A Physically Based Constitutive Model and Continuous Dynamic Recrystallization Behavior Analysis of 2219 Aluminum Alloy during Hot Deformation Process.

The isothermal compression tests of the 2219 Al alloy were conducted at the temperature and the strain rate ranges of 623⁻773 K and 0.01⁻10 s-1, respectively, and the deformed microstructures were observed. The flow curves of the 2219 Al alloy obtained show that flow stress decreases with the increase in temperature and/or the decrease in strain rate. The physically based constitutive model is applied to describe the flow behavior during hot deformation. In this model, Young's modulus and lattice diffusion coefficient are temperature-dependent, and the creep exponent is regarded as a variable. The predicted values calculated by the constitutive model are in good agreement with the experimental results. In addition, it is confirmed that the main softening mechanism of the 2219 Al alloy during hot deformation is dynamic recovery and incomplete continuous dynamic recrystallization (CDRX) by the analysis of electron backscattered diffraction (EBSD) micrographs. Moreover, CDRX can readily occur under the condition of high temperatures, low strain rates, and large strains. Meanwhile, the recrystallization grain size will also be larger.

Trends in the lifetime risk of developing cancer in Great Britain: comparison of risk for those born from 1930 to 1960.

BACKGROUND: Typically, lifetime risk is calculated by the period method using current risks at different ages. Here, we estimate the probability of being diagnosed with cancer for individuals born in a given year, by estimating future risks as the cohort ages. METHODS: We estimated the lifetime risk of cancer in Britain separately for men and women born in each year from 1930 to 1960. We projected rates of all cancers (excluding non-melanoma skin cancer) and of all cancer deaths forwards using a flexible age-period-cohort model and backwards using age-specific extrapolation. The sensitivity of the estimated lifetime risk to the method of projection was explored. RESULTS: The lifetime risk of cancer increased from 38.5% for men born in 1930 to 53.5% for men born in 1960. For women it increased from 36.7 to 47.5%. Results are robust to different models for projections of cancer rates. CONCLUSIONS: The lifetime risk of cancer for people born since 1960 is >50%. Over half of people who are currently adults under the age of 65 years will be diagnosed with cancer at some point in their lifetime.

Predictors of paravalvular aortic regurgitation following self-expanding Medtronic CoreValve implantation: the role of annulus size, degree of calcification, and balloon size during pre-implantation valvuloplasty and implant depth.

OBJECTIVES: We sought to investigate the role of balloon size during pre-implantation valvuloplasty in predicting AR and optimal Medtronic CoreValve (MCS) implantation depth. BACKGROUND: Paravalvular aortic regurgitation (AR) is common following MCS implantation. A number of anatomical and procedural variables have been proposed as determinants of AR including degree of valve calcification, valve undersizing and implantation depth. METHODS: We conducted a multicenter retrospective analysis of 282 patients who had undergone MCS implantation with prior cardiac CT annular sizing between 2007 and 2011. Native valve minimum (Dmin), maximum (Dmax) and arithmetic mean (Dmean) annulus diameters as well as agatston calcium score were recorded. Nominal and achieved balloon size was also recorded. AR was assessed using contrast angiography at the end of each procedure. Implant depth was measured as the mean distance from the nadir of the non- and left coronary sinuses to the distal valve frame angiographically. RESULTS: 29 mm and 26 mm MCS were implanted in 60% and 39% of patients respectively. The majority of patients (N=165) developed AR <2 following MCS implantation. AR ≥3 was observed in 16% of the study population. High agatston calcium score and Dmean were found to be independent predictors of AR ≥3 in multivariate analysis (P<0.0001). Nominal balloon diameter and the number of balloon inflations did not influence AR. However a small achieved balloon diameter-to-Dmean ratio (≤0.85) showed modest correlation with AR ≥3 (P=0.04). This observation was made irrespective of the degree of valve calcification. A small MCS size-to-Dmean ratio is also associated with AR ≥3 (P=0.001). A mean implantation depth of ≥8+2mm was also associated with AR ≥3. Implantation depth of ≥12 mm was associated with small MCS diameter-to-Dmean ratio and increased 30-day mortality. CONCLUSION: CT measured aortic annulus diameter and agatston calcium score remain important predictors of significant AR. Other procedural predictors include valve undersizing and low implantation depth. A small achieved balloon diameter-to-Dmean ratio might also predict AR ≥3. Our findings confirm that a small achieved balloon size during pre-implantation valvuloplasty predicts moderate-severe AR in addition to previously documented factors.

Identification of MAGEA antigens as causal players in the development of tamoxifen-resistant breast cancer.

The antiestrogen tamoxifen is a well-tolerated, effective treatment for estrogen receptor-α-positive (ER+) breast cancer, but development of resistance eventually limits its use. Here we show that expression of MAGEA2, and related members of this cancer-testis antigen family, is upregulated in tamoxifen-resistant tumor cells. Expression of MAGEA2 in tumor lines grown in vitro or as xenografts led to continued proliferation in the presence of tamoxifen. At the molecular level, we demonstrate that MAGEA2 protein localizes to the nucleus and forms complexes with p53 and ERα, resulting in repression of the p53 pathway but increased ER-dependent signaling. In a series of ER+, tamoxifen-treated breast cancer patients, we show a highly significant (P=0.006) association between MAGEA (melanoma-associated antigen) expression and reduced overall survival, confirming the clinical significance of our observations.

Association between DNA methylation of HSPB1 and death in low Gleason score prostate cancer.

BACKGROUND: Heat shock protein 27 (Hsp-27) encoded by gene HSPB1 is a critical regulator of the behavioral phenotype of human prostate cancer (PCa) cells, enhanced expression being associated with highly aggressive disease and poor clinical outcome. In contrast, the protein is not expressed in PCas of low malignant potential. To gain insight into the mechanism regulating its expression, we tested the hypothesis that differential methylation of CpG islands within HSPB1 controls transcription and subsequent translation of the gene. METHODS: We studied prostate epithelial cell lines and tissue biopsies, including 59 BPH and 415 PCas, of which 367 were a cohort of men with up to 20 years of follow-up. Methylation across the gene (DNA methylation (DNAme)) was assayed by pyrosequencing. Hsp-27 expression was assessed by western blot and immunohistochemistry. RESULTS: In cancer tissues, methylation increased in a 3' direction (P < 0.0001) whereas in benign hyperplasia methylation was constantly below 5%, a cutoff giving a specificity of 100% and sensitivity of 50%. Although methylation of the promoter region was significantly discriminating between benign and malignant prostatic epithelia, it compared poorly with methylation of the first intron. The prognostic value of HSPB1 DNAme was confirmed by both univariate (hazard ratio 1.77 per 50% increment, P = 0.02) and multivariate models. Interaction between HSPB1 methylation and Gleason score revealed high DNAme to be a reliable prognostic marker of poor outcome in men with low Gleason score (P = 0.014). CONCLUSIONS: Our data indicate CpG methylation of the first HSPB1 intron to be an important biomarker that identifies aggressive PCas otherwise regarded as low risk by current clinical criteria but that, biologically, require immediate active management.

Cancer incidence in the United Kingdom: projections to the year 2030.

BACKGROUND: Projections of cancer incidence are important for planning health services and to provide a baseline for assessing the impact of public health interventions. METHODS: Rates estimated from smooth function age-period-cohort modelling of cancer incidence data from Great Britain 1975 to 2007 are extrapolated to 2030 and applied to UK population projections. Prostate and breast cancer projections take into account the effect of screening. RESULTS: Overall rates of cancer are projected to be stable over the next 20 years, but this masks individual changes. In both sexes, age-standardised rates of cancers of the stomach, larynx, bladder and leukaemia are projected to fall by ≥1% per year, whereas cancers of the lip, mouth and pharynx (ICD-10 C00-C14) and melanoma are projected to increase by ≥1% per year. The growing and aging populations will have a substantial impact: numbers of cancers in men and women are projected to increase by 55% (from 149,169 to 231,026) and 35% (from 148,716 to 200,929), respectively, between 2007 and 2030. The model used yields similar results to those of Nordpred, but is more flexible. CONCLUSION: Without new initiatives for smoking and obesity reduction, the number of cancers in the United Kingdom will increase substantially reflecting the growing and aging populations.

Radiation therapy in hyperbaric oxygen for head and neck cancer at Royal Adelaide Hospital--1964 to 1980.

This report describes experience with radiation therapy in hyperbaric oxygen in 201 patients with squamous carcinoma arising in the mobile portion of tongue (anterior 2/3), oropharynx, hypopharynx, and supraglottic larynx, treated between the years 1964 and 1980. Although not statistically different, the overall 5-year determinate survival figures of 35% for all patients with tumors arising in the hypopharynx, 87.5% for Stage I and II, 55% for Stage III, and 27.1% for Stage IV supraglottic carcinoma were perceptibly better than those obtained in a contemporary but not randomly controlled series of patients treated in air at Royal Adelaide Hospital from 1970 to 1980. The results obtained for tumors arising in the oropharynx and mobile portion of tongue however were found to be very similar to those achieved in air. The results achieved in this series are discussed in the context of experience at other centers and the role of randomly controlled clinical studies in evaluating new treatment modalities is emphasized.