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Objective: Timely cancer treatment improves survival and anxiety for some sites. Patients with esophageal cancer require specific workup before treatment, which can prolong the time from diagnosis to treatment (treatment interval [TI]). The geographical variation of this interval remains uninvestigated in patients with esophageal cancer. Methods: This retrospective population-level study conducted in Ontario used linked administrative health care databases. Patients treated for esophageal cancer between 2013 and 2018 were included. The TI was time from diagnosis to treatment. Patients were assigned a geographical Local Health Integration Network on the basis of postal code. Covariates included patient, disease, and diagnosing physician characteristics. Quantile regression modeled TI length at the 50th and 90th percentile and identified associated factors. Results: Of 7509 patients, 78% were male and most were aged between 60 and 69 years. The 50th and 90th percentile TI was 36 (interquartile range, 22-55) and 77 days, respectively. The difference between the Local Health Integration Network with the longest and shortest TI at the 50th and 90th percentile was 18 and 25 days, respectively. Older age (P

Patients with resectable esophageal cancer are recommended to undergo chemoradiotherapy before esophagectomy. A longer time to surgery (TTS) and/or time to consultation (TTC) may be associated with inferior cancer-related outcomes and heightened anxiety. Thoracic cancer surgery centers (TCSCs) oversee esophageal cancer management, but differences in TTC/TTS between centers have not yet been examined. This Ontario population-level study used linked administrative healthcare databases to investigate patients with esophageal cancer between 2013–2018, who underwent neoadjuvant chemoradiotherapy and then surgery. TTC and TTS were time from diagnosis to the first surgical consultation and then to surgery, respectively. Patients were assigned a TCSC based on the location of the surgery. Patient, disease, and diagnosing physician characteristics were investigated. Quantile regression was used to model TTS/TTC at the 50th and 90th percentiles and identify associated factors. The median TTS and TTC were 130 and 29 days, respectively. The adjusted differences between the TCSCs with the longest and shortest median TTS and TTC were 32 and 18 days, respectively. Increasing age was associated with a 16-day longer median TTS. Increasing material deprivation was associated with a 6-day longer median TTC. Significant geographic variability exists in TTS and TTC. Therefore, the investigation of TCSC characteristics is warranted. Shortening wait times may reduce patient anxiety and improve the control of esophageal cancer.

Abstract Background The 8th edition UICC/AJCC TNM8 (Tumour, Nodes, Metastasis) melanoma staging system introduced several modifications from the 7th edition (TNM7), resulting in changes in survival and subgroup composition. We set out to address the limited validation of TNM8 (stages I-IV) in large population-based datasets. Methods This retrospective cohort-study included 6,414 patients from the population-based Ontario Cancer Registry diagnosed with cutaneous melanoma between January 1, 2007 and December 31, 2012. Kaplan–Meier curves estimated the melanoma-specific survival (MSS) and overall survival (OS). Cox proportional hazard models were used to estimate adjusted hazard ratios for MSS and OS across stage groups. The Schemper-Henderson measure was used to assess the variance explained in the Cox regression. Results In our sample, 21.3% of patients were reclassified with TNM8 from TNM7; reclassifications in stage II were uncommon, and 44.1% of patients in stage III were reclassified to a higher subgroup. Minimal changes in MSS curves were observed between editions, but the stage IIB curve decreased and the stage IIIC curve increased. For TNM8, Stage I (n = 4,556), II (n = 1,206), III (n = 598), and IV (n = 54) had an estimated 5-year MSS of 98.4%, 82.5%, 66.4%, and 14.4%, respectively. Within stage III, IIIA 5-year MSS was 91.7% while stage IIID was 23.5%. HRs indicated that TNM8 more evenly separates subgroups once adjusted for patient- and disease-characteristics. The variance in MSS explained by TNM7 and TNM8 is 18.9% and 19.7%, respectively. Conclusion TNM8 performed well in our sample, with more even separation of stage subgroups and a modest improvement in predictive ability compared to TNM7.

We introduce a new experience design tool, an experience journey map, to assist youth professionals in planning engagement, immersion, and absorption activities. Experience journey maps are based on customer journey maps, which are widely used in business service design. This new approach highlights strategies for engendering deep structured experiences during the activity. An experience journey map is a matrix of columns and rows. Columns represent the sequence of activity stages. Rows are experience-structuring strategies derived from the theory of structured experience. These strategies include service performance strategies, deep structured experience strategies, and engagement, immersion, and absorption strategies. We present a case study showing how the experience journey map can be used to plan impactful youth activities.

Abstract The emergence of infections by carbapenem resistant Enterobacteriaceae (CRE) pathogens has created an urgent public health threat, as carbapenems are among the drugs of last resort for infections caused by a growing fraction of multi-drug resistant (MDR) bacteria. There is global consensus that new preventive and therapeutic strategies are urgently needed to combat the growing problem of MDR bacterial infections. Here, we report on the efficacy of a novel macrocyclic peptide, minimized theta-defensin (MTD)-12813 in CRE sepsis. MTD12813 is a theta-defensin inspired cyclic peptide that is highly effective against CRE pathogens K. pneumoniae and E. coli in vivo. In mouse septicemia models, single dose administration of MTD12813 significantly enhanced survival by promoting rapid host-mediated bacterial clearance and by modulating pathologic cytokine responses, restoring immune homeostasis, and preventing lethal septic shock. The peptide lacks direct antibacterial activity in the presence of mouse serum or in peritoneal fluid, further evidence for its indirect antibacterial mode of action. MTD12813 is highly stable in biological matrices, resistant to bacterial proteases, and nontoxic to mice at dose levels 100 times the therapeutic dose level, properties which support further development of the peptide as a first in class anti-infective therapeutic.

Objectives Regional variation in cancer survival is an important health system performance measurement. We evaluated if regional variation in colon cancer survival may be driven by differences in the patient population, their health and healthcare utilisation, and/or cancer care delivery.Design Population-based retrospective cohort study using routinely collected linked health administrative data.Setting Ontario, Canada.Participants Patients with colon cancer diagnosed between 1 January 2009 and 31 December 2012.Outcome Cancer-specific survival was compared across the province’s 14 health regions. Using accelerated failure time models, we assessed whether regional survival variations were mediated through differences in case mix, including age, sex, comorbidities, stage at diagnosis and colon subsite, potential marginalisation and/or prediagnosis healthcare.Results The study population included 16 895 patients with colon cancer. There was statistically significant regional variation in cancer-specific survival. Three regions had cancer-specific survival that was between 30% (95% CI 1.03 to 1.65) and 39% (95% CI 1.13 to 1.71) longer and one region had cancer-specific survival that was 26% shorter (95% CI 0.58 to 0.93) than the reference region. For three of these regions, case mix explained between 26% and 56% of the survival variation. Further adjustment for rurality explained 22% of the remaining survival variation in one region. Adjustment for continuity of primary care and the diagnostic interval length explained 10% and 11% of the remaining survival variation in two other regions. Socioeconomic marginalisation, recent immigration and colonoscopy history did not explain colon cancer survival variation.Conclusions Case mix accounted for much of the regional variation in colon cancer survival, indicating that efforts to monitor the quality of cancer care through survival metrics should consider case mix when reporting regional survival differences. Future work should repeat this approach in other settings and other cancer sites considering a broad range of potential mediators.

Abstract Background Advanced cancer stage at diagnosis may explain high cancer mortality among patients with a severe psychiatric illness (SPI). Studies to date investigating advanced stage cancer at diagnosis as a potential explanation for high cancer mortality in individuals with a history of mental illness have been inconclusive. We examined the relationship between a SPI history and unknown cancer stage at diagnosis in colorectal cancer (CRC) patients. Methods This was a population-based, cross-sectional study using linked administrative databases of CRC patients diagnosed between 01/04/2007 and 31/12/2012. Individuals who had a history of mental illness but did not meet the definition of a SPI were excluded. An SPI was measured in the 5 years prior to the cancer diagnosis and categorized as inpatient, outpatient or no SPI. Individuals with a best stage in Stage 0 to Stage IV were considered staged and absence of staging information was defined as unknown stage. The risk of unknown stage cancer was estimated using modified Poisson regression. Results The final study cohort included 24,507 CRC patients. 258 (1.1%) individuals experienced a history of inpatient SPI and 482 (2.0%) experienced outpatient SPI. After adjusting for confounders, CRC patients with an inpatient or outpatient history of SPI were at greater risk of having missing TNM stage at diagnosis, compared to patients with no history of a mental illness (RR 1.45 (95% CI: 1.14–1.85) and RR1.17 (95% CI 0.95–1.43), respectively). The results did not change when alternate practices to assign SPI history using administrative data were used. Conclusions Individuals with an SPI, especially those with a psychiatric admission, were more likely to have missing stage data compared to individuals without a history of a mental illness. Incomplete and low quality cancer staging data likely undermines the quality of cancer care following initial diagnosis. Understanding why patients with an SPI are missing this information is a critical first step to providing excellent care to this vulnerable population.

Abstract Background In order to maximize later health, there are established components and guidelines for quality follow-up care of breast cancer survivors. However, adherence to quality follow-up in Canada may not be optimal, and may vary by province. We determined and compared the proportion of patients in each province who received adherent and non-adherent surveillance for recurrence, new cancers and late effects, recommended preventive care, and recommended physician visits for comorbidities. Methods Cohorts consisted of all adult women diagnosed with incident invasive breast cancer between 2007 and 2010/2012 in four Canadian provinces (British Columbia (BC) N = 9338; Manitoba N = 2688; Ontario N = 23,700; Nova Scotia (NS) N = 2735), identified from provincial cancer registries, alive and cancer-free at 30 months post-diagnosis. Their healthcare utilization was determined from one to 5 years post-treatment, using linked administrative databases. Adherence, underuse, and overuse of recommended services were evaluated yearly and compared using descriptive statistics. Results In all provinces and follow-up years, the majority of survivors had more than the recommended number of visits to either an oncologist or primary care physician (range 53.8% NS Year 3; 85.8% Ontario Year 4). The proportion of patients with the guideline-recommended number of oncologist visits varied by province (range 29.8% BC Year 5; 74.8% Ontario Year 5), and the proportion of patients with less than the recommended number of specified breast cancer-related visits with either an oncologist or primary care physician ranged from 32.6% (Ontario Year 2) to 84.4% (NS Year 3). Underuse of surveillance breast imaging was identified in NS and BC. The proportion of patients receiving imaging for metastatic disease (not recommended in the guidelines) in BC, Manitoba, and Ontario (not reported in NS) ranged from 20.3% (BC Year 5) to 53.3% (Ontario Year 2). Compliance with recommended physician visits for patients with several chronic conditions was high in Ontario and NS. Preventive care was less than optimal in all provinces with available data. Conclusions Quality of breast cancer survivor follow-up care varies among provinces. Results point to exploration of factors affecting differences, province-specific opportunities for care improvement, and the value of administrative datasets for health system assessment.

Abstract Background The overuse of medical tests leads to higher costs, wasting of resources, and the potential for overdiagnosis of disease. This study was designed to determine whether the patients of family doctors who order more routine medical tests are diagnosed with more cancers. Method A retrospective population‐based cross‐sectional study using administrative health care data in Ontario Canada. We investigated the ordering of 23 routine laboratories and imaging tests 2008‐20012 by 6849 Ontario family physicians on their 4.9 million rostered adult patients. We compared physicians’ test utilization and calculated case‐mix adjusted observed to expected (O:E) utilization ratios to categorize physicians as Typical, Higher or Lower testers. Age‐sex standardized rates (cases/10 000 patient years) and Rate Ratios were determined for cancers of the thyroid, prostate, breast, lymphoma, kidney, melanoma, uterus, ovary, lung, esophagus, and pancreas for each tester group. Results There was wide variation in the use of the 23 tests by Ontario physicians. 26% and 24% of physicians were deemed Higher Testers for laboratory and imaging tests, while 41% and 38% were Typical Testers. The patients of higher test users were diagnosed with more cancers of thyroid (laboratory [RR 1.61, 95% CI 1.39‐1.87] and imaging [RR 2.08, 95% CI 0.88‐2.30]) and prostate (laboratory [RR 1.10, 95% CI 1.03‐1.18] and imaging [RR 1.05, 95% CI 1.00‐1.10]). Conclusion There is a wide variation in the ordering of routine and common medical tests among Ontario family doctors. The patients of higher testers were diagnosed with more thyroid and prostate cancers.

IntroductionThere is an evidence gap regarding the duration of SARS-CoV-2 shedding and of its variability across different care settings and by age, sex, income, and co-morbidities. Such evidence is part of understanding of infectivity and reinfection. We examine direct measures of viral shedding using a linked population-based health administrative dataset.MethodsLaboratory and sociodemographic databases for Ontario, Canada were linked to identify those testing positive (RT-PCR) between Jan. 15 and April 30, 2020 who underwent subsequent testing by May 31, 2020. To maximise use of available data, we computed two shedding duration estimates defined as the time between initial positive and most recent positive (documented shedding) or second of two negative tests (documented resolution). We also report multivariable results using quantile regression to examine subgroup differences.ResultsIn Ontario, of the 16,595 who tested positive before April 30, 2020, 6604 had sufficient subsequent testing to allow shedding duration calculation. Documented shedding median duration calculated in 4,889 (29% of 16,595) patients was 19 days (IQR 12-28). Documented resolution median duration calculated in 3,219 (19% of the 16,595) patients was 25 days (IQR 18-34). Long-term care residents had 3-5 day longer shedding durations using both definitions. Shorter documented shedding durations of 2-4 days were observed in those living in higher income neighbourhoods. Shorter documented resolution durations of 2-3 days were observed at the 25th% of the distribution in those aged 20-49. Only 11.5% of those with definitive negative test results reverted to negative status by day 14.ConclusionsViral shedding continued well beyond 14 days among this large subset of a population-based group with COVID-19, and longer still for long-term care residents and those living in less affluent neighborhoods. Our findings do not speak to duration of infectivity but are useful for understanding the expected duration of RT-PCR positivity and for identifying reinfection.

Introduction Despite recommendations, most studies examining health inequalities fail to report both absolute and relative summary measures. We examine colorectal cancer (CRC) survival for patients with and without severe psychiatric illness (SPI) to demonstrate the use and importance of relative and absolute effects. Objectives and Approach We conducted a retrospective cohort study of CRC patients diagnosed between 01/04/2007 and 31/12/2012, using linked administrative databases. SPI was defined as diagnoses of major depression, bipolar disorder, schizophrenia, and other psychotic illnesses six months to five years preceding cancer diagnosis and categorized as inpatient, outpatient or none. Associations between SPI history and risk of death were examined using Cox Proportional Hazards regression to obtain hazard ratios and Aalen’s semi-parametric additive hazards regression to obtain absolute differences. Both models controlled for age, sex, primary tumour location, and rurality. Results The final cohort included 24,507 CRC patients, 482 patients had an outpatient SPI history and 258 patients had an inpatient SPI history. 58.1% of patients with inpatient SPI history died, and 47.1% of patients with outpatient SPI history died. Patients with an outpatient SPI history had a 40% (HR 1.40, 95% CI: 1.22-1.59) increased risk of death and patients with an inpatient SPI history had a 91% increased risk of death (HR 1.91, 95% CI: 1.63-2.25), relative to no history of a mental illness. An outpatient SPI history was associated with an additional 33 deaths per 1000 person years, and an inpatient SPI was associated with an additional 82 deaths per 1000 person years after controlling for confounders. Conclusion / Implications We demonstrated that reporting of both relative and absolute effects is possible and calculating risk difference is relatively simple using Aalen models. We encourage future studies examining inequalities with time-to-event data to use this method and report both relative and absolute effect measures.

OBJECTIVES/GOALS: The “hidden curriculum” is a set of unofficial rules outside of the formal curriculum that allows medical students to succeed. It is often not accessible to those who are first-generation in medicine. This study created a novel survey tool to directly evaluate the hidden curriculum, its contributing factors, and its effects on students. METHODS/STUDY POPULATION: Using available literature as a guide, a novel survey tool to evaluate different aspects of the hidden curriculum was created. This survey consists of 17 Likert scale questions on topics varying from sense of belongingness to dress code, self-guided studying, mentorship, and confidence in knowing how to succeed. This survey tool was embedded into a larger survey evaluating health disparities and diversity, inclusion, accessibility, and justice (DEIAJ) in the curricular and extracurricular spaces. This survey packet was administered to all medical students at a large U.S. medical school. RESULTS/ANTICIPATED RESULTS: 166 medical students from all years responded to this survey. 70% were female, 27% male, and 3% non-binary or prefer not to say. 67% of respondents agreed or strongly agreed that there is a hidden curriculum accessible to only those who have family members in medicine. 57% agreed or strongly agreed that the medical school gave them the adequate training and resources to succeed. 48% agreed or strongly agreed that they would perform better academically if they had more money with 11% stating they often feel embarrassed in a professional setting due to lack of money. Fellow classmen, faculty members, and upperclassmen were identified as the most useful resources to learn how to succeed in medical school. Students on average reported feeling like they knew what to do to succeed in medical school half of the time. DISCUSSION/SIGNIFICANCE: This data strongly supports the existence of a hidden curriculum and gives insight into the importance of financial support for low-income students and peer support groups for those who do not have family members in medicine. This data will be used to inform future interventions to address the hidden curriculum.

ObjectivesTo identify inequalities in cancer survival rates for patients with a history of severe psychiatric illness (SPI) compared to those with no history of mental illness and explore differences in the provision of recommended cancer treatment as a potential explanation.DesignPopulation-based retrospective cohort study using linked cancer registry and administrative data at ICES.SettingThe universal healthcare system in Ontario, Canada.ParticipantsColorectal cancer (CRC) patients diagnosed between April 1st, 2007 and December 31st, 2012. SPI history (schizophrenia, schizoaffective disorders, other psychotic disorders, bipolar disorders or major depressive disorders) was determined using hospitalization, emergency department, and psychiatrist visit data and categorized as 'no history of mental illness, 'outpatient SPI history', and 'inpatient SPI history'.Main outcome measuresCancer-specific survival, non-receipt of surgical resection, and non-receipt of adjuvant chemotherapy or radiation.Results24,507 CRC patients were included; 482 (2.0%) had an outpatient SPI history and 258 (1.0%) had an inpatient SPI history. Individuals with an SPI history had significantly lower survival rates and were significantly less likely to receive guideline recommended treatment than CRC patients with no history of mental illness. The adjusted HR for cancer-specific death was 1.69 times higher for individuals with an inpatient SPI (95% CI 1.36-2.09) and 1.24 times higher for individuals with an outpatient SPI history (95% CI 1.04-1.48). Stage II and III CRC patients with an inpatient SPI history were 2.15 times less likely (95% CI 1.07-4.33) to receive potentially curative surgical resection and 2.07 times less likely (95% CI 1.72-2.50) to receive adjuvant radiation or chemotherapy. These findings were consistent across multiple sensitivity analyses.ConclusionsIndividuals with an SPI history experience inequalities in colorectal cancer care and survival within a universal healthcare system. Increasing advocacy and the availability of resources to support individuals with an SPI within the cancer system are warranted to reduce the potential for unnecessary harm.

Introduction: Breast cancer is detected through screening or through signs and symptoms. In Canada, mammograms for breast cancer screening are offered in organized programs or independently (opportunistic screening). Province of Ontario breast Diagnostic Assessment Units (DAUs) are facility-based programs that provide coordinated breast cancer diagnostic services, as opposed to usual care, in which the primary care provider arranges the tests and consultations. This study describes breast cancer detection method, diagnostic interval and DAU use across Ontario. Methods: The study cohort consisted of 6898 women with invasive breast cancer diagnosed in 2011. We used the Ontario Cancer Registry linked to administrative health care databases. We determined the detection method using the Ontario Breast Screening Program (OBSP) data and physician claims. The diagnostic interval was the time between the initial screen, specialist referral or first diagnostic test and the cancer diagnosis. The diagnostic route (whether through DAU or usual care) was determined based on the OBSP records and biopsy or surgery location. We mapped the diagnostic interval and DAU coverage geographically by women’s residence. Results: In 2011, 36% of Ontario breast cancer patients were screen-detected, with a 48% rate among those aged 50 to 69. The provincial median diagnostic interval was 32 days, with county medians ranging from 15 to 65 days. Provincially, 48.4% were diagnosed at a DAU, and this ranged from zero to 100% across counties. Conclusion: The screening detection rate in age-eligible breast cancer patients was lower than published population-wide screening rates. Geographic mapping of the diagnostic interval and DAU use reveals regional variations in cancer diagnostic care that need to be addressed.

Introduction. Le cancer du sein est détecté soit par un examen de dépistage, soit à l’aide de signes et symptômes. Au Canada, les mammographies pour le dépistage du cancer du sein sont offertes dans le cadre de programmes organisés ainsi qu'en contexte indépendant (dépistage opportuniste). Les unités d’évaluation diagnostique (UED) de la province de l’Ontario sont des programmes en établissement qui fournissent des services diagnostiques coordonnés pour le cancer du sein, à la différence des soins habituels où le fournisseur de soins de première ligne organise les examens et les consultations. Cette étude décrit les méthodes de détection, l’intervalle diagnostique et l’utilisation des UED pour le cancer du sein en Ontario. Méthodologie. L’étude a porté sur une cohorte de 6 898 femmes ayant reçu un diagnostic de cancer du sein envahissant en 2011. Nous avons utilisé le Registre d’inscription des cas de cancer de l’Ontario jumelé à des bases de données administratives sur les soins de santé. Nous avons déterminé la méthode de détection à l’aide des données du Programme ontarien de dépistage du cancer du sein (PODCS) et des demandes de règlement des médecins. L’intervalle diagnostique a été défini comme le temps écoulé entre le dépistage initial, l’aiguillage vers un spécialiste ou la première épreuve diagnostique et le diagnostic de cancer lui-même. Le parcours diagnostique (qu'il passe par les UED ou les soins habituels) a été déterminé en fonction des dossiers du PODCS et du lieu de biopsie ou d’intervention chirurgicale. Nous avons cartographié l’intervalle diagnostique et de la couverture des UED en fonction du lieu de résidence des femmes. Résultats. En 2011, 36 % des cas de cancer du sein en Ontario ont été détectés par dépistage, dont 48 % chez des femmes de 50 à 69 ans. L’intervalle diagnostique provincial médian était de 32 jours, les médianes par comté variant entre 15 et 65 jours. À l’échelle provinciale, 48,4 % des cas ont été diagnostiqués dans une UED, ce pourcentage variant entre 0 et 100 % selon les comtés. Conclusion. Le taux de détection au dépistage correspondant aux patientes admissibles du fait de leur âge s'est révélé inférieur au taux de dépistage officiel du cancer du sein pour l’ensemble de la population. La répartition géographique de l’intervalle diagnostique et du recours aux UED révèle des variations régionales dans les soins diagnostiques en oncologie qu'il est nécessaire de corriger.

Motor imagery refers to the phenomenon of imagining performing an action without action execution. Motor imagery and motor execution are assumed to share a similar underlying neural system that involves primary motor cortex (M1). Previous studies have focused on motor imagery of manual actions, but articulatory motor imagery has not been investigated. In this study, transcranial magnetic stimulation (TMS) was used to elicit motor-evoked potentials (MEPs) from the articulatory muscles [orbicularis oris (OO)] as well as from hand muscles [first dorsal interosseous (FDI)]. Twenty participants were asked to execute or imagine performing a simple squeezing task involving a pair of tweezers, which was comparable across both effectors. MEPs were elicited at six time points (50, 150, 250, 350, 450, 550 ms post-stimulus) to track the time course of M1 involvement in both lip and hand tasks. The results showed increased MEP amplitudes for action execution compared to rest for both effectors at time points 350, 450 and 550 ms, but we found no evidence of increased cortical activation for motor imagery. The results indicate that motor imagery does not involve M1 for simple tasks for manual or articulatory muscles. The results have implications for models of mental imagery of simple articulatory gestures, in that no evidence is found for somatotopic activation of lip muscles in sub-phonemic contexts during motor imagery of such tasks, suggesting that motor simulation of relatively simple actions does not involve M1.

* Context.--In 2014, the College of American Pathologists developed an evidence-based guideline to address analytic validation of immunohistochemical assays. Fourteen recommendations were offered. Per the National Academy of Medicine standards for developing trustworthy guidelines, guidelines should be updated when new evidence suggests modifications. Objective.--To assess evidence published since the release of the original guideline and develop updated evidence-based recommendations. Design.--The College of American Pathologists convened an expert panel to perform a systematic review of the literature and update the original guideline recommendations using the Grading of Recommendations Assessment, Development and Evaluation approach. Results.--Two strong recommendations, 1 conditional recommendation, and 12 good practice statements are offered in this updated guideline. They address analytic validation or verification of predictive and nonpredictive assays, and recommended revalidation procedures following changes in assay conditions. Conclusions.--While many of the original guideline statements remain similar, new recommendations address analytic validation of assays with distinct scoring systems, such as programmed death receptor-1 and analytic verification of US Food and Drug Administration approved/ cleared assays; more specific guidance is offered for validating immunohistochemistry performed on cytology specimens. (Arch Pathol Lab Med. 2024;148:e111-e153; doi: 10.5858/arpa.2023-0483-CP, In 2014, the Pathology and Laboratory Quality Center for Evidence-Based Guidelines ('The Center') of the College of American Pathologists (CAP) published a clinical practice guideline that created recommendations for analytic [...]

Students with learning disabilities (LD), such as dyslexia, are at a greater risk of not completing their postsecondary education compared to their peers. Completion broadly and success more generally rest on how students navigate assessment experiences during postsecondary education. Generally, assessment is viewed as a controlling practice. From a self-determination theory (SDT) lens, highly controlling elements of schoolwork frustrate rather than satisfy students' basic psychological needs. Importantly, satisfaction, rather than frustration, supports intrinsic motivation and wellbeing. The current study examines the experiences of classroom assessment as satisfying or frustrating for students with dyslexia through an online methodology involving both Likert questions and written responses to structured open-ended questions. Overall, when students reported basic psychological need satisfaction, they likewise indicated that they received higher grades and felt more successful. From the open-ended data, we extracted three main themes and 12 sub-themes from the interviews: (a) student characteristics (including dyslexia, effort, prior knowledge, and emotions), (b) the role of others (including help, demeanor, structure, and choice), and (c) outcomes (including grades, knowledge and skills, reactions, and future impact). Taken together, when students experience classroom assessment in a way that supports their basic psychological needs, they experience better outcomes (e.g., high grades and perceived success) than when their basic psychological needs are frustrated. We discuss these results in terms of suggestions for instruction and assessment.

The present study aimed to determine the emotional characteristics of the Trait-Meta-Mood-Scale (TMMS-24) in music-oriented secondary school students in Italy. A 24-item self-assessment protocol was applied to measure the level of perceived emotional intelligence according to 3 dimensions: attention, clarity and repair. This tool represents one of the most widely used self-assessment measures of perceived emotional intelligence. The objective of the study was to conduct construct validation to examine reliability of the Italian version of the TMMS-24 in order to identify its feasibility for the assessment of emotional intelligence. Exploratory and confirmatory factorial analyses were conducted on a sample of music-oriented secondary school students in Italy (n=402). Exploratory factor analysis outcomes revealed that the three dimensions of the original scale (attention, clarity and emotional repair) are supported in the examined context, showing adequate internal consistency and describing 52.6% of overall variance. Outcomes were confirmed via confirmatory analysis, obtaining good fit indices (CFI=0.986; TLI=0.985; RMSEA=0.038). The TMMS-24 scale is a valid and reliable instrument for measuring the emotional intelligence of secondary school students in Italy.

Post-secondary students with learning disabilities like dyslexia experience a wide range of emotions related to classroom assessment, perhaps in part because assessment may feel unfair and undermine principles related to wellbeing. To mitigate negative emotions, researchers tend to focus on teaching students how to cope with test anxiety and exam stress or encouraging instructors to improve assessment formats. These approaches, however, do not attend to the psychological experience of assessment. The purpose of this study was to examine associations amongst perceived fairness, three basic psychological needs, and six discrete emotions in the domain of classroom assessment. Results of a parallel multiple mediator analysis showed that perceptions of fairness were positively associated with psychological need satisfaction. In turn, satisfaction of competence and autonomy were related to students' emotions; whereas, relatedness was not. We describe specific recommendations for supporting students' wellbeing in assessment with particular attention to nuances for students with dyslexia.

Ovarian cancer has poor survival outcomes particularly for advanced stage, metastatic disease. Metastasis is promoted by interactions of stromal cells, such as cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), with tumor cells. CAFs play a key role in tumor progression by remodeling the TME and extracellular matrix (ECM) to result in a more permissive environment for tumor progression. It has been shown that fibroblasts, in particular myofibroblasts, utilize metabolism to support ECM remodeling. However, the intricate mechanisms by which CAFs support collagen production and tumor progression are poorly understood. In this study, we show that the fibrillar collagen receptor, Discoidin Domain Receptor 2 (DDR2), promotes collagen production in human and mouse omental CAFs through arginase activity. CAFs with high DDR2 or arginase promote tumor colonization in the omentum. In addition, DDR2-depleted CAFs had decreased ornithine levels leading to decreased collagen production and polyamine levels compared to WT control CAFs. Tumor cell invasion was decreased in the presence CAF conditioned media (CM) depleted of DDR2 or arginase-1, and this invasion defect was rescued in the presence of CM from DDR2-depleted CAFs that constitutively overexpressed arginase-1. Similarly, the addition of exogenous polyamines to CM from DDR2-depleted CAFs led to increased tumor cell invasion. We detected SNAI1 protein at the promoter region of the arginase-1 gene, and DDR2-depleted CAFs had decreased levels of SNAI1 protein at the arginase-1 promoter region. Furthermore, high stromal arginase-1 expression correlated with poor survival in ovarian cancer patients. These findings highlight how DDR2 regulates collagen production by CAFs in the tumor microenvironment by controlling the transcription of arginase-1, and CAFs are a major source of arginase activity and L-arginine metabolites in ovarian cancer models.

Cancer care is complex and exists within the broader healthcare system. The CanIMPACT team sought to enhance primary cancer care capacity and improve integration between primary and cancer specialist care, focusing on breast cancer. In Canada, all medically-necessary healthcare is publicly funded but overseen at the provincial/territorial level. The CanIMPACT Administrative Health Data Group’s (AHDG) role was to describe inter-sectoral care across five Canadian provinces: British Columbia, Alberta, Manitoba, Ontario and Nova Scotia. This paper describes the process used and challenges faced in creating four parallel administrative health datasets. We present the content of those datasets and population characteristics. We provide guidance for future research based on ‘lessons learned’. The AHDG conducted population-based comparisons of care for breast cancer patients diagnosed from 2007-2011. We created parallel provincial datasets using knowledge from data inventories, our previous work, and ongoing bi-weekly conference calls. Common dataset creation plans (DCPs) ensured data comparability and documentation of data differences. In general, the process had to be flexible and iterative as our understanding of the data and needs of the broader team evolved. Inter-sectoral data inconsistencies that we had to address occurred due to differences in: 1) healthcare systems, 2) data sources, 3) data elements and 4) variable definitions. Our parallel provincial datasets describe the breast cancer diagnostic, treatment and survivorship phases and address ten research objectives. Breast cancer patient demographics reflect inter-provincial general population differences. Across provinces, disease characteristics are similar but underlying health status and use of healthcare services differ. Describing healthcare across Canadian jurisdictions assesses whether our provincial healthcare systems are delivering similar high quality, timely, accessible care to all of our citizens. We have provided a description of our experience in trying to achieve this goal and include a list of ‘lessons learned’ and a study process checklist for future use.

This study aimed to characterize effects of coil orientation on the size of Motor Evoked Potentials (MEPs) from both sides of Orbicularis Oris (OO) and both First Dorsal Interosseous (FDI) muscles, following stimulation to left lip and left hand Primary Motor Cortex. Using a 70 mm figure-of-eight coil, we collected MEPs from eight different orientations while recording from contralateral and ipsilateral OO and FDI using a monophasic pulse delivered at 120% active motor threshold. MEPs from OO were evoked consistently for six orientations for contralateral and ipsilateral sites. Contralateral orientations 0°, 45°, 90°, and 315° were found to best elicit OO MEPs with a likely cortical origin. The largest FDI MEPs were recorded for contralateral 45°, invoking a posterior–anterior (PA) current flow. Orientations traditionally used for FDI were also found to be suitable for eliciting OO MEPs. Individuals vary more in their optimal orientation for OO than for FDI. It is recommended that researchers iteratively probe several orientations when eliciting MEPs from OO. Several orientations likely induced direct activation of facial muscles.

We have challenges with poor patient satisfaction scores (Hospital Consumer Assessment of Healthcare Providers and Systems [HCAHPS]) and internal medicine resident (IMR) evaluations of voluntary attending physicians. Using an Observed Structured Teaching Encounter (OSTE), we designed a faculty development project that focused on attendings’ teaching and feedback skills. To assess attending communication with interns and improve attending teaching and feedback skills. All IM attendings on the Long Island Jewish Forest Hills (LIJFH) Emergency Department (ED) call schedule participated. OSTE simulation sessions included two clinical scenarios, standardized patients (SPs), fourth-year medical students trained as ‘interns,’ OSTE checklists, and debriefing. We analyzed ‘intern’ ratings of communication with attendings and attending self-assessment during the OSTE, and attending HCAHPS scores and IMR evaluations of attendings pre- and post-OSTE. Twenty-nine of 29 attendings completed the OSTE. Although an increase was demonstrated pre- to post- for ‘intern’ OSTE ratings of attendings and LIJFH attending self-assessment ratings, there was no statistically significant difference. Mean HCAHPS scores and resident evaluations of attendings also increased from pre- (22% and 3.59) to post-OSTE (30% and 3.87) but did not reach statistical significance. A statistically significant difference for both cases was demonstrated when comparing mean attending self-assessment ratings with ‘intern’ evaluation of attendings. Attending teaching/feedback skills improved between cases, attending self-ratings were higher than ‘intern’ ratings of attendings. HCAHPS and IMR evaluations of attendings improved post-OSTE. Regular intervention utilizing an OSTE may provide a sustained benefit for enhancing attendings’ skills, patient satisfaction, and resident training.