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PubMed2003

Nervous system effects of occupational manganese exposure on South African manganese mineworkers.

Occupational exposure to airborne manganese dust has been shown to produce adverse effects on the central nervous system. Four hundred and eighty-nine blue and white collar manganese mineworkers from South Africa were studied cross-sectionally to investigate the nervous system effects of medium to low occupational manganese exposures. The different facilities included underground mines, surface processing plants, and office locations. A job exposure matrix was constructed using routine occupational hygiene data. Exposure variables included years of service, a cumulative exposure index (CEI) and average intensity of exposure (AINT) across all jobs, and blood manganese. Endpoints included items from the Q16, WHO-NCTB, SPES, and Luria-Nebraska test batteries, and a brief clinical examination. Potential confounders and effect modifiers included age, level of education, past medical history including previous head injury, previous neurotoxic job exposures, tobacco use, alcohol use and home language. Associations were evaluated by multiple linear and logistic regression modeling. Average exposure intensity across all jobs was 0.21mg/m(3) manganese dust. Multivariate analyses showed that none of the symptom nor test results were associated with any measure of exposure including blood manganese, after adjustment for confounders. This relatively large null study indicates that manganese miners exposed on average across all jobs to MnO(2) at levels near the American Conference of Governmental Industrial Hygienists Threshold Limit Value (ACGIH TLV) are unlikely to have a subclinical neurotoxicity problem.

Adult↗

PubMed2001

Genetic and environmental influences on orthographic and phonological skills in children with reading disabilities.

Data from identical and fraternal twins were analyzed to estimate the proportions of genetic and environmental influences on group deficits in accuracy and, when available, speed for printed word recognition and for related skills in phonological decoding (PD), orthographic coding (OC), and phoneme awareness (PA). In addition, bivariate genetic analyses were employed to estimate the degree of common genetic influence on group deficits across these different reading and language skills. About half of the group deficits in each of the skills were due to genetic influences, and the genetic origins were largely shared among the measures (r(g) = .53 - .99), except for those between OC and PA (r(g) = .28 - .39). Implications of the results are discussed for models of reading disability and remediation.

Adolescent↗

PubMed1995

Use of the Unified Medical Language System in patient care at the Columbia-Presbyterian Medical Center.

The Unified Medical Language System (UMLS) project at the United States National Library of Medicine contains and organizes a large number of terms from controlled medical vocabularies. This study examines the suitability of the UMLS for representing patient care information as it exists in the Columbia-Presbyterian Medical Center (CPMC) clinical information system. Comparisons were made between the semantic types, semantic relations and medical concepts of the UMLS and the data model entities, semantic classes, semantic relations and concepts in the CPMC system. Results of the comparison demonstrate that the UMLS structural model is appropriate for representing CPMC vocabularies and patient data and that the UMLS concepts provide excellent coverage of CPMC concepts in many areas. Recommendations are made for enhancing UMLS structure to provide additional coverage of the CPMC model. It is concluded that content expansion to provide better coverage of clinical terminology is possible within the current UMLS model.

Academic Medical Centers↗

PubMed1985

On the nature of the verbal memory deficit in Alzheimer's disease.

Verbal memory was investigated in patients with Alzheimer's disease (AD) with previously documented deficits in word production and comprehension. Procedures were employed to evaluate word recall and recognition within the context of both "multistore" and "levels of processing" models of memory. In addition, memory abilities were evaluated with respect to performance on measures of verbal fluency and language comprehension. As expected, the AD patients performed significantly worse than normal individuals on all tasks. However, in each experiment their pattern of recall across conditions was found to be qualitatively similar to that produced by normal subjects. It was argued that the memory impairment associated with Alzheimer's disease may be largely due to an inability to encode a sufficient number of stimulus features or attributes. Furthermore, this encoding deficit includes, but is not limited to, semantic attributes. Similarities between the performance of the AD patients and reported findings with Korsakoff patients and normal subjects with "weak" memory were discussed.

Aged↗

PubMed1999

Semantic integration in sentences and discourse: evidence from the N400.

In two ERP experiments we investigated how and when the language comprehension system relates an incoming word to semantic representations of an unfolding local sentence and a wider discourse. In Experiment 1, subjects were presented with short stories. The last sentence of these stories occasionally contained a critical word that, although acceptable in the local sentence context, was semantically anomalous with respect to the wider discourse (e.g., Jane told the brother that he was exceptionally slow in a discourse context where he had in fact been very quick). Relative to coherent control words (e.g., quick), these discourse-dependent semantic anomalies elicited a large N400 effect that began at about 200 to 250 msec after word onset. In Experiment 2, the same sentences were presented without their original story context. Although the words that had previously been anomalous in discourse still elicited a slightly larger average N400 than the coherent words, the resulting N400 effect was much reduced, showing that the large effect observed in stories depended on the wider discourse. In the same experiment, single sentences that contained a clear local semantic anomaly elicited a standard sentence-dependent N400 effect (e.g., Kutas &Hillyard, 1980). The N400 effects elicited in discourse and in single sentences had the same time course, overall morphology, and scalp distribution. We argue that these findings are most compatible with models of language processing in which there is no fundamental distinction between the integration of a word in its local (sentence-level) and its global (discourse-level) semantic context.

Adult↗

PubMed2005

The DNA damage response and patient safety: engaging our molecular biology-oriented colleagues.

The imperative to improve patient safety is clear. Biomedical scientists, who account for a large proportion of medical school faculty, and clinicians tend to speak different languages. Biological systems are remarkable for their high robustness, flexibility, and efficiency. Biomedical scientists possess a profound understanding of the complex mechanisms that govern organisms. Their insights may inform the design of safer health care systems. We propose a model to assist in bi-directional communication between these disciplines. We use the principles and mechanisms of the DNA damage response to describe the central concepts of safety science and discuss similarities and differences between the systems of DNA repair and organizational approaches to safety in health care. We suggest that such biomedical scientists can and should be engaged in the effort to bring education about patient safety management into the medical school curriculum and to make patient care safer.

Biomedical Research↗

PubMed1993

Genetic relatedness of lymphoid malignancies. Transformation of chronic lymphocytic leukemia as a model.

OBJECTIVE: Studies concerning the genetic relatedness between chronic lymphocytic leukemia and the more aggressive B-cell cancers that develop in about 10% of affected persons were reviewed. These B-cell cancers include large B-cell lymphoma (the Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia, and multiple myeloma. Two possible relations were evaluated: development from the chronic lymphocytic leukemia clone (clonal evolution) and development of a genetically unrelated, independent second cancer. DATA SOURCES: An English-language medical literature search was done using MEDLINE (1982 to 1992) and CANCERLIT (1982 to 1992). An extensive manual search of the literature that included meeting abstracts and reports was also done. Approximately 500 articles, abstracts, and book chapters were identified; 102 were selected for detailed analysis. DATA ANALYSIS: Analysis of genetic relatedness between the two cancers considered concordance for immunoglobulin gene rearrangements, for immunoglobulin isotypes and idiotypes, and for cytogenetic abnormalities. CONCLUSIONS: In the case of large B-cell lymphoma, generally thought to arise from the chronic lymphocytic leukemia clone, approximately one half of the patients had genetically unrelated cancers. In prolymphocytic transformation, all cases studied appeared to evolve from the chronic lymphocytic leukemia clone. The few studies of acute lymphoblastic leukemia and multiple myeloma showed genetic relatedness in some cases and unrelatedness in others. These data indicate that progression to more aggressive B-cell cancers in persons with chronic lymphocytic leukemia can result from either clonal evolution or from an independent transforming event.

Burkitt Lymphoma↗

PubMed1993

A proposal to provide care to the uninsured through a network of community health centers.

While a national health insurance plan is needed, this alone will not provide access for approximately 30 million persons who face geographic, cultural, language, or health care system barriers, or who live in areas with provider shortages. These barriers often coexist with lack of insurance coverage, but they also affect millions who have public, or even private, coverage. Moreover, large segments of this population suffer from health problems not adequately addressed by the traditional medical model: teenage pregnancy, AIDS, injury, substance abuse, and the like. To provide appropriate care for these underserved persons, we propose to expand the existing network of community health centers over the next 10 years to a total of approximately 3,000. Such an expansion would provide a cost-effective approach to improving provider distribution, increasing consumer input, combining personal health services with health promotion, and removing both financial and nonfinancial barriers to care. This model can be implemented either independent of or in conjunction with other health care system reform efforts.

Community Health Centers↗

PubMed2005

Influential observations in weighted analyses: examples from the National Longitudinal Survey of Children and Youth (NLSCY).

This paper highlights the impact of survey weights on model fit in multiple linear regression with specific reference to the National Longitudinal Survey of Children and Youth (NLSCY) and provides recommendations for the treatment of influential observations. Multiple linear regression was used to estimate the association between child and family factors in the preschool years and vocabulary development at school age. Analyses were performed with and without survey weights. The model fit was assessed by examining the distribution of the studentized residuals and the change in the regression coefficients that would occur if an observation were removed. Two summary measures of influence, Dffits and Cook's D are reported. The models were refit excluding influential observations. Weighting of the linear model resulted in previously non-influential observations having an undue influence on the estimation of the regression parameters in the weighted model. The influential observations were driven primarily by the size of the survey weight as opposed to unusual values of x and y. Researchers working with large national health surveys such as the NLSCY and the National Population Health Survey (NPHS) are advised to include a detailed influence analysis before any final conclusions are made.

Child↗

PubMed2002

Does being bilingual in English and Chinese influence responses to Quality-of-Life scales?

BACKGROUND: It is not known if the inclusion of bilinguals affects the results of research using Quality-of-Life (QoL) scales. OBJECTIVE: To determine the influence of bilingualism on responses to a QoL scale. RESEARCH DESIGN: In this cross sectional study, a population-based, disproportionately stratified random sample of monolingual and bilingual ethnic Chinese completed the Short-Form 36 Health Survey (SF-36) in English or Chinese (representing an alphabet and pictogram based language respectively). Cumulative logit regression models were used to assess the influence of bilingualism on SF-36 scores, while adjusting for the influence of questionnaire language and known determinants of QoL. RESULTS: English or Chinese SF-36 versions were completed by 1331 and 1380 subjects respectively (49% female, aged 21-65 years, 1366 bilingual, 501 English monolingual, 844 Chinese monolingual), with response rates exceeding 85%. Fifty percent of subjects were bilingual. Bilinguals differed from monolinguals in known determinants of QoL, being younger, better educated, and having fewer chronic medical conditions, and had SF-36 scores up to 8 points higher than monolinguals. After adjusting for these differences, bilingualism did not influence scores for any of eight SF-36 scales, whereas questionnaire language influenced scores for four scales. Use of the English SF-36 was associated with higher scores for General Health, Vitality, Role Emotional and Mental Health Scales (odds ratios 1.35-1.41), though the magnitude of these odds ratios suggests this association may not be clinically important. CONCLUSION: Bilingualism did not influence responses to a QoL scale in this large, population-based study of subjects fluent in an alphabet and/or pictogram based language.

Adult↗

PubMed2004

Redefining functional models of basal ganglia organization: role for the posteroventral pallidum in linguistic processing?

Traditionally the basal ganglia have been implicated in motor behavior, as they are involved in both the execution of automatic actions and the modification of ongoing actions in novel contexts. Corresponding to cognition, the role of the basal ganglia has not been defined as explicitly. Relative to linguistic processes, contemporary theories of subcortical participation in language have endorsed a role for the globus pallidus internus (GPi) in the control of lexical-semantic operations. However, attempts to empirically validate these postulates have been largely limited to neuropsychological investigations of verbal fluency abilities subsequent to pallidotomy. We evaluated the impact of bilateral posteroventral pallidotomy (BPVP) on language function across a range of general and high-level linguistic abilities, and validated/extended working theories of pallidal participation in language. Comprehensive linguistic profiles were compiled up to 1 month before and 3 months after BPVP in 6 subjects with Parkinson's disease (PD). Commensurate linguistic profiles were also gathered over a 3-month period for a nonsurgical control cohort of 16 subjects with PD and a group of 16 non-neurologically impaired controls (NC). Nonparametric between-groups comparisons were conducted and reliable change indices calculated, relative to baseline/3-month follow-up difference scores. Group-wise statistical comparisons between the three groups failed to reveal significant postoperative changes in language performance. Case-by-case data analysis relative to clinically consequential change indices revealed reliable alterations in performance across several language variables as a consequence of BPVP. These findings lend support to models of subcortical participation in language, which promote a role for the GPi in lexical-semantic manipulation mechanisms. Concomitant improvements and decrements in postoperative performance were interpreted within the context of additive and subtractive postlesional effects. Relative to parkinsonian cohorts, clinically reliable versus statistically significant changes on a case by case basis may provide the most accurate method of characterizing the way in which pathophysiologically divergent basal ganglia linguistic circuits respond to BPVP.

Aged↗

PubMed2003

A genome scan for developmental dyslexia confirms linkage to chromosome 2p11 and suggests a new locus on 7q32.

Developmental dyslexia is a distinct learning disability with unexpected difficulty in learning to read despite adequate intelligence, education, and environment, and normal senses. The genetic aetiology of dyslexia is heterogeneous and loci on chromosomes 2, 3, 6, 15, and 18 have been repeatedly linked to it. We have conducted a genome scan with 376 markers in 11 families with 38 dyslexic subjects ascertained in Finland. Linkage of dyslexia to the vicinity of DYX3 on 2p was confirmed with a non-parametric linkage (NPL) score of 2.55 and a lod score of 3.01 for a dominant model, and a novel locus on 7q32 close to the SPCH1 locus was suggested with an NPL score of 2.77. The SPCH1 locus has previously been linked with a severe speech and language disorder and autism, and a mutation in exon 14 of the FOXP2 gene on 7q32 has been identified in one large pedigree. Because the language disorder associated with the SPCH1 locus has some overlap with the language deficits observed in dyslexia, we sequenced the coding region of FOXP2 as a candidate gene for our observed linkage in six dyslexic subjects. No mutations were identified. We conclude that DYX3 appears to be important for dyslexia susceptibility in many Finnish families, and a suggested linkage of dyslexia to chromosome 7q32 will need verification in other data sets.

Chromosome Mapping↗

PubMed2006

Polish children's productivity with case marking: the role of regularity, type frequency, and phonological diversity.

57 Polish-speaking children aged from 2;4, to 4;8 and 16 adult controls participated in a nonce-word inflection experiment testing their ability to use the genitive, dative and accusative inflections productively. Results show that this ability develops early: the majority of two-year-olds were already productive with all inflections apart from dative neuter; and the overall performance of the four-year-olds was very similar to that of adults. All age groups were more productive with inflections that apply to large and/or phonologically diverse classes, although class size and token frequency appeared to be more important for younger children (two- and three-year-olds) and phonological diversity for older children and adults. Regularity, on the other hand, was a very poor predictor of productivity. The results support usage-based models of language acquisition and are problematic for the dual mechanism model.

Adult↗

PubMed1993

A graphical user interface to facilitate patient-specific drug dosing.

This paper describes the development of a graphical user-interface (GUI) designed to facilitate the process of generating patient-specific drug doses using bayesian modelling software. The graphical user interface was developed in Visual Basic (Microsoft, Inc.) and runs under the Windows 3.1 (Microsoft, Inc.) operating system. Patient demographic data are stored in a relational database (Access, Microsoft, Inc.). The GUI and the database communicate via dynamic data exchange links. The largely object-oriented nature of the language allowed us to change the entire look and feel of the system with a few simple changes to the underlying code. Use of the relational database to store patient demographic information allows greater flexibility in searching for and displaying patient specific information. The GUI reduces the time required to enter data. The prototype has allowed us to experiment with different presentation methods, greatly improving the clinical acceptance of the dosing programs.

Computer Simulation↗

PubMed2002

The lexical properties of the gene ontology.

The Gene Ontology (GO) is a construct developed for the purpose of annotating molecular information about genes and their products. The ontology is a shared resource developed by the GO Consortium, a group of scientists who work on a variety of model organisms. In this paper we investigate the nature of the strings found in the Gene Ontology and evaluate them for their usefulness in natural language processing (NLP). We extend previous work that identified a set of properties that reliably identifies natural language phrases in the Unified Medical Language System (UMLS). The results indicate that a large percentage (79%) of GO terms are potentially useful for NLP applications. Some 35% of the GO terms were found in a corpus derived from the MEDLINE bibliographic database, and 27% of the terms were found in the current edition of the UMLS.

Genes↗

PubMed2006

Schneider's first rank symptoms and continuous performance disturbance as indices of dysconnectivity of left- and right-hemispheric components of language in schizophrenia.

BACKGROUND: Here we investigate pathophysiological dimensions (language disturbance, negative symptoms, lateralisation and the continuous performance test) in relation to ICD-10 and DSM-IV concepts of diagnosis. METHODS: A total of 32 consecutive psychotic patients with at least one Schneider's first rank symptom (SFRS), 15 depressed patients without SFRS and 17 normal volunteers were assessed with the Clinical Language Disorder Rating Scale (CLANG), SFRS, "pure defect" Huber's basic symptoms (HBS), handedness (Annett's pegboard task), and the A-X Continuous Performance Test (AX-CPT). RESULTS: CLANG total score (an index of severity of language disorder) was correlated with the severity of SFRS, a higher leftward shift of handedness, and poorer performance on AX-CPT. Receiver operating characteristic (ROC) analysis showed that only CLANG and AX-CPT variables had adequate predictive validity in separating cases of ICD-10 schizophrenia from other diagnoses. The logistic regression model predicting the presence of ICD-10 schizophrenia was statistically significant using CLANG and AX-CPT variables, but not SFRS or other variables. HBS did not correlate with other variables and did not predict ICD-10 diagnosis. CONCLUSIONS: A cross-sectional diagnosis based on language disturbance and CPT performance yields a diagnostic construct largely overlapping with the ICD-10 definition of schizophrenia. We suggest that Schneider's first rank symptoms (that play a large role in the DSM-IV concept) can be considered an index of left hemisphere dysconnectivity for language whereas CPT dysfunction reflects dysconnectivity of the right hemisphere for those remoter ("spatial") associations that are closer to Bleuler's core defect and to the chronicity implicit in the ICD definition. Thus the dimensions of language disturbance in psychosis can be traced to specific cortico-cortical dysconnectivities.

Adult↗

PubMed2003

Early setting of grammatical processing in the bilingual brain.

The existence of a "critical period" for language acquisition is controversial. Bilingual subjects with variable age of acquisition (AOA) and proficiency level (PL) constitute a suitable model to study this issue. We used functional magnetic resonance imaging to investigate the effects of AOA and PL on neural correlates of grammatical and semantic judgments in Italian-German bilinguals who learned the second language at different ages and had different proficiency levels. While the pattern of brain activity for semantic judgment was largely dependent on PL, AOA mainly affected the cortical representation of grammatical processes. These findings support the view that both AOA and PL affect the neural substrates of second language processing, with a differential effect on grammar and semantics.

Adult↗

PubMed2001

Web-based educational tool for cleft lip repair using XVL.

Recent web-based technologies have brought a variety of new possibilities to the field of medical information. Nevertheless, transferring 3D patient models through usual low-band-width networks is difficult because of the large size of data file. XVL (eXtensive VRML with Lattice), a new framework for 3D Data representation with high quality surface shape, has solved this problem. In cooperation with Lattice Technology Inc., we have created XVL-formatted patient 3D models. The XVL model takes less than 100 kilobytes, whereas the same quality model in Virtual Reality Modeling Language(VRML) format requires more than 5 megabytes. Because of the many advantages of XVL, we have created a 3D web-based educational tool for repair of cleft lip--plastic surgery for congenital defects of the lips that requires complex incisions and reconstruction. Our system can interact with the model and 3D visualization of the incision lines, displacement of skin flaps, and suturing. Our educational tool for cleft lip repair has demonstrated that the XVL model and its web-based application can open up new possibilities for 3D medical information systems. We are currently refining the XVL model and developing XVL-based applications to simulate the actual surgery on the World Wide Web.

Cleft Lip↗