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PubMed2006

Bringing metabolic networks to life: integration of kinetic, metabolic, and proteomic data.

BACKGROUND: Translating a known metabolic network into a dynamic model requires reasonable guesses of all enzyme parameters. In Bayesian parameter estimation, model parameters are described by a posterior probability distribution, which scores the potential parameter sets, showing how well each of them agrees with the data and with the prior assumptions made. RESULTS: We compute posterior distributions of kinetic parameters within a Bayesian framework, based on integration of kinetic, thermodynamic, metabolic, and proteomic data. The structure of the metabolic system (i.e., stoichiometries and enzyme regulation) needs to be known, and the reactions are modelled by convenience kinetics with thermodynamically independent parameters. The parameter posterior is computed in two separate steps: a first posterior summarises the available data on enzyme kinetic parameters; an improved second posterior is obtained by integrating metabolic fluxes, concentrations, and enzyme concentrations for one or more steady states. The data can be heterogeneous, incomplete, and uncertain, and the posterior is approximated by a multivariate log-normal distribution. We apply the method to a model of the threonine synthesis pathway: the integration of metabolic data has little effect on the marginal posterior distributions of individual model parameters. Nevertheless, it leads to strong correlations between the parameters in the joint posterior distribution, which greatly improve the model predictions by the following Monte-Carlo simulations. CONCLUSION: We present a standardised method to translate metabolic networks into dynamic models. To determine the model parameters, evidence from various experimental data is combined and weighted using Bayesian parameter estimation. The resulting posterior parameter distribution describes a statistical ensemble of parameter sets; the parameter variances and correlations can account for missing knowledge, measurement uncertainties, or biological variability. The posterior distribution can be used to sample model instances and to obtain probabilistic statements about the model's dynamic behaviour.

Bayes Theorem↗

PubMed1999

Connecting across the miles: interdisciplinary collaboration in the evaluation of critical thinking.

A pilot study in which faculty from nursing and English departments at two universities in different states shared a common evaluation tool and collaborated through e-mail to evaluate the evidence of critical thinking in writing portfolios of baccalaureate and masters' nursing students. Loxley's (1997) four processes--assessment, building, managing the process, and evaluating--are used as a framework for describing collaboration among the disciplines in the two universities. Social exchange theory was used to explain the collaboration between participants. All six professors learned a great deal from studying and scoring the writings, but they learned most from each other through their e-mail dialogue.

Computer Communication Networks↗

PubMedDate not supplied

Hospital marketing orientation and managed care processes: are they coordinated?

The hospital marketing function has been widely adopted as a way to learn about markets, attract sufficient resources, develop appropriate services, and communicate the availability of such goods to those who may be able to purchase such services. The structure, tasks, and effectiveness of the marketing function have been the subject of increased inquiry by researchers and practitioners alike. A specific understanding of hospital marketing in a growing managed care environment and the relationship between marketing and managed care processes in hospitals is a growing concern. Using Kotler and Clarke's framework for assessing marketing orientation, we examined the marketing orientation of hospitals in a single state at two points in time--1993 and 1999. Study findings show that the overall marketing orientation score decreased from 1993 to 1999 for the respondent hospitals. The five elements of the Kotler and Clarke definition of marketing orientation remained relatively stable, with slightly lower scores related to customer philosophy. In addition, we evaluated the degree to which selected managed care activities are carried out as part of its marketing function. A significant (p < .05) decrease in managed care processes coordinated with the formal marketing function was evident from 1993 to 1999. With increasing numbers of managed care plan enrollees, hospitals are likely focusing on organizational buyers as important customers. In order to appeal to organizational buyers, hospital executives may be focusing more on clinical quality and cost efficiency in the production of services, which will improve a hospital's position with organizational buyers.

Contract Services↗

PubMed2004

Detecting item bias with the Rasch model.

The purpose of this article is to introduce the concept of item bias, highlighting the differences between the definition of the term as it is used within Rasch measurement and the definition of the term as it is used in the true-score model, non-model based approaches, or multi-item parameter latent trait models. The discussion continues with a description of alternative methods of assessing item bias within the Rasch measurement framework and discusses the power of these methods to detect the presence of item bias. The discussion concludes with several examples drawn from a number of different mathematics tests. This includes a comparison of the Rasch separate calibration t-test and the Mantel-Haenszel approaches.

Aptitude Tests↗

PubMed1991

[Treatment of cervix cancer in Denmark].

The current status of cervical cancer treatment in Denmark is discussed. Diagnostic aspects and problems of classification are presented briefly supplemented with a comment on new prognostic parameters based on a semiquantitative score system and flow cytometry. Surgery is the treatment of election for the early stages whereas radiotherapy is the treatment of choice in advanced stages. Chemotherapy should only be employed in the framework of clinical trials. It is concluded that centralised treatment should be maintained.

Denmark↗

PubMed1997

[Technical quality of prenatal visits in Senegal].

The objective of this study is to estimate the quality of antenatal care in Senegal. A survey was conducted in 49 health centers near 70 health workers practising antenatal cares for pregnant women. The quality of cares was assessed on 13 essential actions, which were classified in 4 components. The global score of quality and the specific score of each component were calculated and analysed according to the qualification and the duration of time in the work of the health workers, the location and the equipment of the centers. Global quality of prenatal cares was linked with the qualification of agents. The component "screening for risk factors" had low and worse score and "reception of pregnant women" also. These 2 components were not linked with the qualification of agents, contrary to the 2 others, pregnancy and mother health surveillance. The duration of time in service and the equipment had no influence in global and specific scores. The health workers qualification was linked with many components of quality, but a good basic training is not sufficient to provide prenatal care of high quality. It must be define a framework with screening for unfavorable ends of pregnancy.

Adult↗

PubMed2025

Integrating Imaging-Derived Clinical Endotypes with Plasma Proteomics and External Polygenic Risk Scores Enhances Coronary Microvascular Disease Risk Prediction.

Coronary microvascular disease (CMVD) is an underdiagnosed but significant contributor to the burden of ischemic heart disease, characterized by angina and myocardial infarction. The development of risk prediction models such as polygenic risk scores (PRS) for CMVD has been limited by a lack of large-scale genome-wide association studies (GWAS). However, there is significant overlap between CMVD and enrollment criteria for coronary artery disease (CAD) GWAS. In this study, we developed CMVD PRS models by selecting variants identified in a CMVD GWAS and applying weights from an external CAD GWAS, using CMVD-associated loci as proxies for the genetic risk. We integrated plasma proteomics, clinical measures from perfusion PET imaging, and PRS to evaluate their contributions to CMVD risk prediction in comprehensive machine and deep learning models. We then developed a novel unsupervised endotyping framework for CMVD from perfusion PET-derived myocardial blood flow data, revealing distinct patient subgroups beyond traditional case-control definitions. This imaging-based stratification substantially improved classification performance alongside plasma proteomics and PRS, achieving AUROCs between 0.65 and 0.73 per class, significantly outperforming binary classifiers and existing clinical models, highlighting the potential of this stratification approach to enable more precise and personalized diagnosis by capturing the underlying heterogeneity of CMVD. This work represents the first application of imaging-based endotyping and the integration of genetic and proteomic data for CMVD risk prediction, establishing a framework for multimodal modeling in complex diseases.

Cardiovascular Disease↗

PubMed1997

Hydropathic analysis of the non-covalent interactions between molecular subunits of structurally characterized hemoglobins.

The software program, HINT (Hydropathic INTeractions), which characterizes non-polar-non-polar, polar-polar, and non-polar-polar interactions, has been used to examine subunit interface associations involved in the hemoglobin allosteric transition at a residue and atomic level. HINT differs from many other computational programs in that it is based not on a statistical method or a force-field but employs parameters experimentally determined from solvent transfer experiments. The main focus of this study is to compare HINT scores that are based upon experimentally and thermodynamically derived measurements with experimentally determined thermodynamic results. The HINT analysis yields a good first-order approximation of experimentally measured energies for these interactions as determined by free energies of dimer-tetramer assembly for mutant hemoglobins. The results provide a framework for understanding subunit stabilities based upon individual atom interactions and repulsions. HINT, in agreement with previous analyses, indicates that: (1) the alpha1beta1 and alpha2beta2 subunit contacts are stabilized via several polar and many hydrophobic interactions with few repulsive contact areas in both the T (deoxyhemoglobin) and R (oxyhemoglobin) structures; (2) the alpha1alpha2 subunit contacts are primarily stabilized by polar salt bridge linkages in both T and R states; and (3) the alpha1beta2 and alpha2beta1 contacts have both strong positive and negative interactions in both T and R states with few hydrophobic interactions. The HINT scoring methodology provides a quantitative characterization of the major role of the alpha1beta2 and alpha2beta1 interfaces in the T-->R quaternary transition. HINT also confirms the stronger hydrogen bond formation in mutant Hb Rothschild (Trp 37beta-->Arg) with Asp94alpha1 that gives rise to a low-affinity (deoxy) hemoglobin. HINT shows that the stabilization of the alpha1beta2 interface with mutant Hb Ypsilanti (Asp99alpha-->Tyr) produces a high-affinity (oxy) hemoglobin by reducing hydrophobic-polar contacts in the R state. HINT interaction maps also identified specific sites for mutagenesis at the alpha1beta2 interface that can be explored to shift the allosteric equilibrium in either direction. In addition, the HINT program provides useful diagnostic data for checking the quality of refined crystallographic structures.

Crystallography, X-Ray↗

PubMed2006

QPath: a method for querying pathways in a protein-protein interaction network.

BACKGROUND: Sequence comparison is one of the most prominent tools in biological research, and is instrumental in studying gene function and evolution. The rapid development of high-throughput technologies for measuring protein interactions calls for extending this fundamental operation to the level of pathways in protein networks. RESULTS: We present a comprehensive framework for protein network searches using pathway queries. Given a linear query pathway and a network of interest, our algorithm, QPath, efficiently searches the network for homologous pathways, allowing both insertions and deletions of proteins in the identified pathways. Matched pathways are automatically scored according to their variation from the query pathway in terms of the protein insertions and deletions they employ, the sequence similarity of their constituent proteins to the query proteins, and the reliability of their constituent interactions. We applied QPath to systematically infer protein pathways in fly using an extensive collection of 271 putative pathways from yeast. QPath identified 69 conserved pathways whose members were both functionally enriched and coherently expressed. The resulting pathways tended to preserve the function of the original query pathways, allowing us to derive a first annotated map of conserved protein pathways in fly. CONCLUSION: Pathway homology searches using QPath provide a powerful approach for identifying biologically significant pathways and inferring their function. The growing amounts of protein interactions in public databases underscore the importance of our network querying framework for mining protein network data.

Algorithms↗

PubMedDate not supplied

Development and validation of a derived measure of research utilization by nurses.

BACKGROUND: Theoretical models are needed to guide strategies for the implementation of research into clinical practice. To develop and test such models, including analyses of complex theoretical constructs and causal relationships, rich datasets are needed. Working with existing datasets may mean that important variables are lacking. OBJECTIVE: The aim of this study was to derive a nursing research utilization variable and validate it using the Promoting Action on Research Implementation in Health Services (PARIHS) conceptual framework on research implementation. METHODS: This study was based on data from two surveys of registered nurses. The first survey (1996; N = 600) contained robust research utilization variables but few organizational variables. The second (1998; N = 6,526) was rich in organizational variables but contained no research utilization variables. A linear regression model with predictors common to both datasets was used to derive a research utilization variable in the 1998 dataset. To validate these scores, four separate procedures based on the hypothesis of a positive relationship between context and research utilization were completed. Mutually exclusive groups reflecting various levels of context were created to accomplish these procedures. RESULTS: The derived research utilization variable was successfully mapped onto the cases in the 1998 dataset. The derived scores ranged from 0.21 to 21.40, with a mean of 10.85 (SD = 3.23). The mean score per subgroup ranged from 8.28 for the lowest context group to 12.75 for the highest context group. One of the validation procedures showed that significant differences in mean research utilization existed only among four conceptually unique context groups (p < .001). These groups showed a positive incremental relationship in research utilization (p < .001; the better the context, the higher the research utilization score). The validity of the derived variable was supported by using the three remaining validation procedures. DISCUSSION: The successful creation and validation of a derived research utilization variable will enable advanced modeling of the relationships between research utilization and individual and organizational characteristics. The findings also support the construct validity of the context element of the PARIHS theoretical framework.

Adult↗

PubMed2006

Liver histopathology in Baltic flounder (Platichthys flesus) as indicator of biological effects of contaminants.

Results are presented of a study on liver histopathology in Baltic flounder (Platichthys flesus) carried out in 2001 and 2002 in four coastal sampling areas of the Baltic Sea: Kvädöfjärden (Swedish east coast, reference area), Klaipeda-Butinge (Lithuanian coast), Gulf of Gdansk (Polish coast), and Wismar Bay (German coast) within the framework of the EU-funded BEEP project. Liver lesions were diagnosed and categorised using standardised methodologies and, for a spatial and temporal assessment of the prevalence and types of lesions detected, a scoring system was applied, involving the calculation of mean histopathology lesion scores. 83.0% of the 436 female flounder examined (size range: 20-43 cm total length, age range: 2-8 years) were affected by liver lesions, out of which 74.3% were assigned to the category of non-specific, 3.4% to the category of early toxicopathic non-neoplastic, 4.6% to the category of pre-neoplastic and 0.7% to the category of neoplastic lesions. Mean lesions scores were highest in the areas at the Lithuanian and Swedish coast and there is indication of an impact of the age structure of the flounder populations studied, the sampling season as well as of contaminant effects.

Age Factors↗

PubMed2005

Use of human germline genes in a CDR homology-based approach to antibody humanization.

We report a new method of humanizing antibodies by complementarity determining region (CDR) grafting. Our method differs from others in that we choose human framework sequences from the set of human germline genes based on the structural similarity of the human CDRs to those of the mouse antibody to be humanized. The structural similarity is evaluated by scoring residue-to-residue homology of the mouse CDRs to human candidates with the same Chothia canonical structures. The method is illustrated with the humanization of the anti-lysozyme antibody D1.3.

Amino Acid Sequence↗

PubMed2001

Quality of life and health-risk behaviors among adolescents.

PURPOSE: To assess the association between health-risk behaviors and self-perceived quality of life among adolescents METHODS: A sample of 2801 students (957 seventh and eighth graders and 1844 ninth through twelfth graders) completed the Teen Assessment Survey (TAP) and the surveillance module of the Youth Quality of Life Instrument (YQOL-S). TAP responses were used to determine health-risks related to tobacco use, alcohol use, illicit drug use, and high risk sexual behavior. Separate multivariate analyses of variance showed mean differences in contextual and perceptual items of the YQOL-S for each health-risk behavior. Differences among engagers (adolescents who often engage), experimenters (occasionally engage), and abstainers (never engage) in the health-risk behavior were evaluated by gender and junior/senior high school groups. RESULTS: In general, adolescent abstainers reported higher quality of life (QoL) than engagers and experimenters on YQOL-S items. Adolescents who engaged in multiple risk behaviors scored even lower than those who engaged in only one health-risk behavior. Experimenters tended to rate their QoL more similar to that of abstainers than to that of engagers. CONCLUSIONS: The framework of QoL proved useful in the evaluation of adolescents' engagement in health-risk behaviors. Additionally, assessing the areas of QoL that differ between the groups may provide information for planning interventions aimed at risk reduction among engagers and experimenters.

Adolescent↗

PubMed1998

The family impact of childhood atopic dermatitis: the Dermatitis Family Impact Questionnaire.

Little information is available about the effect of childhood atopic dermatitis (AD) on family function. The aim of this study was to identify the areas of family life most affected and their perceived importance. Intensive qualitative interviews with 34 families were conducted and 11 basic problem areas were identified. A detailed questionnaire was prepared, part of which addressed the perceived importance of particular issues using the framework of multi-attribute utility theory. The results from using this questionnaire in 41 families were analysed and a shorter 10-question one-page Dermatitis Family Impact (DFI) questionnaire designed (maximum score = 30). In affected families the mean DFI score was 9.6 +/- 7.0 (range 0-27, n = 56) and in unaffected families the mean score was 0.4 +/- 0.9 (range 0-3, n = 26, P < 0.0001). The DFI could potentially be used as an extra measure in clinical studies, or to help guide appropriate management of AD.

Adolescent↗

PubMed1998

The prevalence of diagnoses, impairments, disabilities and handicaps in a population of elderly people living in a defined geographical area: the Gospel Oak project.

OBJECTIVE: to measure the prevalence of impairments, disabilities and handicaps in a geographically-defined elderly population. DESIGN: cross-sectional analysis of an interview survey. SETTING: a single North London electoral ward (district). PARTICIPANTS: 654 residents (74%) over the age of 65 years were interviewed from a register of 889. A random sample of 225 had additional data collected which are reported in this analysis. MAIN OUTCOME MEASURES: point prevalence and distribution of the total number of reported diagnoses, impairments and disabilities, and distributions of the Office of Population Censuses and Surveys (OPCS) disability scale and the London Handicap Scale scores. RESULTS: participants had a median of three reported diagnoses and two impairments. Forty-three percent were in the least disabled OPCS disability category (i.e. below the disability threshold) and 41% were able to undertake all of 12 basic activities of daily living without difficulty. Overall handicap scores were heavily skewed towards no health-related disadvantage, with a median score of 83 out of 100, and 37% having a score of 90 or more. All indicators showed deteriorating health with increasing age, but age-adjusted gender differences were small. CONCLUSIONS: an elderly population's health problems were classified using a comprehensive framework, revealing high prevalences of diagnoses, impairments, disabilities and handicaps. The schema is appropriate for health care needs assessment and is a suitable basis for describing the population's health.

Aged↗

PubMed2026

A token-pruning framework enables efficient representation of the human genome for RNA modification analysis.

MOTIVATION: Modelling long genomic sequences remains challenging due to extreme sequence length, high redundancy, and the need for biological interpretability. Although Transformer-based architectures have achieved strong performance across genomic tasks, their high computational cost and reliance on fixed tokenization strategies limit their scalability and ability to focus on biologically informative regions. RESULTS: We propose ATSFormer, a token-pruning Transformer framework for efficient and biologically informed genomic sequence modelling. ATSFormer incorporates an attention-guided and parameter-free Adaptive Token Sampling (ATS) module into Transformer layers. Guided by attention-derived importance scores, ATS dynamically retains informative tokens while probabilistically discarding redundant ones, thereby reducing sequence length, FLOPs, and memory usage without introducing additional learnable parameters or extra training procedures. Importantly, the retained tokens correspond to key contributors to model predictions, enabling ATSFormer to highlight biologically meaningful sites and sequence motifs. We evaluated ATSFormer on four benchmark RNA modification datasets derived from RMVar 2.0, covering A-to-I, m1A, m5C, and m7G. Experimental results show that ATSFormer consistently outperforms existing state-of-the-art methods while achieving substantial computational savings. Furthermore, structural analysis using AlphaFold3 supports the biological relevance of the motifs identified by ATSFormer. AVAILABILITY AND IMPLEMENTATION: The source data and code are freely available at GitHub (https://github.com/1gao2/ATSFormer) and Zenodo (https://doi.org/10.5281/zenodo.21813541).

Humans↗

PubMed2005

FLOSS: flexible ordered subset analysis for linkage mapping of complex traits.

The FLOSS software package is a flexible framework for ordered subset analysis. FLOSS is specifically designed for use with the Merlin linkage analysis package, but FLOSS can be used with any linkage analysis software package that reports NPL Z-scores for each locus and family. When FLOSS is used with the Merlin linkage analysis package, one can use either non-parametric Z-scores or Kong and Cox linear allele sharing model LOD scores. Monte Carlo P-values are calculated using a permutation test with an efficient Besag-Clifford sequential stopping rule. FLOSS also has a flexible tool for assigning family covariate scores from Merlin input files. FLOSS includes user documentation and is written in Java for easy portability. The FLOSS source code is documented and designed to be extensible.

Algorithms↗

PubMed1984

Assessing disablement status in multiple sclerosis.

This paper is based on a critique of selected aspects of previous experience in assessing disablement status in people suffering from multiple sclerosis. It considers the influence of purpose on the approach to assessment by contrasting clinical assessments carried out for individual care with those where it is intended to pool experience for wider application. The nature of assessment is then discussed, and technical considerations such as correlation, scoring, statistical tests, and distributional characteristics. Previous work on MS is then set alongside the approach followed in the World Health Organization's International Classification of Impairments, Disabilities, and Handicaps. A comprehensive conceptual framework is discussed, and the terminology appropriate to this area. An important challenge concerns the scope of assessments, which dimensions should be taken into account. Aspects of importance in application of the WHO scheme are also noted.

Activities of Daily Living↗