Evaluating teachers' and trainers' development in a large scale curriculum development project in South Yorkshire

The evaluative research upon which the paper is based focuses on the first three years of a six-year project “Pathways to Success” (PW) currently taking place in South Yorkshire and funded by the European Social Fund (ESF) as part of the Objective 1 programme from 2001-2007. Matched funding has been provided by schools, colleges and LEAs. The PW project is concerned with developing innovative curricula to raise achievement and improve youngsters' employability skills. The project is set in the context of regional regeneration in an area where unemployment is higher than the European (and national) average, due to the decline of traditional steel and coal industries and where the gross domestic product is less than 75% of the European average. South Yorkshire is also an area where overall achievement in schools at all stages is lower than the national average and participation in post-16 education and higher education is persistently below national figures. Although employment is slowly rising due to reorientation from manufacturing towards a service and knowledge-based economy, pockets of severe unemployment and deprivation remain and are among the ten worst in the country.</p

Evaluation of valued youth: a national peer-tutoring programme to increase self confidence and motivation

Established first in the USA, Valued Youth has operated in the UK since 1996, and is currently implemented in about 50 schools in 8 regions. The programme is intended to help secondary school students who are at risk of disengaging with school or underperforming for a variety of reasons. These students are selected as tutors, given training on how to work with younger children and placed in a local primary school where they support pupils' learning. Valued Youth can be seen as one of many initiatives in secondary schools on re-engagement in learning and contributes to the UK government strategy of extending opportunities and providing flexible learning experiences to meet individual learners' needs and aptitudes. Evidence from the USA has shown the value of the programme in reducing drop-out, strengthening youngsters' perceptions of self and school, and reducing disciplinary referrals and absenteeism. The evaluation discussed in this paper considers the effect of the programme in a UK context, not only in terms of young people's attendance, attainment and confidence, but also in terms of what sort of youngsters seem to benefit and the effects of financial rewards, if any, on the outcomes. The paper reports on the first year of a two-year evaluation. Data were obtained from a pre- and post-questionnaire survey among tutors, a workshop with coordinators and visits to selected case study schools in several regions. Almost all tutors enjoyed the programme and would recommend the experience to others. There was a relatively low dropout and the programme was warmly appreciated by participating primary schools. We have evidence that Valued Youth markedly raises confidence, improves communication skills and keeps some at risk youngsters on track in school. Many types of youngsters benefit from the experience; those who lack confidence and have poor communication skills seem to make the most progress. Successful tutors tend to be those who are committed to the programme, willing to learn, are flexible and cooperative, and have some ability to interact with others, particularly children and primary teachers.</p

New Pathways: evaluating the implementation of a major work- related programme in Northern England

The evaluative research upon which this paper is based is focussed on the implementation of a three-year programme “Pathways to Success” (usually shortened to “Pathways”) in South Yorkshire, England. It is part of a much larger regional regeneration project funded by the European Social Fund (ESF) from 2001-2004. The Pathways programme is concerned with developing innovative curricula for the 14-19 age range in four Local Education Authorities (LEAs)1 and is taking place in 76 secondary (high) schools. A team from Sheffield Hallam University was responsible for evaluating the success of the Pathways programme and our findings reported here refer to the first year of implementation.</p

Optimization of an Alkylpolyglucoside-Based Dishwashing Detergent Formulation.

The aim of this work was to formulate and optimize the washing performance of an alkylpolyglucoside-based dishwashing detergent. The liquid detergent was formulated with five ingredients of commercial origin: anionic (linear sodium alkylbenzenesulfonate and sodium laurylethersulfate), nonionic (C12–C14 alkylpolyglucoside) and zwitterionic (a fatty acid amide derivative with a betaine structure) surfactants, and NaCl for viscosity control. In addition to the plate test, other properties were investigated including ‘‘cloud point’’, viscosity, and emulsion stability. Statistical analysis software was used to generate a central composite experimental design. Then, a second order design and analysis of experiments approach, known as the Response Surface Methodology, was set up to investigate the effects of the five components of the formulation on the studied properties in the region covering plausible component ranges. The method proved to be efficient for locating the domains of concentrations where the desired properties were met

Cancer stem cells, not bulk tumor cells, determine mechanisms of resistance to SMO inhibitors.

The emergence of treatment resistance significantly reduces the clinical utility of many effective targeted therapies. Although both genetic and epigenetic mechanisms of drug resistance have been reported, whether these mechanisms are stochastically selected in individual tumors or governed by a predictable underlying principle is unknown. Here, we report that the dependence of cancer stem cells (CSCs), not bulk tumor cells, on the targeted pathway determines the molecular mechanism of resistance in individual tumors. Using both spontaneous and transplantable mouse models of sonic hedgehog (SHH) medulloblastoma (MB) treated with an SHH/Smoothened inhibitor, sonidegib/LDE225, we show that genetic-based resistance occurs only in tumors that contain SHH-dependent CSCs (SD-CSCs). In contrast, SHH MBs containing SHH-dependent bulk tumor cells but SHH-independent CSCs (SI-CSCs) acquire resistance through epigenetic reprogramming. Mechanistically, elevated proteasome activity in SMOi-resistant SI-CSC MBs alters the tumor cell maturation trajectory through enhanced degradation of specific epigenetic regulators, including histone acetylation machinery components, resulting in global reductions in H3K9Ac, H3K14Ac, H3K56Ac, H4K5Ac, and H4K8Ac marks and gene expression changes. These results provide new insights into how selective pressure on distinct tumor cell populations contributes to different mechanisms of resistance to targeted therapies. This insight provides a new conceptual framework to understand responses and resistance to SMOis and other targeted therapies

Cells activated for wound repair have the potential to direct collective invasion of an epithelium.

Mechanisms regulating how groups of cells are signaled to move collectively from their original site and invade surrounding matrix are poorly understood. Here we develop a clinically relevant ex vivo injury invasion model to determine whether cells involved in directing wound healing have invasive function and whether they can act as leader cells to direct movement of a wounded epithelium through a three-dimensional (3D) extracellular matrix (ECM) environment. Similar to cancer invasion, we found that the injured cells invade into the ECM as cords, involving heterotypical cell-cell interactions. Mesenchymal cells with properties of activated repair cells that typically locate to a wound edge are present in leader positions at the front of ZO-1-rich invading cords of cells, where they extend vimentin intermediate filament-enriched protrusions into the 3D ECM. Injury-induced invasion depends on both vimentin cytoskeletal function and MMP-2/9 matrix remodeling, because inhibiting either of these suppressed invasion. Potential push and pull forces at the tips of the invading cords were revealed by time-lapse imaging, which showed cells actively extending and retracting protrusions into the ECM. This 3D injury invasion model can be used to investigate mechanisms of leader cell-directed invasion and understand how mechanisms of wound healing are hijacked to cause disease