98 research outputs found

    Measuring academic learning and exam self-efficacy at admission to university and its relation to first-year attrition: an IRT-based multi-program validity study

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    Self-efficacy is associated with both academic performance and attrition in higher education. Whether it is possible to measure students’ academic self-efficacy after admission and prior to commencing higher education (i.e. pre-academic self-efficacy) in a valid and reliable way has hardly been studied. Aims: 1) to evaluate the construct validity and psychometric properties of two short scales to measure Pre-Academic Learning Self-Efficacy (PAL-SE) and Pre-Academic Exam Self-Efficacy (PAE-SE) using Rasch measurement models, 2) to investigate whether pre-academic self-efficacy was associated with half-year attrition across degree programs and institutions. Data consisted of 2686 Danish students admitted to nine different university degree programs across two institutions. Item analyses showed both scales to be essentially objective and construct valid, however, all items from the PAE-SE and two from the PAL-SE were locally dependent. Differential item functioning was found for the PAL-SE  relative to degree programs. Reliability of the PAE-SE was .77, and varied for the PAL-SE  from .79 to .86 across degree programs. Targeting was good only for the PAL-SE, thus we proceeded with the PAL-SE. PAL-SE was found to be associated with half-year attrition: A difference in PAL-SE from minimum to maximum was associated with a difference in half-year attrition of approximately 7%. This association was found both in the bivariate model and in the multivariate models with control of degree program, and with control of degree program and individual covariates such as earlier educational achievement and social background variables. Results thus also indicate that PAL-SE has a causal effect on half-year attrition

    Determination of dissimilatory sulfate reduction rates in marine sediment via radioactive S-35 tracer

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    Rates of dissimilatory sulfate reduction in aquatic sediments have been measured over many years with S-35-radiotracer, and the method has been continuously modified and optimized. This article discusses the sequence of procedures that constitutes the method from sediment handling before incubation, via incubation and distillation, to statistical analysis of the results. We test modifications that have been added since previous method descriptions, and we recommend sound experimental procedures. We discuss the measurement of extremely low sulfate reduction rates whereby only one count per minute labeled sulfide may be produced. We show by numerical modeling that the measured rates are mostly representative for a small volume around the point where (SO42-)-S-35 is injected and that this can be used as an advantage to avoid edge effects. Finally, we show that oxidation will spoil samples during storage unless the samples are stored frozen. The main focus is on marine sediment, but the discussions are equally relevant for freshwater

    An experimental investigation of partially shrouded propellers

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    Results are reported for a series of experiments in which forces associated with a propeller fitted with a partial shroud are measured. The shroud is partial in the sense that it subtends only 180 of the propeller circumference rather than the full circumference, as is commonly the case. S. J. Gordon in 1966 proposed that such a shroud could be used as a rudder if mounted so that it can be moved from one side to another on the propeller circumference.http://www.archive.org/details/experimentalinve00tarpThis thesis document was issued under the authority of another institution, not NPS. At the time it was written, a copy was added to the NPS Library collection for reasons not now known.  It has been included in the digital archive for its historical value to NPS.  Not believed to be a CIVINS (Civilian Institutions) title.Lieutenant Commander, United States Nav

    A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and <i>TOP2A</i> gene amplification

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    ᅟ: The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TOP2A gene amplification in their tumor cells. BACKGROUND: Epirubicin is an anthracycline that targets DNA topoisomerase 2-α enzyme encoded by the TOP2A gene. It is used for treatment of several malignancies, but currently not in CRC. TOP2A gene amplifications predict improved efficacy of epirubicin in patients with breast cancer and thus could be an alternative option for patients with CRC and amplified TOP2A gene. We have previously analysed the frequency of TOP2A gene aberrations in CRC and found that 46.6 % of these tumors had TOP2A copy gain and 2.0 % had loss of TOP2A when compared to adjacent normal tissue. The TOP2A gene is located on chromosome 17 and when the TOP2A/CEN-17 ratio was applied to identify tumors with gene loss or amplifications, 10.5 % had a ratio ≥ 1.5 consistent with gene amplification and 2.6 % had a ratio ≤ 0.8 suggesting gene deletions. Based on these observations and the knowledge gained from treatment of breast cancer patients, we have initiated a prospective clinical, phase II protocol using epirubicin (90 mg/m2 iv q 3 weeks) in mCRC patients, who are refractory to treatment with oxaliplatin. METHODS/DESIGN: The study is an open label, single arm, phase II study, investigating the efficacy of epirubicin in patients with oxaliplatin refractory mCRC and with a cancer cell TOP2A/CEN-17 ratio ≥ 1.5. TOP2A gene amplification measured by fluorescence in situ hybridization. A total of 25 evaluable patients (15 + 10 in two steps) will be included (Simon’s two-stage minimax design). Every nine weeks, response is measured by computed tomography imaging and evaluated according to RECIST 1.1. The primary end-point of the study is progression-free survival. TRIAL REGISTRATION: Eudract no. 2013-001648-79

    The potential role of Alu Y in the development of resistance to SN38 (Irinotecan) or oxaliplatin in colorectal cancer

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    BACKGROUND: Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in the treatment of colorectal cancer. However, the frequent development of resistance to these drugs represents a considerable challenge in the clinic. Alus as retrotransposons comprise 11% of the human genome. Genomic toxicity induced by carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains unknown. RESULTS: We applied reduced representation bisulfite sequencing (RRBS) to investigate the DNA methylome in SN38 or oxaliplatin resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of ‘DNA methylation entropy’ to estimate the diversity of DNA methylation states of the identified resistance phenotype-associated methylation loci observed in the cell line models. We identified different loci being characteristic for the different resistant cell lines. Interestingly, 53% of the identified loci were Alu sequences- especially the Alu Y subfamily. Furthermore, we identified an enrichment of Alu Y sequences that likely results from increased integration of new copies of Alu Y sequence in the drug-resistant cell lines. In the clinical samples, SOX1 and other SOX gene family members were shown to display variable DNA methylation states in their gene regions. The Alu Y sequences showed remarkable variation in DNA methylation states across the clinical samples. CONCLUSION: Our findings imply a crucial role of Alu Y in colorectal cancer drug resistance. Our study underscores the complexity of colorectal cancer aggravated by mobility of Alu elements and stresses the importance of personalized strategies, using a systematic and dynamic view, for effective cancer therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1552-y) contains supplementary material, which is available to authorized users

    Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer

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    BACKGROUND: No biomarker exists to guide the optimal choice of chemotherapy for patients with metastatic colorectal cancer. We examined the copy numbers (CN) of topoisomerase I (TOP1) as well as the ratios of TOP1/CEN-20 and TOP1/CEN-2 as biomarkers for irinotecan efficacy in patients with metastatic colorectal cancer. METHODS: From a national cohort, we identified 163 patients treated every third week with irinotecan 350 mg/m(2) as second-line therapy. Among these 108 were eligible for analyses and thus entered the study. Primary tumors samples were collected and tissue microarray (TMA) blocks were produced. FISH analysis was performed using two probe-mixes: TOP1/CEN-20 and TOP1/CEN-2. Only samples harboring all three signals (TOP1, CEN-20 and CEN-2) using FISH were included in the analyses. RESULTS: In the TOP1/CEN-20 probe-mix the median TOP1- and CEN-20 CN were 4.46 (range: 1.5–9.5) and 2.00 (range: 0.55–4.55), respectively. The median TOP1- and CEN-2 CN in the TOP1/CEN-2 probe-mix, were 4.57 (range: 1.82–10.43) and 1.98 (range: 1.22–6.14), respectively. The median TOP1/CEN-20 ratio and TOP1/CEN-2 ratio were 1.25 (range: 0.92–2.90) and 2.05 (range: 1.00–6.00), respectively. None of the markers TOP1 CN, TOP1/CEN-20-ratio or TOP1/CEN-2-ratio were associated with progression free survival, overall survival or baseline characteristics. Yet, we observed a borderline association for a stepwise increase of the TOP1 CN in relation to objective response as hazard ratio were 1.35 (95% CI 0.96–1.90; p = 0.081). CONCLUSIONS: We verified a borderline significant association between increasing TOP1 CN and objective response as previously reported. Applying the probes representing CEN-20 and CEN-2, in order to investigate the ratios of TOP1/CEN-20 and TOP1/CEN-2 provided no further information in search of a biomarker driven patient stratification. Other biomarkers to be paired with TOP1 CN are therefore highly warranted
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