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Biomedical subjects

K Dunbar

Publications and source records attributed to K Dunbar.

17 recordsLinked to original sources

2.45 GHz radiofrequency fields alter gene expression in cultured human cells.

The biological effect of radiofrequency (RF) fields remains controversial. We address this issue by examining whether RF fields can cause changes in gene expression. We used the pulsed RF fields at a frequency of 2.45 GHz that is commonly used in telecommunication to expose cultured human HL-60 cells. We used the serial analysis of gene expression (SAGE) method to measure the RF effect on gene expression at the genome level. We observed that 221 genes altered their expression after a 2-h exposure. The number of affected genes increased to 759 after a 6-h exposure. Functional classification of the affected genes reveals that apoptosis-related genes were among the upregulated ones and the cell cycle genes among the downregulated ones. We observed no significant increase in the expression of heat shock genes. These results indicate that the RF fields at 2.45 GHz can alter gene expression in cultured human cells through non-thermal mechanism.

Dose-Response Relationship, Radiation↗

A comparison of pulmonary exacerbations with single and multiple organisms in patients with cystic fibrosis and chronic Burkholderia cepacia infection.

STUDY OBJECTIVES: To compare pulmonary exacerbations with single and multiple organisms in patients with chronic Burkholderia cepacia infection. DESIGN: Data was collected over a 23-month period and for each of the patients two episodes of pulmonary exacerbation were identified, one with B. cepacia isolated as the sole respiratory pathogen and the other with one or more coinfecting organisms grown from the sputum culture. SETTING: Regional tertiary referral center for Respiratory Medicine and Adult Cystic Fibrosis Center for Northern Ireland, Belfast City Hospital. PATIENTS: Adult (over 16 years) CF patients with chronic (more than 4 years) B. cepacia complex infection who attended the Belfast City Hospital between January 1997 and November 1998. MEASUREMENTS: Forced expiratory volume in 1s, forced vital capacity, forced expiratory flow rate 25-75, C-reactive protein, leucocyte count and body mass index were measured before and after two weeks of treatment and analysed for any differences in change between the two episodes. RESULTS: All variables in both groups improved following treatment except for body mass index, which remained unchanged. No significant differences between the measurements were identified on comparison of single (monomicrobial) and multiple (polymicrobial) isolate episodes. CONCLUSION: Patients with chronic B. cepacia infection who develop a pulmonary exacerbation improve, as reflected by clinical and biochemical markers, following IV antibiotic treatment. Pulmonary exacerbations with multiple organisms are no more severe than those where only B. cepacia is isolated.

Adolescent↗

Cytokine concentrations and neutrophil elastase activity in bronchoalveolar lavage and induced sputum from patients with cystic fibrosis, mild asthma and healthy volunteers.

BACKGROUND: Induced sputum (IS) has been proposed as a non-invasive alternative to bronchoalveolar lavage (BAL) for the assessment and monitoring of airways inflammation. The aim of this study was to compare both methods in patients with cystic fibrosis (CF). The possible differences between subjects with CF, mild asthma and healthy volunteers (HV) was also assessed. METHOD: In a single centre, randomised, two way crossover study, 11 patients with CF, 9 mild asthmatics (MA) and 11 HV underwent BAL and hypertonic saline induction on consecutive days. Free neutrophil elastase (NE), neutrophil elastase/alpha(1)-anti-trypsin complex (NE-AAT), tumour necrosis factor receptor (p55) and interleukin-8 (IL-8) were measured in cell free supernatants. RESULTS: Three CF patients reported serious adverse events following BAL. NE was usually undetectable in both IS or BAL samples and NE-AAT concentrations did not differ consistently between the two sampling methods. IL-8 and p55 levels in the CF patients tended to be higher in IS samples compared with BAL samples (median 19,860 vs. 3,855 pg/ml and 2.55 vs. 0.29 ng/ml, respectively). There was a significant difference in mean p55 concentrations between CF, MA and HV in IS samples (P=0.003) but not in BAL samples (P=0.36). The difference in mean IL-8 concentrations in IS samples between subject groups was statistically different (P=0.023). CONCLUSIONS: IS samples can be safely obtained from CF patients. Analysis of IS samples can help to characterize the inflammatory process in the airways of CF patients. The serious adverse events following BAL in 3 CF patients highlight an inherent risk associated with this procedure.

Adult↗

The effects of frontal lobe lesions on goal achievement in the water jug task.

Patients with prefrontal cortex lesions are impaired on a variety of planning and problem-solving tasks. We examined the problem-solving performance of 27 patients with focal frontal lobe damage on the Water Jug task. The Water Jug task has never been used to assess problem-solving ability in neurologically impaired patients nor in functional neuroimaging studies, despite sharing structural similarities with other tasks sensitive to prefrontal cortex function, including the Tower of Hanoi, Tower of London, and Wisconsin Card Sorting Task (WCST). Our results demonstrate that the Water Jug task invokes a unique combination of problem-solving and planning strategies, allowing a more precise identification of frontal lobe lesion patients' cognitive deficits. All participants (patients and matched controls) appear to be utilizing a hill-climbing strategy that does not require sophisticated planning; however, frontal lobe lesion patients (FLLs) struggled to make required "counterintuitive moves" not predicted by this strategy and found within both solution paths. Left and bilateral FLLs were more impaired than right FLLs. Analysis of the left hemisphere brain regions encompassed by the lesions of these patients found that poor performance was linked to left dorsolateral prefrontal cortex damage. We propose that patients with left dorsolateral prefrontal cortex lesions have difficulty making a decision requiring the conceptual comparison of nonverbal stimuli, manipulation of select representations of potential solutions, and are unable to appropriately inhibit a response in keeping with the final goal.

Brain Diseases↗

The in vivo/in vitro approach to cognition: the case of analogy.

A new way of investigating cognition is proposed that combines naturalistic (in vivo) and experimental (in vitro) methods into a single approach. Investigating analogical reasoning by scientists 'live' at laboratory meetings (in vivo) we found that the types of analogies they use change with their goals. Unlike subjects in many cognitive 'reminding' experiments, scientists frequently used structural similarities in their analogies, as opposed to superficial similarities. By subsequently using the in vitro approach, we found that the use of structural information was associated with being asked to generate analogies and with the use of complex scenarios. Similar results are obtained in other areas of reasoning such as hypothesis testing and causal reasoning.

Journal Article↗

An embarrassment of sortases - a richness of substrates?

A range of surface proteins is anchored to the cell walls of Gram-positive pathogens such as Staphylococcus aureus by the transpeptidase sortase. Until now, sortase-like proteins and their substrates appeared to be limited mainly to such pathogens. However, by searching for sortase homologues among complete and incomplete genome sequences, we have found them to be present in almost all Gram-positives, a single Gram-negative bacterium and an archaean. There is usually more than one sortase-like protein encoded in each Gram-positive genome, and the genes encoding the sortase-like proteins are often clustered with genes encoding their likely substrates.

Amino Acid Sequence↗

Improved cultural detection of Burkholderia cepacia from sputum in patients with cystic fibrosis.

AIMS: To evaluate the sensitivity and specificity of two selective media for the isolation of Burkholderia cepacia from sputum specimens in patients with cystic fibrosis (CF). METHODS: In total, 149 expectorated sputum specimens from 113 patients with CF (32 cepacia colonised patients and 81 non-cepacia colonised patients) attending three CF centres were examined for the presence of B cepacia on two selective media: (1) MAST selective agar, a commercially available selective medium widely used in the UK and (2) BCSA (B cepacia selective agar), a new medium recently described, which is used predominantly in North America. RESULTS: Burkholderia cepacia was isolated from 53 of 149 (35.6%) specimens examined, representing 32 of 113 (28.3%) patients, using both the MAST and BCSA media. Growth was most rapid on BCSA with all (53 of 53) isolates detectable after 48 hours, compared with 50 of the 53 isolates on MAST agar, with the remaining three isolates detectable at five days. Twenty eight contaminants were identified on MAST agar and 13 on BCSA agar; mainly Alcaligenes xylosoxidans and yeast on MAST agar and Flavobacterium indologenes on BCSA medium. BCSA was equivalent to MAST agar in its ability to isolate B cepacia from patients with CF with a history of B cepacia infection. CONCLUSIONS: The increased selectivity and reduced time to detection of BCSA makes it an attractive alternative to MAST. However, its present limited commercial availability in the UK may delay its use in routine diagnostic laboratories because of complications with media preparation and quality control.

Adult↗

Analogy use in naturalistic settings: the influence of audience, emotion, and goals.

The ways in which analogy was used in a nonexperimental environment-politics-was investigated. We used the framework developed in analogy research to analyze the selection of analogical sources in political discourse. We took all the analogies reported in newspapers during the final week of a referendum campaign in Canada and analyzed the features of the different analogies used. We identified 234 analogies and analyzed the range over which analogies were used, semantic categories of analogies, goals of the analogizer, and emotional connotation of the analogies. Our results reveal that analogy was frequently used, that over two-thirds of the analogical sources were nonpolitical, and that many of the sources had strong emotional connotations. Furthermore, the goal of the analogizer influenced the selection of sources. We conclude that characteristics of the audience and emotionality of the source analog are important features in the selection of source analogs.

Canada↗

How analogies are generated: the roles of structural and superficial similarity.

Laboratory studies of analogical reasoning have shown that subjects are mostly influenced by superficial similarity in the retrieval of source analogs. However, real-world investigations have demonstrated that people generate analogies using deep structural features. We conducted three experiments to determine why laboratory and real-world studies have yielded different results. In the first two experiments, we used a "production paradigm" in which subjects were asked to generate sources for a given target. Results show that the majority of the analogies that were generated displayed low levels of superficial similarity with the target problem. Moreover, most of the analogies were based on complex underlying structures. The third experiment used a "reception paradigm" methodology. The subjects had to retrieve predetermined sources instead of generate their own. In this case, retrieval was largely constrained by surface similarity. We conclude that people can use structural relations when given an appropriate task and that this ability has been underestimated in previous research on analogy.

Association Learning↗

Priming, analogy, and awareness in complex reasoning.

The mechanisms by which a concept used in solving one complex task can influence performance on another complex task were investigated. We tested the hypothesis that even when subjects do not spontaneously make an analogy between two domains, knowledge of one domain can still spontaneously influence reasoning about the other domain via the mechanism of priming. Four groups of subjects (two experimental and two control) were given a simulated biochemistry problem on Day 1 and a simulated molecular genetics problem on Day 2. For the two experimental groups, the solution to the biochemistry problem involved inhibition. For the two control groups, the solution did not involve inhibition. On Day 2, all subjects received the same version of the molecular genetics problem in which the solution involved the concept of inhibition. Subjects in the experimental conditions were more likely to attain the correct answer, to propose inhibition, and to propose inhibition early in the problem-solving session than were subjects in the control conditions. However, subjects in the experimental conditions made no reference to the biochemistry problem either in their verbal protocols or in a post-task questionnaire. The results are interpreted as demonstrating that an implicit process--priming--can make old knowledge available for current problem solving.

Awareness↗

Heuristics for scientific experimentation: a developmental study.

Scientific discovery involves search in a space of hypotheses and a space of experiments. We describe an investigation of developmental differences in the search constraint heuristics used in scientific reasoning. Sixty-four subjects (technically trained college students, community college students with little technical training, 6th graders, and 3rd graders) were taught how to use a programmable robot. Then they were presented with a new operation, provided with a hypothesis about how it might work, and asked to conduct experiments to discover how the new operation really did work. The suggested hypothesis was always incorrect, as subjects could discover if they wrote informative experiments, and it was either plausible or implausible. The rule for how the unknown operation actually worked was either very similar or very dissimilar to the given hypothesis. Children focused primarily on plausible hypotheses, conducted a limited set of experiments, designed experiments that were difficult to interpret, and were unable to induce implausible (but correct) hypotheses from data. Adults were much better than children in discovering implausible rules. The performance deficits we found were not simply the result of children's inadequate encoding or mnemonic skills. Instead, the adults appear to use domain-general skills that go beyond the logic of confirmation and disconfirmation and deal with the coordination of search in two spaces: a space of hypotheses and a space of experiments.

Adolescent↗

On the control of automatic processes: a parallel distributed processing account of the Stroop effect.

Traditional views of automaticity are in need of revision. For example, automaticity often has been treated as an all-or-none phenomenon, and traditional theories have held that automatic processes are independent of attention. Yet recent empirical data suggest that automatic processes are continuous, and furthermore are subject to attentional control. A model of attention is presented to address these issues. Within a parallel distributed processing framework, it is proposed that the attributes of automaticity depend on the strength of a processing pathway and that strength increases with training. With the Stroop effect as an example, automatic processes are shown to be continuous and to emerge gradually with practice. Specifically, a computational model of the Stroop task simulates the time course of processing as well as the effects of learning. This was accomplished by combining the cascade mechanism described by McClelland (1979) with the backpropagation learning algorithm (Rumelhart, Hinton, & Williams, 1986). The model can simulate performance in the standard Stroop task, as well as aspects of performance in variants of this task that manipulate stimulus-onset asynchrony, response set, and degree of practice. The model presented is contrasted against other models, and its relation to many of the central issues in the literature on attention, automaticity, and interference is discussed.

Attention↗

Training and Stroop-like interference: evidence for a continuum of automaticity.

Three experiments varied the extent of practice in an analog of the Stroop color-work task. Each experiment involved four phases: (a) baseline naming of four familiar colors, (b) training in consistently naming four novel shapes by using the names of the same four colors, (c) naming the colors when they appeared in the form of the shapes, and (d) naming the shapes when they appeared in color. In Experiment 1, with up to 2 hr of training in shape naming, colors were named much faster than shapes. Interference was observed only in Phase 4. In Experiment 2, with 5 hr of training, shape naming sped up, but was still slower than color naming. Nevertheless, there was symmetrical interference in Phases 3 and 4, and this persisted 3 months later without further training. Experiment 3 replicated this pattern and then extended practice to 20 hr, by which time shape and color naming were equally rapid. After 20 hr, interference appeared only in Phase 3, reversing the original asymmetry. The overall pattern is inconsistent with a simple speed of processing account of interference. The alternative idea of a continuum of automaticity--a direct consequence of training--remains plausible, and the implications of this perspective are considered.

Attention↗

A horse race of a different color: Stroop interference patterns with transformed words.

Four experiments investigated Stroop interference using geometrically transformed words. Over experiments, reading was made increasingly difficult by manipulating orientation uncertainty and the number of noncolor words. As a consequence, time to read color words aloud increased dramatically. Yet, even when reading a color word was considerably slower than naming the color of ink in which the word was printed, Stroop interference persisted virtually unaltered. This result is incompatible with the simple horse race model widely used to explain color-word interference. When reading became extremely slow, a reversed Stroop effect--interference in reading the word due to an incongruent ink color--appeared for one transformation together with the standard Stroop interference. Whether or not the concept of automaticity is invoked, relative speed of processing the word versus the color does not provide an adequate overall explanation of the Stroop phenomenon.

Attention↗

Detection of mycobacterial DNA from sputum of patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) are at high risk from atypical mycobacterial infections. There have been few attempts to delineate the intensity of mycobacterial infection in CF patients in Ireland. AIMS: To examine the incidence of mycobacterial DNA in an archived collection of genomic DNA extracted from the sputa of CF patients within the Northern Ireland population. METHODS: One hundred and eighty-two CF patients (66 adults and 116 children) were examined for the presence of mycobacterial DNA in their sputum by a genus specific PCR assay based on 16S rRNA, followed by direct automated sequencing of the PCR amplicons. RESULTS: One of 116 (0.9%) children and 2 of 66 adults were positive. Sequence identity revealed Mycobacterium xenopi in the paediatric patient and M. xenopi and M. chelonei in the two adult patients. False-positive results occurred in 11 patients (four adults), mainly due to Corynebacterium spp. CONCLUSIONS: There was a low prevalence of Mycobacterium spp in the CF patient population. All PCR positive results should be confirmed by direct automated sequencing and an alternative specific assay employed. Enhanced molecular screening will contribute in understanding their role as opportunistic pathogens in patients with worsening lung function.

Adult↗