988 resultados para Allelic Variation
Resumo:
BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8-10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample.
Resumo:
Extreme temperatures have been shown to have a detrimental effect on health. Hot temperatures can increase the risk of mortality, particularly in people suffering from cardiorespiratory diseases. Given the onset of climate change, it is critical that the impact of temperature on health is understood, so that effective public health strategies can correctly identify vulnerable groups within the population. However, while effects on mortality have been extensively studied, temperature–related morbidity has received less attention. This study applied a systematic review and meta–analysis to examine the current literature relating to hot temperatures and morbidity.
Resumo:
Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.
Resumo:
The Giant Long-Armed Prawn, Macrobrachium lar is a freshwater species native to the Indo-Pacific. M. lar has a long-lived, passive, pelagic marine larval stage where larvae need to colonise freshwater within three months to complete their development. Dispersal is likely to be influenced by the extensive distances larvae must transit between small oceanic islands to find suitable freshwater habitat, and by prevailing east to west wind and ocean currents in the southern Pacific Ocean. Thus, both intrinsic and extrinsic factors are likely to influence wild population structure in this species. The present study sought to define the contemporary broad and fine-scale population genetic structure of Macrobrachium lar in the south-western Pacific Ocean. Three polymorphic microsatellite loci were used to assess patterns of genetic variation within and among 19 wild adult sample sites. Statistical procedures that partition variation implied that at both spatial scales, essentially all variation was present within sample sites and differentiation among sites was low. Any differentiation observed also was not correlated with geographical distance. Statistical approaches that measure genetic distance, at the broad-scale, showed that all south-western Pacific Islands were essentially homogeneous, with the exception of a well supported divergent Cook Islands group. These findings are likely the result of some combination of factors that may include the potential for allelic homoplasy, through to the effects of sampling regime. Based on the findings, there is most likely a divergent M. lar Cook Islands clade in the south-western Pacific Ocean, resulting from prevailing ocean currents. Confirmation of this pattern will require a more detailed analysis of nDNA variation using a larger number of loci and, where possible, use of larger population sizes.
Resumo:
The likely phenological responses of plants to climate warming can be measured through experimental manipulation of field sites, but results are rarely validated against year-to-year changes in climate. Here, we describe the response of 1-5 years of experimental warming on phenology (budding, flowering and seed maturation) of six common subalpine plant species in the Australian Alps using the International Tundra Experiment (ITEX) protocol.2. Phenological changes in some species (particularly the forb Craspedia jamesii) were detected in experimental plots within a year of warming, whereas changes in most other species (the forb Erigeron bellidioides, the shrub Asterolasia trymalioides and the graminoids Carex breviculmis and Poa hiemata) did not develop until after 2-4 years; thus, there appears to be a cumulative effect of warming for some species across multiple years.3. There was evidence of changes in the length of the period between flowering and seed maturity in one species (P. hiemata) that led to a similar timing of seed maturation, suggesting compensation.4. Year-to-year variation in phenology was greater than variation between warmed and control plots and could be related to differences in thawing degree days (particularly, for E. bellidioides) due to earlier timing of budding and other events under warmer conditions. However, in Carex breviculmis, there was no association between phenology and temperature changes across years.5. These findings indicate that, although phenological changes occurred earlier in response to warming in all six species, some species showed buffered rather than immediate responses.6. Synthesis. Warming in ITEX open-top chambers in the Australian Alps produced earlier budding, flowering and seed set in several alpine species. Species also altered the timing of these events, particularly budding, in response to year-to-year temperature variation. Some species responded immediately, whereas in others the cumulative effects of warming across several years were required before a response was detected.
Resumo:
The central thesis in the article is that the venture creation process is different for innovative versus imitative ventures. This holds up; the pace of the process differs by type of venture as do, in line with theory-based hypotheses, the effects of certain human capital (HC) and social capital (SC) predictors. Importantly, and somewhat unexpectedly, the theoretically derived models using HC, SC, and certain controls are relatively successful explaining progress in the creation process for the minority of innovative ventures, but achieve very limited success for the imitative majority. This may be due to a rationalistic bias in conventional theorizing and suggests that there is need for considerable theoretical development regarding the important phenomenon of new venture creation processes. Another important result is that the building up of instrumental social capital, which we assess comprehensively and as a time variant construct, is important for making progress with both types of ventures, and increasingly, so as the process progresses. This result corroborates with stronger operationalization and more appropriate analysis method what previously published research has only been able to hint at.
Resumo:
Understanding information technology’s (ITs) contribution to business value is an imperative issue, and while we have attempted to untangle the relationship between IT and business value with some success, our knowledge of specific factors leading to ITs contribution to business value still remains limited. In this paper we propose that complementing IT resources, by establishing a sound IT platform with capable organisational resources may aid in ITs ability to contribute to business value. We suggest that performance measurement of this contribution be undertaken at the business process level first, and then mapped through to firm level performance measurement to obtain a better understanding of the path of IT business value contribution.
Resumo:
Purpose. To investigate whether diurnal variation occurs in retinal thickness measures derived from spectral domain optical coherence tomography (SD-OCT). Methods. Twelve healthy adult subjects had retinal thickness measured with SD-OCT every 2 h over a 10 h period. At each measurement session, three average B-scan images were derived from a series of multiple B-scans (each from a 5 mm horizontal raster scan along the fovea, containing 1500 A-scans/B-scan) and analyzed to determine the thickness of the total retina, as well as the thickness of the outer retinal layers. Average thickness values were calculated at the foveal center, at the 0.5 mm diameter foveal region, and for the temporal parafovea (1.5 mm from foveal center) and nasal parafovea (1.5 mm from foveal center). Results. Total retinal thickness did not exhibit significant diurnal variation in any of the considered retinal regions (p > 0.05). Evidence of significant diurnal variation was found in the thickness of the outer retinal layers (p < 0.05), with the most prominent changes observed in the photoreceptor layers at the foveal center. The photoreceptor inner and outer segment layer thickness exhibited mean amplitude (peak to trough) of daily change of 7 ± 3 μm at the foveal center. The peak in thickness was typically observed at the third measurement session (mean measurement time, 13:06). Conclusions. The total retinal thickness measured with SD-OCT does not exhibit evidence of significant variation over the course of the day. However, small but significant diurnal variation occurs in the thickness of the foveal outer retinal layers.