Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.     

Ethnically bounded homeownership: qualitative insights on Los Angeles immigrant homeowners’ experiences during the U.S. Great Recession

Immigrant homeowners’ function within ethnic boundaries in the housing market may have helped or hindered them during the recent U.S. Great Recession. This research explores this theme through interviews with immigrant and non-immigrant homeowners from four ethnic communities in Los Angeles County and the non-profit organizations that tried to assist them. Immigrant homeowners turned to co-ethnics for advice and support and formed multigenerational households as a strategy to achieve and sustain homeownership. Language and cultural barriers primed them for risky loans and thwarted their pursuit of refinance and modification when they struggled to make mortgage payments. These findings conform to existing evidence of ethnic segmentation in the housing market and imply that analyses of home buying and homeownership in areas with significant immigrant populations should factor in the role of ethnicity.     

Robust production planning and control for multi-stage systems with flexible final assembly lines

Production planning of final assembly systems is a challenging task, as the often fluctuating order volumes require flexible solutions. Besides, the calculated plans need to be robust against the process-level disturbances and stochastic nature of some parameters like manual processing times or machine availability. In the paper, a simulation-based optimisation method is proposed that utilises lower level shop floor data to calculate robust production plans for final assembly lines of a flexible, multi-stage production system. In order to minimise the idle times when executing the plans, the capacity control that specifies the proper operator–task assignments is also determined. The analysed multi-stage system is operated with a pull strategy, which means that the production at the final assembly lines generates demands for the preceding stages providing the assembled components. In order to guarantee the feasibility of the plans calculated for the final assembly lines, a decomposition approach is proposed to optimise the production plan of preceding stages. By this way, the robust production can be ensured resulting in reduced losses and overall production costs even though the system is exposed to changes and disturbances.     

Synthesis and Cell Growth Inhibitory Activity of Six Non-glycosaminoglycan-Type Heparin-Analogue Trisaccharides

The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Herein, we present the efficient synthesis of five Glc-GlcA-Glc-sequenced and one Glc-IdoA-Glc-sequenced non-glycosaminoglycan, heparin-related trisaccharides with various sulfation/sulfonylation and methylation patterns. The cell growth inhibitory effects of the compounds were tested against four cancerous human cell lines and two non-cancerous cell lines. Two d -glucuronate-containing tetra-O-sulfated, partially methylated trisaccharides displayed remarkable and selective inhibitory effects on the growth of ovary carcinoma (A2780) and melanoma (WM35) cells. Methyl substituents on the glucuronide unit proved to be detrimental, whereas acetyl substituents were beneficial to the cytostatic activity of the sulfated derivatives.     

Measurement invariance of the Gifted Rating Scales—School Form across five cultural groups.

This study examined measurement invariance of the Gifted Rating Scales—School Form (GRS–S) across the United States, Puerto Rico, China, South Korea, and Turkey, using multigroup confirmatory factor analysis. A total of 1,817 students were rated by 287 teachers using either translated versions of GRS–S or the original English GRS–S. Results indicate a similar factor structure for the GRS–S across the five locations; six factors with each of the 72 items equivalently loaded to the same latent variable across groups. The metric invariance test and the factor variance and covariance invariance tests reveal that the patterns of factor loadings and the factor variances and covariances are invariant across the five groups. Moreover, the scalar invariance test indicates that item means are equivalent across the groups. These results suggest that the GRS–S has intercultural utility and can be similarly interpreted. Implications and limitations of the present research for gifted identification are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)