Predictive alternating runs and random task-switching sequences produce dissociative switch costs in the Consonant-Vowel/Odd-Even task.

Task-switching is commonly used to investigate working memory and attentional control processes. The current study compares predictive versus non-predictive task-sequencing effects on task-switching performance. Participants completed four blocks of the Consonant-Vowel/Odd-Even (CVOE) task: Two single task pure blocks, a predictable switch block where task switching occurred every two trials, and a random switch block where switching was unpredictable. In addition to mean error rates and response times (RTs), we assessed sequence effects on local switch costs (i.e., switch vs. nonswitch trials) and global costs (i.e., nonswitch vs. pure trials) for both error rates and RTs along with their underlying distributions. Overall, we show that while predictive and random switching produced similar patterns for mean error rates and RTs, a dissociation occurred in RT switch costs. When switching was random, local costs were inflated. In contrast, predictive switching increased global costs. Increased local costs for random versus predictive switching reflect an increase in task-set reconfiguration processes as participants struggle to reconfigure to an unpredictable task type in working memory on a subsequent trial. Separately, increased global costs for predictive switching reflect declines in task-set maintenance processes, as participants must maintain both task types in working memory while simultaneously monitoring their progress through the trial sequencing.

Affordance norms for 2825 concrete nouns.

Objects are commonly described based on their relations to other objects (e.g., associations, semantic similarity, etc.) or their physical features (e.g., birds have wings, feathers, etc.). However, objects can also be described in terms of their actionable properties (i.e., affordances), which reflect interactive relations between actors and objects. While several normed datasets have been developed to categorize various aspects of meaning (e.g., semantic features, cue-target associations, etc.), to date, norms for affordances have not been generated. We address this limitation by developing a set of affordance norms for 2825 concrete nouns. Using an open-response format, we computed affordance strength (AFS; i.e., the probability of an item eliciting a particular action response), affordance proportion (AFP; i.e., the proportion of participants who provided a specific action response), and affordance set size (AFSS; i.e., the total number of unique action responses) for each item. Because our stimuli overlapped with Pexman et al.'s, Behavior Research Methods, 51, 453-466, (2019) body-object interaction norms (BOI), we tested whether AFS, AFP, and AFSS were related to BOI, as objects with more perceived action properties may be viewed as being more interactive. Additionally, we tested the relationship between AFS and AFP and two separate measures of relatedness: cosine similarity (Buchanan et al., Behavior Research Methods, 51, 1849-1863, 2019a, Behavior Research Methods, 51, 1878-1888, 2019b) and forward associative strength (Nelson et al., Behavior Research Methods, Instruments, & Computers, 36(3), 402-407, 2004). All analyses, however, revealed weak relationships between affordance measures and existing semantic norms, suggesting that affordance properties reflect a separate construct.

Leptin Activation of Dorsal Raphe Neurons Inhibits Feeding Behavior.

Leptin is a homeostatic regulatory element that signals the presence of adipocyte energy stores, reduces food intake, and increases energy expenditure. Similarly, serotonin (5-HT), a signaling molecule found in both the central and peripheral nervous systems, also controls food intake. Using neuronal tract tracing, pharmacologic and optogenetic approaches, and in vivo microdialysis, combined with behavioral end points, we tested the hypothesis that leptin controls food intake not only by activating hypothalamic leptin receptors (LepRs) but also through activation of LepRs expressed by serotonergic raphe neurons that send projections to the arcuate (ARC). We showed that microinjection of leptin directly into the dorsal raphe nucleus (DRN) reduced food intake in rats. This effect was mediated by LepR-expressing neurons in the DRN, because selective optogenetic activation of these neurons at either their DRN cell bodies or their ARC terminals reduced food intake. Anatomically, we identified a unique population of serotonergic raphe neurons expressing LepRs that send projections to the ARC. Finally, by using in vivo microdialysis, we showed that leptin administration to the DRN increased 5-HT efflux into the ARC, and specific antagonism of the 5-HT2C receptors in the ARC diminished the leptin anorectic effect. Overall, this study identified a novel circuit for leptin-mediated control of food intake through a DRN-ARC pathway, identifying a new level of interaction between leptin and serotonin to control food intake. Characterization of this new pathway creates opportunities for understanding how the brain controls eating behavior and opens alternative routes for the treatment of eating disorders.

Presynaptic Rac1 in the hippocampus selectively regulates working memory.

One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.

Bridging Gaps: A Quality Improvement Project for the Continuing Medical Education on Stick (CMES) Program.

BACKGROUND: Aimed at bridging the gap in continuing medical education (CME) resource availability in low- and middle-income countries (LMICs), the "Continuing Medical Education on Stick" (CMES) program introduces two technological solutions: a universal serial bus (USB) drive and the CMES-Pi computer facilitating access to monthly updated CME content without data cost. Feedback from users suggests a lack of content on tropical infectious diseases (IDs) and content from a Western perspective, which may be less relevant in LMIC settings. METHODS: This quality improvement project was intended to identify areas for improvement of the CMES database to better meet the educational needs of users. We compared the CMES content with the American Board of Emergency Medicine (ABEM) Exam content outline to identify gaps. The curriculum map of the CMES library, encompassing content from 2019 to 2024, was reviewed. An anonymous survey was conducted among 47 global users to gather feedback on unmet educational needs and suggestions for content improvements. All healthcare workers who were members of the CMES WhatsApp group were eligible to participate in the survey. RESULTS: The curriculum map included 2,572 items categorized into 23 areas. The comparison with the ABEM outline identified gaps in several clinical areas, including procedures, traumatic disorders, and geriatrics, which were represented -5%, -5%, and -4% in the CMES library compared with the ABEM outline, respectively. Free responses from users highlighted a lack of content on practical skills, such as electrocardiogram (ECG) interpretation and management of tropical diseases. Respondents identified emergency medical services (EMS)/prehospital care (81%), diagnostic imaging (62%), and toxicology/pharmacology (40%) as the most beneficial areas for clinical practice. In response to feedback from users, new content was added to the CMES platform on the management of sickle cell disease and dermatologic conditions in darkly pigmented skin. Furthermore, a targeted podcast series called "ID for Users of the CMES Program (ID4U)" has been launched, focusing on tropical and locally relevant ID, with episodes now being integrated into the CMES platform. CONCLUSIONS: The project pinpointed critical gaps in emergency medicine (EM) content pertinent to LMICs and led to targeted enhancements in the CMES library. Ongoing updates will focus on including more prehospital medicine, diagnostic imaging, and toxicology content. Further engagement with users and education on utilizing the CMES platform will be implemented to maximize its educational impact. Future adaptations will consider local relevance over the ABEM curriculum to better serve the diverse needs of global users.

Presynaptic Rac1 in the hippocampus selectively regulates working memory.

One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory is selectively impaired following the expression of a genetically encoded Rac1-inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.

Item-specific and relational encoding are effective at reducing the illusion of competence.

Metamemory, or the ability to understand the capacities of one's own memory, is important for learning. To investigate questions surrounding metamemory, researchers commonly have participants make judgments of learning (JOLs) at encoding, in which participants rate their likelihood of recalling the target in a cue-target word pair when shown only the cue at test. However, the associative direction of cue-target pairs can affect the calibration of JOLs. Unlike forward associates (e.g., credit-card), in which JOLs often accurately predict recall, an illusion of competence has been reported for backward associates (e.g., card-credit), symmetrical associates (e.g., salt-pepper), and unrelated cue-target pairs (e.g., artery-bronze) such that JOLs overestimate later recall. The present study evaluates whether the illusion of competence can be reduced when participants apply deep item-specific or relational encoding tasks relative to silent reading. Across two experiments, we show that both item-specific and relational encoding strategies reduce the illusion of competence for backward associates and unrelated pairs while improving the calibration between JOLs and recall. Our findings suggest that these encoding strategies are effective at reducing the illusion of competence, with increased calibration primarily reflecting improved recall. Thus, item-specific and relational encoding strategies primarily affect retrieval processes rather than metacognitive processes that participants engage in at encoding.

Is discriminability a requirement for reactivity? Comparing the effects of mixed vs. pure list presentations on judgment of learning reactivity.

Providing judgments of learning (JOLs) at study tends to produce reactive effects on recall of cue-target word pairs. This reactivity generally produces memory improvements (i.e., positive reactivity) but only for related word pairs. For unrelated pairs, reactivity is typically not observed. Researchers have primarily investigated reactivity using study lists that contain at least two distinct pair types (i.e., related vs. unrelated pairs). Using these mixed lists, reactivity may occur because participants use distinguishing pair characteristics to inform their study goals (i.e., prioritizing related vs. unrelated pairs). The present study examined whether detection of separate pair types within mixed lists is a requisite for reactivity to occur. Experiment 1 replicated previous work showing that in mixed lists, JOLs produced positive reactivity on related pairs but are nonreactive on unrelated pairs. Importantly, Experiment 1 also found that these patterns extended to pure lists, in which only one pair type is presented. Experiments 2 and 3 then extended these patterns to backward and symmetrical paired associates. Finally, across experiments, reactivity patterns reported for JOLs extended to frequency of co-occurrence judgments across pair and list types. Our findings that reactivity patterns consistently emerge using pure lists supports a cue-strengthening account of reactivity.

Distinctive Sans Forgetica font does not benefit memory accuracy in the DRM paradigm.

A common method used by memory scholars to enhance retention is to make materials more challenging to learn-a benefit termed desirable difficulties. Recently, researchers have investigated the efficacy of Sans Forgetica, a perceptually disfluent/distinctive font which may increase processing effort required at study and enhance memory as a result. We examined the effects of Sans Forgetica relative to a standard control font (Arial) on both correct memory and associative memory errors using the Deese/Roediger-McDermott (DRM) false memory paradigm, to evaluate Sans Forgetica effects on overall memory accuracy. Across four experiments, which included nearly 300 participants, Sans Forgetica was found to have no impact on correct or false memory of DRM lists relative to a standard Arial control font, regardless of whether font type was manipulated within or between subjects or whether memory was assessed via free recall or recognition testing. Our results indicate that Sans Forgetica is ineffective for improving memory accuracy even when accounting for associative memory errors.

Virtual Adaptation of an International Exchange Program in Medical Education.

Medical education has drastically transformed during the COVID-19 pandemic. Measures such as adopting telemedicine visits, minimizing the number of trainees on service, discontinuing external rotations, and converting in-person to online didactics have been broadly and swiftly implemented. While these innovations have promoted greater interconnectivity amongst institutions and made continuing medical education possible, international exchange programs in medical education are still largely disrupted. In response to the changing guidelines and restrictions necessitated by the COVID-19 pandemic, the authors used Kern's six-step approach to design and implement a virtual curriculum to replace the in-person activities of the 2020-2021 Neurology Peru-Rochester exchange program (NeuroPro). Twenty-seven trainees participated in this virtual adaptation. The average daily attendance was ≥85% and the program was rated 9/10 on average in a feedback survey (63% response rate). The median percentage of correct answers during the pre-test was 64% and it increased to 79% during the post-test (P = 0.003). Virtual adaptation of international exchange programs in medical education is feasible to safely continue international collaborative efforts to promote symbiotic building of local expertise and cross-cultural exchange during the ongoing COVID-19 pandemic and beyond.

Reactivity from judgments of learning is not only due to memory forecasting: evidence from associative memory and frequency judgments.

Research has shown that judgments of learning (JOLs) often produce a reactive effect on the learning of cue-target pairs in which target recall differs between participants who provide item-based JOLs at study versus those who do not. Positive reactivity, or the memory improvement found when JOLs are provided, is typically observed on related pairs, while no reactivity is commonly found on unrelated pairs. In four experiments, we examined JOL reactivity effects by comparing JOL and no-JOL groups to other groups who engaged in relational-type encoding/judgment tasks. Experiment 1 replicated positive JOL reactivity effects with related pairs with an extension to symmetrically related pairs. Next, Experiment 2 found that providing judgments of associative memory-a task that does not involve memory predictions-yielded equivalent reactivity patterns as JOLs. Experiment 3 replicated this reactivity pattern using a frequency of co-occurrence judgment task. Finally, In Experiment 4, a similar positive reactivity pattern was found using a relational encoding task when compared to a standard JOL. Collectively, our results suggest that previous JOL reactivity patterns are not solely due to memory forecasting processes via JOLs and likely reflect relational encoding that is strategically applied towards related, but not unrelated pairs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11409-022-09301-2.

Drawing individual images benefits recognition accuracy in the Deese-Roediger-McDermott paradigm.

We examined the effects of drawing on correct and false recognition within the Deese-Roediger-McDermott (DRM) false memory paradigm. In Experiment 1, we compared drawing of a word's referent using either a standard black pencil or coloured pencils relative to a read-only control group. Relative to reading, drawing in either black or coloured pencil similarly boosted correct recognition and reduced false recognition. Signal-detection analyses indicated that drawing reduced the amount of encoded memory information for critical lures and increased monitoring, indicating that both processes contributed to the false recognition reduction. Experiment 2 compared drawing of individual images of DRM list items relative to drawing integrated images using sets of DRM list items. False recognition was lower for drawing of individual images relative to integrated images-a pattern that reflected a decrease in encoded memory information but not monitoring. Therefore, drawing individual images improves memory accuracy in the DRM paradigm relative to a standard read-control task and an integrated-drawing task, which we argue is due to the recruitment of item-specific processing.

The lrd package: An R package and Shiny application for processing lexical data.

Recall testing is a common assessment to gauge memory retrieval. Responses from these tests can be analyzed in several ways; however, the output generated from a recall study typically requires manual coding that can be time intensive and error-prone before analyses can be conducted. To address this issue, this article introduces lrd (Lexical Response Data), a set of open-source tools for quickly and accurately processing lexical response data that can be used either from the R command line or through an R Shiny graphical user interface. First, we provide an overview of this package and include a step-by-step user guide for processing both cued- and free-recall responses. For validation of lrd, we used lrd to recode output from cued, free, and sentence-recall studies with large samples and examined whether the results replicated using lrd-scored data. We then assessed the inter-rater reliability and sensitivity and specificity of the scoring algorithm relative to human-coded data. Overall, lrd is highly reliable and shows excellent sensitivity and specificity, indicating that recall data processed using this package are remarkably consistent with data processed by a human coder.

Private sector initiatives to tackle the burden of COVID-19: experiences from the Nigerian frontline.

Across Africa, there is some evidence of COVID-19 private sector activities to tackle COVID-19 which include the development of rapid diagnostic kits, deployment of e-health platforms for bespoke health workforce training, disease surveillance, reporting, auto-screening and advisories. Inequities in living and access to care by disadvantaged populations in the rural areas have been ameliorated by multi-pronged responses such as that mounted by the Joseph Ukpo Hospitals and Research Institute (JUHRI) in Nigeria. The provision, production and donation of personal protective equipment (PPE), the production of hand sanitizers and the engagement of the local community in the process represents an effective strategy to contain COVID-19, protect health workers and provide pathways for economic support for people whose sources of income have been upended during the pandemic. The JUHRI experience underpinned by Catholic medical ethics provides concrete evidence of the value of private sector participation in dealing with public health emergencies.

High-fat diet induces neuroinflammation and reduces the serotonergic response to escitalopram in the hippocampus of obese rats.

Clinical studies indicate that obese individuals have an increased risk of developing co-morbid depressive illness and that these patients have reduced responses to antidepressant therapy, including selective serotonin reuptake inhibitors (SSRIs). Obesity, a condition of chronic mild inflammation including obesity-induced neuroinflammation, is proposed to contribute to decreases in synaptic concentrations of neurotransmitters like serotonin (5HT) by decreasing 5HT synthesis in the dorsal raphe nucleus (DRN) and/or affecting 5HT reuptake in DRN target regions like the hippocampus. In view of these observations, the goal of the current study was to examine inflammatory markers and serotonergic dynamics in co-morbid obesity and depression. Biochemical and behavioral assays revealed that high-fat diet produced an obesity and depressive-like phenotype in one cohort of rats and that these changes were marked by increases in key pro-inflammatory cytokines in the hippocampus. In real time using fast scan cyclic voltammetry (FSCV), we observed no changes in basal levels of hippocampal 5HT; however responses to escitalopram were significantly impaired in the hippocampus of obese rats compared to diet resistant rats and control rats. Further studies revealed that these neurochemical observations could be explained by increases in serotonin transporter (SERT) expression in the hippocampus driven by elevated neuroinflammation. Collectively, these results demonstrate that obesity-induced increases in neuroinflammation adversely affect SERT expression in the hippocampus of obese rats, thereby providing a potential synaptic mechanism for reduced SSRI responsiveness in obese subjects with co-morbid depressive illness.

Advanced care planning during the COVID-19 pandemic: ceiling of care decisions and their implications for observational data.

BACKGROUND: Observational studies investigating risk factors in coronavirus disease 2019 (COVID-19) have not considered the confounding effects of advanced care planning, such that a valid picture of risk for elderly, frail and multi-morbid patients is unknown. We aimed to report ceiling of care and cardiopulmonary resuscitation (CPR) decisions and their association with demographic and clinical characteristics as well as outcomes during the COVID-19 pandemic. METHODS: Retrospective, observational study conducted between 5th March and 7th May 2020 of all hospitalised patients with COVID-19. Ceiling of care and CPR decisions were documented using the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process. Unadjusted and multivariable regression analyses were used to determine factors associated with ceiling of care decisions and death during hospitalisation. RESULTS: A total of 485 patients were included, of whom 409 (84·3%) had a documented ceiling of care; level one for 208 (50·9%), level two for 75 (18·3%) and level three for 126 (30·8%). CPR decisions were documented for 451 (93·0%) of whom 336 (74·5%) were 'not for resuscitation'. Advanced age, frailty, White-European ethnicity, a diagnosis of any co-morbidity and receipt of cardiovascular medications were associated with ceiling of care decisions. In a multivariable model only advanced age (odds 0·89, 0·86-0·93 p < 0·001), frailty (odds 0·48, 0·38-0·60, p < 0·001) and the cumulative number of co-morbidities (odds 0·72, 0·52-1·0, p = 0·048) were independently associated. Death during hospitalisation was independently associated with age, frailty and requirement for level two or three care. CONCLUSION: Ceiling of care decisions were made for the majority of patients during the COVID-19 pandemic, broadly in line with known predictors of poor outcomes in COVID-19, but with a focus on co-morbidities suggesting ICU admission might not be a reliable end-point for observational studies where advanced care planning is routine.

The deceptive nature of associative word pairs: the effects of associative direction on judgments of learning.

The accuracy of judgments of learning (JOLs) in forecasting later recall of cue-target pairs is sensitive to associative direction. JOLs are generally well calibrated for forward associative pairs (e.g., credit-card), but recall accuracy is often overestimated for backward pairs (e.g., card-credit). The present study further examines the effect of associative direction on JOL accuracy by comparing forward and backward pairs to unrelated pairs and symmetrical associates (e.g., salt-pepper)-a novel comparison. The correspondence between initial JOLs and recall accuracy was examined when study was either self-paced with concurrent JOLs (Experiment 1), when study/JOL duration was equated across pair types (Experiment 2), when JOLs were made immediately following study (Experiment 3), and when JOLs were made after a delay (Experiment 4). Across experiments, JOLs accurately estimated correct recall for forward pairs, but overestimated recall for symmetrical, backward, and unrelated pairs-an overestimation that was particularly robust for backward pairs. Calibration plots depicting JOL ratings against their corresponding recall accuracy indicated overestimations occurred for all pair types, though overestimations only occurred at high JOL ratings for symmetrical and forward pairs, a qualitative difference that was not captured in standard analyses of mean JOL and recall rates.

Insight Into Myocardial Microstructure of Athletes and Hypertrophic Cardiomyopathy Patients Using Diffusion Tensor Imaging.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) remains the commonest cause of sudden cardiac death among young athletes. Differentiating between physiologically adaptive left ventricular (LV) hypertrophy observed in athletes' hearts and pathological HCM remains challenging. By quantifying the diffusion of water molecules, diffusion tensor imaging (DTI) MRI allows voxelwise characterization of myocardial microstructure. PURPOSE: To explore microstructural differences between healthy volunteers, athletes, and HCM patients using DTI. STUDY TYPE: Prospective cohort. POPULATION: Twenty healthy volunteers, 20 athletes, and 20 HCM patients. FIELD STRENGTH/SEQUENCE: 3T/DTI spin echo. ASSESSMENT: In-house MatLab software was used to derive mean diffusivity (MD) and fractional anisotropy (FA) as markers of amplitude and anisotropy of the diffusion of water molecules, and secondary eigenvector angles (E2A)-reflecting the orientations of laminar sheetlets. STATISTICAL TESTS: Independent samples t-tests were used to detect statistical significance between any two cohorts. Analysis of variance was utilized for detecting the statistical difference between the three cohorts. Statistical tests were two-tailed. A result was considered statistically significant at P ≤ 0.05. RESULTS: DTI markers were significantly different between HCM, athletes, and volunteers. HCM patients had significantly higher global MD and E2A, and significantly lower FA than athletes and volunteers. (MDHCM = 1.52 ± 0.06 × 10-3 mm2 /s, MDAthletes = 1.49 ± 0.03 × 10-3 mm2 /s, MDvolunteers = 1.47 ± 0.02 × 10-3 mm2 /s, P < 0.05; E2AHCM = 58.8 ± 4°, E2Aathletes = 47 ± 5°, E2Avolunteers = 38.5 ± 7°, P < 0.05; FAHCM = 0.30 ± 0.02, FAAthletes = 0.35 ± 0.02, FAvolunteers = 0.36 ± 0.03, P < 0.05). HCM patients had significantly higher E2A in their thickest segments compared to the remote (E2Athickest = 66.8 ± 7, E2Aremote = 51.2 ± 9, P < 0.05). DATA CONCLUSION: DTI depicts an increase in amplitude and isotropy of diffusion in the myocardium of HCM compared to athletes and volunteers as reflected by increased MD and decreased FA values. While significantly higher E2A values in HCM and athletes reflect steeper configurations of the myocardial sheetlets than in volunteers, HCM patients demonstrated an eccentric rise in E2A in their thickest segments, while athletes demonstrated a concentric rise. Further studies are required to determine the diagnostic capabilities of DTI. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 2.