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Localizing haloperidol effects on sensorimotor gating in a predictive model of antipsychotic potency.

The degree to which a startle response to a loud noise is inhibited by a weak prestimulus is an operational measure of sensorimotor gating. Prepulse inhibition (PPI) can be measured across species and is reduced in schizophrenia patients and dopamine (DA)-activated rats. The ability of DA antagonists to restore PPI in apomorphine (APO)-treated rats correlates highly with their clinical antipsychotic potency. We compared the ability of systemic- vs. intracerebrally (i.c.)-administered haloperidol (HAL) to restore PPI in APO-treated rats. Consistent with previous studies, systemic administration of HAL completely restored PPI in rats treated with APO (0.5 mg/kg s.c.), with an ED50 of approximately 0.02 mg/kg. In an otherwise identical paradigm, HAL failed to fully restore PPI after infusion into either the nucleus accumbens (NACcore or NACshell), NACcore + caudate nucleus (CN), ventral subiculum (VS), medial prefrontal cortex (MPFC), or ventral tegmentum (VTA). A subtotal, but statistically significant restoration of PPI was achieved after HAL infusion into all regions, except the NACshell. Statistically significant effects of i.c. HAL tended to be observed at doses that were only approximately 5-10-fold lower than those at which significant effects were observed after systemic administration. The results suggest that systemically administered HAL may restore PPI in APO-treated rats through its action distributed throughout multiple levels of PPI-regulatory circuitry.

Animals↗

A predictive model of varicella-zoster virus infection after autologous peripheral blood progenitor cell transplantation.

Varicella-zoster virus (VZV) frequently causes severe infections in patients who have undergone bone marrow transplantation. The frequency of, characteristics of, and risk factors for this infection were studied in 164 patients undergoing autologous peripheral blood progenitor cell transplantation (PBPCT). Twenty-six patients (15.8%) developed VZV infection, and the actuarial risk was 10% at 1 year. No patient had visceral dissemination or died because of VZV, although one-third of the patients developed postherpetic neuralgia. By multivariate analysis, a CD4(+) lymphocyte count of <200 cells/microL (P<.0001; odds ratio [OR], 2.0) and a CD8(+) lymphocyte count of <800 cells/microL (P=.0073; OR, 2.0) at day 30 after transplantation were factors associated with VZV infection. Patients with both these adverse factors had an actuarial risk of VZV of 48% at 1 year. Patients with deficiency in both CD4(+) and CD8(+) lymphocytes are at high risk of VZV infection. These patients should be considered as candidates for preventive therapy, but whether for antiviral therapy or vaccination remains to be investigated.

Adolescent↗

Staphylococcus aureus growth boundaries: moving towards mechanistic predictive models based on solute-specific effects.

The formulation of shelf-stable intermediate-moisture products is a critical food safety issue. Therefore, knowing the precise boundary for the growth-no-growth interface of Staphylococcus aureus is necessary for food safety risk assessment. This study was designed to examine the effects of various humectants and to produce growth boundary models as tools for risk assessment. The molecular mobility and the effects of various physical properties of humectants, such as their glass transition temperatures, their membrane permeability, and their ionic and nonionic properties, on S. aureus growth were investigated. The effects of relative humidity (RH; 84 to 95%, adjusted by sucrose plus fructose, glycerol, or NaCl), initial pH (4.5 to 7.0, adjusted by HCl), and potassium sorbate concentration (0 or 1,000 ppm) on the growth of S. aureus were determined. Growth was monitored by turbidity over a 24-week period. Toxin production was determined by enterotoxin assay. The 1,792 data points generated were analyzed by LIFEREG procedures (SAS Institute, Inc., Cary, N.C.), which showed that all parameters studied significantly affected the growth responses of S. aureus. Differences were observed in the growth-no-growth boundary when different humectants were used to achieve the desired RH values in both the absence and the presence of potassium sorbate. Sucrose plus fructose was most inhibitory at neutral pH values, while NaCl was most inhibitory at low pH values. The addition of potassium sorbate greatly increased the no-growth regions, particularly when pH was <6.0. Published kinetic growth and survival models were compared with boundary models developed in this work. The effects of solutes and differences in modeling approaches are discussed.

Colony Count, Microbial↗

A prediction model of aerobic exercise in older adults living in a continuing-care retirement community.

OBJECTIVES: The purpose of this study was to test a model of exercise behavior in older adults. It was hypothesized that gender, marital status, chronic illness, mental and physical health, self-efficacy and outcome expectations, fear of falling, and past exercise behavior were directly and/or indirectly associated with current exercise behavior. METHODS: In this descriptive study, interviews were conducted with 201 older adults living in a continuing-care retirement community. RESULTS: Twelve paths were significant, and the model accounted for 40% of the variance in exercise behavior. Self-efficacy expectations, outcome expectations, and prior exercise were directly associated with current exercise; health status, gender, and marital status were indirectly associated with current exercise behavior through self-efficacy and outcome expectations. DISCUSSION: Recognizing and treating mental and physical health problems may directly influence self-efficacy and outcome expectations related to exercise. Moreover, interventions that strengthen self-efficacy and outcome expectations related to exercise may improve exercise behavior.

Aged↗

Application of breast cancer risk prediction models in clinical practice.

Breast cancer risk assessment provides an estimation of disease risk that can be used to guide management for women at all levels of risk. In addition, the likelihood that breast cancer risk is due to specific genetic susceptibility (such as BRCA1 or BRCA2 mutations) can be determined. Recent developments have reinforced the clinical importance of breast cancer risk assessment. Tamoxifen chemoprevention as well as prevention studies such as the Study of Tamoxifen and Raloxifene are available to women at increased risk of developing breast cancer. In addition, specific management strategies are now defined for BRCA1 and BRCA2 mutation carriers. Risk may be assessed as the likelihood of developing breast cancer (using risk assessment models) or as the likelihood of detecting a BRCA1 or BRCA2 mutation (using prior probability models). Each of the models has advantages and disadvantages, and all need to be interpreted in context. We review available risk assessment tools and discuss their application. As illustrated by clinical examples, optimal counseling may require the use of several models, as well as clinical judgment, to provide the most accurate and useful information to women and their families.

Breast Neoplasms↗

A predictive model for the effect of temperature and predrying treatments in reducing Listeria monocytogenes populations during drying of beef jerky.

The objective of this study was to model the effect of drying temperatures (52, 57, and 63 degrees C) and predrying treatments on the inactivation of Listeria monocytogenes on beef jerky. Before drying, beef slices were inoculated with a 10-strain composite of L. monocytogenes and then treated with the following: (i) nothing (C), (ii) traditional marinade (M), or (iii) dipping in 5% acetic acid solution for 10 min, followed by M (AM). In addition, sequential stresses (exposure to 10% NaCl, followed by an adjustment of the pH to 5.0 and, subsequently, a water bath at 45 degrees C) were applied to the inocula before beef contamination and drying at 63 degrees C. Surviving L. monocytogenes were determined on tryptic soy agar plus 0.6% yeast extract (TSAYE) and on PALCAM agar at 0, 2, 4, 6, 8, and 10 h during drying. Data were modeled by a linear regression (treatment AM) and a logistic-based equation capable of fitting biphasic inactivation curves without initial shoulder (treatments C and M). The total log reductions expressed as the CFU per square centimeter of L. monocytogenes (3.9 to 5.1) for the samples treated with M (3.5 to 5.4) when compared with C were similar, whereas AM-treated samples had higher (6.1 to 6.8) reductions. All survival curves were characterized by an initial rapid decrease in populations within the first 2 h, which was followed by a secondary death phase at a lower rate. No significant (P > or = 0.05) differences in inactivation were observed due to drying temperatures in the range (52 to 63 degrees C) tested. Inactivation differences between recovered counts of stressed and unstressed cells were significant (P < 0.05) in PALCAM but not in TSAYE. The acidified predrying treatment (AM) had higher pathogen inactivation during drying than other treatments, regardless of drying temperature. The models developed may be useful in designing effective drying processes for beef jerky.

Animals↗

Comparing air dispersion model predictions with measured concentrations of VOCs in urban communities.

Air concentrations of nine volatile organic compounds were measured over 48-h periods at 23 locations in three communities in the Minneapolis-St. Paul metropolitan area. Concentrations at the same times and locations were modeled using a standard regulatory air dispersion model (ISCST3). The goal of the study was to evaluate model performance by comparing predictions with measurements using linear regression and estimates of bias. The modeling, done with mobile and area source emissions resolved to the census tract level and characterized as model area sources, represents an improvement over large-scale airtoxics modeling analyses done to date. Despite the resolved spatial scale, the model did not fully capture the spatial resolution in concentrations in an area with a sharp gradient in emissions. In a census tract with a major highway at one end of the tract (i.e., uneven distribution of emissions within the tract), model predictions atthe opposite end of the tract overestimated measured concentrations. This shortcoming was seen for pollutants emitted mainly by mobile sources (benzene, ethylbenzene, toluene, and xylenes). We suggest that major highways would be better characterized as line sources. The model also failed to fully capture the temporal variability in concentrations, which was expected since the emissions inventory comprised annual average values. Based on our evaluation metrics, model performance was best for pollutants emitted mainly from mobile sources and poorest for pollutants emitted mainlyfrom area sources. Important sources of error appeared to be the source characterization (especially location) and emissions quantification. We expect that enhancements in the emissions inventory would give the greatest improvement in results. As anticipated for a Gaussian plume model, performance was dramatically better when compared to measurements that were not matched in space or time. Despite the limitations of our analysis, we found thatthe regulatory air dispersion model was generally able to predict space and time matched 48-h average ambient concentrations of VOC species within a factor of 2 on average, results that meet regulatory model acceptance criteria.

Air Movements↗

Prediction models for sound leakage through noise barriers.

Two numerical models are presented for the prediction of sound leakage through openings in thin hard barriers. The first numerical method is based on a simple procedure of numerical integration that can be implemented straightforwardly. This model is a more general approach, suitable for barriers with arbitrary gaps. The second model is a new method that permits prediction of sound leakage due to the presence of horizontal gaps in a long barrier. In the new method, effective barriers of appropriate heights represent the edges of the horizontal gaps. The sound diffracted by each effective barrier is calculated by a closed-form analytic expression. The total sound-pressure level is determined from a sum of these diffracted fields. Hence, the new method is fast, simple, and intuitive, allowing the leakage to be assessed accurately. The validity of these two numerical models is confirmed by precise experimental measurements.

Journal Article↗

Predictive model for immunotherapy of alopecia areata with diphencyprone.

BACKGROUND: Immunotherapy with diphencyprone (diphenylcyclopropenone) is used in the treatment of alopecia areata (AA). Response rates have varied in the literature. OBJECTIVES: To determine the efficacy of diphencyprone therapy for AA in the largest reported cohort of patients; to identify patient and treatment factors predictive of therapeutic success; and to develop a practical model for predicting patient response. METHODS: The medical records of 148 consecutive patients treated with diphencyprone were reviewed. A clinically significant response to diphencyprone therapy was defined as a cosmetically acceptable response or greater than 75% terminal hair regrowth. Survival analyses using the Kaplan-Meier method and the Cox proportional hazards model were performed to determine significant factors predictive of regrowth and relapse. RESULTS: Using a survival analysis model, the cumulative patient response at 32 months was 77.9% (95% confidence interval, 56.8%-98.9%). Variables independently associated with clinically significant regrowth were age at onset of disease and baseline extent of AA. Older age at onset of AA portended a better prognosis. A cosmetically acceptable end point was obtained in 17.4% of patients with alopecia totalis/universalis, 60.3% with 75% to 99% AA, 88.1% with 50% to 74% AA, and 100% with 25% to 49% AA. A lag of 3 months was present between initiation of therapy and development of significant hair regrowth in the first responders. Relapse after achieving significant regrowth developed in 62.6% of patients. CONCLUSIONS: Response to diphencyprone treatment in AA is affected by baseline extent of AA and age at disease onset. A prolonged treatment course might be necessary. A predictive model has been developed to assist with patient prognostication and counseling.

Adolescent↗

Demonstrating attainment of the air quality standards: integration of observations and model predictions into the probabilistic framework.

This paper introduces an integrated observational-modeling approach to transform the deterministic nature of attainment demonstrations of the National Ambient Air Quality Standard (NAAQS) into the probabilistic framework. While the methods presented here can be used to address any air quality standard that is based on extreme values, this paper focuses on the application to the 1-hr and 8-hr NAAQS for ozone. Extreme value statistics and resampling techniques are applied to estimate the probability of exceeding the NAAQS for both 1-hr and 8-hr ozone concentrations. Within the integrated observation-modeling analysis approach, we show that the model-to-model differences in the predicted responses to emission reductions are smaller than the model-to-model differences in predicted absolute ozone concentrations. We illustrate that the emission reductions stemming from a real-world emission control strategy would substantially reduce the probability of exceeding the NAAQS over a large portion of the eastern United States, especially for the 8-hr average ozone concentrations.

Air Pollution↗

MRI based diffusion and perfusion predictive model to estimate stroke evolution.

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/- 0.19 and 1.20 +/- 0.36. For recovered tissue the mean values were 0.99 +/- 0.25 and 1.87 +/- 0.71, respectively. There was a significant difference between these two regions for both measures (p < 0.003 and p < 0.001, respectively). Mean absolute measures of CBF (ml/100g/min) and CBV (ml/100g) for the total infarcted territory were 33.9 +/- 9.7 and 4.2 +/- 1.9. For recovered MTT tissue, the mean values were 41.5 +/- 7.2 and 5.3 +/- 1.2, respectively. A significant difference was also found for these regions (p < 0.009 and p < 0.036, respectively). The mean measures of sensitivity, specificity, positive and negative predictive values for modeling infarct evolution for the validation patient data were 0.72 +/- 0.05, 0.97 +/- 0.02, 0.68 +/- 0.07 and 0.97 +/- 0.02. We propose that this automated strategy may allow possible guided therapeutic intervention to stroke patients and evaluation of efficacy of novel stroke compounds in clinical drug trials.

Aged↗

Post kidney transplant quality of life prediction models.

UNLABELLED: Quality of life (QoL) is generally found to improve for renal transplant recipients, although some patients continue to experience health-related problems. It was within this context that we undertook our investigation which focused on identifying the factors predictive of QoL following kidney transplantation. METHODS: The sample included 91 non-diabetic patients of which 69 provided 6-month data and 68 provided 12-month data. Three QoL questionnaires were administered to capture as many QoL dimensions as possible. Repeated measure analyses of variance with multiple post hoc comparisons of LS means was conducted to determine how QoL outcomes differed over time. Correlational analyses were performed on the 12-month dataset to determine which variables to include in the modeling process. Multiple stepwise regression with forward and backward entry were used in the prediction modeling. RESULTS: Essentially all patients experienced a significant improvement in QoL and the improvement occurred early and appeared to be sustained. Five separate prediction models were constructed, each including number of hospital days in first 6 months, employment, and social support. CONCLUSIONS: The similarity of the five models is of note. It is not necessarily these specific variables per se that predict QoL outcomes, but rather what they conceptually represent. These findings provide direction for interventions designed to enhance post-transplant QoL.

Adult↗