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Narrative research approaches provide the opportunity for constructing a detailed understanding of lived experiences relevant to medical education, in areas such as illness narratives, explorations of doctor-patient relationships, and the development of professional identities in students and educators. The benefits of the depth of data gathered in narrative research are, however, counterbalanced by possible weaknesses relating to a focus on individual cases and the risk of identification of participants where subjects are sensitive or unique. To address these concerns, researchers from a variety of social science disciplines, carrying out research employing a range of methodological approaches, have begun to use ‘composite narratives’ in which the commonalities in the experiences of research participants are combined to create joint narrative or narratives which illustrate participants’ shared experiences. Composite narratives have been used both as a component of the methodological approach and as a method of presenting the results of research in a variety of methodologies. This A Qualitative Space paper explores the role, strengths, and weaknesses of narrative research, before outlining the ways in which composite narrative has been defined within existing research. Distinctions between the various approaches to creating composite narratives are discussed, highlighting the differences in the types of data utilised, and the approaches taken to data analysis and presentation. A key distinction is identified between the use of composite narratives as part of an integrated methodology and as an approach to the presentation of data. Finally, issues relating to trustworthiness, reflexivity, and implications for researchers are considered.

Supplementary Figures 1-5, Tables 1-8. Supplementary Figure 1: Overview of the analytic approach. Supplementary Figure 2: QQ plots of SNPs with MAF ≥0.02 and imputation r2 ≥0.9 associated with Overall Survival in A. Supplementary Figure 3: ‘All OCAC’ histology-adjusted analysis. Supplementary Figure 4: Forest plots of promising SNPs. Supplementary Figure 5: KM-Plotter graphs of significant associations with outcome. Supplementary Table 1: All studies (OCAC & TCGA) eligible for analyses according to first-line chemotherapy. Supplementary Table 2: Description of individual OCAC studies included in the secondary 'all OCAC' analysis. Supplementary Table 3a: Overall Survival estimates for selected SNPs (MAF ≥0.02) comparing iCOGS imputed (r2 ≥0.3) and iPLEX genotyped samples. Supplementary Table 3b: Progression-free Survival estimates for selected SNPs (MAF ≥0.02) comparing iCOGS imputed (r2 ≥0.3) and iPLEX genotyped samples. Supplementary Table 4: SNPs with imputation r2 ≥0.9, EAF ≥0.02 and p ≤ 1E-05 for at least one of four outcomes analyzed in cases selected according to first-line chemotherapy. Supplementary Table 5: Meta-analysis of largest possible sample (TCGA, non-overlapping iCOGS and iplex genotyped) for selected promising SNPs analyzed in cases selected according to first-line chemotherapy. Supplementary Table 6: Significant association between protein-coding genes within 1Mb of promising SNPs and ovarian cancer outcomes. Supplementary Table 7: SNPs with imputation r-sq≥0.9 and p ≤ 1E-05 for Overall Survival in histology-adj 'all OCAC' analysis. Supplementary Table 8: iCOGS estimates for SNPs previously identified to be associated with response to chemotherapy as reported in the aNHGRI GWAS catalog.

Supplementary Methods, Figures 1-5. Supplementary Figure 1. Outline of cohort selection. Supplementary Figure 2. Example of whole-genome single-nucleotide polymorphism (SNP)array profile and genome alteration print (GAP). Supplementary Figure 3. Pre-treatment serum CA125 levels. Supplementary Figure 4. Progression-free and overall survival in patients with SBT-EOC and EOC without adjacent SBT. Supplementary Figure 5. Progression-free and overall survival of patients with Grade 3 SBTEOC and Grade 3 EOC without adjacent SBT

Purpose: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome.Experimental Design: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis.Results: Five SNPs were significantly associated (P ≤ 1.0 × 10−5) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23), and rs6674079 (1q22), were located in long noncoding RNAs (lncRNAs) RP11-179A10.1, RP11-314O13.1, and RP11-284F21.8, respectively (P ≤ 7.1 × 10−6). ENCODE ChIP-seq data at 1q22 for normal ovary show evidence of histone modification around RP11-284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression and high-density lipoprotein (HDL)-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA ≤6 × 10−3).Conclusions: We have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies. Clin Cancer Res; 21(23); 5264–76. ©2015 AACR.

Supplementary Highlighted Methods. This document contains the revised supplementary methods and results with changes highlighted

Supplementary Tables 1-7. Supplementary Table 1. SBT-EOC cases used for molecular analyses Supplementary Table 2. Mutations Screened on the Sequenom/OncoMap3 Platform Supplementary Table 3. Primer sequences for the indicated exons of TP53, ERBB2 and NRAS Supplementary Table 4. Clinico-pathologic characteristics of the subset of SBT-EOC used for molecular analysis compared to the entire SBT-EOC cohort Supplementary Table 5A. Somatic mutations found in borderline and invasive ovarian tumors Supplementary Table 5B. Genes in which somatic mutations were found according to grade and co-existing serous borderline regions Supplementary Table 6. Genes differentially expressed between paired borderline and invasive regions of SBTEOC (p

Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies.Experimental Design: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling.Results: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC.Conclusion: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. Clin Cancer Res; 20(24); 6618–30. ©2014 AACR.

In Pakistan, the term ‘Doctor Brides’ is in constant parlance in media and refers to those females who leave the profession after graduation to take the roles of wives and mothers (1-4). Whilst they are commonly blamed for the shortage of physicians in the country, there is a lack of official data which explores the attrition of female doctors in the country. According to a 2019 news report, 85,000 female doctors have already left work in the country (5). It has also been estimated that 70% of all medical students in Pakistan are female, half of whom do not continue in the medical profession after graduation (6). In 2014, the Pakistan Medical & Dental Council (PMDC) attempted to restrict female admissions to 50%. This was, however, challenged in the Punjab High Court and this decision was put on hold (7, 8).

BACKGROUND Neoadjuvant chemotherapy (NACT) and oesophagectomy is the standard of care for resectable oesophageal adenocarcinomas. Survival outcomes following resection have been improving over time while NACT remain largely unchanged. Indeed, a recent meta-analysis of randomized control trials did not demonstrate a survival benefit in adding NACT, raising the possibility that improved surgical techniques may be reducing the perceived effectiveness of NACT. AIM To compare the effect of addition of NACT to a standardized surgery and lymphadenectomy on overall and disease-free survival in patients undergoing curative oesophagectomy for oesophageal adenocarcinoma. METHODS Patient data were analysed from a prospectively maintained surgical survival database. Demographic, surgical, and survival outcomes were compared between groups according to treatment and nodal count. RESULTS The data of 243 consecutive patients were identified. 79 patients were given NACT and 162 had surgery only. The NACT group were younger, and there was less frequent stage I adenocarcinoma. Overall survival was similar between NACT and surgery only groups (5YS: 48.7% vs 42.5%; P = 0.113), as was disease-free survival (5YS: 40.6% vs 39.9%; P = 0.635). There were ≥ 30 nodes removed in 46 patients, and < 30 in 197 patients, but were otherwise similar. There was improved survival in patients with ≥ 30 nodes removed than those with < 30 nodes (5YS: 64.4% vs 40.7%; P = 0.015), and a better disease-free survival that neared significance (5YS: 54.9% vs 36.6%; P = 0.078). CONCLUSION NACT did not appear to affect overall or disease-free survival. However, an overall survival benefit was observed in patients with ≥ 30 lymph nodes removed, and a benefit in disease-free survival which was not significant.

The incidence of adenocarcinoma of the distal oesophagus (DO) and gastro-oesophageal junction (GOJ) are increasing. They may represent differing disease processes. This study aimed to assess clinicopathological and survival differences between patients with DO and GOJ adenocarcinomas.Data were extracted from a prospective single-surgeon database of consecutive patients undergoing an open Ivor-Lewis oesophagectomy for oesophageal adenocarcinoma (distal oesophagus, Siewert type I and II). Differences in clinicopathological characteristics and survival were evaluated and prognostic factors examined using univariate and multivariate survival analyses.The data were available for 234 patients who underwent an oesophagectomy between 1992 and 2019. DO tumours had higher rates of Barrett's oesophagus (P 0.001), presented with lower tumour stage (P = 0.02) and were more likely to be associated with fewer lymph nodes resected (P = 0.003) than GOJ tumours. The median overall survival for distal oesophageal tumours was 29.2 months, while gastro-oesophageal tumours was 38.6 months. Kaplan Meier analysis did not show a difference in overall survival between the two groups (P = 0.08). However, when adjusted for potential confounders, GOJ tumours were associated with a reduced adjusted hazard of death (adjusted HR 0.58, 95% CI 0.36-0.92, P = 0.022) compared with DO tumours.This study suggests that GOJ cancers have different clinicopathological characteristics and improved survival compared to DO tumours.

Purpose The current research study investigates the speech therapy experiences of an individual who covertly stuttered for approximately 40 years; at the time of the interview, she was in her mid-40s. Method The single-case study is a qualitative thematic analysis of the speech therapy experiences of one individual across her life span. In addition to her stuttering, the participant lives with a significant primary diagnosis that she has had since birth, which impacts her activities in daily living. Interview questions were open-ended and conducted via Skype. The interview was transcribed, and a thematic analysis of the recorded transcripts was conducted to investigate her experiences in speech therapy as an individual who covertly stutters. Findings The current findings reveal five major themes regarding the speech therapy experiences of an individual who covertly stutters: (a) nonindividualized treatment and goals, (b) blaming and shaming associated with speech therapy and stuttering, (c) positive self-regard during speech therapy attendance, (d) the use of avoidance strategies and relation to speech therapy, and (e) the evolution of therapy goals. Direct quotations from the participant are used to support these themes. Discussion The significant impact of covert stuttering on an individual is discussed. Results from the participant's experiences indicate an essential need to conduct individualized speech therapy for people who stutter. Speech-language pathologists and others working with persons who stutter maintain a responsibility to recognize the role that case history and counseling play in order to appropriately serve people who covertly stutter.

This paper examines hbo’s The Young Pope through a cultural approach and ritual view to communication first developed by James W. Carey (2009). After a discussion of mediatization of society and its impacts on culture, the essay explores the deeper meanings The Young Pope conveys about self-discovery and the power of love through a textual analysis of the mythic structure of the hero’s journey (Campbell, 1949/2008; Kluckhohn, 1959) in order to understand how religious belief systems and media content paired together can offer a particular view of the world to those who ascribe to them. Ultimately, this paper serves as a piece of media criticism that suggests that television series like The Young Pope can operate as “sites of interpretive struggle” (Peterson, 2008, p. 119) for viewers as they draw conclusions about and question the world around them.

Background Anesthetic induction and other procedures performed by anesthetists are potentially stressful for children. Pediatric anesthetists use communication to rapidly establish rapport and engagement with children and reduce anxiety and discomfort. Communication in pediatric anesthesia is increasingly topical, but there is limited discussion regarding which specific techniques should be taught to trainees. Aims The aim of this research was to identify which communication techniques used locally by pediatric anesthetic specialists, trainees, and nurses are viewed as the most effective and valuable to teach trainees. Methods Qualitative semi-structured focus groups (7) and in-depth interviews (7) were used to gather data from 30 specialist pediatric anesthetists, trainees, and assistants from a major tertiary pediatric anesthetic department. Inductive and deductive thematic data analysis explored communication techniques used locally. Results The research identified the range of communication techniques being utilized to establish rapport and engage with children, including methods for distraction and focusing attention such as storytelling, guided imagery, and positive suggestions. Thematic analysis revealed a series of core overarching principles for successful application, using social skills within an adaptable, competent, child-centered approach. Drawing on the experiences of specialist practitioners and trainees, teaching these communication techniques would ideally employ an interactive approach involving both modeling and specific communication education with focus on developing communication skills via experiential learning using self-reflection and feedback. Conclusions Within the range of communication techniques being utilized by pediatric anesthetists exist a series of core principles that are essential to engaging and building rapport with children. Focusing on the importance of these common core elements in trainee education, in addition to the range of techniques available, may provide a pragmatic framework for centers providing pediatric anesthesia to consider when designing their trainee curriculum.

[Manuscript accepted for publication in the Journal of Early Adolescence, July 11, 2021.] This study investigated attitudes towards restrictive gender norms among adolescents in Côte d’Ivoire and Sierra Leone (pooled N = 1,793, Mage(baseline) = 10.3, Mage(follow-up) = 11.6, 50% boys/girls). We examined individual and contextual predictors of gender attitudes, assessed change in gender attitudes over two years, and estimated the effect of a community-based norms diffusion intervention. Multiple regression analyses revealed that being a boy, exposure to violence against women, and restrictive norms among same-gender peers predicted support for a patriarchal division of adult roles, lower educational status for girls, and acceptance of gender-based violence. In contrast to evidence from Western contexts, we found limited evidence of increased flexibility in gender attitudes during early adolescence. However, the intervention significantly reduced support for restrictive gender norms, especially among boys. Findings reveal novel pathways through which young adolescents acquire beliefs about gender, and provide encouraging evidence regarding community-based approaches to shifting adolescents’ gender attitudes.

The WNT (Wingless and Int-1) proteins play a role in stem cell development and cell differentiation. Mutations in the WNT proteins lead to the development of various tumours, including gastric tumours. Porcupine (PORCN) is a palmitoyltransferase and Wntless (WLS) is a dedicated WNT transport protein that modify and fold the WNT proteins respectively and are involved in their proper secretion and binding to the frizzled (FZD) receptor and the lipoprotein receptor-related protein 5 or 6 (LRP5/6). We investigated how modifications of PORCN and WLS result in changes in WNT expression and secretion from cells under stress conditions that occur in the tumour microenvironment (hypoxia, oxidative stress, endoplasmic reticulum (ER) stress). In the present study, we found the mRNA expression of both PORCN and WLS were significantly increased with treatments inducing oxidative stress (antimycin A) and proteasome inhibition (MG-132), in human colon cancer (HCT116) and human intestinal epithelial cell-6 (HIEC-6) cells. Treatment with ER stressors thapsigargin, tunicamycin, and dithiolthreitol significantly increased PORCN gene expression, while treatment with thapsigargin and dithiolthreitol increased WLS gene expression. The expression of PORCN and WLS proteins increased with hypoxia and ER stressor treatments in both HCT116 and HIEC-6 cells. All stressors used in this study increased beta-catenin (β-catenin) expression in HCT116 cells. Our results suggest that these stressors alter PORCN, WLS and β-catenin expression and function which may, in turn, alter WNT secretion. Silencing the expression of PORCN and WLS with siRNA expression reduced the expression of WLS and WNT3A in HCT116 cells. The possibility exists that PORCN specifically may be involved in a novel signaling pathway, independent of its palmitoleation of the WNT proteins and its role in their secretion, that is rate-limiting for cancer cell growth and tumorigenesis, within the tumour microenvironment.

Pragmatic measures of therapist delivery of evidence-based practice (EBP) are critical to assessing the impact of large-scale, multiple EBP implementation efforts. As an initial step in the development of pragmatic measurement, the current study examined the concordance between therapist and observer ratings of items assessing delivery of EBP strategies considered essential for common child EBP targets. Possible EBP-, session-, and therapist-levels factors associated with concordance were also explored. Therapists and independent observers rated the extensiveness of therapist (n = 103) EBP strategy delivery in 680 community psychotherapy sessions in which six EBPs were used. Concordance between therapist- and observer-report of the extensiveness of therapist EBP strategy use was at least fair (ICC ≥ .40) for approximately half of the items. Greater therapist-observer concordance was observed in sessions where a structured EBP was delivered and in sessions where therapists reported being able to carry out planned activities. Findings highlighted conditions that may improve or hinder therapists' ability to report on their own EBP strategy delivery in a way that is consistent with independent observers. These results can help inform the development of pragmatic therapist-report measures of EBP strategy delivery and implementation efforts more broadly.

At a time when UK general practice is facing significant challenges and departments of academic general practice in UK universities are in decline, this cross-sectional qualitative case study examines the experiences of general practitioner (GP) academics in a Scottish university department of general practice undergraduate education. The study explores GPs’ reasons for entering academic careers, their routes into academic careers and their experiences of balancing clinical and academic work through examining the individual narratives of GP academics. Data were gathered through autobiographical written narrative, individual interviews and an autoethnographic study, and were analysed using a thematic narrative approach. Findings are presented as composite narratives synthesising the predominant experiences of three distinct groups of GPs who entered academia at different stages of their careers. GP academics described limited understanding of academic general practice prior to taking up an academic post. Entry to academic general practice was associated with an interest in teaching and was often prompted by a dissatisfaction with clinical practice. Academic GPs described concerns about career prospects and changing professional identity but valued the scholarship and creativity associated with their academic roles. This study provides insights into the motivations of academic GPs and the factors influencing academic career progression.

BACKGROUND Curative oesophagectomy for oesophageal cancer is associated with considerable potential mortality. Surgeons are increasingly treating older patients presenting with oesophageal cancer as the population ages. The question remains as to the survival in an older population group, many of whom are not fit for combined multimodal therapy. This study aimed to assess the effect of age on overall survival and disease-free survival in patients undergoing curative oesophagectomy for cancer. METHODS Patient data were analysed from a prospectively maintained database. Demographic, surgical and survival outcomes were compared between groups according to age less than 75 years or 75 and older. RESULTS Oesophagectomy was performed in 351 patients between 1990 and 2019 (283 patients

Purpose: The majority of gastric cancer patients are diagnosed with late-stage disease, for which distinct molecular subtypes have been identified that are potentially amenable to targeted therapies. However, there exists no molecular classification system with prognostic power for early-stage gastric cancer (EGC) because the molecular events promoting gastric cancer initiation remain ill-defined. Experimental Design: miRNA microarrays were performed on gastric tissue from the gp130F/F preclinical EGC mouse model, prior to tumor initiation. Computation prediction algorithms were performed on multiple data sets and independent gastric cancer patient cohorts. Quantitative real-time PCR expression profiling was undertaken in gp130F/F-based mouse strains and human gastric cancer cells genetically engineered for suppressed activation of the oncogenic latent transcription factor STAT3. Human gastric cancer cells with modulated expression of the miR-200 family member miR-429 were also assessed for their proliferative response. Results: Increased expression of miR-200 family members is associated with both tumor initiation in a STAT3-dependent manner in gp130F/F mice and EGC (i.e., stage IA) in patient cohorts. Overexpression of miR-429 also elicited contrasting pro- and antiproliferative responses in human gastric cancer cells depending on their cellular histologic subtype. We also identified a miR-200 family–regulated 15-gene signature that integrates multiple key current indicators of EGC, namely tumor invasion depth, differentiation, histology, and stage, and provides superior predictive power for overall survival compared with each EGC indicator alone. Conclusions: Collectively, our discovery of a STAT3-regulated, miR-200 family–associated gene signature specific for EGC, with predictive power, provides a molecular rationale to classify and stratify EGC patients for endoscopic treatment. Clin Cancer Res; 24(6); 1459–72. ©2018 AACR.

The inhibition of host innate immunity pathways is essential for the persistence of attaching and effacing pathogens such as enteropathogenic Escherichia coli (EPEC) and Citrobacter rodentium during mammalian infections. To subvert these pathways and suppress the antimicrobial response, attaching and effacing pathogens use type III secretion systems to introduce effectors targeting key signaling pathways in host cells. One such effector is the arginine glycosyltransferase NleB1 (NleBCR in C. rodentium) that modifies conserved arginine residues in death domain-containing host proteins with N-acetylglucosamine (GlcNAc), thereby blocking extrinsic apoptosis signaling. Ectopically expressed NleB1 modifies the host proteins Fas-associated via death domain (FADD), TNFRSF1A-associated via death domain (TRADD), and receptor-interacting serine/threonine protein kinase 1 (RIPK1). However, the full repertoire of arginine GlcNAcylation induced by pathogen-delivered NleB1 is unknown. Using an affinity proteomic approach for measuring arginine-GlcNAcylated glycopeptides, we assessed the global profile of arginine GlcNAcylation during ectopic expression of NleB1, EPEC infection in vitro, or C. rodentium infection in vivo. NleB overexpression resulted in arginine GlcNAcylation of multiple host proteins. However, NleB delivery during EPEC and C. rodentium infection caused rapid and preferential modification of Arg117 in FADD. This FADD modification was extremely stable and insensitive to physiological temperatures, glycosidases, or host cell degradation. Despite its stability and effect on the inhibition of apoptosis, arginine GlcNAcylation did not elicit any proteomic changes, even in response to prolonged NleB1 expression. We conclude that, at normal levels of expression during bacterial infection, NleB1/NleBCR antagonizes death receptor-induced apoptosis of infected cells by modifying FADD in an irreversible manner.

A small proportion of patients with malignant pleural mesothelioma (MPM) achieve pathological complete response (CR) following treatment with current practice induction chemotherapy. Our analysis of 58 patients with MPM treated with platinum-based chemotherapy showed 4 patients (7%) attained pathological CR at subsequent extrapleural pneumonectomy (EPP). Patient and tumour factors such as age, gender, smoking habit, histological subtype, and clinical stage were not found to be associated with pathological CR. Patients with pathological CR had longer disease-free survival (29.2 vs. 13.8 months; p = 0.08) and overall survival (76.4 vs. 23.4 months; p = 0.06) but this did not reach statistical significance. Our study suggests that patients who achieve pathological CR after chemotherapy may have improved survival in MPM.

Context: There is a need to improve both primary palliative care (PPC) education and its assessment in graduate medical education (GME). We developed an instrument based on published palliative care (PC) competencies to assess resident competency and educational interventions. Objectives: To describe the development and psychometric properties of a novel, competency-based instrument to measure resident knowledge and self-efficacy in PPC. Methods: We created a 2-part instrument comprised of a knowledge test (KT) and a self-efficacy inventory (SEI) addressing 18 consensus, core PC resident competencies across 5 domains: pain and symptom management; communication; psychosocial, spiritual, and cultural aspects of care; terminal care and bereavement; and PC principles and practice. The instrument was distributed to 341 internal medicine residents during academic years 2015 to 2016 and 2016 to 2017. A standard item analysis was performed on the KT. Internal consistency (Cronbach α) and variable relationships (factor analysis) were measured for the SEI. Results: One hundred forty-four residents completed the survey (42% response). For 15 KT items, difficulty ranged from 0.17 to 0.98, with 7 items ranging 0.20 to 0.80 (typical optimum difficulty); discrimination ranged from 0.03 to 0.60 with 10 items ≥0.27 (good to very good discrimination). Cronbach α was 0.954 for 35 SEI items. Factor analysis of combined 2015 to 2016 items yielded 4 factors explaining the majority of variance for the entire set of variables. Conclusion: Our instrument demonstrates promising psychometric properties and reliability in probing the constructs of PC and can be further utilized in PC GME research to assess learners and evaluate PPC educational interventions.

Background The Myc oncogene family has been implicated in many human malignancies and is often associated with particularly aggressive disease, suggesting Myc as an attractive prognostic marker and therapeutic target. However, for epithelial ovarian cancer (EOC), there is little consensus on the incidence and clinical relevance of Myc aberrations. Here we comprehensively investigated alterations in gene copy number, expression, and activity for Myc and evaluated their clinical significance in EOC. Methods To address inconsistencies in the literature regarding the definition of copy number variations, we developed a novel approach using quantitative polymerase chain reaction (qPCR) coupled with a statistical algorithm to estimate objective thresholds for detecting Myc gain/amplification in large cohorts of serous (n = 150) and endometrioid (n = 80) EOC. MYC, MYCN, and MYCL1 mRNA expression and Myc activity score for each case were examined by qPCR. Kaplan–Meier and Cox-regression analyses were conducted to assess clinical significance of Myc aberrations. Results Using a large panel of cancer cell lines (n = 34), we validated the statistical algorithm for determining clear thresholds for Myc gain/amplification. MYC was the most predominantly amplified of the Myc oncogene family members, and high MYC mRNA expression levels were associated with amplification in EOC. However, there was no association between prognosis and increased copy number or gene expression of MYC/MYCN/MYCL1 or with a pan-Myc transcriptional activity score, in EOC, although MYC amplification was associated with late stage and high grade in endometrioid EOC. Conclusion A systematic and comprehensive analysis of Myc genes, transcripts, and activity levels using qPCR revealed that although such aberrations commonly occur in EOC, overall they have limited impact on outcome, suggesting that the biological relevance of Myc oncogene family members is limited to certain subsets of this disease.

Introduction Patients with lung cancer who harbor multiple pulmonary sites of disease have been challenging to classify; a subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee was charged with developing proposals for the eighth edition of the tumor, node, and metastasis (TNM) classification to address this issue. Methods A systematic literature review and analysis of the International Association for the Study of Lung Cancer database was performed to develop proposals for revision in an iterative process involving multispecialty international input and review. Results Details of the evidence base are summarized in other articles. Four patterns of disease are recognized; the clinical presentation, pathologic correlates, and biologic behavior of these suggest specific applications of the TNM classification rules. First, it is proposed that second primary lung cancers be designated with a T, N, and M category for each tumor. Second, tumors with a separate tumor nodule of the same histologic type (either suspected or proved) should be classified according to the location of the separate nodule relative to the index tumor—T3 for a same-lobe, T4 for a same-side (different lobe), and M1a for an other-side location—with a single N and M category. Third, multiple tumors with prominent ground glass (imaging) or lepidic (histologic) features should be designated by the T category of the highest T lesion, the number or m in parentheses (#/m) to indicate the multiplicity, and a collective N and M category for all. Finally, it is proposed that diffuse pneumonic-type lung cancers be designated by size (or T3) if in one lobe, T4 if involving multiple same-side lobes, and M1a if involving both lungs with a single N and M category for all areas of involvement. Conclusion We propose to tailor TNM classification of multiple pulmonary sites of lung cancer to reflect the unique aspects of four different patterns of presentation. We hope that this will lead to more consistent classification and clarity in communication and facilitate further research in the nature and optimal treatment of these entities.

Background: Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer. Methods: CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis. Results: Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1-mediated activation of Src was observed in cultured cells and mouse xenografts. Conclusions: CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer.

Background: New targets for ovarian cancer treatment are critically needed. The Wnt receptors ROR1 and ROR2 are overexpressed in all subtypes of ovarian cancer and appear to play a role in both the tumor and surrounding microenvironment (1). In vitro studies support the approach of targeting these receptors together to inhibit ovarian cancer migration and invasion (2, 3). Aim: To investigate the role of ROR1 and ROR2 in ovarian cancer progression, survival and chemoresistance, to determine their feasibility as therapeutic targets. Methods: Analysis of RNA-Seq data from publicly available ovarian cancer datasets was performed to determine associations with overall survival and platinum resistance. ROR1 IHC using a recently released monoclonal antibody (4A5, BD Bioscience) was performed on a cohort of ovarian cancer patients. ROR1 and/or ROR2 were silenced in a unique preclinical organotypic model of platinum-resistant ovarian cancer metastasis. Results: There is a significant increase (p=0.01) in ROR1 expression in both primary resistant and acquired resistant (p=0.03) high-grade serous ovarian cancer (HGSOC). ROR2 expression is not significantly associated with chemoresistance. High ROR1 (P=0.002, HR 1.93) or high ROR2 (P=0.004, HR 1.9) expression is associated with a significantly shorter overall survival (OS) in the Tothill cohort (4). Patients expressing both high ROR1 and high ROR2 have the shortest OS (P=0.0003, HR 2.38). ROR1 protein expression was detected in 97% of HGSOC patients via IHC, with 59% of HGSOC expressing “high ROR1” (IHC score 2 or 3). Overall, patients with higher-grade tumors expressed significantly higher ROR1 levels (P=0.001) than patients with low-grade tumors. Silencing ROR1 and ROR2 in combination inhibits adhesion and invasion of platinum resistant ovarian cancer in a 3D organotypic coculture model. Conclusion: Our data support targeting both ROR1 and ROR2 as a new approach to treating ovarian cancer. The development of a number of monoclonal antibodies targeting ROR1 and ROR2 that are currently in phase 1 trials for other tumor types makes this clinically feasible in the future. These data also suggest that this may be most effective in the context of HGSOC with platinum resistance. References: 1. Henry CE et al. Distinct patterns of stromal and tumor expression of ROR1 and ROR2 in histological subtypes of epithelial ovarian cancer. Transl Oncol 2017;10(3):346-56. 2. Henry C, Hacker NF, Ford CE. Silencing ROR1 and ROR2 inhibits invasion and adhesion in an organotypic model of ovarian cancer metastasis. Oncotarget 2017;8(68):112727-38. 3. Henry C et al. ROR1 and ROR2 are upregulated in chemoresistant ovarian cancer and promote migration and invasion. Oncogenesis 2016;5(5):doi: 10.1038/oncsis.2016.32. 4. Tothill RW et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res 2008;14(16):5198-208. Citation Format: Dongli Liu, Miya John, Claire E. Henry, Elizabeth L. Christie, David D.L. Bowtell, Kristina Tang, Viola Heinzelmann-Schwarz, Catherine Kennedy, Jessica Boros, Anna DeFazio, Caroline E. Ford. ROR1 is associated with ovarian cancer progression and chemoresistance [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A41.

Citrobacter rodentium is a mouse restricted pathogen that was originally isolated from laboratory mouse colonies and causes transmissible colonic hyperplasia, characterized by thickening of the colon and inflammation. As a natural pathogen of mice, the infection model has proven critical to the development of our understanding of the pathogenesis of enteric disease and the mucosal immune response. In addition to this, some features of disease such as dysbiosis, inflammation, and wound healing replicate features of human inflammatory bowel diseases. As such, the C. rodentium infection model has become a key tool in investigations of many aspects of mucosal immunology.

Purpose – Interprofessional education (IPE) is a method to create an environment that fosters interprofessional communication, understanding the roles and responsibilities of each profession, learning the skills to organize and communicate information for patients, families and members of the health care team. Providing IPE to health professional students can prepare them in the workforce to have the necessary skills to function in a collaborative practice ready environment. The purpose of this paper is to demonstrate the methods used in developing IPE curriculum, faculty training as debriefers/facilitators, identify learning objectives and outcomes. Design/methodology/approach – The faculty and student surveys utilized a Likert scale. Learning objectives for the student survey assessed learning objective including communication of roles and responsibilities, communication and organization of information, engagement of other health professions (HP) in shared patient-centered problem solving, interprofessional assessment of patient status, and preparation of patients from transition of care to home. The faculty survey assessed faculty experience levels in IPE, role as facilitator/debriefer, and future needs for sustainability of the program. Findings – Student evaluation of IPE simulation experience revealed students believed they improved their interprofessional communication skills and had a better understanding of health professional roles and responsibilities. Faculty feedback indicated that HP students achieved learning objectives and their continued commitment to IPE however additional training and development were identified as areas of need. Practical implications – This paper can assist other educational institutions in developing IPE and structuring IPE assessment particularly in the HPs. Social implications – The public health care will be impacted positively by having health care providers specifically trained to work in teams and understand collaborative care. Student graduates in the HPs will be better prepared to function as a team in real clinical care following their participation in interprofessional simulation. Originality/value – This interprofessional simulation curriculum involves student learners from eight different HPs and participation of over 30 faculty from differing professions. This curriculum is unique in its bread and depth of collaboration and true teamwork across disciplines.

Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies. Experimental Design: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling. Results: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC. Conclusion: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. Clin Cancer Res; 20(24); 6618–30. ©2014 AACR.

Neutrophils use Toll-like receptor and IL-18 signaling to reprogram Fas-induced death. The regulation of neutrophil lifespan is critical for a circumscribed immune response. Neutrophils are sensitive to Fas/CD95 death receptor signaling in vitro, but it is unknown if Fas regulates neutrophil lifespan in vivo. We hypothesized that FasL-expressing CD8+ T cells, which kill antigen-stimulated T cells during chronic viral infection, can also induce neutrophil death in tissues during infection. With the use of LysM-Cre Fasfl/fl mice, which lack Fas expression in macrophages and neutrophils, we show that Fas regulates neutrophil lifespan during lymphocytic choriomeningitis virus (LCMV) infection in the lung, peripheral blood, and spleen. Fas also contributed to the regulation of neutrophil numbers in the colon of Citrobacter rodentium-infected mice. To examine the effects of infection on Fas activation in neutrophils, we primed neutrophils with TLR ligands or IL-18, resulting in ablation of Fas death receptor signaling. These data provide the first in vivo genetic evidence that neutrophil lifespan is controlled by death receptor signaling and provide a mechanism to account for neutrophil resistance to Fas stimulation during infection.

INTRODUCTION: Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons.METHODS: Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and "best" stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases.RESULTS: The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage.CONCLUSIONS: The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts.

Background: Tubular carcinoma (TC) of the breast has a very favourable prognosis. The role for axillary staging in small TC was questioned. This study investigated the frequency of axillary metastases and prognostic factors in pure TC of the breast. It involved a retrospective review of prospectively collected data. Methods: Aconsecutive series of patients presenting to The Strathfield Breast Centre (TSBC) between 1988 and 2011 were reviewed. Only pure TC was included. Information collected included demographics, surgery, pathology, adjuvant therapy and survival. Results: Pure TC accounted for 146 out of 6110 cases of operable breast cancer. Ninety-five per cent were node negative (micrometastases and isolated tumour cells excluded). Ninety-eight per cent of those with known oestrogen receptor status were oestrogen receptor positive. Median tumour size was 10 mm (range 1‐52 mm). Tenyear survival was 97%. Twelve per cent of patients had more than one tumour (either ipsilateral or contralateral). Eight patients had recurrent disease. All were node negative. Three of these patients died of their disease. Conclusion: Axillary metastases are uncommon in pure TC. Recurrent disease is not readily predicted by tumour size or node status.

BackgroundResearch on strategies for addressing multiple health-related behaviors (HRBs) in one intervention are needed because resources are sparse and clarification is needed regarding the relationship between multiple HRBs.PurposeDetermine undergraduate students' health behavior co-occurring pairs of smoking cigarettes (SC), alcohol consumption (AC), smoking marijuana (SM), physical activity (PA), and fruit and vegetable consumption (FV) and identify the characteristics of the pairs.MethodsNine hundred and twenty-eight undergraduate students enrolled in a health and wellness course were surveyed. A combination of phi statistical test and logistic regression identifies behavior pairs and the variations of paired behaviors by sociodemographic characteristics.ResultsFive of the 10 pair combinations had a relationship (P

Nodal categories for malignant pleural mesothelioma are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer developed a multinational database to generate evidence-based recommendations to inform the eighth edition of the TNM classification of malignant pleural mesothelioma.Data from 29 centers were entered prospectively (n = 1566) or by transfer of retrospective data (n = 1953). Survival according to the seventh edition N categories was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Survival was measured from the date of diagnosis.There were 2432 analyzable cases: 1603 had clinical (c) staging, 1614 had pathologic (p) staging, and 785 had both. For clinically staged tumors there was no separation in Kaplan-Meier curves between cN0, cN1 or cN2 (cN1 versus cN0 hazard ratio [HR] = 1.06, p = 0.77 and cN2 versus cN1 HR = 1.04, p = 0.85). For pathologically staged tumors, patients with pN1 or pN2 tumors had worse survival than those with pN0 tumors (HR = 1.51, p 0.0001) but no survival difference was noted between those with pN1 and pN2 tumors (HR = 0.99, p = 0.99). Patients with both pN1 and pN2 nodal involvement had poorer survival than those with pN2 tumors only (HR = 1.60, p = 0.007) or pN0 tumors (HR = 1.62, p0.0001).A recommendation to collapse both clinical and pN1 and pN2 categories into a single N category comprising ipsilateral, intrathoracic nodal metastases (N1) will be made for the eighth edition staging system. Nodes previously categorized as N3 will be reclassified as N2.

Interprofessional education (IPE) in health profession training is recognized as a key to improving patient care in practice settings. Though recognized as extremely important, implementation of IPE remains a challenge for many health profession programs. Despite challenges, the seven health profession (HP) programs at D’Youville College initiated IPE using healthcare simulation with professional actors serving as simulated patients. Faculty from chiropractic, dietetics, nursing, occupational therapy, pharmacy, physical therapy and physician assistant programs collaborated in this year-long implementation process. This manuscript provides a description of the planning, delivery and assessment of this innovative interprofessional simulation and the creation of the campus Interprofessional Clinical Advancement Center. Students reported enhanced understanding and respect of professional roles and responsibilities and ability to communicate effectively. Faculty reported an ability to encourage interaction and collaboration among HP students. Suggestions for curricular improvements and program sustainability included professional development and compensation. This manuscript should assist other health professional programs seeking guidance to implement and evaluate interprofessional education in academic institutions.

Successful infection by enteric bacterial pathogens depends on the ability of the bacteria to colonize the gut, replicate in host tissues and disseminate to other hosts. Pathogens such as Salmonella, Shigella and enteropathogenic and enterohaemorrhagic (EPEC and EHEC, respectively) Escherichia coli use a type III secretion system (T3SS) to deliver virulence effector proteins into host cells during infection that promote colonization and interfere with antimicrobial host responses. Here we report that the T3SS effector NleB1 from EPEC binds to host cell death-domain-containing proteins and thereby inhibits death receptor signalling. Protein interaction studies identified FADD, TRADD and RIPK1 as binding partners of NleB1. NleB1 expressed ectopically or injected by the bacterial T3SS prevented Fas ligand or TNF-induced formation of the canonical death-inducing signalling complex (DISC) and proteolytic activation of caspase-8, an essential step in death-receptor-induced apoptosis. This inhibition depended on the N-acetylglucosamine transferase activity of NleB1, which specifically modified Arg 117 in the death domain of FADD. The importance of the death receptor apoptotic pathway to host defence was demonstrated using mice deficient in the FAS signalling pathway, which showed delayed clearance of the EPEC-like mouse pathogen Citrobacter rodentium and reversion to virulence of an nleB mutant. The activity of NleB suggests that EPEC and other attaching and effacing pathogens antagonize death-receptor-induced apoptosis of infected cells, thereby blocking a major antimicrobial host response.

Introduction: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM. Methods: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases. The M component as it currently stands was validated by confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to overall survival (OS) between the clinical MO (cM0) and cM1 categories. Candidate stage groups were developed by using a recursive partitioning and amalgamation algorithm applied to all cM0 cases. Results: Of 3519 submitted cases, 2414 were analyzable and 84 were cM1 cases. Median OS for cM1 cases was 9.7 months versus 13.4 months (p = 0.0013) for the locally advanced (T4 or N3) cM0 cases, supporting inclusion of only cM1 in the stage IV group. Exploratory analyses suggest a possible difference in OS for single- versus multiple-site cM1 cases. A recursive partitioning and amalgamation generated survival tree on the OS outcomes restricted to cM0 cases with the newly proposed (eighth edition) T and N components indicates that optimal stage groupings for the eighth edition will be as follows: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4), and stage IV (any M1). Conclusions: This first evidence-based revision of the TNM classification for MPM leads to substantial changes in the T and N components and the stage groupings. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Background Addressing evidence-practice gaps in primary care remains a significant public health challenge and is likely to require action at different levels of the health system. Whilst Continuous Quality Improvement (CQI) is associated with improvements in overall delivery, little is known about delivery of different types of care processes, and their relative improvement during CQI. Methods We used data from over 15,000 clinical audit records of clients with Type 2 diabetes collected as part of a wide-scale CQI program implemented between 2005 and 2014 in 162 Aboriginal and Torres Strait Islander health centres. We abstracted data from clinical records on 15 service items recommended in clinical guidelines and categorised these items into five modes of care on the basis of the mechanism through which care is delivered: laboratory tests; generalist-delivered physical checks; specialist-delivered checks; education/counselling for nutrition and physical activity and education/counselling for high risk substance use. We calculated delivery for each patient for each of mode of care by determining the proportion of recommended services delivered for that mode. We used multilevel regression models to quantify variation attributable to health centre or client level factors and to identify factors associated with greater adherence to clinical guidelines for each mode of care. Results Clients on average received 43 to 60 % of recommended care in 2005/6. Different modes of care showed different patterns of improvement. Generalist-delivered physical checks (delivered by a non-specialist) showed a steady year on year increase, delivery of laboratory tests showed improvement only in the later years of the study, and delivery of counselling/education interventions showed early improvement which then plateaued. Health centres participating in CQI had increased odds of top quartile service delivery for all modes compared to baseline, but effects differed by mode. Health centre factors explained 20–52 % of the variation across jurisdictions and health centres for different modes of care. Conclusions Levels of adherence to clinical guidelines and patterns of improvement during participation in a CQI program differed for different modes of care. Policy and funding decisions may have had important effects on the level and nature of improvements achieved.

Introduction Stage classification provides a consistent language to describe the anatomic extent of disease and is therefore a critical tool in caring for patients. The Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer developed proposals for revision of the classification of lung cancer for the eighth edition of the tumor, node, and metastasis (TNM) classification, which takes effect in 2017. Methods An international database of 94,708 patients with lung cancer diagnosed in 1999–2010 was assembled. This article describes the process and statistical methods used to refine the lung cancer stage classification. Results Extensive analysis allowed definition of tumor, node, and metastasis categories and stage groupings that demonstrated consistent discrimination overall and within multiple different patient cohorts (e.g., clinical or pathologic stage, R0 or R-any resection status, geographic region). Additional analyses provided evidence of applicability over time, across a spectrum of geographic regions, histologic types, evaluative approaches, and follow-up intervals. Conclusions An extensive analysis has produced stage classification proposals for lung cancer with a robust degree of discriminatory consistency and general applicability. Nevertheless, external validation is encouraged to identify areas of strength and weakness; a sound validation should have discriminatory ability and be based on an independent data set of adequate size and sufficient follow-up with enough patients for each subgroup.

Background Potentially preventable chronic diseases are the greatest contributor to the health gap between Aboriginal and Torres Strait Islander peoples and non-­Indigenous Australians. Preventive care is important for earlier detection and control of chronic disease, and a number of recent policy initiatives have aimed to enhance delivery of preventive care. We examined documented delivery of recommended preventive services for Indigenous peoples across Australia and investigated the influence of health center and client level factors on adherence to best practice guidelines. Methods Clinical audit data from 2012 to 2014 for 3,623 well adult clients (aged 15–54) of 101 health centers from four Australian states and territories were analyzed to determine adherence to delivery of 26 recommended preventive services classified into five different modes of care on the basis of the way in which they are delivered (e.g., basic measurement; laboratory tests and imaging; assessment and brief interventions, eye, ear, and oral checks; follow-up of abnormal findings). Summary statistics were used to describe the delivery of each service item across jurisdictions. Multilevel regression models were used to quantify the variation in service delivery attributable to health center and client level factors and to identify factors associated with higher quality care. Results Delivery of recommended preventive care varied widely between service items, with good delivery of most basic measurements but poor follow-up of abnormal findings. Health center characteristics were associated with most variation. Higher quality care was associated with Northern Territory location, urban services, and smaller service population size. Client factors associated with higher quality care included age between 25 and 34 years, female sex, and more regular attendance. Conclusion Wide variation in documented preventive care delivery, poor follow-up of abnormal findings, and system factors that influence quality of care should be addressed through continuous quality improvement approaches that engage stakeholders at multiple levels (including, for example, access to care in the community, appropriate decision support for practitioners, and financial incentives and context appropriate guidelines).