Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer

Table S1. Patient characteristics. Table S2. Hazard ratios from multivariate analysis. Table S3. Sequences of primers used for qRT-PCR. Figure S1. Distribution of average centrosome number per cell in the breast cancer patients represented in our TMA. Figure S2. Correlations between centrosome amplification and nodal status, patient age, and tumor size. Figure S3. Centrosome clustering but not structural abnormalities correlate with worse outcomes in breast cancer. Figure S4. CIN is prognostic of worse breast cancer-related survival. Figure S5. Centrosome amplification correlates with adverse clinical factors. Figure S6. CA correlates with higher ploidy and CIN. (DOCX 6223 kb

High-throughput gene discovery in the rat

The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3′ ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to ∼50,000 rat UniGene clusters. We have identified, arrayed, and derived 5′ ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI

Childhood Apraxia of Speech (CAS) in two patients with 16p11.2 microdeletion syndrome

We report clinical findings that extend the phenotype of the ~550 kb 16p11.2 microdeletion syndrome to include a rare, severe, and persistent pediatric speech sound disorder termed Childhood Apraxia of Speech (CAS). CAS is the speech disorder identified in a multigenerational pedigree (\u27KE\u27) in which half of the members have a mutation in FOXP2 that co-segregates with CAS, oromotor apraxia, and low scores on a nonword repetition task. Each of the two patients in the current report completed a 2-h assessment protocol that provided information on their cognitive, language, speech, oral mechanism, motor, and developmental histories and performance. Their histories and standard scores on perceptual and acoustic speech tasks met clinical and research criteria for CAS. Array comparative genomic hybridization analyses identified deletions at chromosome 16p11.2 in each patient. These are the first reported cases with well-characterized CAS in the 16p11.2 syndrome literature and the first report of this microdeletion in CAS genetics research. We discuss implications of findings for issues in both literatures

Seeking a pedagogy of difference: what Aboriginal students and their parents in North Queensland say about teaching and their learning\ud

This study presents the outcomes of the first phase of a three phase research initiative which begins by identifying through the voices of Aboriginal 1 students and community members the teaching practices that influence Aboriginal student engagement and learning. The study occurs within the Diocese of Townsville Catholic Education schools in North Queensland, primarily in the Mount Isa area. Through open-ended interviews, Aboriginal students and community members express their views of the characteristics of effective teachers and effective teaching. Considering that the national education discourse in Australia is monopolised by discussion on teaching and teacher quality, we problematize this discourse based upon what members of the local Aboriginal community assert as characteristics of effective teachers and their practice. Further phases of this research initiative, which investigate the effect of adjusted practice based upon community members' assertions, are also presented

Recruitment strategies and consent rates in a national prospective colorectal cancer screening cohort: results from year 1 of the Voyage Study

Objective To identify the optimal incentive protocol for maximising participation while managing study costs during the Voyage trial.Design Prospective cohort (Voyage trial) of colorectal cancer (CRC) incidence and mortality outcomes in individuals screened with multitarget stool DNA (mt-sDNA) served as the population. A subset was randomised to receive postage stamps as a pre-consent incentive, or as a post-consent incentive after completion of the consent and questionnaire. Descriptive statistics from year 1 are reported.Results During year 1 of the Voyage trial, a total of 600 258 individuals with mt-sDNA orders received at Exact Sciences Laboratories were randomly selected and invited to participate. Of those, 26 429 (4.4%) opted in, 14 365 of whom (54.3%) consented. The opt-in and consent samples were similar to the target population with respect to sex but differed by geographic residence and age (p<0.001). For the embedded incentive experiment, 2333 were randomised to the pre-incentive arm, while 2342 were randomised to the post-incentive arm. Overall consent rate in the incentive trial was 56.4% (60.9% for the pre-consent incentive arm (1421/2333) vs 52.0% for the post-consent incentive arm (1217/2342), p<0.001). Cost reduction was observed for the pre-consent incentive group, and higher response rates were seen among older versus younger individuals.Conclusions Pre-consent incentive option was associated with a higher participation rate and lower costs and was used for the remainder of study recruitment. CRC incidence and mortality vary with age; thus, adjusting for differential participation by age and region will be important in analyses of Voyage data.Trial registration number NCT04124406

FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States

Abstract Background Population screening for FMR1 mutations has been a topic of considerable discussion since the FMR1 gene was identified in 1991. Advances in understanding the molecular basis of fragile X syndrome (FXS) and in genetic testing methods have led to new, less expensive methodology to use for large screening endeavors. A core criterion for newborn screening is an accurate understanding of the public health burden of a disease, considering both disease severity and prevalence rate. This article addresses this need by reporting prevalence rates observed in a pilot newborn screening study for FXS in the US. Methods Blood spot screening of 14,207 newborns (7,312 males and 6,895 females) was conducted in three birthing hospitals across the United States beginning in November 2008, using a PCR-based approach. Results The prevalence of gray zone alleles was 1:66 females and 1:112 males, while the prevalence of a premutation was 1:209 females and 1:430 males. Differences in prevalence rates were observed among the various ethnic groups; specifically higher frequency for gray zone alleles in males was observed in the White group compared to the Hispanic and African-American groups. One full mutation male was identified (>200 CGG repeats). Conclusions The presented pilot study shows that newborn screening in fragile X is technically feasible and provides overall prevalence of the premutation and gray zone alleles in the USA, suggesting that the prevalence of the premutation, particularly in males, is higher than has been previously reported