TM”) model, using the PRECEDE-PROCEED model as the underlying Cook-EdTM framework. A review of the food and cooking skills education literature informed the content of the Cook-EdTM model. Cook-EdTM was critiqued by experts in consumer behaviour, cooking and nutrition education research and education until consensus on model content and format was reached. Cook-EdTM leads cooking program developers through eight distinct stages, engaging key stakeholders in a co-design process from the outset to tailor programs to address the need of individuals and inform the development of program content, program delivery, and evaluation. A Cook-EdTM scenario applied in practice is described. The proposed Cook-EdTM model has potential to be adapted for use in domestic cooking education programs delivered in clinical, community, school or research settings. Further research will establish Cook-EdTM’s utility in enhancing program development and in improving food and cooking skills, dietary patterns and health outcomes.Domestic cooking education programs are typically designed to improve an individual’s food and cooking skills, although not necessarily diet quality. Currently, there are no comprehensive models to guide the planning, implementation and evaluation of domestic cooking education programs that focus on improving diet and health. Our aim was to address this through development of the Cooking Education (“Cook-Ed There is a paucity of empirical research regarding which theoretical constructs contribute to producing domestic cooking programs effective in modifying dietary behaviours and diet-related health outcomes ,2. Few cPoor dietary patterns and excessive energy intakes are key risk factors contributing to the current chronic disease epidemic . Many coCooking skills are primarily learned from the mother ,17 with Cooking education programs occur in a range of settings ,4,6 fromHealth education program developers use health promotion models and planning frameworks to ensure program design, implementation and evaluation utilise commonly accepted health behaviour change theories . HoweverTM”) model for planning, implementing and evaluating domestic food and cooking skill education programs that aim to improve diet and health outcomes. This paper will identify key considerations for curricula development when prioritising cooking education components within finite program schedules in different countries, settings and target groups. One scenario for applying the model is presented.Given that the prevalence of diet-related chronic disease is escalating rapidly worldwide, the link between cooking and food skills with diet quality and rising interest of cooking education programs, there is a need to promote evidence-based teaching of cooking and food skills. Of particular importance are programs that promote alignment with food-based guidelines and address specific nutrition needs of the individuals for whom they are developed, while also understanding the contextual factors and barriers that the target population faces. Therefore, the aim of this paper is to describe the development of the Cooking Education , two development and implementation (Stages 4 and 5), and three program evaluation stages (Stages 6–8).TM model lists the factors preceding broader cooking-related health behaviour change on the left, and the health, environmental and societal outcomes that healthy domestic cooking programs ultimately aim to address on the right. Outcomes, practices and their contributing factors are initially explored in program planning Stages 1 and 2, findings then inform program development in Stage 4, and this forms the basis of program evaluation in Stages 7 and 8.The inner section of the Cook-EdTM model components and each stage are described in further detail below. Detailed practical guidance to assist program developers, and a non-exhaustive list of evidence-based resources that may be used to measure each of the constructs listed in the model, are provided  and local food regulations;Where necessary, conduct risk assessment and obtain human research ethics approval.Stage 3—Capacity assessment:TM model development phase, the findings from the planning phase are used to develop and test program content that is tailored to the needs, preferences, skills and resources of the target population. Evaluation data from earlier programs, feasibility studies or pilot data can be used at this stage to iteratively develop or modify programs.In the Cook-EdDefine program aims to address the health issues identified in Stage 1;Define program objectives to address the cooking-related practices and predisposing, reinforcing and enabling factors identified in Stage 2;Align content with program aims, objectives and capacity assessment (Stage 3);To promote the development of cooking and food skills of highest priority, consider relevant food-based guidelines when selecting recipes and determining program content;Select program format such as face-to-face, demonstration, hands-on and/or virtual delivery;Select a pedagogy, or behaviour change strategies to guide the teaching and the development of learning resources. Consider using a participant-centred education approach such as Experiential Learning, as opposed to a teacher-centred approach;If required, engage an Occupational Therapist (OT) in a consultative capacity in program design;Consider building in provisions to allow facilitators to tailor the program to the needs of individuals and/or groups, depending on the demands of the activities on individuals, whether activities need modification, or what supports ) may be required;An OT can complete comprehensive assessments with individuals to inform the use of adapted activities, graded assistance, and enable access to AT. Develop processes to enable timely referral to an OT for assessment if needed;Develop and select process, impact and outcome evaluation tools and measures .Stage 5—Pilot or feasibility or efficacy or effectiveness study:Pilot the program during development to test recruitment strategies, program content and resources, and evaluation tools and methods;Feasibility may be enhanced by adopting an iterative process based on feedback and evaluation (Stages 6–8).Stage 4—Develop program content and facilitation guides:Stages 6–8TM model evaluation stages gather information on program delivery, short and long-term program effectiveness. This can strengthen the evidence-base for domestic cooking education as a strategy to improve diet and health.The Cook-EdConduct process evaluation throughout, and post-program implementation to examine recruitment, participant retention and exposure to the intervention, and to assess the degree to which the program was implemented as intended ;Process evaluation instruments can be individualised to unique cooking programs.Stage 6—Conduct process evaluation:Conduct impact and outcome evaluation pre- and post-program implementation;Impact evaluation examines the predisposing, reinforcing and enabling factors (identified in Stage 2) which the program aimed to modify, and how these influenced the cooking-related practices of participants;Outcome evaluation measures refer to the broader long-term health outcomes. Align outcome evaluation measures with program aims, and that address the cooking-related need or problem identified in Stage 1;Where available, use validated instruments to conduct impact and outcome evaluation .Stage 7 and 8—Conduct impact and outcome evaluation:In addition to process, impact and outcome evaluation, examine capacity gain and conduct economic evaluation to provide information on sustainability and efficiency, respectively . DissemiTM model can be applied in practice.In the next section, a scenario for developing a specific cooking education program is described to illustrate how the Cook-EdBackground: A disability support provider identifies a need for, and interest in, a healthy home cooking education program for their young adult clients with mild–moderate intellectual disability. Intellectual disability can be classified depending on severity. When given the right support, people with mild-moderate intellectual disability can acquire the skills needed for relatively independent living, compared to more severe forms of intellectual disability which may require considerably greater support and supervision . A partnTM model for planning, implementing and evaluating cooking education programs was informed by: the existing evidence-base for cooking education; the PRECEDE-PROCEED model for health promotion; other public health nutrition program planning, implementation and evaluation models; experiential learning and the consensus of our international team who have expertise in cooking and food skill education programs or research studies. The Cook-EdTM model identifies candidate factors for evaluation in pre-program planning to inform content development and post-program evaluation. This can be used to refine cooking education programs and help to advance the evidence base for healthy cooking programs’ effectiveness in improving dietary behaviour and diet-related health outcomes. The scenario presented demonstrates how Cook-EdTM can be applied to develop a new cooking education program.The Cook-EdCooking education programs can be resource-intensive, requiring suitably qualified staff to develop and implement curricula, recruit participants and evaluate the cooking program outcomes. Considering which programs exist in the community and forming partnerships with organisations can be useful to achieve efficient and economic program development and delivery . AdoptinTM model. Cooking program developers should consider those most relevant and applicable to their target population. By examining sociodemographic factors, programs that are culturally, socioeconomically and age appropriate can be developed. Cooking confidence, food skill confidence and self-efficacy in one’s abilities is associated with the increased use of basic ingredients and increased willingness to experiment with different foods, having a greater repertoire of meals to prepare, and healthier food choices [A number of personal and environmental factors influencing healthy domestic cooking practices were identified during the development of the Cook-Ed choices ,38,39,40 choices  and furt choices . While a choices .Limited access to utensils for cooking and suitable areas for food preparation and storage in the home are other factors that may influence cooking behaviour ,44. The Program developers should select a pedagogy to guide teaching and the development of learning resources. Hollywood et al.  notes thCooking education programs may include hands-on or demonstration-based cooking instruction or a combination. Wolfson et al.  proposesA frequently reported limitation of existing cooking interventions is the limited use of high-quality, validated instruments to assess the factors influencing healthy cooking behaviour and program outcomes ,4,9, howTM model is that the evidence of what contributes to cooking interventions’ effectiveness in improving diet-related behaviour and health outcomes is inconsistent. Tools to evaluate cooking education programs are, at present, restricted to only a few validated tools that we are aware of. Cooking education for improving diet-related health is an important but emerging area of research, which would benefit from more robust research, including rigorous study designs and the development of validated tools for use in program evaluation.A limitation of the Cook-EdTM model’s effectiveness in improving cooking-related health outcomes of real-world cooking education programs. We recommend that future research studies use the model to guide the planning, implementation and evaluation of cooking education programs to facilitate future refinement to the model and its implementation. Reporting should clearly identify whether the Cook-EdTM model was used and how each component of the model was applied, or not, to enable the utility and effectiveness of the Cook-EdTM model to be evaluated in differing research and community health settings and population groups.The current paper presents a number of factors for consideration when planning, implementing and evaluating cooking education programs and maps an existing intervention against the evidence base. Further research is required to establish the Cook-Ed


Tissue accumulation of abnormal aggregates of amyloidogenic proteins such as prion protein, α-synuclein, and tau represents the hallmark of most common neurodegenerative disorders and precedes the onset of symptoms by years. As a consequence, the sensitive and specific detection of abnormal forms of these proteins in patients’ accessible tissues or fluids as biomarkers may have a significant impact on the clinical diagnosis of these disorders. By exploiting seeded polymerization propagation mechanisms to obtain cell-free reactions that allow highly amplified detection of these amyloid proteins, novel emerging in vitro techniques, such as the real-time quaking-induced conversion assay (RT-QuIC) have paved the way towards this important goal. Given its high accuracy in identifying misfolded forms of prion protein from Creutzfeldt-Jakob disease (CJD) CSF, RT-QuIC has already been included in the diagnostic criteria for the clinical diagnosis of sporadic CJD, the most common human prion disease. By showing that this assay may also accurately discriminate between Lewy body disorders and other forms of parkinsonisms or dementias, more recent studies strongly suggested that CSF RT-QuIC can also be successfully applied to synucleinopathies. Finally, preliminary encouraging data also suggested that CSF RT-QuIC might also work for tau protein, and accurately distinguish between 3R- and 4R tauopathies, including Pick’s disease, progressive supranuclear palsy, and corticobasal degeneration. Here we will review the state of the art of cell-free aggregation assays, their current diagnostic value and putative limitations, and the future perspectives for their expanded use in clinical practice. The most common neurodegenerative diseases feature protein misfolding, aggregation, and accumulation of protein amyloids inside or outside cells . ConsequWe searched Google Scholar and PubMed using the terms “prion”, “Creutzfeldt-Jakob disease”, “alfa-synuclein”, “tau protein”, “parkinsonism”, “Lewy body”, “tauopathy”, “Parkinson’s disease”, “MSA”, “PSP”, “CBD”, “AD” and “Pick’s disease”, each in combination with “real time-quaking-induced conversion” or “RT-QuIC” or “PMCA”. Studies and articles written in English were selected based on our rating of the methodological aspects and of their relevance to the diagnosis of human neurodegenerative diseases. A few articles providing reference to basic concepts or general information were added based on personal knowledge of the scientific literature.C, into a β-sheet enriched conformation as in the abnormal scrapie prion protein, PrPSc [The concept of cell-free aggregation assays stems from the discovery of the protein-only mechanism for the propagation of the prion protein (PrP) as the sole pathogenic agent of transmissible spongiform encephalopathies including CJD and other human and animal prion diseases, such as scrapie in sheep, and chronic wasting disease in cervids , 69. Aggn, PrPSc , 15. Then, PrPSc . Moreoven, PrPSc , 77.Sc isolated from prion-infected hamsters was partially denatured in guanidine-HCl and incubated with 35S-labelled recombinant PrPC derived from uninfected hamster’s brain. The demonstrations of proteinase K (PK) resistance labeled PrP confirmed the de novo formation of misfolded species.In the attempt to better understand PrP conversion, in the mid ‘90s, Kocisko and co-workers successfully generated aggregated species of PrP in a cell-free assay . In thisSc in the presence of an excess of healthy brain homogenate as a source of PrPC. In this assay, termed protein misfolding cyclic amplification (PMCA), sonication provided the energy required to break aggregated species of PrP into misfolded, aggregation-competent species, while incubation allowed the conversion of the monomers into their pathogenic form. Through various sonication and incubation passages, the researchers were able to amplify the original PrPSc seeds greatly. As in the original assay, the detection relied on partial digestion with PK, followed by western blotting using specific PrP antibodies. Strikingly, PMCA was able to detect the presence of PrPSc in the brain of pre-symptomatic hamsters [As a significant technical implementation to this assay, Saborio and co-workers  introduchamsters , renderihamsters , 20.C [The use of bacterially expressed recombinant PrP as reaction substrate overcame the need for brain homogenates as the source of PrPC , allowinMethodological improvement of the aggregation assay included the swap of sonication with automated shaking, defined as quaking-induced conversion (QuIC). In addition to the clear advantages of an automated system, with this novel methodology, Atarashi and co-workers  were ablIn parallel, Colby and co-workers  developeBy combining the PMCA and QuIC cyclic amplification with the real-time detection of the products by ThT, Wilham and co-workers  developeFrom here, several studies tested the RT-QuIC for its diagnostic accuracy in prion disease and other neurodegenerative conditions. Nowadays, the diagnostic criteria for sporadic CJD (sCJD) already include RT-QuIC , and effIn the next sections, we will review the results with clinical diagnostic implications obtained to date with the three main RT-QuIC assays thus far developed, namely PrP RT-QuIC, alfa-synuclein (α-syn) RT-QuIC, and tau RT-QuIC Fig. . A few sDespite their low prevalence, prion diseases encompass a broad spectrum of clinicopathological variants with significant heterogeneity in disease duration, symptomatology, and type or regional distribution of brain lesions. Current classification of prion diseases includes four major phenotypic entities, namely Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), fatal insomnia (FI), and variably protease-sensitive prionopathy (VPSPr)  Table 11.Table PRNP, and by the type (1 or 2) of abnormal prion protein (PrPSc) accumulating in the brain  [Moreover, some of these groups include disease subtypes with distinguishing molecular and clinicopathological features. Most significantly, CJD, by far the most prevalent prion disease in humans, comprises six subtypes, which are primarily determined by the genotype at the polymorphic codon 129  in V2, MV2) –65  . On the V2, MV2) . AccordiV2, MV2) , 92, 93.V2, MV2) . In thisV2, MV2) . Of notiV2, MV2) .Similarly, CSF assays based on surrogate markers such as protein 14–3-3 and t-tau yield false-positive results in at least 10% of clinically selected cases , with a wide diagnostic specificity range among studies (between 57 and 97%), Moreover, despite an overall good sensitivity (range 81–96%), they have relatively poor performance (sensitivity varies from ~ 70% in MV2K to ~ 10% in VPSPr) in atypical subtypes such as MV2K, MM2C, MM2T, and VPSPr , 50. ThuThe recent development of the RT-QuIC assay provided a reliable and robust tool to improve the early diagnosis of human prion diseases . ResultsThe assay demonstrated a good reproducibility in the inter-laboratory setting and across various CSF storage conditions, such as short-term CSF storage at different temperatures, long-term storage, repeated freezing and thawing cycles , 55. TheModifications in the protocol, leading to the RT-QuIC of the second generation , allowed the experimental run time to be reduced to 1–2 days only and lead to a further overall increase in the sensitivity of the assay without affecting specificity . These mRegarding the application of RT-QuIC to other tissues and body fluids, recent promising studies that used either the olfactory mucosa or skin biopsies as seed showed high test sensitivities from 89 to 100%, suggesting equal or even better diagnostic accuracy than CSF RT-QuIC , 59, 61.In summary, regardless of the type of protocol Table , all stuFinally, questions about the assay’s presumed absolute specificity and the effect of prion strains and disease subtypes on test sensitivity deserve further discussion.The development of an RT-QuIC assay with sufficient sensitivity requires a high concentration of recombinant substrate and a reaction environment favoring the seeded aggregation mechanism. Consequently, there is a need to monitor any spontaneous substrate aggregation that may generate false-positive signals. To this aim, samples are loaded four times in the standard RT-QuIC set-up, and a definite positive read requires that at least two of the four replicates generate a signal above a pre-set threshold, whereas a single positive well is considered an unclear result, prompting the repetition of the assay.Sc, which led to the conclusion that this might have been a case of subclinical prion disease, who died from DLB comorbidity. In other recent reports [Some studies on prion RT-QuIC reported a few unexpected positive results , 50, 54. reports , 72, an  reports .Sc type nor the codon 129 genotype alone had a significant impact on the RT-QuIC response. Nevertheless, PrPSc type 1 patients carrying MM at codon 129 showed a faster response that those carrying MV or VV (who most commonly harbor PrPSc type 2). Moreover, disease duration, which, once again, mainly depends on the disease subtype, had an impact on the test results, with patients with a shorter disease course (who most commonly have PrPSc type 1) showing higher seeding efficiency in the RT-QuIC response. In a large study including 186 pathologically confirmed sCJD cases with subtype classification, [Sc type 2 .Only a few studies examined a significant number of CJD stratified according to the disease subtype. Using the first generation of the assay, Cramm et al.  reportedication,  RT-QuIC As far as the second generation RT-QuIC is concerned, Foutz et al.  found thn = 22; V203I, n = 2), GSS  or FFI . Results were comparable between the groups, with only a slightly higher sensitivity in GSS compared to FFI and gCJD (90% vs. 83.3%). In contrast, other groups, using different protocols, consistently reported a reduced sensitivity of RT-QuIC in FFI (0–57%), and GSS (0-50%) compared with gCJD (83.3–100%) [PRNP mutations, it is very likely that different disease-associated mutations might influence the test’s diagnostic value [As for the sCJD subtypes, only a few studies tested a significant number of cases affected by genetic prion disease. Using PQ RT-QuIC, Sano et al.  analyzed.3–100%) , 31, 72..3–100%) . FinallyIn the next sections, we will review the successful adaptation of the RT-QuIC for the detection of pathogenic forms of α-syn and, to a lesser extent, of tau in human CSF.Synucleinopathies, including PD, DLB, and multiple system atrophy (MSA) are neurodegenerative diseases characterized by the intracellular accumulation of toxic α-syn aggregates  forming Moreover, current diagnostic criteria usually require the association of clinical findings, multiple diagnostic investigations, and an adequate follow-up of several years, to reach the accurate identification of the disorder , 66. MosIncreasing evidence supporting the prion-like behavior of α-syn, together with those indicating that the seeding conversion mechanism could be replicated in vitro by aggregation assays such as PMCA , 82, pron = 20) and neuropathologically confirmed DLB (n = 12) cases. Results showed a 92–95% sensitivity and a 100% specificity against 35 healthy controls and 5 PSP/CBD cases. Interestingly, three samples derived from patients affected by iRBD also gave a positive result, providing preliminary evidence that, in the clinical frame of a prodromic syndrome, the RT-QuIC may predict the future onset of a synucleinopathy. In an adaptation of the PMCA technique for the detection of misfolded α-syn that firmly reminds the RT-QuIC, as it makes use of a recombinant substrate, intermittent shaking and ThT, Shahnawaz et al. [n = 76) and controls with other neurological diseases (n = 97). This novel α-syn PMCA assay distinguished PD from other neurologic disorders with 88.5% sensitivity and 97% specificity  and DLB (n = 17) against AD cases (n = 16) and controls (n = 12).Whereas the original assay  showed aTo further explore its diagnostic value in the clinical contest, the authors applied α-syn RT-QuIC to CSF samples from a prospective observational cohort of 118 patients with parkinsonism of uncertain clinical diagnosis at lumbar puncture (LP) . The oven = 15; asymptomatic carriers, n = 16) with either idiopathic PD or healthy controls, the assay sensitivity was surprisingly rather low  in the former group, whereas it was comparable to previous studies (90%) in the idiopathic (non-genetic) PD group. The assay specificity, however, dropped to 80%. The finding supports the prevalent idea that LRRK2 carriers may not necessarily have an underlying synucleinopathy. Indeed, neuropathological studies demonstrated, at least in a few of such cases, a nigral degeneration in the absence of protein deposition [In another study, the RT-QuIC was used to detect α-syn seeding activity in patients carrying mutations in LRRK2 (Leucine-rich repeat kinase 2 gene) , the mosposition  or the pposition .n = 77), irrespectively of the clinical diagnosis  resulted in a 92.8% sensitivity and 95.9% specificity. Additional results obtained in a clinical cohort of 36 cases showed an 85% sensitivity in the group of probable DLB and, intriguingly, a 0% sensitivity in those (n = 6) with possible DLB. Finally, there were no positive reads also in a group of 10 cases with a clinical diagnosis of probable AD.The high sensitivity of α-syn RT-QuIC for the diagnosis of DLB was confirmed in another study evaluating a series of atypical cases referred to laboratories specialized in CJD diagnosis because of a rapidly progressive course . The diaIn the first attempt to cross-validate α-syn seeding aggregation assays developed by independent laboratories, Kang et al.  undertooIn a recent study, using the standard protocol developed by Caughey’s lab, but a wild-type recombinant α-synuclein substrate rather than the mutant form used by Groveman et al. , Rossi aIn the most recent of these studies, Iranzo and colleagues  applied Lastly, following the successful application of PrP RT-QuIC on peripheral tissues, De Luca et al.,  applied The results of the studies mentioned above demonstrated that RT-QuIC is highly accurate in diagnosing synucleinopathies, with values almost as good as those previously obtained in prion disease. However, they also showed divergent findings and significant variability in the predictive values of the test, which are likely related to critical variables such as the choice of recombinant substrate and experimental setting, the accuracy of the final diagnosis , and the number of examined cases in each diagnostic group.For example, specificity was very high among studies focusing on neuropathologically verified cohorts (95.9–100%) , 37, 74,In contrast to neuropathologically verified cohorts, the results obtained in clinical groups consistently showed false-positive reads , 74, 89,In some cases, the percentage of apparently false-positive results in clinically diagnosed cohorts was related to a specific pathological condition, leaving different open interpretations. For example, in AD, LB-related co-pathology is a relatively frequent finding at post-mortem examination. Accordingly, the 7 out of 43 AD cases that were positive by RT-QuIC in the study by Rossi et al.  might haSimilarly, the evaluation of unexpected positive results in clinical “healthy” controls should take into account that Lewy pathology affects 5–8% of people over 60 in the absence of extrapyramidal signs , 28. SinConcerning the diagnostic sensitivity, most studies demonstrated high values (above 90%) across the entire spectrum of syndromes associated with LB synuclein pathology , 74, 89.The variable but generally very low sensitivity of α-syn RT-QuIC in MSA deserves a separate comment. Two studies to date analyzed a significant number of MSA cases. They reported a 6.1%  and 35% Nonetheless, when compared to controls, CSF samples from MSA patients gave a higher number of positive reads than controls, suggesting a certain degree of cross-reactivity with the α-syn recombinant substrate. Thus, the use of novel substrates or the modification of other parameters in the RT-QuIC reaction might allow to increase the sensitivity for α-syn seeding activity in MSA cases and to distinguish them from controls and other synucleinopathies.Tau RT-QuIC represents the latest developed adaptation of the seeding conversion assays. Tau is a protein whose insoluble filaments are found in AD as well as in several other neurodegenerative diseases, collectively termed tauopathies. In vitro evidence , 80 indiHowever, the tau protein complexity arising from the presence of six isoforms, which differ one another for the inclusion of amino-terminal regions  and either 3 or 4 microtubule-binding repeats , challenged the development of tau RT-QuIC until very recently.The first successful RT-QuIC assay for the detection of misfolded tau species in the CSF was put forward by Saijo and co-workers . The assUsing similar RT-QuIC conditions, but employing different tau constructs, the same group adapted the RT-QuIC for the detection of tau misfolded species from mixed (3R/4R) tauopathies, such as AD and chronic traumatic encephalopathy patients, or 4R tauopathies, such as PSP and CBD , 79. WhiAfter its original implementation 10 years ago , the RT-Despite these significant advances, however, many challenges and unanswered questions remain. The recombinant substrate, which is critical for the RT-QuIC method’s accuracy, must be standardized and produced on a larger scale to be more readily available to laboratories worldwide. Most recent RT-QuIC protocols need validation in the inter-laboratory setting and the accuracy of the RT-QuIC using peripheral tissues such as the skin and nasal brushes further testing. In prion disease, there is also a need for improved RT-QuIC protocols to differentiate between sCJD subtypes and detect atypical prion diseases with higher sensitivity in vivo.In synucleinopathies, future studies should establish the impact of RT-QuIC on clinical diagnostic criteria, determine the assay performance on other accessible specimens, and search for variations in the RT-QuIC set-up that might correctly detect α-syn seeding activity in MSA. Moreover, the application of RT-QuIC to genetically determined PD cases and other rare atypical forms of PD should help to establish the real spectrum of LB-related PD, and distinguishing PD associated with LB pathology from PD cases caused by primary neuronal degeneration in the substantia nigra without LB formation. Finally, protocols must be developed further to bring tau RT-QuIC to the level of diagnostic accuracy shown by the prion and α-syn assays. If successful, these and other advancements will likely make the RT-QuIC of critical importance for the early diagnosis and treatment of most of these devastating disorders.


In 2014, a Nutrition Report Card (NRC) was developed as a sustainable, low-cost framework to assess the healthfulness of children’s food environments and highlight action to support healthy eating. We summarise our experiences in producing, disseminating, evaluating and refining an annual NRC in a Canadian province from 2015 to 2019.To produce the NRC, children’s food environment indicator data are collected, analyzed and compiled for consensus grading by an Expert Working Group of researchers and practitioners. Knowledge translation activities are tailored annually to the needs of target audiences: researchers, practitioners, policymakers and the public. Evaluation of reach is conducted through diverse strategies, including tracking media coverage and website traffic. Assessment of impact on diets and health outcomes is planned.Alberta, Canada.Not applicable.The grading process has facilitated refining the NRC to enhance its relevance and utility as a tool for its target audiences. Its public release consistently captures media interest and policymakers’ attention. The importance of partnerships in revealing data sources and in strategising to enhance policy approaches to improve food environments is apparent. The NRC has benchmarked progress and stimulated dialogue regarding healthy food environments for children.The NRC may help to foster a supportive climate for improving the quality of children’s food environments. As an engaging and accessible document, the NRC represents a key mechanism for collating data related to children’s food environments and ensuring it reaches the audiences best positioned to use it. Efforts are underway to expand the NRC across Canada. Ready access to energy-dense, nutrient-poor foods facilitated by current food environments may be contributing to the high prevalence of unhealthy eating behaviours among children and youth in Canada,3. This is concerning because childhood represents a critical period for establishing healthy eating behaviours. Additionally, diet-related chronic diseases are one of the greatest contributors to premature mortality in Canada.Food environments shape the availability, affordability and social acceptability of food ‘choices’,6–8, prompt action is required to ensure that children’s food environments support, rather than undermine, their health. Benchmarking and publicising government tobacco control initiatives have previously helped to generate support for stronger government actions and policies to reduce tobacco consumption. Similar measures might be leveraged to incite action to improve childhood nutrition.Given the tendency for unhealthy eating behaviours and determinants of these behaviours  to persist across the life course–12. Annual Report Card release elicits substantial media and public attention and has been cited by policymakers as an evidence source during policy development. Moreover, this Report Card is well-regarded internationally, such that in 2014, fifteen nations released their own contextualised physical activity Report Cards.In 2005, a Report Card on Physical Activity for Children and Youth was created to evaluate Canadian progress in improving children’s physical activity behaviours and environments. As part of this initiative, the team oversaw the conceptualisation of a framework for Alberta’s Nutrition Report Card on Food Environments for Children and Youth, hereafter abbreviated as the ‘NRC’ . The goals of the NRC are ‘to monitor the state of children’s food environments and supportive policies, inform stakeholders of the state of these environments and policies, engage society in a national discussion, and outline a policy-relevant research agenda for further study’, p. 287. In this way, the collaborative aimed to advance a solutions-oriented agenda related to childhood health promotion. Target stakeholder groups of the NRC include researchers, practitioners, policymakers and the public.Given the success of the physical activity Report Card, the absence of a similar mechanism to monitor and report progress in improving the quality of children’s food environments represented a missed opportunity to identify strengths and possibilities for change. In 2013, researchers, practitioners and policymakers seized a funding opportunity to form a collaborative to provide leadership and support to develop, implement and evaluate policy activities for chronic disease prevention. Briefly, the NRC framework includes five environment domains identified as influencing children’s eating behaviours: physical, communication, social, economic and political  for the Canadian province of Alberta. Specifically, we reflect on NRC: (i) production, (ii) knowledge translation activities, (iii) refinements, (iv) successes and challenges, (v) lessons learned and (vi) future directions.Building on this foundation, the objectives of this article are to describe how our aforementioned collaborative applied this frameworkSeveral stepwise procedures are undertaken to produce the NRC each year. These procedures require the involvement of many key players, including the Expert Working Group (EWG).The EWG is currently comprised of thirteen researchers and practitioners working in diverse fields  in different provinces  across Canada. Most EWG members have participated in NRC production from its inception, although there has been some flux in membership along the way. In addition to grading NRC indicators and helping to craft themes and recommendations, the EWG is engaged sporadically throughout the year for purposes such as reviewing data collected to date to ensure that key sources of information are not overlooked and in facilitating data access.,17. Grades of A through F are assigned that reflect achievement of, supports for and monitoring of indicator-specific benchmarks. Each grader assesses the indicators individually based upon a summary data document. Individual grades are synthesised into a single document, and graders then convene in a full-day consensus meeting to reach agreement on the grades and discuss potential recommendations for action. The grading process serves to highlight current strengths within Alberta’s food environments and areas for improvement, with unmet benchmarks serving as a call to action. After grading, research, practice and policy recommendations are created for each indicator. Final products include a full-length written report (with detailed explanations of grades and underlying data), a summary report and an infographic (started in 2017). Although the first NRC was published in the month of January, subsequent NRC were and continue to be published annually in September, capitalising on the increased attention paid to children’s wellness at the start of the school year.Annual NRC production involves the following steps: data collection and analysis, individual grading, grading consensus process, calculation of final grades, development of recommendations and compilation of a final report. Graduate and undergraduate students contribute to year-round data collection, using general web searches; keyword literature searches; government, institutional and non-governmental organisation websites; policy databases; contacting key informants by telephone and email; and networking with established health organisations. A stepwise grading process Fig.  guides eAlberta Policy Coalition for Chronic Disease Prevention. The Coalition is a collaborative consisting of seventeen organisations that have come together to coordinate efforts, generate evidence and advocate for policy change to reduce chronic disease in Alberta. The collaborative conducts evidence syntheses on NRC-related topics, such as nutrition labelling and sugar-sweetened beverage taxation, which support our annual literature updates concerning NRC indicators. The Coalition also plays an important knowledge translation role, drawing from NRC recommendations when advocating for policy changes to promote healthy food environments.Alberta Health Services is the provincial health authority. Connections with Alberta Health Services facilitate access to key data required for grading. In addition, as a result of EWG collaboration with this health authority, there has been movement towards incorporating the NRC as a tool to support provincial dietetic practice. In 2018, an Alberta Health Services webinar showed how public health dietitians could use the NRC to enhance their work, thereby expanding the scope of the NRC to health practitioners and promoting its sustainability.Alberta Healthy Schools Community Wellness Fund. The Wellness Fund supports projects that enhance children’s health and wellness to create healthy school communities. Acquiring school-based nutrition data for the NRC can be challenging, but EWG relationships with the Wellness Fund have facilitated inclusion of nutrition-related questions into their annual school health survey, responses to which were then used to inform NRC indicators.Evidently, these partnerships were fundamental not just to NRC production but to knowledge translation as well.Building upon the EWG’s social networks, we established a list of key informants and their respective organisations from whom we collect data and share final reports with annually. Examples of such partnerships include those with research groups at other Canadian universities, provincial governments and non-profit organisations. In some instances, the data shared have already been analyzed, while in others, we are provided with raw data requiring secondary analysis. For example, environmental health inspectors provide us with lists of all food outlets in the province, which we then code based on their healthfulness to assess the quality of physical food environments. In turn, gathering these data led us to consider additional analytic approaches for understanding that data, such as expanding beyond the NRC indicators to explore competitive food environments surrounding children’s activity settings. Illustrations of key partnerships that played an integral role in NRC production are outlined below:Disseminating the NRC. A proactive dissemination strategy is constructed each year in partnership with communications experts available in house to maximise reach and impact. Our distribution list expands annually as we become aware of additional stakeholders and knowledge users. In 2017, we began delivering communication toolkits to stakeholders and knowledge users , including the key informants described earlier, to accompany NRC release. This mobilisation toolkit assists partners to extend the research of the NRC and facilitates its use. Toolkit contents include key messages, quotes, prepared social media posts, an infographic, an email script, a newsletter article and a media release. Through our dissemination efforts over the years, NRC reach has spread around the globe, having been downloaded online in a total of sixteen countries to date.Conducting media and public awareness activities. Our public relations and media strategy engage local and regional media contacts . Public release of the NRC consistently garners significant media attention, although there has been some flux over the years. Media and public awareness activities are evaluated by assessing media coverage and website traffic  within the Alberta government. Over the past 5 years, we have sent out thirty-two letters and received twelve response letters from ministers indicating their interest in the NRC. Additionally, these letters have resulted in five invitations to consult with government officials.Symposia. To date, our team has delivered more than forty presentations about the NRC in four different countries to a wide variety of audiences, including academics, practitioners, government, non-profit community organisations and parents. The purpose of these presentations has ranged from academic keynotes to building local capacity to use NRC data to foster community food environment change. These presentations have consistently been well-received, demonstrated by requests for follow-up presentations and invitations for collaborations, such as a current multi-province collaboration that has applied for funding to expand the NRC to multiple jurisdictions in Canada.Knowledge translation activities include (i) disseminating the NRC; (ii) conducting media and public awareness activities and (iii) knowledge exchange through consultations and symposia. We fulfill these activities through the following:. With policies, regulations and monitoring systems in place, there was no rationale for further assessment; therefore, this benchmark was removed in 2016. In its place, the EWG added a benchmark concerning sodium, given the 2016 release of Canada’s Healthy Eating Strategy which targets sodium as a ‘nutrient of concern’, in addition to fat and sugar. Through discussion with the EWG, changes have also been made to indicators and benchmarks to increase clarity of wording.The NRC is continuously refined to enhance its relevance as a knowledge translation tool for its target audiences of researchers, practitioners, policymakers and the general public. In bringing experts around the table for discussion, the grading process has proved useful in refining indicators, benchmarks, the grading scheme and overall formatting, helping to simplify the NRC and enhance its relevance for policy impact and public understanding of the importance of healthy food environments. The NRC began with forty-two indicators and was streamlined to thirty-seven indicators in 2016. Indicators and benchmarks have been removed or added based on their topical relevance. For example, a 2015 NRC benchmark addressed concerns about the presence of artificial trans fats in commercially prepared foods. However, this issue was subsequently resolved with Canada’s ban on the use of the main source of artificial trans fats  by the food industryTo improve the utility of the NRC for the public, we have modified the visual design and content of the report over the years. In 2017, ‘on the horizon’ highlights were added to the NRC to acknowledge work in progress. For example, as observed in Fig. –25, likely presents a more compelling case for action than could be achieved by, for example, publicising findings from individual studies through separate media releases over an extended time period. We have continued with this strategy since 2017. In 2017, youths’ vulnerability to unhealthy food environments emerged as an important concern within the EWG, as we observed how nutrition-related policies tended to concentrate on the health of younger children, while overlooking the needs of older youth. Hence, the theme of ‘vulnerable youths’ was featured. In 2018, the theme of ‘municipal action’ was selected, targeting municipalities for their potential to leverage social change. ‘Municipality muscle’ highlights were thus incorporated to increase municipalities’ awareness of their power and actions that they could take to improve food environments , which they may have previously overlooked. The example in Fig. Another adjustment to our knowledge translation strategy included the 2017 decision to format the NRC around a specific theme each year, providing an overarching narrative linking key findings that emerge from each subsection. This narrative, supported by multiple lines of evidence and depicted as a one-page infographicThese refinements have been integral to the ongoing success of the NRC. We highlight key successes, and challenges, below. through the following:Monitoring. The first NRC in 2015 served as a baseline for future data collection, identifying where policy was succeeding and where work was needed to support healthy food environments. By way of NRC monitoring practices, we have tracked cultural shifts in children’s food environments in Alberta, and Canada at large, that align with NRC recommendations. For example, at the provincial level, Alberta’s School Nutrition Program, which provides healthy meals and snacks to students, was piloted in 2016 and has since been implemented province wide. At the federal level, Canada’s Healthy Eating Strategy, introduced in 2016, addresses the need for regulated front-of-package nutrition labelling. The NRC is valuable in regard to its ability to capture and monitor these positive changes in policy. The NRC also captures declines in the healthfulness of food environments, such as the cessation or reduction of government funding for healthy eating initiatives. In doing so, governments are held accountable to their responsibilities in promoting children’s health, given that announcements are rarely made to publicise funding cessation, leaving the public otherwise unaware.Informing. Knowledge translation activities have informed a growing list of stakeholders about the importance of investing in policy change to support positive change to children’s food environments in Canada. In its push for transparency, the NRC can help to drive policy change. Further, the NRC is supported by peer-reviewed funding, generated in a respected institution and produced by a world-renowned team of investigators, enhancing its credibility. As one means of gauging success in informing stakeholders, we conducted a stakeholder survey after the release of the 2015 and 2016 NRC. Those who downloaded the NRC were prompted to complete a pop-up survey which asked about their willingness to participate in future research. A survey, open for 2–3 months post-launch, was then emailed to those interested. Descriptive statistics were used to summarise the 2015 (n 20) and 2016 (n 14) data , which has developed a comprehensive and detailed system to monitor public and private sector policies and actions, and indicators of key aspects of the healthiness of food environments for global application at a population level,28,29. The NRC should be regarded as complementary to this work, with its more targeted set of indicators specific to children, primary reliance on existing data and different intended audiences.Studying. Unique to the NRC is its multi-level framework, acknowledging that continuing to frame unhealthy diets as an individual problem is unproductive. Most research on diet-related chronic diseases has been at the individual level  or more ‘downstream’ at the population level , neglecting broader socio-structural factors,31. Rather than a traditional problem-oriented approach to the study of diet-related chronic disease, the NRC is solution-oriented, in that it provides recommendations for action based on indicator grades. The NRC has also revealed its utility in identifying research gaps, whereby indicators with incomplete data for grading are highlighted as areas warranting further research.The NRC demonstrated its ability to fulfill its aforementioned goals of (i) monitoring, (ii) informing, (iii) engaging and (iv) studyingData collection. Issues inherent to data collection include the lack and timeliness of data for some indicators. However, we hope that by identifying research gaps, data availability and quality will improve over time. Because the NRC relies largely on publicly available data, we are not always aware of relevant proprietary data.Resource requirements. NRC production requires extensive human resources and financial capital to support said resources. While the NRC was designed to be inexpensive to conduct, ongoing funding and organisational partnerships will nevertheless be required to enable annual generation and dissemination of NRC. Data collection and analyses are time intensive processes, requiring intimate knowledge of the provincial policy context to ensure adequate representation, sufficient nutritional knowledge to accurately assess the healthfulness of foods available, as well as geographic information systems expertise. Having a web-based, automatic system for nutritional assessments could help to decrease human resource requirements .Health inequities. Our high-level assessments may fail to capture nuances at the local community level. For example, the NRC does not delve into the intricacies of Alberta’s multicultural landscape and the need for culturally appropriate food environments for those from different heritages. Within the NRC, it is rarely possible to address equity issues as there are limited nutrition data relating to disadvantaged groups, such as Indigenous populations, in Alberta. Because population health data in Alberta tend to be shared in aggregate form rather than by sub-populations, it becomes challenging to study inequities and discern how vulnerable populations may be differentially affected by current food environments and policies.Subjectivity of grading. Despite objective data, the grading process is fraught with value judgements, requiring discussion and debate by the EWG. For example, as part of the grading scheme  researchers, (ii) practitioners, (iii) policymakers and (iv) the general public.Researchers. The exercise of identifying indicator areas in which it appears important to intervene, and collating the supporting evidence for each indicator, has identified important gaps in the evidence base that should be targeted in future studies. Specifically, the NRC identifies policy-relevant questions that require answers, which may help researchers to avoid generating ‘policy free evidence’ that they are often accused of producing, p. 813. Evaluations of the effectiveness, and in particular, cost-effectiveness of policies to reduce socioeconomic inequalities in children’s food environments are especially important. According to policymakers, one of the most convincing types of evidence concerns the financial ‘costs of action, or inaction’, p. 812.Practitioners. The NRC offers practitioners a flexible tool for use in their daily work which can be adapted to their practice setting. For example, school health facilitators can collect data for school-related indicators within the NRC  and advocate for changes  based on the results. Practitioners have a unique ability to make immediate changes in their practice. This was evident in the case of Alberta Health Services public health dietitians who have been able to use the NRC as a tool to assess local community food environments, with analytic support from our university-based research team.Policymakers. The NRC collates a broad array of evidence in an accessible, readable document, which can serve to amplify its impact. Moreover, the media attention generated by the NRC release increases policymakers’ awareness of its existence. This awareness may in turn prompt action or, if the time is not right to act now, will provide readily available evidence to inform policy decisions at critical time points when policy windows open in the future. Given the importance of timely action during such ‘window openings’, the NRC’s role in this respect should not be underestimated. If evidence-based policy is to become the norm, rather than the exception, stronger linkages will be needed between researchers and policymakers. Additionally, the local data generated from the NRC may have more impact in decision-making processes affecting these jurisdictions than research that has been conducted elsewhere.The media and general public. The NRC can aid the media and general public in drawing policymakers’ attention to the issues that concern them, by providing a compelling evidence-based case for action packaged into a single, engaging document. Indeed, policymakers have highlighted how ‘a good story’ can influence politics, p. 812.The longitudinal impact of the NRC on policy readiness, environmental change, children’s diets and health outcomes will be described in future publications. Efforts are underway to institutionalise the NRC to ensure maximum benefits are derived from this work, a prospect that will require a stable source of long-term funding. While the NRC is currently intended for application at a provincial/territorial level in Canada, we aim to produce a national NRC in the future, once a critical mass of jurisdictions has adopted the NRC. Work on a national scale will enable benchmarking of food environments between jurisdictions. A number of Canadian provinces are currently establishing the infrastructure needed to produce their own provincial NRC. Our team has developed a ‘NRC toolkit’ (available upon request) to facilitate this process, and we plan to create an online hub with NRC resources.Over the past 5 years, the NRC has demonstrated its value as an engaging and accessible tool for benchmarking progress in improving children’s food environments in Alberta, Canada. The NRC framework, production process and knowledge translation strategy have been increasingly refined to enhance its relevance and utility for its target audiences of researchers, practitioners, policymakers and the general public. Partnerships, including those with the EWG, have been essential to annual NRC production and knowledge translation. Working alongside the EWG, such as through grading NRC indicators, has facilitated reflection on lessons learned from our successes and challenges in producing the NRC each year. Overall, the NRC may help to foster a supportive climate for policy adoption and implementation by stimulating dialogue about the importance of healthy food environments for children and youth. Efforts are in place to expand the NRC across Canada.


Patients with ovarian clear cell carcinoma (OCCC) have a poor prognosis because they show low sensitivity to platinum-based chemotherapy. New treatments for refractory OCCC are urgently needed.ARID1A. The patient was administered pembrolizumab combined with bevacizumab triweekly. Her serum CA-125 level decreased dramatically after the first cycle. A computerized tomography scan showed marked regression of the recurrent masses after 3 cycles, and the patient reached complete remission after 9 cycles. She showed good recovery from cachexia. We observed no marked side effects except for mild polyarthritis of the small joints.We present a patient with refractory OCCC in whom conventional chemotherapy failed. Cachexia was induced by the disseminating recurrent tumors. Tumor tissue staining and genomic analysis revealed PD-L1 negativity, a low tumor burden, stable microsatellite instability, and two mutations in ARID1A mutations are warranted.The therapeutic effect of checkpoint inhibitors combined with angiogenesis inhibitors is very promising in our patient with OCCC. Further clinical trials of tumors including  ARID1A mutations and overexpression of vascular endothelial growth factor (VEGF), annexin A4, and mammalian target of rapamycin (mTOR), have been reported in OCCC [Epithelial ovarian cancer (EOC) is one of the most lethal malignancies in the female reproductive system. Various subtypes of EOC exhibit histological and genomic heterogeneity . Among t in OCCC . A preciWe present a patient with refractory OCCC who was successfully treated with a combination of an immune checkpoint inhibitor, pembrolizumab, and the angiogenesis inhibitor bevacizumab. This case report was approved by the institutional review board of Shuang Ho Hospital (N201909048).A 42-year-old Asian woman, gravida 0, para 0, underwent laparoscopic cystectomy for a suspected ovarian chocolate cyst at Kaiser Hospital in southern California, USA, in March 2014. Pathology revealed clear cell carcinoma. An optimal debulking operation was subsequently performed, and the patient was found to have FIGO stage II disease. She was administered adjuvant chemotherapy with paclitaxel and carboplatin for 7 cycles. However, an increasing serum CA-125 level and recurrent pelvic tumors were noted in January 2016. She underwent a secondary debulking operation, followed by administration of adjuvant chemotherapy using carboplatin and gemcitabine. However, secondary recurrence deep in the pelvic cavity close to the sigmoid colon, rectum, and bladder was found in September 2017. Her recurrence progressed despite the administration of salvage chemotherapy, including liposomal doxorubicin and topotecan. In February 2019, she presented to a medical center in Taiwan and underwent a third debulking surgery including resection of the sigmoid colon, rectum, and bladder, followed by small bowel bypass, T-colostomy and bilateral percutaneous nephrostomy. Tumor recurrence occurred, with two major masses observed in the pelvis and abdomen soon after surgery. Palliative treatment was suggested because she was refractory to cancer treatment. Immune cell therapy with unknown immunological cells was attempted at a clinic but was ineffective.ARID1A  and revealed a stable microsatellite status, low mutation burden, and two mutations in 1A Table , as evidClinicalTrials.gov identifier: NCT02674061) recruited 376 patients with recurrent ovarian cancer for pembrolizumab monotherapy . The objective response rate was only 8.0% . The median progression-free survival was 2.1 months  [Pembrolizumab (trade name Keytruda) is a humanized antibody that targets programmed cell death protein 1 (PD-1) on lymphocytes. In 2014, the US Food and Drug Administration approved pembrolizumab for treatment of melanoma, non-small cell lung cancer, head and neck squamous cell cancer, Hodgkin lymphoma, urothelial carcinoma, stomach cancer, solid tumors with mismatch repair deficiency or microsatellite instability, and recurrent or metastatic cervical cancer expressing PD-L1, but the drug was not approved for ovarian cancer . The phaARID1A may be predictive for immune checkpoint inhibitors in OCCC [ARID1A (AT-rich interactive domain-containing protein 1A), an important subunit of the SWI/SNF (SWItch/Sucrose NonFermentable) chromatin remodeling complex, can alter the positions of nucleosomes along DNA [ARID1A can recruit MSH2 to chromatin during DNA replication and promote mismatch repair, and ARID1A inactivation compromises mismatch repair and increases mutagenesis and neoantigen levels [ARID1A-deficient ovarian cancer tumor displayed an increased mutation load, increased PD-L1 expression, and elevated numbers of tumor-infiltrating lymphocytes because of neoantigen production. Treatment with an anti-PD-L1 antibody reduced the tumor burden and prolonged the survival of mice bearing ARID1A-deficient but not ARID1A wild-type ovarian tumors. In addition to increased PD-L1, ARID1A may regulate other factors associated with oncogenic pathways such as PIK3CA-activating mutations, DNA methylation, or VEGF [ARID1A (p.M1154fs*7 and p.Y788*). In a clinical cohort report, progression-free survival after immune checkpoint blockade therapy was significantly longer in patients with ARID1A-altered tumors (n = 46) than in patients with wild-type ARID1A (n = 329) (p = 0.006) [ARID1A alterations could predict longer progression-free survival after checkpoint blockade , independent of microsatellite instability or the mutational burden. These reports demonstrate that the functional loss of ARID1A may act in conjunction with immune checkpoint blockade therapy.Mutations in  in OCCC . ARID1A long DNA . The mamlong DNA . ARID1A n levels . In a sy or VEGF . The levBevacizumab (trade name Avastin) is an angiogenesis inhibitor that blocks vascular endothelial growth factor A . In receARID1A mutations. Many clinical trials (NCT03596281 and NCT04361370) to determine the efficacy of this combination therapy for ovarian cancer are on the way. Since our manuscript was submitted, a phase 2 nonrandomized clinical trial  testing pembrolizumab combined with bevacizumab and oral metronomic cyclophosphamide in the treatment of recurrent ovarian cancer was published [In conclusion, OCCC is a subtype of EOC that is prevalent in Asia and has a poor prognosis. Combination treatment with pembrolizumab and bevacizumab may be considered in OCCC, particularly with ublished . While tAdditional file 1: Supplementary Figure 1. Immunohistochemistry (IHC) of the PD-L1 control. (a) Positive control of PD-L1 staining . (b) Positive control of PD-L1 staining


Assessing competencies or program learning outcomes in educational programs is often a leadership challenge. This case study reports medical education program’s efforts to document undergraduate competency attainment using a pre-post, third-party, objective testing service that allows for inter-university comparison, a testing service that is being adopted by some certification and accrediting bodies.p-values). MANOVA models of sub-competency difference scores were also evaluated.Students completed a pre-test after program acceptance and a post-test at the end of the last didactic semester (1.5 years later) just prior to their required internships. Scores and subscores were evaluated using t-tests . These improvements were independent of ethnicity, age, gender, and grades. The average student improved by 12.85 points (95% CI of 10.52 to 15.18) with the largest improvements in strategic planning and leadership competency areas .Results indicate competency improvement for each of the 12 areas based on the The third-party pre-post has some face validity given that student performance improved after completing a related curriculum as would be expected. Congruent with earlier studies, we find that repeated testing helps document competency attainment and that a single method for assessment is insufficient. We further document limitations of this 3d-party exam. Assessing the efficacy of undergraduate program success in achieving program goals is difficultAn undergraduate medical program adopted Internet-based pre-post competency testing as part of assessmentp-values show improvement in all competency areas, confirming program efficacyPaired tests with Holm-adjusted MANOVA of difference scores as a function of demographics and grades shows effects only from differencingThis type of pre-post testing is important to verify the efficacy of the curriculum interventionThe 3d-party tool provides inter-university comparisons but requires improvementCompetency-based medical education (CBME) is the standard for many education programs in the medical field . In the The primary purpose of a CBME-based program is to produce graduates who possess specific competencies required of the profession. Using the definition of Gervais, competency-based education (CBE) is outcome-based and incorporates delivery and assessment modes for evaluating “mastery of learning by students through their demonstration of knowledge, attitude, values, skills, and behaviors required for the degree sought” . HealthcAssessing CBME for medical education programs is both non-trivial and often non-standardized. Some research has suggested that a systems perspective is necessary and that any evaluation should leverage academic advisors . Other rThere are exceptions, however. For example, Germany is leading an effort to build valid competency assessment tools for engineering, economics, social sciences, educational science, psychology, and teacher training. This effort is multi-institutional, international, and collaborative . Part ofAlso, there are efforts for longitudinal assessment of competency attainment of undergraduate students in some organizations. A specific example is the Valid Assessment of Learning in Undergraduate Education (VALUE) program implemented by Queen’s University. VALUE evaluates longitudinally student attainment of competencies as well as critical thinking, cognitive skills, lifelong learning, problem solving, and transferrable learning orientations for bachelor of arts, bachelor of computing, bachelor of education, bachelor of nursing science, and bachelor of science in engineering programs. While not specifically related to HAML, the initiative demonstrates a focus on quantification of competency attainment by students for system-wide educational improvement .Prior HAML-program studies have examined the effectiveness of CBME from different perspectives using survey instruments. For instance, one study assessed the effectiveness of competency-based programs by comparing survey ratings from preceptors with residents/fellows competency self-ratings and they found that residents/fellows tended to rate themselves higher than the preceptors . BradleyWhile the approaches used by the studies may be appropriate for qualitative measurement of competency attainment, they are non-standardized, non-objective, and non-a priori. Students may arrive with high-level competencies, so the effectiveness of the program cannot be known without time-sequenced assessments or (at least) pre-post testing and evaluation. At a minimum, both pre and post evaluations of competencies are required to determine the efficacy of a program curriculum “treatment.” Further, preceptor and self-assessments as well as oral examinations of competency attainment may be biased due to the halo effect as well as other sources . ExclusiThere appears to be little standardization of competency-assessment in HAML programs. We found one HAML study (a student self-assessment for an interdisciplinary leadership program) that used any pre-post analysis to determine whether students improved . To addrThe purpose of this study was to assess the effectiveness of a program-based CBME for an undergraduate HAML program  in a college of health professions using testing provided by a third party, Peregrine Academic Services (PAS), based on program competencies. The intent was to evaluate whether program performance might be assessed at the student level for individual competency attainment, at the program level for quality improvement, and at the national level for benchmarking. This type of multi-dimensional assessment is required for certification of many programs. Limitations of this test are evaluated in the discussion. Since a pre-post difference should be expected, this was the first attempt at evaluating some face validity of the proposed test as well.The significance of this study involves program certification and performance improvement. Regardless of program type, certification or accreditation typically requires assessment of student competency attainment as well as program assessment for quality improvement purposes. Grades in courses do not effectively translate to individual competencies, as a single course might address small portions of various competencies. For example, the ability to communicate is a competency often found in multiple courses, yet the grade for those courses are likely not specific to the communication competency. Using PAS competency assessment testing based on AUPHA requirements allowed for one objective assessment. Coupled with preceptor and individual assessments, a 360-degree view of a program’s strengths and weaknesses might better be obtained.The primary research question investigates whether pre-post, third-party objective testing provides evidence that the medical education programs in the study effectively increases competency performance scores (and associated percentile rankings) as well as scores for each of the subordinate competencies. The subordinate competencies that compose this score are defined by the Healthcare Leadership Alliance  and measThis study is significant in that it evaluates pre-post performance of an entire program in developing student competencies using PAS as defined by HLC. Since PAS is a platform that AUPHA is considering for undergraduate program certification assessment, it is important to assess its prima facia validity, strengths, and weaknesses. On a larger scale, “assessing an assessment instrument” is important for the larger medical education community. While one would expect increases in performance after a program’s worth of instruction, it is possible that these increases might be despite the assessment instrument rather than because of it. This study also illustrates the importance of using metrics to drive program direction.The setting for this study is a large, public university in Texas that is Southern Association of Colleges and Schools (SACS) accredited with a health administration undergraduate program that is AUPHA certified and located in a college of health professions. The study program has up to 160 students at any given time. The university is a Hispanic-Serving Institution (HIS-greater than 25% Hispanic students), and the program itself has closer to 30–50% Hispanic students at any given time.https://rpubs.com/R-Minator/PASTesting.PAS provides on online test based on competencies for health administration, business administration, and other disciplines. PAS individual test results include the overall test score and percentile ranking based on other academic programs. PAS also provides scores for each assessed competency area.. For the study program students, the testing seeks to measure competency attainment. Notable exceptions omitted from this study are the quantitative analysis competency and communication .  The PAS test questions themselves are multiple choice. One should note that PAS testing is only one of 34 assessments used by the program to assess competencies and program outcomes. A complete list of program and student learning objective assessments  is available online: While PAS questions evaluate largely at the “knowledge” level, some of the questions assess at the application level of Bloom’s taxonomy . PAS is The PAS assessment as implemented in this setting provides students 10 random questions in each of the formally assessed competency areas (120 question). For the pre-test, students receive three minutes per question on average. For the post-test (given at least 1.5 years after the pre-test), two hours are provided. Extending the test beyond two minutes per question has shown no improvement in individual performance within the program; diminishing returns are experienced. The undergraduate medical program funds the cost of each test. The testing is not currently computer adaptive, and the questions are not assigned a difficulty rating (see the detailed discussion in the limitations section).n = 54). Some students completed only the post-test during early adoption, while others have completed only the pre-test pending matriculation. These students comprise the cohort-based, sequential sample for this study. Students must take the pre-test as a condition for entering the program and must pass the post-test based on faculty-determined criteria prior to their internships. Currently, students must obtain overall scores above the 50th percentile to pass the examination; however, that is being adjusted upward to 50th percentile for each of the 12 measured competencies. The Texas State University Institutional Review Board deemed this research exempt (IRB application 7234).The study university has been using Peregrine testing in Fall 2018 and implemented pre-post testing in January 2019. Since the start of testing, students have taken 243 valid tests, and about a quarter of them completed both the pre-test and the post-test . The three outliers depicted in Fig. The mean GPA for students in the study was 3.20 . Since the minimum requirement for program admission is 2.75 with the follow-on requirement that 3.0 or better must be maintained, these values seem appropriate. The GPA did not statistically differ based on ethnicity or gender as shown in Fig. The average days between the pre-test and post-test was 435.54 . This time between tests mitigate any concern that there was test improvement based solely on content learned from the pre-test.p = .09). Most interestingly, the pre-test performance is not related to the post-test performance (ρ = .199) when not accounting for individual test-taking performance. Figure The relationships among age, GPA, pre-test scores, and post-test scores are not very revealing. Only GPA and age are statistically related, and that relationship is slightly negative (r = − 0.29). Age and pre-test scores are weakly and positively correlated (r = .236), but the evidence is weak supporting this relationship  and the percentile ranking relative to undergraduates from all universities who took the post-test. The “average” student increased 12.85 points, from 58.65 to 71.51 in final score. The medians were comparable indicating little skew. The largest gains were in the areas of strategic planning and marketing, leadership skills and behavior, general management, and financial management (median gains of 20 points each). Little overall improvement was seen in the legal environment of healthcare, organizational climate and culture, managing change, and information management (median gains of 10 points each). Figure Table Fig. Pre-test percentile scores for students in the study university averaged 58.7 (median of 63). For the post-test, the average jumped to 80.44 (median of 84). The mean percentile increase was 21.7 percentile points, a significant jump. Figure n = 119 post-tests). The utility of such analysis is that it informs performance improvement.Analysis of post-test results against other universities was revealing. The study university was compared to other SACS-accredited bodies as well as those accredited by the Higher Learning Commission (HLC). Also, the study university was compared against hybrid, online and traditional campuses. Table p-values were adjusted via Holm’s method. In all cases, the findings were statistically significant at the .05 level; there was evidence that student performance improved. Table p-values.Paired sample t-tests were run for the final score and each competency separately. To account for familywise error, the https://rpubs.com/R-Minator/PASTesting.After failing to reject the null assumption of multivariate normality via Mardia’s test , MANOVA p < .001. In comparison to other universities’ post-tests, the study university’s average scores of 71.5 are higher than any of the comparative groups: SACS programs, HLC programs, hybrid programs, online programs, traditional programs. The ability to compare across programs allows for benchmarking.The primary research question investigated whether pre-post, third-party objective testing provided evidence that a medical education program effectively increases one or more of the 12 student competencies assessed. The results confirm that all competencies were improved through the program curriculum intervention as would be expected. This type of improvement is suggestive of some face validity. The “average” student increased approximately 13 points (from 59 to 72), and mean post-test scores were statistically better than the pre-test scores in all competency areas with In the study program, all evaluated competency areas improved significantly. The largest raw score improvement was in strategic management (21.3 points). The smallest improvement was in health information management (8.3 points). This information was used as part of program performance improvement to review and revamp the Health Information Management course. While testing is certainly not the panacea for program assessment, it did identify an area for improvement.Multivariate models of the difference scores resulted in no statistically significant associations with GPA, ethnicity, gender, or age. Only the differences themselves  remain statistically significant. For many medical education programs that serve ethnically and racially diverse populations, evaluating test effects by diversity is something that must be considered.To date, various competency assessments and related competency models have been developed and utilized to validate HAML programs , 34–36. Many university programs have opted to create their own internal method of competency assessments (some to include both pre-post assessments). The use of non-standardized assessments results in ambiguity of competency assessment terminology and methodological deployment . FurtherThere are several important considerations for medical educators. First, multiple methods and multiple assessments are necessary for competency evaluation . One sinWhile HAML certifying and accrediting bodies (AUPHA and CAHME) coupled with educational institutions are assisting PAS in building a repository of questions that demonstrate content validity in assessing competencies beyond the knowledge level of Bloom’s taxonomy, there are many associated with PAS testing. First, PAS is not structured based on computer adaptive testing (CAT) such as the Graduate Record Examination (GRE). Computer adaptive testing results in greater achievement measurement precision and improved student motivation and engagement . Since qAnother limitation of PAS is the inability of faculty to review the questions in the databank. The questions are under review through AUPHA experts, but the end date for that review is unknown. Understandably, PAS would like to keep this information proprietary; however, doing so requires that students keep records of questions which area questionable.A third limitation is induced incentive bias. Since the pre-test is not graded, students have little incentive to perform well other than internal motivation. Reasonable performance on the post-testis necessary for students to proceed to the residency, though.The questions of PAS often are knowledge rather than pure competency based, an added limitation. While some questions require students to apply acquired knowledge, many require only a base knowledge level. Further, the PAS pre-packaged health administration competencies do not include quantitative skills, so the study program had to request the use of business school competencies for assessment.The PAS questions are unable to assess competencies such as communication skills and leadership. “Soft skills,” the ones sought by many organizations when making management hiring decisions, are not well-assessed by examinations of this nature.Despite these limitations, the results show some prima facia validity in that one would expect an educational intervention to result in improved performance on a test designed to measure competencies in the program area. The limitations in the PAS testing process are to be addressed as part of process improvement; however, PAS in its current state does provide a third-party, objective measure for evaluating competencies.The PAS healthcare administration examination is relatively new to AUPHA and the program under study. Performance improvement requires continuous assessment of the examination and its ability to measure competencies effectively. Ongoing analysis of exam results will continue to provide valuable program and industry-level information to healthcare administration education stakeholders. Programs investing in this external exam are encouraged to perform their own program-level analyses, as well as the potential for valuable inter-program collaboration to best improve the development of future healthcare leaders.This study is ongoing, and analysis is conducted every semester based on the outcomes. If PAS improves and adds computer adaptive testing, programs using this third-party tool may benefit from increased student satisfaction and achievement based on previous research . Further