Students’ and Teachers’ Experiences With the Implementation of Problem-Based Learning at a University Law School

A few years ago, the Erasmus School of Law implemented problem-based learning (PBL) as an instructional method in the bachelor’s program. Transition to a PBL program often brings some difficulties for the teaching staff. To find out whether the implementation at the Erasmus School of Law has been successful, students and teachers were asked about their experiences with and perceptions of the PBL program. Both students and teachers reported positive study behaviors, such as regular studying and active involvement of students as a result of PBL. However, some issues also arose after implementing PBL: staff members reported dissatisfaction regarding the PBL program and students reported feelings of insufficient preparation for the legal profession. Recommendations on how to address these issues are discussed

Development and application of a positive–negative selectable marker system for use in reverse genetics in Plasmodium

A limitation of transfection of malaria parasites is the availability of only a low number of positive selectable markers for selection of transformed mutants. This is exacerbated for the rodent parasite Plasmodium berghei as selection of mutants is performed in vivo in laboratory rodents. We here report the development and application of a negative selection system based upon transgenic expression of a bifunctional protein (yFCU) combining yeast cytosine deaminase and uridyl phosphoribosyl transferase (UPRT) activity in P.berghei followed by in vivo selection with the prodrug 5-fluorocytosine (5-FC). The combination of yfcu and a positive selectable marker was used to first achieve positive selection of mutant parasites with a disrupted gene in a conventional manner. Thereafter through negative selection using 5-FC, mutants were selected where the disrupted gene had been restored to its original configuration as a result of the excision of the selectable markers from the genome through homologous recombination. This procedure was carried out for a Plasmodium gene (p48/45) encoding a protein involved in fertilization, the function of which had been previously implied through gene disruption alone. Such reversible recombination can therefore be employed for both the rapid analysis of the phenotype by targeted disruption of a gene and further associate phenotype and function by genotype restoration through the use of a single plasmid and a single positive selectable marker. Furthermore the negative selection system may also be adapted to facilitate other procedures such as ‘Hit and Run’ and ‘vector recycling’ which in principle will allow unlimited manipulation of a single parasite clone. This is the first demonstration of the general use of yFCU in combination with a positive selectable marker in reverse genetics approaches and it should be possible to adapt its use to many other biological systems

Impact hotspots of reduced nutrient discharge shift across the globe with population and dietary changes

This is the final version. Available from Nature Research via the DOI in this recordReducing nutrient discharge from wastewater is essential to mitigating aquatic eutrophication; however, energy- and chemicals-intensive nutrient removal processes, accompanied with the emissions of airborne contaminants, can create other, unexpected, environmental consequences. Implementing mitigation strategies requires a complete understanding of the effects of nutrient control practices, given spatial and temporal variations. Here we simulate the environmental impacts of reducing nutrient discharge from domestic wastewater in 173 countries during 1990–2050. We find that improvements in wastewater infrastructure achieve a large-scale decline in nutrient input to surface waters, but this is causing detrimental effects on the atmosphere and the broader environment. Population size and dietary protein intake have the most significant effects over all the impacts arising from reduction of wastewater nutrients. Wastewater-related impact hotspots are also shifting from Asia to Africa, suggesting a need for interventions in such countries, mostly with growing populations, rising dietary intake, rapid urbanisation, and inadequate sanitation.Beijing Nova ProgramBeijing Talents FoundationNational Natural Science Foundation of ChinaYouth Innovation Promotion Association of the Chinese Academy of SciencesK. C. Wong Education Foundatio

Re-evaluating safety risks of multifunctional dikes with a probabilistic risk framework

It is not uncommon for a flood defence to be combined with other societal uses as a multifunctional flood defence, from housing in urban areas to nature conservation in rural areas. The assessment of the safety of multifunctional flood defences is often done using conservative estimates. This study synthesizes new probabilistic approaches to evaluate the safety of multifunctional flood defences employed in the Netherlands and explores the results of these approaches. In this paper a case representing a typical Dutch river dike combining a flood safety function with a nature and housing function is assessed by its probability of failure for multiple reinforcement strategies considering multiple relevant failure mechanisms. Results show how the conservative estimates of multifunctional flood defences lead to a systematic underestimation of the reliability of these dikes. Furthermore, in a probabilistic assessment uncertainties introduced by multifunctional elements affect the level of safety of the dike proportional to the reliability of the dike itself. Hence, dikes with higher protection levels are more suitable to be combined with potentially harmful uses for safety, whereas dikes with low protection levels can benefit most from uses that contribute to safety.</p

Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material

Background: Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods: Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results: The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5-10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions: We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers

A novel online food recall checklist for use in an undergraduate student population : a comparison with diet diaries

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