After the Bell: Youth Activity Engagement in Relation to Income and Metropolitan Status

In this brief, author Sarah E. Leonard uses data from the 2012 National Survey of Children’s Health to examine involvement in activities among youth ages 12–18 across income categories and metropolitan status in the hopes of informing policy aimed at attenuating inequalities in participation. While not a complete profile of youth activities, determining participation rates helps us understand what youth are doing in their out-of-school hours and how these activities vary by income and metropolitan status. The relationship between extracurricular participation, academic success, and well-being is potentially linked in complex ways, yet access to extracurricular activities and employment is growing more unequal, and as a result lower-income youth may be increasingly disadvantaged compared to middle- and upper-income children. She reports that higher-income youth are twice as likely to be employed and one-and-a-half times as likely to participate in extracurricular activities as their lower-income counterparts. More urban youth participate in extracurricular activities than rural youth, but rural youth are more likely to be employed than urban youth. The share of youth who are reading, using television, and using electronics is comparable across income groups, though lower-income youth report participating in these activities for longer hours than their higher-income counterparts. In conclusion, she suggests actions that policy makers and school systems could take to give adolescents--regardless of their income or metropolitan status--the opportunity to participate in and benefit from extracurricular activities

Rethinking Grading: Exploring High School Teachers\u27 Experiences with Changing to a Nontraditional Grading System

This exploratory case study examined the experiences of high school teachers who made sense of and enacted a gradeless system in their classes. The study explored what led the teacher participants to make such a significant shift in their thinking and practice as well as what supports and/or challenges they experienced in the process of implementing a nontraditional grading system. The three participants constituted a unique case as they explored an alternative grading model quite different from the traditional 0-100-point model that tends to be the dominant system in public high schools. The findings revealed that the nontraditional systems they developed were grounded in student growth, proficiency, and demonstration of soft skills. As the participants worked to make sense of this system, their beliefs about grading and their past experiences shaped their implementation. They shared that support from colleagues and administrators was paramount to them enacting this change in their classes. This support helped them overcome the challenges they experienced along the way. Participants revealed an increase in student ownership and equity were outcomes that made the system worth using. Implications for scholarship and practice in the study focus on additional research being done on the nontraditional model and exhort educators to engage in introspection surrounding their grading practices as well as finding a supportive community as they move to a nontraditional model

Advancing Feminism Online. Online Tools, Visibility, and Women in Classics

Can online tools address gender bias in classics? Through two case studies, this article explores the use of crowd-sourcing in order to develop digital tools that amplify women and provide them with a firmer online identity. The first, Wikipedia.org, is already entrenched in the popular research realm, and the second, WOAH (Women of Ancient History), is currently being developed as a reference tool. Wikipedia.org is the most influential source of knowledge in the world, but it has a stubborn gender bias against women. This distortion is particularly evident in the field of classics, where prior to 2017 only 7% of biographies of classicists featured women. Here, ‘classics’ is an inclusive term, and is broadly conceived to include the field of Late Antiquity. This short article details how the Women’s Classical Committee (UK)’s Wikipedia editing initiative, #WCCWiki, and the development of WOAH, have successfully increased the visibility of women online. Consequently, it offers a model to mobilize change with few physical or financial resources, but rather facilitated by digital tools and social media. Through digital feminist activism, there is the potential to reverse the gender skew of classicists online and in the public discourse, while also creating an inclusive space that is professional, proactive, and accessible to all

Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors

Src-family kinases (SFKs) play important roles in human biology and are key drug targets as well. However, achieving selective inhibition of individual Src-family kinases is challenging due to the high similarity within the protein family. We describe rhodium(II) conjugates that deliver both potent and selective inhibition of Src-family SH3 domains. Rhodium(II) conjugates offer dramatic affinity enhancements due to interactions with specific and unique Lewis-basic histidine residues near the SH3 binding interface, allowing predictable, structure-guided inhibition of SH3 targets that are recalcitrant to traditional inhibitors. In one example, a simple metallopeptide binds the Lyn SH3 domain with 6 nM affinity and exhibits functional activation of Lyn kinase under biologically relevant concentrations (EC50 ∼ 200 nM)

Real-time analysis and display of quantitative measures to track and improve clinical workflow

PURPOSE: Radiotherapy treatment planning is a complex process with multiple, dependent steps involving an interdisciplinary patient care team. Effective communication and real-time tracking of resources and care path activities are key for clinical efficiency and patient safety. MATERIALS AND METHODS: We designed and implemented a secure, interactive web-based dashboard for patient care path, clinical workflow, and resource utilization management. The dashboard enables visualization of resource utilization and tracks progress in a patient\u27s care path from the time of acquisition of the planning CT to the time of treatment in real-time. It integrates with the departmental electronic medical records (EMR) system without the creation and maintenance of a separate database or duplication of work by clinical staff. Performance measures of workflow were calculated. RESULTS: The dashboard implements a standardized clinical workflow and dynamically consolidates real-time information queried from multiple tables in the EMR database over the following views: (1) CT Sims summarizes patient appointment information on the CT simulator and patient load; (2) Linac Sims summarizes patient appointment times, setup history, and notes, and patient load; (3) Task Status lists the clinical tasks associated with a treatment plan, their due date, status and ownership, and patient appointment details; (4) Documents provides the status of all documents in the patients\u27 charts; and (5) Diagnoses and Interventions summarizes prescription information, imaging instructions and whether the plan was approved for treatment. Real-time assessment and quantification of progress and delays in a patient\u27s treatment start were achieved. CONCLUSIONS: This study indicates it is feasible to develop and implement a dashboard, tailored to the needs of an interdisciplinary team, which derives and integrates information from the EMR database for real-time analysis and display of resource utilization and clinical workflow in radiation oncology. The framework developed facilitates informed, data-driven decisions on clinical workflow management as we seek to optimize clinical efficiency and patient safety

Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor negative breast cancer

Calcium signaling is a critical regulator of cell proliferation. Elevated expression of calcium channels and pumps is a characteristic of some cancers, including breast cancer. We show that the plasma membrane calcium channel TRPV6, which is highly selective for Ca(2+), is overexpressed in some breast cancer cell lines. Silencing of TRPV6 expression in a breast cancer cell line with increased endogenous TRPV6 expression lead to a reduction in basal calcium influx and cellular proliferation associated with a reduction in DNA synthesis. TRPV6 gene amplification was identified as one mechanism of TRPV6 overexpression in a sub-set of breast cancer cell lines and breast tumor samples. Analysis of two independent microarray expression datasets from breast tumor samples showed that increased TRPV6 expression is a feature of estrogen receptor negative breast tumors encompassing the basal-like molecular subtype, as well as HER2-positive tumors. Breast cancer patients with high TRPV6 levels had decreased survival compared to patients with low or intermediate TRPV6 expression. Our findings suggest that inhibitors of TRPV6 may offer a novel therapeutic strategy for the treatment of estrogen receptor-negative breast cancers

Lexicality and frequency in specific language impairment: accuracy and error data from two nonword repetition tests

Purpose: Deficits in phonological working memory and deficits in phonological processing have both been considered potential explanatory factors in Specific Language Impairment (SLI). Manipulations of the lexicality and phonotactic frequency of nonwords enable contrasting predictions to be derived from these hypotheses. Method: 18 typically developing (TD) children and 18 children with SLI completed an assessment battery that included tests of language ability, non-verbal intelligence, and two nonword repetition tests that varied in lexicality and frequency. Results: Repetition accuracy showed that children with SLI were unimpaired for short and simple high lexicality nonwords, whereas clear impairments were shown for all low lexicality nonwords. For low lexicality nonwords, greater repetition accuracy was seen for nonwords constructed from high over low frequency phoneme sequences. Children with SLI made the same proportion of errors that substituted a nonsense syllable for a lexical item as TD children, and this was stable across nonword length. Conclusions: The data show support for a phonological processing deficit in children with SLI, where long-term lexical and sub-lexical phonological knowledge mediate the interpretation of nonwords. However, the data also suggest that while phonological processing may provide a key explanation of SLI, a full account is likely to be multi-faceted

PEITC-mediated inhibition of mRNA translation is associated with both inhibition of mTORC1 and increased eIF2α phosphorylation in established cell lines and primary human leukemia cells.

Increased mRNA translation drives carcinogenesis and is an attractive target for the development of new anti-cancer drugs. In this work, we investigated effects of phenethylisothiocyanate (PEITC), a phytochemical with chemopreventive and anti-cancer activity, on mRNA translation. PEITC rapidly inhibited global mRNA translation in human breast cancer-derived MCF7 cells and mouse embryonic fibroblasts (MEFs). In addition to the known inhibitory effects of PEITC on mTORC1 activity, we demonstrate that PEITC increased eIF2α phosphorylation. PEITC also increased formation of stress granules which are typically associated with eIF2α phosphorylation and accumulation of translationally stalled mRNAs. Analysis of genetically modified MEFs demonstrated that optimal inhibition of global mRNA translation by PEITC was dependent on eIF2α phosphorylation, but not mTORC1 inhibition. We extended this study into primary leukemic B cells derived from patients with chronic lymphocytic leukaemia (CLL). CLL cells were stimulated in vitro with anti-IgM to mimic binding of antigen, a major driver of this leukemia. In CLL cells, PEITC increased eIF2α phosphorylation, inhibited anti-IgM-induced mTORC1 activation and decreased both basal and anti-IgM-induced global mRNA translation. PEITC also inhibited transcription and translation of MYC mRNA and accumulation of the MYC oncoprotein, in anti-IgM-stimulated cells. Moreover, treatment of CLL cells with PEITC and the BTK kinase inhibitor ibrutinib decreased anti-IgM-induced translation and induced cell death to a greater extent than either agent alone. Therefore, PEITC can inhibit both global and mRNA specific translation (including MYC) via effects on multiple regulatory pathways. Inhibition of mRNA translation may contribute to the chemopreventive and anti-cancer effects of PEITC

Prevalence of Suspected Hereditary Cancer Syndromes and Germline Mutations Among a Diverse Cohort of Probands Reporting a Family History of Prostate Cancer: Toward Informing Cascade Testing for Men.

BACKGROUND: Prostate cancer (PCa) is increasingly recognized as part of hereditary cancer syndromes (HCSs). HCS prevalence among diverse probands seeking genetic evaluation with PCa family history (FHx) has not been reported and has implications for cascade genetic testing. OBJECTIVE: To evaluate the rates of HCSs among probands reporting PCa FHx and germline mutations among probands. DESIGN, SETTING, AND PARTICIPANTS: A prospective genetic testing database queried for individuals with PCa FHx. Pedigrees analyzed for three HCSs: hereditary breast and ovarian cancer (HBOC), hereditary PCa, and Lynch syndrome. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between HCS overall, and with plausible link to PCA FHx and race evaluated using Fisher\u27s exact test. Germline mutation rates described among probands with a suspicion of an HCS connected with PCa FHx. RESULTS AND LIMITATIONS: A total of 345 probands reported PCa FHx: 53 African American (AA) and 292 Caucasian (Wh). Overall, 220 probands (63.8%) met the criteria for at least one HCS with a potential link to PCa FHx (75.5% AA; 61.6% Wh). HBOC linked to PCa FHx was identified in a higher percentage of AA than Wh probands (90.2% vs 74.6%, p=0.04). Among probands who underwent genetic testing with any HCS potentially linked to PCa FHx (n=169), 19.5% had germline mutations identified; five AA probands had germline mutations (all in BRCA1/2), while 28 Wh probands had mutations in a spectrum of genes. CONCLUSIONS: A significant percentage of AA probands with PCa FHx meet the criteria for HCSs, with HBOC identified at the highest rate. Although limited in sample size, our findings implicate BRCA mutations in AA families with HCSs linked with PCa, underscoring the need for greater enrollment of AA participants in genetic studies. PATIENT SUMMARY: Hereditary cancer syndromes potentially linked to prostate cancer are common in patients reporting a family history of prostate cancer. African-American patients may need special attention with regard to testing for hereditary breast and ovarian cancer syndrome, which may impact men with prostate cancer in these families