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At least 163 records · Page 9Linked to original sources
PubMed1997

Patient-specific predictions of outcomes in myocardial infarction for real-time emergency use: a thrombolytic predictive instrument.

BACKGROUND: Thrombolytic therapy can be life-saving in patients with acute myocardial infarction. However, if given too late or insufficiently selectively, it may provide little benefit but still cause serious complications and incur substantial costs. OBJECTIVE: To develop a thrombolytic predictive instrument for real-time use in emergency medical service settings that could 1) identify patients likely to benefit from thrombolysis and 2) facilitate the earliest possible use of this therapy. DESIGN: Creation and validation of logistic regression-based predictive instruments based on secondary analysis of clinical data. PATIENTS: 4911 patients who had acute myocardial infarction and ST-segment elevation on electrocardiogram; 3483 received thrombolytic therapy. MEASUREMENTS: Data were obtained from 13 major clinical trials and registries and directly from medical records, including electrocardiograms obtained at presentation. Input variables include presenting clinical and electrocardiography features; predictive models generate probabilities for acute (30-day) mortality if and if not treated with thrombolysis, 1-year mortality rates if and if not treated with thrombolysis, cardiac arrest if and if not treated with thrombolysis, thrombolysis-related intracranial hemorrhage, and thrombolysis-related major bleeding episode requiring transfusion. Together, these models constitute the thrombolytic predictive instrument. RESULTS: The predictive models generated the following mean predictions for patients in the Thrombolytic Predictive instrument Database: 30-day mortality rate, 7.1%; 1-year mortality rate, 10.9%; rate of cardiac arrest, 3.7%; rate of thrombolysis-related intracranial hemorrhage. 0.6%; and rate of other thrombolysis-related major bleeding episodes, 5.0%. They discriminated with between persons having and those not having the predicted outcome; areas under the receiver-operating characteristic (ROC) curve were between 0.77 and 0.84 for the five outcomes. Calibration between each instrument's predicted and observed served rates was excellent. Validation of the predictive instruments of 30-day and 1-year mortality, done on a separate test dataset, yielded areas under the ROC curve of 0.76 for each CONCLUSIONS: After the basic features of a clinical presentation are entered into a computerized electrocardiograph, the predictions of the thrombolytic predictive instrument can be printed on the electrocardiogram report. This decision aid may facilitate earlier and more appropriate use of thrombolytic therapy in patients with acute myocardial infarction.

Cerebral Hemorrhage↗
PubMed1990

Modeling sound generation in stenosed coronary arteries.

Acoustic measurements obtained from sensitive microphones placed on the chest are being used in a procedure to noninvasively diagnose coronary artery disease. Utilizing specially developed signal processing techniques, the spectral content of isolated diastolic heart sounds has been estimated and usually shows an increase in high-frequency components in patients with occlusive coronary arteries. In order to establish a theory for the origin of these spectral features, a sound source model has been developed which combines an incremental network model of the left coronary artery tree with a transfer function model describing arterial chamber resonant characteristics. The network model predicts flow in both normal and stenosed coronary arteries. From this flow information, the arterial chamber transfer function model predicts the development of acoustic signals from the chamber resonant characteristics. The transfer function of a segment of coronary artery demonstrates two resonance frequencies. These resonance frequencies depend upon the length and diameter of the chamber segment, as well as upon the distal hydraulic impedance loading the segment. The lower resonance frequency can be excited by the usual flow fluctuations (low frequency) in the coronary artery. In cases of stenosis, the wideband spectral characteristics of the turbulence produced by the stenosis excites both the low and high resonance frequencies. In a small sample of patients, the spectra obtained from isolated diastolic acoustic signals recorded by a chest microphone agree well with those predicted by this theory.

Coronary Circulation↗
PubMed1997

Synthesis of Cr(IV)-GSH, its identification and its free hydroxyl radical generation: a model compound for Cr(VI) carcinogenicity.

Current models of Cr(VI) carcinogenesis suggest an important role for Cr(IV) as an intermediate, toxic, carcinogenic species, but direct chemical evidence has been lacking. This is because Cr(IV) is a highly reactive oxidation state of Cr and few Cr(IV)-based compounds are known that can be used as a model compound containing a biological ligand. This study reports the isolation of such a stable Cr(IV) complex. The Cr(IV)-GSH complex has been synthesized through the reaction of Cr(VI) with GSH. Its electron paramagnetic resonance (EPR) spectrum exhibits g = 1.9629 and a peak-to-peak line width of 480 G in aqueous medium as well as in the powder form. Magnetic susceptibility measurements showed that the compound has a magnetic moment of 2.53 Bohr magneton per Cr, establishing that the Cr ion has two unpaired electrons, hence its identity as Cr(IV). The Cr(IV)-GSH complex is able to generate hydroxyl (.OH) radical in the presence of molecular oxygen in aqueous medium. Catalase inhibited the .OH radical generation while H2O2 enhanced it, indicating that the .OH radical was generated via a Fenton-like reaction, H2O2 being generated as an intermediate in the reduction of molecular oxygen. Metal ion chelators, deferoxamine and 1,10-phenanthroline, attenuated the generation of Cr(IV)-mediated .OH radical. In the case of deferoxamine, a deferoxamine-derived free radical was generated as shown by EPR measurements. The results imply that Cr(IV) may play an important role in the mechanism of Cr(VI)-induced carcinogenesis and Cr(IV)-GSH can be used as a model compound to study the role of Cr(IV) in this mechanism.

Carcinogens↗
PubMed1996

Monte Carlo-based treatment planning for boron neutron capture therapy using custom designed models automatically generated from CT data.

PURPOSE: A Monte Carlo-based treatment planning code for boron neutron capture therapy (BNCT), called NCTPLAN, has been developed in support of the New England Medical Center-Massachusetts Institute of Technology program in BNCT. This code has been used to plan BNCT irradiations in an ongoing peripheral melanoma BNCT protocol. The concept and design of the code is described and illustrative applications are presented. METHODS AND MATERIALS: NCTPLAN uses thin-slice Computed Tomography (CT) image data to automatically create a heterogeneous multimaterial model of the relevant body part, which is then used as input to a Monte Carlo simulation code, MCNP, to derive distributions within the model. Results are displayed as isocontours superimposed on precisely corresponding CT images of the body part. Currently the computational slowness of the dose calculations precludes efficient treatment planning per se, but does provide the radiation oncologist with a preview of the doses that will be delivered to tumors and to various normal tissues, and permits neutron irradiation times in Megawatt-minutes (MW-min) to be calculated for specific dose prescriptions. The validation of the NCTPLAN results by experimental mixed-field dosimetry is presented. A typical application involving a cranial parallel-opposed epithermal neutron beam irradiation of a human subject with a glioblastoma multiforme is illustrated showing relative biological effectiveness-isodose (RBE) distributions in normal CNS structures and in brain tumors. Parametric curves for the MITR-II M67 epithermal neutron beam, showing the gain factors (gain factor = minimum tumor dose/maximum normal brain dose) for various combinations of boron concentrations in tumor and in normal brain, are presented. RESULTS: The NCTPLAN code provides good computational agreement with experimental measurements for all dose components along the neutron beam central axis in a head phantom. For the M67 epithermal beam the gain factor for 1, boronophenylalanine for a small midline brain tumor under typical distribution assumptions is 1.4-1.8 x . Implementation of the code under clinical conditions is demonstrated. CONCLUSION: The NCTPLAN code has been shown to be well suited to treatment-planning applications in BNCT. Comparison of computationally derived dose distributions in a phantom compared with experimental measurements demonstrates good agreement. Automatic superposition of isodose contours with corresponding CT image data provides the ability to evaluate BNCT doses to tumor and to normal structures. Calculation of gain factors suggests that for the M67 epithermal neutron beam, more advantage is gained from increasing boron concentrations in tumor than from increasing the boron tumor-to-normal brain ratio.

Boron Neutron Capture Therapy↗
PubMed1997

Detecting linkage for a complex disease using simulated extended pedigrees.

The simulated extended pedigree data of the Genetic Analysis Workshop 10 were used to examine the relationship between several quantitative traits (Q1-Q5), an environmental factor, age and sex and to identify genes contributing to the quantitative traits. A forward selection procedure was used to identify regression models for each trait. Residuals from these regression models were used as quantitative traits in linkage analysis. Two-point sib-pair analysis was performed on Replicate 1 of the data set using SIBPAL. Sixteen regions on 8 chromosomes yielded two-point p-values < 0.005 in Replicate 1. Two strategies for utilizing a second data set were evaluated. In a two-stage approach, only those regions with p-value < 0.005 in Replicate 1 were followed up in the second data set. Nine of these regions had p-values < 0.05 in Replicate 2; four were associated with major genes included in the generating model and the remaining five regions were false positives. An alternative strategy was to perform a repeat genome wide screen in the second data set. This strategy resulted in the identification of 20 regions with p-values < 0.05 in both replicates; five of which included major genes included in the generating model. Although the false positive rate increased when a complete genome screen was performed on both data sets, the two-stage screen, with a more stringent initial criterion for identifying suggestive linkages, had a higher rate of false negatives. For some studies, conducting two complete genome screens in a split-sample design may be worthwhile.

Age Distribution↗
PubMed1994

A network model for generating differential symmetry axes of shapes via receptive fields.

Some symmetries (e.g. bilateral, rotational, translational) only describe quite specialized shapes, but differential symmetry axes (e.g. Blum, J. Theoret. Biol. 38, 205-287, 1973; Brady and Asada, Int. J. Robotics Res. 3, 36-61, 1984) describe more general shapes. Such axes are of interest in part because they form the 'backbone' of generalized cylinder and other shape representations used in shape recognition (e.g. Marr, Vision, W. H. Freeman and Co., NY, 1982; Biederman, Psychol. Rev. 94, 115-147, 1987). However, despite the popularity of these representations as psychological models, algorithms from machine vision for computing them have strong limitations as psychological models. This paper presents two versions of a network model, one of which is more plausible as a psychological model because it derives symmetry axes from the activations of idealized visual receptive fields.

Form Perception↗
PubMed2000

A mathematical model of solute coupled water transport in toad intestine incorporating recirculation of the actively transported solute.

A mathematical model of an absorbing leaky epithelium is developed for analysis of solute coupled water transport. The non-charged driving solute diffuses into cells and is pumped from cells into the lateral intercellular space (lis). All membranes contain water channels with the solute passing those of tight junction and interspace basement membrane by convection-diffusion. With solute permeability of paracellular pathway large relative to paracellular water flow, the paracellular flux ratio of the solute (influx/outflux) is small (2-4) in agreement with experiments. The virtual solute concentration of fluid emerging from lis is then significantly larger than the concentration in lis. Thus, in absence of external driving forces the model generates isotonic transport provided a component of the solute flux emerging downstream lis is taken up by cells through the serosal membrane and pumped back into lis, i.e., the solute would have to be recirculated. With input variables from toad intestine (Nedergaard, S., E.H. Larsen, and H.H. Ussing, J. Membr. Biol. 168:241-251), computations predict that 60-80% of the pumped flux stems from serosal bath in agreement with the experimental estimate of the recirculation flux. Robust solutions are obtained with realistic concentrations and pressures of lis, and with the following features. Rate of fluid absorption is governed by the solute permeability of mucosal membrane. Maximum fluid flow is governed by density of pumps on lis-membranes. Energetic efficiency increases with hydraulic conductance of the pathway carrying water from mucosal solution into lis. Uphill water transport is accomplished, but with high hydraulic conductance of cell membranes strength of transport is obscured by water flow through cells. Anomalous solvent drag occurs when back flux of water through cells exceeds inward water flux between cells. Molecules moving along the paracellular pathway are driven by a translateral flow of water, i.e., the model generates pseudo-solvent drag. The associated flux-ratio equation is derived.

Animals↗
PubMed1992

Production of chickens with marginal vitamin A deficiency.

Marginally vitamin A-deficient 1-d-old chickens capable of remaining healthy for at least 6 weeks were produced using a two-generation model. In this model, hens fed on diets with a limited vitamin A content were used to obtain 1-d-old chickens which were marginally deficient in vitamin A. Only hens with a narrow range of plasma retinol values (0.60-0.85 mumol/l) were satisfactory for this purpose. Above this range the 1-d-old chickens were not marginally vitamin A deficient. Below this range egg production and hatchability were affected to some extent depending on the degree of vitamin A deficiency. Even when egg production and hatchability remained at a high level in such birds, the 1-d-old chickens produced were not sufficiently strong to survive the first weeks of life. The advantages of the two-generation model for producing marginally vitamin A-deficient chickens are the increased uniformity and predictability of the chickens with respect to body-weight, general health and vitamin A status. However, it does take about 3 months to produce such chickens.

Animals↗
PubMed1995

Validation of a quick modeling program generating clearance estimates at steady state for routine therapeutic drug monitoring.

Therapeutic drug monitoring (TDM) of chronic treatments is justified for several reasons, including relative over- or underdosage due to variable individual elimination, pharmacokinetic interactions in drug combinations, and noncompliance. In all these circumstances, the prescribing physician is interested in having an estimation of the patient's clearance of the drug, even from one measurement. We compare a validated bayesian program, USC*Pack of Jelliffe, found difficult to use in daily routine, with a "home-made" program. The latter, which is capable of taking data from a clinical database, will generate a graphic simulation of daily plasma drug concentrations together with an estimation of steady-state clearance more rapidly than does USC*Pack. Both programs were run with only one measured plasma level. The patients were 83 children or young adults treated with phenobarbital (PB), carbamazepine (CBZ), and/or Valproic acid (VPA) who were resistant to monotherapy and who were to be sampled two to four times between doses. Drugs were routinely assayed by high-performance liquid chromatography (HPLC). Despite the rough character of Phacile (numeric integration and adjustment of only two of three parameters, without an acknowledged minimization algorithm), the results are comparable to those obtained with USC*Pack for estimating clearance and predicting plasma drug concentrations. Phacile algorithm, although simple, has proven of interest in routine TDM and as an introduction for medical students to the bayesian approach of population pharmacokinetics.

Adolescent↗
PubMed1996

Economic evaluation of allogeneic bone marrow transplantation: a rudimentary model to generate estimates for the timely formulation of clinical policy.

PURPOSE: To provide an evidence-based approach to the formulation of clinical policy with respect to allogeneic bone marrow transplantation (BMT) that involves perceived trade offs between two major factors: costs and consequences. The report also highlights key informational deficiencies. PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML) in second complete remission (2CR) and those with acute lymphoblastic leukemia (ALL) in first complete remission (1CR) were assigned to BMT or control groups solely on the availability of a suitable donor. All hospital-borne costs were estimated, based on services used according to manual chart review, in four categories: diagnostic and therapeutic costs, professional fees, drug costs, and ward costs. Incremental costs and incremental life-years were calculated, and the quotient determined a cost per life-year gained by BMT for AML (2CR) and ALL (1CR). RESULTS: The incremental cost (in 1992 Canadian dollars) per life-year gained by BMT (cost-effectiveness) for AML (2CR) was $29,200; and for ALL (1CR) it was minus $29,200. CONCLUSION: For AML (2CR), allogeneic BMT creates better outcomes than standard treatment, but is more costly. For ALL (1CR), both the costs and outcomes are similar for BMT and standard therapy. Quality adjustments made to life-years gained did not change these conclusions.

Adolescent↗
PubMed1991

Implementing Boissonnat's method for generating surface models of craniofacial cartilages.

Surface modeling of embryonic craniofacial morphology typically is accomplished using data derived from planar contours. Methods currently available for reconstructing embryonic craniofacial anatomy from contour data rely on shortest-path algorithms in order to interpolate surfaces. However, these techniques either fail or require a considerable amount of user interaction when complex surfaces are modeled since foramina and structural divisions cannot be interpolated properly. Recently, a new approach has been described by Boissonnat that constructs a polyhedral volume between sets of planar contours. Surfaces are interpolated by identifying the planes formed when the contours intersect the polyhedron. The purpose of this study is to determine whether craniofacial cartilages from embryonic mice can be reconstructed in an accurate and reliable fashion using this method. Embryonic mice were collected and processed for routine histological sectioning. Serial sections of the anterior cranial base and nasal capsule were obtained, subjected to videomicroscopy, and modeled. Reconstructions of the anterior cranial base and nasal capsule from embryonic mice were compared to the same structures in age-matched specimens that were processed with whole-mount staining procedures. The models compared well with the whole-mount preparations. In addition, the reconstruction technique accurately rendered complex surface features of the embryonic anterior cranial base and nasal capsule including foramina and structural branches.

Algorithms↗
PubMed1985

Smoking behavior, cessation techniques, and the health decision model.

The magnitude of the problem of smoking challenges health providers to persuade patients of the importance of trying to quit. Smoking behavior and cessation techniques are discussed in terms of the health decision model, a third-generation model combining health beliefs, decision analysis, and behavioral decision theory. This review suggests the need for physicians to emphasize factors such as health beliefs, self-efficacy, social support, and reduction of stress in smoking cessation efforts. Patients experiencing symptoms, particularly relating to the lungs or heart, may have stronger health beliefs and are clearly more likely to quit smoking. In the absence of a clear-cut advantage for any particular smoking cessation technique, physicians should provide advice about smoking as a regular part of every patient visit.

Adult↗
PubMed1978

Computer-generated graphic models of the N2-substituted deoxyguanosine adducts of 2-acetylaminofluorene and benzo[a]pyrene and the O6-substituted deoxyguanosine adduct of 1-naphthylamine in the DNA double helix.

Computer models of three deoxyguanosine-carcinogen adducts in double-helical DNA are presented. The carcinogen moiety is rotated and the best fit within the double helix is evaluated. The 2-acetylaminofluorene (AAF) derivative, 3-(deoxyguanosin-N2-yl)-AAF, is found to be situated within the minor groove, has very little freedom of rotation and causes little helical distortion. The (+)-anti-benzo[a]-pyrene (BP)-diol epoxide-N2 adduct, 10beta-(deoxyguanosin-N2-yl)-7beta, 8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydro-BP, has a similar fit with a greater degree of steric interaction, suggesting that this adduct could cause some local destabilization. The 1-naphthylamine (NA) derivative, N1-(deoxyguanosine-O6-yl)-1-NA, resides within the major groove, does not perturb the helix and has considerable freedom of movement.

1-Naphthylamine↗
PubMed1992

Computer-generated bone models in the planning of osteotomy of multidirectional distal radius malunions.

Computer-assisted design and manufacturing technology has been used to create solid models of five unusually complex, multidirectional malunions of distal radius fractures. Preoperative planning was dramatically enhanced by the ability to perform the surgical procedure on these models, with a model of the uninjured limb used for comparison. All five patients had significant malunions, with malrotation in the horizontal plane in five and an impacted articular fragment in two. A satisfactory outcome was achieved in each case.

Adult↗
PubMed2026

CRISPR/Cpf1-mediated knockout of FLG in human induced pluripotent stem cells generates a model for studying epidermal barrier dysfunction.

Loss of filaggrin (FLG) function impairs skin barrier formation and contributes to common inflammatory skin diseases. In this study, we established a FLG knockout human induced pluripotent stem cell (iPSC) line based on KOLF2.1&#xa0;J using CRISPR/Cas12a (Cpf1)-mediated genome editing. A guide RNA targeting exon 2 introduced a homozygous mutation, which was confirmed by sequencing. The edited cells maintained typical pluripotent stem cell morphology, expressed key undifferentiated markers, and retained the ability to differentiate into all three germ layers. Karyotype and copy number variation (CNV) analyses confirmed genomic stability and parental origin; the cells were free of mycoplasma. This cell line enables studies of FLG-associated skin biology and pathology.

Humans↗
PubMed2024

Model-directed generation of artificial CRISPR-Cas13a guide RNA sequences improves nucleic acid detection.

CRISPR guide RNA sequences deriving exactly from natural sequences may not perform optimally in every application. Here we implement and evaluate algorithms for designing maximally fit, artificial CRISPR-Cas13a guides with multiple mismatches to natural sequences that are tailored for diagnostic applications. These guides offer more sensitive detection of diverse pathogens and discrimination of pathogen variants compared with guides derived directly from natural sequences and illuminate design principles that broaden Cas13a targeting.

CRISPR-Cas Systems↗