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Biomedical subjects

D Barker

Publications and source records attributed to D Barker.

At least 19 recordsLinked to original sources

A novel use of a unilateral hinged partial denture.

This report describes a unilateral removable partial denture with a hinged arm with magnetic retention and a prosthetic flange component that was provided for a patient with localised periodontal tissue loss. While a unilateral partial denture is not generally advocated because of the risk of swallowing or aspiration, this case illustrates the effective use of such a design.

Adult↗

A model of technical variation of microarray signals.

We describe a mathematical model of signal from single-channel direct hybridization microarray platforms. The model establishes a linear relationship between microarray signals and their standard deviations from a minimum set of assumptions. We use the model to precisely define important microarray quality characteristics: resolved fold change and dynamic range. The definitions lead to closed form expressions relating these characteristics to physical parameters of the microarray experiment in the case when both specific and nonspecific binding of target to probe are governed by the Langmuir hybridization isotherm. The predictions of the model are in close agreement to data obtained from spike-in experiments. Given the generality of the model, the introduced definitions of dynamic range and resolved concentration fold-change can be used to conduct cross-platform comparisons and to guide improvement of the microarray platform.

Computational Biology↗

CRT improves the exercise capacity and functional reserve of the failing heart through enhancing the cardiac flow- and pressure-generating capacity.

BACKGROUND: While information on how cardiac resynchronisation therapy (CRT) affects cardiac performance at rest is readily available, the mechanisms whereby CRT alters cardiac function during maximal exercise are unclear. AIMS: We examined the medium-term effects of CRT on cardiac and physical functional reserve of patients with severe heart failure (CHF) and prolonged QRS duration. METHODS: Seventeen consecutive patients with severe CHF (NYHA III-IV) and widened QRS underwent maximal cardiopulmonary exercise testing with non-invasive central haemodynamic measurements before and 6-8 weeks after CRT pacemaker implantation. RESULTS: After CRT there were significant increases in exercise cardiac output by 19.3% (P=0.0048) from 9.5+/-3.4 l min(-1), peak mean arterial blood pressure by 14.1% (P=0.0001) from 91.3+/-13.6 mm Hg, and peak cardiac power output by 37.2% (P=0.0008) from 1.92+/-0.74 W. There were no significant changes in these variables at rest. Exercise duration (+42.3%, P=0.0002), NYHA functional class (P=0.0001) and SF-36 symptom score (P=0.0006) were also significantly improved. Powerful surrogate indicators of prognosis were also significantly improved with CRT: peak O(2) consumption (+20.9%, P=0.0007), VE/VCO(2) slope (-20.0%, P=0.005) and circulatory power (+42.0%, P=0.0012). CONCLUSION: In this cohort of patients, post-implant CRT significantly improved the flow-, pressure- and power-generating capacity of the failing hearts. This may be causally related to the improvements observed in exercise capacity, functional class and symptom scores.

Aged↗

Upper limits on a stochastic background of gravitational waves.

The Laser Interferometer Gravitational-Wave Observatory has performed a third science run with much improved sensitivities of all three interferometers. We present an analysis of approximately 200 hours of data acquired during this run, used to search for a stochastic background of gravitational radiation. We place upper bounds on the energy density stored as gravitational radiation for three different spectral power laws. For the flat spectrum, our limit of omega0 < 8.4 x 10(-4) in the 69-156 Hz band is approximately 10(5) times lower than the previous result in this frequency range.

Journal Article↗

Tooth wear as a result of pica.

This paper reports a case of tooth surface loss as a result of the eating disorder pica. Background to the condition is discussed and the clinical findings and treatment of the patient outlined. The case illustrates a rare cause of wear which should be considered when patients present with an unusual pattern of tooth surface loss.

Crowns↗

Limits on gravitational-wave emission from selected pulsars using LIGO data.

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10(-5) for the four closest pulsars.

Journal Article↗

Expression of axotomy-inducible and apoptosis-related genes in sensory nerves of rats with experimental diabetes.

In diabetes, peripheral nerves suffer deficient neurotrophic support-a situation which resembles axotomy. This raises the question: does inappropriate establishment of an axotomised neuronal phenotype contribute to diabetic neuropathy, and in extremis, does this provoke apoptosis? We hybridized reverse-transcribed RNA, from the dorsal root ganglia (DRG) of 8-week streptozotocin (STZ)-induced diabetic rats, to Affymetrix Rat Genome U34A chips and scanned the array for expression of (a) genes that are upregulated by axotomy, (b) proapoptotic and (c) anti-apoptotic genes. Expression of the axotomy-responsive genes coding for growth-associated protein 43 (GAP-43), galanin, neuropeptide Y (NPY), pre-pro-vasoactive intestinal polypeptide (pre-pro-VIP), neuronal nitric oxide synthase (nNOS), protease nexin 1, heat-shock protein 27 (HSP 27) and myosin light chain kinase II (MLCK II) was unaffected in ganglia from diabetic rats compared to controls; thus, no axotomised phenotype was established. The expression of the majority of proapoptotic genes in the DRG was also unaltered (bax, bad, bid, bok, c-Jun, p38, TNFR1, caspase 3 and NOS2). Similarly there was no change in expression of the majority of antiapoptotic genes (bcl2, bcl-xL, bcl-w, NfkappaB). These alterations in gene expression make it clear that neither axotomy nor apoptotic phenotypes are established in neurones in this model of diabetes.

Animals↗

More 'cries from the joints': assessment of the musculoskeletal system is poorly documented in routine paediatric clerking.

OBJECTIVES: The aim of this study was to describe the assessment of the musculoskeletal (MSK) system in comparison with other systems in routine paediatric medical clerking. Furthermore, to survey trainee paediatricians (SPRs, specialist registrars) about their self-rated confidence in assessing the MSK system. METHODS: Case notes of consecutive general paediatric medical patients admitted to three UK hospitals over a 4-week period were assessed using a standard pro forma. All patients had been assessed by a consultant paediatrician during their admission. A postal questionnaire was sent to all SPRs in training in each of the hospitals, regarding their confidence in assessing the MSK system compared with other systems and their exposure to MSK teaching. RESULTS: Case notes of 257 patients [117 females, median age 3 yr (range 1-18 yr)] were reviewed. The most common reason for admission was acute infection, although the spectrum of other recorded diagnoses varied between hospitals. Thirteen children (5%) had an acute problem (e.g. infection) against a background of chronic disease. The case note documentation showed that cardiovascular (CVS), respiratory (RS) and gastrointestinal (GI) systems were assessed in the vast majority (>90%) of patients, irrespective of the underlying diagnosis. However, other systems were less well recorded; the trend being the same in each hospital and in descending order, the neurological system (38%), skin (32%), eyes (10%) and musculoskeletal system (4%). Only 2.7% (7/257) patients were documented to have been asked about MSK symptoms, and only 1.6% (4/257) had any documentation of joint examination--in all cases this was limited (e.g. range of movement of the knee only), and no patients had documentation of gait being examined, even in those children presenting with 'limp'. The response rate to the postal questionnaire was 60% (67/112). The self-rated confidence in MSK assessment was markedly low in comparison with other systems, even though 61/67 recalled some teaching of the MSK system as an undergraduate (61/67) or postgraduate (50/67). Of note none could recall teaching as an undergraduate in paediatric MSK assessment and where there had been postgraduate rheumatology MSK teaching this had been delivered by paediatric rheumatologists in many cases (34/50), reflecting the centres participating in the study. CONCLUSIONS: In routine general paediatric medical in-patient clerking and throughout the admission, MSK assessment was rarely documented, and even where present was limited. This contrasts markedly with other systems which were examined in most children irrespective of the presenting complaint. Self-rated confidence in MSK assessment is low amongst SPRs compared with other systems, despite most recalling some teaching. This discrepancy between teaching and clinical practice needs to be addressed in undergraduate and postgraduate training.

Adolescent↗

LVB: parsimony and simulated annealing in the search for phylogenetic trees.

UNLABELLED: The program LVB seeks parsimonious phylogenies from nucleotide alignments, using the simulated annealing heuristic. LVB runs fast and gives high quality results. AVAILABILITY: The software is available at http://www.rubic.reading.ac.uk/lvb/ SUPPLEMENTARY INFORMATION: SUPPLEMENTARY INFORMATION may be downloaded from http://www.rubic.reading.ac.uk/~daniel/

Algorithms↗

HIV serostatus and recovery from severe childhood malnutrition. A retrospective matched case-control study.

The world-wide epidemic of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) has led to an increase in the number of HIV positive children, mainly through perinatal transmission. HIV/AIDS can lead to severe childhood malnutrition (SCM) and has been noted as an increasingly common cause of secondary SCM. In this context, it is important to make assessments of the appropriateness of current approaches to treatment of severe malnutrition in HIV positive children. A retrospective matched case-control study of ten HIV positive children admitted to the Tropical Metabolism Research Unit (TMRU) was conducted. There were few differences between cases and matched controls on admission to the ward. Oral candidiasis and lower respiratory tract infections appeared to occur more frequently, and serum globulin concentrations were significantly higher among HIV positive cases when compared to their controls. Despite the fact that the differences between cases and controls appeared to be small, four cases died; there were no deaths among the controls. The duration of the maintenance phase was approximately five days longer (p = 0.024) among cases than controls but the time between the end of the maintenance phase and discharge from the ward was not significantly longer for the cases. The results of this matched case-control study suggest that there are likely to be important differences between HIV positive and negative patients with SCM that influence risk of mortality and morbidity, particularly in the maintenance phase of treatment. Prospective studies will be required in order to explore these differences and to develop better approaches to the care of HIV positive children with SCM.

AIDS-Related Opportunistic Infections↗

Ensembl 2002: accommodating comparative genomics.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.

Animals↗

The effects of the Pro12Ala polymorphism of the PPARgamma-2 gene on lipid metabolism interact with body size at birth.

Body size at birth is an indicator of the intrauterine environment. The effects of the Pro12Pro genotype and the 12Ala allele of the PPARgamma-2 gene on glucose and insulin metabolism in adult life depend on body size at birth. A low birth weight is associated with insulin resistance and type 2 diabetes. The peroxisome proliferator-activated receptor-gamma (PPARgammas) are also regulators of adipocyte differentiation, and the PPARgamma-2 gene could also contribute to the development of dyslipidemia. Therefore, the effects of the Pro12Ala polymorphisms of the PPARgamma-2 gene on lipid metabolism were measured in 476 elderly persons whose birth weight was known. The Ala12 allele was associated with increased serum total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol concentrations but only among those who had birth weights below 3000 g. These interactions between the effects of the PPARgamma-2 gene on adult traits and the effects of birth weight may be interpreted as examples of gene-environmental interactions, which underlie plasticity during development.

Aged↗

Obesity from cradle to grave.

BACKGROUND: Obesity is known to track from early life into adult life. OBJECTIVE: To examine the relation of obesity in adult life to growth and living conditions during childhood. DESIGN: Birth cohort study. PARTICIPANTS: A total of 4515 people (2135 men and 2380 women) who were born at Helsinki University Central Hospital between 1934 and 1944, who attended child welfare clinics and were still resident in Finland in the year 2000. MEASUREMENTS: Incidence of obesity based upon lifetime maximum body mass index (BMI) ascertained from a postal questionnaire and defined as a BMI>or=30 kg/m(2). The main explanatory measurements were size at birth, childhood growth, and socioeconomic status in childhood and in adult life. RESULTS: The cumulative incidence of obesity was 33.8% in men and 32.4% in women. The incidence rose with increasing body size at birth. From birth the mean weight and BMI of people who later became obese exceeded the average and remained above average at a statistically significant level at all ages from 6 months to 12 y. Childhood BMI was a stronger predictor of adult obesity than body size at birth. A higher maternal BMI in pregnancy was associated with a more rapid childhood growth and an increased risk of becoming obese in adult life. Higher socioeconomic status and better educational attainment were associated with a lower prevalence of obesity. There was no association between the duration of breastfeeding and later obesity. CONCLUSIONS: These results emphasize the importance of early life factors in the pathogenesis of adult obesity.

Adolescent↗

Crowns and other extra-coronal restorations: try-in and cementation of crowns.

Having successfully negotiated the planning, preparation, impression and prescription of your crown, the cementation stage represents the culmination of all your efforts. This stage is not difficult, but a successful outcome needs as much care as the preceding stages. Once a restoration is cemented there is no scope for modification or repeat You have to get it right first time. Decemented crowns often have thick layers of residual cement suggesting problems with either initial seating or cement handling. When the fate of restorations costing hundreds of pounds depends on correct proportioning of cements and the quality of the mix, the value of a well-trained and experienced dental nurse is easy to see. Both dentist and nurse need a working knowledge of the materials they are handling.

Cementation↗

Crowns and other extra-coronal restorations: impression materials and technique.

Well-fitting indirect restorations can only be made if there are accurate models of the oral tissues available, made from high quality impressions. Waiting for an impression to set may be more stressful for the dentist than the patient. Should the impression need to be repeated there is the embarrassment of having to explain this to the patient, the cost implications of material and time wasted and the aggravation of running late for the next appointment. Yet, if a 'Nelsonian' eye is turned to a defective impression we can only expect a substandard restoration in return.

Crowns↗

The Ensembl genome database project.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.

Computational Biology↗