Comparison of the evaluation of formative assessment at two medical faculties with different conditions of undergraduate training, assessment and feedback.

Introduction: Both formative and summative assessments have their place in medical curricula: formative assessment to accompany the learning process and summative assessment to ensure that minimum standards are achieved. Depending on the conditions of undergraduate training, assessment and feedback, students place more or less importance on formative assessment, and thus the fulfilment of its function may be questionable. This study describes how the low-stakes formative Berlin Progress Test (BPT) is embedded at two medical faculties with partially different framework conditions and what effects these have on the students' testing efforts and the evaluation of the test, especially the perception of its benefits and (intangible) costs, such as non-participation in contemporaneous activities and emotional impairments. Methods: In this study, the proportion of non-serious BPT participants at two medical faculties (total sample: NF1=1,410, NF2=1,176) in winter term 2015/16 was determined both by the number of unanswered questions on the test itself and in a survey using a standardized instrument (NF1=415, NF2=234). Furthermore, open questions were asked in this survey about perceived benefits and perceived costs, which were analyzed with qualitative and quantitative methods. Results: The BPT is generally better accepted at Faculty 2. This can be seen in the higher proportion of serious test takers, the lower perceived costs and the higher reported benefit, as well as the higher proportion of constructive comments. Faculty 2 students better understood the principle of formative testing and used the results of the BPT as feedback on their own knowledge progress, motivation to learn and reduction of exam fear. Discussion: When medical faculties integrate formative assessments into the curriculum, they have to provide a framework in which these assessments are perceived as an important part of the curriculum. Otherwise, it is questionable whether they can fulfil their function of accompanying the learning process.

The model medical degree programme "human medicine" in Oldenburg - the European Medical School Oldenburg-Groningen.

In the summer of 2012 the School of Medicine and Health Sciences at the Carl von Ossietzky University of Oldenburg became the first new medical faculty to be founded in Germany in more than 20 years. The faculty was established within the framework of the European Medical School Oldenburg Groningen, a cooperation project between the University of Oldenburg and the University of Groningen. In addition to the University of Groningen and its faculty of medical sciences (Universitair Medisch Centrum Groningen - UMCG), four hospitals in Oldenburg are involved in the programme as cooperation partners, as well as a network of general practitioner practices that provide training and academic teaching hospitals across northwest Germany. The programme itself is a model medical degree programme with a modular structure, a highly integrative approach and an early and consistent focus on practical skills and patient-centredness. In addition to the early introduction to outpatient care in the first years of study, longitudinal pathways and a strong focus on research with early integration of scientific activities into medical studies are the defining characteristics of this programme. The two faculties in Oldenburg and Groningen coordinated their respective curriculums during the founding phase and recognise each other's study modules as equivalent to their own. This has created the preconditions for students from Oldenburg to obtain Dutch qualifications (Bachelor of Human Life Sciences and/or Master of Science in Medicine) in addition to the German "Staatsexamen" (the state examination in medicine) under certain circumstances. Irrespective of whether they intend to obtain these qualifications, all students from Oldenburg must spend at least a year studying at the partner university in Groningen. In exchange, up to 40 students from Groningen have the option to complete part of their studies in Oldenburg.

Do different medical curricula influence self-assessed clinical thinking of students?

OBJECTIVES: As a fundamental element of medical practice, clinical reasoning should be cultivated in courses of study in human medicine. To date, however, no conclusive evidence has been offered as to what forms of teaching and learning are most effective in achieving this goal. The Diagnostic Thinking Inventory (DTI) was developed as a means of measuring knowledge-unrelated components of clinical reasoning. The present pilot study examines the adequacy of this instrument in measuring differences in the clinical reasoning of students in varying stages of education in three curricula of medical studies. METHODS: The Diagnostic Thinking Inventory (DTI) comprises 41 items in two subscales ("Flexibility in Thinking" and "Structure of Knowledge in Memory"). Each item contains a statement or finding concerning clinical reasoning in the form of a stem under which a 6-point scale presents opposing conclusions. The subjects are asked to assess their clinical thinking within this range. The German-language version of the DTI was completed by 247 student volunteers from three schools and varying clinical semesters. In a quasi-experimental design, 219 subjects from traditional and model courses of study in the German state of North Rhine-Westphalia took part. Specifically, these were 5(th), 6(th) and 8(th) semester students from the model course of study at Witten/Herdecke University (W/HU), from the model (7(th) and 9(th) semester) and traditional (7(th) semester) courses of study at the Ruhr University Bochum (RUB) and from the model course of study (9(th) semester) at the University of Cologne (UoC). The data retrieved were quantitatively assessed. RESULTS: The reliability of the questionnaire in its entirety was good (Cronbach's alpha between 0.71 and 0.83); the reliability of the subscales ranged between 0.49 and 0.75. The different groups were compared using the Mann-Whitney test, revealing significant differences among semester cohorts within a school as well as between students from similar academic years in different schools. Among the participants from the model course of study at the W/HU, scores increased from the 5(th) to the 6(th) semester and from the 5(th) to the 9(th) semester. Among individual cohorts at RUB, no differences could be established between model and traditional courses of study or between 7(th) and 9(th) semester students in model courses of study. Comparing all participating highest semester students, the 8(th) semester participants from the W/HU achieved the highest scores - significantly higher than those of 9(th) semester RUB students or 9(th) semester UoC students. Scores from the RUB 9(th) semester participants were significantly higher than those of the 9(th) semester UoC participants. DISCUSSION: The German-language version of the DTI measures self-assessed differences in diagnostic reasoning among students from various semesters and different model and traditional courses of study with satisfactory reliability. The results can be used for discussion in the context of diverse curricula. The DTI is therefore appropriate for further research that can then be correlated with the different teaching method characteristics and outcomes of various curricula.

Arabinogalactan isolated from cowshed dust extract protects mice from allergic airway inflammation and sensitization.

BACKGROUND: Extract from cowshed dust (CDE) is a source of immunomodulating substances. We have previously shown that such substances protect from experimental allergic disorders in a mouse model of asthma. OBJECTIVE: The objective of this study was to identify immunomodulatory molecules in extracts of dust from an allergy protective farming environment. METHODS: Polysaccharides were isolated from CDE and plants by chromatography and precipitation with specific reagents. Polysaccharides were then characterized by nuclear magnetic resonance spectroscopy. Subsequently, the allergy-protective potential of isolated polysaccharides was tested in a mouse model of asthma. RESULTS: The authors demonstrate that plant arabinogalactans are contained in CDE in high concentrations. The source of this arabinogalactan is fodder, in particular a prevalent grass species known as Alopecurus pratensis. Treatment of murine dendritic cells with grass arabinogalactan resulted in autocrine IL-10 production. Interestingly, these dendritic cells were not able to induce an allergic immune response. Furthermore, intranasal application of grass arabinogalactan protected mice from developing atopic sensitization, allergic airway inflammation and airway hyperreactivity in a mouse model of allergic asthma. This allergy-protective effect is specific for grass arabinogalactan because control experiments with arabinogalactan from gum arabic and larch revealed that these molecules do not show allergy-protective properties. This is likely because of structural differences because we were able to show by nuclear magnetic resonance spectroscopy that although they are predominantly composed of arabinose and galactose, the molecules differ in structure. CONCLUSIONS: The authors conclude that grass arabinogalactans are important immunomodulatory substances that contribute to the protection from allergic airway inflammation, airway hyperresponsiveness, and atopic sensitization in a mouse model of asthma.

Modulation of dendritic cell function by cowshed dust extract.

We have shown previously that inhalation of cowshed dust extract (CDE) resulted in decreased airway reactivity, eosinophilic inflammation and sensitization in a mouse model of allergic asthma. Our data suggested down-regulation of allergic immune response rather than activation of a Th1 response towards the model allergen. However, the precise mechanism of allergy protection is not yet understood in detail. To gain deeper insight into CDE-induced immune modulation, we have analysed the effects of CDE on dendritic cell biology. Dendritic cells were generated from murine bone marrow cells (BMDC). Cells were stimulated with CDE and subsequently used to sensitize mice via the airways. Our results showed that cells were not able to prime mice for allergic immune response when they were treated with CDE 2 days before pulsing with allergen, whereas cells that were stimulated with CDE simultaneously to OVA pulsing induced a fully developed allergic immune response. Surprisingly, CDE-treated cells that were not able to prime mice for allergic immune response exhibit an activated phenotype with high expression of the co-stimulatory surface molecule CD86. Moreover, CDE-treated cells transiently produced high amounts of cytokines such as IL-10, IL-12p70 and TNF-alpha. Interestingly, blocking of autocrine-produced IL-10 in vitro partially restored the allergy-inducing capacity of CDE-exposed cells. Thus, we conclude that prolonged exposure to CDE reduces the allergy-inducing capacity of dendritic cells. Furthermore, we present evidence that an autocrine IL-10 dependent mechanism seems to be involved in down-regulation of dendritic cell function due to stimulation with CDE.

Anti-BDCA-4 (neuropilin-1) antibody can suppress virus-induced IFN-alpha production of plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (PDC) in human blood are the main source of virus-induced interferon (IFN)-alpha. They exhibit a lineage-negative phenotype but all express BDCA-4, which is homologous to the neuronal receptor neuropilin-1. Specific staining with anti-BDCA-4 antibody is used for positive isolation of PDC from blood by magnetic cells sorting. Here, it is demonstrated that these positively selected PDC showed reduced or completely abolished IFN-alpha release compared to unstained PDC, which were negatively selected by magnetic depletion of lineage-positive blood mononuclear cells. In addition, treatment of these unstained PDC with anti-BDCA-4 mAb also resulted in at least two-fold lower or reduced virus-induced IFN-alpha production. It is shown that the antibody not only affects cell survival or block virus attachment but also reduces IFN-alpha release induced by non-viral CpG oligodeoxynucleotides. In conclusion, data suggest an immunoregulatory role for BDCA-4 on PDC as demonstrated for IFN-alpha response to virus.

Lysine as a critical amino acid for IgE binding in Phl p 5b C terminus.

BACKGROUND: Allergens induce the formation of specific immunoglobulin (Ig)E and harbor at least two IgE-binding regions (epitopes) to facilitate crosslinking of basophilic or mast-cell-bound specific IgE antibodies. Studies mapping linear epitopes have shown that these regions often contain charged or hydrophobic amino acids. Nevertheless, these studies are hampered by limited significance due to the often conformational nature of IgE epitopes. This prompted us to study the role of lysines in the context of an intact 3-dimensional model. METHODS: Major allergen Phl p 5b from timothy grass bears 12 lysines in its C-terminal half. Using site-directed mutagenesis, we substituted all 10 surface-exposed lysines by alanines. RESULTS: Although structural integrity of the lysine-deficient mutant was not altered, IgE-binding capacity measured by ELISA inhibition tests and crosslinking activity in ex vivo basophil stimulation and in vivo skin prick tests were significantly diminished. Interestingly, binding of specific IgG antibodies was considerably less reduced by loss of lysines. CONCLUSION: Lysine is an important amino acid for IgE binding in more than one epitope of major grass pollen allergen Phl p 5b C terminus. Allergenicity, but not IgG binding of the molecule, is substantially diminished by single amino acid substitutions without structural integrity being hampered.

Characterization of modified allergen extracts by in vitro beta-hexosaminidase release from rat basophils.

BACKGROUND: To date, there is no well-established test available that can be used to measure functional properties of modified allergens (allergoids). Due to the cross-linking process, the IgE-binding capacity of the allergens, normally necessary for their characterization, is lost. The aim of this study was to test whether the rat basophilic leukaemia (RBL) cell assay (beta-hexosaminidase release by rat basophils upon allergen stimulation) can be adopted to characterize allergoids and to evaluate the assay for testing allergoids and native allergens as well. METHODS: Mice were immunized with native and modified Phleumpratense extracts in the presence of alum. Their sera were used to sensitize RBL-2H3 cells and measure basophil stimulation induced by different allergen extracts in the presence or absence of various additives. RESULTS: Sera containing specific IgE against both extract formulations were obtained. Native as well as modified extracts induced dose-dependent beta-hexosaminidase release from RBL cells. Both extracts were used to evaluate the characteristics of the assay, which showed high precision. Storage conditions were chosen to enhance extract degradation, which could be read directly from the altered stimulatory capacity of the extracts. Additives turned out to have diverse effects on the assay, whereas phenol had no measurable effect, alum had an inhibitory effect and glycerol elevated basophil activation. CONCLUSIONS: For the first time, a reliable, precise in vitro assay is available that is able to directly measure the properties of modified allergen extracts after their production process. The test is well evaluated and its advantages and limitations are discussed in this report.

Atopic phenotype in children is associated with decreased virus-induced interferon-alpha release.

BACKGROUND: Interferon-alpha (IFN-alpha) production in humans is an early event in the nonspecific cellular response to viruses and mediates a wide range of antiviral and immunoregulatory activities. Little is known about the role of IFN-alpha in allergic disease. METHODS: In the present study, we performed a retrospective comparative analysis of 88 children with and without an atopic phenotype for virus-induced IFN-alpha production in blood cultures. RESULTS: We were able to demonstrate that patients with allergic asthma (aA) produced significantly lower amounts of virus-induced IFN-alpha than healthy children and patients with nonallergic asthma (naA). Furthermore, the number of eosinophils in atopic children as a marker for allergic inflammation correlated negatively with the IFN-alpha level in blood cultures. Additionally, we found differences between aA and naA patients with respect to the capacity to produce IFN-gamma. Although atopy is thought to be associated with a Th2 cytokine response, in our study, IFN-gamma release was not reduced in the allergic children. In contrast, patients with allergic rhinitis showed a significant increase in IFN-gamma release compared to naA patients. CONCLUSIONS: In our study, an early atopic phenotype was related to a reduction in virus induced IFN-alpha release from blood cultures. Thus, after further prospective evaluation, the IFN-alpha level may serve as an additional in vitro marker for the definition of atopy in children.