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Quantification of dopamine transporter binding using [18F]FP-beta-CIT and positron emission tomography.

The purpose of this study was to compare different kinetic and semi-quantitative methods for analysing human [18F]FP-beta-CIT studies: plasma input models, simplified (SRTM) and full (FRTM) reference tissue models, standard uptake values (SUV) and SUV ratios (SUVr). Both simulations and clinical evaluations were performed to determine the effects of noise, scan duration and blood volume on Akaike model selection, and on precision and accuracy of estimated parameters. For typical noise levels (COV approximately 2.5%) and scan durations (<90 mins), simulations provided poor fits (Akaike criterion) in case of reversible plasma input models showing a relatively high number of outliers compared with the two-tissue irreversible model. Reference tissue models provided more reliable fits, which were nearly independent of noise and scan duration. For clinical data, two tissue irreversible and reversible plasma input models fitted striatum curves equally well (Akaike criterion). BP with plasma input models were less precise and contained more outliers than BP obtained with SRTM or FRTM. Among all methods tested, SRTM showed the highest contrast between patients and controls. When differentiating between patients and controls, SUVr performed almost equally well as SRTM, although contrast between striatum and background was lower. In conclusion, SRTM provided BP estimates with the highest precision and accuracy. Moreover, SRTM provided good contrast between patients and controls, and between striatum and background. SRTM is therefore the method of choice for quantitative [18F]FP-beta-CIT studies. SUVr might be an alternative for larger clinical trials.

Aged↗

Research utilization and the CNS: confronting the issues.

Utilization of research in nursing is still inconsistent despite nearly two decades of published models and studies on the subject, and of leaders urging that the profession must increase its use of research. In fact, several questions regarding research utilization in nursing remain unanswered. A review of selected models of research utilization is presented, as well as a review of the published studies of utilization barriers and facilitators. Three key questions for the profession as a whole and for the clinical nurse specialist (CNS) in particular are advanced, and concrete answers for the practicing CNS are offered.

Clinical Nursing Research↗

Selecting amplification characteristics for young hearing-impaired children.

The task of selecting the electroacoustic characteristics of hearing aids for young hearing-impaired children continues to challenge many clinical audiologists. The rationale for a theoretically based approach to this problem is presented. Additionally, issues related to the choice of an idealized speech spectrum for a theoretical selection model are considered in relation to the acoustic environment and auditory needs of young hearing-impaired children. Finally, the preliminary version of a computer assisted speech spectrum approach, which facilitates the initial selection of frequency/gain and frequency/SSPL characteristics is presented.

Child, Preschool↗

Comparison of different models of orientation selectivity based on distinct intracortical inhibition rules.

Aim of this work is to present simple models of orientation selectivity in the visual cortex, which do not require massive computational effort. Three different models are compared, in order to gain deeper insight into the structure of cortical circuits generating inhibitory signals. All models represent a single hypercolumn. They differ as to the arrangement of inhibitory connections: in the first ("antiphase inhibition model") inhibition is in phase opposition with excitation, but with a similar orientation tuning; in the second ("in-phase inhibition model"), inhibition is in phase with excitation, but with larger orientation tuning. In these two models the orientation width of inhibition increases with contrast. Finally, a third model ("center-surround model") assumes that inhibition comes from the same cells providing excitation, hence the inhibition tuning is contrast-independent. All models, with suitable values of the intracortical synapse parameters, are able to mimic experimental results in the literature. A few differences are evident between the "center-surround model" and the other two, especially as to the dependence of cortical cell response on spatial frequency. The models can represent practical tools to test hypotheses on the disposition of cortical synapses avoiding massive computational efforts.

Contrast Sensitivity↗

Modelling neutral and selective evolution of protein folding.

We examine a model evolutionary space consisting of genotypes mapped to their corresponding phenotypes. This mapping is derived from a lattice model for proteins which, despite its highly idealized nature, has been shown to share general properties with real proteins. Large evolutionary networks are observed, with genotypes corresponding to non-lethal phenotypes linked by unit mutational steps. Neutral mutations are necessary for traversing the evolutionary networks, and even one neutral mutation in a genotype can change the phenotypes attainable by a unit mutational step.

Biological Evolution↗

Prevention of the selection of clarithromycin-resistant Mycobacterium avium-intracellulare complex.

The prevalence of clarithromycin-resistant mutants in untreated bacterial populations of Mycobacterium avium-intracellulare complex (MAC) has been demonstrated to be between 10(-7) and 10(-8) colony-forming units (CFUs) in the beige mouse model. Selection of these mutants occurred during clarithromycin monotherapy if treatment was initiated when the bacterial population size reached approximately 10(8) CFUs per spleen. Likewise, selection of clarithromycin-resistant MAC was induced in AIDS patients during therapy with clarithromycin alone or in combination with drugs that were ineffective for the treatment or prevention of MAC infection. Because the emergence of clarithromycin resistance during preventive therapy was observed exclusively in AIDS patients with CD4+ cell counts < or = 25 cells/microliter, clarithromycin monotherapy can be recommended for the prevention of MAC infection in AIDS patients with CD4+ cell counts of > or = 50 cells/microliter. However, a clarithromycin-containing combination regimen is recommended for patients with CD4+ cell counts < 50 cells/microliter. Since preliminary animal experiments and clinical trials indicate that amikacin, ethambutol or rifabutin in combination with clarithromycin may prevent, or at least delay, the selection of clarithromycin-resistant mutants, further preventive trials are urgently needed to confirm these observations.

AIDS-Related Opportunistic Infections↗

The distance from the skin to the subarachnoid space can be predicted in premature and former-premature infants.

PURPOSE: Spinal anesthesia can be technically challenging in young infants. We studied whether the distance between the skin and the lumbar subarachnoid space in premature and former-premature young infants could be predicted prior to lumbar puncture. METHODS: The distance from skin entry point to tip of the spinal needle was measured using a caliper after lumbar spinal anesthesia at the L4-5 interspace. This distance was correlated to the patient's weight, postconceptual age and lumbar ultrasonographic measurement of the skin-to-subarachnoid space and predictive statistical models were sought. RESULTS: Thirty-five premature or former-premature infants were studied. Three models were examined: all three independent variables, weight and postconceptual age only, and weight only. The model selected contained the weight and postconceptual age, because it had the highest value for adjusted R squared, as well as the lowest value for the mean squared error. Adding the ultrasonic measurement to the model worsened the results. The statistical model that described the depth of the subarachnoid space at the L4-5 level was Y = 13.19 + 0.0026 x W - 0.12 x PCA, where Y is the distance (mm) from the skin to the subarachnoid space, W is the patient's weight (g) and PCA is the postconceptual age (weeks). Adjusted R squared was 0.72, mean square error was 2.63 and P < 10(-9). CONCLUSION: The distance between the skin and the subarachnoid space at the level of L4-5 interspace can be predicted using a statistical model based on the infant's weight and postconceptual age. Spinal ultrasound has no value in L4-5 subarachnoid space depth prediction.

Anesthesia, Spinal↗

School health services: a Hub of Services to children and their families.

The Corporate/Community Schools of America (C/CSA) is a not-for-profit coalition of business executives, concerned educators, and community leaders working to reform urban public education in the United States. This article reports on the C/CSA Chicago and the Hub of Services, which is a central component of the school design. The Hub of Services concept is described and compared to traditional school health program management models. Selected outcomes of the program are summarized as well as replication issues. Given the competing demands for increased school-based services and increased fiscal constraints, this unique experiment provides a school health service model that offers a solution for both of these demands.

Chicago↗

An application of exposure modeling in exposure assessments for a university chemistry teaching laboratory.

Chemical exposures in a university teaching lab were assessed using a tiered approach to modeling. Zero ventilation and well mixed room models estimated air concentrations of ethyl ether, n-hexane, and methylene chloride during distillation and extraction exercises. A simple, zero ventilation model determined that health risks from the ethyl ether exercise were minimum. N-hexane and methylene chloride exposures were evaluated with higher tiered, well mixed room models. An assumption that all of the solvent evaporated during the lab resulted in estimated n-hexane concentrations well below the occupational exposure limit. Methylene chloride concentration estimates using this approach were only one-half the occupational exposure limit, so the model was refined using information on the actual amount of solvent that evaporated. This resulted in a concentration estimate approximately one-fifth of the occupational exposure limit. Air sampling was done to evaluate model performance. Measured concentrations were higher than modeled concentrations by up to a factor of two but were still below applicable occupational exposure limits. The exposure models selected were deemed useful in the assessment of exposure acceptability in these labs.

Air Pollution, Indoor↗

Resource allocation in public hospitals: is it effective?

The allocative inefficiency is a fundamental flaw in the public hospitals of the developing countries. The inefficiencies drain the limited public resources allotted for healthcare. Sri Lanka's public health system faces worsening budget constraints. The resource allocation practices of the Ministry of Health focus on increasing the cadre of hospital staff, consequently crowding out the investments on facility development. The purpose of the study is to assess the impact of resource allocation in the tertiary-care public hospitals that are under the central Ministry of Health. The model is based on the assumption that the hospital managers and other agents of a public hospital pursue the objective of quality maximization (in the absence of a profit motive). The inpatient mortality rate is selected as the indicator of quality. With the use of panel data fixed-effects, and first-differencing estimation methods, we study the impact of the resource allocation on the hospital mortality rates. The selected models are statistically significant at 0.1% level. The elasticity effect of the capital is considerably larger than the effects of the human resources, in servicing the patients. The results suggest that the human resource utilization is suboptimal, due to the inadequacy of the capital (i.e. medical equipment, etc.). The reorientation of the resource allocation towards the capital investments may save more lives.

Efficiency, Organizational↗

An investigation into the characteristics and drug release properties of multiple W/O/W emulsion systems containing low concentration of lipophilic polymeric emulsifier.

Multiple W/O/W emulsions with high content of inner phase (Phi1=Phi2=0.8) were prepared using relatively low concentrations of lipophilic polymeric primary emulsifier, PEG 30-dipolyhydroxystearate, and diclofenac diethylamine (DDA) as a model drug. The investigated formulations were characterized and their stability over the time was evaluated by dynamic and oscillatory rheological measurements, microscopic analysis and in vitro drug release study. In vitro release profiles of the selected model drug were evaluated in terms of the effective diffusion coefficients and flux of the released drug. The multiple emulsion samples exhibited good stability during the ageing time. Concentration of the lipophilic primary emulsifier markedly affected rheological behaviour as well as the droplet size and in vitro drug release kinetics of the investigated systems. The multiple emulsion systems with highest concentration (2.4%, w/w) of the primary emulsifier had the lowest droplet size and the highest apparent viscosity and highest elastic characteristics. Drug release data indicated predominately diffusional drug release mechanism with sustained and prolonged drug release accomplished with 2.4% (w/w) of lipophilic emulsifier employed.

Anti-Inflammatory Agents, Non-Steroidal↗

Have all won and must all have prizes? Revisiting Luborsky et al.'s verdict.

Although most reviews of comparative psychotherapy literature have failed to find significant differences among treatments, it is premature to give up the search for differential effects. There are a large number of patient, therapist, and treatment variables that may mediate the effects of treatments. Given the enormity of the task of exploring potential interactions among the many patient, therapist, and psychotherapy types, a guiding model is needed by which to narrow our search for variables that mediate between treatment type and outcome. However, theoretical constructs that represent both patient and therapy variations frequently are poorly defined. Tests of treatment selection models that cut across narrow theoretical differences among psychotherapies and that operationalize definitions of patient types hold promise for revealing meaningful Patient x Therapist interaction effects in psychotherapy.

Follow-Up Studies↗

Mixed effects logistic regression models for multiple longitudinal binary functional limitation responses with informative drop-out and confounding by baseline outcomes.

In the context of analyzing multiple functional limitation responses collected longitudinally from the Longitudinal Study of Aging (LSOA), we investigate the heterogeneity of these outcomes with respect to their associations with previous functional status and other risk factors in the presence of informative drop-out and confounding by baseline outcomes. We accommodate the longitudinal nature of the multiple outcomes with a unique extension of the nested random effects logistic model with an autoregressive structure to include drop-out and baseline outcome components with shared random effects. Estimation of fixed effects and variance components is by maximum likelihood with numerical integration. This shared parameter selection model assumes that drop-out is conditionally independent of the multiple functional limitation outcomes given the underlying random effect representing an individual's trajectory of functional status across time. Whereas it is not possible to fully assess the adequacy of this assumption, we assess the robustness of this approach by varying the assumptions underlying the proposed model such as the random effects structure, the drop-out component, and omission of baseline functional outcomes as dependent variables in the model. Heterogeneity among the associations between each functional limitation outcome and a set of risk factors for functional limitation, such as previous functional limitation and physical activity, exists for the LSOA data of interest. Less heterogeneity is observed among the estimates of time-level random effects variance components that are allowed to vary across functional outcomes and time. We also note that. under an autoregressive structure, bias results from omitting the baseline outcome component linked to the follow-up outcome component by subject-level random effects.

Aged↗

Generalized hierarchical multivariate CAR models for areal data.

In the fields of medicine and public health, a common application of areal data models is the study of geographical patterns of disease. When we have several measurements recorded at each spatial location (for example, information on p>/= 2 diseases from the same population groups or regions), we need to consider multivariate areal data models in order to handle the dependence among the multivariate components as well as the spatial dependence between sites. In this article, we propose a flexible new class of generalized multivariate conditionally autoregressive (GMCAR) models for areal data, and show how it enriches the MCAR class. Our approach differs from earlier ones in that it directly specifies the joint distribution for a multivariate Markov random field (MRF) through the specification of simpler conditional and marginal models. This in turn leads to a significant reduction in the computational burden in hierarchical spatial random effect modeling, where posterior summaries are computed using Markov chain Monte Carlo (MCMC). We compare our approach with existing MCAR models in the literature via simulation, using average mean square error (AMSE) and a convenient hierarchical model selection criterion, the deviance information criterion (DIC; Spiegelhalter et al., 2002, Journal of the Royal Statistical Society, Series B64, 583-639). Finally, we offer a real-data application of our proposed GMCAR approach that models lung and esophagus cancer death rates during 1991-1998 in Minnesota counties.

Bayes Theorem↗

Ensembles of Bayesian-regularized genetic neural networks for modeling of acetylcholinesterase inhibition by huprines.

Acetylcholinesterase inhibition was modeled for a set of huprines using ensembles of Bayesian-regularized Genetic Neural Networks. In the Bayesian-regularized Genetic Neural Network approach the Bayesian regularization avoids overfitted regressions and the genetic algorithm allows exploring a wide pool of three-dimensional descriptors. The predictive capacity of our selected model was evaluated by averaging multiple validation sets generated as members of neural network ensembles. When 60 members are assembled, the neural network ensemble provides a reliable measure of training and test set R(2)-values of 0.945 and 0.850 respectively. In other respects, the ability of the nonlinear selected genetic algorithm space for differentiate the data were evidenced when total data set was well distributed in a Kohonen self-organizing map. The analysis of the self-organizing map zones allows establishing the main structural features differentiated by our vectorial space.

Acetylcholinesterase↗

Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle.

Inclusion body myositis (IBM), the most common age-related muscle disease in the elderly population, is an incurable disorder leading to severe disability. Sporadic IBM has an unknown etiology, although affected muscle fibers are characterized by many of the pathobiochemical alterations traditionally associated with neurodegenerative brain disorders such as Alzheimer's disease. Accumulation of the amyloid-beta peptide, which is derived from proteolysis of the larger amyloid-beta precursor protein (betaAPP), seems to be an early pathological event in Alzheimer's disease and also in IBM, where in the latter, it predominantly occurs intracellularly within affected myofibers. To elucidate the possible role of betaAPP mismetabolism in the pathogenesis of IBM, transgenic mice were derived in which we selectively targeted betaAPP overexpression to skeletal muscle by using the muscle creatine kinase promoter. Here we report that older (>10 months) transgenic mice exhibit intracellular immunoreactivity to betaAPP and its proteolytic derivatives in skeletal muscle. In this transgenic model, selective overexpression of betaAPP leads to the development of a subset of other histopathological and clinical features characteristic of IBM, including centric nuclei, inflammation, and deficiencies in motor performance. These results are consistent with a pathogenic role for betaAPP mismetabolism in human IBM.

Amyloid beta-Protein Precursor↗

Soft selection and quantitative genetic variation: a laboratory experiment.

The effect of environmental heterogeneity on the genetic variation of different quantitative characters was studied in two laboratory and two recently captured populations of Drosophila melanogaster. Two different culture media (habitats R and G) were used. Coarse-grained heterogeneity with independent density control in each habitat (R + G), and fine-grained (R/G) heterogeneity were simulated in population cages. Control populations in both R and G habitats were also maintained. Genetic differences for oviposition-site preference, larval preference and/or within-habitat viability were found between subpopulations sampled from different media. This happened in all four populations maintained on R + G, two populations maintained on R/G, and one control population. Thus, environmental heterogeneity seems to protect genetic variability responsible for between-habitat genetic differentiation, particularly when such heterogeneity corresponds to the 'soft selection' model (R + G). However, for the quasi-neutral trait sternopleural bristle number, no genetic between-habitat differentiation, nor increased heritability were observed in populations maintained under any kind of environmental heterogeneity. Hence, although soft selection seems to be a real force in determining adaptation to heterogeneous environments, the genetic variability maintained may be small in relation to the whole genome.

Animals↗

Value of self-reportable screening criteria to identify asymptomatic individuals in the general population for urogential Chlamydia trachomatis infection screening.

Submission of samples from the home allows screening for Chlamydia trachomatis without preceding professional assessment of clinical risk factors. Therefore, a validation of self-reportable information for use as selective screening criteria is needed. We asked a total of 1175 women and 1033 men who participated in an in-home sampling screening study to provide information on behavior and sociodemographic characteristics. In a multivariate model, selective screening criteria were developed on the basis of information from a random part of the tested population (development group), and the validity was assessed for the remaining part of the tested population (validation group). To find all infections, 95% of the subjects had to be screened, and screening 63% of them would have detected 86% of infections. Low predictive values were found when selective screening criteria from other studies were assessed. Selective screening by means of in-home sampling strategies among men and women aged 21-23 years cannot be recommended in the area studied.

Adult↗