A Window into Practice: Examining Elementary Writing Methods Instruction

We know very little about what happens in elementary literacy methods courses, particularly those that focus on writing instruction. In this study, we offer a window into writing methods instruction, examining three pedagogies of practice used by experienced teacher educators (TEs) across one U.S. state —representations, decompositions, and approximations of practice (Grossman, Compton, Igra, Ronfeldt, Shahan, & Williamson, 2009). We found a variety of ways that instructors use these pedagogies of practice, both in isolation and in combination, in their instruction. We provide implications and suggestions for the support and development of elementary writing methods TEs

Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941

SummaryHerceptin (trastuzumab) is the backbone of HER2-directed breast cancer therapy and benefits patients in both the adjuvant and metastatic settings. Here, we describe a mechanism of action for trastuzumab whereby antibody treatment disrupts ligand-independent HER2/HER3 interactions in HER2-amplified cells. The kinetics of dissociation parallels HER3 dephosphorylation and uncoupling from PI3K activity, leading to downregulation of proximal and distal AKT signaling, and correlates with the antiproliferative effects of trastuzumab. A selective and potent PI3K inhibitor, GDC-0941, is highly efficacious both in combination with trastuzumab and in the treatment of trastuzumab-resistant cells and tumors

Acute Reperfusion Therapy in ST-elevation Myocardial Infarction from 1994-2003

Background—Appropriate utilization of acute reperfusion therapy is not a national performance measure for ST-elevation myocardial infarction at this time, and the extent of its contemporary use among ideal patients is unknown. Methods—From the National Registry of Myocardial Infarction, we identified 238,291 patients enrolled from June 1994 to May 2003 who were ideally suited for acute reperfusion therapy with fibrinolytic therapy or primary percutaneous coronary intervention. We determined rates of not receiving therapy across 3 time periods (June 1994–May 1997, June 1997–May 2000, June 2000– May 2003) and evaluated factors associated with underutilization. Results—The proportion of ideal patients not receiving acute reperfusion therapy decreased by one-half throughout the past decade (time period 1: 20.6%; time period 2: 11.4%; time period 3: 11.6%; P\u3c0.001). Utilization remained significantly lower in key subgroups in the most recent time period: those without chest pain (OR, 0.29; 95% CI, 0.27–0.32); those presenting 6 to 12 hours after symptom onset (OR, 0.57; 95% CI, 0.52–0.61); those 75 years or older (OR, 0.63 compared with patients \u3c55 years old; 95% CI, 0.58–0.68); women (OR, 0.88; 95% CI, 0.84–0.93); and non-whites (OR, 0.90; 95% CI, 0.83–0.97). Conclusions—Utilization of acute reperfusion therapy in ideal patients has improved over the last decade, but more than 10% remain untreated. Measuring and improving its use in this cohort represents an important opportunity to improve care

Concurrent Exposure of Bottlenose Dolphins (Tursiops truncatus) to Multiple Algal Toxins in Sarasota Bay, Florida, USA

Sentinel species such as bottlenose dolphins (Tursiops truncatus) can be impacted by large-scale mortality events due to exposure to marine algal toxins. In the Sarasota Bay region (Gulf of Mexico, Florida, USA), the bottlenose dolphin population is frequently exposed to harmful algal blooms (HABs) of Karenia brevis and the neurotoxic brevetoxins (PbTx; BTX) produced by this dinoflagellate. Live dolphins sampled during capture-release health assessments performed in this region tested positive for two HAB toxins; brevetoxin and domoic acid (DA). Over a ten-year study period (2000–2009) we have determined that bottlenose dolphins are exposed to brevetoxin and/or DA on a nearly annual basis (i.e., DA: 2004, 2005, 2006, 2008, 2009; brevetoxin: 2000, 2004, 2005, 2008, 2009) with 36% of all animals testing positive for brevetoxin (n = 118) and 53% positive for DA (n = 83) with several individuals (14%) testing positive for both neurotoxins in at least one tissue/fluid. To date there have been no previously published reports of DA in southwestern Florida marine mammals, however the May 2008 health assessment coincided with a Pseudo-nitzschia pseudodelicatissima bloom that was the likely source of DA observed in seawater and live dolphin samples. Concurrently, both DA and brevetoxin were observed in common prey fish. Although no Pseudo-nitzschia bloom was identified the following year, DA was identified in seawater, fish, sediment, snails, and dolphins. DA concentrations in feces were positively correlated with hematologic parameters including an increase in total white blood cell (p = 0.001) and eosinophil (p<0.001) counts. Our findings demonstrate that dolphins within Sarasota Bay are commonly exposed to two algal toxins, and provide the impetus to further explore the potential long-term impacts on bottlenose dolphin health

Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts