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Biomedical subjects

David Jones

Publications and source records attributed to David Jones.

17 recordsLinked to original sources
PubMed2004

Relations between violence, calendar events and ambient conditions.

National assault injury surveillance has identified major seasonal variation, but it is not clear whether assault injury is a seasonal problem in large cities. Relationships between community violence, calendar events and ambient conditions were investigated with reference to prospective, Accident and Emergency (A&E) derived information obtained from people injured in assaults in Cardiff between 1 May 1995 and 30 April 2000. Records of daily local ambient conditions included data relating to temperature, rainfall and sunshine hours and data of major local sporting events and annual holidays were studied. Pearson correlation coefficients were used to evaluate associations between variables. Overall, 19,264 assault-related A&E attendances were identified over the 5-year period. Almost three-quarters were males. Violence was clustered predominantly on Saturdays and Sundays, New Year and rugby international days. Temperature, rainfall and sunlight hours did not correlate significantly with violence (P > 0.05). The findings indicate that injury reduction effort should be intensified at the known risk times for violence and that in a capital city/regional centre violence cannot be predicted on the basis of ambient conditions.

Adolescent↗
PubMed2003

Predicting reliable regions in protein alignments from sequence profiles.

For applications such as comparative modelling one major issue is the reliability of sequence alignments. Reliable regions in alignments can be predicted using sub-optimal alignments of the same pair of sequences. Here we show that reliable regions in alignments can also be predicted from multiple sequence profile information alone. Alignments were created for a set of remotely related pairs of proteins using five different test methods. Structural alignments were used to assess the quality of the alignments and the aligned positions were scored using information from the observed frequencies of amino acid residues in sequence profiles pre-generated for each template structure. High-scoring regions of these profile-derived alignment scores were a good predictor of reliably aligned regions. These profile-derived alignment scores are easy to obtain and are applicable to any alignment method. They can be used to detect those regions of alignments that are reliably aligned and to help predict the quality of an alignment. For those residues within secondary structure elements, the regions predicted as reliably aligned agreed with the structural alignments for between 92% and 97.4% of the residues. In loop regions just under 92% of the residues predicted to be reliable agreed with the structural alignments. The percentage of residues predicted as reliable ranged from 32.1% for helix residues to 52.8% for strand residues. This information could also be used to help predict conserved binding sites from sequence alignments. Residues in the template that were identified as binding sites, that aligned to an identical amino acid residue and where the sequence alignment agreed with the structural alignment were in highly conserved, high scoring regions over 80% of the time. This suggests that many binding sites that are present in both target and template sequences are in sequence-conserved regions and that there is the possibility of translating reliability to binding site prediction.

Algorithms↗
PubMed2003

Monitoring the decrease of circulating malignant T cells in cutaneous T-cell lymphoma during photopheresis and interferon therapy.

BACKGROUND: The prognosis of patients with stage IV cutaneous T-cell lymphoma (CTCL) is grim and therapeutic options are limited. Treatment of advanced-stage CTCL is aimed at suppressing the dominant T-cell clone, which is typically present in the skin, peripheral blood, and lymph nodes. OBSERVATIONS: We detected the expansion of 1 T-cell clone expressing the T-cell receptor V beta 14 in the peripheral blood of a patient with stage IVA CTCL. Before initiation of combination therapy with photopheresis and low-dose interferon alpha, the dominant T-cell clone represented 84% of the total T-cell population. After successful therapy, this clone showed a dramatic decrease to 6% of the T-cell population after 6 months of treatment. This reduction in the percentage of the malignant T-cell population in response to therapy was paralleled by clinical skin improvement from initial generalized erythroderma to undetectable skin disease. CONCLUSIONS: This case demonstrates that response to combination treatment with photopheresis and low-dose interferon alpha in patients with advanced CTCL may be accurately and quantitatively followed up by monitoring the percentage of the malignant T-cell clone (when identifiable) within the total circulating T-cell population by flow cytometry.

Antineoplastic Agents↗
PubMed2003

Cost-effectiveness of anastrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer.

BACKGROUND: In a recent trial of first-line therapy in 353 postmenopausal women with predominantly hormone receptor-positive advanced breast cancer (the North American trial), anastrozole 1 mg QD produced a significantly longer time to disease progression (TTP) than tamoxifen 20 mg QD (11.1 months vs 5.6 months; P = 0.005). Both treatments were well tolerated, but there were fewer thromboembolic events and a reduced incidence of vaginal bleeding with anastrozole. OBJECTIVE: The aim of this study was to conduct an economic analysis of anastrozole versus tamoxifen based on data from the North American trial. METHODS: Quality-adjusted TTP (QATTP) was determined by combining TTP values with uniform or graded weights for adverse events using the Quality-adjusted Time Without Symptoms and Toxicity method. Direct health care costs before and after disease progression were determined from the perspective of 4 types of health care insurers in the United States: health maintenance organizations (HMOs), indemnity plans, preferred provider organizations (PPOs), and point-of-service (POS) plans. RESULTS: Median QATTP with graded weights was 9.7 months for anastrozole, compared with 4.6 months for tamoxifen (P = 0.003). A resultant reduction in health care resource utilization was observed, particularly the requirements for hospitalization, outpatient visits, and chemotherapy, but the statistical significance of this observation was not assessed. Incremental cost savings per patient before and after disease progression were observed with anastrozole compared with tamoxifen (9064 dollars for HMO, 9678 dollars for indemnity plan, 14,273 dollars for PPO, and 12,715 dollars for POS; all P < 0.01). CONCLUSIONS: In the US managed care setting, anastrozole produced a higher QATTP and incurred lower treatment costs than tamoxifen in a population of postmenopausal women with predominantly hormone receptor-positive advanced breast cancer. Therefore, anastrozole was more cost-effective than tamoxifen as first-line endocrine therapy in the population studied.

Anastrozole↗
PubMed2003

Joint torques and dynamic joint stiffness in elderly and young men during stepping down.

OBJECTIVE: To compare the joint torque pattern and dynamic joint stiffness at the knee and ankle in elderly and young men during stepping down. BACKGROUND: Adequate joint stiffness is critical during the single support phase to control forward and downward body momentum. DESIGN: Six active elderly men (mean 67.7) and six young men (mean 23.6) of similar body mass and height, were filmed stepping down from one force platform to another. Repeated trials were undertaken at three different step heights (200, 250, and 300 mm). METHOD: Joint torques were determined for the ankle and knee of the support limb throughout the single support phase. The gradient of the joint torque-angle graph was calculated to define dynamic joint stiffness of the ankle and knee in two phases; (I) from initiation of movement until heel-off of the supporting limb, and (II) from heel-off of the supporting limb to contra-limb touch down. RESULTS: Maximum ankle torque values were lower in the elderly and occurred at a larger dorsiflexion angle (P<0.05). Knee torque patterns were similar in both groups. Phase I ankle stiffness was significantly less in the elderly (4.0-5.2 Nm/ degrees ) at all step heights compared to the young (7.6 - 8.7 Nm/ degrees ). In both groups ankle stiffness in Phase II increased with step height, while knee joint stiffness decreased. CONCLUSIONS: The different torque pattern and lower dynamic ankle stiffness in the elderly, particularly for Phase I, suggested an altered control strategy. These findings highlight the importance of dynamic ankle joint stiffness in stepping down. RELEVANCE: Understanding how the elderly step down may be important in developing strategies to prevent falls.

Adaptation, Physiological↗
PubMed2003

Multivariate exploratory tools for microarray data analysis.

The ultimate success of microarray technology in basic and applied biological sciences depends critically on the development of statistical methods for gene expression data analysis. The most widely used tests for differential expression of genes are essentially univariate. Such tests disregard the multidimensional structure of microarray data. Multivariate methods are needed to utilize the information hidden in gene interactions and hence to provide more powerful and biologically meaningful methods for finding subsets of differentially expressed genes. The objective of this paper is to develop methods of multidimensional search for biologically significant genes, considering expression signals as mutually dependent random variables. To attain these ends, we consider the utility of a pertinent distance between random vectors and its empirical counterpart constructed from gene expression data. The distance furnishes exploratory procedures aimed at finding a target subset of differentially expressed genes. To determine the size of the target subset, we resort to successive elimination of smaller subsets resulting from each step of a random search algorithm based on maximization of the proposed distance. Different stopping rules associated with this procedure are evaluated. The usefulness of the proposed approach is illustrated with an application to the analysis of two sets of gene expression data.

Algorithms↗
PubMed2003

Predictors of attributions of self-blame and internalizing behavior problems in sexually abused children.

BACKGROUND: The purpose of the present study was to identify predictors of two potential sequelae of child sexual abuse, self-blame attributions and internalizing behavior problems. METHODS: In the study, detailed information was collected on 218 victims of sexual abuse aged 4 to 17, involved in criminal cases, about their background, the abuse, and their mother's reaction following discovery of the abuse. RESULTS: Increased attributions of self-blame were predicted by the child having a close relationship with the perpetrator, experiencing severe sexual abuse (e.g., long-lasting abuse that involved penetration), perceiving the abuse as disgusting, and coping with the abuse by pretending it was not happening. Similar factors did not emerge as predictors of internalizing behavior problems. CONCLUSIONS: Results suggest that different child and abuse characteristics predict the two sequelae often associated with childhood sexual abuse. Thus, although self-blame attributions and behavior problems are often considered similar consequences of sexual abuse, there appears a need to distinguish the two types of outcomes following sexual victimization in childhood.

Adolescent↗
PubMed2003

An exploratory study of language interpretation services provided by videoconferencing.

We explored the feasibility and acceptability of the remote provision of a language interpretation service during general practice consultations. Three methods were used to provide an interpretation service: a physically present interpreter (PI), a remote interpreter accessed using an ISDN videoconferencing link at 128 kbit/s (VI) and a remote interpreter accessed by telephone (TI). Thirty-six non-English-speaking patients were invited to take part and 35 agreed to do so. Twenty-nine (83%) of the patients recruited were female. The age range of the participants was 24-51 years. Fourteen consultations took place with a physically present interpreter, 11 using videoconferencing and 10 using the telephone. Mean scores on the Patient Enablement Instrument were 5.2 for the PI group, 2.3 for the VI group and 5.1 for the TI group. Mean scores on the Medical Interview Satisfaction Scale were 5.3 for the PI group, 4.9 for the VI group and 5.3 for the TI group. The visual quality and sound quality of remote interpreting were satisfactory. Both videoconferencing and hands-free telephones can deliver an acceptable interpreting service in primary care.

Adult↗
PubMed2002

Summer-time distribution of air pollutants in Sequoia National Park, California.

Concentrations of air pollutants were monitored during the May November 1999 period on a network of forested sites in Sequoia National Park, California. Measurements were conducted with: (1) active monitors for nitric oxide (NO), nitrogen dioxide (NO2) and ozone (O3); (2) honeycomb denuder/filter pack systems for nitric acid vapor (HNO3), nitrous acid vapor (HNO2), ammonia (NH3), sulfur dioxide (SO2), particulate nitrate (NO3-), ammonium (NH4+), and sulfate (SO4(2-)); and (3) passive samplers for O3, HNO3 and NO2. Elevated concentrations of O3 (seasonal means 41-71 ppb), HNO3 (seasonal means 0.4-2.9 microg/m3), NH3 (seasonal means 1.6-4.5 microg/m3), NO3 (1.1-2.0 microg/m3) and NH4+ (1.0-1.9 microg/m3) were determined. Concentrations of other pollutants were low. With increasing elevation and distance from the pollution source area of O3, NH3 and HNO3 concentrations decreased. Ammonia and NH4+ were dominant N pollutants indicating strong influence of agricultural emissions on forests and other ecosystems of the Sequoia National Park.

Agriculture↗
PubMed2002

Continual production of phosphatidic acid by phospholipase D is essential for antigen-stimulated membrane ruffling in cultured mast cells.

Phospholipase Ds (PLDs) are regulated enzymes that generate phosphatidic acid (PA), a putative second messenger implicated in the regulation of vesicular trafficking and cytoskeletal reorganization. Mast cells, when stimulated with antigen, show a dramatic alteration in their cytoskeleton and also release their secretory granules by exocytosis. Butan-1-ol, which diverts the production of PA generated by PLD to the corresponding phosphatidylalcohol, was found to inhibit membrane ruffling when added together with antigen or when added after antigen. Inhibition by butan-1-ol was completely reversible because removal of butan-1-ol restored membrane ruffling. Measurements of PLD activation by antigen indicate a requirement for continual PA production during membrane ruffling, which was maintained for at least 30 min. PLD1 and PLD2 are both expressed in mast cells and green fluorescent protein-tagged proteins were used to identify PLD2 localizing to membrane ruffles of antigen-stimulated mast cells together with endogenous ADP ribosylation factor 6 (ARF6). In contrast, green fluorescent protein-PLD1 localized to intracellular vesicles and remained in this location after stimulation with antigen. Membrane ruffling was independent of exocytosis of secretory granules because phorbol 12-myristate 13-acetate increased membrane ruffling in the absence of exocytosis. Antigen or phorbol 12-myristate 13-acetate stimulation increased both PLD1 and PLD2 activity when expressed individually in RBL-2H3 cells. Although basal activity of PLD2-overexpressing cells is very high, membrane ruffling was still dependent on antigen stimulation. In permeabilized cells, antigen-stimulated phosphatidylinositol(4,5)bisphosphate synthesis was dependent on both ARF6 and PA generated from PLD. We conclude that both activation of ARF6 by antigen and a continual PLD2 activity are essential for local phosphatidylinositol(4,5)bisphosphate generation that regulates dynamic actin cytoskeletal rearrangements.

ADP-Ribosylation Factor 1↗
PubMed2002

The osteoblast mechano-receptor, microgravity perception and thermodynamics.

Mechano-sensing in cells is tightly obliged with changes in intracellular free calcium (IFC), regulation of specific genes and activation of specific second messenger systems. To investigate whether single non-professional cells like osteoblasts can detect microgravity through the mechano-sensor, measurements on a sub-orbital rocket and parabolic flights observing the IFC and gene expression were performed. We find that microgravity did neither effect IFC nor gene expression. Thermal and mechanical noise within cells is too high in relation to the change of force due to the change from gravity to microgravity. Complementary force measurements have shown that cells exert high forces on the substrate and that these high forces have to be applied for activation.

Journal Article↗
PubMedDate not supplied

High-level expression of recombinant IgG in the human cell line per.c6.

The number of therapeutic monoclonal antibodies in production is expected to rise rapidly in the next few years. As a result, there is much focus on the optimization of antibody expression platforms. Several issues are important including the speed of transition from bench to manufacturing, yield of IgG, and quality (particularly of the glycan structures present on immunoglobulins). We have characterized the human cell line PER.C6 for its ability to produce recombinant IgG. Production yields are still being optimized, but in nonfed batch culture, PER.C6 is able to grow to a cell density of 5 x 10(6) cells/mL and produce 300-500 mg/L IgG; this is likely to increase significantly in fed batch cultures. The generation of antibody-producing cell lines is fast, as rounds of amplification of inserted genes are not required for high production yields. The gene copy number of inserted genes is in the region of 1-10 copies per genome. In addition, PER.C6 is a human cell line, and so does not add glycans, which are immunogenic in humans. A core fucose molecule is essentially always present, and galactose residues are present at a physiological level (0, 1, and 2 galactose residues per glycan are present at a ratio of 1:2:1). No hybrid or high-mannose structures are seen.

Bioreactors↗
PubMedDate not supplied

Accuracy of 11-gauge vacuum-assisted core biopsy of mammographic breast lesions.

BACKGROUND: Image-guided percutaneous biopsy has largely replaced excisional biopsy of mammographic lesions. Vacuum-assisted core biopsy has improved sampling of such lesions. The objectives of this study were to define the accuracy of the vacuum-assisted 11-gauge stereotactic core biopsy in sampling of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) and to define histologic and mammographic features of target lesions, which predict sampling errors. METHODS: Between October 1996 and March 2000, 1341 patients underwent stereotactic 11-gauge vacuum-assisted biopsy. Patients with ADH or DCIS were encouraged to undergo excisional biopsy. RESULTS: Surgical excision of 37 ADH lesions revealed 5 missed DCIS lesions and 1 missed invasive cancer. Twelve of 91 DCIS lesions were upstaged to invasive cancer upon excision. The underestimation rate was highest in patients with DCIS when the target lesion for biopsy was a zone of calcifications >1.5 cm. No correlation existed between the histologic features of DCIS lesions diagnosed by stereotactic biopsy and the presence of infiltrating disease on excision. CONCLUSIONS: Vacuum-assisted 11-gauge stereotactic core biopsy understages 13.2% and 13.5% of DCIS and ADH lesions, respectively. In patients with DCIS found by stereotactic biopsy, a target zone of calcifications >1.5 cm is associated with a higher underestimation rate of infiltrating disease.

Biopsy, Needle↗