Comparative Achievement of Students in a Freshman Academy with Those Not in a Freshman Academy by Race and Gender in One East Tennessee High School.

The purpose of this study was to compare the achievement of students who participated in a freshman academy program to the achievement of those who participated in the traditional high school curriculum. The researcher used grade point average and composite ACT score as determinants of achievement. The population consisted of the graduating classes of 2009 and 2010 at one East Tennessee high school. Independent sample t tests evaluated the relationship between achievement and type of freshman experience. The independent variables were participation in the freshman academy, being male, being female, and race. The dependent variables were grade point average and ACT composite score. The researcher made comparisons between all students, female students, male students, African American students, and white students in both programs. The quantitative findings revealed that males who participated in the freshmen academy achieved at a significantly higher rate than males who did not. In addition, the findings indicated white students who participated in the academy performed at a significantly higher rate than African American students who participated in the academy. There were no significant differences in the achievement of the entire population of each class, female students, white students, or African American students

A Clinical Trial to Increase the Identification, Genetic Counseling Referral and Genetic Testing of Women at risk for Hereditary Breast and/or Ovarian Cancer

Background: Approximately 1/300 individuals in the general population are at risk for hereditary breast and ovarian cancer due to an inherited mutation in the BRCA1/BRCA2 genes. BRCA mutations are associated with dramatically increased risks for breast cancer, especially at younger ages, in addition to ovarian cancer. Enhanced screening and risk reduction strategies can significantly reduce associated morbidity and mortality. The United States Preventive Services Task Force (USPSTF) recommends identifying women at-risk for BRCA mutations for receipt of genetic counseling and if appropriate, testing. The Breast Cancer Genetics Referral Screening Tool (B-RST) is a validated screen endorsed by USPSTF to facilitate this process. This implementation study seeks to evaluate the most effective means of follow-up for screen-positive women to maximize the number who are referred to, and receive, cancer genetic counseling (CGC) services. Methods: B-RST (v3.0) was used in three Emory Healthcare breast-imaging centers. Screen-positive women were randomized into three methods of follow-up (patient initiated, physician notification, or staff phone call). Primary outcomes were to compare the number of screen positive individuals who were referred for, scheduled, and completed a CGC appointment among the three groups. Results: Of 3,419 women approached, 63% participated and 579 (27%) screened positive. Appointments were scheduled by 7% of Group 1 participants, 17% of Group 2 individuals, and 11% of Group 3. Conclusions: Genomic medicine is receiving increased attention in the public health arena. Screening with B-RST 3.0 in mammography settings can improve identification of individuals at-risk for BRCA mutations and facilitate referral to CGC services. Despite B-RST’s ability to easily and accurately identify individuals appropriate for CGC, additional strategies are needed to facilitate completion of CGC in routine clinical practice

BIM MATURITY ASSESSMENT AND CERTIFICATION IN CONSTRUCTION PROJECT TEAM SELECTION

Abstract: To implement BIM in a construction project successfully, all the project participants as BIM users must have minimum BIM capabilities. Before any project starts, assessing BIM capabilities of project stakeholders is a concern for construction clients. The main problem of public clients regarding BIM is that they have no mechanism to ensure that the key participants, they hire for a BIM project, have the minimum capabilities (i.e. BIM Infrastructure, processes and qualified resources) to participate in design and delivery of the project. The high variability of firms' readiness to work with BIM may impose a high cost for the client and other mature members of the supply chain. Therefore, construction clients need a way to ensure minimum BIM maturity of participants, such as a maturity audit to assess BIM competency of potential project team members. From a client's perspective, "minimum BIM qualification" means "minimum capability to use BIM". The current BIM maturity models try to assess BIM capabilities level of firms, but lack BIM uses assessment. This research proposes a prototype that focuses on capability of firms in specific BIM uses, while measuring their general BIM capabilities. The research methodology is based on an iterative literature review followed by focus group discussions. Through literature review, the researchers propose BIM platform maturity model. Then, BIM experts discuss on possible improvements. It is expected that by using this model, construction clients may achieve more BIM benefits, i.e. reduced cost, time, and increased quality of project, through selection of BIM-qualified project team members

The maize brown midrib6 (bm6) mutation encodes a functional GTP Cyclohydrolase1

Brown midrib mutations in maize (Zea mays L.) and sorghum (Sorghum bicolor L.) alter lignin composition and enhance cell wall digestibility. These mutations are prime candidates for silage breeding. Six brown midrib mutants are currently known, brown midrib1 (bm1) to brown midrib6 (bm6). The bm1 and bm3 mutations are being used commercially for silage. The underlying genes responsible for five of the six bm mutations in maize (bm1, bm2, bm3, bm4, and bm5) are known. Chen and co-workers (2012) characterized the bm6 mutation, demonstratingthat bm6 increases cell wall digestibility and physically mapped bm6 within a 180 kilobase region on chromosome 2. The present investigation utilized map-based cloning to identify the candidate gene responsible for the bm6 phenotype as GTP Cyclohydrolase1 (GCH1) and validated the candidate gene through reverse genetics. Orthologs of bm6 include at least one paralogous gene in maize on chromosome 10 and various homologs in other grasses and dicots. The discovery that GCH1 is  responsible for the maize bm6 phenotype suggests that GCH1 plays a role in the tetrahydrofolate biosynthetic process

IgE and T cell reactivity to a comprehensive panel of cockroach allergens in relation to disease

IgE sensitization to cockroach allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach allergens we previously reported for the same cohort

Analysis of 8-oxo-7,8-dihydro-2′-deoxyguanosine by ultra high pressure liquid chromatography–heat assisted electrospray ionization–tandem mass spectrometry

Increased amounts of reactive oxygen species (ROS), generally termed oxidative stress, are frequently hypothesized to be causally associated with many diseases. Analyses of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in DNA and urine are widely used biomarkers for oxidative stress. Over the years it became clear that analysis of 8-oxo-dG in DNA is challenging due to artifactual formation during sample work up. The present study demonstrates that 8-oxo-dG can be measured reliably and accurately when appropriate precautions are taken. First, the presence of an antioxidant, metal chelator, or free radical trapping agent during sample preparation improves reproducibility. Second, sample enrichment by HPLC fraction collection was used to optimize sensitivity. Third, heat assisted electrospray ionization (HESI) eliminated potential interferences and improved assay performance and sensitivity. Subsequently, the UPLC–HESI–MS/MS method was applied to show the biphasic dose response of 8-oxo-dG in H2O2-treated HeLa cells. Application of this method to human lymphocyte DNA (n = 156) gave a mean±SD endogenous amount of 1.57±0.88 adducts per 106 dG, a value that is in agreement with the suggested amount previously estimated by European Standard Committee on Oxidative DNA Damage (ESCODD) and others. These results suggest that the present method is well suited for application to molecular toxicology and epidemiology studies investigating the role of oxidative stress

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children.

Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes

Distinct Pigmentary and Melanocortin 1 Receptor–Dependent Components of Cutaneous Defense against Ultraviolet Radiation

Genetic variation at the melanocortin 1 receptor (MC1R) is an important risk factor for developing ultraviolet (UV) radiation–induced skin cancer, the most common form of cancer in humans. The underlying mechanisms by which the MC1R defends against UV-induced skin cancer are not known. We used neonatal mouse skin (which, like human skin, contains a mixture of melanocytes and keratinocytes) to study how pigment cells and Mc1r genotype affect the genome-level response to UV radiation. Animals without viable melanocytes (Kit(W-v)/Kit(W-v)) or animals lacking a functional Mc1r (Mc1r(e)/Mc1r(e)) were exposed to sunburn-level doses of UVB radiation, and the patterns of large-scale gene expression in the basal epidermis were compared to each other and to nonmutant animals. Our analysis revealed discrete Kit- and Mc1r-dependent UVB transcriptional responses in the basal epidermis. The Kit-dependent UVB response was characterized largely by an enrichment of oxidative and endoplasmic reticulum stress genes, highlighting a distinctive role for pigmented melanocytes in mediating antioxidant defenses against genotoxic stresses within the basal epidermal environment. By contrast, the Mc1r-dependent UVB response contained an abundance of genes associated with regulating the cell cycle and oncogenesis. To test the clinical relevance of these observations, we analyzed publicly available data sets for primary melanoma and melanoma metastases and found that the set of genes specific for the Mc1r-dependent UVB response was able to differentiate between different clinical subtypes. Our analysis also revealed that the classes of genes induced by UVB differ from those repressed by UVB with regard to their biological functions, their overall number, and their size. The findings described here offer new insights into the transcriptional nature of the UV response in the skin and provide a molecular framework for the underlying mechanisms by which melanocytes and the Mc1r independently mediate and afford protection against UV radiation

Variability in German Cockroach Extract Composition Greatly Impacts T Cell Potency in Cockroach-Allergic Donors

German cockroach extract is used clinically to evaluate allergen-specific sensitization and for subcutaneous allergen-specific immunotherapy, though there are no guidelines for standardization in its manufacture. We performed an immunological evaluation of 12 different cockroach extracts prepared from different sources and their potency to induce allergen-specific T cell reactivity. PBMC from 13 cockroach allergic donors were expanded in vitro with 12 different German cockroach extracts. After culture expansion, cells were re-stimulated with the different extracts and T cell responses were assessed by FluoroSpot (IL-5, IFNγ and IL-10 production). In parallel to the extracts, single allergen peptide pools for allergens from groups 1, 2, 4, 5, and 11 were tested to determine allergen immunodominance. Furthermore, to assess allergy specificity, PBMC from 13 non-allergic donors were also tested with the most potent extract and T cell responses were compared to the allergic cohort. Dramatic variations in T cell reactivity were observed to the different cockroach extract batches. Response magnitudes varied over 3 logs within a single donor. IL-5 production in the allergic cohort was significantly higher compared to the non-allergic cohort (p=0.004). Allergen content determination by ELISA detected much lower concentrations of Bla g 5 compared to Bla g 1 and 2. Mass spectrometric analysis revealed that Bla g 5 was present in similar amounts to Bla g 1 and 2 in extracts made from whole body, whereas it was not detected in extracts made from fecal matter, suggesting that Bla g 5 is not excreted into feces. Different donors exhibit different response patterns to different extracts, potentially dependent on the donor-specific T cell allergen immunodominance pattern and the allergen content of the extract tested. These findings have dramatic implications for the selection of potent extracts used for diagnostic purposes or allergen-specific immunotherapy

Gene expression profiling of tumour epithelial and stromal compartments during breast cancer progression

The progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) marks a critical step in the evolution of breast cancer. There is some evidence to suggest that dynamic interactions between the neoplastic cells and the tumour microenvironment play an important role. Using the whole-genome cDNA-mediated annealing, selection, extension and ligation assay (WG-DASL, Illumina), we performed gene expression profiling on 87 formalin-fixed paraffin-embedded (FFPE) samples from 17 patients consisting of matched IDC, DCIS and three types of stroma: IDC-S ( 10 mm from IDC or DCIS). Differential gene expression analysis was validated by quantitative real time-PCR, immunohistochemistry and immunofluorescence. The expression of several genes was down-regulated in stroma from cancer patients relative to normal stroma from reduction mammoplasties. In contrast, neoplastic epithelium underwent more gene expression changes during progression, including down regulation of SFRP1. In particular, we observed that molecules related to extracellular matrix (ECM) remodelling (e.g. COL11A1, COL5A2 and MMP13) were differentially expressed between DCIS and IDC. COL11A1 was overexpressed in IDC relative to DCIS and was expressed by both the epithelial and stromal compartments but was enriched in invading neoplastic epithelial cells. The contributions of both the epithelial and stromal compartments to the clinically important scenario of progression from DCIS to IDC. Gene expression profiles, we identified differential expression of genes related to ECM remodelling, and specifically the elevated expression of genes such as COL11A1, COL5A2 and MMP13 in epithelial cells of IDC. We propose that these expression changes could be involved in facilitating the transition from in situ disease to invasive cancer and may thus mark a critical point in disease development