Visual variability affects early verb learning

Research demonstrates that within-category visual variability facilitates noun learning; however, the effect of visual variability on verb learning is unknown. We habituated 24-month-old children to a novel verb paired with an animated star-shaped actor. Across multiple trials, children saw either a single action from an action category (identical actions condition, for example, travelling while repeatedly changing into a circle shape) or multiple actions from that action category (variable actions condition, for example, travelling while changing into a circle shape, then a square shape, then a triangle shape). Four test trials followed habituation. One paired the habituated verb with a new action from the habituated category (e.g., ‘dacking’ + pentagon shape) and one with a completely novel action (e.g., ‘dacking’ + leg movement). The others paired a new verb with a new same-category action (e.g., ‘keefing’ + pentagon shape), or a completely novel category action (e.g., ‘keefing’ + leg movement). Although all children discriminated novel verb/action pairs, children in the identical actions condition discriminated trials that included the completely novel verb, while children in the variable actions condition discriminated the out-of-category action. These data suggest that – as in noun learning – visual variability affects verb learning and children's ability to form action categories

The Grizzly, September 11, 2003

Unique Organizations Attract New Members at Activities Fair • To Party or Not to Party: How is the Question • Reflections on the Post-September 11th World • An Anniversary Like No Other • A Major Decision • A Day in the Life: Lounge Living • Student Spotlight: Locks for Love • Activities Coming to You • Family Day at UC • John Mayer & Counting Crows • Opinions: Please Read: E-mail Abuse is Annoying; A Continuing Story: Out of the Middle East; The [De] Stabilized Situation in Iraq • 9/11: Reliving the Tragedy • SIGI Plus to the Rescue • UC on File Sharing: Joining the Bandwagon • Party Etiquette 101 • Price Comparison: Popular CDs • The Wit and Wisdom of J. D. Salinger • Bears Knock Out Susquehanna, 24-17 • Volleyball Team Makes it Three in a Row • TCNJ Field Hockey Blanks Ursinus • Men\u27s Soccer Comes out Even • Ursinus Women Dominate Soccer Classic • The Kobe Bryant Sagahttps://digitalcommons.ursinus.edu/grizzlynews/1540/thumbnail.jp

Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women

Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 × 10–8 as genome-wide significant, and p-values < 1 × 10–5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 × 105. The strongest evidence was found for rs4674019 (p-value = 2.27 × 10–7), which showed genome-wide significant interaction (p-value = 3.8 × 10–8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen–progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association

A likelihood ratio approach for utilizing case-control data in the clinical classification of rare sequence variants:Application to BRCA1 and BRCA2

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.</p

Common variants in breast cancer risk loci predispose to distinct tumor subtypes.

BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction

Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10 ) and AC058822.1 (P = 1.47 × 10 ), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10 ), demonstrating the importance of diversifying study cohorts. [Abstract copyright: © 2023. The Author(s).

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Effects of Motor Cortical Stimulation during Planar Reaching Movement

Background: The purpose was to examine the effects of single pulse transcranial magnetic stimulation (TMS) over primary motor cortex delivered at different times during a center-out reaching task in a robot reaching environment. Methods: Eleven right-handed subjects participated. Movement hotspots and thresholds were determined for each subject, and the stimulation intensity was set at 120% of the movement threshold. TMS was delivered at rest and when subjects performed a series of reaching tasks. The 5 different conditions were: no stimulation, sham stimulation, and stimulation at 150, 500, or 1000 ms post go cue. Outcome measures included TMS-evoked movement during rest and in the 150ms condition, trajectory deviations (no stimulation, sham, and 150ms conditions), and peak velocity (PV), path length, reaction time, acceleration time, and deceleration time for all conditions. Results: When TMS was applied at 150 ms, the evoked path lengths were significantly shorter than at rest and had less deviation than the no-stimulation condition (p &lt; 0.05). Peak velocities were lowest during the no-stimulation condition and highest during the 500ms condition (p &lt; 0.05). Path lengths were significantly shorter during the no-stimulation, sham, and 150ms condition compared to the 500ms and 1000ms conditions. Conclusions: TMS applied during the reaction time phase suppressed movements evoked by TMS, decreased trajectory deviations, and shortened path length, while TMS delivered after movement onset increased PV and path length. TMS stimulation may be delivered to enhance movement parameters and potentially facilitate reach training in the robotic rehabilitation environment