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A radiation hybrid map of 506 STS markers spanning human chromosome 11.

We present a high resolution radiation hybrid map of human chromosome 11 using 506 sequence tagged sites (STSs) scored on a panel of 86 radiation hybrids. The 506 STSs fall into 299 unique positions (average resolution of about 480 kilobases (kb)) that span the whole chromosome. A subset of 260 STSs (143 positions) form a framework map that has a resolution of approximately 1 megabase between adjacent positions and is ordered with odds of at least 1,000:1. The centromere was clearly defined with pericentric markers unambiguously assigned to the short or long arm. The map contains most genes (125) and expressed sequence tags (26) currently assigned to chromosome 11 and more than half of the STSs are polymorphic microsatellite loci. These markers and the map can be used for high resolution physical and genetic mapping.

Animals↗

University students' learning approaches in three cultures: an investigation of Biggs's 3P model.

The relationship of various learning approaches to students' academic achievement, abilities, and other characteristics was examined in a sample of university students in Hong Kong, mainland China, and the United States. The theoretical framework for this project was J. B. Biggs's (1987) theory of student learning approaches. The participants completed the Study Process Questionnaire (based on Biggs's theory) and provided a variety of demographic information. The participants' achievement scores and self-rated scores on analytical, creative, and practical abilities were also obtained. Results indicated that scores on certain subscales of the Study Process Questionnaire statistically predicted participants' achievement beyond their self-rated abilities. In addition, certain learning approaches were significantly related to the participants' ages, gender, parents' education levels, and their travel and work experiences. Implications of these findings are discussed as they relate to teaching and learning.

Achievement↗

A simple implementation of a normal mixture approach to differential gene expression in multiclass microarrays.

MOTIVATION: An important problem in microarray experiments is the detection of genes that are differentially expressed in a given number of classes. We provide a straightforward and easily implemented method for estimating the posterior probability that an individual gene is null. The problem can be expressed in a two-component mixture framework, using an empirical Bayes approach. Current methods of implementing this approach either have some limitations due to the minimal assumptions made or with more specific assumptions are computationally intensive. RESULTS: By converting to a z-score the value of the test statistic used to test the significance of each gene, we propose a simple two-component normal mixture that models adequately the distribution of this score. The usefulness of our approach is demonstrated on three real datasets.

Algorithms↗

Alternative strategies for creating "relational" family data.

A major problem facing family clinicians and researchers is creating data that will reflect the family as a unit. To address this problem, we present a framework for family assessment based on three measurement strategies: individual family member assessment, relational family assessment, and transactional family assessment. Within this context, we present several categories of methods for combining individual family member data into "relational" scores that reflect the couple or family as a unit. The problems and benefits of each method are presented, and it is suggested that the choice of method is dependent upon the content of the assessment, the theory underlying the content, and the statistical properties of the individual family member scores.

Data Collection↗

A pan-cancer single-cell atlas uncovers the role of sex hormones and chromosomes in sex-divergent reprogramming of the tumor microenvironment.

BACKGROUND: Sex bias is pervasive in tumors; however, how sex chromosomes and hormone-responsive signaling shape the tumor microenvironment (TME) remains insufficiently characterized. Considering the critical impact of the TME on tumor progression and response to immunotherapy, a pan-cancer investigation of sex-specific and cancer-context-dependent TME features is warranted. METHOD: Based on stringent inclusion criteria, we constructed a high-resolution pan-cancer single-cell sequencing atlas by integrating 31 publicly available single-cell RNA-seq datasets, comprising a total of 1,831,436 cells by integrating 468 samples from eight types of non-sex-specific solid tumors (282 males and 186 females). After correcting for batch effects, we identified major and minor cellular subsets. Multiple computational approaches were applied to investigate sex-associated differences in cellular composition, gene expression, pathway activity, malignant cell states and intercellular communication. RESULTS: We systematically compared sex-specific TME features across eight common solid malignancies. Male-biased CD8+ T cell exhaustion emerged as a recurrent but non-uniform feature, with its magnitude varying across cancer types and being modified by tissue-specific contexts. This pattern was associated with androgen-response signature scores and expression-based loss of the Y chromosome (LOY) scores. M2-like macrophage polarization showed a more cancer-type-dependent pattern; although female-biased enrichment was observed in selected malignancies, it did not represent a uniform pan-cancer feature. Expression-based X chromosome inactivation (XCI)/XCI escape-related programs, estrogen-response signature scores and stromal components, including fibroblasts and endothelial cells, were associated with macrophage and immune-regulatory states in specific tumor contexts. Tumor cells of male origin displayed higher genomic instability and more aggressive phenotypes, with androgen-response signatures and LOY contributing to the development of a male biased malignant state. Furthermore, expression-based LOY scores in malignant cells were associated with CD8+ T cell exhaustion based on transcriptomic proxies. CONCLUSION: Our study uncovers extensive but heterogeneous sex-specific differences in the TME across multiple cancer types. We propose a regulatory framework linking sex chromosomes, hormone-responsive signaling and TME interactions, which is consistent with recurrent male-biased CD8⁺ T cell exhaustion and context-dependent M2-like macrophage polarization. Importantly, the magnitude and, in some cancers, the direction of these sex-biased features are modified by tissue-specific contexts. These findings underscore the need to include sex chromosome and hormone status as essential biological variables in studies of the tumor microenvironment and the design of immunotherapies.

Tumor Microenvironment↗

A reproducible computational transcriptomic framework for cell-type-resolved fibroinflammatory-AKT remodeling in human heart failure.

BACKGROUND: Human heart failure involves multicellular transcriptional remodeling, but public transcriptomic studies often remain disconnected from cell-type localization and perturbational interpretation. METHODS: We developed a reproducible computational workflow integrating human left-ventricular bulk transcriptomes, donor-level cell-type pseudobulk results from a human heart-failure single-cell/single-nucleus atlas, external snRNA-seq support, curated module scoring, focused ligand-receptor prioritization and LINCS/L1000 perturbational matching. RESULTS: Cross-cohort analysis identified 14,358 same-direction HF-associated genes, including 1633 replicated HF-up and 785 replicated HF-down genes. Donor-level pseudobulk analysis localized disease remodeling to cardiomyocyte, fibroblast and myeloid compartments. Activated fibroblast and inflammatory myeloid programs defined a fibroinflammatory remodeling axis connected to context-dependent AKT-associated transcriptional shifts. External snRNA-seq support was strongest for fibroblast activation and AKT-associated remodeling, with etiology-dependent heterogeneity across validation resources. L1000FWD screening prioritized safety-aware perturbational hypotheses, including glimepiride and simvastatin as interpretable candidates requiring experimental validation. CONCLUSIONS: This study provides a computational transcriptomic framework linking reproducible human HF signatures, cell-type-resolved fibroinflammatory remodeling and perturbational genomic prioritization without claiming drug efficacy or AKT causality.

Humans↗

The development of the Louis MACRO (Mother and Child Risk Observation) forms: assessing parent-infant-child risk in the presence of maternal mental illness.

OBJECTIVE: The theoretical framework and psychometric properties of the MACRO (Mother and Child Risk Observation) 1 and 2 forms (age 0 to 4 year) are presented. The MACRO forms provide ratings on five domains--three related to parenting, two on infant (or child) characteristics and maternal mental state. Case vignettes illustrate their clinical utility. METHOD: Ratings on the MACRO of 110 mother-infant and 85 mother-toddler consecutive admissions to a South Australian psychiatric in-patient mother-infant unit provided data on internal consistency, interrater, and test-retest reliability. RESULTS: Internal consistency was between .79 and .95 for all MACRO domains. Item-total correlations were between .39 and .90 with the exception of one item. Social Support. Distributions of item scores indicated acceptable discrimination. Interrater reliability was .79 or above for all domains. Test-retest reliability after 7 days was .71 or above. CONCLUSIONS: Preliminary psychometric investigations of the MACRO was favorable. Should further validity investigations prove satisfactory, the MACRO will provide a valuable clinical and research tool. The MACRO offers a convenient framework for assessing risk and interpreting the impact of maternal mental illness upon children within a context that permits consideration of factors such as illness severity, parenting practices, and child contribution to outcome.

Adolescent↗

Clinical evaluation of fiber-reinforced composite inlay FPDs.

PURPOSE: This clinical study evaluated the behavior of inlay fixed partial dentures (IFPD) with conventional and modified framework designs over a period of 12 to 48 months. MATERIALS AND METHODS: Forty-one glass fiber-reinforced composite IFPDs were made to replace one missing maxillary or mandibular tooth. The frameworks were made only with parallel fibers in 19 restorations (group 1) and built with parallel and woven fibers modifying the design of the pontic element in 22 IFPDs (group 2) according to the manufacturer's instructions. All restorations were evaluated by color match, marginal discoloration, secondary caries, surface texture, marginal adaptation, fracture, and postoperative sensitivity. RESULTS: Three partial adhesive-cohesive veneering composite fractures occurred in the pontic element in group 1 after 3, 4, and 8 months, respectively. One cohesive fracture occurred in an abutment in group 2 after 46 months. Group 1 showed a 16% fracture failure rate; group 2 showed a 5% failure rate. However, no statistical difference was detected between the groups. IFPDs received the highest score at the following rates: color match 71%, marginal discoloration 96%, secondary caries 99%, surface texture 88%, marginal adaptation 98%, fracture 90%, and postoperative sensitivity 100%. Statistical analysis indicated significant deterioration of color match from baseline to last recall. CONCLUSION: There were nonsignificantly fewer fractures of the veneering composite with the modified design of the framework than with the conventional design. Repair of the fractured veneer of IFPDs may lengthen the lifespan of the restorations, but it is advisable only for slight damage.

Adolescent↗

Patterns of attractor dimensions of sleep EEG.

Low dimensional chaos is a property of many physiological oscillatory systems including the brain. Time series of sleep EEG records have been analyzed in the framework of recent developments in nonlinear dynamics. One of the characteristics of a chaotic time series is its attractor dimension. The running attractor dimension of a chaotic time series may reflect changes in states more accurately than manually scored records. In the present study the attractor dimensions of consecutive EEG segments of five sleep records were analyzed. The block of the EEG segment (window) was shifted by various lengths along the entire sleep data of each subject thus producing a running attractor dimension curve for each record. The attractor dimension values for different sleep stages were significantly different. The pattern of the running attractor dimension closely matched the scored hypnograms in these five sleep records.

Adolescent↗

Air pollution and climate gradients in western Oregon and Washington indicated by epiphytic macrolichens.

Human activity is changing air quality and climate in the US Pacific Northwest. In a first application of non-metric multidimensional scaling to a large-scale, framework dataset, we modeled lichen community response to air quality and climate gradients at 1416 forested 0.4 ha plots. Model development balanced polluted plots across elevation, forest type and precipitation ranges to isolate pollution response. Air and climate scores were fitted for remaining plots, classed by lichen bioeffects, and mapped. Projected 2040 temperatures would create climate zones with no current analogue. Worst air scores occurred in urban-industrial and agricultural valleys and represented 24% of the landscape. They were correlated with: absence of sensitive lichens, enhancement of nitrophilous lichens, mean wet deposition of ammonium >0.06 mg l(-1), lichen nitrogen and sulfur concentrations >0.6% and 0.07%, and SO(2) levels harmful to sensitive lichens. The model can detect changes in air quality and climate by scoring re-measurements.

Air Pollution↗

Environmental performance policy indicators for the public sector: the case of the defence sector.

The development of environmental performance policy indicators for public services, and in particular for the defence sector, is an emerging issue. Despite a number of recent initiatives there has been little work done in this area, since the other sectors usually focused on are agriculture, transport, industry, tourism and energy. This type of tool can be an important component for environmental performance evaluation at policy level, when integrated in the general performance assessment system of public missions and activities. The main objective of this research was to develop environmental performance policy indicators for the public sector, specifically applied to the defence sector. Previous research included an assessment of the environmental profile, through the evaluation of how environmental management practices have been adopted in this sector and an assessment of environmental aspects and impacts. This paper builds upon that previous research, developing an indicator framework--SEPI--supported by the selection and construction of environmental performance indicators. Another aim is to discuss how the current environmental indicator framework can be integrated into overall performance management. The Portuguese defence sector is presented and the usefulness of this methodology demonstrated. Feasibility and relevancy criteria are applied to evaluate the set of indicators proposed, allowing indicators to be scored and indicators for the policy level to be obtained.

Conservation of Natural Resources↗

Conceptualizing oral health and oral health-related quality of life.

This investigation considers oral health from a health-related quality of life perspective using a multidimensional concept representing a combination of impairment, function, perceptions, and/or opportunity. A subset of dentate individuals aged 18 and older from a national probability sample of the U.S. was selected for the reported analysis with data available from personal interviews, self-administered questionnaires, and oral examinations. Impairment was represented by clinically assessed active diseases and sequelae of diseases and self-reported acute symptoms. Other domains are represented by self-reported problems with function, perception of control over oral health, satisfaction with teeth, value attributed to oral health, and opportunity to obtain dental care. Principal components analysis with varimax rotation provided a structure to interpret four factors: accumulated oral neglect, self-perceived symptoms and problems, reparable oral diseases, and oral health values and priorities. Approximately 50% of the variance was explained by these four factors. Factor-based scores, envisioned as an index or summary measure representing the combination of variables identified in each factor, were used to assess potential validity. Whites had lower levels of accumulated oral neglect, fewer symptoms, and less reparable oral disease, but similar oral health values, than non-whites. Level of formal education was associated with each of the four factor-based scores. Age was directly associated with accumulated oral neglect, but the youngest age group had significantly more reparable oral diseases. Individuals with a dental visit in the past two years had considerably less accumulated oral neglect, fewer self-perceived problems, less reparable oral disease, and higher values of oral health than those without a dental visit in the past two years. Ordinary least square regressions were performed on each of the four factor-based scores using eight sociodemographic and economic variables. All four regression models were significant, with only the education variable being significant across all models. These analyses provide no evidence for one unique factor representing oral health. Rather, a conceptual framework for oral health appears to be represented by a set of reasonably independent components, including two groups of clinically assessed oral health, which together more fully represent oral health than any one single variable. Conceptualizing and measuring oral health multidimensionally leads us closer to examining it as part of general health.

Adolescent↗

Effectiveness of an intervention to increase Pap test screening among Chinese women in Taiwan.

This study assessed the effectiveness of a theory-based direct mail campaign in encouraging non-compliant women, aged 30 and older or younger if married, to obtain a Pap test. Participants were female family members of inpatients admitted to one of the major teaching hospitals in Taiwan during August-September 1999. A total of 424 women were recruited in the randomized intervention trial. Three months following implementation of the intervention, women in the intervention group reported a higher rate of Pap test screening than women in the comparison group (50% versus 32%) (p = 0.002). Women in the intervention group also showed higher perceived pros of a Pap test at follow-up (p = 0.031). Although women in both groups showed an increased knowledge and intention to obtain a Pap, only the intervention group had significantly higher follow-up scores on perceived pros and susceptibility. The results shows that the intervention was effective in increasing Pap test screening among Chinese women within three months. The results also support the use of Intervention Mapping, a systematic program development framework for planning effective interventions.

Adult↗

Measuring the intensity of pregnancy planning effort.

This study validated a measure of pregnancy planning effort based on Miller's conceptual framework in two clinical settings. The questionnaire's main items deal with general behaviour with regard to pregnancy, timing and proception (proception being the reverse of contraception). Values for these three items are added to yield a continuous score ranging from 0 to 12. The study population comprised 448 women of different cultural backgrounds recruited in prenatal, fertility and family planning clinics in Quebec and North Carolina. The results indicate that the internal consistency between the three items pertaining to pregnancy planning was excellent (Cronbach's alpha of 0.83). Test-retest reliability after a 4-week interval was excellent, with an intraclass correlation coefficient of 0.86 for the planning score. The planning score median for women attending family planning clinics (1.00) was significantly lower than that for those recruited in fertility clinics (11.00), confirming the discriminant ability of the instrument. Path analysis shows that the conceptual model corroborates the observed data and explains 53% of the pregnancy planning variability. In conclusion, this is the first questionnaire specifically designed to assess the intensity of pregnancy planning effort, a potentially important variable in epidemiological studies and clinical practice.

Family Planning Services↗

Comparison of two questionnaires with a tri-axial accelerometer to assess physical activity patterns.

Two physical activity questionnaires were evaluated against cardiorespiratory fitness (VO2 peak), and a tri-axial accelerometer for movement registration (Tracmor) in 166 men, aged 40 years, within the framework of the Leuven Longitudinal Study on Lifestyle, Fitness, and Health. Tracmor data were obtained during four successive days. Besides the work index, the sport index, and the total activity index from the Baecke questionnaire, the subjective activity score, calculated energy expenditure during work, work index, and the total activity index from the Tecumseh Community questionnaire showed significant correlation coefficients with the mean Tracmor output (r = 0.26-0.47, p < 0.01). The questionnaire submeasures and the Tracmor output as generated in the same physical activity dimension showed the same relationships (r = 0.22-0.50, p < 0.01). Multiple stepwise regression and stepwise discriminant analyses showed the Baecke questionnaire as the best indicator of the subject's physical activity level. Extra information about the physical activity level was given by two Tecumseh submeasures, e.g. energy expenditure during work and sleeping time. The results indicated that the Baecke questionnaire is superior in large-scale studies because of simplicity. However, the Tecumseh questionnaire can give detailed information about physical activity patterns and energy expenditure.

Activities of Daily Living↗

The physiopathological bases of recovery processes: the bases of stroke rehabilitation. The CASSINO project. Computer Assisted Somatosensory Stimulation Inducing New Organizations.

Post-stroke recovery was monitored with electrophysiological means. Twenty stroke patients were enrolled in a discrimination task using an oddball paradigm for somatosensory event related potentials. The disability was evaluated, both at time of admission and at discharge. During training event related potentials (ERPs) took place as a positive-negative complex between 105 and 160 ms. They were recorded all over the scalp, but the amplitude was lower on the affected hemisphere. The interval had a prognostic value, since short intervals were correlated with high Functional Independence Measure (FIM) score at dismission. Motor biofeedback was also used. The patients treated with the learning procedure had a better FIM recovery than a control group. In stroke patients, ERPs can be used both as an active tool in the framework of cortical remodeling following learning procedures as well as a monitoring tool of rehabilitation programs. Nowadays, stroke rehabilitation exploits neurobiological data.

Aged↗

Work outcomes for female liver transplant recipients with alcohol-related liver disease.

The purpose of this retrospective survey was to describe post-liver transplant work outcomes for female liver transplant recipients with histories of alcohol-related liver disease. The theoretical framework guiding the study was Laffrey's conception of health. The Short Michigan Alcohol Screening Test was used to measure alcohol-related liver disease. Forty-seven female liver transplant recipients whose Short Michigan Alcohol Screening Test scores were indicative of alcohol-related liver disease comprised the convenience sample. Using a mailed questionnaire, post-transplant work and daily activities were assessed. Work was operationally defined as including either employment or household work. Results revealed that 59% of the female recipients were working post-transplant and that working recipients had higher conception of health scores than did non-working recipients.

Adult↗

An alternative foundation for the planning and evaluation of linkage analysis. I. Decoupling "error probabilities" from "measures of evidence".

The lod score, which is based on the likelihood ratio (LR), is central to linkage analysis. Users interpret lods by translating them into standard statistical concepts such as p values, alpha levels and power. An alternative statistical paradigm, the Evidential Framework, in contrast, works directly with the LR. A key feature of this paradigm is that it decouples error probabilities from measures of evidence. We describe the philosophy behind and the operating characteristics of this paradigm--based on new, alternatively-defined error probabilities. We then apply this approach to linkage studies of a genetic trait for: I. fully informative gametes, II. double backcross sibling pairs, and III. nuclear families. We consider complete and incomplete penetrance for the disease model, as well as using an incorrect penetrance. We calculate the error probabilities (exactly for situations I and II, via simulation for III), over a range of recombination fractions, sample sizes, and linkage criteria. We show how to choose linkage criteria and plan linkage studies, such that the probabilities of being misled by the data (i.e. concluding either that there is strong evidence favouring linkage when there is no linkage, or that there is strong evidence against linkage when there is linkage) are low, and the probability of observing strong evidence in favour of the truth is high. We lay the groundwork for applying this paradigm in genetic studies and for understanding its implications for multiple tests.

Computer Simulation↗