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111.
Wordsworth S Buchanan J Regan R Davison V Smith K Dyer S Campbell C Blair E Maher E Taylor J Knight SJ 《Genomic Medicine》2007,1(1-2):35-45
Array based comparative genomic hybridisation (aCGH) is a powerful technique for detecting clinically relevant genome imbalance
and can offer 40 to > 1000 times the resolution of karyotyping. Indeed, idiopathic learning disability (ILD) studies suggest
that a genome-wide aCGH approach makes 10–15% more diagnoses involving genome imbalance than karyotyping. Despite this, aCGH
has yet to be implemented as a routine NHS service. One significant obstacle is the perception that the technology is prohibitively
expensive for most standard NHS clinical cytogenetics laboratories. To address this, we investigated the cost-effectiveness
of aCGH versus standard cytogenetic analysis for diagnosing idiopathic learning disability (ILD) in the NHS. Cost data from
four participating genetics centres were collected and analysed. In a single test comparison, the average cost of aCGH was
£442 and the average cost of karyotyping was £117 with array costs contributing most to the cost difference. This difference
was not a key barrier when the context of follow up diagnostic tests was considered. Indeed, in a hypothetical cohort of 100 ILD
children, aCGH was found to cost less per diagnosis (£3,118) than a karyotyping and multi-telomere FISH approach (£4,957).
We conclude that testing for genomic imbalances in ILD using microarray technology is likely to be cost-effective because
long-term savings can be made regardless of a positive (diagnosis) or negative result. Earlier diagnoses save costs of additional
diagnostic tests. Negative results are cost-effective in minimising follow-up test choice. The use of aCGH in routine clinical
practice warrants serious consideration by healthcare providers.
Copyright statement The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive
licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd, and its Licensees
to permit this article (if accepted) to be published in BMJ editions and any other BMJPGL products and to exploit all subsidiary
rights, as set out in our licence (bmj.com/advice/copyright.shtml).
Authorship The authors included on this paper fulfil the criteria of authorship and no one who fulfils the criteria has been excluded
from authorship. The authors made a substantial contribution to the conception, design, analysis and interpretation of data.
They were involved in drafting the article or revising it critically for important intellectual content and approving the
version to be published.
Contributorship Sarah Wordsworth (Guarantor): Planning, conducting and reporting work, interpretation of data, drafting and revising article.
James Buchanan: Conducting and reporting work, interpretation of data, revising article.
Regina Regan: Completing costing questionnaire, providing protocol details, other costing information, interpretation of data,
information about learning disability and genome imbalance and revising article.
Val Davison: Completing costing questionnaire, providing protocol details, sharing overall laboratory experience and drafting
article.
Kim Smith: Completing costing questionnaire, providing protocol details, drafting article.
Sara Dyer: Completing costing questionnaire and providing protocol details.
Carolyn Campbell: Completing costing questionnaire and providing protocol details.
Edward Blair: Critical appraisal of article for clinical content and revising article.
Eddy Maher: Completing costing questionnaire, providing protocol details, sharing overall laboratory experience and drafting
article.
Jenny Taylor: Planning and facilitating work between centres. Drafting and revising article.
Samantha JL Knight: Completing costing questionnaire, providing protocol details, other costing information, interpretation
of data, providing information about learning disability and genome imbalance, drafting and revising article.
Jenny Taylor and Samantha JL Knight contributed equally to the work presented. 相似文献
112.
Objective: Our aim was to examine whether secular trends in childhood overweight and obesity during five decades could be explained by economic growth. Research Methods and Procedures: Annual measurements of height and weight were available for all children born between 1930 and 1983 attending primary school in the Copenhagen Municipality: 165,389 boys and 163,609 girls from the age of 7 through 13 years. After computerization, we calculated BMI (kg/m2) and estimated the prevalence of overweight and obesity, according to international age‐ and gender‐specific criteria, by year of birth and of measurement, and separately by each age group and gender. Economic growth was indicated by the Gross National Product and the overall consumption per capita, adjusted for inflation. Results: The prevalence of overweight occurred in phases: an increase from 1930 until the 1950s, followed by a plateau period between the 1950s and the 1960s and a steep increase thereafter. This pattern was apparent across all age groups and in both genders. Obesity trends showed a similar phase pattern; the prevalence remained relatively stable from 1930 until the 1940s, increased until the mid‐1950s, followed by a plateau until 1965, and thereafter a second steep increase. Obesity trends were similar among boys across all age groups, although only among girls from 11 to 13 years of age. In both genders, increments were most pronounced in the upper BMI percentiles. After stagnation until 1947, the economic growth indicators showed a steady increase; i.e., after the first increase started in overweight and obesity, whether analyzed by year of birth or year of measurement, there were no indications of phases in the rise thereafter. Discussion: Prevalence of overweight and obesity among Danish children rose in phases, which were not paralleled by trends in economic growth. The macroeconomic growth indicators seem inappropriate as proxies for the environmental exposures that have elicited the obesity epidemic. 相似文献
113.
Peterson RS Fernando G Day L Allen TA Chapleau JD Menjivar J Schlinger BA Lee DW 《Developmental neurobiology》2007,67(14):1867-1878
Estrogens can be neuroprotective following traumatic brain injury. Immediately after trauma to the zebra finch hippocampus, the estrogen-synthetic enzyme aromatase is rapidly upregulated in astrocytes and radial glia around the lesion site. Brain injury also induces high levels of cell proliferation. Estrogens promote neuronal differentiation, migration, and survival naturally in the avian brain. We suspect that glia are a source of estrogens promoting cell proliferation after neural injury. To explore this hypothesis, we examined the spatial and temporal relationship between glial aromatase expression and cell proliferation after neural injury in adult female zebra finches. Birds were ovariectomized and given a blank implant or one filled with estradiol; some birds were also administered an aromatase inhibitor or vehicle. All birds received penetrating injuries to the right hippocampus. Twenty-four hours after lesioning, birds were injected once with BrdU to label mitotically active cells and euthanized 2 h, 24 h, or 7 days later. The brains were processed for double-label BrdU and aromatase immunocytochemistry. Injury-induced glial aromatase expression was unaffected by survival time and aromatase inhibition. BrdU labeling was significantly reduced at 24 h by ovariectomy and by aromatase inhibition; effects were partially reversed by E2 replacement. Irrespective of ovariectomy, the densities of aromatase immunoreactive astrocytes and BrdU-labeled cells at known distances from the lesion site were highly correlated. These data suggest that injury-induced glial aromatization may influence the reorganization of injured tissue by providing a rich estrogenic environment available to influence cellular incorporation. 相似文献
114.
Clonal diversity in asexual populations may be maintained if different clones are favoured under different environmental conditions. For aphids, parasitoids are an important variable of the biotic environment. To test whether parasitoids can mediate selection among host clones, we used experimental populations consisting of 10 clones of the peach-potato aphid, Myzus persicae, and allowed them to evolve for several generations either without parasitoids or in the presence of two species of parasitoid wasps. In the absence of parasitoids, strong shifts in clonal frequencies occurred, mostly in favour of clones with high rates of increase. The parasitoid Diaeretiella rapae hardly affected aphid densities but changed the outcome of competition by favouring one entirely resistant clone and disfavouring a highly susceptible clone. Aphidius colemani, the more infective parasitoid, strongly reduced aphid densities and dramatically changed host clonal frequencies. The most resistant clone, not a successful clone without parasitoids, became totally dominant. These results highlight the potential of temporal or spatial variation in parasitoid densities to maintain clonal diversity in their aphid hosts. 相似文献
115.
116.
Kathleen M. Gorman Esther Meyer Detelina Grozeva Egidio Spinelli Amy McTague Alba Sanchis-Juan Keren J. Carss Emily Bryant Adi Reich Amy L. Schneider Ronit M. Pressler Michael A. Simpson Geoff D. Debelle Evangeline Wassmer Jenny Morton Diana Sieciechowicz Eric Jan-Kamsteeg Alex R. Paciorkowski Manju A. Kurian 《American journal of human genetics》2019,104(5):948-956
117.
Cocoa grows under shade, but some cultivars develop successfully in full sunlight. In order to characterize the response to photosynthetic photon flux density (PPFD) of a Modern Criollo cocoa clone, gas exchange, photochemical activity and leaf traits, and their relation to growth were measured in seedlings growing in a greenhouse at three different values of PPFD, as well as in adults in full sunlight and shade in the field. Plants showed changes in physiological, biochemical, and morpho‐anatomical traits in response to the different light conditions, and in the phenotypic plasticity of these variables. Seedlings subjected to high PPFD in the greenhouse showed decreases in photosynthetic rate, apparent quantum yield of CO2 fixation and photochemical quenching, and increases in non‐photochemical quenching, suggesting down‐regulation of PSII. In contrast, trees under full sunlight in the field showed a marked reduction in maximum quantum yield of PSII, indicating photoinhibition and supporting that cocoa is a shade tolerant crop. Cocoa showed higher plasticity of physiological and biochemical variables than morpho‐anatomical variables in response to PPFD. Effects of time under treatment in the greenhouse and plant age (greenhouse vs field) on plasticity were observed. The acclimation observed in some of the variables studied after 6 months in high light did not represent a particular advantage to seedlings, since relative growth rate was lower than in low‐ and medium‐light seedlings. 相似文献
118.
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120.
Jinkook Lee Jenny Wilkens Erik Meijer T. V. Sekher David E. Bloom Peifeng Hu 《PLoS medicine》2022,19(1)
BackgroundHypertension is the most important cardiovascular risk factor in India, and representative studies of middle-aged and older Indian adults have been lacking. Our objectives were to estimate the proportions of hypertensive adults who had been diagnosed, took antihypertensive medication, and achieved control in the middle-aged and older Indian population and to investigate the association between access to healthcare and hypertension management.Methods and findingsWe designed a nationally representative cohort study of the middle-aged and older Indian population, the Longitudinal Aging Study in India (LASI), and analyzed data from the 2017–2019 baseline wave (N = 72,262) and the 2010 pilot wave (N = 1,683). Hypertension was defined as self-reported physician diagnosis or elevated blood pressure (BP) on measurement, defined as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg. Among hypertensive individuals, awareness, treatment, and control were defined based on self-reports of having been diagnosed, taking antihypertensive medication, and not having elevated BP, respectively. The estimated prevalence of hypertension for the Indian population aged 45 years and older was 45.9% (95% CI 45.4%–46.5%). Among hypertensive individuals, 55.7% (95% CI 54.9%–56.5%) had been diagnosed, 38.9% (95% CI 38.1%–39.6%) took antihypertensive medication, and 31.7% (95% CI 31.0%–32.4%) achieved BP control. In multivariable logistic regression models, access to public healthcare was a key predictor of hypertension treatment (odds ratio [OR] = 1.35, 95% CI 1.14–1.60, p = 0.001), especially in the most economically disadvantaged group (OR of the interaction for middle economic status = 0.76, 95% CI 0.61–0.94, p = 0.013; OR of the interaction for high economic status = 0.84, 95% CI 0.68–1.05, p = 0.124). Having health insurance was not associated with improved hypertension awareness among those with low economic status (OR = 0.96, 95% CI 0.86–1.07, p = 0.437) and those with middle economic status (OR of the interaction = 1.15, 95% CI 1.00–1.33, p = 0.051), but it was among those with high economic status (OR of the interaction = 1.28, 95% CI 1.10–1.48, p = 0.001). Comparing hypertension awareness, treatment, and control rates in the 4 pilot states, we found statistically significant (p < 0.001) improvement in hypertension management from 2010 to 2017–2019. The limitations of this study include the pilot sample being relatively small and that it recruited from only 4 states.ConclusionsAlthough considerable variations in hypertension diagnosis, treatment, and control exist across different sociodemographic groups and geographic areas, reducing uncontrolled hypertension remains a public health priority in India. Access to healthcare is closely tied to both hypertension diagnosis and treatment.Jinkook Lee and colleagues investigate hypertension management and its association with healthcare access in middle-aged and older adults in India. 相似文献