Analysis of existing mathematics textbooks for use in secondary schools.

Thesis (Ed.M.)--Boston University Thesis (M.A.)--Boston Universit

Unscreened water-diversion pipes pose an entrainment risk to the threatened green sturgeon, Acipenser medirostris.

Over 3,300 unscreened agricultural water diversion pipes line the levees and riverbanks of the Sacramento River (California) watershed, where the threatened Southern Distinct Population Segment of green sturgeon, Acipenser medirostris, spawn. The number of sturgeon drawn into (entrained) and killed by these pipes is greatly unknown. We examined avoidance behaviors and entrainment susceptibility of juvenile green sturgeon (35±0.6 cm mean fork length) to entrainment in a large (>500-kl) outdoor flume with a 0.46-m-diameter water-diversion pipe. Fish entrainment was generally high (range: 26-61%), likely due to a lack of avoidance behavior prior to entering inescapable inflow conditions. We estimated that up to 52% of green sturgeon could be entrained after passing within 1.5 m of an active water-diversion pipe three times. These data suggest that green sturgeon are vulnerable to unscreened water-diversion pipes, and that additional research is needed to determine the potential impacts of entrainment mortality on declining sturgeon populations. Data under various hydraulic conditions also suggest that entrainment-related mortality could be decreased by extracting water at lower diversion rates over longer periods of time, balancing agricultural needs with green sturgeon conservation

Mirror Prescription Regression: A Differential Interferometric Technique

We present a remote, differential method for measuring the prescription of aspheric mirrors using null interferometry in the center-of-curvature configuration. The method requires no equipment beyond that used in a basic interferometery setup (i.e., there are no shearing elements or absolute distance meters). We chose this configuration because of its widespread use. However, the method is generalizable to other configurations with an adjustment of the governing equation. The method involves taking a series of interferograms before and after small, known misalignments are applied to the mirror in the interferometry setup and calculating the prescription (e.g., radius of curvature and conic constant) of the mirror, based on these differential measurements, using a nonlinear regression. We apply this method successfully to the testing of a Space Optics Research Lab off-axis parabola with a known focal length of 152.4 mm, a diameter of 76.2 mm, and an off-axis angle of 12°

Use of diagnosis codes for detection of clinically significant opioid poisoning in the emergency department: A retrospective analysis of a surveillance case definition

Abstract Background Although fatal opioid poisonings tripled from 1999 to 2008, data describing nonfatal poisonings are rare. Public health authorities are in need of tools to track opioid poisonings in near real time. Methods We determined the utility of ICD-9-CM diagnosis codes for identifying clinically significant opioid poisonings in a state-wide emergency department (ED) surveillance system. We sampled visits from four hospitals from July 2009 to June 2012 with diagnosis codes of 965.00, 965.01, 965.02 and 965.09 (poisoning by opiates and related narcotics) and/or an external cause of injury code of E850.0-E850.2 (accidental poisoning by opiates and related narcotics), and developed a novel case definition to determine in which cases opioid poisoning prompted the ED visit. We calculated the percentage of visits coded for opioid poisoning that were clinically significant and compared it to the percentage of visits coded for poisoning by non-opioid agents in which there was actually poisoning by an opioid agent. We created a multivariate regression model to determine if other collected triage data can improve the positive predictive value of diagnosis codes alone for detecting clinically significant opioid poisoning. Results 70.1 % of visits (Standard Error 2.4 %) coded for opioid poisoning were primarily prompted by opioid poisoning. The remainder of visits represented opioid exposure in the setting of other primary diseases. Among non-opioid poisoning codes reviewed, up to 36 % were reclassified as an opioid poisoning. In multivariate analysis, only naloxone use improved the positive predictive value of ICD-9-CM codes for identifying clinically significant opioid poisoning, but was associated with a high false negative rate. Conclusions This surveillance mechanism identifies many clinically significant opioid overdoses with a high positive predictive value. With further validation, it may help target control measures such as prescriber education and pharmacy monitoring

Posterior lung herniation after a coughing spell: a case report

Lung hernias are rare, occurring most commonly after trauma or surgery. Spontaneous lung hernias are even rarer and have only been reported as occurring anteriorly. We present a 72-year-old male who developed a spontaneous posterior lung hernia after a severe coughing episode. We describe the evaluation and surgical management of this unusual condition and provide a brief review of the literature

A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial.

BACKGROUND: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. METHODS: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). PRIMARY ENDPOINT: invasive loco-regional control (ILRC); secondary overall survival. FINDINGS: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99-1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82-2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99-2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28-1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7-119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07-15.5, p = 0.978) radiotherapy. INTERPRETATION: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. FUNDING: Cancer Research UK, NIHR, MRC

Genotyping with a 198 Mutation Arrayed Primer Extension Array for Hereditary Hearing Loss: Assessment of Its Diagnostic Value for Medical Practice

Molecular diagnostic testing of individuals with congenital sensorineural hearing loss typically begins with DNA sequencing of the GJB2 gene. If the cause of the hearing loss is not identified in GJB2, additional testing can be ordered. However, the step-wise analysis of several genes often results in a protracted diagnostic process. The more comprehensive Hereditary Hearing Loss Arrayed Primer Extension microarray enables analysis of 198 mutations across eight genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5, MTRNR1 and MTTS1) in a single test. To evaluate the added diagnostic value of this microarray for our ethnically diverse patient population, we tested 144 individuals with congenital sensorineural hearing loss who were negative for biallelic GJB2 or GJB6 mutations. The array successfully detected all GJB2 changes previously identified in the study group, confirming excellent assay performance. Additional mutations were identified in the SLC26A4, SLC26A5 and MTRNR1 genes of 12/144 individuals (8.3%), four of whom (2.8%) had genotypes consistent with pathogenicity. These results suggest that the current format of this microarray falls short of adding diagnostic value beyond the customary testing of GJB2, perhaps reflecting the array's limitations on the number of mutations included for each gene, but more likely resulting from unknown genetic contributors to this phenotype. We conclude that mutations in other hearing loss associated genes should be incorporated in the array as knowledge of the etiology of hearing loss evolves. Such future modification of the flexible configuration of the Hereditary Hearing Loss Arrayed Primer Extension microarray would improve its impact as a diagnostic tool

Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Rapid Intraoperative Molecular Characterization of Glioma

IMPORTANCE: Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1). OBSERVATIONS: This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96% sensitivity (95% CI, 90%–99%) and 100% specificity (95% CI, 95%–100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe. CONCLUSIONS AND RELEVANCE: The genotyping method described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations