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At least 649 records · Page 36Linked to original sources
PubMed2004

Reversal of sensorimotor gating deficits in Brattleboro rats by acute administration of clozapine and a neurotensin agonist, but not haloperidol: a potential predictive model for novel antipsychotic effects.

Prepulse inhibition (PPI) of acoustic startle is decreased in unmedicated schizophrenia patients and similar deficits can be induced in rats through pharmacological, environmental, or neuroanatomical manipulations. Recently, we reported that Brattleboro (BB) rats, a Long Evans (LE) strain with a single gene mutation, have inherent deficits in PPI homologous to those observed in schizophrenia patients. We also reported that PPI deficits in BB rats could be reversed by chronic but not acute administration of 0.5 mg/kg haloperidol. No other dose or drug was tested in that experiment. In this study, we tested the effects of acute subcutaneous administration of several doses of haloperidol as well as the second-generation antipsychotic, clozapine, and the putative novel antipsychotic, PD149163, a neurotensin mimetic that crosses the blood-brain barrier. Consistent with our previous report, BB rats exhibited PPI deficits compared to LE rats and none of the doses of haloperidol produced a significant effect on this PPI deficit. In contrast, 10 and 15 mg/kg of clozapine and all the doses of PD149163 tested reversed the PPI deficits in BB rats. In addition, haloperidol, but not clozapine or PD149163 produced significant catalepsy in BB rats, supporting the notion that PD149163 has a profile consistent with atypical antipsychotics and providing support for the predictive validity of the PPI results. These results further strengthen the notion that the BB rat is a useful predictive model of antipsychotic efficacy and suggest that this model may differentiate between antipsychotics belonging to different therapeutic categories, for example, first- and second-generation agents.

Animals↗
PubMedDate not supplied

Failure to validate a predictive model for refusal of care to emergency-department patients.

OBJECTIVE: To determine whether previously developed triage criteria for refusal of care to patients presenting to an emergency department (ED) with nonurgent problems could be validated for an independent patient population. METHODS: A convenience sample of 534 adults presenting to a municipal hospital ED between July 1, 1992, and October 15, 1992, who met preestablished criteria for refusal of care were entered into a prospective, observational, cohort study. The single target outcome variable was hospitalization. In order to optimize the criteria's performance, both the triage nurse and the physician caring for the patient had to agree that all criteria for "refusal of care" were specifically met. No patient was refused care, nor was a patient's management or disposition interfered with in any way by the investigators. All patients were followed until hospital admission or release from the ED. RESULTS: Six (1.1%) of 534 patients (95% CI 0.4-2.4) who met the criteria for refusal of care were hospitalized. This represents a greater than 50-fold difference in incidence of hospitalization when compared with that found by other investigators, who reported that only 0.02% (95% CI 0.0004-0.04) of those patients who were refused care subsequently required hospitalization (p < 10 (-7)). CONCLUSION: The authors were unable to validate a previously developed predictive model for refusal of care to patients presenting to an ED. Refusal of care to selected ED patients based on current guidelines is not a viable solution to overcrowding. Alternative strategies must be sought.

Adult↗
PubMed2006

Muscle fatigue and endurance during repetitive intermittent static efforts: development of prediction models.

Localized muscle fatigue has received growing attention as a potential design variable and exposure metric in research towards prevention of musculoskeletal disorders in the workplace. While fatigue during sustained static work has been investigated extensively, effects during tasks comprising work-rest cycles are less clear. Work-rest models for static intermittent work have been presented in several reports, but the applicability is often limited to specific conditions. A study was conducted that facilitated a description of the relationships between static intermittent efforts and muscle endurance and fatigue. Exercises consisted of 1 h (maximum) of repetitive static arm abductions, involving a range of muscle contraction levels (10-30% maximum voluntary exertion), duty cycles (0.2-0.8) and cycle times (20-180 s). A between-subject central composite experimental design was used and 15 different exercise conditions were examined with six participants (three females and three males) for each. Along with endurance times, temporal changes related to fatigue were monitored using muscle strength, ratings of discomfort and electromyography (EMG) obtained from the middle-deltoid muscle during the contraction phase of the work cycles. The results of this study showed the influence of contraction level and duty cycle on the majority of fatigue measures used, while cycle time tended to affect EMG spectral measures. Using a response surface methodology, several fatigue prediction models and contour plots were developed that can be employed as an aid for design and evaluation of light repetitive static tasks. Good correspondence was generally found between discomfort rating and other measures of fatigue, suggesting the usefulness of this measure for rapid assessments of local fatigue in the workplace.

Adult↗
PubMed1998

Predictive model for capillary electrophoretic peptide mobility in 2,2,2-trifluoroethanol-water solution.

Using capillary electrophoresis (CE) on a set of 21 peptides with a molecular mass ranging from about 350 to 1850 Da, the Stokes radii at different protonation stages and the acidic dissociation constants in water and in a 2,2,2-trifluoroethanol (TFE) water mixture (30% v/v) were determined. These results permitted us to establish separately the reliability of semiempirical models utilized for the prediction of peptide size and charge at different acidic pHapp (pHapp range: 2.00-4.25). The data obtained on size and charge were utilized in order to provide suitable mobility predictions on the basis of the charge-to-size ratio. The best predictive conditions for size and charge were found at the most acidic range of pHapp studied (2.00-2.25), either in water or a TFE-water mixture, and reliable predictive equations for peptide mobility were established at this pHapp.

Electrophoresis, Capillary↗
PubMed1995

Testing models predicting severity of respiratory syncytial virus infection on the PICNIC RSV database. Pediatric Investigators Collaborative Network on Infections in Canada.

OBJECTIVES: To determine the sensitivity and specificity of published prognostic models to predict morbidity resulting from lower respiratory tract disease caused by respiratory syncytial virus in an independent pediatric population and to assess the accuracy of single risk factors in predicting adverse outcome. DESIGN: All articles obtained from a MEDLINE search that used the terms prognosis or sequelae and respiratory syncytial virus, and from the references of these articles, were reviewed. Studies were included if risk factors and outcomes were defined and if information was available in a database of prospectively enrolled patients with respiratory syncytial virus infections. A probability of adverse outcome was assigned to each patient in the cohort using prognostic models described in the articles. A test was considered positive if the probability of the adverse outcome was 5% or more. PATIENTS: Six hundred eighty-nine patients hospitalized with respiratory syncytial virus in seven tertiary care centers across Canada were prospectively enrolled in the Pediatric Investigators Collaborative Network on Infections in Canada database. MAIN OUTCOME MEASURES: The sensitivity and specificity of single predictors and of models in predicting severe disease were determined. RESULTS: The sensitivity of single predictors varied from 17% to 46%. A model that used age and oxygen saturation at admission in previously well infants had a sensitivity of 98% and a specificity of 47% when predicting intensive care unit admission. Another model that included age at hospitalization, gestational age, presence of an underlying condition, and respiratory syncytial virus subtype used to predict the outcome of a high severity index had a sensitivity of 77% and a specificity of 76%. When the above model was modified by exclusion of viral subgroup, sensitivity increased to 94%, but specificity decreased to 46%. CONCLUSION: Previously described prognostic models were generalizable to an independent study population.

Canada↗
PubMed1997

Development of a predictive model to describe the effects of temperature and water activity on the growth of spoilage pseudomonads.

A combined temperature and water activity model for the growth of psychrotrophic pseudomonads was developed using turbidimetric data. Psychrotrophic pseudomonads were isolated from various modified and whole milks. The fastest growing strain was identified and used to develop the model. Generation time estimates calculated by turbidimetric and viable count data differed but this difference was constant with respect to temperature and was incorporated into the modelling process so that all models are constructed to predict generation times equivalent to those calculated by viable counts, the standard method for enumerating microorganisms in food products.

Animals↗
PubMed1999

Predictive model of functional independence in stroke patients admitted to a rehabilitation programme.

OBJECTIVE: To develop a prognostic model to estimate the probability of patients being independent in ambulation and in activities of daily living (ADL) after six months of stroke. DESIGN: Cohort analytical study. SETTING: Rehabilitation departments of two district general hospitals. SUBJECTS: Ninety-two consecutive stroke patients admitted to a rehabilitation programme. MAIN OUTCOME MEASURES: Independent ambulation was defined as a Functional Ambulation Classification (FAC) > or =4, and the independence in ADL as a Barthel Index (BI) > or =285. All patients were assessed on admission to rehabilitation, and in the first, second, third, fourth and six months after stroke. RESULTS: Prognostic factors were identified by means of a multivariate survival analysis using Cox regression. Three variables were predictors for a FAC > or =4: (1) The patients in the motor (M), motor-sensitive (MS) and motor-sensitive with hemianopsia (MSH) groups (relative risk (RR) 5.43 of M with respect to MSH, and 2.41 of MS to MSH). (2) A Motricity Index >25 (RR 3.19). (3) An age <70 years old (RR 1.99). For a BI > or =85 three predictors were selected: (1) The classification M-MS-MSH (RR 6.02 M to MSH, and 1.52 MS to MSH). (2) An initial BI >20 (RR 3.45); the highest contribution in the achievement of an initial BI >20 was bowel and bladder continence. (3) The antecedent of previous independence (RR 2.68). The predictive models, constructed by means of multiple logistic regression correctly classified 77% and 79% of the patients who obtained FAC > or =4 and a BI > or =85 respectively. CONCLUSIONS: The syndromic classification M, MS and MSH, together with other routinely available data, such as the Motricity Index, BI, the age and the previous functionality, can be used to obtain a patient prognosis level with regard to ambulation and ADL independence.

Activities of Daily Living↗
PubMed1997

Validation of an outcome prediction model for critically ill trauma patients without head injury.

BACKGROUND: The Acute Physiology and Chronic Health Evaluation (APACHE) II system is inaccurate in predicting the risk of death in trauma patients, especially those without head injury. Using multivariate analysis of the APACHE II system in a development set, a new predictive equation was modeled. The four variables that were independently associated with mortality were PaO2/FiO2 ratio, mean arterial pressure, temperature, and the need for inotropic support. This model was tested prospectively in an independent validation set of 300 patients. METHODS: Risk of death was calculated using the APACHE II system with the diagnostic category of multiple trauma and weighting for operative intervention as required. The new model was similarly assessed using the four predictor variables and their beta-coefficients for each mechanism of injury and the entire group. The predicted risk of death derived by both models was compared with the observed mortality rate. Discrimination was calculated using a 2 x 2 decision matrix with a decision threshold of r = 0.5 and receiver operating characteristic curves. Calibration was assessed graphically and by statistical correlation. RESULTS: The observed mortality rate was 28.3% and the predicted mortality risk was 27.4% for the model and 6.26% for APACHE II. The sensitivity and specificity of the model were 58.8 and 90.7%, and the sensitivity and specificity of APACHE II were 1.2 and 100%. The areas under the receiver operating characteristic curves were 0.84 and 0.78 for the model and the APACHE II system, respectively. Calibration of the model was superior within all deciles of risk (model, R2 = 0.93, p < 0.001; APACHE II, R2 = 0.82, p = 0.02). CONCLUSION: The model accurately predicted the risk of death for the entire group. It is superior to the APACHE II system and is the highest reported sensitivity for 24-hour intensive care unit predictive models that have been applied to the critically injured.

APACHE↗
PubMed2002

A mathematical model predicts that calreticulin interacts with the endoplasmic reticulum Ca(2+)-ATPase.

A robust mathematical model developed from single cell calcium (Ca(2+)) dynamics has enabled us to predict the consequences of over-expression of endoplasmic reticulum-located chaperones. Model predictions concluded that calreticulin interacts with the lumenal domain of the sarcoplasmic and endoplasmic reticulum Ca(2+)-activated ATPase (SERCA) pump, altering pump affinity for Ca(2+) (K(1/2) switches from 247 to 431 nM) and hence generating Ca(2+) oscillations. Expression of calreticulin in the ER generated an average of six transient-decline oscillations during the Ca(2+) recovery phase, upon exposure to maximal levels of the agonist ATP. In contrast, normal cells produced a single Ca(2+) transient with few or no oscillations. By conditioning the model to experimental data, parameters for generation and decay of IP(3) and SERCA pump kinetics were determined. To elucidate the possible source of the oscillatory behavior three possible oscillators, 1) IP(3), 2) IP(3)R, and 3) SERCA pump, were investigated and parameters constrained by experimental data to produce the best candidate. Each of the three oscillators generated very good fits with experimental data. However, converting a normal exponential recovery to a transient-decline oscillator predicted that the SERCA pump is the most likely candidate for calreticulin-mediated Ca(2+) release, highlighting the role of this chaperone as a signal protein within the endoplasmic reticulum.

Calcium↗
PubMed2001

Predictive modeling and heterogeneity of baseline risk in meta-analysis of individual patient data.

We developed and evaluated methods for the analysis and interpretation of the baseline risk heterogeneity in meta-analysis of individual patient data (MIPD) based on information on predictive factors. We used data from a typical MIPD of eight clinical trials (1792 patients, 2947 years of follow-up) on the efficacy of high-dose acyclovir in human immunodeficiency virus infection. Cox models with four predictive factors (age, disease state, CD4 cell count and hemoglobin levels) were used to estimate predicted individual hazards both for single trials and for various MIPD modeling methods (simple pooling, adjusted for study, stratified per study, fixed and random effects for predictors). For each study and for each method of MIPD synthesis, we estimated the odds ratio for death in the upper versus the lower quartile of predicted risk (Extreme Quartile Odds Ratio, EQuOR) and the respective rate ratio (Extreme Quartile Rate Ratio, EQuRR). Only the CD4 cell count showed a significantly heterogeneous predictive effect across the eight studies (P =.024). The EQuOR of single studies ranged from 3.5 (little heterogeneity) to 24 (intermediate heterogeneity), substantially lower than the EQuOR of the MIPD (167 to 275, depending on the model used). The EQuRR values ranged from 3.5 to 77 for single studies and from 77 to 116 for the various MIPD models. Predictive modeling can be a major strength of MIPD, when performed and interpreted with standardized approaches. All models consistently show that MIPD may be a study design with extreme heterogeneity of patient baseline risk.

Acquired Immunodeficiency Syndrome↗
PubMed2001

An isomer prediction model for PCNs, PCDD/Fs, and PCBs from municipal waste incinerators.

Isomer patterns of polychlorinated naphthalenes (PCNs), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated biphenyls (PCBs), and polychlorinated dibenzofurans (PCDFs) from municipal waste incinerators (MWIs) were predicted by a model based on symmetry numbers and preferential chlorination positions. Fly ash isomer patterns from five stoker and seven fluidized bed incinerators were compared to validate the prediction model. The isomer patterns of the highly chlorinated PCN homologues from stoker type incinerators were successfully predicted. The relative equilibrium concentrations of tetrachloronaphthalenes (TeCNs), calculated by an ab initio method, cannot explain the field isomer patterns. Formation pathways involving chlorophenol precursor condensation reactions should be examined to see whether these isomer patterns provide a better fit to the field PCDD data. The PCB isomer patterns were fit reasonably well, but this finding could merely be an artifact of the limited data and the large number of isomers. The prediction equations of PCDFs, revised from prior work to include a symmetry number for each isomer, represented the field data patterns for the higher chlorinated isomers very well. Successful prediction of isomer patterns for partial homologue ranges suggests that these patterns are determined by a mechanism governed by Cl-position-specific preferences.

Benzofurans↗
PubMed1998

A prediction model for strike in the sheep nasal fly, Oestrus ovis, in Namibia.

A model was developed for predicting outbreaks of Oestrus ovis throughout the main sheep farming areas of Namibia. Pupal developmental periods were studied, concomitant air and soil temperatures enabling degree-day calculations to be made for prediction of adult fly strike. Monitoring of larval infection established seasonal incidence of O. ovis infestation and acted as verification of predictions. The establishment of relevant isothermal maps for Namibia made possible extrapolation from the several study sites to the entire sheep farming area. Retrospective and actual predictions of the important first peak after winter were considered accurate enough to recommend timing of control measures. No evidence of overwintering of first stage instars was found, the strategy used instead being extended pupation. Adult fly energy reserves were determined.

Animals↗
PubMed2000

Major complications after angioplasty in patients with chronic renal failure: a comparison of predictive models.

Novel modeling approaches were investigated to predict major complications in patients with chronic renal failure (CRF) or end-stage renal disease (ESRD) undergoing percutaneous transluminal coronary angioplasty (PTCA). The following hypotheses were explored: (1) Pre-angioplasty patient risk factors, demographic characteristics and procedural information may be used to predict major complications after PTCA; and (2) Rough sets and artificial neural nets (ANN) may be used to build models that are better than standard logistic regression models. Several variables were found to be predictive of major complications for patients with CRF or ESRD undergoing PTCA. The presence of shock at presentation portends poor outcome but congestive heart failure and prior history of myocardial infarction increases the risk tenfold and 25-fold, respectively. The discriminatory ability of the ANN model was better than both Rough Sets and Logistic Regression for the test set.

Analysis of Variance↗
PubMed2006

An investigation of the Gamma hypothesis: a predictive modelling study of the effect of combined inhibitors (salt, pH and weak acids) on the growth of Aeromonas hydrophila.

The Gamma hypothesis, that multiple inhibitory factors combine independently, is the underlying hypothesis for the quantification of the Hurdle concept used in food manufacture. The literature, however, is confused as to whether interactive effects exist and under which circumstances they occur, if at all. Using the method of time to detection (TTD), the inhibitory effect of pH, salt and specific weak acids (acetic, propionic, sorbic and benzoic) and combinations of these with respect to the growth of Aeromonas hydrophila (ATCC 7966) were analysed. A model based on the relative rate to detection described all combinations analysed as having independent effects on the TTD. No synergistic interactions were found between pH and salt, between pH and individual weak acids or between combinations of weak acids and pH for any of the systems under study. This study supports the validity of the Gamma concept -- that individual environmental effects act independently and should, in turn, facilitate attempts to model the growth of other microorganisms under a variety of conditions.

Acids↗