo directly and reveal biological phenomena that are hidden from view. Furthermore, these imaging procedures also can be repeatedly performed before and after interventions, thereby allowing each subject to be used as its own control. In these studies, the radiolabeled compounds used as imaging probes for non-invasive assays of biochemical processes should have defined in vivo behaviors that can provide valuable information on the physiological and pharmacological processes. This paper describes the principle of the nuclear medical imaging systems, rational design of radiolabeled imaging probes, and the application to in vivo investigation of the change of various neurotransmission systems under disease and drug treatment. The efficient utilization of these nuclear medical imaging technologies will accelerate biomedical studies and drug development.

Alzheimer Disease↗

Studies of factors in relapse to alcohol, drug and nicotine use: a critical review of methodologies and findings.

OBJECTIVE: To critically review the methodologies used to study relapse in substance abusers and compare some of the findings these methodologies have produced. METHOD: Representative studies that have used retrospective, prospective, or near real time methodologies to study antecedents or consequences of relapse are presented and the strengths and weaknesses of each methodology are reviewed. Limitations in the ability of substance abusers to accurately report internal states are considered. Degree of convergence in findings across methodologies is examined. RESULTS: Retrospective reports can provide perhaps the most detailed accounts of circumstances and experiences leading up to relapse, but are also more likely to be inaccurate due to the limitations of memory. Prospective studies are less likely to be affected by memory problems, but may not capture factors that immediately precede relapse. The near real time methodology, which uses palm-top computers to gather data, has many advantages over other methodologies, but a number of limitations as well. The two studies in which retrospective reports were directly compared to either prospective or near real time reports yielded mixed results regarding degree of agreement. Findings from several areas of research suggest that some substance abusers may have difficulty recognizing and reporting internal states. CONCLUSIONS: Despite memory problems and other limitations of self-report, all three methodologies have produced findings that implicate negative affect states, increased craving, cognitive factors, interpersonal problems, and lack of coping as factors in relapse. Future relapse studies should make use of all three methodologies to obtain data on relapse and consequences, and steps should be taken to enhance the accuracy of the self-reports that are gathered with each method.

Alcoholism↗

[Methodologic problems and initial results of synchronous CTG computer-assisted registration of fetal movements by ultrasound].

Aim of the studies is the registration of latent criteria of hypoxia in fetuses with intrauterin growth retardation diagnosed by ultrasonography. Under standardized conditions, 19 pregnant women with hypotrophic and 20 with eutrophic fetuses were examined between weeks 36 and 40 of gestation. Concomitantly, fetal body and respiratory movements as well as the antenatal phonocardiotocogram were registered. The following apparatuses were used (fig. 1): ultrasound unit "sono Diagnost R" from Philips, FRG; six-channel recorder "6 NEK 401" from VEB Kombinat Messgerätewerk Zwönitz, GDR; lab-oriented computer "K 1520", VEB Kombinat Robotron Dresden, GDR; fetal monitor "MT 810" (with autocorrelation) from Toitu Co., LTD, Tokyo, Japan; There were close correlations between fetal body movements and accelerations in the cardiogram. The duration of the fetal body movements influenced the duration as well as the amplitude of the corresponding accelerations. A. comparison between the two groups examined reveals that these medium term changes in the heart rate were less marked in the hypotrophic fetuses than in the control group. The differences between the two groups were statistically significant (fig. 2, 3, 4, 5). Fetal respiratory movements influence the range of beat-to-beat-variability in the cardiogram. In the group of hypotrophic fetuses this range increased significantly by 1.4 bpm during one segments of respiratory movement. For the group of eutrophic fetuses the increase in the range of beat-to-beat-variability was 1.8 bpm. We did not find a significant difference between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗