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PubMed1989

Reminiscence and strategies of performance in rotary pursuit tracking.

The maximum speed at which man detects and corrects errors is analyzed on the pursuit rotor. During the prerest performance, scores of about 220 msec. are found, for both extravertive and introvertive subjects. During the postrest performance a crossover effect appeared: extraverts had scores near 60 msec., while introverts did not surpass 100 msec. The results are discussed in the framework of Eysenck and Frith's (1977) theory of reminiscence.

Arousal↗

PubMed2006

Improvement of oral health knowledge in a group of visually impaired students.

PURPOSE: The aim of this study was to evaluate the effectiveness of a repeated oral health education programme on oral health knowledge and hygiene of visually impaired students. MATERIALS AND METHODS: The study was conducted at one of the two visually impaired boarding schools of Istanbul, Turkey. The number of subjects was 65, comprising 28 totally and 37 partially visually impaired students between 7 and 17 years of age. A 24-item verbal questionnaire was developed to record their general health, impairment, the socio-economic profile and education level of their parents, oral health knowledge, sources of information about oral health, awareness of sugar in-take/caries risk, frequency of dental check-ups and oral hygiene habits, as well as any difficulties they experienced thereby. They were given individual training on oral care three times with two-month intervals within the nine-month framework of the programme. To measure the oral hygiene status, plaque index (PI) and gingival index (GI) scores were recorded of all teeth at four sites throughout the sessions. After completion of the programme, the oral health knowledge of the students was evaluated using the same questionnaire to determine the effectiveness of the programme. RESULTS: Statistically significant improvements were found at the level of oral health knowledge and oral hygiene status both in totally and partially visually impaired students at the end of the study (p < 0.001) as compared with at the beginning. No significant difference was found between the knowledge of totally visually impaired and partially visually impaired students. CONCLUSION: It was concluded that with an appropriate programme, the oral health knowledge of visually impaired students could be improved. This programme, if conducted on a one-to-one basis, ensures clinical and statistical significance.

Adolescent↗

PubMed1989

[Epidemiologic recording of bronchial asthma in the school child].

Bronchial asthma is the most frequent chronic disease in childhood. Nevertheless, no definition of the disease is known that would enable a satisfactory epidemiological recording of asthma. In 704 schoolchildren, typical signs and symptoms of asthma were recorded within the framework of a standardized interview. The occurrence of asthmatic symptoms was quantified by means of a symptom score. In 555 of the probands, bronchial reactivity was tested by means of an inhalative challenge with carbachol. The information gathered from the interview and the carbachol challenge test was placed in relationship to the family doctor's diagnosis of "bronchial asthma". Lifetime prevalence of asthma diagnosed by the family doctors is 4.97% with a clear male predominance. The asthmatic symptoms showed varying frequencies and validity compared with the family doctor's diagnosis. The occurrence of dyspnoea appears to be particularly sensitive (77%). Dyspnoea coincident with exercise is highly specific (99%). The sensitivity of the combination of carbachol test and symptom score is 92% and the specificity is 75%. The instruments described above offer a reliable possibility for epidemiological field research to record the prevalence of bronchial asthma in schoolchildren.

Adolescent↗

PubMed2003

A clinical ladder program based on Carper's Fundamental Patterns of Knowing in Nursing.

Clinical and career ladder programs were popular adjuncts to recruitment and retention during the nursing shortage of the 1980s. Programs commonly used Benner's work as an organizing framework and typically used activities such as continuing education credit, committee participation, work experience, certifications, academic degrees, community service, and performance appraisal scores as criteria for advancement. The authors present a unique clinical ladder program based on Carper's Fundamental Patterns of Knowing in Nursing. This philosophical work has been debated in the literature for many years, yet to the authors' knowledge, this work has never been used as the conceptual basis for program development. The four patterns of knowing in nursing were found to be consistent with the definition of professional nursing, and provided a meaningful organizing framework that was well received by staff registered nurses. An overall history of clinical ladders is presented, followed by the organization's prior experience with these programs, and finally the details of development and implementation of the program with plans for evaluation.

Attitude of Health Personnel↗

PubMed2004

Inferring pathways and networks with a Bayesian framework.

Numerous mathematical methods have been adapted and developed to quantitatively reverse engineer biological networks, for example, signal transduction pathways, from experimental micro-array data. Compared with stochastic methods, such as Boolean networks, and deterministic methods, such as thermodynamic or differential equation-based models, Bayesian network analysis has the ability to assess, with scoring metrics, causal relations based on conditional probabilities and thus permit hypothesis testing. The goal of this paper is to illustrate the integration of several Bayesian based techniques into a unified Bayesian framework that can infer hepatocellular networks from metabolic data. Reverse engineering of pathways and networks provides a framework for predictive modeling and hypotheses testing to gain deeper insight into living organisms, disease mechanisms, and targeted therapeutics. Evaluating this methodology initially against the known biochemical network provides confidence in the networks that are uncovered from the experimental data using this framework. From the metabolic data we inferred the known sub-networks, such as the tricarboxylic acid (TCA) and urea cycles. In addition, we combined the relationships learned from the data and our current knowledge of the biological system to postulate several alternative metabolic sub-network models that can predict a particular cellular function, such as intracellular triglyceride accumulation.

Algorithms↗

PubMed2006

A corrected pseudo-score approach for additive hazards model with longitudinal covariates measured with error.

In medical studies, it is often of interest to characterize the relationship between a time-to-event and covariates, not only time-independent but also time-dependent. Time-dependent covariates are generally measured intermittently and with error. Recent interests focus on the proportional hazards framework, with longitudinal data jointly modeled through a mixed effects model. However, approaches under this framework depend on the normality assumption of the error, and might encounter intractable numerical difficulties in practice. This motivates us to consider an alternative framework, that is, the additive hazards model, about which little research has been done when time-dependent covariates are measured with error. We propose a simple corrected pseudo-score approach for the regression parameters with no assumptions on the distribution of the random effects and the error beyond those for the variance structure of the latter. The estimator has an explicit form and is shown to be consistent and asymptotically normal. We illustrate the method via simulations and by application to data from an HIV clinical trial.

Acquired Immunodeficiency Syndrome↗

PubMed2003

[Work, stress and cardiovascular diseases].

Classical risk factors such as smoking, hypertension or elevated plasma levels of cholesterol account only for part of the variance in the probability of cardiovascular disease. Work related psychosocial factors such as high job demands, low decision latitude or lack of social support often pertain during extended periods. Such work related stressors may modulate biological risk factors (e.g. by increasing the risk of hypertension) or may elicit adverse health behaviour (increased tobacco consumption). Several longitudinal cohort studies indeed support the notion of an association between work related stressors and the risk of cardiovascular disease. However, the exact biological mechanisms conferring this risk remain in part elusive. The general stress model of allostasis and allostatic load may allow studying possible pathways in more detail and within a common conceptual framework. Allostasis refers to the often useful acute stress reaction that prepares the organism for flight or fight threatening situations. Allostatic load summarizes the wear and tear inflicted upon the organism after repeated or dysregulated allostatic efforts. The framework of allostasis and allostatic load permits to investigate the direct effect of work related stressors on the primary stress reaction (reduced vagal tone, increased sympathetic tone and increased activity of the hypothalamic-pituitary-adrenal axis) as well as the effect on biological process, which are regulated by the acute stress reaction. Longitudinal studies have shown an inverse association between a score operationalizing allostatic load by means of 10 biological measures and functional status/mortality. These studies in elderly individuals remain to be replicated using the same framework for working age populations.

Adaptation, Psychological↗

PubMed1998

Robustness and power of the maximum-likelihood-binomial and maximum-likelihood-score methods, in multipoint linkage analysis of affected-sibship data.

The maximum-likelihood-binomial (MLB) method, based on the binomial distribution of parental marker alleles among affected offspring, recently was shown to provide promising results by two-point linkage analysis of affected-sibship data. In this article, we extend the MLB method to multipoint linkage analysis, using the general framework of hidden Markov models. Furthermore, we perform a large simulation study to investigate the robustness and power of the MLB method, compared with those of the maximum-likelihood-score (MLS) method as implemented in MAPMAKER/SIBS, in the multipoint analysis of different affected-sibship samples. Analyses of multiple-affected sibships by means of the MLS were conducted by consideration of all possible sib pairs, with (weighted MLS [MLSw]) or without (unweighted MLS [MLSu]) application of a classic weighting procedure. In simulations under the null hypothesis, the MLB provided very consistent type I errors regardless of the type of family sample (sib pairs or multiple-affected sibships), as did the MLS for samples with sib pairs only. When samples included multiple-affected sibships, the MLSu led to inflation of low type I errors, whereas the MLSw yielded very conservative tests. Power comparisons showed that the MLB generally was more powerful than the MLS, except in recessive models with allele frequencies <.3. Missing parental marker data did not strongly influence type I error and power results in these multipoint analyses. The MLB approach, which in a natural way accounts for multiple-affected sibships and which provides a simple likelihood-ratio test for linkage, is an interesting alternative for multipoint analysis of sibships.

Computer Simulation↗

PubMed2001

A critical review of the scientific literature on potential endocrine-mediated effects in fish and wildlife.

A rigorous approach to evaluating the reliability and relevance of experimental methods and results is critical for making appropriate, scientifically sound decisions. A literature evaluation framework was modified and adapted based on criteria described by Klimisch et al. (H. J. Klimisch, M. Andrae, and U. Tillman, 1997, Reg. Tox. Pharm. 25, 1-5) and requirements of the USEPA High Product Volume Challenge Program. This simple framework was used to evaluate an appropriate selection of peer-reviewed references to assign a Study Reliability "score" to the study design, endpoints, and conclusions compared to established data quality guidelines. Subsequently, the interpretation of the data was evaluated and assigned a Relevance Index based on the overall strength of evidence of endocrine modulation potential, which was evaluated based on the Weybridge (European Commission (1996). European workshop on the impact of endocrine disrupters on human health and wildlife. Report of proceedings from a workshop held in Weybridge, UK, 2-4 December 1996. Report reference EUR 17549, European Commission, DGXII, Brussels, Belgium.) definition. This report describes the evaluation of 50 peer-reviewed primary publications. The vast majority of studies reviewed were published in the period from 1996 to the present and most examined in vivo responses of fish to natural hormones, organochlorines, or alkylphenolic compounds. Of the studies reviewed, approximately 40% received a score of "2-Reliable with Restrictions," while approximately 60% received a score of "3-Not Reliable," where reliability was interpreted to include scientific integrity, technical credibility, endpoint relevance, and regulatory compliance. The most common deficiencies were inadequate methods, lack of suitable controls, exceeding aqueous solubility, inappropriate statistics, and unsupported conclusions. Based on the Relevance Index, few of the studies examined attained the level of quality necessary to identify the study results as providing an acceptable basis for evaluation of endocrine modulation potential directly resulting from identified deficiencies in meeting the established study reliability criteria.

Animals↗

PubMed2003

Somatic mosaicism and cancer: inference based on a conditional Luria-Delbrück distribution.

Somatic mosaicism for mutations in disease-causing genes has been reported in several recent studies. Examples include hemophilia A, many skin disorders, and several cancers such as retinoblastoma and familial adenomatous polyposis. Many of these disorders require multiple mutations in order to express the disease phenotype. For example, two recessive mutations to the retinoblastoma locus are required to initiate retinoblastomal tumors. I develop a mathematical framework for somatic mosaicism in which two recessive mutations cause disease. With my framework, I analyse the following question: Given an observed frequency of cells with two mutations and an easily scored aberrant phenotype, what is the conditional frequency distribution of cells carrying one mutation and therefore susceptible to transformation by a second mutation? This question is important because a high frequency of carrier cells can cause genetic counselors to misdiagnose a mosaic as an inherited heterozygote carrier and because widespread mosaicism can lead to some germline transmission. As more data accumulate, the observed distribution of mosaics can be compared against my predicted distribution. These sorts of studies will contribute to a broader understanding of the distribution of somatic mutations, a central topic in the study of cancer.

Gene Frequency↗

PubMed2002

Emergency Medical Services Outcomes Project (EMSOP) IV: pain measurement in out-of-hospital outcomes research.

The purpose of the Emergency Medical Services Outcomes Project (EMSOP) is to develop a foundation and framework for out-of-hospital outcomes research. In prior work (EMSOP I), discomfort had the highest weighted score among outcome categories for the top 3 adult conditions (ie, minor trauma, respiratory distress, chest pain) and the first and third highest rankings for children's conditions (ie, minor trauma, respiratory distress). In this fourth article in the EMSOP series, we discuss issues relevant to the measurement of pain in the out-of-hospital setting, recommended pain measures that require evaluation, and implications for outcomes research focusing on pain. For adults, adolescents, and older children, 2 verbal pain-rating scales are recommended for out-of-hospital evaluation: (1) the Adjective Response Scale, which includes the responses "none," "slight," "moderate," "severe," and "agonizing," and (2) the Numeric Response Scale, which includes responses from 0 (no pain) to 100 (worst pain imaginable). The Oucher Scale, combining a visual analog scale with pictures, seems most promising for out-of-hospital use among younger children. Future research in out-of-hospital care should be conducted to determine the utility and feasibility of these measures, as well as the effectiveness of interventions for pain relief.

Adult↗

PubMed1999

Interpolated markov chains for eukaryotic promoter recognition.

MOTIVATION: We describe a new content-based approach for the detection of promoter regions of eukaryotic protein encoding genes. Our system is based on three interpolated Markov chains (IMCs) of different order which are trained on coding, non-coding and promoter sequences. It was recently shown that the interpolation of Markov chains leads to stable parameters and improves on the results in microbial gene finding (Salzberg et al., Nucleic Acids Res., 26, 544-548, 1998). Here, we present new methods for an automated estimation of optimal interpolation parameters and show how the IMCs can be applied to detect promoters in contiguous DNA sequences. Our interpolation approach can also be employed to obtain a reliable scoring function for human coding DNA regions, and the trained models can easily be incorporated in the general framework for gene recognition systems. RESULTS: A 5-fold cross-validation evaluation of our IMC approach on a representative sequence set yielded a mean correlation coefficient of 0.84 (promoter versus coding sequences) and 0.53 (promoter versus non-coding sequences). Applied to the task of eukaryotic promoter region identification in genomic DNA sequences, our classifier identifies 50% of the promoter regions in the sequences used in the most recent review and comparison by Fickett and Hatzigeorgiou ( Genome Res., 7, 861-878, 1997), while having a false-positive rate of 1/849 bp.

Algorithms↗

PubMed2003

CREME: a framework for identifying cis-regulatory modules in human-mouse conserved segments.

MOTIVATION: The binding of transcription factors to specific regulatory sequence elements is a primary mechanism for controlling gene transcription. Recent findings suggest a modular organization of binding sites for transcription factors that cooperate in the regulation of genes. In this work we establish a framework for finding recurrent cis-regulatory modules in the promoters of a selected set of genes and scoring their statistical significance. RESULTS: Proceeding from a database of identified binding site motifs and their genomic locations we seek motifs whose frequency in the selected promoters is different than in a background promoter set. We present several statistical tests designed for this purpose. We provide a hashing algorithm for detecting combinations of these motifs that co-occur in clusters within the selected promoters. The significance of such co-occurrences is evaluated using novel statistical scores. Our methods are combined in CREME, a suite of software which includes a browser for viewing the pattern of occurrence of selected cis-regulatory modules. We applied our methodology to find modules within human-mouse conserved promoter segments, focusing on cell cycle regulated genes and stress response related genes. To validate the biological significance of the identified modules we tested whether the associated genes tended to be co-expressed or share similar function. In the cell cycle set five of the seven identified sets of genes were coherently expressed. On the stress response data four of the six detected sets fell predominantly into well-defined functional sub-categories.

Algorithms↗

PubMed2004

Computer-aided multimedia training in orthopedic rehabilitation.

OBJECTIVE: To compare a computer-aided training program with a conventional training program in orthopedic rehabilitation. DESIGN: The study was a randomized, nonblinded, controlled trial in which follow-up data were obtained at 6 mos. In an inpatient rehabilitation center, a consecutive sample was taken of patients with first total hip replacements or first total knee replacements 23-42 days after surgery. Indication groups were examined separately. The study population included 189 women and 85 men. Mean age was 69 yrs (38-86 yrs). Patients received either computer-aided training (case group) or conventional training (control group) within the framework of their inpatient rehabilitation program. The main outcome measures were levels of acceptance and effectiveness (Harris Hip Score, Hospital for Special Surgery Score, FIM instrument, and Hanover Functional Ability Questionnaire). RESULTS: Both forms of training showed significant improvements until discharge in scores and items used for the result evaluation independent of patient sex, age, and educational level. The 6-mo follow-up showed that between the groups, there was no statistically significant difference in the level of improvement concerning functional capacity. Furthermore, patients displayed their acceptance of the system by rating it with average values between "good" and "very good." CONCLUSIONS: For patients with total hip replacements or total knee replacements, computer-aided training can be regarded as the equivalent to conventional training in relationship to the results of the rehabilitation program. The system is a new tool in orthopedic rehabilitation. To identify the relative importance of the system, further research is needed.

Adult↗

PubMed2002

Sociotropy, autonomy, and personality disorder criteria in psychiatric patients.

Sociotropy and autonomy (Beck, 1983) are sets of beliefs, concerns, and behavioral tendencies that are proposed to create vulnerability to depression and other psychopathology and to influence its manifestation and treatment response. Other theoretical frameworks (Blatt, 1974) have made similar suggestions. We investigated the differential relations of sociotropy and autonomy to dimensional scores for each DSM-III-R personality disorder (PD) in a sample of 188 psychiatric patients, controlling for the other set of characteristics and for the other PDs. Histrionic and dependent PD traits were related specifically to sociotropy. Paranoid, schizoid, schizotypal, and passive-aggressive PD traits were related specifically to autonomy. Borderline, narcissistic, avoidant, and self-defeating PD traits were related significantly and about equally to both sociotropy and autonomy. Obsessive-compulsive PD traits were not related consistently to either. Results were mostly as predicted and suggest that sociotropy and autonomy may be useful constructs for understanding and treating PDs.

Adolescent↗

PubMed2004

Score tests for dose effect in the presence of non-responders.

When only a certain proportion of subjects respond to treatment ('responders') or may never experience an event of interest (thus 'cured'), mixture models often lead to increased understanding of the treatment or disease process. This paper focuses on hypothesis testing in a dose-response framework and shows that increased power is possible by using a mixture model where both the logit of the response rate and the response mean are linear functions of the dose level. Three score tests are developed for testing an overall effect and permutation methods are used to control the type I error. Extensive simulations establish the power properties of the tests and show that our proposed score test has the best performance. The approach is illustrated by a multi-country clinical trial of rapid acting Intramuscular Olanzapine.

Algorithms↗

PubMed2000

A score test for the linkage analysis of qualitative and quantitative traits based on identity by descent data from sib-pairs.

We propose a general likelihood-based approach to the linkage analysis of qualitative and quantitative traits using identity by descent (IBD) data from sib-pairs. We consider the likelihood of IBD data conditional on phenotypes and test the null hypothesis of no linkage between a marker locus and a gene influencing the trait using a score test in the recombination fraction theta between the two loci. This method unifies the linkage analysis of qualitative and quantitative traits into a single inferential framework, yielding a simple and intuitive test statistic. Conditioning on phenotypes avoids unrealistic random sampling assumptions and allows sib-pairs from differing ascertainment mechanisms to be incorporated into a single likelihood analysis. In particular, it allows the selection of sib-pairs based on their trait values and the analysis of only those pairs having the most informative phenotypes. The score test is based on the full likelihood, i.e. the likelihood based on all phenotype data rather than just differences of sib-pair phenotypes. Considering only phenotype differences, as in Haseman and Elston (1972) and Kruglyak and Lander (1995), may result in important losses in power. The linkage score test is derived under general genetic models for the trait, which may include multiple unlinked genes. Population genetic assumptions, such as random mating or linkage equilibrium at the trait loci, are not required. This score test is thus particularly promising for the analysis of complex human traits. The score statistic readily extends to accommodate incomplete IBD data at the test locus, by using the hidden Markov model implemented in the programs MAPMAKER/SIBS and GENEHUNTER (Kruglyak and Lander, 1995; Kruglyak et al., 1996). Preliminary simulation studies indicate that the linkage score test generally matches or outperforms the Haseman-Elston test, the largest gains in power being for selected samples of sib-pairs with extreme phenotypes.

Journal Article↗

PubMed1991

A platform for biological sequence comparison on parallel computers.

We have written two programs for searching biological sequence databases that run on Intel hypercube computers. PSCANLIB compares a single sequence against a sequence library, and PCOMPLIB compares all the entries in one sequence library against a second library. The programs provide a general framework for similarity searching; they include functions for reading in query sequences, search parameters and library entries, and reporting the results of a search. We have isolated the code for the specific function that calculates the similarity score between the query and library sequence; alternative searching algorithms can be implemented by editing two files. We have implemented the rapid FASTA sequence comparison algorithm and the more rigorous Smith-Waterman algorithm within this framework. The PSCANLIB program on a 16 node iPSC/2 80386-based hypercube can compare a 229 amino acid protein sequence with a 3.4 million residue sequence library in approximately 16 s with the FASTA algorithm. Using the Smith-Waterman algorithm, the same search takes 35 min. The PCOMPLIB program can compare a 0.8 million amino acid protein sequence library with itself in 5.3 min with FASTA on a third-generation 32 node Intel iPSC/860 hypercube.

Algorithms↗