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At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Single-dose model for predicting steady-state valproic acid serum concentrations in seizure patients.

Valproic acid serum concentrations predicted by a single-dose prediction model were compared with steady-state serum concentrations measured after the start of therapy in seizure patients. Ten patients receiving valproic acid for the first time or who had not been taking the drug for two or more weeks were entered into the study. The patients' therapies were initiated with the prescribed doses of valproic acid and then maintained on fixed doses and dosing intervals until steady-state trough serum samples were obtained. Initial 5-ml blood samples were collected six to 14 hours after the ingestion of the first dose; a 5-ml steady-state trough sample was drawn in the same manner three to seven days later. Both free and total drug concentrations were determined within 48 hours of sample collection using gas-liquid chromatography. The elimination rate constant was estimated from age-specific population half-life values found in the literature. Six patients (five children, aged four to 16 years) and one adult (aged 87 years) completed the study. There was a statistically significant correlation between predicted and measured steady-state valproic acid serum concentrations for both free and total concentrations. The single-dose prediction model accurately predicted steady-state valproic acid serum concentrations in these seizure patients.

Adolescent↗
PubMed2026

Massively parallel characterization and predictive modelling of neuronal regulatory variation.

Disease-associated variants reside frequently in noncoding cis-regulatory elements (CREs), yet their functional consequences remain poorly understood. We performed a large-scale lentiMPRA in human excitatory neurons, quantifying the impact of >46,000 naturally occurring variants across >27,000 candidate CREs near 524 disease-associated genes. These data improved regulatory variant effect predictions beyond state-of-the-art models. Significant allelic effects occurred at comparable rates across common, rare, and singleton variants, demonstrating that, within MPRA-measurable effects, population frequency carries limited information about per-variant regulatory impact. Variant effect detectability and magnitude were governed primarily by baseline activity of the enclosing regulatory element and local sequence context. Regulatory effects were distributed across numerous transcription factors rather than concentrated in master regulators, consistent with a combinatorial enhancer architecture. We establish a large-scale functional variant catalog and provide a complementary benchmark and resource for developing and evaluating models of noncoding regulatory variation.

Journal Article↗
PubMed1988

A prediction model of suicide among youth.

Epidemiological relationships were studied between adolescent (ages 15 to 24 years) suicide rates and population shifts among adolescents. Suicide rates among adolescents tripled from 1956 to 1977 and have subsequently leveled off. Increases (and decreases) in adolescent suicide rates corresponded to increases (and decreases, respectively) in the proportion of adolescents in the United States. Opposite trends have been found among older age groups. Projected population fluctuations were used to predict trends in adolescent suicide rates to the year 2000: the current decrease in rates is predicted to continue until the mid-1990s. Recent data indicating a decrease in adolescent suicide rates tend to support the population model hypothesis. The data suggest that demographic variables may be of explanatory and predictive use in understanding the epidemiological trends of suicide. Early intervention and prevention strategies emerge from this model, and various social, public health, and research implications exist. However, the results must be viewed with caution because of the methodological problems inherent in using national mortality data, the possibility that other variables may account for the observed relationships, and the length of time required to test such prospective epidemiological propositions.

Adolescent↗
PubMed1989

Monte Carlo modeling of light propagation in highly scattering tissue--I: Model predictions and comparison with diffusion theory.

Using optical interaction coefficients typical of mammalian soft tissues in the red and near infrared regions of the spectrum, calculations of fluence-depth distributions, effective penetration depths and diffuse reflectance from two models of radiative transfer, diffusion theory, and Monte Carlo simulation are compared for a semi-infinite medium. The predictions from diffusion theory are shown to be increasingly inaccurate as the albedo tends to zero and/or the average cosine of scatter tends to unity.

Light↗
PubMed1992

Macro model prediction of elderly people's injury and death in road traffic accidents in Croatia.

The case of elderly people injured and killed in traffic accidents in Croatia is used to illustrate a prediction method. This method consists of several steps. First, the most important variables are selected. Second, to overcome intercorrelation, new variables are constructed that include the old ones. Third, the new variables and its first derivatives are used in a rank correlation method. The results show good predictive capabilities.

Accidents, Traffic↗
PubMed1979

A prediction model for bovine ostertagiasis.

A mathematical model based on development and mortality rates, and incorporating data on the infectivity, fecundity and migratory behaviour of Ostertagia ostertagi, was used to predict the level of pasture contamination and the occurrence of clinical ostertagiasis in grazing calves during 1975 and 1976. A comparison of the predicted and observed events showed a good correlation.

Animals↗
PubMed1990

Migration of 99mTc-labelled syngeneic lymphocytes in the rat. Biological and theoretical models predict radiation damage and poor scintigraphic detectability.

The possibility of obtaining useful scintigrams of secondary lymphoid organs after infusion of syngeneic lymphocytes labelled with technetium-99m (99mTc) was explored in a rat model. Thoracic duct lymphocyte (TDL) accumulation in various organs was measured with both 99mTc and 51Cr labelled cells, the latter processed with a method that has been shown not to damage lymphocytes. 99mTc labelled TDL did not localize properly in the lymph nodes and spleen. We could not visualize lymph nodes in scintigrams, neither could we demonstrate any difference between normal and hyperplastic spleens. Our conclusion is that radiation from the 99mTc label readily influences lymphocyte migration so that useful scintigraphy in rats and other small experimental animals becomes impossible. This was supported by results from culture experiments with 99mTc labelled, radiosensitive mouse haemopoietic progenitor cells. Theoretical considerations, including the calculations of lymphocyte self-irradiation and signal/noise ratios during scintigraphy of rat tissues, supported our conclusion that scintigraphy in small animals, to disclose the physiological migration of lymphocytes, may be impossible with the present sensitivity of gamma cameras.

Animals↗
PubMed1990

The prevalence of Trypanosoma cruzi and the demography of dog populations after insecticidal spraying of houses: a predictive model.

A three-year demographic and seroparasitological follow-up of the canine population of a rural area of Argentina endemic for Chagas' disease was carried out in order to (a) describe the population dynamics of domestic dogs, and (b) predict the decrease in the prevalence of Trypanosoma cruzi among these reservoirs after indoor spraying of houses with residual insecticides. For the latter project we designed an age-structured model with a discrete time scale. We assumed a time-dependent exponential decay in the frequency of infected hosts proportional to the host mortality rate, and also assumed and that no differential mortality existed between infected and non-infected dogs. Validation of the model was carried out, and yielded an extremely close fit between observed and theoretical values. The relevance of the model as an aid to designing strategies for the control of animal domestic reservoirs of T. cruzi, and the role of dogs as efficient sentinels of re-infestation of an area, are discussed.

Animals↗
PubMed1991

A predictive model for the clearance of soluble phospholipase A2 during septic shock.

Circulating phospholipase A2 (PLA2) has been recognized as a mediator of cardiovascular collapse in septic shock. Proximal mediators of endotoxemia, including tumor necrosis factor and interleukin 1, induce PLA2 synthesis and release, but the factors regulating PLA2 elimination are unknown. Similarly, the kinetics of PLA2 clearance during recovery from septic shock have not been examined. An autoregressive mathematical model was developed to describe the rate of PLA2 clearance during the recovery phase of septic shock. This model (which estimates that the current day's PLA2 level is 77% of the previous day's level), accounted for 89% of the variability seen in the data. The estimated circulating half-life of soluble PLA2 in septic shock in man was 32 hours. Since elevation in serum PLA2 activity is closely associated with bacteremia or endotoxemia, a significant deviation from predicted PLA2 values may denote impending relapse.

Adult↗
PubMed1990

To assess the efficacy of prophylaxis in digestive tract surgery using a predictive model of complication risk.

One hundred and ninety-one patients, all candidates for major clean-contaminated surgery, were classified according to the risk of developing postoperative wound infection, using clinical and nutritional factors. A widely validated nutritional assessment model, the Prognostic Nutritional Index (PNI), was used preoperatively to evaluate the risk and probability of post-operative septic complications. Based on the predicted outcome, patients were assigned to either a poor or a good risk group for statistical comparison. A prospective, double-blind, randomized trial was performed to compare the effectiveness of the monocyclic beta-lactam, aztreonam, with gentamicin for short-term perioperative prophylaxis. In the poor risk group (PNI greater than 40), aztreonam prophylaxis significantly reduced postoperative septic complications (p less than 0.05). The use of an objective scoring system to assess the risk of postoperative sepsis is recommended for future studies on antibiotic prophylaxis as it offers a realistic assessment basis.

Aztreonam↗
PubMed2024

Predictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients.

Epithelial ovarian cancer (EOC) has a low overall survival rate, largely due to frequent recurrence and acquiring resistance to platinum-based chemotherapy. EOC with homologous recombination (HR) deficiency has increased sensitivity to platinum-based chemotherapy because platinum-induced DNA damage cannot be repaired. Mutations in genes involved in the HR pathway are thought to be strongly correlated with favorable response to treatment. Patients with these mutations have better prognosis and an improved survival rate. On the other hand, mutations in non-HR genes in EOC are associated with increased chemoresistance and poorer prognosis. For this reason, accurate predictions in response to treatment and overall survival remain challenging. Thus, analyses of 360 EOC cases on NCI's The Cancer Genome Atlas (TCGA) program were conducted to identify novel gene mutation signatures that were strongly correlated with overall survival. We found that a considerable portion of EOC cases exhibited multiple and overlapping mutations in a panel of 31 genes. Using logistical regression modeling on mutational profiles and patient survival data from TCGA, we determined whether specific sets of deleterious gene mutations in EOC patients had impacts on patient survival. Our results showed that six genes that were strongly correlated with an increased survival time are BRCA1, NBN, BRIP1, RAD50, PTEN, and PMS2. In addition, our analysis shows that six genes that were strongly correlated with a decreased survival time are FANCE, FOXM1, KRAS, FANCD2, TTN, and CSMD3. Furthermore, Kaplan-Meier survival analysis of 360 patients stratified by these positive and negative gene mutation signatures corroborated that our regression model outperformed the conventional HR genes-based classification and prediction of survival outcomes. Collectively, our findings suggest that EOC exhibits unique mutation signatures beyond HR gene mutations. Our approach can identify a novel panel of gene mutations that helps improve the prediction of treatment outcomes and overall survival for EOC patients.

Humans↗
PubMedDate not supplied

Comparison of R-R interval prediction models.

Changes in the sequence or pattern of R-R intervals is an integral part of electrocardiogram detection of most clinically important arrhythmias. Moreover, there is inherent interest in these patterns and their method of study as basic physiological phenomena. Prediction of R-R interval changes based on past history and detection of departure from an established pattern have been utilized in automated monitoring strategies and algorithms. The studies described her further clarify the usefulness of Markov processes for this purpose, compare the accuracy of linear and nonlinear regression models, and indicate some advantages of both.

Arrhythmias, Cardiac↗