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Philip Jones

Publications and source records attributed to Philip Jones.

At least 19 recordsLinked to original sources

The Ontology Lookup Service, a lightweight cross-platform tool for controlled vocabulary queries.

BACKGROUND: With the vast amounts of biomedical data being generated by high-throughput analysis methods, controlled vocabularies and ontologies are becoming increasingly important to annotate units of information for ease of search and retrieval. Each scientific community tends to create its own locally available ontology. The interfaces to query these ontologies tend to vary from group to group. We saw the need for a centralized location to perform controlled vocabulary queries that would offer both a lightweight web-accessible user interface as well as a consistent, unified SOAP interface for automated queries. RESULTS: The Ontology Lookup Service (OLS) was created to integrate publicly available biomedical ontologies into a single database. All modified ontologies are updated daily. A list of currently loaded ontologies is available online. The database can be queried to obtain information on a single term or to browse a complete ontology using AJAX. Auto-completion provides a user-friendly search mechanism. An AJAX-based ontology viewer is available to browse a complete ontology or subsets of it. A programmatic interface is available to query the webservice using SOAP. The service is described by a WSDL descriptor file available online. A sample Java client to connect to the webservice using SOAP is available for download from SourceForge. All OLS source code is publicly available under the open source Apache Licence. CONCLUSION: The OLS provides a user-friendly single entry point for publicly available ontologies in the Open Biomedical Ontology (OBO) format. It can be accessed interactively or programmatically at http://www.ebi.ac.uk/ontology-lookup/.

Database Management Systems↗

PRIDE: a public repository of protein and peptide identifications for the proteomics community.

PRIDE, the 'PRoteomics IDEntifications database' (http://www.ebi.ac.uk/pride) is a database of protein and peptide identifications that have been described in the scientific literature. These identifications will typically be from specific species, tissues and sub-cellular locations, perhaps under specific disease conditions. Any post-translational modifications that have been identified on individual peptides can be described. These identifications may be annotated with supporting mass spectra. At the time of writing, PRIDE includes the full set of identifications as submitted by individual laboratories participating in the HUPO Plasma Proteome Project and a profile of the human platelet proteome submitted by the University of Ghent in Belgium. By late 2005 PRIDE is expected to contain the identifications and spectra generated by the HUPO Brain Proteome Project. Proteomics laboratories are encouraged to submit their identifications and spectra to PRIDE to support their manuscript submissions to proteomics journals. Data can be submitted in PRIDE XML format if identifications are included or mzData format if the submitter is depositing mass spectra without identifications. PRIDE is a web application, so submission, searching and data retrieval can all be performed using an internet browser. PRIDE can be searched by experiment accession number, protein accession number, literature reference and sample parameters including species, tissue, sub-cellular location and disease state. Data can be retrieved as machine-readable PRIDE or mzData XML (the latter for mass spectra without identifications), or as human-readable HTML.

Databases, Protein↗

Pharmacokinetics and metabolism studies on (3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy) pyrazolo[1,5-d][1,2,4]triazine, a functionally selective GABA(A) alpha5 inverse agonist for cognitive dysfunction.

(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (1) was recently identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5 receptors and enhances performance in animal models of cognition. The routes of metabolism of this compound in vivo in rat have been well characterised, the identities of the major metabolites are confirmed by synthesis and their biological profiles were evaluated. An unusual oxidation of the pyrazolo[1,5-d][1,2,4]triazine core to the corresponding pyrazolo[1,5-d][1,2,4]triazin-4(5H)-one scaffold by aldehyde oxidase has been observed.

Animals↗

The influence of race on health status outcomes one year after an acute coronary syndrome.

OBJECTIVES: The goal of this study was to compare health status (symptoms, function, and quality of life) outcomes of whites and blacks one year after an acute coronary syndrome (ACS). BACKGROUND: Although racial differences in the use of angiography and revascularization after ACS are known to exist, differences in health status outcomes have not been described. METHODS: We conducted a prospective registry of 1,159 consecutive ACS patients treated between February 1, 2000 and October 31, 2001. One-year health status was quantified with the Seattle Angina Questionnaire (SAQ) and Short Form-12 Physical Component Score (SF-12 PCS). Multivariable models were used to adjust for racial differences in sociodemographic, clinical, and treatment characteristics. RESULTS: Mortality rates were similar among the 196 black and 963 white patients (7.1% vs. 7.0%, p = 0.93); 81 died during follow-up, and 199 (17%) could not be interviewed. At one year, blacks had a higher prevalence of angina (43.4% vs. 27.1%), worse quality of life (SAQ score = 70.6 +/- 28.3 vs. 83.9 +/- 20.8), and poorer physical function (SF-12 PCS = 36.8 +/- 12.3 vs. 43.2 +/- 11.4; p < 0.0001 for all). Multivariable models, including hospital treatments, revealed a trend for more angina (odds ratio 1.46 [95% confidence interval 0.91 to 2.34]) and significantly worse quality of life (mean difference = -7.7 +/- 2.4, p = 0.002) and physical function (-3.6 +/- 1.3, p = 0.005). CONCLUSIONS: Blacks have more angina, worse quality of life, and worse physical function one year after an ACS than do whites. Closer surveillance of black ACS patients is needed to determine whether additional treatment can improve their outcomes.

Acute Disease↗

Relation of anemia at discharge to survival after acute coronary syndromes.

Two-year survival rate was assessed among 1,038 patients who had acute coronary syndromes that were classified by discharge hematocrit values as normal (>39%, n = 360, 34.7%), mildly anemic (33.1% to 39%, n = 430, 41.4%), or moderately/severely anemic (< or = 33%, n = 248, 23.9%). Worsening anemia was associated with a decreased 2-year survival rate (normal 95.8%, mild anemia 91.2%, moderate/severe anemia 81.5%, p < 0.001). In multivariable analyses, adjusted hazard ratios for all-cause mortality were 1.57 (95% confidence interval 0.82 to 2.96) for mild anemia and 2.46 (95% confidence interval 1.25 to 4.85) for moderate/severe anemia.

Aged↗

Staphylococcus aureus endocarditis: a consequence of medical progress.

CONTEXT: The global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown. OBJECTIVES: To document the international emergence of health care-associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: S aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care-associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care-associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons). CONCLUSIONS: S aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation.

Cross Infection↗

Dasty and UniProt DAS: a perfect pair for protein feature visualization.

In this study, we present two freely available and complementary Distributed Annotation System (DAS) resources: a DAS reference server that provides up-to-date sequence and annotation from UniProt, with additional feature links and database cross-references from InterPro and a DAS client implemented using Java and Macromedia Flash that is optimized for the display of protein features.

Algorithms↗

PRIDE: the proteomics identifications database.

The advent of high-throughput proteomics has enabled the identification of ever increasing numbers of proteins. Correspondingly, the number of publications centered on these protein identifications has increased dramatically. With the first results of the HUPO Plasma Proteome Project being analyzed and many other large-scale proteomics projects about to disseminate their data, this trend is not likely to flatten out any time soon. However, the publication mechanism of these identified proteins has lagged behind in technical terms. Often very long lists of identifications are either published directly with the article, resulting in both a voluminous and rather tedious read, or are included on the publisher's website as supplementary information. In either case, these lists are typically only provided as portable document format documents with a custom-made layout, making it practically impossible for computer programs to interpret them, let alone efficiently query them. Here we propose the proteomics identifications (PRIDE) database (http://www.ebi.ac.uk/pride) as a means to finally turn publicly available data into publicly accessible data. PRIDE offers a web-based query interface, a user-friendly data upload facility, and a documented application programming interface for direct computational access. The complete PRIDE database, source code, data, and support tools are freely available for web access or download and local installation.

Computational Biology↗

5th HUPO BPP Bioinformatics Meeting at the European Bioinformatics Institute in Hinxton, UK--Setting the analysis frame.

The Bioinformatics Committee of the HUPO Brain Proteome Project (HUPO BPP) meets regularly to execute the post-lab analyses of the data produced in the HUPO BPP pilot studies. On July 7, 2005 the members came together for the 5th time at the European Bioinformatics Institute (EBI) in Hinxton, UK, hosted by Rolf Apweiler. As a main result, the parameter set of the semi-automated data re-analysis of MS/MS spectra has been elaborated and the subsequent work steps have been defined.

Computational Biology↗

Monitoring clinical changes in patients with heart failure: a comparison of methods.

BACKGROUND: Although monitoring the clinical status of patients with heart failure rests at the core of clinical medicine, the ability of different techniques to reflect clinical change has not been evaluated. This study sought to describe changes in various measures of disease status associated with gradations of clinical change. METHODS: A prospective, 14-center cohort of 476 outpatients was assessed at baseline and 6 +/- 2 weeks to compare changes in 7 heart failure measures with clinically observed change. Measures included health status instruments (the Kansas City Cardiomyopathy Questionnaire [KCCQ], Short Form-12, and EQ-5D), physician-assessed functional class (New York Heart Association [NYHA]), an exercise test (6-minute walk), patient weight, and a biomarker (B-type natriuretic peptide). Cardiologists, blinded to all measures except weight and NYHA, categorized clinical change ranging from large deterioration to large improvement. RESULTS: The KCCQ, NYHA, and 6-minute walk test were most sensitive to clinical change. For patients with large, moderate, and small deteriorations, the KCCQ decreased by 25 +/- 16, 17 +/- 14, and 5.3 +/- 11 points, respectively. For patients with small, moderate, and large improvements, the KCCQ increased by 5.7 +/- 16, 10.5 +/- 16, and 22.3 +/- 16 points, respectively (P < .01 for all compared with the no change group). New York Heart Association and 6-minute walk distance were significantly different for those with moderate and large changes (P < .05) but neither revealed a difference between those with small versus no clinical deterioration. The KCCQ had the highest c statistic for monitoring individual patients, followed by NYHA and 6-minute walk. CONCLUSION: The KCCQ, followed by the NYHA and the 6-minute walk test, most accurately reflected clinical change in patients with heart failure.

Diagnostic Tests, Routine↗

Prognostic value of health status in patients with heart failure after acute myocardial infarction.

BACKGROUND: Disease-specific health status instruments such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) can quantify symptoms, functional limitations, and quality of life in patients with heart failure. Understanding the relationship between KCCQ scores and prognosis may assist clinicians in both interpreting KCCQ scores and stratifying risk in patients. METHODS AND RESULTS: We examined the prognostic value of the KCCQ in a prospective, international cohort of 1516 patients with heart failure after a recent acute myocardial infarction. We focused on the relationship between the KCCQ overall score (KCCQ-os), measured at the first outpatient visit (4 weeks after enrollment), and subsequent 1-year cardiovascular mortality or hospitalization (n=258, 20.3%). KCCQ-os was strongly associated with subsequent cardiovascular events in that those with a score > or =75 had an 84% 1-year event-free survival compared with 59% for those with a score <25 (P<0.001). After demographic and other clinical characteristics were controlled for in multivariable models, KCCQ-os remained strongly associated with outcome (hazard ratio, 2.02; 95% CI, 1.24 to 3.27 for KCCQ-os <25; P<0.001). CONCLUSIONS: In outpatients with heart failure complicating an acute myocardial infarction, KCCQ-os is strongly associated with subsequent 1-year cardiovascular mortality and hospitalization. Use of the KCCQ in outpatient clinical practice can both quantify patients' health status and provide insight into their prognosis.

Adult↗

The peripheral artery questionnaire: a new disease-specific health status measure for patients with peripheral arterial disease.

BACKGROUND: The most common indication for treating patients with peripheral arterial disease is to improve their health status: their symptoms, function, and quality of life. Quantifying health status requires a valid, reproducible, and sensitive disease-specific measure. The Peripheral Artery Questionnaire (PAQ) is a 20-item questionnaire developed to meet this need by quantifying patients' physical limitations, symptoms, social function, treatment satisfaction, and quality of life. METHODS: Psychometric and clinical properties of the PAQ were evaluated in a prospective cohort study of 44 patients undergoing elective percutaneous peripheral revascularization. To establish reproducibility, 2 assessments were performed 2 weeks apart and before revascularization. The change in scores before and 6 weeks after revascularization were used to determine the instruments' responsiveness and were compared with the Short Form-36 and the Walking Impairment Questionnaire. A series of cross-sectional analyses were performed to establish the construct validity of the PAQ. RESULTS: The 7 domains of the PAQ were internally reliable, with Cronbach alpha = 0.80 to 0.94. The test-retest reliability analyses revealed insignificant mean changes of 0.6 to 2.3 points (P = not significant for all). Conversely, the change after revascularization ranged from 13.7 to 41.9 points (P < or =.001 for all), reflecting substantial sensitivity of the PAQ to clinical improvement. The PAQ Summary Scale was the most sensitive of all scales tested. Construct validity was established by demonstrating correlations with other measures of patient health status. CONCLUSIONS: The PAQ is a valid, reliable, and responsive disease-specific measure for patients with peripheral arterial disease. It may prove to be a useful end point in clinical trials and a potential aid in disease management.

Aged↗

Helicobacter pylori: antibiotic resistance and eradication rates in Suffolk, UK, 1991-2001.

Helicobacter pylori infection causes a number of gastrointestinal diseases and its current treatment is based on multidrug regimes including acid suppression and antimicrobials. The success of these regimes is determined by a number of factors including antibiotic resistance, which varies widely but is an increasing problem. Local data are important in establishing the most cost-effective eradication regime. Data have been collected prospectively on antibiotic resistance at Ipswich Hospital (Suffolk, UK) in all consecutive isolates of H. pylori from 1991 to 2001. The success of regimes consisting of a proton pump inhibitor, amoxycillin and metronidazole (PPI/A/M) has also been evaluated in patients found positive on serological testing in primary care using urea breath testing. Overall, metronidazole resistance was found in 31.7 % of isolates and clarithromycin resistance in 5.3 %. A significant increase in metronidazole resistance from 29.1 to 37.0 % (P = 0.022) and a decrease in clarithromycin resistance from 10.3 to 3.8 % (P = 0.014) was seen over the study period. Metronidazole resistance was significantly more common in women (P < 0.001) and young patients (P < 0.001). Eradication with PPI/A/M was successful in 89.9 % of patients and did not change significantly over the study period. Eradication rates were lower in young patients (P < 0.001). Whilst metronidazole resistance is increasing in Suffolk, this does not seem to have a significant effect on eradication rates. Metronidazole-based regimes are still effective first-line treatments in most patients.

Adult↗

Effects of infection with transmissible gastroenteritis virus on concomitant immune responses to dietary and injected antigens.

Normal piglets weaned onto soy- or egg-based diets generated antibody responses to fed protein. Concurrent infection with transmissible gastroenteritis virus (TGEV) did not affect the responses to dietary antigens at weaning, nor did it affect the subsequent development of tolerance. However, TGEV infection did enhance the primary immunoglobulin M (IgM) and IgG1, but not IgG2, antibody responses to injected soy in comparison to those of uninfected animals. Paradoxically, TGEV-infected animals showed an enhanced primary IgG1 antibody response to injected soy at 4 weeks of age, but they subsequently showed a reduced secondary response after an intraperitoneal challenge at 9 weeks of age in comparison to uninfected animals. The results suggest that an enteric virus, either used as a vaccine vector or present as a subclinical infection, may not have significant effects on the development of dietary allergies but may have effects both on the primary response and on the subsequent recall response to systemic antigens to which the animal is exposed concurrently with virus antigens.

Administration, Oral↗

Depressive symptoms are the strongest predictors of short-term declines in health status in patients with heart failure.

OBJECTIVES: The purpose of this study was to assess whether depressive symptoms are independently associated with changes in heart failure (HF)-specific health status. BACKGROUND: Depression is common in patients with HF, but the impact of depressive symptoms on the health status of these patients over time is unknown. METHODS: We conducted a multicenter prospective cohort study of outpatients with HF. Data from 460 patients who completed a baseline Medical Outcomes Study-Depression Questionnaire and both a baseline and follow-up (6 +/- 2 weeks) Kansas City Cardiomyopathy Questionnaire (KCCQ) were analyzed. The KCCQ measures HF-specific health status, including symptoms, physical and social function, and quality of life. Multivariable regression was used to evaluate depressive symptoms as a predictor of change in KCCQ scores, adjusting for baseline KCCQ scores and other patient variables. The primary outcome was change in KCCQ summary scores (range 0 to 100; higher scores indicate better health status; 5 points is a clinically meaningful change). RESULTS: Approximately 30% (139/460) of the patients had significant depressive symptoms at baseline. Depressed patients had markedly lower baseline KCCQ summary scores (beta = -19.6; p < 0.001). After adjustment for potential confounders, depressed patients were at risk for significant worsening of their HF symptoms, physical and social function, and quality of life (average change in KCCQ summary score = -7.1 points; p < 0.001). Depressive symptoms were the strongest predictor of decline in health status in the multivariable models. CONCLUSIONS: Depressive symptoms are a strong predictor of short-term worsening of HF-specific health status. The recognition and treatment of depression may be an important component of HF care.

Aged↗

Health status predicts long-term outcome in outpatients with coronary disease.

BACKGROUND: Although patient-reported health status measures have been used as end points in clinical trials, they are rarely used in other settings. Demonstrating that they independently predict mortality and hospitalizations among outpatients with coronary disease could emphasize their clinical value. METHODS AND RESULTS: This study evaluated the prognostic utility of the Seattle Angina Questionnaire (SAQ), a disease-specific health status measure for patients with coronary artery disease. Patients were enrolled in a prospective cohort study from 6 Veterans Affairs General Internal Medicine Clinics. All patients reporting coronary artery disease who completed a SAQ and had 1 year of follow-up were analyzed (n=5558). SAQ predictor variables were the physical limitation, angina stability, angina frequency, and quality-of-life scores. The primary outcome was 1-year all-cause mortality, and a secondary outcome was hospitalization for acute coronary syndrome (ACS). Lower SAQ scores were associated with increased risks of mortality and ACS admissions. Prognostic models controlling for demographic and clinical characteristics demonstrated significant independent mortality risk with lower SAQ physical limitation scores; odds ratios for mild, moderate, and severe limitation were 1.5, 2.0, and 4.0 versus minimal limitation (P<0.001). Odds ratios for mild, moderate, and severe angina frequency were 0.8, 1.2, and 1.6 (P=0.078). The odds ratios for ACS admission among those with mild, moderate, and severe angina frequency were 1.4, 2.0, and 2.2, respectively (P=0.016). CONCLUSIONS: SAQ scores are independently associated with 1-year mortality and ACS among outpatients with coronary disease and may serve a valuable role in the risk stratification of such patients.

Aged↗

Synthesis and preliminary analytical evaluation of the chemiluminescence from (4-[4-(dichloromethylsilanyl)-butyl]-4'-methyl-2,2'-bipyridyl)bis(2,2'-bipyridyl)ruthenium(II) covalently bonded to silica particles.

This paper describes, for the first time, a simple and effective synthetic route for covalently bonding the chemiluminescence reagent, (4-[4-(dichloromethylsilanyl)-butyl]-4'-methyl-2,2'-bipyridyl)bis(2,2'-bipyridyl)ruthenium(II) onto silica particles. The subsequent preparation of chemically regeneratable detection cells and their preliminary analytical evaluation with both sequential injection analysis and flow injection analysis are also reported. Unoptimised analytical figures of merit were established for standard solutions of codeine and sodium oxalate with detection limits calculated from three times the standard deviation of the blank signal, of 1 x 10(-8) M and 3 x 10(-7) M respectively. The chemically immobilised reagent exhibited some intriguing solvent and kinetic effects, which are also briefly discussed.

Journal Article↗