A highly predictive cardiac positron emission tomography (PET) risk score for 90-day and one-year major adverse cardiac events and revascularization.

BACKGROUND: With the increase in cardiac PET/CT availability and utilization, the development of a PET/CT-based major adverse cardiovascular events, including death, myocardial infarction (MI), and revascularization (MACE-Revasc) risk assessment score is needed. Here we develop a highly predictive PET/CT-based risk score for 90-day and one-year MACE-Revasc. METHODS AND RESULTS: 11,552 patients had a PET/CT from 2015 to 2017 and were studied for the training and development set. PET/CT from 2018 was used to validate the derived scores (n = 5049). Patients were on average 65 years old, half were male, and a quarter had a prior MI or revascularization. Baseline characteristics and PET/CT results were used to derive the MACE-Revasc risk models, resulting in models with 5 and 8 weighted factors. The PET/CT 90-day MACE-Revasc risk score trended toward outperforming ischemic burden alone [P = .07 with an area under the curve (AUC) 0.85 vs 0.83]. The PET/CT one-year MACE-Revasc score was better than the use of ischemic burden alone (P < .0001, AUC 0.80 vs 0.76). Both PET/CT MACE-Revasc risk scores outperformed risk prediction by cardiologists. CONCLUSION: The derived PET/CT 90-day and one-year MACE-Revasc risk scores were highly predictive and outperformed ischemic burden and cardiologist assessment. These scores are easy to calculate, lending to straightforward clinical implementation and should be further tested for clinical usefulness.

Pathologists aren't pigeons: exploring the neural basis of visual recognition and perceptual expertise in pathology.

Visual (perceptual) reasoning is a critical skill in many medical specialties, including pathology, diagnostic imaging, and dermatology. However, in an ever-compressed medical curriculum, learning and practicing this skill can be challenging. Previous studies (including work with pigeons) have suggested that using reward-feedback-based activities, novices can gain expert levels of visual diagnostic accuracy in shortened training times. But is this level of diagnostic accuracy a result of image recognition (categorization) or is it the acquisition of diagnostic expertise? To answer this, the authors measured electroencephalographic data (EEG) and two components of the human event-related brain potential (reward positivity and N170) to explore the nature of visual expertise in a novice-expert study in pathology visual diagnosis. It was found that the amplitude of the reward positivity decreased with learning in novices (suggesting a decrease in reliance on feedback, as in other studies). However, this signal remained significantly different from the experts whose reward positivity signal did not change over the course of the experiment. There were no changes in the amplitude of the N170 (a reported neural marker of visual expertise) in novices over time. Novice N170 signals remained statistically and significantly lower in amplitude compared to experts throughout task performance. These data suggest that, while novices gained the ability to recognize (categorize) pathologies through reinforcement learning as quantified by the change in reward positivity, increased accuracy, and decreased time for responses, there was little change in the neural marker associated with visual expertise (N170). This is consistent with the multi-dimensional and complex nature of visual expertise and provides insight into future training programs for novices to bridge the expertise gap.

Exploring the development of interprofessional competence and professional identity: A Situated Learning Theory study.

Workplace-based learning provides medical students exposure to interprofessional competencies through repeated exposures and active participation in interprofessional learning activities. Using Situated Learning Theory as our theoretical lens, we explored with medical students how interacting with existing interprofessional teams contributes to development of an expanded health care professional identity. An embedded mixed methods study using semi-structured interviews and questionnaires to assess readiness for interprofessional learning was conducted with 14 medical students completing an elective at an interprofessional pain medicine clinic. Within this workplace-based context, a model identifying key themes and supporting factors contributing to the development of an extended professional identity was developed. These findings help describe the processes by which students gain interprofessional collaboration competence.

What role does basic research have in an applied field?

Research in health professions education has often been portrayed as an applied field, one that draws on more basic forms of research in pursuing what are primarily practical ends. While there is an undeniable practical side to much of the work published in our field, and in this Journal in particular, this can be problematic when the necessary basic research is not extant. In this editorial, two of this Journal's editors consider some of the challenges in bridging these basic research gaps in an erstwhile applied field, and the implications for the kinds of research we undertake and for the identity of the field as a whole.

Building Clinical Skills Teaching Materials: A Study of Cognitive Task Analysis Versus Free Recall Instruction to Teach Canine Indirect Ophthalmoscopy.

Ophthalmoscopy is a core component of a complete ophthalmic examination. Due to its complex technical aspects and patients becoming uncooperative if the procedure is prolonged, it can be a difficult skill for a novice to learn and develop proficiency in. Skills instruction is typically provided by subject matter experts (SMEs) through free recall without an agreed-upon instructional framework. This can lead to unintentional omission of essential steps and knowledge required to perform skills correctly. Cognitive task analysis (CTA) allows for construction of standardized instructional protocols that encompass the knowledge and skills experts apply when performing tasks. The objectives of this study were to (a) develop a CTA-based teaching protocol for canine indirect ophthalmoscopy and (b) compare the steps verbalized or demonstrated by SMEs during free recall instruction versus those ultimately identified by CTA. Four SMEs participated in free recall instructional sessions and interviews used for the development of a CTA-based teaching protocol for novice learners. The CTA-based protocol identified 66 steps and sub-steps considered essential for successfully performing canine indirect ophthalmoscopy. During instructional sessions, SMEs on average failed to verbalize 57.1% of clinical knowledge steps, did not verbalize or demonstrate 68.3% and 9.5% of action steps, and did not verbalize or demonstrate 73.2% and 40.4% of decision steps, respectively. This study demonstrates that SMEs teaching indirect ophthalmoscopy by free recall may unintentionally omit important steps, suggesting that compared with free recall, CTA may generate more comprehensive and thus potentially more effective instructional materials for teaching technical skills in veterinary medicine.

What Matters Most to Residency and Intern Selection Committees in Veterinary Medicine?

A recent survey of members of residency selection committees for the American College of Veterinary Internal Medicine and American College of Veterinary Surgeons boards found letters of recommendation to be the most important factor when reviewing a resident's application followed by class rank as the second most important factor. These statistics indicate an interesting, but possibly troubling trend. This Letter to The Editor discusses the major problems concerning these findings and what residency program committees might consider as an alternative.

Comparing Entrustment and Competence: An Exploratory Look at Performance-Relevant Information in the Final Year of a Veterinary Program.

Workplace-based assessments and entrustment scales have two primary goals: providing formative information to assist students with future learning; and, determining if and when learners are ready for safe, independent practice. To date, there has not been an evaluation of the relationship between these performance-relevant information pieces in veterinary medicine. This study collected quantitative and qualitative data from a single cohort of final-year students (n = 27) across in-training evaluation reports (ITERs) and entrustment scales in a distributed veterinary hospital environment. Here we compare progression in scoring and performance within and across student, within and across method of assessment, over time. Narrative comments were quantified using the Completed Clinical Evaluation Report Rating (CCERR) instrument to assess quality of written comments. Preliminary evidence suggests that we may be capturing different aspects of performance using these two different methods. Specifically, entrustment scale scores significantly increased over time, while ITER scores did not. Typically, comments on entrustment scale scores were more learner specific, longer, and used more of a coaching voice. Longitudinal evaluation of learner performance is important for learning and demonstration of competence; however, the method of data collection could influence how feedback is structured and how performance is ultimately judged.

Development of and Validity Evidence for a Canine Ocular Model for Training Novice Veterinary Students to Perform a Fundic Examination.

Indirect fundoscopy is challenging for novice learners, as patients are often intolerant of the procedure, impeding development of proficiency. To address this, we developed a canine ocular simulator that we hypothesized would improve student learning compared to live dogs. Six board-certified veterinary ophthalmologists and 19 second-year veterinary students (novices) performed an indirect fundic examination on the model and live dog. Prior to assessment, novices were introduced to the skill with a standardized teaching protocol and practiced (without feedback) with either the model (n = 10) or live dog (n = 9) for 30 minutes. All participants evaluated realism and usefulness of the model using a Likert-type scale. Performance on the live dog and model was evaluated in all participants using time to completion of task, performance of fundic examination using a checklist and global score, identification of objects in the fundus of the model, and evaluation of time spent looking at the fundus of the model using eye tracking. Novices (trained on simulator or live dogs) were compared in fundic examination performance on the live dog and identification of shapes in the model. In general, experts performed the fundic examination faster (p ≤ .0003) and more proficiently than the novices, although there were no differences in eye tracking behavior between groups (p ≥ .06). No differences were detected between training on simulator versus live dog in development of fundoscopy skills in novices (p ≥ .20). These findings suggest that this canine model may be an effective tool to train students to perform fundoscopy.

Photoconversion of DAPI and Hoechst dyes to green and red-emitting forms after exposure to UV excitation.

The fluorescent dye 4'-6-Diamidino-2-phenylindole (DAPI) is frequently used in fluorescence microscopy as a chromosome and nuclear stain because of its high specificity for DNA. Normally, DAPI bound to DNA is maximally excited by ultraviolet (UV) light at 358 nm, and emits maximally in the blue range, at 461 nm. Hoechst dyes 33258 and 33342 have similar excitation and emission spectra and are also used to stain nuclei and chromosomes. It has been reported that exposure to UV can convert DAPI and Hoechst dyes to forms that are excited by blue light and emit green fluorescence, potentially confusing the interpretation of experiments that use more than one fluorochrome. The work reported here shows that these dyes can also be converted to forms that are excited by green light and emit red fluorescence. This was observed both in whole tissues and in mitotic chromosome spreads, and could be seen with less than 10-s exposure to UV. In most cases, the red form of fluorescence was more intense than the green form. Therefore, appropriate care should be exercised when examining tissues, capturing images, or interpreting images in experiments that use these dyes in combination with other fluorochromes.

Dynamics of change in multiethnic societies: An archaeological perspective from colonial North America.

This Perspective presents an overview of the archaeology of pluralistic colonies (approximately late 1500s-1800s) in North America. It complements the other special feature papers in this issue on ancient societies in Mesoamerica, the Near East, the Armenian Highlands, Peru, and China by presenting another body of literature for examining the dynamics of change in multiethnic societies from a different time and place. In synthesizing archaeological investigations of mercantile, plantation, and missionary colonies, this Perspective shows how this research is relevant to the study of pluralism in both historic and ancient societies in three ways. (i) It enhances our understanding of interethnic relationships that took place in complex societies with imposing political hierarchies and labor structures. (ii) It helps us to refine the methods used by archaeologists to define and analyze multiethnic communities that were spatially delimited by ethnic neighborhoods. Finally, (iii) it presents more than a half century of experimentation with various models (e.g., acculturation, creolization, ethnogenesis, and hybridity) that have been used to study the dynamics of culture change in multiethnic societies.

Corp Regulates P53 in Drosophila melanogaster via a Negative Feedback Loop.

The tumor suppressor P53 is a critical mediator of the apoptotic response to DNA double-strand breaks through the transcriptional activation of pro-apoptotic genes. This mechanism is evolutionarily conserved from mammals to lower invertebrates, including Drosophila melanogaster. P53 also transcriptionally induces its primary negative regulator, Mdm2, which has not been found in Drosophila. In this study we identified the Drosophila gene companion of reaper (corp) as a gene whose overexpression promotes survival of cells with DNA damage in the soma but reduces their survival in the germline. These disparate effects are shared by p53 mutants, suggesting that Corp may be a negative regulator of P53. Confirming this supposition, we found that corp negatively regulates P53 protein level. It has been previously shown that P53 transcriptionally activates corp; thus, Corp produces a negative feedback loop on P53. We further found that Drosophila Corp shares a protein motif with vertebrate Mdm2 in a region that mediates the Mdm2:P53 physical interaction. In Corp, this motif mediates physical interaction with Drosophila P53. Our findings implicate Corp as a functional analog of vertebrate Mdm2 in flies.

Frequency and prognostic factors of olfactory dysfunction after traumatic brain injury.

OBJECTIVE: To assess the frequency and factors associated with posttraumatic olfactory dysfunction, including anosmia, in a follow-up of patients with moderate and severe traumatic brain injury (TBI). METHODS: The setting was a cross-sectional study of patients that were consecutively included in the Trondheim TBI database, comprising injury-related variables. Eligible participants 18-65 years were contacted 9-104 months post trauma and asked olfactory-related questions. Those reporting possible posttraumatic change of olfaction were invited to further examination using the Sniffin' Sticks panel. RESULTS: Of 211 eligible participants, 182 (86.3%) took part in telephone interviews and 25(13.7%) were diagnosed with olfactory dysfunction. 60% of these, or 8.2% of all participants, had anosmia. In age-adjusted logistic regression analyses, fall (OR 2.5, 95% CI 1.0-6.2), skull base fracture (OR 2.9, 95% CI 1.2-7.1) and cortical contusion(s) (OR 6.0, 95% CI 2.1-17.3) were associated with olfactory dysfunction. In an analysis of anosmia, fall (OR 3.4, 95% CI 1.1-10.6) and cortical contusion(s) (OR 19.7, 95% CI 2.5-156.0) were associated with the outcome. CONCLUSION: Of the study participants 13.7% had olfactory dysfunction and 8.2% had anosmia. Higher age, trauma caused by fall and CT displaying skull base fracture and cortical contusion(s) were related to olfactory dysfunction.

Selection for family medicine residency training in Canada: How consistently are the same students ranked by different programs?

OBJECTIVE: To examine the consistency of the ranking of Canadian and US medical graduates who applied to Canadian family medicine (FM) residency programs between 2007 and 2013. DESIGN: Descriptive cross-sectional study. SETTING: Family medicine residency programs in Canada. PARTICIPANTS: All 17 Canadian medical schools allowed access to their anonymized program rank-order lists of students applying to FM residency programs submitted to the first iteration of the Canadian Resident Matching Service match from 2007 to 2013. MAIN OUTCOME MEASURES: The rank position of medical students who applied to more than 1 FM residency program on the rank-order lists submitted by the programs. Anonymized ranking data submitted to the Canadian Resident Matching Service from 2007 to 2013 by all 17 FM residency programs were used. Ranking data of eligible Canadian and US medical graduates were analyzed to assess the within-student and between-student variability in rank score. These covariance parameters were then used to calculate the intraclass correlation coefficient (ICC) for all programs. Program descriptions and selection criteria were also reviewed to identify sites with similar profiles for subset ICC analysis. RESULTS: Between 2007 and 2013, the consistency of ranking by all programs was fair at best (ICC = 0.34 to 0.39). The consistency of ranking by larger urban-based sites was weak to fair (ICC = 0.23 to 0.36), and the consistency of ranking by sites focusing on training for rural practice was weak to moderate (ICC = 0.16 to 0.55). CONCLUSION: In most cases, there is a low level of consistency of ranking of students applying for FM training in Canada. This raises concerns regarding fairness, particularly in relation to expectations around equity and distributive justice in selection processes.

Target engagement and histopathology of neuraxial resiniferatoxin in dog.

OBJECTIVE: To evaluate target engagement of intracisternally (IC) delivered TRPV1 agonist, resiniferatoxin (RTX), as measured by primary afferent and dorsal horn substance P immunoreactivity (sP-IR), histopathology and thermal escape latencies in dogs. STUDY DESIGN: Prospective experimental trial. ANIMALS: Fourteen adult male Beagle dogs, weighing 10.3-13.2 kg; 11 dogs surviving to scheduled euthanasia. METHODS: Anesthetized dogs were randomly assigned to be administered IC RTX (3.6 µg, 0.1 mL kg-1) in a hyperbaric (hRTX, n = 6), normobaric (nRTX, n = 4) vehicle or a hyperbaric vehicle (hVehicle, n = 4). Over 16 days, animals were examined for thoracic and pelvic limb paw thermal withdrawal latencies and neurologic function. Spinal cords, trigeminal ganglia and dorsal root ganglia (DRGs) were assessed for morphologic changes and sP-IR. RESULTS: IC RTX in anesthetized dogs resulted in a < 1 hour increase in blood pressure. Acute reactions leading to euthanasia within 8 hours occurred in three dogs (two hRTX, one nRTX). All other animals recovered with normal neurologic, bowel and bladder function. Final groups were: vehicle n = 4, hRTX n = 4 and nRTX n = 3. Animals in nRTX and hRTX showed increases in escape latencies in thoracic paws and, to a lesser extent, in pelvic paws, correlating to a loss of sP-IR in cervical cord with smaller reductions in thoracic and lumbar cord. In animals surviving to euthanasia, thickening of the arachnoid membrane (predominantly in the cervical region) was the most consistent change. This change, present in controls, was interpreted to be vehicle related. There was no evidence of structural changes in brain and spinal cord. CONCLUSIONS AND CLINICAL RELEVANCE: IC RTX produced localized loss of spinal and DRG sP with a corresponding thermal analgesia, absent motor impairment or spinal pathology. Loss of three animals emphasizes the need to refine the use of this promising therapeutic modality in managing companion animal pain.

Sedation levels in dogs: a validation study.

BACKGROUND: The aim of this study was to assess validation evidence for a sedation scale for dogs. We hypothesized that the chosen sedation scale would be unreliable when used by different raters and show poor discrimination between sedation protocols. A sedation scale (range 0-21) was used to score 62 dogs scheduled to receive sedation at two veterinary clinics in a prospective trial. Scores recorded by a single observer were used to assess internal consistency and construct validity of the scores. To assess inter-rater reliability, video-recordings of sedation assessment were randomized and blinded for viewing by 5 raters untrained in the scale. Videos were also edited to allow assessment of inter-rater reliability of an abbreviated scale (range 0-12) by 5 different raters. RESULTS: Both sedation scales exhibited excellent internal consistency and very good inter-rater reliability (full scale, intraclass correlation coefficient [ICCsingle] = 0.95; abbreviated scale, ICCsingle = 0.94). The full scale discriminated between the most common protocols: dexmedetomidine-hydromorphone (median [range] of sedation score, 11 [1-18], n = 20) and acepromazine-hydromorphone (5 [0-15], n = 36, p = 0.02). CONCLUSIONS: The hypothesis was rejected. Full and abbreviated scales showed excellent internal consistency and very good reliability between multiple untrained raters. The full scale differentiated between levels of sedation.

Chk2 and p53 regulate the transmission of healed chromosomes in the Drosophila male germline.

When a dicentric chromosome breaks in mitosis, the broken ends cannot be repaired by normal mechanisms that join two broken ends since each end is in a separate daughter cell. However, in the male germline of Drosophila melanogaster, a broken end may be healed by de novo telomere addition. We find that Chk2 (encoded by lok) and P53, major mediators of the DNA damage response, have strong and opposite influences on the transmission of broken-and-healed chromosomes: lok mutants exhibit a large increase in the recovery of healed chromosomes relative to wildtype control males, but p53 mutants show a strong reduction. This contrasts with the soma, where mutations in lok and p53 have the nearly identical effect of allowing survival and proliferation of cells with irreparable DNA damage. Examination of testes revealed a transient depletion of germline cells after dicentric chromosome induction in the wildtype controls, and further showed that P53 is required for the germline to recover. Although lok mutant males transmit healed chromosomes at a high rate, broken chromosome ends can also persist through spermatogonial divisions without healing in lok mutants, giving rise to frequent dicentric bridges in Meiosis II. Cytological and genetic analyses show that spermatid nuclei derived from such meiotic divisions are eliminated during spermiogenesis, resulting in strong meiotic drive. We conclude that the primary responsibility for maintaining genome integrity in the male germline lies with Chk2, and that P53 is required to reconstitute the germline when cells are eliminated owing to unrepaired DNA damage.

Vegetation effects on impulsive events in the acoustic signature of fires.

Acoustic impulse events have long been used as diagnostics for discrete phenomena in the natural world, including the detection of meteor impacts and volcanic eruptions. Wildland fires display an array of such acoustic impulse events in the form of crackling noises. Exploratory research into the properties of these impulse events revealed information regarding the specific properties of plant material. Unique acoustic frequency bands in the upper end of the sonic spectrum correlated to changes in vegetation properties. The signature of acoustic impulse events as they relate to plant species and plant water stress, were investigated in controlled laboratory combustion experiments. Correlation in the frequency range of 6.0-15.0 kHz was found for both species and water stress, indicating the possibility that a digital filter may be capable of identifying vegetation properties during wildland fire events.

Working memory, reasoning, and expertise in medicine-insights into their relationship using functional neuroimaging.

Clinical reasoning is dependent upon working memory (WM). More precisely, during the clinical reasoning process stored information within long-term memory is brought into WM to facilitate the internal deliberation that affords a clinician the ability to reason through a case. In the present study, we examined the relationship between clinical reasoning and WM while participants read clinical cases with functional magnetic resonance imaging (fMRI). More specifically, we examined the impact of clinical case difficulty (easy, hard) and clinician level of expertise (2nd year medical students, senior gastroenterologists) on neural activity within regions of cortex associated with WM (i.e., the prefrontal cortex) during the reasoning process. fMRI was used to scan ten second-year medical students and ten practicing gastroenterologists while they reasoned through sixteen clinical cases [eight straight forward (easy) and eight complex (hard)] during a single 1-h scanning session. Within-group analyses contrasted the easy and hard cases which were then subsequently utilized for a between-group analysis to examine effects of expertise (novice > expert, expert > novice). Reading clinical cases evoked multiple neural activations in occipital, prefrontal, parietal, and temporal cortical regions in both groups. Importantly, increased activation in the prefrontal cortex in novices for both easy and hard clinical cases suggests novices utilize WM more so than experts during clinical reasoning. We found that clinician level of expertise elicited differential activation of regions of the human prefrontal cortex associated with WM during clinical reasoning. This suggests there is an important relationship between clinical reasoning and human WM. As such, we suggest future models of clinical reasoning take into account that the use of WM is not consistent throughout all clinical reasoning tasks, and that memory structure may be utilized differently based on level of expertise.

Hemispheric activation differences in novice and expert clinicians during clinical decision making.

Clinical decision making requires knowledge, experience and analytical/non-analytical types of decision processes. As clinicians progress from novice to expert, research indicates decision-making becomes less reliant on foundational biomedical knowledge and more on previous experience. In this study, we investigated how knowledge and experience were reflected in terms of differences in neural areas of activation. Novice and expert clinicians diagnosed simple or complex (easy, hard) cases while functional magnetic resonance imaging (fMRI) data were collected. Our results highlight key differences in the neural areas activated in novices and experts during the clinical decision-making process. fMRI data were collected from ten second year medical students (novices) and ten practicing gastroenterologists (experts) while they diagnosed sixteen (eight easy and eight hard) clinical cases via multiple-choice questions. Behavioral data were collected for diagnostic accuracy (correct/incorrect diagnosis) and time taken to assign a clinical diagnosis. Two analyses were performed with the fMRI data. First, data from easy and hard cases were compared within respective groups (easy > hard, hard > easy). Second, neural differences between novices and experts (novice > expert, expert > novice) were assessed. Experts correctly diagnosed more cases than novices and made their diagnoses faster than novices on both easy and hard cases (all p's < 0.05). Time taken to diagnose hard cases took significantly longer for both novices and experts. While similar neural areas were activated in both novices and experts during the decision making process, we identified significant hemispheric activation differences between novice and expert clinicians when diagnosing hard clinical cases. Specifically, novice clinicians had greater activations in the left anterior temporal cortex and left ventral lateral prefrontal cortex whereas expert clinicians had greater activations in the right dorsal lateral, right ventral lateral, and right parietal cortex. Hemispheric differences in activation were not observed between novices and experts while diagnosing easy clinical cases. While clinical decision-making engaged the prefrontal cortex (PFC) in both novices and experts, interestingly we observed expertise related differences in the regions and hemispheres of PFC activation between these groups for hard clinical cases. Specifically, in novices we observed activations in left hemisphere neural regions associated with factual rule-based knowledge, whereas in experts we observed right hemisphere activation in neural regions associated with experiential knowledge. Importantly, at the neural level, our data highlight differences in so called type 2 clinical decision-making processes related to prior knowledge and experience.