Expanding Kane's argument-based validity framework: What can validation practices in language assessment offer health professions education?

CONTEXT: One central consideration in health professions education (HPE) is to ensure we are making sound and justifiable decisions based on the assessment instruments we use on health professionals. To achieve this goal, HPE assessment researchers have drawn on Kane's argument-based framework to ascertain the validity of their assessment tools. However, the original four-inference model proposed by Kane - frequently used in HPE validation research - has its limitations in terms of what each inference entails and what claims and sources of backing are housed in each inference. The under-specification in the four-inference model has led to inconsistent practices in HPE validation research, posing challenges for (i) researchers who want to evaluate the validity of different HPE assessment tools and/or (ii) researchers who are new to test validation and need to establish a coherent understanding of argument-based validation. METHODS: To address these identified concerns, this article introduces the expanded seven-inference argument-based validation framework that is established practice in the field of language testing and assessment (LTA). We explicate (i) why LTA researchers experienced the need to further specify the original four Kanean inferences; (ii) how LTA validation research defines each of their seven inferences and (iii) what claims, assumptions and sources of backing are associated with each inference. Sampling six representative validation studies in HPE, we demonstrate why an expanded model and a shared disciplinary validation framework can facilitate the examination of the validity evidence in diverse HPE validation contexts. CONCLUSIONS: We invite HPE validation researchers to experiment with the seven-inference argument-based framework from LTA to evaluate its usefulness to HPE. We also call for greater interdisciplinary dialogue between HPE and LTA since both disciplines share many fundamental concerns about language use, communication skills, assessment practices and validity in assessment instruments.

Effect of a curriculum transformation on pharmacy student self-efficacy, self-reported activities, and satisfaction in degree and career choice.

BACKGROUND: Curriculum revision in healthcare programs occurs frequently, but to undergo a whole degree transformation is less common. Also, the outcomes of curriculum redesign interventions on the selfreported clinical decision making, experiences, and perceptions of graduates of health education programs is unclear. This study evaluated these factors as an outcome of a pharmacy degree whole-curriculum transformation. METHODS: A 25-item cross-sectional end-of-course survey was developed to evaluate pharmacy student decisions, experiences, and perceptions upon completion of degree, pre- and post- curriculum transformation. A two-way analysis of variance (ANOVA) was used to determine whether the responses to the items classed within the main factors differed across the two cohorts. Independent t-tests were used to examine the student responses to the individual questions between the two cohorts. RESULTS: Graduates from the transformed degree had greater self-efficacy in clinical activities, were more satisfied with their education, found course activities more useful, and were more confident in their career choice. Transformed pharmacy degree students also reported spending more time on weekdays and weekends on activities such as attending lectures and working. Student satisfaction with their choice to attend pharmacy school was also significantly higher in transformed degree students. CONCLUSIONS: Responses to the end of degree survey indicate that students who completed the transformed pharmacy curriculum have had positive experiences throughout their degree and felt more prepared for practice as pharmacists in comparison to students who completed the established degree. These results add value to those collected from other sources (e.g., student evaluations, assessment scores, preceptors focus groups, and other stakeholder inputs) consistent with a comprehensive quality improvement model.

Current pharmacological models of social withdrawal in rats: relevance to schizophrenia.

Social dysfunction in schizophrenia is one of the core negative symptoms, which to date is not adequately addressed by treatment with both typical and atypical antipsychotics. A number of different pharmacological models of social withdrawal are used to mimic social dysfunction in rats, such as amphetamine, N-methyl-D-aspartic acid antagonists, cannabinergic and serotonergic receptor ligands. The purpose of this review is to discuss and compare these models of social withdrawal with a focus on their face, construct and predictive validities. Various techniques and strategies used to observe and analyze rodent social behaviour and other factors that are of relevance to this paradigm have also been examined. After comparing the reports, we are of the opinion that to improve replicability of any given model and its antipsychotic screening potential and the reliability of comparisons made, efforts need to be directed towards cross-laboratory standardization of variables that may confound experimental outcomes and cause discrepancies in results reported. In keeping with an earlier suggestion this may be facilitated through the creation of an online consortium for behavioural neuroscientists to share and compare methodologies, laboratory layouts and perhaps even raw data.

The effect of Delta9-tetrahydrocannabinol on sensorimotor gating in socially isolated rats.

Rearing rats in isolation produces behavioural and neurochemical alterations similar to those observed in schizophrenia. Cannabinoids have also been implicated in inducing psychotic symptoms. In this study, we investigate the effect of the major psychoactive constituent of cannabis and partial cannabinoid CB(1) receptor agonist Delta(9)-tetrahydrocannabinol (THC) on prepulse inhibition (%PPI) of the acoustic startle reflex and on habituation in socially isolated and grouped rats. Deficits in %PPI are reminiscent of sensorimotor gating deficits observed in psychoses. Male Sprague-Dawley rat pups (21 days old) were housed in either single cages (isolated) or in group cages of six per cage (grouped). Eight weeks later the effect of vehicle, THC and the CB(1) receptor antagonist SR 141716 on %PPI was tested. Vehicle treated isolated rats exhibited significantly reduced PPI compared with grouped rats. Isolated rats treated with THC had significantly lower %PPI than vehicle treated groups. This further decrease of %PPI by THC was reversed by pre-treatment with SR 141716, indicating that this effect was mediated by CB(1) receptors. THC had no significant effect on %PPI in grouped rats. SR 141716 had no significant effect on %PPI in either grouped or isolated rats. Habituation did not significantly alter in any treatment group in any treatment group. These results suggest that THC produces significant decreases in sensorimotor gating in rats with already dysfunctional sensorimotor gating processes, but not in normal rats. The lack of effect of SR 141716 in either grouped or isolated rats suggests that normal endocannabinoid function is not critical in sensorimotor gating processes.

Does cannabidiol have a role in the treatment of schizophrenia?

Schizophrenia is a debilitating psychiatric disorder which places a significant emotional and economic strain on the individual and society-at-large. Unfortunately, currently available therapeutic strategies do not provide adequate relief and some patients are treatment-resistant. In this regard, cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, has shown significant promise as a potential antipsychotic for the treatment of schizophrenia. However, there is still considerable uncertainty about the mechanism of action of CBD as well as the brain regions which are thought to mediate its putative antipsychotic effects. We argue that further research on CBD is required to fast-track its progress to the clinic and in doing so, we may generate novel insights into the neurobiology of schizophrenia.

A two-hit model: behavioural investigation of the effect of combined neonatal MK-801 administration and isolation rearing in the rat.

This study combined two neurodevelopmental manipulations, neonatal MK-801 treatment and isolation rearing, to produce a 'two-hit' model and determine whether two hits induce a more robust behavioural phenotype of an animal model of aspects of schizophrenia compared with individual manipulations alone. The effect of clozapine was also assessed. Male Sprague-Dawley rats received 0.2 mg/kg MK-801 or saline intraperitoneally (i.p.) once daily on postnatal days (PNDs) 7-10 and were assigned to group or isolation rearing at weaning (PND 21). From PND 77, they received a vehicle or 5 mg/kg clozapine (i.p.) treatment regimen and were subjected to three prepulse inhibition (PPI) tests, a locomotor activity assessment and a novel object recognition task. MK-801-treated rats reared in isolation displayed robust PPI disruptions which were consistently manifested in all three tests. PPI deficits were also detected in saline-treated rats reared in isolation but not in all tests. Only the two-hit rats demonstrated hyperlocomotion and impaired object recognition memory. Clozapine restored PPI anomalies in the two-hit rats. The two-hit model showed greater psychotic-like effects than either neonatal MK-801 or isolation rearing alone. The preliminary predictive validity shown with clozapine suggests this model may be useful for predicting the efficacy of putative antipsychotics.

Consequences of early life MK-801 administration: long-term behavioural effects and relevance to schizophrenia research.

Animal models contribute significantly to advancing the understanding of schizophrenia neurobiology, in addition to being an important tool for the screening of antipsychotic potential of new compounds. However, the entire spectrum or all the symptoms manifested in schizophrenia cannot be straightforwardly reproduced in animals due to the complexity of the disorder, difference in mental capacities and behaviours, and the ability to quantify or measure the changes. Blockade of the NMDA receptor by the use of MK-801, a non-competitive NMDA receptor antagonist, during the early postnatal period has been proposed to be an experimental model which induces behavioural changes that mimic several aspects of the disorder. The long term behavioural profile arising from this early life manipulation is reviewed herein, with a specific focus on behaviours relevant to a schizophrenia-like condition. Some of the reported neurochemical changes are also compiled. Although this method may be suitable to model some aspects of schizophrenia in rodents, there are unmet areas which need to be addressed, notably the characterisation of its predictive value.

Effect of cannabidiol in a MK-801-rodent model of aspects of schizophrenia.

Cannabidiol is a non-psychoactive phytocannabinoid which, based on several previous preclinical and clinical reports, is purported to have antipsychotic potential. The purpose of this investigation was to further investigate if these effects would be seen using an MK-801-induced rat model of aspects of schizophrenia. MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviours which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia. Following a 4-day acclimatisation to the holding room, rats were acclimatised to startle chambers on day 5 and their prepulse inhibition (PPI) determined on day 6 following treatment with cannabidiol or vehicle and MK-801 or vehicle. On day 9, rats were acclimatised to the social interaction testing arena and on day 10, were tested for social interaction and locomotor activity following the same treatments. Cannabidiol treatment alone disrupted PPI and produced hyperactivity but had no effect on social behaviour. Cannabidiol had no effect on MK-801-induced disruption of PPI or hyperactivity but showed potential towards inhibiting MK-801-induced social withdrawal. As a comparator, we also tested the effect of the atypical antipsychotic clozapine which only partially reversed MK-801-induced disruption of PPI but was able to reverse MK-801-induced hyperactivity and social withdrawal. In conclusion, cannabidiol showed both propsychotic activity and partial antipsychotic activity in an MK-801-induced model of aspects of schizophrenia. Further behavioural studies would be required using a range of species, strains, animal models and testing paradigms to conclusively establish the antipsychotic potential of cannabidiol.

Isolation rearing in rats: effect on expression of synaptic, myelin and GABA-related immunoreactivity and its utility for drug screening via the subchronic parenteral route.

Depriving weaned rats of social contact by rearing them in isolation brings about a spectrum of behavioural and neuropathological changes in adulthood which resemble some of the characteristics observed in schizophrenia. Hence, isolation rearing provides a non-pharmacological means to induce in an animal model certain aspects of schizophrenia with a neurodevelopmental origin. We compared the prepulse inhibition and locomotor activity behaviours in group-reared and isolation-reared rats in the context of determining the robustness of any behavioural changes following a subchronic parenteral drug administration protocol. The expression of synaptic, myelin and GABA-related proteins was also assessed in the brains of these rats using semi-quantitative fluorescence immunohistochemistry. Compared to their group-reared counterparts, isolation-reared rats displayed disruption in prepulse inhibition which was lost after repeated testing and subchronic vehicle administration. However, isolation-reared rats showed open-field hyperlocomotion post-subchronic vehicle treatment compared to group-reared rats. Isolation rearing resulted in reduced expression of synaptophysin, synapsin I, myelin basic protein and GABA(B1) receptor proteins, along with an increase in 2',3'-cyclic nucleotide 3'-phosphodiesterase. Of the brain areas examined these observed changes were localised to the hippocampal regions and the substantia nigra. These results suggest an alteration in the synaptic, myelin and GABA-related functions in the brains of isolation-reared rats that displayed behavioural anomalies. Since dysfunction in these systems has also been implicated in schizophrenia, our findings provide additional evidence to support the use of isolation rearing for schizophrenia research; however, its use in the screening of putative antipsychotics following subchronic administration needs to be undertaken warily.

Effect of testing conditions on the propsychotic action of MK-801 on prepulse inhibition, social behaviour and locomotor activity.

The present paper reports on two investigations designed with the aim of refining existing animal models representing several aspects of psychosis, used to evaluate antipsychotic potential of novel compounds. The aim of the first investigation was to determine the effect of habituating rats to the injection procedure on three behavioural testing paradigms, social interaction, locomotor activity and prepulse inhibition (PPI) of the acoustic startle response. Results showed that while there was no effect on social behaviour or locomotor activity, the habituating to injection procedure decreased startle magnitude. For the second study, the aim was to determine whether the order in which the tests were conducted would affect sensitivity to the effects of dizocilpine (MK-801), a non-competitive NMDA receptor antagonist known to induce social withdrawal, increase locomotor activity and disrupt PPI. Either social interaction or locomotor activity tests were carried out 3 days prior to PPI tests (protocol 1), or PPI tests were carried out 3 days prior to social interaction and locomotor activity tests (protocol 2). Results showed that protocol 2 rats were more sensitive to the social withdrawal-inducing, hyperlocomotive- and PPI-disruptive effects of MK-801. Based on these results, the testing conditions appear to have a significant influence on the outcome of experiments aimed at observing the propsychotic action of MK-801.

Cannabidiol reverses the reduction in social interaction produced by low dose Delta(9)-tetrahydrocannabinol in rats.

While Delta(9)-tetrahydrocannabinol (THC) is the main psychoactive constituent of the cannabis plant, a non-psychoactive constituent is cannabidiol (CBD). CBD has been implicated as a potential treatment of a number of disorders including schizophrenia and epilepsy and has been included with THC in a 1:1 combination for the treatment of conditions such as neuropathic pain. This study investigated the effect of THC and CBD, alone or in combination, on some objective behaviours of rats in the open field. Pairs of rats were injected with CBD or vehicle followed by THC or vehicle and behaviour in the open field was assessed for 10 min. In vehicle pretreated rats THC (1 mg/kg) significantly reduced social interaction between rat pairs. Treatment with CBD had no significant effect alone, but pretreatment with CBD (20 mg/kg) reversed the THC-induced decreases in social interaction. A higher dose of THC (10 mg/kg) produced no significant effect on social interaction. However, the combination of high dose CBD and high dose THC significantly reduced social interaction between rat pairs, as well as producing a significant decrease in locomotor activity. This data suggests that CBD can reverse social withdrawal induced by low dose THC, but the combination of high dose THC and CBD impairs social interaction, possibly by decreasing locomotor activity.