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Biomedical subjects

Andrew Robinson

Publications and source records attributed to Andrew Robinson.

At least 19 recordsLinked to original sources

Best Practice Guidelines on Publication Ethics: a publisher's perspective.

These Best Practice Guidelines on Publication Ethics describe Blackwell Publishing's position on the major ethical principles of academic publishing and review factors that may foster ethical behavior or create problems. The aims are to encourage discussion, to initiate changes where they are needed, and to provide practical guidance, in the form of Best Practice statements, to inform these changes. Blackwell Publishing recommends that editors adapt and adopt the suggestions outlined to best fit the needs of their own particular publishing environment.

Authorship↗

SSRPrimer and SSR Taxonomy Tree: Biome SSR discovery.

Simple sequence repeat (SSR) molecular genetic markers have become important tools for a broad range of applications such as genome mapping and genetic diversity studies. SSRs are readily identified within DNA sequence data and PCR primers can be designed for their amplification. These PCR primers frequently cross amplify within related species. We report a web-based tool, SSR Primer, that integrates SPUTNIK, an SSR repeat finder, with Primer3, a primer design program, within one pipeline. On submission of multiple FASTA formatted sequences, the script screens each sequence for SSRs using SPUTNIK. Results are then parsed to Primer3 for locus specific primer design. We have applied this tool for the discovery of SSRs within the complete GenBank database, and have designed PCR amplification primers for over 13 million SSRs. The SSR Taxonomy Tree server provides web-based searching and browsing of species and taxa for the visualisation and download of these SSR amplification primers. These tools are available at http://bioinformatics.pbcbasc.latrobe.edu.au/ssrdiscovery.html.

Classification↗

Recovery and evolutionary analysis of complete integron gene cassette arrays from Vibrio.

BACKGROUND: Integrons are genetic elements capable of the acquisition, rearrangement and expression of genes contained in gene cassettes. Gene cassettes generally consist of a promoterless gene associated with a recombination site known as a 59-base element (59-be). Multiple insertion events can lead to the assembly of large integron-associated cassette arrays. The most striking examples are found in Vibrio, where such cassette arrays are widespread and can range from 30 kb to 150 kb. Besides those found in completely sequenced genomes, no such array has yet been recovered in its entirety. We describe an approach to systematically isolate, sequence and annotate large integron gene cassette arrays from bacterial strains. RESULTS: The complete Vibrio sp. DAT722 integron cassette array was determined through the streamlined approach described here. To place it in an evolutionary context, we compare the DAT722 array to known vibrio arrays and performed phylogenetic analyses for all of its components (integrase, 59-be sites, gene cassette encoded genes). It differs extensively in terms of genomic context as well as gene cassette content and organization. The phylogenetic tree of the 59-be sites collectively found in the Vibrio gene cassette pool suggests frequent transfer of cassettes within and between Vibrio species, with slower transfer rates between more phylogenetically distant relatives. We also identify multiple cases where non-integron chromosomal genes seem to have been assembled into gene cassettes and others where cassettes have been inserted into chromosomal locations outside integrons. CONCLUSION: Our systematic approach greatly facilitates the isolation and annotation of large integrons gene cassette arrays. Comparative analysis of the Vibrio sp. DAT722 integron obtained through this approach to those found in other vibrios confirms the role of this genetic element in promoting lateral gene transfer and suggests a high rate of gene gain/loss relative to most other loci on vibrio chromosomes. We identify a relationship between the phylogenetic distance separating two species and the rate at which they exchange gene cassettes, interactions between the non-mobile portion of bacterial genomes and the vibrio gene cassette pool as well as intragenomic translocation events of integrons in vibrios.

DNA, Bacterial↗

Distribution and genetic diversity of the ABC transporter lipoproteins PiuA and PiaA within Streptococcus pneumoniae and related streptococci.

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. The existence of approximately 90 antigenically distinct capsular serotypes has greatly complicated the development of an effective pneumococcal vaccine. Virulence-associated proteins common and conserved among all capsular types now represent the best strategy to combat pneumococcal infections. PiuA and PiaA are the lipoprotein components of two pneumococcal iron ABC transporters and are required for full virulence in mouse models of infection. Here we describe a study of the distribution and genetic diversity of PiuA and PiaA within typical and atypical S. pneumoniae, Streptococcus oralis, and Streptococcus mitis strains. The genes encoding both PiuA and PiaA were present in all typical pneumococci tested, (covering 20 and 27 serotypes, respectively). The piuA gene was highly conserved within the typical pneumococci (0.3% nucleotide divergence), but was also present in "atypical" pneumococci and the closely related species S. mitis and S. oralis, showing up to 10.4% nucleotide divergence and 7.5% amino acid divergence from the typical pneumococcal alleles. Conversely, the piaA gene was found to be specific to typical pneumococci, 100% conserved, and absent from the oral streptococci, including isolates of S. mitis known to possess pneumolysin and autolysin. These are desirable qualities for a vaccine candidate and as a diagnostic tool for S. pneumoniae.

ATP-Binding Cassette Transporters↗

Is self-care a cost-effective use of resources? Evidence from a randomized trial in inflammatory bowel disease.

OBJECTIVES: To determine if a whole-system approach to self-management in inflammatory bowel disease (IBD), using a guidebook developed with patients and physicians trained in patient-centred care, leads to cost-effective use of health system resources. METHODS: Cost-effectiveness analysis over a one-year time horizon comparing the whole systems self-management approach to treatment with usual treatment. Nineteen hospitals in the northwest England were randomized to the intervention or to be controls; 651 patients (285 at intervention sites and 366 at control sites) with established IBD were included. The economic evaluation related differential health service costs, from a UK NHS perspective, to differences in quality-adjusted life years (QALYs) based on patients' responses to the EQ-5D. RESULTS: The intervention was associated with a mean reduction in costs of 148 pounds sterling per patient and a small mean reduction in QALYs of 0.00022 per patient compared with the control group. This resulted in an incremental cost per QALY gained of 676,417 pounds sterling for treatment as usual and a probability of around 63% that the whole-system approach to self-management is cost-effective, assuming a willingness to pay up to 30,000 pounds sterling for an additional QALY. CONCLUSIONS: Although there is uncertainty associated with these estimates, more widespread use of this method in chronic disease management seems likely to reduce health care costs without evidence of adverse effect on patient outcomes.

Cost-Benefit Analysis↗

PiuA and PiaA, iron uptake lipoproteins of Streptococcus pneumoniae, elicit serotype independent antibody responses following human pneumococcal septicaemia.

Streptococcus pneumoniae causes considerable morbidity and mortality worldwide. The need for a cheap and effective pneumococcal vaccine has necessitated the evaluation of common virulence-associated proteins as potential vaccine antigens. PiuA and PiaA are the lipoprotein components of two pneumococcal iron ABC transporters. Here, we show that patients with culture confirmed pneumococcal septicaemia have elevated levels of antibody to PiuA and PiaA in convalescent-phase, compared with acute-phase serum. Additionally, sera from septicaemic patients infected with 13 pneumococcal strains covering eight different serotypes, cross-reacted with recombinant PiuA-His(6) and PiaA-His(6) from a single pneumococcal strain, indicating that this immune response is serotype independent. Anti-PiuA and anti-PiaA antibodies were also found in healthy seven-month-old infants, indicating that they are immunogenic at a very early age.

ATP-Binding Cassette Transporters↗

Uncovering the limits of patient-centeredness: implementing a self-management trial for chronic illness.

Research evaluating self-management of chronic conditions points to the effectiveness of interventions' changing the health behavior of individuals. However, we know little about how self-management is negotiated within health services. The authors designed a qualitative investigation to illuminate the quantitative findings of a randomized controlled trial (RCT) of a self-management program for people with inflammatory bowel disease. They conducted in-depth interviews with physicians and patients, and qualitative analysis illuminated the nature of doctor-patient encounters and possible reasons for lack of change in patient satisfaction with the consultation. The findings suggest that factors inhibiting effective patient-centered consultations include failure of physicians to incorporate expressed need relevant to people's self-management activities fully, interpretation of self-management as compliance with medical instructions, and the organization of outpatients' clinics. Giving attention to these barriers might maximize the opportunities for patient self-management of chronic illness based on a therapeutic alliance with health care professionals.

Adult↗

Integron-associated mobile gene cassettes code for folded proteins: the structure of Bal32a, a new member of the adaptable alpha+beta barrel family.

The wide-ranging physiology and large genetic variability observed for prokaryotes is largely attributed, not to the prokaryotic genome itself, but rather to mechanisms of lateral gene transfer. Cassette PCR has been used to sample the integron/gene cassette metagenome from different natural environments without laboratory cultivation of the host organism, and without prior knowledge of any target protein sequence. Since over 90% of cassette genes are unrelated to any sequence in the current databases, it is not clear whether these genes code for folded functional proteins. We have selected a sample of eight cassette-encoded genes with no known homologs; five have been isolated as soluble protein products and shown by biophysical techniques to be folded. In solution, at least three of these proteins organise as stable oligomeric assemblies. The tertiary structure of one of these, Bal32a derived from a contaminated soil site, has been solved by X-ray crystallography to 1.8 A resolution. From the three-dimensional structure, Bal32a is found to be a member of the highly adaptable alpha+beta barrel family of transport proteins and enzymes. In Bal32a, the barrel cavity is unusually deep and inaccessible to solvent. Polar side-chains in its interior are reminiscent of catalytic sites of limonene-1,2-epoxide hydrolase and nogalonic acid methyl ester cyclase. These studies demonstrate the viability of direct sampling of mobile DNA as a route for the discovery of novel proteins.

Amino Acid Sequence↗

Improving networks between acute care nurses and an aged care assessment team.

BACKGROUND: Acute care nurses have an important role in the discharge planning of older people from hospital to home. However, few nurses understand the changing aged care system or the consequences of poor referral on the lives of older people postdischarge. AIMS AND OBJECTIVES: This paper reports the findings of a research project, which aimed to investigate the possibilities for facilitating the transition of older people from hospital to home through improving the working relationship between nurses and members of a multidisciplinary aged care assessment team (ACAT). DESIGN AND METHODS: The paper reports one action research cycle from a larger project. Action research was chosen because its focus on knowledge development and action leads to practical solutions to clinical problems. The research approach included interactive forums designed to facilitate effective collaboration between the nurses and ACAT in the discharge planning of older people. Data collection strategies included audiotapes of ACAT research discussions, field notes, policy documents, referral forms and an evaluation tool. RESULTS AND CONCLUSIONS: The findings illustrate that ward nurses have, at best, a limited knowledge and understanding of the aged care system, its function, or how to access services. They need assistance to develop their knowledge of services available to support older people following discharge. The conduct of interactive forums, which utilize a case study approach, facilitated such knowledge development and empowered the nurses to become more involved in discharge planning. Participation in the forums also facilitated new collaborative partnerships between the nurses and ACAT, which enhanced effective discharge planning. RELEVANCE TO CLINICAL PRACTICE: The paper outlines practical strategies to support collaboration between ward nurses and community providers and/or multi disciplinary assessment services. It provides a list of key considerations for the development of effective ward/community networks to facilitate the discharge of older people.

Acute Disease↗

Incorporating patients' views and experiences of life with IBS in the development of an evidence based self-help guidebook.

To become active partners in chronic illness management, patients need relevant information which clearly explains treatment choices. This paper describes a method of producing information to feed into production of a guidebook for people with irritable bowel syndrome (IBS). Users were involved throughout the development process. Five focus groups were held involving 23 people with IBS out of 147 who responded to a newspaper article asking for help with a study of self-care in IBS. Qualitative analysis of transcripts from these meetings formed the basis of guidebook development. Patients described their experiences, coping strategies, experiences of the healthcare system, treatments and social consequences of the condition. Medical literature searches were made to find answers to identified areas of information need. The book includes direct quotes from patients describing their own experiences. Guided and practical ways of support are required for people with IBS who want to self-manage their condition.

Adaptation, Psychological↗

A cluster-randomised controlled trial of a patient-centred guidebook for patients with ulcerative colitis: effect on knowledge, anxiety and quality of life.

A randomised controlled trial was undertaken to evaluate the impact of a patient-centred, evidence-based guidebook on knowledge, anxiety and quality of life (QoL) in patients with ulcerative colitis. The information in the book was developed closely with patients and focused on their identified needs. All 240 subjects in the study were on long-term follow-up for ulcerative colitis and were effectively responsible for the day-to-day management of their condition in the community. Outcomes were measured at 1 month and 9 months. Patients attended outpatient clinics at six hospitals: three hospitals were randomised to be control sites; and three were intervention sites where patients were given a copy of the guidebook. The results showed that patients receiving the guidebook demonstrated significantly better knowledge of their ulcerative colitis at 1 month, which persisted at 9 months, than patients in the control group. Anxiety and QoL scores were unchanged throughout. The present authors conclude that appropriate information is an essential prerequisite to greater patient involvement in chronic disease management. Patient-centred information increases knowledge without increasing anxiety and should be made available to patients through an appropriate health provider.

Adolescent↗

Neisseria lactamica protects against experimental meningococcal infection.

Immunological and epidemiological evidence suggests that the development of natural immunity to meningococcal disease results from colonization of the nasopharynx by commensal Neisseria spp., particularly with N. lactamica. We report here that immunization with N. lactamica killed whole cells, outer membrane vesicles, or outer membrane protein (OMP) pools and protected mice against lethal challenge by a number of diverse serogroup B and C meningococcal isolates in a model of bacteremic infection. Sera raised to N. lactamica killed whole cells, OMPs, or protein pools were found to cross-react with meningococcal isolates of a diverse range of genotypes and phenotypes. The results confirm the potential of N. lactamica to form the basis of a vaccine against meningococcal disease.

Animals↗

Effect of vaccination with carrier protein on response to meningococcal C conjugate vaccines and value of different immunoassays as predictors of protection.

In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM(197)) and diphtheria-tetanus vaccines given for boosting at school entry or leaving. Children (n = 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, or concurrently with one of three MCC vaccines conjugated to CRM(197) or TT. All of the MCC vaccines induced high antibody responses to the serogroup C polysaccharide that were indicative of protection. The immune response to the MCC-TT vaccine was reduced as a result of prior immunization with a tetanus-containing vaccine, but antibody levels were still well above the lower threshold for protection. Prior or simultaneous administration of a diphtheria-containing vaccine did not affect the response to MCC-CRM(197) vaccines. The immune responses to the carrier proteins were similar to those induced by a comparable dose of diphtheria or tetanus vaccine. The results also demonstrate that, for these conjugate vaccines in these age groups, both standard enzyme-linked immunosorbent assays and those that measure high-avidity antibodies to meningococcal C polysaccharide correlated equally well with assays that measure serum bactericidal antibodies, the established serological correlate of protection for MCC vaccines.

Adolescent↗

Evaluation of Ventricular dP/dt Before and After Open Heart Surgery Using Transesophageal Echocardiography.

The mean dP/dt during isovolumetric contraction (mean dP/dt(ic)) is a new echocardiographic index of ventricular function that has been shown to approximate and closely correlate with invasively measured peak dP/dt. It is amenable to rapid measurement via transesophageal echocardiography (TEE) and is theoretically independent of variations in ventricular anatomy and wall motion. It is therefore well suited for the assessment of ventricular function during surgery. The purpose of this study was to assess the clinical value of TEE determinations of mean dP/dt(ic) before and after cardiopulmonary bypass (CPB). The mean dP/dt(ic) of 50 patients undergoing open heart surgery for a variety of congenital and acquired heart defects was measured before and 15-30 minutes after CPB. Mean dP/dt(ic) averaged 1147 +/- 492 before and 1428 +/- 702 mmHg/sec after CPB (P < 0.01). Mean dP/dt(ic) was unchanged or increased in 45 patients and fell in only 5 patients. It increased significantly even among patients who did not receive supplemental inotropic agents. Mean dP/dt(ic) correlated well with the shortening fraction, especially among patients without segmental left ventricular wall-motion abnormalities. The general patterns observed for mean dP/dt(ic) were also seen when the data was corrected for variations in heart rate. A preoperative mean dP/dt(ic) < 765 mmHg/sec or a heart rate corrected mean dP/dt(ic) < 620 mmHg/sec indicated a high likelihood that inotropic support would be needed to facilitate weaning from CPB. Mean dP/dt(ic) may be a clinically useful, quantitative TEE index of perioperative changes in ventricular contractility.

Journal Article↗