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Results for “model credibility”

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PubMed2005

The establishment of the hemangioma model in nude mouse.

BACKGROUND/PURPOSE: Hemangioma is one of the most common benign tumors in children. Most of them could regress spontaneously; however, the pathogenesis and triggering of regression are still unknown. Here, we introduce a new means in which the specimen of human hemangioma was transplanted into nude mice subcutaneously. At the same time, high dose of estradiol was administered to the experimental nude mice intramuscularly to promote implantation and proliferation of hemangioma endothelial cells. By this means, a credible animal model of human hemangioma was established. Further studies on pathogenesis and medical intervention of hemangioma could be carried on with this model. METHODS: The specimen of grafted hemangioma was taken from a 6-month-old girl, in whom the hemangioma grew rapidly, by surgery. The fresh estrogen receptor-positive strawberry hemangioma specimens were sliced and inoculated subcutaneously into 16 nude mice that were divided randomly into 2 groups, namely, group 1 (n = 8) with normal diet and group 2 (n = 8) with normal diet and 10(-7) mg estradiol administered intramuscularly every week additionally. The size of grafts was measured weekly. All of the experimental mice were killed at 90 days after graft. Hemangioma tissues were harvested and sliced into 4 to 5 microm sections. Living grafts were subjected to histopathologic examination and immunohistochemistry for CD34 and Ki-67. RESULTS: All of the sizes of hemangioma tissues in group 1 were diminished distinctly in 30 days. Thirteen samples of hemangioma were almost absorbed and disappeared completely in 90 days. The sizes of hemangioma in group 2 were larger than primary specimens. It was observed from the section of hemangioma that endothelial cells proliferate vividly and fresh capillary blood vessels grew up into the body of hemangioma. The mean positive cell rate of CD34 in group 2 was 48.49 +/- 3.90 and the Ki-67 was 15.04 +/- 2.44. The transplanted tumor cell retained the histologic characters of original tumor. CONCLUSION: The capillary hemangioma model established in nude mice retains almost all the biologic character of original human hemangioma and could be widely used in further study on hemangioma.

Animal Feed↗

PubMed2004

Modelling diatom growth in turbulent waters.

Algal models used as tools in the management of algal blooms may be inaccurate because representation of mixing processes is often oversimplified. A testable 3-D algal model for prediction of algal growth in turbulent surface waters was developed based on the Eulerian water quality model, HYDRO-3D. Out-door mesocosm experiments on the growth of the diatom Skeletonema costatum showed no evidence that diatom growth is significantly affected by light/dark fluctuations brought about by turbulent mixing, and no direct effects of turbulence on phytoplankton physiology were required in the algal model. The algal model was successfully calibrated and validated against mesocosm data and field data from Poplar Dock, London Docklands. Application of the model gave credible results for the hypothetical growth of S. costatum in Poplar Dock under a wide range of wind speeds and surface irradiances. However, differences between the results of a full 3-D simulation and a simplified 1-D representation of Poplar Dock were minimal, and no clear conclusions could be drawn on the superiority of 3-D models over 1-D models for simulation of complex flows in natural water bodies.

Diatoms↗

PubMed2006

Phenomenological model of bone remodeling cycle containing osteocyte regulation loop.

Biological parameters, such as bone resorption and formation constants, are important variables to achieve optimised hard tissue scaffolds design. To help to understand the modelling process that occurs when a scaffold is implanted it is vital to understand the rather complex bone remodeling process prevalent in native bone. One approach to developing a mathematical model that predicts osteoactivity both in scaffolds, as well as in bone in vivo, is based on a bio-cybernetic vision of basic multicellular unit (BMU) action -. In the case of the model presented in this paper, an additional loop of regulation based on osteocyte activity has been added. This approach has resulted in a four-dimensional system, which shows steady-quasi-cyclic behaviour using a particular range of constants with real biological meaning. The initial findings suggesting that the basic steady-state appears as a torus in multidimensional phase space have been discussed. The existence of this surface in the osteoclasts-osteoblasts-osteocytes-bone subspace indicates that there is a first integral for this dynamic system. Biological and physical interpretation of this integral as a conservative value has been proposed. It is possible to draw an analogy between this conservative value, as a kind of substrate-energy regenerative potential of the bone remodeling system with a molecular nature, to the classical physical value (energy). There are clear indications that there is recovering potential within the BMU that results in a steady operating genetically predominated bone remodeling process. This recovering potential is directed against both mechanical and biomechanical damage to the bone. The current model has credibility when compared to the normal bone remodeling process. However, additional work is required to study a wider range of constants.

Animals↗

PubMed2004

Common factors are not islands--they work through models: a response to Sexton, Ridley, and Kleiner.

In this article, we respond to Sexton, Ridley, and Kleiner (this issue) from three different perspectives. First, we discuss their criticisms as rooted in a portrait of common factors to which we do not subscribe. Second, we discuss points of agreement and partial agreement between our two articles. Finally, we discuss our areas of clear disagreement with their points of view. In these areas of disagreement we put forth the common factors approach as an empirically supported lens; we discuss the influence of investigator allegiance on the specificity conclusion; and we challenge the idea that the common factors lens is simple. In conclusion, we illustrate how common factors work through a credible therapy model using functional family therapy as an example.

Attitude of Health Personnel↗

PubMed2006

Economics on trial: the use and abuse of economic methods in third party tobacco litigation.

OBJECTIVE: To analyse how the tobacco industry responded to economic models and methods used in third party payer tobacco litigation that has occurred since 1994. METHODS: Identified 12 third party payer cases and reviewed the transcripts using WinMax qualitative software. Focused on defendant's opening and closing statements, followed by trial testimony, depositions, and plaintiff's transcripts. RESULTS: Tobacco industry defendants tried to create doubt and confusion about whether or not smoking caused disease and by extension led to health care costs; argued that the economic models used were not legitimate and were not appropriate for estimating the costs incurred by plaintiffs; and criticised the data sources used because they did not consist of the individuals whose health care costs were being sought. CONCLUSIONS: Faced with a new and unprecedented wave of anti-tobacco litigation from third party payers, the tobacco industry tried to adapt strategies that had been used successfully in the past-creation of unfounded doubt and confusion, and manipulation of the discovery process to force plaintiffs to withdraw or concede defeat. The strategies failed because credible economic models of the health care costs of smoking had been developed that were able to quantify the damages to a large group of health care recipients, because plaintiff's attorneys were able to commit significant resources and willing to undertake substantial financial risk to defend their new legal approaches, and because previous arguments related to individual responsibility were deemed irrelevant in third party litigation.

Cost of Illness↗

PubMed1998

Double blind test of magnetic field effects on neurite outgrowth.

Previous work reported that nerve growth factor-stimulated neurite outgrowth in PC-12 cells could be altered by exposure to parallel alternating current (AC) and direct current (DC) magnetic fields under a variety of exposure conditions, producing results that are consistent with the predictions of the ion parametric resonance (IPR) model. The credibility of these results, considered extraordinary by some scientists, could be strengthened if the cell response were found to persist under alternate assay conditions. We replaced part of our standard assay procedure with a double blind procedure. This new procedure obscured 1) whether a particular set of dishes of cells was exposed or not, and 2) which individual dish was in which exposure system. The goal was to determine whether the previously observed responses of PC-12 cells to magnetic fields would be sufficiently robust to decode the imposed blinding, thereby removing any question of experimenter bias in reported results. We placed three coded dishes of cells in each of two otherwise identical exposure systems, one not energized and one energized to produce exposure conditions predicted to maximally suppress neurite outgrowth (Bdc of 36.6 microT, parallel 45 Hz AC of 23.8 microT rms). Each of the six dishes were recoded before assay to further obscure the exposure identity of any individual dish. The combined results of four distinct runs of these double blind experiments unequivocally demonstrated that 1) there was a clear, distinctive, repeatable consistency with the actual energization of the exposure systems and location of each dish, and with the predictions of the IPR model; 2) only the explicitly stated experimental variables influenced the experiment; and 3) the reported response of the cells was very improbably due to chance (P = .000024).

Animals↗

PubMed2002

Minimal model S(I)=0 problem in NIDDM subjects: nonzero Bayesian estimates with credible confidence intervals.

The minimal model of glucose kinetics, in conjunction with an insulin-modified intravenous glucose tolerance test, is widely used to estimate insulin sensitivity (S(I)). Parameter estimation usually resorts to nonlinear least squares (NLS), which provides a point estimate, and its precision is expressed as a standard deviation. Applied to type 2 diabetic subjects, NLS implemented in MINMOD software often predicts S(I)=0 (the so-called "zero" S(I) problem), whereas general purpose modeling software systems, e.g., SAAM II, provide a very small S(I) but with a very large uncertainty, which produces unrealistic negative values in the confidence interval. To overcome these difficulties, in this article we resort to Bayesian parameter estimation implemented by a Markov chain Monte Carlo (MCMC) method. This approach provides in each individual the S(I) a posteriori probability density function, from which a point estimate and its confidence interval can be determined. Although NLS results are not acceptable in four out of the ten studied subjects, Bayes estimation implemented by MCMC is always able to determine a nonzero point estimate of S(I) together with a credible confidence interval. This Bayesian approach should prove useful in reanalyzing large databases of epidemiological studies.

Bayes Theorem↗

PubMed2005

Three-dimensional structure of a macromolecular assembly that regulates type III secretion in Yersinia pestis.

Yersinia pestis, the causative agent of plague, utilizes a type III secretion system (T3SS) to inject effector proteins directly into the cytosol of mammalian cells where they interfere with signal transduction pathways that regulate actin cytoskeleton dynamics and inflammation, thereby enabling the bacterium to avoid engulfment and destruction by macrophages. Type III secretion normally does not occur in the absence of close contact with eukaryotic cells. Negative regulation is mediated in part by a multiprotein complex that has been proposed to act as a physical impediment to type III secretion by blocking the entrance to the secretion apparatus prior to contact with mammalian cells. This complex is composed of YopN, its heterodimeric secretion chaperone SycN-YscB, and TyeA. Here, we report two crystal structures of YopN in complex with its heterodimeric secretion chaperone SycN-YscB and the co-regulatory protein TyeA, respectively. By merging these two overlapping structures, it was possible to construct a credible theoretical model of the YopN-SycN-YscB-TyeA complex. The modeled assembly features the secretion signaling elements of YopN at one end of an elongated structure and the secretion regulating TyeA binding site at the other. A patch of highly conserved residues on the surface of the C-terminal alpha-helix of TyeA may mediate its interaction with structural components of the secretion apparatus. Conserved arginine residues that reside inside a prominent cavity at the dimer interface of SycN-YscB were mutated in order to investigate whether they play a role in targeting the YopN-chaperone complex to the type III secretion apparatus. One of the mutants exhibited a phenotype that is consistent with this hypothesis.

Amino Acid Sequence↗

PubMed1995

Cost management in community-acquired lower respiratory tract infection.

Pharmacoeconomic analysis must determine a credible cost model, including healthcare-related, non-healthcare-related, and intangible costs, and must identify important treatment outcomes. Outcomes can be ranked in terms of their sensitivity to different treatments or weighted in terms of cost. Two recent studies of community-acquired lower respiratory tract infection have shown that inadequate treatment is a frequent cause of repeat visits to the physician's office, involving extra costs that could presumably be avoided by more effective first-line treatment. When economic data are to be incorporated into clinical trials, it is important to collect data outside as well as within the trial center and to concentrate on data likely to be of significance to the decision makers the trial is designed to influence. The best way of achieving internal validity in such trials is through randomization, which minimizes bias, chance imbalance, and confounding factors. The three major determinants of the cost-effectiveness of treatment are efficacy, the value attached to preventing treatment failure, and the accuracy of diagnosis. The latter is important because a drug can only benefit patients if they have the disease for which it is an effective treatment.

Anti-Bacterial Agents↗

PubMed2002

Recent advances in inducible expression in transgenic mice.

In order to accurately analyze gene function in transgenic mice, as well as to generate credible murine models of human diseases, the ability to regulate temporal- and spatial-specific expression of target genes is absolutely critical. Pioneering work in inducible transgenics, begun in the 1980s and continuing to the present, has led to the development of a variety of different inducible systems dedicated to this goal, the shared basis of which is the accurate conditional expression of a given transgene. Recent advances in inducible transgene expression in mice are discussed.

Animals↗

PubMed2001

Preventing the 'professional cleansing' of nurse educators.

The purpose of this paper is to argue that contrary to perceived wisdom nursing education ought to abandon the lecturer practitioner role on the grounds that it is a flawed concept predicated on a false assumption. In addition, and more seriously, it is in effect a significant hidden subsidy to service at the expense of education. It is suggested that by restructuring the nurse educator's role using the concepts of primary nursing as a method of organizing nurse educator's core activities, the perception and reality of teaching practice could be transformed. Calpin-Davies suggests that such a strategy enables nurse educators to be considered as practising nurses. It also has the added advantage that it is consistent with the form of organizing nursing expected of clinical colleagues. In addition it provides a basis for partnership with clinical nurses and with students, it responds to the imagined theory--practice gap, and affords nurse educators the means of becoming a credible role model.

Education, Nursing↗

PubMedDate not supplied

Development of controlled release spheroids using natural polysaccharide as release modifier.

A polysaccharide hydrogel was isolated from the seeds of Tamarindus indica (tamarind) and was used as release modifier for the preparation of diclofenac sodium spheroids, using extrusion-spheronization technique. The process was studied for the effect of variables to arrive at spheroids with satisfactory particle shape, size and size-distribution. The prepared spheroids were characterized for surface morphology, qualitative surface porosity, friability, bulk density, and flow properties. The in vitro release studies exhibited a zero-order release kinetics that was confirmed by Higuchi's and Peppas' models. A credible correlation was obtained among swelling index, viscosity, surface roughness of the polysaccharide, and in vitro dissolution profile of the spheroids. In the comparative bioavailability study, we found that the developed spheroids were able to sustain the drug release over 8 hr and could improve the extent of absorption and bioavailability of the drug.

Administration, Oral↗

PubMed2002

A consistent radionuclide vector after the Chernobyl accident.

The radionuclide vector in the release plume from the destroyed unit 4 of the Chernobyl Nuclear Power Plant was assessed. Emphasis was laid on radionuclides relevant for the internal dose, including those with short half-lives, and on the radionuclide vector in the 30-km zone where practically no data in air or foodstuff are available. An evaluation of data was performed by comparing core analysis data and actual measurements of air filters and deposition data. The derived nuclide vector is consistent with most measurements and core analysis data. The ratios of the various radionuclides with regard to the guide isotope 137Cs vary both with direction of release and with increasing distance from the power plant. The variation and its causes are discussed, and a credible, consistent model for the vector at arbitrary distances from the nuclear power plant, in particular with regard to non-volatile radionuclides, is given. In that way the observed large discrepancies of the radionuclide vector determined by Russian and Ukrainian researchers, and those measured in Central and Northern European are explained by the fact that 90Sr, 95Zr, 140Ba, and 144Ce, which showed a much higher ratio to 137Cs close to the reactor than at 1,000 km distance, were attached to particle sizes of 8 microm and thus quicker deposited than the volatile radionuclides which were attached to 1 microm particulates on average. Also, the 131I to 137Cs ratio changes with distance by almost one order of magnitude which is explained by the higher deposition velocity of iodine.

Air Pollutants, Radioactive↗

PubMed2006

Sparse Bayesian kernel survival analysis for modeling the growth domain of microbial pathogens.

Survival analysis is a branch of statistics concerned with the time elapsing before "failure," with diverse applications in medical statistics and the analysis of the reliability of electrical or mechanical components. We introduce a parametric accelerated life survival analysis model based on kernel learning methods that, at least in principal, is able to learn arbitrary dependencies between a vector of explanatory variables and the scale of the distribution of survival times. The proposed kernel survival analysis method is then used to model the growth domain of Clostridium botulinum, the food processing and storage conditions permitting the growth of this foodborne microbial pathogen, leading to the production of the neurotoxin responsible for botulism. A Bayesian training procedure, based on the evidence framework, is used for model selection and to provide a credible interval on model predictions. The kernel survival analysis models are found to be more accurate than models based on more traditional survival analysis techniques but also suggest a risk assessment of the foodborne botulism hazard would benefit from the collection of additional data.

Artificial Intelligence↗

PubMed2002

Interaction among four residues distributed through the secretin pharmacophore and a focused region of the secretin receptor amino terminus.

The amino terminus of the secretin receptor (SecR) is known to be critical for natural agonist action, although the role it plays is still unclear. We have demonstrated that photolabile residues within both the amino-terminal (position 6) and carboxyl-terminal (positions 22 and 26) halves of secretin each covalently label receptor amino-terminal tail residues [Dong et al., J Biol Chem, 274:19161-19167 (1999), 274:903-909 (1999), and 275:26032-26039 (2000)]. Here, we extend this series of studies with an additional probe having its site of covalent attachment in a distinct region of the peptide, between amino- and carboxyl-terminal helical domains. This probe incorporated a photolabile (epsilon-p-benzoylbenzoyl)lysine in position 18 and a site for oxidative radioiodination [(tyrosine(10),(benzoyl-benzoyl)lysine(18))rat secretin-27]. This analog represented a full agonist, stimulating cAMP accumulation in Chinese hamster ovary-SecR cells in a concentration-dependent manner. It bound to the SecR specifically and saturably, and was able to efficiently label that molecule within its amino terminus. Sequential specific cleavage, purification, and sequencing demonstrated that this probe labeled receptor residue arginine(14), in the same subdomain as that labeled by previous probes. Consistent with the importance of this residue, alanine replacement mutagenesis (R14A) resulted in substantial reductions in the potency (127-fold) and binding affinity (400-fold) of secretin relative to its action at the wild-type receptor. We have been able to accommodate all four extant pairs of residue-residue approximations between divergent regions of the secretin pharmacophore and the first forty residues of the SecR into a credible molecular model of this interaction. Additional experimentally derived constraints will be necessary to determine the spatial positioning of this complex with the remainder of the SecR.

Amino Acid Sequence↗

PubMed1996

Where in the world am I? Sex and handedness differences in knowledge of geography.

218 college students (96 men and 122 women, including nearly equal numbers of right-handers and left-handers) were administered a modified version of the "Gallup Geography Test." Men outperformed women, and left-handed women outperformed right-handed women. We suggest that these results cannot be easily explained by any credible sociocultural model but are consistent with a neuropsychological model of sex and handedness differences in spatial ability advanced by Harshman, Hampson, and Berenbaum in 1983.

Adolescent↗

PubMed2026

Dynamic Protein Structure Paradox: An Integrative Framework for Endpoint-Conditioned Evidentiary Sufficiency in Structure-to-Function Claims.

Accurate coordinates for a represented protein state do not, by themselves, establish activity or any other condition-specific function. This article defines the Dynamic Protein Structure Paradox (DPSP) as the apparent conflict between structural accuracy and functional underdetermination and develops it as an integrative evidentiary assessment framework rather than a new theory or paradigm. The underlying problem has been longstanding, since structural genomics, function annotation, allostery, and disorder research each established that fold does not determine function and that function does not determine fold. DPSP consolidates those results into one endpoint-conditioned rule. Once a measurable endpoint is defined, it assesses four coupled dimensions: relevant-state completeness, context completeness, ensemble or kinetic dependence, and chemical dependence. A rubric rates each dimension as adequate, uncertain, or missing, and a materiality test determines which gaps influence the stated decision. The outcome is one of three mutually exclusive modes of utilization: geometry-led, conditional, or function-measured. The deliverable is a concise evidence statement delineating what the structure supports, which decisive variable remains unmeasured, and what corroboration is necessary. DPSP complements, rather than replaces, existing structural, ensemble, and computational approaches. The framework remains unvalidated, its thresholds are provisional, and the studies necessary to confirm or refute it are specified.

Proteins↗

PubMed2005

Smoke-free nurses: leading by example.

Occupational health nurses' scope of practice includes health promotion and restoration of health from environmental hazards (American Association of Occupational Health Nurses, n.d.). Because the nursing profession is the largest constituent of health care providers, it is essential that occupational health nurses tackle the smoking epidemic among the nursing profession. By encouraging smoking cessation among nurses, occupational health nurses reduce the environmental hazard of second-hand smoke and improve the health of nurses who smoke. When occupational health nurses take an active role in encouraging smoking cessation among nurses, they become leaders in reducing smoking within their communities. Members of the nursing profession are also role models. Occupational health nurses must help nurses become healthy role models and credible educators in the battle against smoking.

Cardiovascular Diseases↗