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PubMed2005

MOLE: a data management application based on a protein production data model.

MOLE (mining, organizing, and logging experiments) has been developed to meet the growing data management and target tracking needs of molecular biologists and protein crystallographers. The prototype reported here will become a Laboratory Information Management System (LIMS) to help protein scientists manage the large amounts of laboratory data being generated due to the acceleration in proteome research and will furthermore facilitate collaborations between groups based at different sites. To achieve this, MOLE is based on the data model for protein production devised at the European Bioinformatics Institute (Pajon A, et al., Proteins in press).

Algorithms↗

PubMed2003

Disentangling the dynamic core: a research program for a neurodynamics at the large-scale.

My purpose in this paper is to sketch a research direction based on Francisco Varela's pioneering work in neurodynamics (see also Rudrauf et al. 2003, in this issue). Very early on he argued that the internal coherence of every mental-cognitive state lies in the global self-organization of the brain activities at the large-scale, constituting a fundamental pole of integration called here a "dynamic core". Recent neuroimaging evidence appears to broadly support this hypothesis and suggests that a global brain dynamics emerges at the large scale level from the cooperative interactions among widely distributed neuronal populations. Despite a growing body of evidence supporting this view, our understanding of these large-scale brain processes remains hampered by the lack of a theoretical language for expressing these complex behaviors in dynamical terms. In this paper, I propose a rough cartography of a comprehensive approach that offers a conceptual and mathematical framework to analyze spatio-temporal large-scale brain phenomena. I emphasize how these nonlinear methods can be applied, what property might be inferred from neuronal signals, and where one might productively proceed for the future. This paper is dedicated, with respect and affection, to the memory of Francisco Varela.

Brain↗

PubMedDate not supplied

The relationship between language spoken and smoking among Hispanic-Latino youth in New York City.

This study was designed to examine the relationship between language spoken and smoking (at least once a month) among New York City Hispanic-Latino adolescents, using a large sample of specific Hispanic-Latino subgroups (Puerto Rican, Dominican, Colombian, and Ecuadorian youth) and controlling for social and environmental factors. The sample included 3,129 Hispanic-Latino students in 47 New York City public and parochial schools. Of the total sample, 43 percent were Puerto Rican, 20 percent Dominican, 7 percent Colombian, and 7 percent Ecuadorian. The students completed questionnaires that were designed to assess social and environmental influences on their smoking and determine what languages they spoke (English and Spanish) with parents and friends. Self-reported smoking data were collected by means of the bogus pipeline to enhance the veracity of self-reports. In the logistic regression model, including background, social influence, and language use variables, 101 students were smokers. Logistic regression analysis indicated that being bicultural (speaking both English and Spanish) at home and with friends appeared to increase the odds of currently smoking. Separate logistic regression analyses for girls and boys revealed that being bicultural at home increased the odds of currently smoking for boys but not girls. Results are discussed in terms of their implications for prevention.

Acculturation↗

PubMed1982

Neuroevolutionary mechanisms of cerebral asymmetry in man.

Cerebral asymmetry in man has by and large been interpreted in terms of differences at the level of hemispheric organization. The inadequacy of a hemispheric interpretation as a biological account of asymmetry is discussed and a model of the neural mechanisms of cerebral asymmetry is developed. The model focuses on the functional organization of the inferior parietal cortex in human and non-human primates and accounts for the evolution and expression of cerebral asymmetry in man in terms of specific adaptations in select neural systems of ancestral primate brains.

Animals↗

PubMed2005

Scalable molecular dynamics with NAMD.

NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This article, directed to novices as well as experts, first introduces concepts and methods used in the NAMD program, describing the classical molecular dynamics force field, equations of motion, and integration methods along with the efficient electrostatics evaluation algorithms employed and temperature and pressure controls used. Features for steering the simulation across barriers and for calculating both alchemical and conformational free energy differences are presented. The motivations for and a roadmap to the internal design of NAMD, implemented in C++ and based on Charm++ parallel objects, are outlined. The factors affecting the serial and parallel performance of a simulation are discussed. Finally, typical NAMD use is illustrated with representative applications to a small, a medium, and a large biomolecular system, highlighting particular features of NAMD, for example, the Tcl scripting language. The article also provides a list of the key features of NAMD and discusses the benefits of combining NAMD with the molecular graphics/sequence analysis software VMD and the grid computing/collaboratory software BioCoRE. NAMD is distributed free of charge with source code at www.ks.uiuc.edu.

Algorithms↗

PubMed2001

Methods of cognitive analysis to support the design and evaluation of biomedical systems: the case of clinical practice guidelines.

This article provides a theoretical and methodological framework for the use of cognitive analysis to support the representation of biomedical knowledge and the design of clinical systems, using clinical-practice guidelines (CPGs) as an example. We propose that propositional and semantic analyses, when used as part of the system-development process, can improve the validity, usability, and comprehension of the resulting biomedical applications. The framework we propose is based on a large body of research on the study of how people mentally represent information and subsequently use it for problem solving. This research encompasses many areas of psychology, but the more important ones are the study of memory and the study of comprehension. Of particular relevance is research devoted to investigating the comprehension and memory of language, expressed verbally or in text. In addition, research on how contextual variables affect performance is informative because these psychological processes are influenced by situational variables (e.g., setting, culture). One important factor limiting the acceptance and use of clinical-practice guidelines (CPGs) may be the mismatch between a guideline's recommended actions and the physician-user's mental models of what seems appropriate in a given case. Furthermore, CPGs can be semantically complex, often composed of elaborate collections of prescribed procedures with logical gaps or contradictions that can promote ambiguity and hence frustration on the part of those who attempt to use them. An improved understanding of the semantics and structure of CPGs may help to improve such matching, and ultimately the comprehensibility and usability of CPGs. Cognitive methods of analysis can help guideline designers and system builders throughout the development process, from the conceptual design of a computer-based system to its implementation phases. By studying how guideline creators and developers represent guidelines, both mentally and in text, and how end-users understand and make decisions with such guidelines, we can inform the development of technologies that seek to improve the match between the representations of experts and practitioners. We urge informaticians to recognize the potential relevance of cognitive analysis methods and to begin more extensive experimentation with the their use in biomedical informatics research.

Cognition↗

PubMed2004

An evaluation of the adequacy of outpatient monitoring of thyroid replacement therapy.

OBJECTIVES: Hypothyroid patients managed with excessive or insufficient thyroid replacement therapy are often difficult to clinically recognize. Monitoring may prevent or minimize the consequences of adverse drug events (ADEs). We sought to develop an explicit model of medication monitoring and to evaluate monitoring processes and ADEs in patients taking levothyroxine. METHODS: A retrospective chart review of 400 outpatients receiving levothyroxine therapy between 1 January 2000 and 1 January 2001 at a large North American tertiary care hospital. We measured the proportion of patients satisfying minimum monitoring criteria, experiencing specific monitoring errors and having levothyroxine-related ADEs. Explicit monitoring criteria were derived from the literature and through expert opinion. Adverse drug events were identified using structured implicit reviews. RESULTS: Overall, only 56% (95% confidence interval [95% CI] 51-62%) of the patients prescribed levothyroxine received the minimal recommended monitoring. Errors were identified at all stages of the monitoring model. Patients who received the recommended monitoring had fewer levothyroxine-related ADEs (1% vs. 6%, P=0.013) than those who did not. Minority status (white people 2% vs. black people 4% vs. Hispanics 14%, P=0.023) and primary language (English 3% vs. Non-English 20%, P=0.002) were the patient characteristics associated with levothyroxine-related ADEs. CONCLUSION: Only half of outpatients taking levothyroxine at one tertiary care hospital received the recommended monitoring during one year of follow-up. Levothyroxine-related ADEs were more frequent in patients with lower-quality monitoring and in minorities and non-English speakers.

Ambulatory Care↗

PubMed2004

Aligning words in French-English non-parallel medical texts: effect of term frequency distributions.

In this paper, we present a method for aligning words based on a statistical model of word distribution similarity. The basis underlying our method is that there is a correlation between the patterns of word co-occurrences in texts of different languages. Using automatically downloaded pages from different medical web sites and a combined bilingual lexicon of general and medical terms as language sources, a similarity score is assigned to each proposed translated pair of words, based on the distributional contexts of these two words. We vary several parameters of the method. Experimental results confirm a positive effect of frequency, show that medical words are better handled than less specialized words, and do not evidence a clear influence of context window size. Future directions for improvement include working with very large, part-of-speech tagged corpora.

Algorithms↗

PubMed2005

Predictors of endoscopy in minority women.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. Underrepresented minorities suffer disproportionately from CRC largely because of disparities in CRC screening rates, particularly by endoscopic methods. This study evaluates the association between socioeconomic, medical and psychosocial factors and the use of endoscopy in low-income minority women. METHODS: The participants were recruited from community health fairs, tenant association meetings, senior centers and local medical clinics. A survey instrument was administered to the minority women. RESULTS: Eighty-one women age >50 were included in this analysis (44 African Americans and 37 Hispanics). The two ethnic groups were demographically similar. The factors associated with having had endoscopy were language spoken (English versus Spanish), physician recommendation, cancer cons and decisional balance (difference between cancer cons and cancer pros). When endoscopy was modeled as a function of decisional balance and language spoken, only decisional balance was a significant predictor of endoscopy. CONCLUSIONS: Physician recommendation and decisional balance have a tremendous influence on whether minority women undergo endoscopy. These data suggest that if physicians increase their communication with patients regarding the benefits of screening and address patients concerns, adherence with endoscopic CRC screening can be improved in minority women.

Black or African American↗

PubMed2006

Steroidal contraceptives: effect on bone fractures in women.

BACKGROUND: Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. However, osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally. OBJECTIVES: To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women SEARCH STRATEGY: We searched MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies of fracture or bone health and hormonal contraceptives. We wrote to investigators to find additional trials. SELECTION CRITERIA: Randomized controlled trials were considered if they examined fractures, bone mineral density (BMD), or bone turnover in women with hormonal contraceptive use prior to menopause. Studies were excluded if hormones were provided for treatment of a specific condition rather than for contraception. Interventions could include comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive. Interventions could also include the provision of a supplement versus a placebo. DATA COLLECTION AND ANALYSIS: We assessed for inclusion all titles and abstracts identified through the literature searches with no language limitation. The weighted mean difference (WMD) was computed with 95% confidence interval (CI) using a fixed-effect model. MAIN RESULTS: No trial had fracture as an outcome. Combination contraceptives did not appear to affect bone health. Of progestin-only methods, depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density, while results were inconsistent for implants. The two placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo. AUTHORS' CONCLUSIONS: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. Due to different interventions, no trials could be combined for meta-analysis. Many trials had small numbers of participants and some had large losses to follow up. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

Bone Density↗

PubMed2001

A light knowledge model for linguistic applications.

Content extraction from medical texts is achievable today by linguistic applications, in so far as sufficient domain knowledge is available. Such knowledge represents a model of the domain and is hard to collect with sufficient depth and good coverage, despite numerous attempts. To leverage this task is a priority in order to benefit from the awaited linguistic tools. The light model is designed with this goal in mind. Syntactic and lexical information are generally available with large lexicons. A domain model should add the necessary semantic information. The authors have designed a light knowledge model for the collection of semantic information on the basis of the recognized syntactical and lexical attributes. It has been tailored for the acquisition of enough semantic information in order to retrieve terms of a controlled vocabulary from free texts, as for example, to retrieve Mesh terms from patient records.

Information Storage and Retrieval↗

PubMed1995

European participation in major intensive care journals.

To evaluate the recent evolution of the European contribution to the international literature in intensive care medicine, we reviewed the source of all original articles and case reports published from 1989 to 1993 in 5 major journals: Critical Care Medicine, Intensive Care Medicine, Chest, The American Review of Respiratory Disease and Circulatory Shock. There was an overall decline in the US contributions and a corresponding increase in the European participations to Chest and the American Review of Respiratory Disease, but not to Critical Care Medicine or Circulatory Shock. The European participation to Intensive Care Medicine remained largely predominant. The evaluation of the contributions of major European countries to these 5 journals revealed a progressive increase in the French, Italian and Spanish contributions, whilst the German contribution remained stable and the UK contributions decreased. The UK contribution, which was the first in 1989, became second in 1993, after France.

Authorship↗

PubMed2004

An X-linked three allele model of hand preference and hand posture for writing.

This paper describes a genetic model of hand preferences for writing and for handwriting posture (HWP). The challenge of devising an X-linked model for these aspects of human handedness was posed by the results of a large family handedness study (McKeever, 2000) that showed evidence of such linkage. Because X-linkage for handedness has been widely regarded as untenable, the prospects for developing such a model were not initially encouraging, but ultimately a viable model did suggest itself. Family studies of handedness and leading theories of handedness are briefly described, as is some of the research on HWP motivated by the theory of Levy and Nagylaki (1972). It is argued that there is evidence that HWP reflects a biological dictate and not just individual "choices" or "adaptations" to writing in a left-to-right direction with the left hand. The model proposes that inverted handwriting posture is not necessarily highly related to speech and language lateralities of sinistrals, but that it reveals an interhemispheric mediation of writing. It is hypothesised that it reflects a specialisation of the left angular gyrus (with some possible extension into the supramarginal gyrus) for the storage of movement and timing sequences of cursive writing, and right hemisphere motor programming of the motor output of writing. It is also argued that no family handedness study conducted to date is adequate for testing the predictions of extant handedness theories, and the often wide variations between the results of family handedness studies are noted. It is suggested that fMRI studies could definitively test the HWP hypotheses of the model and that the hypothesis of X-linkage could be tested definitively should studies of the human genome identify a gene for handedness.

Chromosomes, Human, X↗

PubMed2000

Comparing the use of physician time and health care resources among patients speaking English, Spanish, and Russian.

BACKGROUND AND OBJECTIVES: The number of US residents with limited English proficiency (LEP) is 14 million and rising. The goal of this study was to estimate the effects of LEP on physician time and resource use. DESIGN: This was a prospective, observational study. SETTING AND SUBJECTS: The study included 285 Medicaid patients speaking English (n = 112), Spanish (n = 62), or Russian (n = 111) visiting the General Medicine and Family Practice Clinics at the UC Davis Medical Center in 1996-1997 (participation rate, 85%). Bilingual research assistants administered patient questionnaires, abstracted the medical record, and conducted detailed time and motion studies. MAIN OUTCOME MEASURES: We used seemingly unrelated regression models to evaluate the effect of language on visit time, controlling for patient demographics and health status, physician specialty, visit type, and resident involvement in care. We also estimated the effect of LEP on cross-sectional utilization of health care resources and adherence to follow-up with referral and testing appointments. RESULTS: The 3 language groups differed significantly by age, education, and reason for visit but not gender, number of active medical conditions, physical functioning, or mental health. Physician visit time averaged 38+/-20 minutes (mean+/-SD). Compared with English-speaking patients and after multivariate adjustment, Spanish and Russian speakers averaged 9.1 and 5.6 additional minutes of physician time, respectively (P <0.05). The language effect was confined largely to follow-up visits with resident physicians (house staff). Compared with English speakers, Russian speakers had more referrals (P = 0.003) and Spanish speakers were less likely to follow-up with recommended laboratory studies (P = 0.031). CONCLUSIONS: In these academic primary care clinics, some groups of patients using interpreters required more physician time than those proficient in English Additional reimbursement may be needed to ensure continued access and high-quality care for this special population.

California↗

PubMed2004

Magnetocephalography: a noninvasive alternative to the Wada procedure.

OBJECT: In this study the authors evaluated the sensitivity and selectivity of a noninvasive language mapping procedure based on magnetoencephalography (MEG), for determining hemispheric dominance for language functions. METHODS: Magnetic activation profiles of the brain were obtained from 100 surgical candidates (age range 8-56 years) with medically intractable seizure disorder by using a whole-head MEG system within the context of a word recognition task. The degree of language-specific activity was indexed according to the number of consecutive sources (modeled as single, moving current dipoles) in perisylvian brain areas. Only activity sources that were observed with a high degree of spatial and temporal overlap in two split-half data sets were used to compute the MEG laterality index. Independently, all patients underwent Wada testing for the determination of hemispheric dominance for language. Independent clinical judgments based on MEG and Wada data showed a high degree of concordance (87%). Magnetoencephalography laterality judgments had an overall sensitivity of 98%, but a lower selectivity of 83%, which was due to the fact that MEG detected more activity in the nondominant hemisphere than was predicted based on the Wada test. A number of objective criteria were derived based on this large patient series to ensure data quality and bolster the clinical usefulness of MEG for language mapping. CONCLUSIONS: Although the availability of MEG is still limited across epilepsy surgery centers, this study method may be substituted for the Wada procedure in assessing hemispheric dominance for language in select cases.

Adolescent↗

PubMed1997

The utility of follow-up testing after curative cancer therapy. A critical review and economic analysis.

OBJECTIVE: To review (1) basic principles of follow-up in patients who are in complete remission following curative therapy for cancer; (2) evaluate the available data on follow-up strategies for testicular cancer, Hodgkin's disease, non-Hodgkin's lymphoma, breast cancer, colorectal cancer, small cell and non-small cell lung cancer, and prostate cancer; and (3) analyze the cost of follow-up strategies. METHODS: The English language literature was reviewed utilizing MEDLINE headings for the specific malignancies and the text word "follow-up." Bibliographies of relevant articles also were reviewed. Emphasis was placed on prospective, randomized trials of large retrospective studies in which all patients who potentially could have been evaluated were accounted. The cost of various testing strategies were analyzed utilizing data from the Health Care Finance Administration. DATA SYNTHESIS: Proper follow-up strategies should take into account patterns and time course of recurrence and should be obtained of detection of recurrence would allow meaningful therapeutic intervention. Testing also should be directed at early detection of malignant and nonmalignant complications known to be associated with the primary disease. Testicular cancer is a "model" malignancy in that sensitive tests for recurrence are available and early detection of recurrence allows for potentially curative therapy. CONCLUSIONS: According to the currently available literature, repetitive follow-up laboratory and radiologic testing, except for nonseminomatous germ cell tumors, does not detect the vast majority of cancer relapses, nor does it result in a greater chance of cure or prolonged survival. The majority of recurrences at all disease sites will first be recognized as symptomatic changes in the patient's condition or alterations in the physical examination. A limited panel of blood tests and radiographic studies to detect recurrences, metachronous disease, and complications of therapy (malignant and nonmalignant), will suffice for most cancers. Though data are limited, this more restrictive policy of follow-up testing does not appear to adversely impact patient quality of life and result in dramatic cost of savings to the health care system.

Breast Neoplasms↗

PubMed1993

Jean Martin Charcot and aphasia: treading the line between experimental physiology and pathological anatomy.

During his entire career Jean Martin Charcot published or lectured on aphasia and brain localization in man. He contributed case studies during the early 1860s, while in the 1870s he became the leading French promoter of localizationism. It was in 1883 and 1884 that he summarized his thoughts on aphasia in a series of 14 lectures he delivered at the Salpêtrière Hospice. His paramount ambition was to achieve didactic clarity. His proposed "bell diagram" was widely criticized for its simplicity, but nevertheless gained considerable popularity in France. His teaching borrowed extensively from the writings of contemporary researchers and was clearly associationist in nature. Charcot's major contribution in the history of aphasiology is that he introduced the works of "diagram-makers" to the French scientific community at large. Charcot's lecture series also played a key role in renewing interest in psychology. Charcot's dismissal of experimental physiology as a legitimate means of investigating central nervous functions in man allowed him to define a separate field of research for a new psychology, one, he believed, which should depart from introspection and turn to his clinicoanatomic method for guidance.

Anatomy↗

PubMed2002

Semantics affect the planning but not control of grasping.

The semantic meaning of a word label printed on an object can have significant effects on the kinematics of reaching and grasping movements directed towards that object. Here, we examined how the semantics of word labels might differentially affect the planning and control stages of grasping. Subjects were presented with objects on which were printed either the word "LARGE" or "SMALL." When the grip aperture in the two conditions was compared, an effect of the words was found early in the reach, but this effect declined continuously as the hand approached the target. This continuously decreasing effect is consistent with a planning/control model of action, in which cognitive and perceptual variables affect how actions are planned but not how they are monitored and controlled on-line. The functional and neurological bases of semantic effects on planning and control are discussed.

Hand Strength↗