Learning Outcomes Report

Aim of the study The learning outcomes study, conducted as part of WP3 of the BioApp project, has as objectives: (a) generating a comprehensive list of the learning outcomes; (b) reaching an agreement on the scope and priority of the learning outcomes, and (c) making suggestions for the further development of the Biomedical Design module. Method To address the objectives of the study, the group concept mapping approach was applied. Group Concept Mapping (GCM) is a systematic approach that objectively identifies an expert group’s shared vision on a particular issue, in our case the Biomedical Design module learning outcomes. The method involved the participants in activities that most professionals are used to: idea generation, sorting of ideas into groups and rating the ideas on some values (e.g., importance and difficulty to achieve). The analysis applied multi-dimensional scaling and cluster analysis to visually depict the experts’ shared representations on the learning outcomes as thematic groups. One of the distinguishing characteristics of GCM is the visualisation of the results from the analysis. Visualisation allows the emerging data structures and their interrelationships to be grasped. This facilitates decision making. Group Concept Mapping produces three main types of visualisations: conceptual maps, pattern matches and go-zones. Results The following thematic groups (clusters) of learning outcomes emerged from the data: ‘Attention to the end user’, ‘New approaches to design’, ‘Design process’, ‘Regulation and Ethics’, ‘Commercialisation’, ‘Knowledge integration’, ‘Communication’, ‘Collaboration’, ‘Higher order skills’, ‘Problem solving process’, ‘Connecting domains’, and ‘Learning goals’. Five more global areas of interest could be identified after conceptually related clusters were combined: ‘Design’ ( including ‘Design process’, ‘New approaches’, and ‘Attention to end user’); ‘Marketing’ (containing ‘Commercialization’ and ‘Regulation and Ethics’); ‘Interdisciplinary group dynamics’ (comprised of ‘Communication’ and ‘Collaboration’); ‘Learning objectives’ (consisting of ‘Learning goals’, ‘Higher order skills’ and ‘Problem solving process’) and ‘Creative combination’ (which includes ‘Knowledge integration’ and ‘Connecting domains’). Furthermore, the learning outcomes could be classified into two major categories: a) technical skills (new advancements in design process with special attention to users, also commercialisation and standardisation), and b) transversal skills, which include working effectively in teams (‘communication’ and ‘collaboration’) and creative problem solving (‘problem solving process’). The rating results indicate that the most important groups of learning outcomes are ‘Higher order skills’ and ‘Communication’. At the same time, however, these outcomes are deemed to be the most difficult to achieve. Other difficult to achieve learning outcomes are ‘Learning goals’, ‘Problem solving process’ and ‘Connecting domains’. The least important group of learning outcomes is ‘Commercialization’ and the easiest to achieve is ‘Regulation and Ethics’. The framework of learning outcomes consists of not only learning outcomes related to traditional topics such as ‘Design process’ and ‘Creative problem solving’, but also themes not very popular in curriculums on design such as ‘Commercialisation’, ‘Standardisation’, ‘Regulations’, and ‘Ethics’. The results also show there is a moderate correlation between the two values of importance and difficulty to achieve on the cluster level. The clusters ‘Problem solving process’, ‘Connecting domains’ and ‘Commercialization’ score lower on importance but higher on difficulty to achieve. In contrast, ‘Regulation and Ethics’ scores higher on importance but relatively lower on difficulty to achieve. Conclusions This study provided not only an empirical basis for identifying the main learning outcomes areas for an educational module on Biomedical Design, but also suggested how to operationally define them (through the statements in each cluster). The study emphasizes the need for addressing the highest level of learning taxonomy (analysis, synthesis, problem solving, creativity) when defining learning outcomes. It further reveals the need to teach students to integrate knowledge from different professional domains. However, the overall conclusion must be that the study not only identified learning outcomes for the Biomedical Design module when considered in isolation from the encompassing curriculum, but that the identified learning outcomes can only be effectively achieved when further integration of the module in the curriculum is allowed

Potentiation of latent inhibition by haloperidol and clozapine is attenuated in Dopamine D2 receptor (Drd-2) deficient mice: Do antipsychotics influence learning to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms?

Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it has previously been shown that Drd-2 is not necessary for antipsychotic drugs to reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure of learning to ignore irrelevant stimuli. Weiner's 'two-headed' model indicates that antipsychotics not only reverse LI disruption, 'disrupted LI', but also potentiate LI when low/absent in controls, 'persistent' LI. We investigated whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2 -/- mice, suggesting moderation of this effect of antipsychotics in the absence of Drd-2. Haloperidol potentiated LI similarly in both Drd1 -/- and wild-type mice, indicating no such moderation in Drd1 -/-. These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced. Identification of the non-Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis

Overshadowing depends on cue and reinforcement sensitivity but not schizotypy

There is evidence for impaired selective learning mechanisms in individuals high in schizotypy. Overshadowing provides a direct test of selective learning based on cue salience and has previously been reported to be impaired in relation to schizotypy scores. The present study tested for overshadowing using food allergy and Lego construction task variants. Both variants used the same number of conditioned stimulus (CS) cues and the same number of learning trials. CS cues were trained in compound pairs or in isolation and overshadowing was subsequently tested on trials followed by negative versus positive outcomes. Participants also completed the O-LIFE to measure schizotypy and BIS-BAS scales to measure reinforcement sensitivity. Learning was demonstrated for both cue variants; however overshadowing emerged only in the Lego variant and only on the trials followed by the negative outcome. Contrary to expectations, there was no evidence for any relationship between overshadowing and O-LIFE scores. However, there was evidence of a positive relationship between overshadowing and BAS-Drive as well as a negative relationship with BIS-Anxiety, for the trials followed by the positive outcome in the food allergy variant. These results suggest that the development of overshadowing depends on cue and reinforcement sensitivity, but not necessarily on schizotypy

Family Loneliness: Its Effects in the Development of Empathy, Teamwork and Lifelong Learning Abilities in Medical Students

Context: Family offers an important source of social support where individuals acquire social abilities that are necessary to create positive human relationships. This influence has been discussed by different sociological and psychological theories along the life span of individuals. In medicine, empathy, teamwork, and lifelong learning have been described as specific elements of professionalism that have special importance in the interaction with patients and in physicians’ well-being at the workplace. This study was performed with the aim of demonstrating the following hypothesis: In the absence of specific training in empathy and teamwork and lifelong learning abilities, their development in medical students is associated with the students’ perception of loneliness from their family environment. Methods: A cross-sectional study was performed in the only two medical schools of Cusco (Peru), one private and the other public. Jefferson Scales of Empathy, Teamwork, and Lifelong Learning were used as the main measures. Mother–son and father–son relationships and family loneliness were measured to characterize the family environment. In addition, information related to sex, medical school, academic achievements, and place of origin were collected to control possible biases. Comparative, correlation, and multiple regression analyses were performed among the variables studied. Results: In a sample of 818 medical students, differences by school appeared in empathy, teamwork, lifelong learning, and family loneliness. In addition, family loneliness showed an inverse correlation with empathy, teamwork, and learning measures. While having a positive relationship with the mother was associated with a greater development of empathy and learning abilities in the entire sample, a similar effect was observed in father–son relationships, but only in the private medical school group. Finally, in the public medical group, a multiple regression model explained 43% of the variability of empathy based on a lineal relationship with teamwork (p < 0.001), lifelong learning (p < 0.001), and family loneliness (p < 0.001). Conclusion: These findings confirm how family loneliness is detrimental to the development of medical professionalism. Also, they support the important role that the family, and especially parents, plays in the development of empathy, teamwork, and abilities in medical students. Finally, these findings highlighted important differences among students enrolled in public and private medical schools.National Council of Science, Technology and Technological Innovation (CONCYTEC)National University San Antonio Abad del Cusco (UNSAAC) E041-2017-UNSAAC-0

Deficient NRG1-ERBB signaling alters social approach: relevance to genetic mouse models of schizophrenia

Growth factor Neuregulin 1 (NRG1) plays an essential role in development and organization of the cerebral cortex. NRG1 and its receptors, ERBB3 and ERBB4, have been implicated in genetic susceptibility for schizophrenia. Disease symptoms include asociality and altered social interaction. To investigate the role of NRG1-ERBB signaling in social behavior, mice heterozygous for an Nrg1 null allele (Nrg1+/−), and mice with conditional ablation of Erbb3 or Erbb4 in the central nervous system, were evaluated for sociability and social novelty preference in a three-chambered choice task. Results showed that deficiencies in NRG1 or ERBB3 significantly enhanced sociability. All of the mutant groups demonstrated a lack of social novelty preference, in contrast to their respective wild-type controls. Effects of NRG1, ERBB3, or ERBB4 deficiency on social behavior could not be attributed to general changes in anxiety-like behavior, activity, or loss of olfactory ability. Nrg1+/− pups did not exhibit changes in isolation-induced ultrasonic vocalizations, a measure of emotional reactivity. Overall, these findings provide evidence that social behavior is mediated by NRG1-ERBB signaling

Genetic Mapping of Social Interaction Behavior in B6/MSM Consomic Mouse Strains

Genetic studies are indispensable for understanding the mechanisms by which individuals develop differences in social behavior. We report genetic mapping of social interaction behavior using inter-subspecific consomic strains established from MSM/Ms (MSM) and C57BL/6J (B6) mice. Two animals of the same strain and sex, aged 10 weeks, were introduced into a novel open-field for 10 min. Social contact was detected by an automated system when the distance between the centers of the two animals became less than ~12 cm. In addition, detailed behavioral observations were made of the males. The wild-derived mouse strain MSM showed significantly longer social contact as compared to B6. Analysis of the consomic panel identified two chromosomes (Chr 6 and Chr 17) with quantitative trait loci (QTL) responsible for lengthened social contact in MSM mice and two chromosomes (Chr 9 and Chr X) with QTL that inhibited social contact. Detailed behavioral analysis of males identified four additional chromosomes associated with social interaction behavior. B6 mice that contained Chr 13 from MSM showed more genital grooming and following than the parental B6 strain, whereas the presence of Chr 8 and Chr 12 from MSM resulted in a reduction of those behaviors. Longer social sniffing was observed in Chr 4 consomic strain than in B6 mice. Although the frequency was low, aggressive behavior was observed in a few pairs from consomic strains for Chrs 4, 13, 15 and 17, as well as from MSM. The social interaction test has been used as a model to measure anxiety, but genetic correlation analysis suggested that social interaction involves different aspects of anxiety than are measured by open-field test

Increased expression of receptor phosphotyrosine phosphatase-β/ζ is associated with molecular, cellular, behavioral and cognitive schizophrenia phenotypes

Schizophrenia is a serious and chronic mental disorder, in which both genetic and environmental factors have a role in the development of the disease. Neuregulin-1 (NRG1) is one of the most established genetic risk factors for schizophrenia, and disruption of NRG1 signaling has been reported in this disorder. We reported previously that NRG1/ErbB4 signaling is inhibited by receptor phosphotyrosine phosphatase-β/ζ (RPTP β/ζ) and that the gene encoding RPTPβ/ζ (PTPRZ1) is genetically associated with schizophrenia. In this study, we examined the expression of RPTPβ/ζ in the brains of patients with schizophrenia and observed increased expression of this gene. We developed mice overexpressing RPTPβ/ζ (PTPRZ1-transgenic mice), which showed reduced NRG1 signaling, and molecular and cellular changes implicated in the pathogenesis of schizophrenia, including altered glutamatergic, GABAergic and dopaminergic activity, as well as delayed oligodendrocyte development. Behavioral analyses also demonstrated schizophrenia-like changes in the PTPRZ1-transgenic mice, including reduced sensory motor gating, hyperactivity and working memory deficits. Our results indicate that enhanced RPTPβ/ζ signaling can contribute to schizophrenia phenotypes, and support both construct and face validity for PTPRZ1-transgenic mice as a model for multiple schizophrenia phenotypes. Furthermore, our results implicate RPTPβ/ζ as a therapeutic target in schizophrenia

D-amphetamine and antipsychotic drug effects on latent inhibition in mice lacking dopamine D2 receptors

Drugs that induce psychosis, such as D-amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd2/), we first investigated whether D2 is required for AMP disruption of latent inhibition (LI). LI is a process of learning to ignore irrelevant stimuli. Disruption of LI by AMP models impaired attention and abnormal salience allocation consequent to dysregulated dopamine relevant to schizophrenia. AMP disruption of LI was seen in both wild-type (WT) and Drd2/. This was in contrast to AMP-induced locomotor hyperactivity, which was reduced in Drd2/. AMP disruption of LI was attenuated in mice lacking dopamine receptor D1 (Drd1/), suggesting that D1 may play a role in AMP disruption of LI. Further supporting this possibility, we found that D1 antagonist SKF83566 attenuated AMP disruption of LI in WT. Remarkably, both haloperidol and clozapine attenuated AMP disruption of LI in Drd2/. This demonstrates that antipsychotic drugs can attenuate AMP disruption of learning to ignore irrelevant stimuli in the absence of D2 receptors. Data suggest that D2 is not essential either for AMP to disrupt or for antipsychotic drugs to reverse AMP disruption of learning to ignore irrelevant stimuli and further that D1 merits investigation in the mediation of AMP disruption of these processes

Dysregulation of specialized delay/interference-dependent working memory following loss of dysbindin-1A in schizophrenia-related phenotypes

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A -/-, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A -/-showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A -/-provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects