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Biomedical subjects

P Bradley

Publications and source records attributed to P Bradley.

At least 19 recordsLinked to original sources

Towards automated cellular image segmentation for RNAi genome-wide screening.

The Rho family of small GTPases is essential for morphological changes during normal cell development and migration, as well as during disease states such as cancer. Our goal is to identify novel effectors of Rho proteins using a cell-based assay for Rho activity to perform genome-wide functional screens using double stranded RNA (dsRNAs) interference. We aim to discover genes could cause the cell phenotype changed dramatically. Biologists currently attempt to perform the genome-wide RNAi screening to identify various image phenotypes. RNAi genome-wide screening, however, could easily generate more than a million of images per study, manual analysis is thus prohibitive. Image analysis becomes a bottleneck in realizing high content imaging screens. We propose a two-step segmentation approach to solve this problem. First, we determine the center of a cell using the information in the DNA-channel by segmenting the DNA nuclei and the dissimilarity function is employed to attenuate the over-segmentation problem, then we estimate a rough boundary for each cell using a polygon. Second, we apply fuzzy c-means based multi-threshold segmentation and sharpening technology; for isolation of touching spots, marker-controlled watershed is employed to remove touching cells. Furthermore, Voronoi diagrams are employed to correct the segmentation errors caused by overlapping cells. Image features are extracted for each cell. K-nearest neighbor classifier (KNN) is employed to perform cell phenotype classification. Experimental results indicate that the proposed approach can be used to identify cell phenotypes of RNAi genome-wide screens.

Algorithms↗

Sensitivity of human gamma interferon assay and tuberculin skin testing for detecting infection with Mycobacterium tuberculosis in patients with culture positive tuberculosis.

SETTING: Nine university-affiliated chest clinics in Australia. OBJECTIVE: To evaluate the sensitivity of a whole blood human gamma-interferon assay (HGIA, QuantiFERON-TB) for specific T lymphocyte responses and Tuberculin skin testing (TST) for the detection of Mycobacterium tuberculosis infection in subjects with culture-proven M. tuberculosis disease (TBCP). DESIGN: Prospective testing of 129 patients with recent TBCP and 100 patients with non-tuberculosis lung disease (NTBLD). RESULTS: Using a defined level of specific IFN-gamma production and TST 10mm as positive cut-offs, the sensitivity of HGIA was 81% compared to 89% for TST (p=0.06). When positive responses in both TST and HGIA were combined, 96% of TB patients were detected. For the NTBLD group, 43% of whom were born overseas, 73% were negative for both the HGIA and TST. Prior immunization with M. bovis (bacille Calmette-Guerin) (BCG) or the type of TB had no effect on the sensitivities of the assays. For those treated for <2 months, the sensitivities for both assays were 84%, but for those treated for >2 months the sensitivity of TST (90%) tended to be higher than for HGIA (81%) (p=0.07). The distribution of TST results in TB patients showed a broad peak between 10 and 25 mm, while the results in the HGIA were bimodal in both TB and NTBLD patients. CONCLUSION: HGIA may prove an alternative to skin testing for detecting M. tuberculosis infection in certain settings.

Adult↗

To lead or not to lead? Prospective controlled study of emergency nurses' provision of advanced life support team leadership.

BACKGROUND AND OBJECTIVES: In many emergency departments advanced life support (ALS) trained nurses do not assume a lead role in advanced resuscitation. This study investigated whether emergency nurses with previous ALS training provided good team leadership in a simulated cardiac arrest situation. METHODS: A prospective study was conducted at five emergency departments and one nurses' association meeting. All participants went through the same scenario. Details recorded included baseline blood pressure and pulse rate, time in post, time of ALS training, and subjective stress score (1 = hardly stressed; 10 = extremely stressed). Scoring took into account scenario understanding, rhythm recognition, time to defibrillation, appropriateness of interventions, and theoretical knowledge. RESULTS: Of 57 participants, 20 were ALS trained nurses, 19 were ALS trained emergency senior house officers (SHOs), and 18 were emergency SHOs without formal ALS training. The overall mean score for doctors without ALS training was 69.5%, compared with 72.3% for ALS trained doctors and 73.7% for ALS trained nurses. Nurses found the experience less stressful (subjective stress score 5.78/10) compared with doctors without ALS training (6.5/10). The mean time taken to defibrillate from the appearance of a shockable rhythm on the monitor by the nurses and those SHOs without ALS training was 42 and 40.8 seconds, respectively. CONCLUSION: ALS trained nurses performed as well as ALS trained and non ALS trained emergency SHOs in a simulated cardiac arrest situation and had greater awareness of the potentially reversible causes of cardiac arrest. Thus if a senior or middle grade doctor is not available to lead the resuscitation team, it may be appropriate for experienced nursing staff with ALS training to act as ALS team leaders rather than SHOs.

Advanced Cardiac Life Support↗

PRINTS and its automatic supplement, prePRINTS.

The PRINTS database houses a collection of protein fingerprints. These may be used to assign uncharacterised sequences to known families and hence to infer tentative functions. The September 2002 release (version 36.0) includes 1800 fingerprints, encoding approximately 11 000 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. In addition to its continued steady growth, we report here the development of an automatic supplement, prePRINTS, designed to increase the coverage of the resource and reduce some of the manual burdens inherent in its maintenance. The databases are accessible for interrogation and searching at http://www.bioinf.man.ac.uk/dbbrowser/PRINTS/.

Amino Acid Motifs↗

Deaths associated with restraint use in health and social care in the UK. The results of a preliminary survey.

Many aspects of the management of acutely disturbed behaviour have only relatively recently come under systematic scrutiny. Perhaps regrettably one of the last amongst the range of strategies that may be employed to be subjected to rigorous examination has been physical restraint. Considerable debate has recently taken place around what represents good practice in this sensitive and controversial area but the continuing dearth of research in some aspects of this area of practice has meant that this discussion has arguably been over reliant on 'expert' opinion. Questions continue regarding some fundamental issues of restraint, including the relative risks involved in alternative approaches, and anxieties have been expressed about the potential for injuries and death to result from restraint. This article outlines the results of a survey that sought to explore the incidence of deaths associated with restraint in health and social care settings in the UK. The outcome of an initial analysis of the cases identified is then discussed, with reference to the literature on restraint-related deaths, in order to identify the implications for practice.

Adult↗

Setting up a clinical skills learning facility.

OBJECTIVE: This paper outlines the considerations to be made when establishing a clinical skills learning facility. CONSIDERATIONS: Establishing a clinical skills learning facility is a complex project with many possible options to be considered. A number of professional groups, undergraduate or postgraduate, may be users. Their collaboration can have benefits for funding, uses and promotion of interprofessional education. Best evidence and educational theory should underpin teaching and learning. The physical environment should be flexible to allow a range of clinical settings to be simulated and to facilitate a range of teaching and learning methods, supported by computing and audio-visual resources. Facilities should be available to encourage self-directed learning. The skills programme should be designed to support the intended learning outcomes and be integrated within the overall curriculum, including within the assessment strategy. Teaching staff may be configured in a number of ways and may be drawn from a variety of backgrounds. Appropriate staff development will be required to ensure consistency and quality of teaching with monitoring and evaluation to assure appropriate standards. Patients can also play a role, not only as passive teaching material, but also as teachers and assessors. Clinical, diagnostic and therapeutic equipment will be required, as will models and manikins. The latter will vary from simple part task trainers to highly sophisticated human patient simulators. Care must be taken when choosing equipment to ensure it matches specified requirements for teaching and learning. CONCLUSION: Detailed planning is required across a number of domains when setting up a clinical skills learning facility.

Clinical Competence↗

Survey of total mercury in total diet food composites and an estimation of the dietary intake of mercury by adults and children from two Canadian cities, 1998-2000.

Total mercury was measured in 259 total diet food composites from two Canadian cities. Levels were generally low, with 46% of the composites having concentrations below the limit of detection, which ranged from 0.026 to 0.506 ng g(-1). The fish category contained the highest mercury concentrations, which averaged 67 ng g(-1) and ranged from 24 to 148 ng g(-1). All composites were below the Canadian guideline for total mercury in fish of 0.5 ppm. Dietary intakes of mercury averaged 0.022 microg kg(-1) body weight/day (microg kg(-1) day(-1)), and ranged from 0.012 microg kg(-1) day(-1) for females over 65 years old to 0.062 microg kg(-1) day(-1) for 0-1-month-old infants. For fish consumers, fish contributed to more than half of the ingested mercury. All intakes were well below Joint FAO/WHO Expert Committee on Food Additives Provisional Tolerable Weekly Intakes, expressed on a daily basis, of 0.71 microg kg(-1) day(-1) total mercury and 0.47 microg kg(-1) day(-1) methyl mercury, and also below a recent Health Canada recommended maximum methyl mercury intake of 0.2 microg kg(-1) day(-1) for children and women of child-bearing age.

Adolescent↗

Simulations of silicon microdosimetry measurements in fast neutron therapy.

Experimental silicon microdosimetry measurements were performed at a Fast Neutron Therapy facility. Monte Carlo based calculations of these measurements were made using the GEANT4 toolkit. Reasonable agreement between theoretical and experimental results was obtained and the contribution of elastic and inelastic reaction products to the final microdosimetric spectrum was determined.

Computer Simulation↗

Perceived quality of health care in macular disease: a survey of members of the Macular Disease Society.

AIM: To investigate the experiences of people with macular disease within the British healthcare system. METHOD: The Macular Disease Society Questionnaire, a self completion questionnaire designed to survey the experiences of people with macular disease, was sent to 2000 randomly selected members of the Macular Disease Society. The questionnaire incorporated items about people's experiences with health professionals and the information and support provided by them at the time of diagnosis and thereafter. RESULTS: Over 50% thought their consultant eye specialist was not interested in them as a person and 40% were dissatisfied with their diagnostic consultation. 185 people thought their general practitioner (GP) was well informed about macular disease but twice as many people thought their GP was not well informed. About an equal number of people thought their GP was supportive as those who thought their GP was not supportive. A total of 1247 people were told "nothing can be done to help with your macular disease." A number of negative emotional reactions were experienced by those people as a result, with 61% of them reporting feeling anxious or depressed. Of 282 people experiencing visual hallucinations after diagnosis with macular disease, only 20.9% were offered explanations for them. CONCLUSIONS: Many people with macular disease have unsatisfactory experiences of the healthcare system. Many of the reasons for dissatisfaction could be resolved by healthcare professionals if they were better informed about macular disease and had a better understanding of and empathy with patients' experiences.

Aged↗

BETAWRAP: successful prediction of parallel beta -helices from primary sequence reveals an association with many microbial pathogens.

The amino acid sequence rules that specify beta-sheet structure in proteins remain obscure. A subclass of beta-sheet proteins, parallel beta-helices, represent a processive folding of the chain into an elongated topologically simpler fold than globular beta-sheets. In this paper, we present a computational approach that predicts the right-handed parallel beta-helix supersecondary structural motif in primary amino acid sequences by using beta-strand interactions learned from non-beta-helix structures. A program called BETAWRAP (http://theory.lcs.mit.edu/betawrap) implements this method and recognizes each of the seven known parallel beta-helix families, when trained on the known parallel beta-helices from outside that family. BETAWRAP identifies 2,448 sequences among 595,890 screened from the National Center for Biotechnology Information (NCBI; http://www.ncbi.nlm.nih.gov/) nonredundant protein database as likely parallel beta-helices. It identifies surprisingly many bacterial and fungal protein sequences that play a role in human infectious disease; these include toxins, virulence factors, adhesins, and surface proteins of Chlamydia, Helicobacteria, Bordetella, Leishmania, Borrelia, Rickettsia, Neisseria, and Bacillus anthracis. Also unexpected was the rarity of the parallel beta-helix fold and its predicted sequences among higher eukaryotes. The computational method introduced here can be called a three-dimensional dynamic profile method because it generates interstrand pairwise correlations from a processive sequence wrap. Such methods may be applicable to recognizing other beta structures for which strand topology and profiles of residue accessibility are well conserved.

Bacteria↗

Specialist epilepsy nurses for treating epilepsy.

BACKGROUND: Epilepsy is the most common serious neurological condition after stroke, with a 0.5 per cent prevalence, and a two to three per cent life time risk of being given a diagnosis of epilepsy in the developed world. As a result of the perceived deficiencies and suggestions to improve the quality of care offered to people with epilepsy, two models of service provision have been suggested by researchers: specialist epilepsy out-patient clinics (as opposed to the management of patients in general neurology clinics or general medical clinics) and nurse-based liaison services between primary (GP) and secondary/tertiary (hospital based) care. OBJECTIVES: The aim of this review is to overview the evidence from controlled trials investigating the effectiveness of specialist epilepsy nurses compared to routine care. SEARCH STRATEGY: The following databases were searched: The Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 1999), MEDLINE, GEARS, BIDS (EMBASE=Excepta Medica), ECRI, Effectiveness Healthcare Bulletin, Effectiveness Matters, Bandolier, Evidence Based Purchasing, National Research Register, Vignettes and expert panels from Standing Group on Health Technology Assessment, PsycLit database, World Wide Web sites and reference lists of articles. SELECTION CRITERIA: All randomized controlled and quasi-randomized trials which considered specialist epilepsy nurse interventions with standard or alternative care were included in this review. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) seizure frequency (b) appropriateness of medication prescribed (c) social or psychological functioning scores (d) knowledge about epilepsy scores (e) objective measures of general health status/quality of life (f) patients' reports of information received (g) number of days spent on sick leave/missing school and employment status (h) costs of care (i) adverse effects. MAIN RESULTS: Three trials were included, two based in general practice and one in a neurology centre. The population of patients differed between trials, for example one study excluded patients with learning disabilities, and one only recruited patients with a new diagnosis. In view of this heterogeneity we decided not to pool results in a meta-analysis. As yet, there is no convincing evidence that specialist epilepsy nurses improve outcomes for people with epilepsy overall. Important outcomes (e.g. seizure frequency, psychosocial functioning, knowledge of epilepsy, general health status, work days lost, depression and anxiety scores) show no significant improvement. There is some evidence that those patients who have not had an epileptic seizure in the last six months are less at risk for depression. There is also evidence that newly diagnosed patients whose knowledge about epilepsy is poor may improve their epilepsy knowledge scores after nurse intervention. REVIEWER'S CONCLUSIONS: It is clearly plausible that specialist epilepsy nurses could improve quality in epilepsy care. However, there is as yet little evidence to support this assumption as the present research base is small. Further research is needed to investigate the effectiveness of specialist epilepsy nurses before such recommendations can be made.

Epilepsy↗

Epilepsy clinics versus general neurology or medical clinics.

BACKGROUND: Epilepsy is the most common serious neurological condition after stroke, with a 0.5 per cent prevalence, and a two to three per cent life time risk of being given a diagnosis of epilepsy in the developed world. As a result of perceived deficiencies of the quality of care offered to people with epilepsy, two models of service provision have been suggested by researchers: specialist epilepsy out-patient clinics (as opposed to the management of patients in general neurology clinics or general medical clinics) and nurse-based liaison services between primary (GP) and secondary/tertiary (hospital based) care. OBJECTIVES: The aim of this review was to overview the evidence from controlled trials investigating the effectiveness of specialist epilepsy clinics compared to routine care. A second similar review investigating the effectiveness of specialist epilepsy nurses is also underway. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 4, 1999), MEDLINE (January 1966 to December 1999), GEARS, BIDS (EMBASE=Excepta Medica(1998-99)), ECRI, Effectiveness Healthcare Bulletin, Effectiveness Matters, Bandolier, Evidence Based Purchasing, National Research Register, Vignettes and expert panels from Standing Group on Health Technology Assessment, PsycLit database, World Wide Web sites and reference lists of articles. In addition, we contacted experts in the field. SELECTION CRITERIA: All randomized controlled and quasi-randomized trials which considered specialist epilepsy clinic interventions with standard or alternative care were included in this review. DATA COLLECTION AND ANALYSIS: No controlled trials of suitable quality were identified for inclusion in the review. MAIN RESULTS: No controlled trials of suitable quality were identified for inclusion in the review. REVIEWER'S CONCLUSIONS: It is not known whether specialist epilepsy clinics improve outcomes for people with epilepsy. As yet, there is no high quality evidence which describes their effectiveness in improving care for people with epilepsy.

Epilepsy↗

A basic protocol for functional assessment of voice pathology, especially for investigating the efficacy of (phonosurgical) treatments and evaluating new assessment techniques. Guideline elaborated by the Committee on Phoniatrics of the European Laryngological Society (ELS).

The proposal of this basic protocol is an attempt to reach better agreement and uniformity concerning the methodology for functional assessment of pathologic voices. The purpose is to allow relevant comparisons with the literature when presenting/publishing the results of voice treatment, e.g. a phonosurgical technique, or a new/improved instrument or procedure for investigating the pathological voice. Meta-analyses of the results of voice treatments are generally limited and may even be impossible owing to the major diversity in the ways functional outcomes are assessed. A multidimensional set of minimal basic measurements suitable for all "common" dysphonias is proposed. It includes five different approaches: perception (grade, roughness, breathiness), videostroboscopy (closure, regularity, mucosal wave and symmetry), acoustics (jitter, shimmer, Fo-range and softest intensity), aerodynamics (phonation quotient), and subjective rating by the patient. The protocol is elaborated on the basis of an exhaustive review of the literature, of the experience of the Committee members, and of plenary discussions within the European Laryngological Society. Instrumentation is kept to a minimum, but it is considered essential for professionals performing phonosurgery.

Clinical Protocols↗