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PubMed1997

Synthesis and structure-activity relationships of a new model of arylpiperazines. 2. Three-dimensional quantitative structure-activity relationships of hydantoin-phenylpiperazine derivatives with affinity for 5-HT1A and alpha 1 receptors. A comparison of CoMFA models.

A series of 48 bicyclohydantoin-phenylpiperazines (1-4) with affinity for 5-HT1A and alpha 1 receptors was subjected to three-dimensional quantitative structure-affinity relationship analysis using comparative molecular field analysis (CoMFA), in order to get insight into the structural requirements that are responsible for 5-HT1A/alpha 1 selectivity. Good models (high cross-validation correlations and predictive power) were obtained for 5-HT1A and alpha 1 receptors. The resulting 3D-QSAR models rationalize steric and electrostatic factors which modulate binding to 5-HT1A and alpha 1 receptors. A comparison of these models gives an additional understanding for 5-HT1A/alpha 1 selectivity: (a) Substitution at the ortho position by a group with negative potential is favorable to affinity for both receptors. (b) The meta position seems to be implicated in 5-HT1A/alpha 1 selectivity. While the 5-HT1A receptor is able to accommodate bulky substituents in the region of its active site, the steric requirements of the alpha 1 receptor are more restricted (optimum volume of substituent 11-25 A3). (c) For both receptors the para position represents a region where the volume accessible by the ligands is limited. (d) The hydantoin moiety and the side chain length seem to modulate not only the affinity but also 5-HT1A/alpha 1 selectivity. The 3D-QSAR models reveal an useful predictive information for the design of new selective ligands.

Animals↗

PubMed1998

Model misspecification effects within a family of alternative discrete reliability-growth models.

We describe a family of related discrete reliability-growth methodologies potentially applicable to one-shot systems undergoing a test-analyze-and-fix development process. The common feature shared by the models is their connection to Duane's renowned learning-curve property. The major difference, however, lies in their applicability in the context of two intrinsically different sampling schemes. For each model, a summary of the statistical properties of various estimators of the parameters as well as the reliability of the system, are reported. For purposes of assessing model misspecification, a particular text execution scenario conforming to a inverse sampling scheme is adopted. In reliability applications, it is not an uncommon practice to borrow inference results from models which are inappropriate in this setting. A detailed study of the potential impact of such misspecification on the estimation of system reliability is presented.

Computer Simulation↗

PubMed1998

Fourth-generation model for corticosteroid pharmacodynamics: a model for methylprednisolone effects on receptor/gene-mediated glucocorticoid receptor down-regulation and tyrosine aminotransferase induction in rat liver.

A fourth-generation pharmacokinetic/pharmacodynamic (PK/PD) model for receptor/genemediated effects of corticosteroids was developed. Male adrenalectomized Wistar rats received a 50 mg/kg i.v. bolus dose of methylprednisolone (MPL). Plasma concentrations of MPL, hepatic glucocorticoid receptor (GR) messenger RNA (mRNA) and GR density, tyrosine amino-transferase (TAT) mRNA, and TAT activity in liver were determined at various time points up to 72 hr after MPL dosing. Down-regulation of GR mRNA and GR density were observed: GR mRNA level declined to 45-50% of the baseline in 8-10 hr, and slowly returned to predose level in about 3 days; GR density fell to 0 soon after dosing and returned to the baseline in two phases. The first phase, occurring in the first 10 hr, entailed recovery from 0 to 30%. The second phase was parallel to the GR mRNA recovery phase. Two indirect response models were applied for GR mRNA dynamics regulated by activated steroid-receptor complex. A full PK/PD model for GR mRNA/GR down-regulation was proposed, including GR recycling theory. TAT mRNA began to increase at about 1.5 hr, reached the maximum at about 5.5 hr, and declined to the baseline at about 14 hr after MPL dosing. TAT induction followed a similar pattern with a delay of about 1-2 hr. A transcription compartment was applied as one of the cascade events leading to TAT mRNA and TAT induction. Pharmacodynamic parameters were obtained by fitting seven differential equations piecewise using the maximum likelihood method in the ADAPT II program. This model can describe GR down-regulation and the precursor/product relationship between TAT mRNA and TAT in receptor/gene-mediated corticosteroid effects.

Animals↗

PubMed2003

A model-fitting implementation of the DeFries-Fulker model for selected twin data.

In this research note, DeFries-Fulker (DF) regression analysis is reframed in model-fitting terms, where an individual's expected score is modeled as a function of their co-twin's proband status. This more flexible implementation of the DF model allows DZ-O twins to be incorporated in a sex-limitation model. Brief simulation results are presented along with the Mx scripts used.

Computer Simulation↗

PubMed2004

Building a model to understand youth service access: the gateway provider model.

Enhancing the functioning of parents, teachers, juvenile justice authorities, and other health and mental heal professionals who direct children and adolescents to services is a major mental health services concern. The Gateway Provider Model is an elaborated testable subset of the Network-Episode Model (NEM; B. A. Pescosolido & C. A. Boyer, 1999) that synthesizes it with Decision (D. H. Gustafson, et al., 1999) and organizational theory (C. Glisson, 2002; C. Glisson & L. James, 1992, 2002). The Gateway Provider Model focuses on central influences that affect youth's access to treatment, i.e., the individual who first identifies a problem and sends a youth to treatment (the "gateway provider"); and the need those individuals have for information on youth problems and relevant potential resources. Preliminary studies by the authors and other applicable studies (D. Carise & O. Gurel, 2003) show that providers' perception of need, and their knowledge of resources, and their environment are related to the decision to offer or refer to services, supporting key aspects of the Model.

Adolescent↗

PubMed2002

Examining the utility of a temperament model for modelling non-melancholic depression.

OBJECTIVE: Depression is currently modelled dimensionally, along severity, duration and recurrency dimensions. An alternative model allows dimensional expressions of temperament and personality to influence risk to onset as well as persistence. Here, we examine the utility of a temperament model. METHOD: A questionnaire assessing temperament dimensions and a number of depression variables was administered to a large routine general practice sample and with the temperament measure also completed by a small clinical sample. RESULTS: 'Anxious worrying' and 'irritable' dimensions were identified as internalizing and externalizing expressions of a trait anxiety dimension, three other 'temperament' dimensions (i.e. 'introversion', 'self-centred' and 'obsessive') were refined, while a 'self-blame' dimension intruded into the factor analytic solution. High scores on the 'anxious worrying' dimension were associated with all depression parameters. The 'irritable', 'introversion' and 'self-blame' dimensions were less clearly linked with depression variables, while higher scores on the 'self-centred' and 'obsessional' dimensions did not appear to increase the chance of depression onset, persistence or recourse to treatment. CONCLUSION: A temperament-based approach appears to have some conceptual utility in modelling depression, and particularly, the non-melancholic disorders. It is likely, however, to require complementing with refined at-risk personality dimensions.

Adult↗

PubMed2003

Animal models of melanoma: an HGF/SF transgenic mouse model may facilitate experimental access to UV initiating events.

Cutaneous malignant melanoma, the most lethal of the skin cancers, known for its intractability to current therapies, continues to increase in incidence, providing a significant public health challenge. There is a consensus that skin cancer is initiated by sunlight exposure. For non-melanoma skin cancer there is substantial evidence that chronic exposure to the ultraviolet B radiation (UVB) (280-320 nm) portion of the sunlight spectrum is responsible. Experimentally, UVB is mutagenic and chronic UVB exposure can cause non-melanoma skin cancer in laboratory animals. Non-melanoma tumors in animals and in humans show characteristic UVB signature lesions in the tumor suppressor p53 and/or in the patched (PTCH) gene. An action spectrum or wavelength dependence for squamous cell carcinoma in the mouse shows a major peak of efficacy in the UVB. For malignant melanoma, however, the situation is unclear and the critical direct target(s) of sunlight in initiating melanoma and even the wavelengths responsible are as yet unidentified. This lack of information is in major part a result of a paucity of animal models for melanoma which recapitulate the role of sunlight in initiating this disease. The epidemiology of melanoma differs significantly from non-melanoma skin cancer. Intense sporadic sunlight exposure in childhood, probably exacerbated by additional adult exposure, is associated with elevated melanoma risk. Melanoma is also a disease of gene-environment interactions with underlying genetic factors playing a significant role. These major differences indicate that extrapolation from information for non-melanoma skin cancer to melanoma is unlikely to be useful. We summarize in this review the experimental information available on the role of UV radiation in melanoma and give an overview of animal melanoma models. A new model derived by neonatal UV irradiation of hepatocyte growth factor/scatter factor (HGF/SF) transgenic mice is described which recapitulates the etiology, the histopathology and molecular pathogenesis of human disease. It is anticipated that the HGF/SF transgenic model will provide a means to access the mechanism(s) by which sunlight initiates this lethal disease and provide an appropriate vehicle for derivation of appropriate therapeutic and preventive strategies.

Animals↗

PubMed2001

Integration of the ecological and error models of overconfidence using a multiple-trace memory model.

A memory processes account of the calibration of probability judgments was examined. A multiple-trace memory model, Minerva-Decision Making (MDM; M. R. P. Dougherty, C. F. Gettys, & E. E. Ogden, 1999), used to integrate the ecological (Brunswikian) and the error (Thurstonian) models of overconfidence, is described. The model predicts that overconfidence should decrease both as a function of experience and as a function of encoding quality. Both increased experience and improved encoding quality result in lower variance in the output of the model, which in turn leads to improved calibration. Three experiments confirmed these predictions. Implications of MDM's account of overconfidence are discussed.

Humans↗

PubMed1998

The primacy model: a new model of immediate serial recall.

A new model of immediate serial recall is presented: the primacy model. The primacy model stores order information by means of the assumption that the strength of activation of successive list items decreases across list position to form a primacy gradient. Ordered recall is supported by a repeated cycle of operations involving a noisy choice of the most active item followed by suppression of the chosen item. Word-length and list-length effects are attributed to a decay process that occurs both during input, when effective rehearsal is prevented, and during output. The phonological similarity effect is attributed to a second stage of processing at which phonological confusions occur. The primacy model produces accurate simulations of the effects of word length, list length, and phonological similarity.

Humans↗

PubMed2001

Evaluation of thrombolysis in a porcine model of chronic deep venous thrombosis: an endovascular model.

PURPOSE: The advancement of catheter-based interventions for vascular recanalization has underscored the need for an experimental animal model of vascular thrombosis that can be used for the evaluation of interventional therapies. In this model, a porcine model of deep venous thrombosis with a novel endovascular technique was described, and the efficacy of thrombolytic therapy with urokinase was evaluated. METHODS: An endovascular device that consisted of a tapered polytetrafluoroethylene graft attached within a self-expanding nitinol stent was delivered to bilateral common iliac veins in 20 pigs. Venous thrombosis occurred as a result of flow stasis created by the intrastent stenosis. Catheter-directed pulse-spray thrombolysis with urokinase (250,000 units) and heparin (5000 IU) was performed on one limb while the contralateral limb received control saline solution. Thrombolysis was performed in 1 hour (n = 4), 8 hours (n = 4), 3 days (n = 4), 7 days (n = 4), and 14 days (n = 4) after the stent-graft deployment. Venography and intravascular ultrasound were used to evaluate the efficacy of thrombolysis. Light microscopy was used for histologic analysis of the thrombus. RESULTS: Complete thrombolysis was achieved in groups with deep vein thrombosis that were younger than 1 day. Angioplasty of the tapered stent-grafts in the completely thrombolysed iliac vein was successful in restoring venous flow. The efficacy of thrombolysis in 3-day, 7-day, and 14-day groups was 86% +/- 7%, 73% +/- 13%, and 42% +/- 23%, respectively. The thrombolytic efficacy was enhanced to 92% +/- 16% and 86% +/- 18% (P <.05) in 3-day and 7-day groups, respectively, when doses of the pulse-spray thrombolysis were doubled. Increased dosages of the thrombolytic agent, however, did not significantly enhance the thrombus dissolution in the 14-day group. CONCLUSION: The thrombolytic efficacy of urokinase correlated with the chronicity of deep venous thrombosis in our model. An increased dose of urokinase may be used to enhance the efficacy of thrombolysis in a 1-week-old thrombus.

Animals↗

PubMed2005

Continuum of care model for managing mild traumatic brain injury in a workers' compensation context: a description of the model and its development.

Mild traumatic brain injuries are a significant health problem that can result in distress and disability for people who go on to develop post-concussion syndrome or symptoms. In order to improve healthcare outcomes following a mild traumatic brain injury, the Workers' Compensation Board of Alberta developed a continuum of care model to assist its staff (e.g. claim adjudication and case management) to manage these claims. A continuum of care model acts as a road map that illustrates typical recovery patterns and treatment best practices, and builds in checkpoints where decisions for assessment and treatment can be made. The model was developed from a review of the research literature selected to determine the best evidence-based practices for treating mild traumatic brain injury, and the most appropriate timing for assessments and treatments. Local and international experts in the field of brain injury assessment and rehabilitation also contributed to the development of the final model.

Alberta↗

PubMed2005

Stage model of recovery for chemically dependent adolescents: part 2--Model evaluation and treatment implications.

This qualitative study, presented in two parts, refines the model of how chemically dependent adolescents initiate and engage in the recovery process. Part 1 (published in 2004) described the research process and results used to derive the model. In Part 2, this model is compared with extant theories on stages of recovery in chemically dependent adults. Participants' stories in large part followed the stages of Stephanie Brown's adult-based Developmental Model of Recovery, but the intensity and focus of some issues (e.g., relationships) and tasks (e.g., separation/individuation) are different for adolescents than for adults. Consequently, the markers of entry into each stage, the focus of tasks within each stage, and the time required to traverse some stages and phases are different for adolescents. Treatment implications for the adolescent population on the basis of these differences are reviewed, and topics for further research are suggested.

Adolescent↗

PubMedDate not supplied

Biologically relevant models of infantile nystagmus syndrome: the requirement for behavioral ocular motor system models.

Infantile nystagmus syndrome (INS) is a combination of several types of nystagmus, each representing dysfunction in one subsystem of the ocular motor system (OMS) and having characteristic waveforms. Eye-movement recordings are the only certain way to identify IN and differentiate it from other types. The waveform classification scheme in use for 30 years is both accurate, inclusive, and suggests the underlying subsystem instabilities. In different individuals, they may appear at birth (hard wired) or in early infancy (developmental). The primary subsystem instability in IN is hypothesized to lie in the normally underdamped smooth pursuit system; vestibular dysfunction (imbalance) may also be present. Less often, the nucleus of the optic tract may be involved. Ocular motility studies over the past 40 years have demonstrated that saccades and gaze holding are normal in the INS and saccades contained within IN waveforms are always corrective; i.e., they cannot be the initiating movement responsible for IN. Because there are an infinite number of solutions to simulating specific waveforms, models that merely generate waveforms that resemble IN in isolation are of little use, either clinically or to increase our understanding of the underlying mechanisms of IN. A biologically relevant model of the INS should be part of, and operate within, a complete OMS model, capable of reproducing the normal ocular motor behavior of these individuals while still oscillating; i.e., the model, like the patient, must not have oscillopsia and be able to respond correctly to various target inputs.

Humans↗

PubMed1994

Target model of nucleosome particle for track structure calculations and DNA damage modelling.

A non-homogeneous target model of nucleosome particle for track structure calculations and biophysical modelling of radiation-induced DNA damage was developed together with a sampling method for non-homogeneous targets. The model allows one to distinguish energy deposited in the histone core, primary hydration shell and nucleosome DNA. Illustrative results for low energy electrons are presented and compared with results obtained with simpler models of a nucleosome particle.

DNA Damage↗

PubMed1998

The Health Belief Model and HIV risk behaviours: a causal model analysis among Anglos, African-Americans and Mexican-Americans.

A causal model of the Health Belief Model (HBM) is empirically evaluated which emphasizes possible indirect paths linking distal demographic and seriousness/susceptibility variables to HIV risk behaviours among Anglo, African-American, and Mexican-American adults. A specific focus of the paper is upon alcohol-related expectancies (anticipation of disinhibitory effects of alcohol upon sexual behavior) as a 'barrier' to preventive behaviours. Ethnic comparisons stem both from the paucity of available research on the HBM in minority populations and from recent questions regarding the applicability of rational models such as the HBM among minority groups. Analyses of data from a community sample of 1390 adults indicate relatively consistent direct effects of barriers for males and benefits for females upon HIV risk behaviors. The analyses suggest distinct paths operative among males and females. The susceptibility-barriers-risk behaviours path among males may suggest that alcohol-related expectancies (barriers in this model) may be more strongly related to risk behaviours among males than minority females.

Adult↗

PubMed2002

Health promotive action and preventive action model (HPA model) for the classification of health care services in public health nursing.

BACKGROUND: There is a need for an expanded approach to develop knowledge of public health nursing as a sphere of public health. The aim of this paper was to construct a theoretical model for healthcare services in the area of public health nursing based on the analysis and classification of healthcare services used in public health nursing practice. METHODS: Patient records were examined using a qualitative research approach. The categorization and classification of the actions followed certain criteria. Three methods were used for verifying and modifying the concept. RESULTS: Of the identified categories 34 dealt with healthcare services, three with administrative services, and five with coordination. The six recognized domains of the healthcare services are health promotive services, health protective services, diagnostic services, therapeutic services, rehabilitation services, and terminal healthcare services. Using the public health approach, the Health promotive action and preventive action model (HPA model) was constructed in order to visualize where in the course of the process of health-ill health and developmental stages the public health nurses provide healthcare services. Health promotion and the levels of prevention are described on the operational and conceptual levels in this paper. CONCLUSIONS: The result is expected to have an important effect on how public health nurses conceptualize their field of knowledge. The classification reflects current public health policy by focusing on health promotion and illness prevention. The developed HPA model will support health service research.

Attitude of Health Personnel↗

PubMed1992

A probability model for assessing exposure among respirator wearers: Part I--Description of the model.

The basic respirator equation states that the contaminant level inside a respirator (CI) is the product of the contaminant level outside the respirator (CO) and the decimal fraction penetration (P). On the basis of this relation, the authors present a probability model for the lognormal total distribution of CI levels among a respirator-wearing population; the model accounts for between-wearer and within-wearer variability in both CO levels and P values. The assumptions underlying the model are shown to be consistent with current knowledge about the variability in CO levels and P values. The model provides the basis for assessing the probability of overexposure to acute toxicants and to chronic toxicants among a respirator-wearing population.

Air Pollutants, Occupational↗

PubMed2004

What minimal models cannot tell: a comment on "A model of phytoplankton blooms".

Huppert et al. analyzed a simple model describing bottom-up control of phytoplankton blooms. While we appreciate the mathematical aspects of this article, we feel that the fit of their model to data of Lake Kinneret is overly optimistic because the time axis was rescaled in an arbitrary way. Furthermore, one of the main conclusions of the article (bottom-up control is more likely to occur than top-down control) cannot, in our opinion, be drawn from a minimal model because such a model focuses on one explanation. It cannot be used to reveal the relative importance of alternative explanations.

Eutrophication↗