42 resultados para Melanoma Susceptibility

em Deakin Research Online - Australia


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The phytohormone abscisic acid (ABA) plays a major role in the regulation of many physiological stresses although its role in pathogen-induced stress remains poorly understood. We examined the influence of ABA on interactions of Arabidopsis thaliana (L.) Heynh. (Arabidopsis) with a bacterial pathogen, Pseudomonas syringae pv. tomato and an Oomycete, Peronospora parasitica. Both addition of 100 μM ABA to plants and drought stress stimulated increased susceptibility of Arabidopsis to an avirulent isolate of P. syringae pv. tomato. In contrast, an ABA-deficient mutant of Arabidopsis, aba1-1, displayed reduced susceptibility to virulent isolates of P. parasitica. An ABA-insensitive mutant, abi1-1, that is impaired in ABA signal transduction did not alter in susceptibility to either P. syringae pv. tomato or P. parasitica. These results demonstrate that the concentration of endogenous ABA at the time of pathogen challenge is important for the development of susceptibility in Arabidopsis.

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While advanced high strength steels (AHSS) have numerous advantages for the automotive industry, they can be susceptible to interfacial fracture when spot-welded. In this study, the susceptibility of interfacial fracture to spot-weld microstructure and hardness is examined, as well as the corresponding relationships between fatigue, overload performance, and interfacial fracture for a TRIP (transformation induced plasticity) steel. Simple post-weld heat-treatments were used to alter the weld microstructure. The effect on interfacial fracture of diluting the weld pool by welding the TRIP material to non-TRIP steel was examined, along with the effect of altering the base material microstructure. Results show that weld hardness is not a good indicator of either the susceptibility to interfacial fracture, or the strength of the joint, and that interfacial fracture does not necessarily lead to a decrease in strength compared to conventional weld-failure mechanisms, i.e. button pullout. It was also found that while interfacial fracture does affect low cycle to failure behavior, there was no effect on high cycle fatigue.

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Objective To describe the diagnostic performance of SolarScan (Polartechnics Ltd, Sydney, Australia), an automated instrument for the diagnosis of primary melanoma.

Design Images from a data set of 2430 lesions (382 were melanomas; median Breslow thickness, 0.36 mm) were divided into a training set and an independent test set at a ratio of approximately 2:1. A diagnostic algorithm (absolute diagnosis of melanoma vs benign lesion and estimated probability of melanoma) was developed and its performance described on the test set. High-quality clinical and dermoscopy images with a detailed patient history for 78 lesions (13 of which were melanomas) from the test set were given to various clinicians to compare their diagnostic accuracy with that of SolarScan.

Setting Seven specialist referral centers and 2 general practice skin cancer clinics from 3 continents. Comparison between clinician diagnosis and SolarScan diagnosis was by 3 dermoscopy experts, 4 dermatologists, 3 trainee dermatologists, and 3 general practitioners.

Patients Images of the melanocytic lesions were obtained from patients who required either excision or digital monitoring to exclude malignancy.

Main Outcome Measures Sensitivity, specificity, the area under the receiver operator characteristic curve, median probability for the diagnosis of melanoma, a direct comparison of SolarScan with diagnoses performed by humans, and interinstrument and intrainstrument reproducibility.

Results The melanocytic-only diagnostic model was highly reproducible in the test set and gave a sensitivity of 91% (95% confidence interval [CI], 86%-96%) and specificity of 68% (95% CI, 64%-72%) for melanoma. SolarScan had comparable or superior sensitivity and specificity (85% vs 65%) compared with those of experts (90% vs 59%), dermatologists (81% vs 60%), trainees (85% vs 36%; P =.06), and general practitioners (62% vs 63%). The intraclass correlation coefficient of intrainstrument repeatability was 0.86 (95% CI, 0.83-0.88), indicating an excellent repeatability. There was no significant interinstrument variation (P = .80).

Conclusions SolarScan is a robust diagnostic instrument for pigmented or partially pigmented melanocytic lesions of the skin. Preliminary data suggest that its performance is comparable or superior to that of a range of clinician groups. However, these findings should be confirmed in a formal clinical trial.

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Objectives: The objectives of this study were to define appropriate criteria for assessing the presence of lymphedema, and to report the prevalence and risk factors for development of upper limb lymphedema after level I-III axillary dissection for melanoma.
Summary Background Data: The lack of a consistent and reliable objective definition for lymphedema remains a significant barrier to appreciating its prevalence after axillary dissection for melanoma (or breast carcinoma).
Methods: Lymphedema was assessed in 107 patients (82 male, 25 female) who had previously undergone complete level I-III axillary dissection. Of the 107 patients, 17 had also received postoperative axillary radiotherapy. Arm volume was measured using a water displacement technique. Change in volume of the arm on the side of the dissection was referenced to the volume of the other (control) arm. Volume measurements were corrected for the effect of handedness using corrections derived from a control group. Classification and regression tree (CART) analysis was used to determine a threshold fractional arm volume increase above which volume changes were considered to indicate lymphedema.
Results: Based on the CART analysis results, lymphedema was defined as an increase in arm volume greater than 16% of the volume of the control arm. Using this definition, lymphedema prevalence for patients in the present study was 10% after complete level I-III axillary dissection for melanoma and 53% after additional axillary radiotherapy. Radiotherapy and wound complications were independent risk factors for the development of lymphedema.
Conclusions: A suggested objective definition for arm lymphedema after axillary dissection is an arm volume increase of greater than 16% of the volume of the control arm.

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It is generally agreed that stress can impair reproduction. Furthermore, it is often thought that cortisol, which is secreted during stress as a result of activation of the hypothalamo-pituitary adrenal axis, is associated with this stress-induced impairment of reproduction. It has been hypothesized that reproduction in females is particularly susceptible to disruption by acute stress during the series of endocrine events that induce estrus and ovulation. Nevertheless, we found no support for this conjecture when we subjected female pigs to repeated acute stress or repeated acute elevation of cortisol during the period leading up to estrus and ovulation. Conversely, studies have demonstrated that prolonged stress and sustained elevation of cortisol can disrupt reproductive processes in female pigs. Nevertheless, in each study that demonstrated this effect, there were some animals subjected to the prolonged stressor or the sustained elevation of cortisol in which the reproductive parameters that were measured were not affected by the treatment. We propose that reproduction in female pigs is resistant to the effects of acute or repeated acute stress or acute or repeated acute elevation of cortisol even if these occur during the series of endocrine events that induce estrus and ovulation. Furthermore, while reproductive processes in some individuals are compromised, reproduction in a proportion of female pigs appears to be resistant to the effects of prolonged stress or sustained elevation of cortisol.

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Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10-7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.

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Mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) is predominantly expressed on high endothelial venules in inflamed tissues where it assists with leucocyte extravasation. Here we report that MAdCAM-1 has the potential to be more widely expressed outside the endothelial cell lineage than previously appreciated. Thus, MAdCAM-1 RNA transcripts and cell-surface protein were expressed by NIH 3T3 fibroblasts following activation with tumour necrosis factor-alpha (TNF-alpha), and by freshly isolated and cultured primary mouse splenic and tail fibroblasts in the absence of TNF-alpha stimulation. They were constitutively expressed by B16F10 melanoma cells, and expression was enhanced by cell activation with TNF-alpha. Mucosal vascular addressin cell adhesion molecule-1 was expressed on the apical surface of isolated cells, but became predominantly localized to cell junctions in confluent cell monolayers, suggesting it may play a role in the homotypic aggregation of cells. Tumour necrosis factor-alpha enhanced the expression of a firefly luciferase reporter directed by the MAdCAM-1 promoter in NIH 3T3 and B16F10 cells. A DNA fragment extending from nt -1727 to -673 was sufficient to confer cell-type selective expression. Mucosal vascular addressin cell adhesion molecule-1 expressed by NIH 3T3 cells was biologically active, as it supported the adhesion of TK-1 T cells in an alpha4beta7-dependent fashion. The expression of MAdCAM-1 by fibroblasts, and melanomas suggests MAdCAM-1 may play a role in regulating host responses in the periphery, leucocyte transmigration across nonendothelial boundaries, or the homotypic interactions of some malignant melanomas.

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In a developing nation such as India, the national government is pursuing the pathway of ICT supported decentralized programs, to combat endemics, in the social contexts of each State.  The State of Kerala, which has been a exemplar for development, has become susceptible to endemics, brough in by urbanization and non-resident Indian population and compounded be environmental disasters.  In this paper, the authors contend that the psyche of the community which has changed from social amity to self-interest need to be re-awakened with the power ot ICTs and Internet, so as to efficiently combat endemics.  The authors propose a preliminary framework for emergency responses bases on the ICS developed by FEMA in USA and recommended by Indian national government, to suit the context of the State.

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In 1998, using the Index of Receptivity to Tobacco Industry Promotion (IRTIP), it was claimed that tobacco promotion increased youth susceptibility to smoking. Arguably, this claim started the belief that ?cigarette advertising causes smoking? and led to many countries severely restricting cigarette promotion. The problem is, ten years lat... more »er, youth are still lighting up. Could they have gotten it wrong? The IRTIP procedure is widely used to model the link between promotional activities and susceptibility to product use. It is now being used for other products like alcohol, fast-food and colas. This book reports the results of a verification and re-test of the IRTIP model. Using the original data, it was found that IRTIP magnifies Response-Style and Respondent Drop-Out Biases. These biases are shown to lead to the finding of a positive link between tobacco promotion and susceptibility to smoking. Because the IRTIP process is biased, it may be prudent to revisit the many research studies that have used this procedure. The faulty 1998 claim may have harmed efforts to control and limit the use of cigarettes.

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The Index of Receptivity to Tobacco Industry Promotion (IRTIP) is a model that is used by hundreds of articles. The causal claim based on findings from this model is even more pervasive, and has resulted in much of the modern post 1998 tobacco legislation that is still enforced. This thesis tested the link between adolescent receptivity to tobacco industry promotion and susceptibility to smoking. Pierce et al. (1998) reported that they had found a positive and causal association between receptivity and susceptibility by using IRTIP. They claimed that receptivity to tobacco industry promotion was the only significant causal factor affecting adolescent susceptibility to smoking. Exposure to peer and parental smoking was not found to be a significant effect. A review of the literature found that many sections of IRTIP differ from accepted marketing theory on how cigarette advertising and promotions affect adolescent adoption of cigarette smoking. The proxy measures used in IRTIP were shown to diverge from those previously used for measuring the constructs of Attention, Intention, Desire and Action (AIDA) in marketing communications. IRTIP also differs from previous theory by including measures that attempt to quantify the effect of tobacco premiums into a model that was designed to measure the effects of advertising.

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Pierce, Choi, Gilpin, Farkas, and Berry (1998) were the first to claim that they could provide causal evidence that tobacco industry advertising and promotion caused adolescent smoking. This claim continues to significantly influence the theory and conceptualization of how youth react to tobacco marketing. The Pierce et al. (1998) methodology has been used by many researchers to establish the influence of tobacco marketing on adolescent smoking (Goldberg, 2003; NCI, 2006; Sargent, Dalton, & Beach, 2000). Pierce et al. (1998) selected respondents for only the second of their two survey longitudinal study because they chose the extreme-negative response. This choice could be the result of the tendency of some significant number of sample members exhibiting extreme-response bias. The results from an analysis of several questions from the original data used by Pierce et al. (1998) has suggested that there is a significant extreme-response style pattern in the Pierce et al. data. This unaccounted for bias in the responses of their sample was due to the procedure used by Pierce et al. (1998) in the selection of their respondents. The Pierce et al. (1998) sample selection procedure requires more research before the causal link can be claimed.

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The first article to report on a causal connection between tobacco industry promotion and adolescent smoking (Pierce et al. 1998) had, and continues to have, a significant influence on the marketing of cigarettes in many parts of the world. A key construct in determining causality was the ability to identify the respondents’ “susceptibility to smoke”. Through an analysis of the questions, and reanalysis of the original data used by Pierce et al. (1998), it is shown that the construct is flawed, and needs revision before a causal link can be claimed with the original data.