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Publications and source records attributed to A Page.

At least 19 recordsLinked to original sources

Effect of marker cluster design on the accuracy of human movement analysis using stereophotogrammetry.

This paper presents a new, simple model to evaluate the instrumental random errors in kinematic analysis of human movements using stereophotogrammetry. By means of equations analogous to that relate linear or angular momentum with linear or angular velocities, a direct measurement of instantaneous motion can be made without previous finite displacement analysis. Single explicit expressions can be obtained to evaluate the influence of instrumental random errors in the accuracy of the kinematic variables. From these expressions, some conclusions about the effect of marker cluster design on the experimental errors are obtained. An experiment has been carried out in order to validate the proposed technique and to assess the experimental errors in linear and angular velocity measurement and its influence in instantaneous helical axis determination.

Biomechanical Phenomena↗

Normalizing temporal patterns to analyze sit-to-stand movements by using registration of functional data.

Functional data analysis techniques provide an alternative way of representing movement and movement variability as a function of time. In particular, the registration of functional data provides a local normalization of time functions. This normalization transforms a set of curves, records of repeated trials, yielding a new set of curves that only vary in terms of amplitude. Therefore, main events occur at the "same time" for all transformed curves and interesting features of individual recordings remain after averaging processes. This paper presents an application of the registration process to the analysis of the vertical forces exerted on the ground by both feet during the sit-to-stand movement. This movement is particularly interesting in functional evaluations related to balance control, lower extremity dysfunction or low-back pain.

Biomechanical Phenomena↗

Physical activity patterns in nonobese and obese children assessed using minute-by-minute accelerometry.

OBJECTIVE: To determine the levels and patterns of physical activity in a sample of obese (> or =99th percentile body mass index (BMI)) and nonobese (<99th percentile BMI) children. DESIGN: Cross-sectional study. SETTING: Children were recruited from schools in Bristol and from the childhood obesity clinic, Bristol Royal Hospital for Children. Children were instructed in the use of the accelerometer either while at school or in the clinic, and wore the instrument while carrying out their normal daily activities for 7 days. PARTICIPANTS: A total of 133 children (mean age 10.5+/-0.8 y). In all 11 (16.9%) of the 65 girls and 14 (20.6%) of the 68 boys were classified as obese (above the 99th percentile for BMI and corresponding to projected adult BMI of 30). MAIN OUTCOME MEASURES: Objectively measured physical activity volume, intensity and pattern. RESULTS: Obese children were significantly less physically active overall than their nonobese counterparts (31,844+/-13,200 vs 41,844+/-10,430 counts/h; 95% confidence interval 4407 to 15592; P=0.001). Similarly the obese children spent less time in physical activity of moderate or greater intensity than the nonobese children (9.9+/-3.9 vs 12.9+/-4.2 min/h; 95% confidence interval 1.15 to 4.80; P=0.002). Hourly patterns of activity indicated a tendency in obese children to be less active than nonobese children at times when activity was more likely to be determined by free choice, particularly outside of school time. CONCLUSIONS: Obese children demonstrated patterns of physical activity that may have contributed to and are likely to sustain their obesity. Minute-by-minute accelerometry is a valuable tool to investigate physical activity patterns in obese children. It can identify periods when intervention to increase activity may be most appropriate and provide an evidence base for specific exercise prescription in primary and secondary care.

Body Mass Index↗

Age-specific interval breast cancers in New South Wales and meta-analysis of studies of women aged 40-49 years.

OBJECTIVE: To compare interval cancers in the 40-49 year age group with other age groups in New South Wales and with published trials and service studies. SETTING: New South Wales data were derived from the population-based biennial mammography screening program, which achieved state-wide coverage in 1995. Women aged 40-49 years screened during 1995-1998 were included. METHODS: Bilateral two-view mammography with reading by two radiologists was employed for biennial screening examinations. Interval cancers were detected by the screening program and by linkage with the state-wide cancer registry. Incidence of interval cancer based on the date of diagnosis was estimated as a proportion of the expected underlying breast cancer incidence for first- and second-year interval cancers. Sensitivity estimates were also calculated. Comparative data for the 40-49 year age group were derived from the published literature for meta-analyses of trial and service studies. RESULTS: Interval cancer rates for New South Wales decreased with increasing age, with the highest proportional incidence in the 40-49 year age group for first year (56%, 95% confidence interval [CI] 50-62%) and second-year (86%, 95% CI 82-90%) interval cancers. Proportional incidence for women aged 50-69 years for first- and second-year interval cancers was 31% (95%CI 29-33%) and 50% (95% CI 47-52%) respectively. Sensitivity estimates for the program increased significantly with age, with lowest sensitivity estimates evident for women 40-49 years. In women aged 40-49 years the meta-analysed proportional incidence rate for randomised trials of screening for first- and second-year interval cancers was 42% (95% CI 21-62%) and 63% (95% CI 55-71%) respectively, while for service studies it was 44% (95% CI 31-58%) and 72% (95% CI 51-92%). Proportional incidence in the New South Wales program for women aged 40-49 years was not significantly different to the meta-analysed proportional incidences for trial and service studies in the first year, or for service studies in the second year. CONCLUSION: Proportional incidence of interval cancer was significantly higher in women aged 40-49 years in New South Wales relative to older age groups, but did not differ significantly from service studies of women in a similar age group. The effectiveness of mammography screening for this age group needs to be examined in view of the comparatively high rate of interval cancers.

Adult↗

Pain in femoral arteriography. A double-blind, randomized, clinical study comparing safety and efficacy of the iso-osmolar iodixanol 270 mgI/ml and the low-osmolar iomeprol 300 mgI/ml in 9 European centers.

PURPOSE: To compare the injection-associated pain and heat sensation after administration of the iso-osmolar contrast medium (IOCM) iodixanol (Visipaque trade mark 270 mg I/ml) and the low osmolar contrast medium (LOCM) iomeprol (Iomeron trade mark 300 mg I/ml) in femoral arteriography. MATERIAL AND METHODS: 352 patients received iodixanol or iomeprol in a prospective, double-blind, randomized, parallel-group clinical trial. The first injection during femoral arteriography (DSA with automated stepping) was standardized. Injection-associated pain and heat sensation, efficacy and safety up to 72 h were evaluated. RESULTS: The iodixanol group reported significant less injection-associated pain than the iomeprol group after the first injection (7.4% vs. 17.6%; p = 0.007), and after all injections (11% vs. 19.4%; p = 0.045). Iodixanol caused less heat sensation after the first injection (p = 0.007) and after all injections (p = 0.029). Heat sensations in the iodixanol group were less intense after all injections (p < 0.0001). No difference was found between the groups regarding the frequency of patients having adverse reactions (5.1% vs. 4%). CONCLUSION: The IOCM iodixanol caused significantly less frequent injection-associated pain and heat sensation than the LOCM iomeprol during femoral arteriography.

Angiography, Digital Subtraction↗

Birth cohort effects in New South Wales suicide, 1865-1998.

OBJECTIVE: To examine birth cohort effects in New South Wales (NSW) suicide data (1865-1998). METHOD: Aggregate suicide data were examined after controlling for age and period using descriptive statistics and Poisson regression modelling. Three approaches were applied to address the non-identification of age, period and cohort in age-period-cohort (APC) models of suicide. RESULTS: Apparent cohort effects in male and female suicide using a minimum constraints APC model of age, period and cohort were no longer present in female suicide when a surrogate period APC model was used, and were absent in both male and female suicide when identifiable cohort effects were isolated using a 'drift' adjusted approach to APC modelling. CONCLUSION: Increases in youth suicide rates in NSW occurring since the 1960s cannot be attributed to cohort effects, such as family influences on development. The causes of youth suicide are thus effects operating contemporaneously.

Age Factors↗

The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination.

AIM: Children who are uncooperative, due either to their age or medical condition, usually require sedation or a general anaesthetic (GA) to ensure immobility during magnetic resonance imaging (MRI) examination. These procedures have a risk of respiratory compromise and loss of vital reflexes. Melatonin induces a natural sleep with no known complication or risk of respiratory compromise. We aimed to evaluate the use of melatonin in these uncooperative children. MATERIAL AND METHODS: An unselected group of 40 children, who had been referred for an MRI examination of the brain under sedation or GA, were chosen to receive melatonin instead. They all received 10 mg of melatonin and 17 children additionally underwent some form of sleep deprivation. The number of children who went to sleep and had a successful MRI examination was recorded. RESULTS: Twenty-six children (65%) went to sleep and of these 22 (55%) had a successful MRI examination. In the 17 children who underwent sleep deprivation, 13 (76%) went to sleep and had a successful MRI examination. There was no complication. CONCLUSIONS: Melatonin may provide an alternative to conventional sedation regimes and GA for uncooperative children undergoing an MRI examination. The use of sleep deprivation improves the success rate and there is no risk of respiratory compromise.

Adolescent↗

Superior venocaval obstruction secondary to central venous catheter-related thromboses in two patients with metastatic colorectal carcinoma receiving weekly 5-flurouracil. Should adjusted-dose warfarin be used as thromboprophylaxis?

Standard treatment for patients with metastatic colorectal carcinoma (MCC) involves treatment with weekly 5-flurouracil (5-FU) chemotherapy by continuous infusion, requiring the insertion of a central venous catheter (CVC). One of the main complications of CVCs is venous thromboembolic disease (VTE), with an incidence varying between 3 and 54% in different studies. During the past 14 months, 17 patients with MCC have been treated weekly with 5-FU in our unit, comprising 11 males and six females with a mean age of 60 years (range, 49-72 years). Thromboprophylaxis for all patients included 1 mg/day warfarin unless contraindicated. Three patients developed venography-confirmed CVC-related VTE, including two cases of occlusive superior venocaval VTE. All three patients were treated with intravenous thrombolytic drugs; two responded completely and one partially. We wonder whether the incidence of CVC-related VTE may be reduced further by using adjusted-dose warfarin rather than fixed low-dose warfarin. However, one has to be guarded because of the greater risk of bleeding with more intensive anticoagulation, especially in patients with liver metastases. Ongoing studies such as the warfarin prophylaxis study are essential to determine the safety and efficacy of different approaches in order to determine the optimum thromboprophylaxis for this group of patients.

Aged↗

Suicide and political regime in New South Wales and Australia during the 20th century.

STUDY OBJECTIVE: Australia has had a two party parliamentary political system for most of the period since its Federation in 1901, dominated either by a social democratic (Labor) or a conservative ideological perspective. This paper investigates whether such political differences at Federal and State levels have influenced suicide rates in the state of New South Wales (NSW) for the period 1901-1998. DESIGN: Federal government type, NSW State government type, and combinations of both Federal and NSW State government type were examined. Poisson regression models were stratified by sex and controlled for the effects of age, annual change in gross domestic product, sedative availability, drought, and both world wars. RESULTS: When both Federal and NSW State governments were conservative the relative risk of suicide for NSW men was 1.17 (p<0.001) and for women 1.40 (p<0.001) compared with both governments being Labor (1.00). A statistically significant linear trend (p<0.001) in suicide risk was evident across the continuum of Federal/State government combinations, from both Labor (lowest), to mixed (intermediate), to both conservative (highest). CONCLUSION: Significantly higher suicide risk was associated with conservative government tenures compared with social democratic incumbents. Results are discussed in terms of the differences underpinning conservative and social democratic government programme ideology, and their relevance to Durkheim's theories of suicide, social regulation, and integration.

Adolescent↗

Routine breast screening for women aged 65-69: results from evaluation of the demonstration sites.

Routine programme data and specially designed surveys from 3 demonstration sites were analysed to determine the implications of extending the NHS Breast Screening Programme (NHSBSP), to include routine invitations for women up to 69 years. All women aged 65-69 and registered with GPs in these areas received routine invitations for breast screening along with those aged 50-64. Overall uptake was 71% in women aged 65-69 compared with 78% in younger women, but was > or = 90% in both groups who had previously attended within 5 years. Recall rates were lower for older women, but with a higher positive predictive value for cancer. The percentages of invasive cancer in different prognostic categories were similar in the 2 age groups. Older women took no longer to screen than younger women. The costs per woman invited or per woman screened were also similar to those for women aged 50-64, whilst the cost per cancer detected was some 34% lower in older women. Breast screening is as cost effective for women aged 65-69 as for those aged 50-64, with a higher cancer detection rate balancing shorter life expectancy. The proposed extension to the national programme will have considerable workforce implications for the NHSBSP and require additional resources.

Aged↗

The ink4a/arf tumor suppressors cooperate with p21cip1/waf in the processes of mouse epidermal differentiation, senescence, and carcinogenesis.

In mammalian cells, cell cycle withdrawal is a prerequisite for terminal differentiation. Accordingly, in most tissues, including epidermis, the expression of the cyclin-dependent kinase inhibitors increases during differentiation. However, the actual role of cyclin-dependent kinase inhibitors is unclear. Different aspects of epidermal growth and differentiation in ink4a(Delta2,3)-null, p21-null, and ink4a(Delta2,3)/p21-doubly deficient mice were studied. Altered differentiation and decreased age-related senescence were found in the epidermis of ink4a(Delta2,3)/p21-null mice and, to a lesser extent, in ink4a(Delta2,3)- and p21-null mice. ink4a(Delta2,3)/p21-null primary keratinocytes underwent cell cycle arrest upon calcium or transforming growth factor-beta treatment, but failed to differentiate. This differentiation deficiency was not observed in p21- or ink4a(Delta2,3)-deficient keratinocytes. Upon infection with a v-Ha-ras-coding retrovirus, wild-type keratinocytes displayed features indicative of premature cell senescence. In p21- or ink4a(Delta2,3)-deficient keratinocytes, only a partial response was observed. ink4a(Delta2,3)/p21-deficient keratinocytes did not display senescent features, but showed increased tumorigenic potential upon injection into nude mice. These results indicate that ink4a/arf and cip1/waf genes cooperate to allow normal keratinocyte differentiation and that the absence of both favors malignant transformation.

Animals↗

Altered skin development and impaired proliferative and inflammatory responses in transgenic mice overexpressing the glucocorticoid receptor.

Glucocorticoids (GCs) are potent inhibitors of epidermal proliferation and effective anti-inflammatory compounds, which make them the drug of choice for a wide range of inflammatory and hyperproliferative skin disorders. GC action is mediated via the glucocorticoid receptor (GR). To study the role of GR in skin development and the molecular mechanisms underlying its action, we generated transgenic mice overexpressing GR in epidermis and other stratified epithelia, under the control of the keratin K5 promoter. Newborn mice show altered skin development, manifested as variable-sized skin lesions that range from epidermal hypoplasia and underdeveloped dysplastic hair follicles to a complete absence of this tissue. In the most affected individuals, skin was absent at the cranial and umbilical regions, and the vibrissae and eyebrows appear scarce, short, and curly. In addition, as a consequence of transgene expression in other ectodermally derived epithelia, K5-GR mice exhibited further abnormalities that strikingly resemble the clinical findings in patients with ectodermal dysplasia, which includes aplasia cutis congenita. In adult transgenic skin, topical application of the tumor promoter TPA did not elicit hyperplasia or transcriptional induction of several proinflammatory cytokines. This anti-inflammatory role of GR was due at least in part to interference with NF-kB, leading to a strong reduction in the kB-binding activity without altering the transcriptional levels of the inhibitor IkBa.

Animals↗

Regions of microsynteny in Magnaporthe grisea and Neurospora crassa.

A bacterial artificial chromosome (BAC) clone containing 110,467 bp of genomic DNA from Magnaporthe grisea was sequenced, annotated, and compared to the genomes of Neurospora crassa, Candida albicans, and Saccharomyces cerevisiae. Twenty-six open reading frames (ORFs), involved in multiple biochemical pathways, were identified in the BAC sequence. A region of 53 kb, containing 18 of the 26 ORFs, was found to be syntenic to a portion of the N. crassa genome. Subregions of complete colinearity as well as interrupted colinearity were present. No synteny was evident with either C. albicans or S. cerevisiae. The identification of syntenic regions containing highly conserved genes across two genera that have been evolutionarily separated for approximately 200 million years elicits many biological questions as to the function and identity of these genes.

Candida albicans↗

Pathogenic infection and the oxidative defences in plant apoplast.

The structural and functional continuum of the plant apoplast is the first site of contact with a pathogen and plays a crucial role in initiation and coordination of many defence responses. In this paper, we present an overview of the involvement of the plant apoplast in plant-pathogen interactions. The process of infection of French bean (Phaseolus vulgaris L.) plants by Colletotrichum lindemuthianum is analysed. The ultrastructural features of plant defence responses to fungal infection are then compared with those observed in plants or cell suspensions treated with various elicitors. Changes in cell walls and in whole plant cells responding to infection seem to be highly similar in all systems used. Model systems of French bean and white lupin (Lupinus albus L.) are then utilised to provide some biochemical characteristics of oxidative reactions in the apoplast evoked by elicitor treatment. The species specificity of various mechanisms generating reactive oxygen species is discussed, and some details of pH-dependent H2O2-generating activity of peroxidases are demonstrated. As its exocellular nature is an important feature of the oxidative burst, the major consequence of this event, i.e., the oxidative cross-linking of wall components during the papilla formation and strengthening of the walls, is analysed. Finally, the possible involvement of other wall-associated and developmentally regulated H2O2-generating mechanisms, like amine and oxalate oxidases, in plant defence is demonstrated. It is concluded that under stress conditions, such apoplastic mechanisms might be employed to increase plants' chances of survival.

Cell Wall↗

Sequence and chromosomal context effects on variegated expression of keratin 5/lacZ constructs in stratified epithelia of transgenic mice.

The expression of transgene loci in mammals often occurs in a heterocellular fashion resulting in variegated patterns of expression. We have examined the effect of chromosomal integration site, copy number, and transcriptionally activating sequences on the variegation of a keratin 5-lacZ (K5Z) construct in the stratified epithelia of transgenic mice. lacZ expression in these mice is always mosaic, and the beta-gal activity per cell is usually higher in the lines with a higher proportion of expressing cells. Similar constructs, in which cDNAs were exchanged by lacZ sequences, showed no variegation. Also, when a strongly active, nonvariegating construct was coinjected with K5Z, most transgenic lines showed an almost homogeneous lacZ expression. The comparison of transgene arrays of different copies inserted at the same locus (obtained by using a lox/Cre system) showed that the reduction of copy number does not lead to an increase in the proportion of cells that express the transgene. Finally, in most of the variegating or nonexpressing lines the transgenes were located both at intermediate positions and at peritelomeric regions in the long chromosome arms. These findings suggest that the probability and efficiency of expression of K5Z genes depend on both long range chromosomal influences and on sequences in the transgene array.

Animals↗

A cutaneous gene therapy approach to human leptin deficiencies: correction of the murine ob/ob phenotype using leptin-targeted keratinocyte grafts.

Leptin deficiency produces a phenotype of obesity, diabetes, and infertility in the ob/ob mouse. In humans, leptin deficiency occurs in some cases of congenital obesity and in lipodystrophic disorders characterized by reduced adipose tissue and insulin resistance. Cutaneous gene therapy is considered an attractive potential method to correct circulating protein deficiencies, since gene-transferred human keratinocytes can produce and secrete gene products with systemic action. However, no studies showing correction of a systemic defect have been reported. We report the successful correction of leptin deficiency using cutaneous gene therapy in the ob/ob mouse model. As a feasibility approach, skin explants from transgenic mice overexpressing leptin were grafted on immunodeficient ob/ob mice. One month later, recipient mice reached body weight values of lean animals. Other biochemical and clinical parameters were also normalized. In a second human gene therapy approach, a retroviral vector encoding both leptin and EGFP cDNAs was used to transduce HK and, epithelial grafts enriched in high leptin-producing HK were transplanted to immunosuppressed ob/ob mice. HK-derived leptin induced body weight reduction after a drop in blood glucose and food intake. Leptin replacement through genetically engineered HK grafts provides a valuable therapeutic alternative for permanent treatment of human leptin deficiency conditions.

Animals↗