Chromosomal copy number and mutational status are required to authenticate ovarian cancer cell lines as appropriate cell models

Background The mutational status of ovarian cancer cell line IGROV-1 is inconsistent across the literature, suggestive of multiple clonal populations of the cell line. IGROV-1 has previously been categorised as an inappropriate model for high-grade serous ovarian cancer. Methods IGROV-1 cells were obtained from the Netherlands Cancer Institute (IGROV-1-NKI) and the MD Anderson Cancer Centre (IGROV-1-MDA). Cell lines were STR fingerprinted and had their chromosomal copy number analysed and BRCA1/2 genes sequenced. Mutation status of ovarian cancer-related genes were extracted from the literature. Results The IGROV-1-NKI cell line has a tetraploid chromosomal profile. In contrast, the IGROV-1-MDA cell line has pseudo-normal chromosomes. The IGROV-1-NKI and IGROV-MDA are both STR matches (80.7% and 84.6%) to the original IGROV-1 cells isolated in 1985. However, IGROV-1-NKI and IGROV-1-MDA are not an STR match to each other (78.1%) indicating genetic drift. The BRCA1 and BRCA2 gene sequences are 100% identical between IGROV-1-MDA and IGROV-1-NKI, including a BRCA1 heterozygous deleterious mutation. The IGROV-1-MDA cells are more resistant to cisplatin and olaparib than IGROV-1-NKI. IGROV-1 has a mutational profile consistent with both Type I (PTEN, PIK3CA and ARID1A) and Type II ovarian cancer (BRCA1, TP53) and is likely to be a Type II high-grade serous carcinoma of the SET (Solid, pseudo-Endometroid and Transitional cell carcinoma-like morphology) subtype. Conclusions Routine testing of chromosomal copy number as well as the mutational status of ovarian cancer related genes should become the new standard alongside STR fingerprinting to ensure that ovarian cancer cell lines are appropriate models

A Calculus of Bounded Capacities

Resource control has attracted increasing interest in foundational research on distributed systems. This paper focuses on space control and develops an analysis of space usage in the context of an ambient-like calculus with bounded capacities and weighed processes, where migration and activation require space. A type system complements the dynamics of the calculus by providing static guarantees that the intended capacity bounds are preserved throughout the computation

PASCO: Structural panel analysis and sizing code: Users manual - Revised

A computer code denoted PASCO is described for analyzing and sizing uniaxially stiffened composite panels. Buckling and vibration analyses are carried out with a linked plate analysis computer code denoted VIPASA, which is included in PASCO. Sizing is based on nonlinear mathematical programming techniques and employs a computer code denoted CONMIN, also included in PASCO. Design requirements considered are initial buckling, material strength, stiffness and vibration frequency. A user's manual for PASCO is presented

Ferumoxytol-enhanced magnetic resonance angiography for the assessment of potential kidney transplant recipients

Objectives: Traditional contrast-enhanced methods for scanning blood vessels using magnetic resonance imaging (MRI) or CT carry potential risks for patients with advanced kidney disease. Ferumoxytol is a superparamagnetic iron oxide nanoparticle preparation that has potential as an MRI contrast agent in assessing the vasculature. Methods: Twenty patients with advanced kidney disease requiring aorto-iliac vascular imaging as part of pre-operative kidney transplant candidacy assessment underwent ferumoxytol-enhanced magnetic resonance angiography (FeMRA) between December 2015 and August 2016. All scans were performed for clinical indications where standard imaging techniques were deemed potentially harmful or inconclusive. Image quality was evaluated for both arterial and venous compartments. Results: First-pass and steady-state FeMRA using incremental doses of up to 4 mg/kg body weight of ferumoxytol as intravenous contrast agent for vascular enhancement was performed. Good arterial and venous enhancements were achieved, and FeMRA was not limited by calcification in assessing the arterial lumen. The scans were diagnostic and all patients completed their studies without adverse events. Conclusions: Our preliminary experience supports the feasibility and utility of FeMRA for vascular imaging in patients with advanced kidney disease due for transplant listing, which has the advantages of obtaining both arteriography and venography using a single test without nephrotoxicity

Challenges and opportunities for teacher professional development in interactive use of technology in African schools

This paper examines the supporting and constraining factors influencing professional learning about interactive teaching and mobile digital technology use in low-resourced basic schools in sub-Saharan Africa. It draws on a case study of iterative development and refinement of a school-based, peer-facilitated professional learning programme (“OER4Schools”) that integrated use of mobile technologies, digital open educational resources and interactive pedagogy. The research and development involved teachers in three Zambian primary schools and culminated in an extensive multimedia resource. Using an ecological framework, factors emerging were characterised at three levels: teacher, school, and the wider community and policy context. They include school organisation and leadership, teacher motivation and perceptions of opportunities for professional learning and change, teacher views of pupil capabilities, availability of resources, teacher collaboration, and viewpoints of parents and policymakers.We are most grateful to the teachers and the school who participated in our trials for their enthusiasm and support. Thanks also to Masters students Andrew Cross and Melissa Marsden for their roles in the data collection and analysis. The OER4Schools programme was based in the University of Cambridge Centre for Commonwealth Education (CCE) and was supported by the Commonwealth Education Trust, primarily funding the creation of the resource and the research. We greatly appreciate the administrative support provided by various CCE staff throughout the programme.This is the author accepted manuscript. The final version is available from Taylor & Francis via http://dx.doi.org/10.1080/1475939X.2015.109246

Pedagogic change by Zambian primary school teachers participating in the OER4Schools professional development programme for one year

Supporting and upskilling teachers are essential to enhancing the quality of learning in developing contexts – the focus of Education For All – yet little evidence exists concerning what kinds of teacher education are actually most effective and what changes in ‘quality’ are desired and feasible. This paper illustrates how a concrete, research-informed school-based, model of professional development in sub-Saharan Africa can address the quality agenda. It reports on a trial of a pioneering, multimedia programme supporting interactive mathematics and science teaching using open educational resources and classroom digital technology, where available. The programme was carefully adapted to the Zambian context and ran weekly for one school year with 12 teachers in a low-resourced primary school. The study examined the impact on teachers' thinking and classroom practices. Data were derived from observations, lesson and workshop recordings, teacher interviews, portfolios and audio diaries. Through a teacher-led workshop approach and trialling new pedagogical strategies, teachers raised their expectations of pupils, adapted to learners’ knowledge levels, used more practical and group work, and integrated technology use. Pupils built deeper understanding of subject matter, were actively engaged, worked collaboratively and used digital technologies for problem-solving.Commonwealth Education Trus

OER4Schools: Outcomes of a Sustained Professional Development Intervention in Sub-Saharan Africa

© Copyright © 2020 Haßler, Hennessy and Hofmann. Sustaining educational initiatives beyond short-term pilot projects is highly challenging in low-income countries. We describe the outcomes and implications of our iterative Design-Based Implementation Research conducted in Zambia. This focused on a unique, school-based, peer-facilitated professional learning programme for primary teachers: OER4Schools integrates interactive pedagogy, open digital educational resources and mobile learning. Teacher interviews carried out 18 months after a year-long intervention showed that the programme became self-sustaining; earlier participants reported further development of their interactive teaching strategies and awareness of pupil progress; recent joiners developed similarly. Roles of teachers and pupils changed and a new classroom culture emerged. The study identifies the key mechanisms involved in sustainability, including culturally sensitive and participatory development and implementation, semi-structured multimedia materials, and supportive organisational structures for sustained professional learning. Our findings are hence framed by sociocultural influences as well as the wider policy context

OER4Schools: Outcomes of a Sustained Professional Development Intervention in Sub-Saharan Africa

© Copyright © 2020 Haßler, Hennessy and Hofmann. Sustaining educational initiatives beyond short-term pilot projects is highly challenging in low-income countries. We describe the outcomes and implications of our iterative Design-Based Implementation Research conducted in Zambia. This focused on a unique, school-based, peer-facilitated professional learning programme for primary teachers: OER4Schools integrates interactive pedagogy, open digital educational resources and mobile learning. Teacher interviews carried out 18 months after a year-long intervention showed that the programme became self-sustaining; earlier participants reported further development of their interactive teaching strategies and awareness of pupil progress; recent joiners developed similarly. Roles of teachers and pupils changed and a new classroom culture emerged. The study identifies the key mechanisms involved in sustainability, including culturally sensitive and participatory development and implementation, semi-structured multimedia materials, and supportive organisational structures for sustained professional learning. Our findings are hence framed by sociocultural influences as well as the wider policy context

Sustaining and Scaling Pedagogic Innovation in Sub-Saharan Africa: Grounded Insights For Teacher Professional Development

Developing sustainable and scalable educational initiatives is a key challenge in low-income countries where donor-funded short-term projects are limited by both contextual factors and programme design. In this concept paper we examine some of the issues related to in-service teacher development in the context of sub-Saharan Africa, grounded predominantly in our experiences of over 5 years of iteratively developing, refining and evaluating an intensive school-based professional learning programme for primary school teachers. “OER4Schools” integrates interactive pedagogy, Open Educational Resources (OER) and use of mobile devices (where available). The focus of this paper is on identifying what the main factors are perceived to be in sustaining and scaling up such a programme, from the perspectives of participating teachers, workshop facilitators and the research team. Synthesising our previous research and drawing on recent work in the field, we identify the key characteristics of effective and sustainable professional learning in low-resourced contexts. Such characteristics include effective peer facilitation, school-based active learning, explicit programme structure, appropriate scheduling and resourcing, and mitigating resource constraints through use of OER. Our conclusions thereby offer insights concerning the importance and impact of wider influences on participation and engagement of stakeholders and lead to recommendations for programme design and implementation, that should be taken on board by future initiatives

Thromboembolic and neurologic sequelae of discontinuation of an antihyperlipidemic drug during ongoing warfarin therapy

Warfarin and antihyperlipidemics are commonly co-prescribed. Some antihyperlipidemics may inhibit warfarin deactivation via the hepatic cytochrome P450 system. Therefore, antihyperlipidemic discontinuation has been hypothesized to result in underanticoagulation, as warfarin metabolism is no longer inhibited. We quantified the risk of venous thromboembolism (VTE) and ischemic stroke (IS) due to statin and fibrate discontinuation in warfarin users, in which warfarin was initially dose-titrated during ongoing antihyperlipidemic therapy. Using 1999-2011 United States Medicaid claims among 69 million beneficiaries, we conducted a set of bidirectional self-controlled case series studies-one for each antihyperlipidemic. Outcomes were hospital admissions for VTE/IS. The risk segment was a maximum of 90 days immediately following antihyperlipidemic discontinuation, the exposure of interest. Time-varying confounders were included in conditional Poisson models. We identified 629 study eligible-persons with at least one outcome. Adjusted incidence rate ratios (IRRs) for all antihyperlipidemics studied were consistent with the null, and ranged from 0.21 (0.02, 2.82) for rosuvastatin to 2.16 (0.06, 75.0) for gemfibrozil. Despite using an underlying dataset of millions of persons, we had little precision in estimating IRRs for VTE/IS among warfarin-treated persons discontinuing individual antihyperlipidemics. Further research should investigate whether discontinuation of gemfibrozil in warfarin users results in serious underanticoagulation