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Biomedical subjects

Robin Clark

Publications and source records attributed to Robin Clark.

10 recordsLinked to original sources
PubMed2006

Quantifier comprehension in corticobasal degeneration.

In this study, we investigated patients with focal neurodegenerative diseases to examine a formal linguistic distinction between classes of generalized quantifiers, like "some X" and "less than half of X." Our model of quantifier comprehension proposes that number knowledge is required to understand both first-order and higher-order quantifiers. The present results demonstrate that corticobasal degeneration (CBD) patients, who have number knowledge impairments but little evidence for a deficit understanding other aspects of language, are impaired in their comprehension of quantifiers relative to healthy seniors, Alzheimer's disease (AD) and frontotemporal dementia (FTD) patients [F(3,77)=4.98; p<.005]. Moreover, our model attempts to honor a distinction in complexity between classes of quantifiers such that working memory is required to comprehend higher-order quantifiers. Our results support this distinction by demonstrating that FTD and AD patients, who have working memory limitations, have greater difficulty understanding higher-order quantifiers relative to first-order quantifiers [F(1,77)=124.29; p<.001]. An important implication of these findings is that the meaning of generalized quantifiers appears to involve two dissociable components, number knowledge and working memory, which are supported by distinct brain regions.

Aged↗
PubMed2005

Neural basis for generalized quantifier comprehension.

Generalized quantifiers like "all cars" are semantically well understood, yet we know little about their neural representation. Our model of quantifier processing includes a numerosity device, operations that combine number elements and working memory. Semantic theory posits two types of quantifiers: first-order quantifiers identify a number state (e.g. "at least 3") and higher-order quantifiers additionally require maintaining a number state actively in working memory for comparison with another state (e.g. "less than half"). We used BOLD fMRI to test the hypothesis that all quantifiers recruit inferior parietal cortex associated with numerosity, while only higher-order quantifiers recruit prefrontal cortex associated with executive resources like working memory. Our findings showed that first-order and higher-order quantifiers both recruit right inferior parietal cortex, suggesting that a numerosity component contributes to quantifier comprehension. Moreover, only probes of higher-order quantifiers recruited right dorsolateral prefrontal cortex, suggesting involvement of executive resources like working memory. We also observed activation of thalamus and anterior cingulate that may be associated with selective attention. Our findings are consistent with a large-scale neural network centered in frontal and parietal cortex that supports comprehension of generalized quantifiers.

Adult↗
PubMed2004

Analysis of expressed sequence tags from calcifying cells of marine coccolithophorid (Emiliania huxleyi).

An expressed sequence tag (EST) approach was used to investigate gene expression in the unicelluar marine alga Emiliania huxleyi. We randomly selected 3000 EST sequences from a cDNA library of transcripts expressed under conditions promoting coccolithogenesis. Cluster analysis and contig assembly resulted in a unigene set of approximately 1523 ESTs. Only 36% of the unique sequences exhibited significant homology to sequences in GenBank. Of particular interest were the numerous transcripts with homology to sequences associated with sexual reproduction and calcium homeostasis in other unicellular and multicellular organisms. The majority of ESTs (64%) had little or no significant sequence homology to entries in GenBank, suggesting a potential for further novel gene discovery. The catalog of ESTs reported herein represents a significant increase in the limited sequence information currently available for E. huxleyi and should make the coccolithophorid more accessible to powerful genomics and postgenomics technologies.

Base Composition↗
PubMed2004

Verbal mediation of number knowledge: evidence from semantic dementia and corticobasal degeneration.

Patients with corticobasal degeneration (CBD) appear to have impaired number knowledge. We examined the nature of their number deficit while we tested the hypothesis that comprehension of larger numbers depends in part on verbal mediation. We evaluated magnitude judgments and performance on number conservation measures rooted in Piagetian theory in nonaphasic patients with CBD (n=13) and patients with a fluent form of progressive aphasia known as semantic dementia (SD; n=15). We manipulated the numbers of the arrays and the visual-spatial properties of the stimuli being compared during magnitude judgments and Piagetian conservation measures. CBD patients were consistently impaired judging the magnitudes of larger numbers (4-9), while they had minimal difficulty with smaller numbers (magnitudes < or = 3). By comparison, SD patients performed all measures of number knowledge at a ceiling level regardless of number magnitude. Neither patient group was significantly impacted by manipulations of the spatial properties of the stimuli. CBD patients' impairment with larger numbers despite minimal aphasia, and SD patients' intact performance despite an aphasia, challenge the proposal that understanding larger numbers depends on verbal mediation.

Aged↗
PubMed2004

A method for analyzing longitudinal outcomes with many zeros.

Health care utilization and cost data have challenged analysts because they are often correlated over time, highly skewed, and clumped at 0. Traditional approaches do not address all these problems, and evaluators of mental health and substance abuse interventions often grapple with the problem of how to analyze these data in a way that accurately represents program impact. Recently, the traditional 2-part model has been extended to mixed-effects mixed-distribution model with correlated random effects to deal simultaneously with excess zeros, skewness, and correlated observations. We introduce and demonstrate this new method to mental health services researchers and evaluators by analyzing the data from a study of assertive community treatment (ACT). The response variable is the number of days of hospitalization, collected every 6 months over 3 years. The explanatory variable is group: ACT vs. standard case management. Diagnosis (schizophrenia vs. bipolar disorder), time, and the baseline values of hospital days are covariates. Results indicate that clients in the ACT group have a higher probability of hospital admission, but tend to have shorter lengths of stay. The mixed-distribution model provides greater specification of a model to fit these data and leads to more refined interpretation of the results.

Adult↗
PubMed2004

Refined genotype-phenotype correlations in cases of chromosome 6p deletion syndromes.

Clinical reports of cases with deletions in chromosome 6p are relatively rare. We present a detailed study by fluorescent in situ hybridisation (FISH) of six new cases with distinct but overlapping 6p deletions involving the 6p24-pter chromosomal segment. Chromosomal breakpoints in individual cases were investigated using a large panel of probes previously mapped and characterised in our laboratory to cover the distal region of 6p. These cases have allowed refinement of genotype-phenotype correlations and strongly suggest a gene involved in regulating the development of hearing is localised within 6p25. There is also evidence for one or more loci involved in heart, skeletal and craniofacial development in the 6p24-p25 region. Furthermore, the Dandy-Walker malformation is associated with deletion of 6p24-pter.

Abnormalities, Multiple↗
PubMed2002

High-throughput crystallization and structure determination in drug discovery.

High-throughput protein X-ray crystallography offers an unprecedented opportunity to facilitate drug discovery. The key bottlenecks in the path from target gene to three-dimensional protein structure determination are defined. Special emphasis is placed on the concept that drug discovery projects are typically directed at a key protein target whose structure must be solved within a reasonable time frame to have an impact on the drug discovery process. The time-sensitive nature of structural data has placed growing pressure on the need to automate all aspects of protein crystallography, from gene identification to model building and refinement. Current technological innovations and strategies for automation are discussed with respect to the bottleneck they are intended to eliminate.

Automation↗
PubMed2002

Cost-effectiveness of two vocational rehabilitation programs for persons with severe mental illness.

OBJECTIVE: This study sought to determine differences in the cost-effectiveness of two vocational programs: individual placement and support (IPS), in which employment specialists within a mental health center help patients obtain competitive jobs and provide them with ongoing support, and enhanced vocational rehabilitation (EVR), in which stepwise services that involve prevocational experiences are delivered by rehabilitation agencies. METHODS: A total of 150 unemployed inner-city patients with severe mental disorders who expressed an interest in competitive employment were randomly assigned to IPS or EVR programs and were followed for 18 months. Wages from all forms of employment and the number of weeks and hours of competitive employment were tracked monthly. Estimates were made of direct mental health costs and vocational costs. Incremental cost-effectiveness ratios (ICERs) were calculated for competitive employment outcomes and total wages. RESULTS: No statistically significant differences were found in the overall costs of IPS and EVR. Participation in the IPS program was associated with significantly more hours and weeks of competitive employment. However, the average combined earnings-earnings from competitive and noncompetitive employment-were virtually the same both programs. The ICER estimates indicated that participants in the IPS program worked in competitive employment settings for an additional week over the 18-month period at a cost of $283 ($13 an hour). CONCLUSIONS: The analyses suggest that IPS participants engaged in competitive employment at a higher cost. When combined earnings were used as the outcome, data from the statistical analyses were insufficient to enable any firm conclusions to be drawn. The findings illustrate the importance of choice of outcomes in evaluations of employment programs.

Cost-Benefit Analysis↗
PubMed2001

RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51.

RAD51B and RAD51C are two of five known paralogs of the human RAD51 protein that are thought to function in both homologous recombination and DNA double-strand break repair. This work describes the in vitro and in vivo identification of the RAD51B/RAD51C heterocomplex. The RAD51B/RAD51C heterocomplex was isolated and purified by immunoaffinity chromatography from insect cells co-expressing the recombinant proteins. Moreover, co-immunoprecipitation of the RAD51B and RAD51C proteins from HeLa, MCF10A, and MCF7 cells strongly suggests the existence of an endogenous RAD51B/RAD51C heterocomplex. We extended these observations to examine the interaction between the RAD51B/RAD51C complex and the other RAD51 paralogs. Immunoprecipitation using protein-specific antibodies showed that RAD51C is central to a single large protein complex and/or several smaller complexes with RAD51B, RAD51D, XRCC2, and XRCC3. However, our experiments showed no evidence for the inclusion of RAD51 within these complexes. Further analysis is required to elucidate the function of the RAD51B/RAD51C heterocomplex and its association with the other RAD51 paralogs in the processes of homologous recombination and DNA double-strand break repair.

Animals↗