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At least 829 records · Page 46Linked to original sources

PubMed2004

Bioenergetics-based modeling of individual PCB congeners in nestling tree swallows from two contaminated sites on the upper Hudson River, New York.

A bioenergetics-based model was used to simulate the accumulation of total PCBs and 20 PCB congeners by nestling tree swallows at two contaminated sites on the Upper Hudson River, New York. PCB concentrations in birds were calculated as the sum of inherited residues and those acquired through consumption of contaminated insects. Close agreement between simulations and measured residues in 5-, 10-, and 15-day-old nestlings was obtained when PCB concentrations in the diet were set equal to those in food boli taken from adult birds. These simulations were further optimized by fitting the value of a dietary assimilation efficiency constant. Fitted constants for both sites were similar and averaged about 0.7. An evaluation of model performance for individual congeners provided no evidence of metabolic biotransformation. The results of this study are consistent with a companion effort in which principal components analysis was used to compare PCB congener patterns in insects and in tree swallow eggs, nestlings, and adults. Together, these studies establish a quantitative linkage between nestling tree swallows and the insects that they consume and provide strong support for the use of nestling swallows as a biomonitoring species for exposure assessment.

Animals↗

PubMed1994

Equivalent dipole parameter estimation using simulated annealing.

Equivalent-electrical dipole source modeling of evoked potential signals requires complicated non-linear multivariate optimization. Newton and non-linear simplex optimization methods often converge to a local minimum, and their results are affected by the procedure's starting parameter estimates. This paper describes simulated annealing, a more robust and resistant global optimization method. As an illustrative example, both the simplex and simulated annealing algorithms were used for parameter estimation in modeling wave V of the brain-stem auditory evoked potential (BAEP) using a single decaying sinusoid dipole source. Data for a single subject from 3000 responses to stimuli on each of 2 days were recorded, with modeling performed on 1000 response subaverages. Each estimation problem was run with 5 different sets of starting parameters. Simulated annealing always converged to the global minimum regardless of the starting parameter estimates while simplex often converged to markedly different solutions for different starting parameter estimates. No association was apparent between the simplex's converging to a local minimum and the closeness of the starting estimates to the true parameter values. Implementation of simulated annealing is discussed in terms of cooling schedules and other procedure parameters.

Acoustic Stimulation↗

PubMed2006

Two-stage two-locus models in genome-wide association.

Studies in model organisms suggest that epistasis may play an important role in the etiology of complex diseases and traits in humans. With the era of large-scale genome-wide association studies fast approaching, it is important to quantify whether it will be possible to detect interacting loci using realistic sample sizes in humans and to what extent undetected epistasis will adversely affect power to detect association when single-locus approaches are employed. We therefore investigated the power to detect association for an extensive range of two-locus quantitative trait models that incorporated varying degrees of epistasis. We compared the power to detect association using a single-locus model that ignored interaction effects, a full two-locus model that allowed for interactions, and, most important, two two-stage strategies whereby a subset of loci initially identified using single-locus tests were analyzed using the full two-locus model. Despite the penalty introduced by multiple testing, fitting the full two-locus model performed better than single-locus tests for many of the situations considered, particularly when compared with attempts to detect both individual loci. Using a two-stage strategy reduced the computational burden associated with performing an exhaustive two-locus search across the genome but was not as powerful as the exhaustive search when loci interacted. Two-stage approaches also increased the risk of missing interacting loci that contributed little effect at the margins. Based on our extensive simulations, our results suggest that an exhaustive search involving all pairwise combinations of markers across the genome might provide a useful complement to single-locus scans in identifying interacting loci that contribute to moderate proportions of the phenotypic variance.

Alleles↗

PubMed2003

Infection Probability Score (IPS): A method to help assess the probability of infection in critically ill patients.

OBJECTIVE: To develop a simple score to help assess the presence or absence of infection in critically ill patients using routinely available variables. DESIGN: Observational study of a prospective cohort of patients divided into a developmental set (n = 353) and a validation set (n = 140). SETTING: Department of intensive care at an academic tertiary care center. PATIENTS: Four hundred and ninety-three adult patients admitted to the intensive care unit for > or =24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The presence of infection was defined using the Centers for Disease Control definitions. Body temperature, heart rate, respiratory rate, white blood cell count, and C-reactive protein concentrations were measured, and the Sequential Organ Failure Assessment score was calculated throughout the intensive care unit stay. Infection was documented in 92 of the 353 patients (26%) in the developmental set and in 41 of the 140 patients (29%) in the validation set. Univariate logistic regression was used to select significant predictors for infection. Each continuous predictor was transformed in a categorical variable using a robust locally weighted least square regression between infection and the continuous variable of interest. When more than two categories were created, the variable was separated into iso-weighted dummy variables. A multiple logistic regression model predicting infection was calculated with all the variables coded 1 or 0 allowing for relative scoring of the different predictors. The resulting Infection Probability Score consisted of six different variables and ranged from 0 to 26 points (0-2 for temperature, 0-12 for heart rate, 0-1 for respiratory rate, 0-3 for white blood cell count, 0-6 for C-reactive protein, 0-2 for Sequential Organ Failure Assessment score). The best predictors for infection were heart rate and C-reactive protein, whereas respiratory rate was found to have the poorest predictive value. The cutoff value for the Infection Probability Score was 14 points, with a positive predictive value of 53.6% and a negative predictive value of 89.5%. Model performance was very good (Hosmer-Lemeshow statistic, p =.918), and the areas under receiver operating characteristic curves were 0.820 for the developmental set and 0.873 for the validation set. CONCLUSIONS: The Infection Probability Score is a simple score that can help assess the probability of infection in critically ill patients. The variables used are simple, routinely available, and familiar to clinicians. Patients with a score <14 points have only a 10% risk of infection.

Adult↗

PubMed2005

The effect of three-dimensional shape optimization on the probabilistic response of a cemented femoral hip prosthesis.

Probabilistic analyses allow the effect of uncertainty in system parameters on predicted model performance measures to be determined. Furthermore, using performance functions to describe a failure event, the probability of failure can be quantified. The effect of three-dimensional prosthesis shape optimization on the probabilistic response and failure probability of a cemented hip prosthesis system is investigated. Random variables include joint and muscle loading, cortical and cancellous bone and PMMA bone cement elastic properties, and strength parameters describing failure of the bone cement and the prosthesis-bone cement interface. Several performance functions describing the bone cement and prosthesis-cement interface are used to compute the probability of failure. When evaluated deterministically, most performance functions indicated a safe design, with the exception of interface tensile failure. However, when evaluated probabilistically, finite probabilities of failure were computed, some significant. The most likely mode of failure before shape optimization was prosthesis-bone cement interface tensile failure with a predicted probability of failure of 97.9%. Deterministic prosthesis shape optimization reduced the probability of failure for all performance functions and reduced prosthesis-bone cement interface tensile failure by 31.7%. Probability sensitivity factors indicate that the uncertainty in the joint loading, cement strength, and implant-cement interface strength have the greatest effect on the computed probability of failure. Implant shape optimization results in a more robust implant design that is less sensitive to uncertainties in joint loading, which cannot be easily controlled, and more sensitive to cement and interface properties, which are easier to modify.

Cementation↗

PubMed1996

The effect of managed care on ICU length of stay: implications for medicare.

OBJECTIVE: To determine whether insurance status (managed care vs traditional commercial and Medicare) influences resource consumption (as measured by length of stay [LOS]) in the intensive care unit (ICU). DESIGN: Retrospective analysis of the 1992 Massachusetts state hospital discharge database, using prospectively developed and validated risk-stratification models. SETTING: All nonfederal hospitals in Massachusetts. SUBJECTS: Of all adult hospitalizations where an ICU stay was incurred (n=104270), we selected those covered by 1 of 4 payer groups (n=88050): (1) commercial fee-for-service (patients aged <65 years); (2) commercial managed care (patients aged <65 years); (3) traditional Medicare (patients aged >/=65 years); and (4) Medicare-sponsored managed care (patients aged >/=65 years). MAIN OUTCOME MEASURE: Mean ICU LOS. ANALYSIS: The ICU LOS regression models were constructed using split-halves validation to adjust for differences in age, sex, severity of illness, diagnosis, discharge status, and payer. Separate models were constructed for those younger than 65 years and those aged 65 years or older. Robustness of the models was explored using goodness of fit and correlation. The effect of payer on hospital mortality was also explored using logistic regression. Observed minus predicted mean ICU LOS and mortality rates were correlated with managed care penetration at the hospital level. RESULTS: The ICU LOS models performed well (R2=0.84 and R2L [likelihood ratio statistic]=0.92 for the development set, and R2=0.83 and R2L=0.89 for the validation set). Significant covariables affecting LOS included age, severity of principal illness, comorbidity, reason for admission, and discharge status (P<.001 for each). Among the cohort younger than 65 years (n=27805), although unadjusted mean ICU LOS was shorter (2.9 vs 3.43 days; P<.05) for those covered by managed care organizations, payer status had no independent effect on ICU LOS (P=.48). Among those older than 65 years, there was neither a difference in unadjusted ICU LOS (3.94 vs 3.88 days; P>/=.05) nor an independent effect of payer on ICU LOS (P=.35). Unadjusted mortality was lower among managed care patients (3.9% vs 5.1% in patients aged <65 years [P<.05] and 8.7% vs 12.1% in patients aged > or = 65 years [P<.05]). Age, severity of principal diagnosis, comorbidity, and reason for admission significantly influenced mortality (P<.001). After controlling for these factors with the mortality model (R2L=0.92 and 0.89, C statistic [12 df]=8.45 and 17.58, and P=.75 and .13 [where a large P reflects good agreement] for the development and validation sets, respectively), payer continued to have a small but significant effect on mortality (odds ratios ranging from 1.67 at 0.1% probability of death to 1.11 at 30% probability of death.) Managed care penetration among the commercially insured varied across hospitals (n=82) from 0% to 68%. There was no correlation between managed care penetration and either ICU LOS (R2=0.04; P=.09) or mortality (R2=0.0; P=.88). CONCLUSIONS: Though patients covered under managed care consume fewer ICU resources, this appears to be primarily attributable to a difference in patient-related factors. Thus, as managed care case mix changes in the future to include sicker and older patients, the initial advantages of reduced resource consumption may diminish.

Adult↗

PubMed2004

ROC analysis of an erythroblast morphologic scoring system to improve identification of fetal cells in maternal blood.

OBJECTIVES: Nucleated red blood cells are used in research settings as a target cell type for investigations of noninvasive prenatal diagnosis, and these cells have a characteristic nuclear morphology and hemoglobin staining pattern that makes them distinguishable from maternal cells. Recently, we developed an erythroblast scoring system based on these characteristics. Here, we employ statistical analyses to further characterize the utility of this scoring system. METHODS: A total of 170 nucleated red blood cells isolated from peripheral blood of four women undergoing elective termination of a trisomy 21 male fetus were analyzed. Each of the four scoring system parameters, whose values range from 0 to 3 points, served as an independent variable to determine its significance for the correct identification of a cell as fetal or maternal. A logistic regression was used as a multivariable statistical tool. RESULTS: Forty-four patterns of the four parameters were found in the overall series. Some patterns were exclusively associated with maternal cells (e.g. 1-1-1-1 and 1-1-2-2), and others were exclusively associated with fetal cells (e.g. 3-2-2-2 and 3-2-3-2). A detection rate of 73.9% at a false-positive rate of 5% resulted from a random simulation model performed with a 1:5 case:control matched set. The variables most predictive of a cell being fetal were gamma hemoglobin staining intensity of cytoplasm and nuclear roundness. CONCLUSIONS: The modified scoring system presented here improves upon the previously reported, unmodified erythroblast scoring system. These statistical analyses suggest that the scoring system is a promising method that aids in distinguishing fetal and maternal NRBCs for prenatal diagnostic applications and that it may be amenable to automated microscopy by applying the discrete morphological parameters as computational classifiers.

Cell Nucleus↗

PubMed2004

Calculating biological behaviors of epigenetic states in the phage lambda life cycle.

The biology and behavior of bacteriophage lambda regulation have been the focus of classical investigations of molecular control of gene expression. Both qualitative and quantitative aspects of this behavior have been systematically characterized experimentally. Complete understanding of the robustness and stability of the genetic circuitry for the lysis-lysogeny switch remains an unsolved puzzle. It is an excellent test case for our understanding of biological behavior of an integrated network based on its physical, chemical, DNA, protein, and functional properties. We have used a new approach to non-linear dynamics to formulate a new mathematical model, performed a theoretical study on the phage lambda life cycle, and solved the crucial part of this puzzle. We find a good quantitative agreement between the theoretical calculation and published experimental observations in the protein number levels, the lysis frequency in the lysogen culture, and the lysogenization frequency for mutants of O(R). We also predict the desired robustness for the lambda genetic switch. We believe that this is the first successful example in the quantitative calculation of robustness and stability of the phage lambda regulatory network, one of the simplest and most well-studied regulatory systems.

Bacteriophage lambda↗

PubMed2005

Implicit sequence learning in obsessive-compulsive disorder: further support for the fronto-striatal dysfunction model.

BACKGROUND: Obsessive-compulsive disorder (OCD) is conceived as a disease that implicates dysfunctions in fronto-striatal brain systems. According to this model, performance deficits observed in patients with lesions in these brain areas are hypothesized to be present also in OCD patients. Implicit procedural learning, which refers to the acquisition of motor or nonmotor skills by practice, is one candidate function to test this prediction. METHODS: The serial reaction time task was used to assess implicit sequence learning of 33 patients with a diagnosis of OCD and 27 healthy control participants. In addition, explicit (i.e., conscious) knowledge of the sequence was determined. A subgroup of 24 patients was reassessed after intensive cognitive-behavioral psychotherapy. RESULTS: Implicit sequence learning was significantly reduced in the OCD group by 41%, while explicit learning and verbal abilities were unaffected. The deficit remained stable across time, although symptoms remitted substantially. Depressive symptoms did not account for the finding. Partial explicit knowledge of the sequence was not a predictor of the amount of implicit learning. CONCLUSIONS: Reduced implicit learning appears to be a dissociable trait of OCD patients. The results confirm previous findings and add supportive evidence for the fronto-striatal dysfunction model of OCD.

Adult↗

PubMed2001

Prognostic factors in patients with locally advanced pancreatic carcinoma receiving chemoradiotherapy.

BACKGROUND: The combination of radiation therapy and chemotherapy (chemoradiotherapy [CRT]) has been accepted as standard therapy for patients with locally advanced pancreatic carcinoma (PC). This study investigated prognostic factors in patients with locally advanced PC receiving CRT. METHODS: Fifty-five consecutive patients with locally advanced PC, who received concurrent radiotherapy (50.4 grays) and chemotherapy using 5-fluorouracil or cisplatin, were analyzed retrospectively to investigate prognostic factors. RESULTS: Median survival time and overall survival rates at 1 and 2 years were 301 days, 35.1% and 2.4%, respectively. By multivariate analysis using the Cox proportional hazards model, performance status of 0-1 (P < 0.01), absence of regional lymph node swelling (P < 0.01), and serum CA 19-9 level of less than 1000 (P = 0.02) were independent favorable prognostic factors. A prognostic index based on the coefficients of those prognostic factors was used to classify patients into three groups with good, intermediate, and poor prognoses. The median survival times for these three groups were 410, 239, and 143 days, respectively (P < 0.01). CONCLUSIONS: The results may be helpful in predicting life expectancy, determining treatment strategies, and designing future clinical trials.

Adult↗

PubMed1982

Predictive engineering formulations for diver heating.

Predictive heat transfer equations have been developed to estimate the local supplementary heating necessary to support a resting diver. These formulations consider the diver's passive thermal protection in the form of a diving dress and the effects of his ambient environment upon the dress thermal resistance. The mathematical model performs a numerical analysis on discrete regions comprised of the skin, dry protective suit, breathing gas mixture and the surrounding fluid environment. The parametric properties associated with the heat transfer correlations were obtained from validated experimental heat flux and skin temperature data collected under specific environmental conditions. The supplementary heating required to maintain a diver is obtained by determining the heat flux that would be lost were he not heated and subtracting from this the normal heat flux expected from a resting euthermic subject. Applying this principle to each of the regions, it is possible to predict the supplementary heating necessary to compensate for an excessive flux.

Body Temperature Regulation↗

PubMed2004

The affinity of GXXXG motifs in transmembrane helix-helix interactions is modulated by long-range communication.

Sequence motifs are responsible for ensuring the proper assembly of transmembrane (TM) helices in the lipid bilayer. To understand the mechanism by which the affinity of a common TM-TM interactive motif is controlled at the sequence level, we compared two well characterized GXXXG motif-containing homodimers, those formed by human erythrocyte protein glycophorin A (GpA, high-affinity dimer) and those formed by bacteriophage M13 major coat protein (MCP, low affinity dimer). In both constructs, the GXXXG motif is necessary for TM-TM association. Although the remaining interfacial residues (underlined) in GpA (LIXXGVXXGVXXT) differ from those in MCP (VVXXGAXXGIXXF), molecular modeling performed here indicated that GpA and MCP dimers possess the same overall fold. Thus, we could introduce GpA interfacial residues, alone and in combination, into the MCP sequence to help decrypt the determinants of dimer affinity. Using both in vivo TOXCAT assays and SDS-PAGE gel migration rates of synthetic peptides derived from TM regions of the proteins, we found that the most distal interfacial sites, 12 residues apart (and approximately 18 A in structural space), work in concert to control TM-TM affinity synergistically.

Amino Acid Motifs↗

PubMed2005

Automated classification and analysis of the calcium response of single T lymphocytes using a neural network approach.

The gene activities in T lymphocytes that regulate immune responses are influenced by Ca2+ ([Ca2+]i). The intracellular calcium signals are highly heterogeneous and vitally important in determining the immune outcome. The signals in individual cells can be measured using fluorescence microscopy but to group the cells into classes with similar signal kinetics is currently laborious. Here, we demonstrate a method for the automated classification of the responses into four categories formerly identified by an expert's inspection. This method comprises characterising the response by a second-order model, performing frequency analysis, and using derived features as inputs to two multilayer perceptron neural networks (NNs). We compare the algorithm's performance on an example data set against the human classification: it was found to classify identically more than 70% of the data, despite small sample sizes in two categories and significant overlap between the other two classes. The group characterized by an oscillating signal showed the presence of a number of frequencies, which may be important in determining gene activation. A classification threshold enables the automatic identification of patterns with a low-classification certainty. Future refinement of the algorithm may allow the identification of more classes, which may be important in different immune responses associated with disease.

Algorithms↗

PubMed2006

The effects of intradermal and topical mitomycin C on wound healing.

OBJECTIVE: To determine the effect of intradermal and topical mitomycin C (MMC) on skin wound healing. STUDY DESIGN/SETTING: A prospective, controlled study in a rat wound model performed in an academic medical center. RESULTS: Intradermal and topical MMC application decreased wound integrity when compared with saline-treated animals at 1 week, 2 weeks, 1 month, and 6 months. Skin necrosis occurred in animals that received intradermal MMC. Hemotoxylin and eosin and immunohistochemical staining showed no consistent difference between treatment arms. Fibrosis and collagen deposition were reduced in MMC-treated wounds on trichrome staining. CONCLUSIONS: MMC-treated wounds showed decreased wound strength compared with controls. Intradermal MMC can cause skin necrosis. Histologic findings did not always correspond with clinical data. SIGNIFICANCE: The data suggest cautious use of MMC in clinical situations when wound breaking strength is critical.

Animals↗

PubMed1990

Progress in characterizing anatomic injury.

A three-valued description of anatomic injury is presented. Anatomic profile (AP) components A, B, and C summarize serious injuries (greater than AIS 2) to the head/brain or spinal cord; to the thorax or front of the neck; and all remaining serious injuries. Relationships between AP components and survival rate reaffirm the seriousness of head injury. Logistic function models relating AP components and the Injury Severity Score (ISS) to survival probability were based on 20,946 Major Trauma Outcome Study (MTOS) patients (9.2% mortality rate) submitted through 1986. Model performance comparisons were based on 5,939 MTOS patients (7.8% mortality rate) submitted during 1987. The AP better discriminated survivors from nonsurvivors and provided a 31% increase in sensitivity when compared with the ISS. Neither the ISS nor the AP alone reliably predict patient outcome. The predictive power of methods for estimating patient survival probability which include physiologic indices or profiles, patient age, and an anatomic profile should be compared with current methods. The AP, which is based on the severity and location of all serious injuries, provides a more rational basis for comparing patient samples than the ISS.

Humans↗

PubMed1998

Prognostic factors of renal cell carcinoma: a multivariate analysis.

BACKGROUND AND OBJECTIVES: To establish appropriate therapeutic modalities for renal cell carcinoma (RCC), informations on the factors affecting prognosis of patients are essential. For this purpose, multivariate analysis including a large set of variables is necessary. METHODS: Prognostic significance of 14 clinical factors and 19 histologic factors including counting of silver-stained nucleolar organizer regions (AgNORs) were evaluated in 96 patients. Age of patients ranged from 41 to 85 (median 59) yr with a male to female ratio of 4:1. The tumors were staged based on the TNM classification as follows: 7 in stage I, 58 in stage II, 15 in stage III, and 11 in stage IV. RESULTS: The overall and metastasis-free survival rates in all patients were 80.1% and 72.7%, respectively. Multivariate analysis using Cox's proportional hazards model performed on the factors proved to be significant at the univariate analysis. Univariate analysis revealed four clinical factors including presence of macroscopic hematuria, symptoms such as pain and palpable abdominal mass, anemia, and adjuvant therapy, and nine histologic factors, including AgNOR count, to be significant for survival. Multivariate analysis showed that anemia, pathological stage, and AgNOR count were independent factors for overall survival of patients. The AgNOR count, in particular, is the only predictive factor for metastasis-free survival. CONCLUSIONS: Among various clinicopathological factors, anemia, pathological stage, and AgNOR count are significant prognosticators of RCC. The AgNOR count is also predictive factor for metastasis-free survival.

Adult↗

PubMed2002

Submandibular gland tripeptide FEG (Phe-Glu-Gly) and analogues: keys to structure determination.

This study examined the structure activity relationship of NH(3)-Phe-Glu-Gly-COO(-) (FEG), a potent inhibitor of intestinal anaphylaxis. The inhibition by FEG analogues of antigen-provoked contractions of isolated ileal segments obtained from ovalbumin-sensitized rats was determined and molecular modeling performed. A combination of aromaticity of the first residue, minimal extension of the carboxyl group on residue 2, and underivatized N and C termini were essential for biological activity. FEG, WEG, WDG and the d-enantiomeric forms of FEG (feG) and YEG (yeG) retained biological activity. By considering dipole moments, the structural and conformational features critical to biological activity were established as the glutamyl-carboxyl group/Phe side chain and carboxyl/amino termini interactions. Analysis of Ramachandran plots for position 1 sidechains indicate that mobility of the aromatic sidechain must be restricted to retain biological activity. The anti-anaphylactic effects of FEG, characterized by specific structural and conformational restrictions, indicate a selective interaction with a receptor for this peptide in the intestine.

Animals↗

PubMed2002

Sex differences in rapid auditory processing deficits in ectopic BXSB/MpJ mice.

Prior research with rodent models, performed predominantly in males, has demonstrated a significant association between focal neocortical malformations (e.g. ectopias and microgyria) and rate-specific auditory processing deficits. In the current study and consistent with prior findings, we report that ectopic male BXSB/MpJ mice exhibit impairments in detecting a two-tone oddball stimulus at short but not long inter-stimulus interval durations when compared to non-ectopic male littermates. However, ectopic female littermates showed no rapid auditory processing deficit when compared to non-ectopic females on this same task. Current results add growing support to: (1) an association between focal cortical malformations and impaired auditory processing in males; and (2) the existence of sex differences in the behavioral consequences of focal cortical malformations.

Acoustic Stimulation↗