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Biomedical subjects

M Knapp

Publications and source records attributed to M Knapp.

At least 19 recordsLinked to original sources
PubMed2006

Development of a new measure of health-related quality of life for people with dementia: DEMQOL.

BACKGROUND: We identified the need to develop a scientifically rigorous measure of health-related quality of life (HRQL) in dementia that would be appropriate for use at all stages of dementia severity and would be available in both self- and proxy-report versions. METHOD: We used standard psychometric methods to eliminate items with poor psychometric properties (item-reduction field test) and to assess the acceptability, reliability and validity of the item-reduced instruments (psychometric evaluation field test). We developed and validated two versions of DEMQOL: a 28-item interviewer-administered questionnaire that is self-reported by the person with dementia (DEMQOL) and a 31-item interviewer-administered questionnaire that is proxy-reported by a caregiver (DEMQOL-Proxy). RESULTS: DEMQOL shows high reliability (internal consistency and test-retest) and moderate validity in people with mild/moderate dementia. DEMQOL-Proxy shows good acceptability and internal consistency and moderate evidence of validity in people with mild/moderate and severe dementia. Test-retest reliability and performance in people with severe dementia need further testing. CONCLUSIONS: DEMQOL and DEMQOL-Proxy show psychometric properties that are comparable with the best available dementia-specific measures of HRQL. We recommend that DEMQOL and DEMQOL-Proxy are used together. Reliability and validity need to be confirmed in independent samples and responsiveness needs to be evaluated.

Adult↗
PubMed2006

Unusual process of water formation on RuO2(110) by hydrogen exposure at room temperature.

The reduction mechanism of the RuO(2)(110) surface by molecular hydrogen exposure is unraveled to an unprecedented level by a combination of temperature programmed reaction, scanning tunneling microscopy, high-resolution core level shift spectroscopy, and density functional theory calculations. We demonstrate that even at room temperature hydrogen exposure to the RuO(2)(110) surface leads to the formation of water. In a two-step process, hydrogen saturates first the bridging oxygen atoms to form (O(br)-H) species and subsequently part of these O(br)-H groups move to the undercoordinated Ru atoms where they form adsorbed water. This latter process is driven by thermodynamics leaving vacancies in the bridging O rows.

Journal Article↗
PubMed2006

Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIalpha gene (PIP5K2A) with schizophrenia.

Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase IIalpha (PIP5K2A), in a sample of 65 sib-pair families for which linkage had been reported. Evidence for association was obtained for 15 polymorphisms spanning 73.6 kb in the genomic region of the gene between intron 4 and the 3' untranslated region, a region with high degree of linkage disequilibrium. Single nucleotide polymorphism (SNP) rs10828317 located in exon 7 and causing a non-synonymous amino-acid exchange (asparagine/serine) produced a P-value of 0.001 (experiment-wide significance level 0.00275) for over-transmission of the major allele coding for serine, analysed by transmission disequilibrium test using FAMHAP. Association of this SNP with schizophrenia has been also described in a sample of 273 Dutch schizophrenic patients and 580 controls (P=0.0004). PIP5K2A is involved in the biosynthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), one of the key metabolic crossroads in phosphoinositide signalling. PI(4,5)P2 plays a role in membrane transduction of neurotransmitter signals as well as in intracellular signalling, pathways that may be impaired in schizophrenia.

Base Sequence↗
PubMed2006

Assessing services, supports and costs for young families under stress.

BACKGROUND: Despite the attention paid to family support services in legislation and guidance, there is still relatively little evidence on which to base the development of effective services, and even less on the costs and cost-effectiveness of different models of support. METHODS: The study designed and examined the practical feasibility of a methodology for collecting service use data and other information on families. Unit costs of services were calculated and data were collected in interviews with 177 young families under stress in Northern Ireland and South-East England. Service use patterns and costs were analysed. RESULTS: Comparisons showed that families made greater use than the general population of many services. There were marked variations within the sample in the patterns of service use and costs, to some extent reflecting differences in the needs of the young families. DISCUSSION: The methods developed for collecting service use data, calculating unit costs and estimating costs for families were feasible.

Child, Preschool↗
PubMed2006

Quality of life in dementia: more than just cognition. An analysis of associations with quality of life in dementia.

OBJECTIVES: To explore the extent to which commonly used measures of specific outcomes in dementia are an appropriate proxy for quality of life in dementia. METHODS: This was a cross sectional study set in communities in London and Nottingham, comprising 101 people with dementia and their 99 main family caregivers. The main outcome measures were health related quality of life in dementia (measured by the DEMQOL-Proxy), cognition (Mini Mental State Examination), functional impairment (Barthel Index), behavioural and psychological symptoms in dementia (Neuropsychiatric Inventory; NPI), and carer mental health (General Health Questionnaire). RESULTS: On univariate analysis, decreased quality of life was statistically significantly correlated with higher levels of behavioural and psychological disturbance (NPI total score and its agitation, depression, anxiety, disinhibition, and irritability subscales); younger age of the person with dementia; and poorer mental health of the carer. Quality of life was not statistically significantly associated with cognition or carer age. In a multivariate model, psychological and behavioural disturbance and patient age remained statistically significantly associated with quality of life. Carer mental health was no longer statistically significantly associated, and cognition and functional limitation remained statistically insignificant. CONCLUSIONS: These data suggest that quality of life in dementia is complex, and that simple proxy substitutions of discrete measures such as cognition or function are likely to miss important factors.

Activities of Daily Living↗
PubMed2006

Cognitive behavioural therapy in addition to antispasmodic therapy for irritable bowel syndrome in primary care: randomised controlled trial.

OBJECTIVES: To determine whether cognitive behavioural therapy (CBT) in addition to antispasmodic treatment offers a cost-effective benefit to primary care patients with irritable bowel syndrome (IBS) and to identify predictors of outcome. DESIGN: This was a randomised controlled trial in primary care of the addition of CBT to standard general practice management of IBS, using the antispasmodic agent mebeverine hydrochloride. The study set out to compare the addition of a standardised package of IBS-specific CBT to treatment with mebeverine hydrochloride. SETTING: Ten general practices, serving a population of around 45,000 patients, located principally in south London, with some patients resident in north London. PARTICIPANTS: Patients identified as having IBS by their GPs, aged between 17 and 54 (mean 34) years and predominantly white; 82% were female and half had had IBS for more than 5 years. INTERVENTIONS: Practice nurses delivered CBT in a randomised trial of the addition of CBT to mebeverine in patients who had IBS of moderate or greater severity after 2 weeks of GP care and 4 weeks of mebeverine. The Symptom Severity Scale (SSS) was used to identify patients with moderate or severe IBS. Patients who continued to report moderate or severe IBS after 4 weeks of mebeverine at a dose of 270 mg three times a day were randomised to receive six sessions of CBT in addition to mebeverine (72 patients) or mebeverine alone (77 patients). These patients were followed at 3, 6 and 12 months after treatment. As part of the baseline evaluation, blood tests for antiendomysial and antigliadin antibodies were carried out on 141 patients to determine the prevalence of coeliac disease in this population. MAIN OUTCOME MEASURES: The principal outcome measure was the SSS. Others included the Hospital Anxiety and Depression Scale, psychopathology, the Work and Social Adjustment Scale (WASA, disability), a modified version of the Illness Perception Questionnaire (illness perceptions), the Beliefs about Medicine Questionnaire (attitudes to medication), the Reported Adherence to Medication Scale (adherence to prescribed medication), the Client Service Receipt Inventory (economic analysis), the Cognitive Scale for Functional Bowel Disorders (illness cognitions) and the Behaviour Scale for IBS (IBS coping behaviour). RESULTS: The addition of CBT produced a significant benefit compared with the mebeverine-only group at 3 months after treatment on all outcome measures, except for the adherence to medication scales. The difference between the groups was 107.8 points on the SSS, 24.5 points on question 4 of the SSS and 6.3 points on the WASA, representing therapeutic gains of approximately 20%, 28% and 40%, respectively. However, there was also evidence that these improvements began to wane, so that at 6 and 12 months follow-up significant therapeutic benefit of the addition of CBT could only be detected on question 4 of the SSS and on the WASA. The behaviour scale for IBS detected significant, positive changes in coping behaviours at up to 6 months after treatment. Three factors predicting a poor outcome were identified: male gender, believing that IBS had serious consequences and belief in an external aetiology, all of which were associated with greater than average disability at follow-up. The addition of CBT to mebeverine did not reduce overall treatment or social costs. The nested study on testing for coeliac disease provides cautious support for the inclusion of antiendomysial and antigliadin antibody testing in the investigation of patients thought to have IBS. CONCLUSIONS: Specially trained practice nurses can provide effective CBT to primary care patients with a clinical diagnosis of IBS, which although effective does not reduce service or social costs. Using a variety of measures the beneficial therapeutic effects of the addition of CBT to antispasmodic therapy persist for up to 6 months. Future research might include studies of the long-term follow-up of IBS patients treated with CBT, cost-benefit analyses comparing CBT with other therapeutic approaches to IBS, and evaluating means of training both non-specialist health professionals and GPs to deliver CBT.

Adolescent↗
PubMed2005

Ru(0001) model catalyst under oxidizing and reducing reaction conditions: in-situ high-pressure surface X-ray diffraction study.

With surface X-ray diffraction (SXRD) using a high-pressure reaction chamber we investigated in-situ the oxidation of the Ru(0001) model catalyst under various reaction conditions, starting from a strongly oxidizing environment to reaction conditions typical for CO oxidation. With a mixture of O(2) and CO (stoichiometry, 2:1) the partial pressure of oxygen has to be increased to 20 mbar to form the catalytically active RuO(2)(110) oxide film, while in pure oxygen environment a pressure of 10(-5) mbar is already sufficient to oxidize the Ru(0001) surface. For preparation temperatures in the range of 550-630 K a self-limiting RuO(2)(110) film is produced with a thickness of 1.6 nm. The RuO(2)(110) film grows self-acceleratedly after an induction period. The RuO(2) films on Ru(0001) can readily be reduced by H(2) and CO exposures at 415 K, without an induction period.

Journal Article↗
PubMed2005

Promoting mental well-being in the workplace: a European policy perspective.

The nature of the workplace continues to change as Europe adapts to the challenges of competing in a global marketplace. Across the European Union there is a trend of increasing absenteeism and early retirement due to mental health problems, particularly stress and depression. The social and economic costs of lost productivity in Europe are substantial. Moreover, the sustainability of social protection systems may be challenged further by increases in the levels of disability benefits paid to people who have left work on grounds of poor mental health. Yet despite these significant consequences, at both national and pan-European levels, decision-makers have been slow to recognise the importance of promoting mental health within the workplace, although recently there have been some positive developments. This paper outlines some of the socio-economic arguments for the promotion of good mental well-being in the labour force and identifies how they link with different national and European policy agendas around four key issues: economic growth and development, the promotion of a high level of public health, sustainability of social welfare systems and social inclusion. The role and activities to promote mental well-being in the workplace undertaken by both national and international organizations in Europe are outlined along with important gaps and challenges that need to be addressed.

Absenteeism↗
PubMed2005

Treatment and management of challenging behaviours in congregate and noncongregate community-based supported accommodation.

OBJECTIVES: To compare the nature and prevalence of use of procedures employed to treat and manage challenging behaviours across two approaches to providing community-based supported accommodation for people with intellectual disabilities (ID) and severe challenging behaviour: noncongregate settings where the minority of residents have challenging behaviour, and congregate settings where the majority of residents have challenging behaviour. SETTING: Community-based supported accommodation for people with ID and challenging behaviour. DESIGN: Longitudinal matched groups design. MAIN OUTCOME MEASURES: The nature and prevalence of use of procedures employed to treat and manage challenging behaviours. Observed and reported severity of challenging behaviours. RESULTS: Both types of settings were associated with low prevalence of use of behavioural technologies for the reduction of challenging behaviour (less than 15% of participants). In contrast, high proportions of participant received antipsychotic medication in both noncongregate (56%) and congregate (80%) settings. Congregate settings were associated with the increased use of physical restraint as a reactive management strategy, with over half of participants being in receipt of physical restraint by two or more members of staff. DISCUSSION: Changes in reported and observed challenging behaviour over a 10-month period were slight. The use of evidence-based behavioural technologies for the reduction of challenging behaviour may have led to better outcomes.

Adult↗
PubMed2005

Multiple testing in the context of haplotype analysis revisited: application to case-control data.

We have lately presented a testing procedure for family data which accounts for the multiple testing problem that is induced by the enormous number of different marker combinations that can be analyzed in a set of tightly linked markers. Most methods of haplotype based association analysis already require simulations to obtain an uncorrected P value for a specific marker combination. As shown before, it is nevertheless not necessary to carry out nested simulations to obtain a global P value that properly corrects for the multiple testing of different marker combinations without neglecting the dependency of the tests. We have now implemented this approach for case-control data in our program FAMHAP, as this data structure currently plays a dominant role in the field. We consider different ways to deal with phase ambiguities and two different statistical tests for the underlying single marker combinations to obtain uncorrected P values. One test statistic is chi-square based, the other is a haplotype trend regression. The performance of these different tests in the multiple testing situation is investigated in a large simulation study. We obtain a considerable gain in power with our global P values as opposed to Bonferroni corrected P values for all suggested test statistics. Good power was obtained both with the haplotype trend regression approach as well as with the simpler chi-square based test. Furthermore, we conclude that the better strategy to deal with phase ambiguities is to assign to each individual its list of weighted haplotype explanations, rather than to assign to each individual its most likely haplotype explanation. Finally, we demonstrate the usefulness of our approach by a real data example.

Algorithms↗
PubMed2005

Measurement of health-related quality of life for people with dementia: development of a new instrument (DEMQOL) and an evaluation of current methodology.

OBJECTIVES: To develop and validate a psychometrically rigorous measure of health-related quality of life (HRQoL) for people with dementia: DEMQOL. DATA SOURCES: Literature review. Expert opinion. Interviews and questionnaires. REVIEW METHODS: Gold standard psychometric techniques were used to develop DEMQOL and DEMQOL-Proxy. A conceptual framework was generated from a review of the literature, qualitative interviews with people with dementia and their carers, expert opinion and team discussion. Items for each component of the conceptual framework were drafted and piloted to produce questionnaires for the person with dementia (DEMQOL) and carer (DEMQOL-Proxy). An extensive two-stage field-testing was then undertaken of both measures in large samples of people with dementia (n = 130) and their carers (n = 126) representing a range of severity and care arrangements. In the first field test, items with poor psychometric performance were eliminated separately for DEMQOL and DEMQOL-Proxy to produce two shorter, more scientifically robust instruments. In the second field test, the item-reduced questionnaires were evaluated along with other validating measures (n = 101 people with dementia, n = 99 carers) to assess acceptability, reliability and validity. RESULTS: Rigorous evaluation in two-stage field testing with 241 people with dementia and 225 carers demonstrated that in psychometric terms: (1) DEMQOL is comparable to the best available dementia-specific HRQoL measures in mild to moderate dementia, but is not appropriate for use in severe dementia [Mini Mental State Examination (MMSE) <10]; and (2) DEMQOL-Proxy is comparable to the best available proxy measure in mild to moderate dementia, and shows promise in severe dementia. In addition, the DEMQOL system has been validated in the UK in a large sample of people with dementia and their carers, and it provides separate measures for self-report and proxy report, which allows outcomes assessment across a wide range of severity in dementia. CONCLUSIONS: The 28-item DEMQOL and 31-item DEMQOL-Proxy provide a method for evaluating HRQoL in dementia. The new measures show comparable psychometric properties to the best available dementia-specific measures, provide both self- and proxy-report versions for people with dementia and their carers, are appropriate for use in mild/moderate dementia (MMSE >/= 10) and are suitable for use in the UK. DEMQOL-Proxy also shows promise in severe dementia. As DEMQOL and DEMQOL-Proxy give different but complementary perspectives on quality of life in dementia, the use of both measures together is recommended. In severe dementia, only DEMQOL-Proxy should be used. Further research with DEMQOL is needed to confirm these findings in an independent sample, evaluate responsiveness, investigate the feasibility of use in specific subgroups and in economic evaluation, and develop population norms. Additional research is needed to address the psychometric challenges of self-report in dementia and validating new dementia-specific HRQoL measures.

Aged↗
PubMed2005

A randomised controlled comparison of alternative strategies in stroke care.

OBJECTIVES: To compare outcomes between stroke patients managed on the stroke unit, on general wards with stroke team support or at home by specialist domiciliary team and to derive prognostic variables that will identify patients most suitable for management by each strategy. To describe organisational aspects of individual strategies of stroke care and to evaluate cost-effectiveness of each strategy and its acceptability to patients, carers and professionals. DESIGN: Prospective single-blind randomised controlled trial undertaken in patients recruited from a community-based stroke register. SETTING: Suburban district in south-east England. PARTICIPANTS: Patients with disabling stroke who could be supported at home. INTERVENTIONS: The stroke unit gave 24-hour care provided by specialist multidisciplinary team based on clear guidelines for acute care, prevention of complications, rehabilitation and secondary prevention. The stroke team provided management on general wards with specialist team support. The team undertook stroke assessments and advised ward-based nursing and therapy staff on acute care, secondary prevention and rehabilitation aspects. Domiciliary care involved management at home under the supervision of a GP and stroke specialist with support from specialist team and community services. Support was provided for a maximum of 3 months. MAIN OUTCOME MEASURES: The primary measure was death or institutionalisation at 1 year. Secondary measures were dependence, functional abilities, mood, quality of life, resource use, length of hospital stay, and patient, carer and professional satisfaction. RESULTS: Of the 457 patients randomised, 152 patients were allocated to the stroke unit; 152 patients to stroke team and 153 patients to domiciliary stroke care (average age 76 years, 48% women). The groups were well matched for baseline characteristics, stroke type and severity, level of impairment and initial disability. Fifty-one (34%) patients in the domiciliary group were admitted to hospital after randomisation. Mortality and institutionalisation at 1 year were lower on stroke unit compared with stroke team or domiciliary care. Significantly fewer patients on the stroke unit died compared with those managed by the stroke team. The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team or domiciliary care. These differences were present at 3 and 6 months after stroke. Stroke survivors managed on the stroke unit showed greater improvement on basic activities of daily living compared with other strategies. Achievement of higher levels of function was not influenced by strategy of care. Quality of life at 3 months was significantly better in stroke unit and domiciliary care patients. There was greater dissatisfaction with care on general wards compared with stroke unit or domiciliary care. Poor outcome with domiciliary care and on general wards was associated with Barthel Index <5, incontinence and, on general wards, age over 75 years. The total costs of stroke per patient over the 12-month period were pound 11,450 for stroke unit, pound 9527 for stroke team and pound 6840 for home care. However, the mean costs per day alive for the stroke unit were significantly less than those for the specialist stroke team patients, but no different from domiciliary care patients. Costs for the domiciliary group were significantly less than for those managed by the specialist stroke team on general wards. CONCLUSIONS: Stroke units were found to be more effective than a specialist stroke team or specialist domiciliary care in reducing mortality, institutionalisation and dependence after stroke. A role for specialist domiciliary services for acute stroke is not supported by this study. Management of patients with strokes on general medical wards, even with specialist team input, is not supported by this study. The stroke unit intervention was less costly per patient day alive and more effective than the stroke team intervention. The stroke unit was more effective and of equivalent cost when compared to home care. Hence, the stroke unit is a more cost-effective intervention than either stroke team or home care. Further research is needed to understand processes contributing to the reduction in mortality on stroke units and to determine the generalisability of these results and the factors that will influence the implementation of the findings of this study in clinical practice.

Activities of Daily Living↗
PubMed2004

Visualization of atomic processes on ruthenium dioxide using scanning tunneling microscopy.

The visualization of surface reactions on the atomic scale provides direct insight into the microscopic reaction steps taking place in a catalytic reaction at a (model) catalyst's surface. Employing the technique of scanning tunneling microscopy (STM), we investigated the CO oxidation reaction over the RuO2(110) and RuO2(100) surfaces. For both surfaces the protruding bridging O atoms are imaged in STM as bright features. The reaction mechanism is identical on both orientations of RuO2. CO molecules adsorb on the undercoordinated surface Ru atoms from where they recombine with undercoordinated O atoms to form CO2 at the oxide surface. In contrast to the RuO2(110) surface, the RuO2(100) surface stabilizes also a catalytically inactive c(2 x 2) surface phase onto which CO is not able to adsorb above 100 K. We argue that this inactive RuO2(100)-c(2 x 2) phase may play an important role in the deactivation of RuO2 catalysts in the electrochemical Cl2 evolution and other heterogeneous reactions.

Journal Article↗
PubMed2004

Does diagnosis determine delivery? The Islington study of older people's needs and health care costs.

BACKGROUND: Little is known about the factors associated with the receipt of care by older people. This study investigates the use. costs and factors associated with service usage among people aged 65 or older living in inner London. METHOD: A community-based survey, using questionnaires, examined psychiatric and physical morbidity, formal and informal care. The relationships between demographic, pathological features and the costs of health and social care were explored using multivariate regression. RESULTS: A total of 1085 people were interviewed at home of these 18% did not receive any service at all. The total cost of services per week for people with dementia was pound 109, with activity limitation pound 14 and with depression pound 12. The greatest effect of physical limitation was on the receipt of social care. Dementia had the strongest effect on receipt of social care services. Depression increased health care costs to a much greater degree than social care costs. Despite presenting to services, black elders received significantly less health care than other people with the same needs. Older people living alone were more likely to receive social care support and appeared less likely to use health services. CONCLUSIONS: Physical dependency significantly affects both health and social care costs. Increasing cognitive impairment mainly leads to increasing social care costs. Overall costs are increased by physical dependency, dementia, depression, subjective health problems, living alone and are negatively affected by being black.

Activities of Daily Living↗
PubMed2004

Effect of acute exercise and training on metabolism of ceramide in the heart muscle of the rat.

AIM: The sphingomyelin signalling pathway operates in the heart muscle. There are no data on the effect of exercise on the functioning of this pathway in the myocardium and it was the aim of the present study to examine this question. METHODS: The experiments were carried out on male Wistar rats, 300-320 g of body weight. They were divided into three groups: (1) control, (2) run 3 h on a treadmill moving with a speed of 1200 m h(-1) and set at +10 degrees incline, and (3) trained on a treadmill for 6 weeks. The rats were anaesthetized and samples of the left ventricle were taken. They were immediately frozen in liquid nitrogen. Thereafter, lipids were extracted and ceramide and sphingomyelin were isolated by means of thin layer chromatography. Their fatty acids were identified and quantified by means of gas-liquid chromatography. In separate heart samples the activity of neutral, Mg(2+)-dependent sphingomyelinase and acid sphingomyelinase was determined using labelled sphingomyelin as a substrate. RESULTS: Thirteen different ceramides and sphingomyelins were identified based on their fatty acid residue. Exercise markedly reduced the total content of ceramide-fatty acids and had no effect on the total content of sphingomyelin-fatty acids. Training did not affect the total content either of ceramide-, or sphingomyelin-fatty acids. The activity of both neutral Mg(2+)-sphingomyelinase and acid sphingomyelinase was reduced after exercise. Training did not affect the activity of neutral sphingomyelinase and reduced the activity of acid sphingomyelinase. CONCLUSION: It is concluded that acute, prolonged exercise, but not training, markedly affects the operation of the sphingomyelin-signalling pathway in the heart.

Animals↗
PubMed2004

Asthma is associated with single-nucleotide polymorphisms in ADAM33.

BACKGROUND: The ADAM33 gene has recently been associated with asthma and bronchial hyper-reactivity. It codes for a disintegrin and metalloproteinase that triggers intra- and extracellular signalling by protein shedding. OBJECTIVE: We examined whether polymorphisms in ADAM33 are associated with asthma and related traits in two German populations. METHODS: We genotyped 15 intragenic single-nucleotide polymorphisms (SNPs) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of allele-specific primer extension products. The transmission disequilibrium test was used for association analysis in the German asthma family study. Additionally, we tested for association of these SNPs in a case-control sample from the European Community Respiratory Health Study using Armitage's trend test. RESULTS: In both studies, we found SNPs that were significantly associated with asthma and related traits. In the family study, significant associations were observed for the SNPs F+1, ST+4 and ST+5 (with the lowest P-value for F+1, P=0.005). Remarkably, this association is seen even in the absence of linkage with two microsatellite markers from a previous genome scan either 3.1 million bases (Mb) up- or 5.6 Mb downstream. In the case-control study, SNP ST+7 (P=0.008) was significantly associated with asthma. Some of these SNPs overlapped with those found to be associated with elevated total IgE levels and bronchial hyper-responsiveness. CONCLUSION: This study replicates the recently published association between asthma and ADAM33 gene variants. However, most of the associated SNPs were at non-identical positions in the German, UK and US samples. As linkage disequilibrium is high among the tested SNPs, and there is no known functional polymorphism, either not-tested variants in ADAM33, unknown regulatory elements or a gene in close proximity is responsible for this association.

ADAM Proteins↗
PubMed2004

Pathway logic modeling of protein functional domains in signal transduction.

Protein functional domains (PFDs) are consensus sequences within signaling molecules that recognize and assemble other signaling components into complexes. Here we describe the application of an approach called Pathway Logic to the symbolic modeling signal transduction networks at the level of PFDs. These models are developed using Maude, a symbolic language founded on rewriting logic. Models can be queried (analyzed) using the execution, search and model-checking tools of Maude. We show how signal transduction processes can be modeled using Maude at very different levels of abstraction involving either an overall state of a protein or its PFDs and their interactions. The key insight for the latter is our algebraic representation of binding interactions as a graph.

Computational Biology↗