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Nasopharyngeal carcinoma (NPC) is unique among head and neck cancers for its strong causative association with Epstein Barr-Virus and high levels of immune infiltration that play a role in pathogenesis. As such, immunotherapy for the treatment of NPC is a promising area of research in the pursuit of improving patient outcomes. Understanding the tumour immune microenvironment (TIME) of NPC is the key to developing targeted immunotherapies and stratifying patients to determine optimal treatment regimens. Recent research has uncovered distinct characteristics of the TIME in NPC as well as important differences between the different disease subtypes; however, reviewing the state of the field reveals a further need for the application of novel techniques like multiplexed hyperspectral imaging and mass cytometry. These techniques can be used to identify spatial, compositional, and functional aspects of the TIME in NPC such as immune cell sociology, novel immune populations, and differences in immune-related signalling pathways in NPC in order to identify clinically relevant characteristics for targeted immunotherapy development and biomarker discovery.

The aim of this study was to analyze the perceptions of core team members implementing patient-centered medical home (PCMH) within the Veterans Health Administration regarding delegation of work.Significant overlap exists in the performance of work tasks among PCMH team members (primary care providers, RNs, clinical associates, clerks), and scant literature exists on appropriate delegation within PCMH teams.This study conducted used a quantitative and qualitative analysis of 4254 respondents to a 2018 survey.Primary care providers rely heavily on team members, and nurses report being relied upon at high levels. Lack of role clarity and a perceived need for a team leader were concerns voiced by participants.Findings indicated a need for clear guidance on roles and responsibilities within the team. Patient-centered medical home team members need information about the scope of practice of each professional group to allow providers to function at the top of their scope of practice and ensure effective delegation.

Whereas the predominance of leadership research has focused upon top-down influence processes, we examine the process of leading from the inside out, i.e., self-leadership. Based on a meta-analysis...

Liquid biopsies have emerged as a promising tool for the detection of metastases as well as local and regional recurrence in lung cancer. Liquid biopsy tests involve analyzing a patient’s blood, urine, or other body fluids for the detection of biomarkers, including circulating tumor cells or tumor-derived DNA/RNA that have been shed into the bloodstream. Studies have shown that liquid biopsies can detect lung cancer metastases with high accuracy and sensitivity, even before they are visible on imaging scans. Such tests are valuable for early intervention and personalized treatment, aiming to improve patient outcomes. Liquid biopsies are also minimally invasive compared to traditional tissue biopsies, which require the removal of a sample of the tumor for further analysis. This makes liquid biopsies a more convenient and less risky option for patients, particularly those who are not good candidates for invasive procedures due to other medical conditions. While liquid biopsies for lung cancer metastases and relapse are still being developed and validated, they hold great promise for improving the detection and treatment of this deadly disease. Herein, we summarize available and novel approaches to liquid biopsy tests for lung cancer metastases and recurrence detection and describe their applications in clinical practice.

Lung cancer detection and monitoring are hampered by a lack of sensitive biomarkers, which results in diagnosis at late stages and difficulty in tracking response to treatment. Recent developments have established liquid biopsies as promising non-invasive methods for detecting biomarkers in lung cancer patients. With concurrent advances in high-throughput sequencing technologies and bioinformatics tools, new approaches for biomarker discovery have emerged. In this article, we survey established and emerging biomarker discovery methods using nucleic acid materials derived from bodily fluids in the context of lung cancer. We introduce nucleic acid biomarkers extracted from liquid biopsies and outline biological sources and methods of isolation. We discuss next-generation sequencing (NGS) platforms commonly used to identify novel biomarkers and describe how these have been applied to liquid biopsy. We highlight emerging biomarker discovery methods, including applications of long-read sequencing, fragmentomics, whole-genome amplification methods for single-cell analysis, and whole-genome methylation assays. Finally, we discuss advanced bioinformatics tools, describing methods for processing NGS data, as well as recently developed software tailored for liquid biopsy biomarker detection, which holds promise for early diagnosis of lung cancer.

Dysregulation of ubiquitin-proteasome pathway genes through copy number alteration, promoter hypomethylation, and miRNA deregulation is involved in cancer development and progression. Further characterizing alterations in these genes may uncover novel drug targets across a range of diseases in which druggable alterations are uncommon, including hepatocellular carcinoma (HCC). We analyzed 377 HCC and 59 adjacent non-malignant liver tissue samples, focusing on alterations to component genes of the widely studied CRL2pVHL E3 ubiquitin ligase complex. mRNA upregulation of the component genes was common, and was correlated with DNA hypomethylation and copy number increase, but many tumours displayed overexpression that was not explained by either mechanism. Interestingly, we found 66 miRNAs, including 39 previously unannotated miRNAs, that were downregulated in HCC and predicted to target one or more CRL2pVHL components. Several miRNAs, including hsa-miR-101-3p and hsa-miR-139-5p, were negatively correlated with multiple component genes, suggesting that miRNA deregulation may contribute to CRL2pVHL overexpression. Combining miRNA and mRNA expression, DNA copy number, and methylation status into one multidimensional survival analysis, we found a significant association between greater numbers of alterations and poorer overall survival for multiple component genes. While the intricacies of CRL2pVHL complex gene regulation require additional research, it is evident that multiple causes for the deregulation of these genes must be considered in HCC, including non-traditional mechanisms.

Dysregulation of ubiquitin-proteasome pathway genes through copy number alteration, promoter hypomethylation, and miRNA deregulation is involved in cancer development and progression. Further characterizing alterations in these genes may uncover novel drug targets across a range of diseases in which druggable alterations are uncommon, including hepatocellular carcinoma (HCC). We analyzed 377 HCC and 59 adjacent non-malignant liver tissue samples, focusing on alterations to component genes of the widely studied CRL2

The placenta is a vital organ formed during pregnancy, and being the interface between the mother and fetus, it is paramount that placental functioning is strictly controlled. Gene expression in the placenta is finely tuned—with aberrant expression causing placental pathologies and inducing stress on both mother and fetus. Gene regulation is brought upon by several mechanisms, and small non-coding RNAs (sncRNAs) have recently been appreciated for their contribution in gene repression. Their dysregulation has been implicated in a range of somatic and inherited disorders, highlighting their importance in maintaining healthy organ function. Their specific roles within the placenta, however, are not well understood, and require further exploration. To this end, we summarize the mechanisms of microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), and transfer RNAs (tRNAs), their known contributions to human placental health and disease, the relevance of sncRNAs as promising biomarkers throughout pregnancy, and the current challenges faced by placental sncRNA studies.

Purpose To assess differences in Patient Aligned Care Team (PACT) performance between rural and urban primary care clinics within the Veterans Health Administration (VHA). Methods An Explanatory Sequential Mixed Methods design was conducted using VHA administrative data to assess performance of a national sample of 891 VHA primary care clinics. Generalized Estimating Equations with repeated measures were used to estimate associations between rurality and process-oriented endpoints including: chronic disease management through telehealth; use of telephone visits, group visits or secured messaging; same-day access; continuity with primary care provider; and postdischarge follow-up. Qualitative data collected during on-site visits with 5 clinics were used to provide insights into PACT processes from the perspectives of staff in rural and urban clinics. Findings After adjusting for patient- and practice-level characteristics, clinics located in large rural or small/isolated rural areas demonstrated difficulty enhancing access through use of telephone visits, group visits, or secured messaging and completing postdischarge follow-up calls, compared to urban clinics. Qualitative analysis indicated that staff from both rural and urban clinics reported similar barriers implementing these PACT processes. Both patient and staff behaviors and preferences impact implementation of these processes. Distance to care and access to high-speed Internet were also reported as barriers. Conclusions This study contributes to the understanding of PACT performance in rural settings by highlighting ways contextual and behavioral factors relate to performance. Increasing implementation of patient-centered medical home (PCMH) models, such as PACT, will require additional attention to the complex relationships between the practice and surrounding context.

Multiple team membership is common in today's team-based organizations, but little is known about its relationship with collective effectiveness across teams. We adopted a microfoundations framework utilizing existing individual- and team-level research to develop a higher-level perspective on multiple team membership's relationship with performance of entire units of teams. We tested our predictions with data collected from 849 primary care units of the Veterans Health Administration serving over 4.2 million patients. In this context, we found multiple team membership is negatively associated with unit performance, and this negative relationship is exacerbated by task complexity. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

This review focuses on the paradoxical concept of self-leadership—defined as a comprehensive self-influence process capturing how individuals motivate themselves to complete work that is naturally motivating or work that must be done but is not naturally motivating—as a fundamental process that challenges many traditional assumptions in organizational psychology and organizational behavior. We first present a historical review that traces the roots of self-leadership to early psychological theory and research. We next briefly summarize research related to self-leadership at both the individual and team levels of analysis. We then discuss four paradoxes associated with self-leadership: the paradox of self-leadership depletion and strengthening, the paradox of self-leadership through collaboration, the paradox of me-but-not-you self-leadership, and the paradox of needing self-leadership to improve self-leadership. We conclude with guidelines for future research and practice.

Made available in DSpace on 2021-06-25T10:31:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-06-01 Krembil Foundation Canada Foundation for Innovation Natural Sciences and Engineering Research Council of Canada Canadian Institutes of Health Research MicroRNAs (miRNAs) play vital roles in the regulation of normal developmental pathways. However, cancer cells can co-opt these miRNAs, and the pathways that they regulate, to drive pro-tumourigenic phenotypes. Characterization of the miRNA transcriptomes of fetal organs is essential for identifying these oncofetal miRNAs, but it has been limited by fetal sample availability. As oncofetal miRNAs are absent from healthy adult lungs, they represent ideal targets for developing diagnostic and therapeutic strategies. We conducted small RNA sequencing of a rare collection of 25 human fetal lung (FL) samples and compared them to two independent cohorts (n = 140, n = 427), each comprised of adult non-neoplastic lung (ANL) and lung adenocarcinoma (LUAD) samples. We identified 13 oncofetal miRNAs that were expressed in FL and LUAD but not in ANL. These oncofetal miRNAs are potential biomarkers for LUAD detection (AUC = 0.963). Five of these miRNAs are derived from the imprinted C14MC miRNA cluster at the 14q32 locus, which has been associated with cancer development and abnormal fetal and placental development. Additionally, we observed the pulmonary expression of 44 previously unannotated miRNAs. The sequencing of these fetal lung samples also provides a baseline resource against which aberrant samples can be compared. British Columbia Cancer Research Centre International Research Center A.C. Camargo Cancer Center NYU Langone Medical Center British Columbia Children’s Hospital Research Institute Department of Medical Genetics University of British Columbia Division of Orthopedic Surgery Schroeder Arthritis Institute University Health Network Data Science Discovery Centre for Chronic Diseases Krembil Research Institute University Health Network Department of Medical Biophysics University of Toronto Department of Computer Science University of Toronto Faculty of Medicine São Paulo State University (UNESP) Faculty of Medicine São Paulo State University (UNESP) Canada Foundation for Innovation: 203373 Natural Sciences and Engineering Research Council of Canada: 203475 Canada Foundation for Innovation: 30865 Canadian Institutes of Health Research: FDN-143345

Background Learning healthcare systems have invested heavily in training primary care staff to provide care using patient-centered medical home models, but less is known about how to effectively lead such teams to deliver high quality care. Research is needed to better understand which healthcare leadership skills are most utilized or in need of development through additional training. Method Semi-structured telephone interviews with healthcare leaders familiar with Patient-Aligned Care Teams (PACT) implementation in the U.S. Department of Veterans Affairs (VA). We interviewed sixteen (N = 16) physician, nursing, and administrative leaders at VA facilities located in the upper Midwestern United States. Content analysis of interviews transcripts using template techniques. Results Participants described instrumental challenges that they perceived hindered leadership effectiveness, including the supervisory structure; pace of change; complexity of the clinical data infrastructure; an over-reliance on technology for communication; and gaps in available leadership training. Factors perceived as facilitating effective leadership included training in soft skills, face-to-face communication, and opportunities for formal training and mentorship. A cross-cutting theme was the importance of developing “soft skills” for effective PACT leadership. Conclusions Although formal leadership training and development were perceived as beneficial, healthcare leaders familiar with PACT implementation in the VA described a mismatch between the skills and knowledge PACT leaders need to succeed and the training available to them. Closing this gap could improve retention of skilled and knowledgeable healthcare leaders, thereby reducing the costs associated with training and leading to improvements in healthcare delivery.

BackgroundLong non-coding RNAs (lncRNAs) have long been implicated in cancer-associated phenotypes. Recently, a class of lncRNAs, known as cis-acting, have been shown to regulate the expression of neighboring protein-coding genes and may represent undiscovered therapeutic action points. The chromatin architecture modification gene HMGA1 has recently been described to be aberrantly expressed in lung adenocarcinoma (LUAD). However, the mechanisms mediating the expression of HMGA1 in LUAD remain unknown. Here we investigate the deregulation of a putative cis-acting lncRNA in LUAD, and its effect on the oncogene HMGA1.MethodsLncRNA expression was determined from RNA-sequencing data of tumor and matched non-malignant tissues from 36 LUAD patients. Transcripts with significantly deregulated expression were identified and validated in a secondary LUAD RNA-seq dataset (TCGA). SiRNA-mediated knockdown of a candidate cis-acting lncRNA was performed in BEAS-2B cells. Quantitative real-time PCR was used to observe the effects of lncRNA knockdown on the expression of HMGA1.ResultsWe identified the lncRNA RP11.513I15.6, which we refer to as HMGA1-lnc, neighboring HMGA1 to be significantly downregulated in both LUAD cohorts. Conversely, we found HMGA1 significantly overexpressed in LUAD and anticorrelated with HMGA1-lnc. In vitro experiments demonstrated siRNA-mediated inhibition of HMGA1-lnc in immortalized non-malignant lung epithelial cells resulted in a significant increase in HMGA1 gene expression.ConclusionOur results suggest that HMGA1-lnc is a novel cis-acting lncRNA that negatively regulates HMGA1 gene expression in lung cells. Further characterization of this regulatory mechanism may advance our understanding of the maintenance of lung cancer phenotypes and uncover a novel therapeutic intervention point for tumors driven by HMGA1.

BackgroundThe COVID-19 pandemic has had an enormous toll on human health and well-being and led to major social and economic disruptions. Public health interventions in response to burgeoning case numbers and hospitalizations have repeatedly bent down the epidemic curve in many jurisdictions, effectively creating a closed-loop dynamic system. We aim to formalize and illustrate how to incorporate principles of feedback control into pandemic projections and decision making.MethodsStarting with a SEEIQR epidemiological model, we illustrate how feedback control can be incorporated into pandemic management using a simple design (proportional-integral or PI control), which couples recent changes in case numbers or hospital occupancy with explicit policy restrictions. We then analyse a closed-loop system between the SEEIQR model and the designed feedback controller to illustrate the potential benefits of pandemic policy design that incorporates feedback.FindingsWe first explored a feedback design that responded to hospital measured infections, demonstrating robust ability to control a pandemic despite simulating large uncertainty in reproduction number R 0 (range: 1.04-5.18) and average time to hospital admission (range: 4-28 days). The second design compared responding to hospital occupancy to responding to case counts, showing that shorter delays reduced both the cumulative case count and the average level of interventions. Finally, we show that feedback is robust to changing public compliance to public health directives, and to systemic changes associated with new variants of concern and with the introduction of a vaccination program.InterpretationThe negative impact of a pandemic on human health and societal disruption can be reduced by coupling models of disease propagation with models of the decision-making process. This creates a closed-loop system that better represents the coupled dynamics of a disease and public health responses. Importantly, we show that feedback control is robust to delays in both measurements and responses, and to uncertainty in model parameters and the efficacy of control measures.

Objective The aim of this study was to analyze perceptions and experiences of clinicians implementing the patient-centered medical home (PCMH). Background The PCMH model focuses on several important concepts, including team-based care management as well as care coordination and continuity among providers and across settings of care. Methods A qualitative analysis of data collected in 2016 from primary care personnel through a national survey was conducted. Results Four themes were found consistent with care management and care coordination: the importance of teamwork and optimized team member roles, need for adequate prioritization of care management and care coordination, need to refine tools and resources supporting care management and care coordination, and challenges with managing and coordinating care with and across complex systems. Conclusions Successful implementation requires adequate support for teamwork and ensuring team members can work according to their clinical competency. Nurses practicing in expanded roles need clear role guidelines and adequate time to function in these roles.

The tumour immune microenvironment is a crucial mediator of lung tumourigenesis, and characterizing the immune landscape of patient tumours may guide immunotherapy treatment regimens and uncover novel intervention points. We sought to identify the landscape of tumour-infiltrating immune cells in the context of long non-coding RNA (lncRNAs), known regulators of gene expression. We examined the lncRNA profiles of lung adenocarcinoma (LUAD) tumours by interrogating RNA sequencing data from microdissected and non-microdissected samples (BCCRC and TCGA). Subsequently, analysis of single-cell RNA sequencing data from lung tumours and flow-sorted healthy peripheral blood mononuclear cells identified lncRNAs in immune cells, highlighting their biological and prognostic relevance. We discovered lncRNA expression patterns indicative of regulatory relationships with immune-related protein-coding genes, including the relationship between AC008750.1 and NKG7 in NK cells. Activation of NK cells in vitro was sufficient to induce AC008750.1 expression. Finally, siRNA-mediated knockdown of AC008750.1 significantly impaired both the expression of NKG7 and the anti-tumour capacity of NK cells. We present an atlas of cancer-cell extrinsic immune cell-expressed lncRNAs, in vitro evidence for a functional role of lncRNAs in anti-tumour immune activity, which upon further exploration may reveal novel clinical utility as markers of immune infiltration.

Around the globe, epidemiologists, statisticians, biologists, and health officials are grappling with these questions. Though engineering perspectives are uncommon in epidemiological modeling, we believe that in this case public officials could greatly benefit from one. Of course, the COVID-19 pandemic isn't an obvious or typical engineering problem. But in its basic behavior it is an unstable, open-loop system. Left alone, it grows exponentially. However, there's good news, too: Like many such systems, it can be stabilized effectively and efficiently by applying the principles of control theory, most notably the use of feedback.

This article presents a comprehensive synthesis and quantitative review of studies examining relationships between team design characteristics and team performance. Across 398 primary studies, the present study meta-analytically investigated the effects of team composition, team task design, and team leadership characteristics on team performance. The study further investigates how the effects of these team design characteristics differ according to the industry context within which the team is embedded (high technology, manufacturing, service, or student). Overall, this review emphasizes the importance of continued inquiries focusing on team design while also discussing the implications of this review for theory, practice, and future research.

PURPOSE Appropriate delegation of clinical tasks from primary care providers (PCPs) to other team members may reduce employee burnout in primary care. However, (1) the extent to which delegation occurs within multidisciplinary teams, (2) factors associated with greater delegation, and (3) whether delegation is associated with burnout are all unknown. METHODS We performed a national cross-sectional survey of Veterans Affairs (VA) PCP-nurse dyads in Department of VA primary care clinics, 4 years into the VA's patient-centered medical home initiative. PCPs reported the extent to which they relied on other team members to complete 15 common primary care tasks; paired nurses reported how much they were relied on to complete the same tasks. A composite score of task delegation/reliance was developed by taking the average of the responses to the 15 questions. We performed multivariable regression to explore predictors of task delegation and burnout. RESULTS Among 777 PCP-nurse dyads, PCPs reported delegating tasks less than nurses reported being relied on (PCP mean ± standard deviation composite delegation score, 2.97± 0.64 [range, 1-4]; nurse composite reliance score, 3.26 ± 0.50 [range, 1-4]). Approximately 48% of PCPs and 35% of nurses reported burnout. PCPs who reported more task delegation reported less burnout (odds ratio [OR], 0.62 per unit of delegation; 95% confidence interval [CI], 0.49-0.78), whereas nurses who reported being relied on more reported more burnout (OR, 1.83 per unit of reliance; 95% CI, 1.33-2.5). CONCLUSIONS Task delegation was associated with less burnout for PCPs, whereas task reliance was associated with greater burnout for nurses. Strategies to improve work life in primary care by increasing PCP task delegation must consider the impact on nurses.

Introduction: The objectives of this study were to examine if self-reported access to primary care is associated with actual patient wait times and use of telephone visits, and to assess whether this relationship differs by rural residence. Methods: This study used 2016 administrative data from 994 primary care clinics within the Veterans Health Administration. Multiple-linear regression was used to examine relationships between patient perceptions of access and average actual patient wait time, use of telephone visits, and rural residence. Average panel size, clinic type, and panel severity were included as model covariates with cross-product terms for actual wait time, telephone use, and rurality to test for interactions. Results: This study found patient perceptions of access aggregated at the clinic level to be conditional on the relationship between use of telephone visits, actual patient wait times, and rural residence. As actual wait time for routine appointments increases, Veterans served by clinics with a higher percent of rural Veterans perceive telephone visits more positively. Discussion: These findings contribute to our understanding of factors associated with patient perceptions of access by highlighting complex interrelationships between strategies intended to improve access to care and how they can have differing impacts on perceptions among those living in rural or urban locations.

We use a convergent parallel mixed methods approach to explore barriers to the successful implementation of a team-based empowerment initiative within the Veterans Health Administration. Although p...

Delegation research has traditionally focused on delegation as a whole—how much or how little a leader or supervisor is willing to allocate tasks to their subordinates. Although past research has i...

Modern organizations are complex and often require the use of teams to accomplish tasks. But to accomplish such tasks requires the effective assembly of human capital. As such, scholars and practit...

// Adam P. Sage 1,* , Brenda C. Minatel 1,* , Kevin W. Ng 1 , Greg L. Stewart 1 , Trevor J.B. Dummer 2 , Wan L. Lam 1 and Victor D. Martinez 1 1 Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada 2 Centre of Excellence in Cancer Prevention, School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada * These authors have contributed equally to this work Correspondence to: Victor D. Martinez, email: // Keywords : arsenic, cancer, genetics, epigenetics, non-coding RNA Received : November 30, 2016 Accepted : January 24, 2017 Published : February 05, 2017 Abstract Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability. At the epigenetic level, arsenic places a high demand on the cellular methyl pool, leading to global hypomethylation and hypermethylation of specific gene promoters. These arsenic-associated DNA alterations result in the deregulation of both oncogenic and tumour-suppressive genes. Furthermore, recent reports have implicated aberrant expression of non-coding RNAs and the consequential disruption of signaling pathways in the context of arsenic-induced carcinogenesis. This article provides an overview of the oncogenomic anomalies associated with arsenic exposure and conveys the importance of non-coding RNAs in the arsenic-induced carcinogenic process.

Background A particularly useful model for examining implementation of quality improvement interventions in health care settings is the PARIHS (Promoting Action on Research Implementation in Health Services) framework developed by Kitson and colleagues. The PARIHS framework proposes three elements (evidence, context, and facilitation) that are related to successful implementation. Purposes An evidence-based program focused on quality enhancement in health care, termed TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety), has been widely promoted by the Agency for Healthcare Research and Quality, but research is needed to better understand its implementation. We apply the PARIHS framework in studying TeamSTEPPS implementation to identify elements that are most closely related to successful implementation. Methodology/approach Quarterly interviews were conducted over a 9-month period in 13 small rural hospitals that implemented TeamSTEPPS. Interview quotes that were related to each of the PARIHS elements were identified using directed content analysis. Transcripts were also scored quantitatively, and bivariate regression analysis was employed to explore relationships between PARIHS elements and successful implementation related to planning activities. Findings The current findings provide support for the PARIHS framework and identified two of the three PARIHS elements (context and facilitation) as important contributors to successful implementation. Practice implications This study applies the PARIHS framework to TeamSTEPPS, a widely used quality initiative focused on improving health care quality and patient safety. By focusing on small rural hospitals that undertook this quality improvement activity of their own accord, our findings represent effectiveness research in an understudied segment of the health care delivery system. By identifying context and facilitation as the most important contributors to successful implementation, these analyses provide a focus for efficient and effective sustainment of TeamSTEPPS efforts.

Head and neck squamous cell carcinoma (HNSCC) has a poor survival rate mainly due to late stage diagnosis and recurrence. Despite genomic efforts to identify driver mutations and changes in protein-coding gene expression, developing effective diagnostic and prognostic biomarkers remains a priority to guide disease management and improve patient outcome. Recent reports of previously-unannotated microRNAs (miRNAs) from multiple somatic tissues have raised the possibility of HNSCC-specific miRNAs. In this study, we applied a customized in-silico analysis pipeline to identify novel miRNAs from raw small-RNA sequencing datasets from public repositories. We discovered 146 previously-unannotated sequences expressed in head and neck samples that share structural properties highly characteristic of miRNAs. The combined expression of the novel miRNAs revealed tissue and context-specific patterns. Furthermore, comparison of tumor with non-malignant tissue samples (n = 43 pairs) revealed 135 of these miRNAs as differentially expressed, most of which were overexpressed or exclusively found in tumor samples. Additionally, a subset of novel miRNAs was significantly associated with HPV infection status and patient outcome. A prognostic-model combining novel and known miRNA was developed (multivariate Cox regression analysis) leading to an improved death and relapse risk stratification (log rank p < 1e-7). The presence of these miRNAs was corroborated both in an independent dataset and by RT-qPCR analysis, supporting their potential involvement in HNSCC. In this study, we report the discovery of 146 novel miRNAs in head and neck tissues and demonstrate their potential biological significance and clinical relevance to head and neck cancer, providing a new resource for the study of HNSCC.

PURPOSE Patient engagement has been broadly defined as the process of actively involving and supporting patients in health care and treatment decision making. The aim of this study was to identify organizational factors that are associated with greater use of patient engagement care practices in Veterans Health Administration primary care clinics. METHODS We conducted a cross-sectional analysis of data from the 2016 Patient-Aligned Care Team (PACT) national survey of direct care clinicians (primary care clinicians, registered nurses, and clinical associates). Exploratory factor analysis was used to group conceptually related patient engagement survey items into 3 subscales: planning and goal setting; motivational interviewing; and organizational strategies to promote self-management. Our independent variables included literature-based factors reported to promote team-based care and interdisciplinary collaboration in primary care. We used generalized estimating equations with multivariate logistic regression analysis to identify independent correlates of high performance on each patient engagement domain (top 25th vs bottom 25th percentile). RESULTS A total of 2,478 direct care clinicians from 609 clinics completed all patient engagement items in the PACT survey. For all patient engagement sub-scales, respondents at high-performing clinics were more likely to report having regular team meetings to discuss performance improvement and having leadership responsible for implementing PACT. For 2 of 3 patient engagement subscales, high performance was also associated with having fully staffed PACT teams (≥3 team members per primary care clinician) and role clarity. CONCLUSIONS Several desirable organizational and contextual factors were associated with high performance of patient engagement care practices. Strategies to improve the organizational functioning of primary care teams may enhance patient engagement in care.

Recent studies have uncovered microRNAs (miRNAs) that have been overlooked in early genomic explorations, which show remarkable tissue- and context-specific expression. Here, we aim to identify and characterize previously unannotated miRNAs expressed in gastric adenocarcinoma (GA). Raw small RNA-sequencing data were analyzed using the miRMaster platform to predict and quantify previously unannotated miRNAs. A discovery cohort of 475 gastric samples (434 GA and 41 adjacent nonmalignant samples), collected by The Cancer Genome Atlas (TCGA), were evaluated. Candidate miRNAs were similarly assessed in an independent cohort of 25 gastric samples. We discovered 170 previously unannotated miRNA candidates expressed in gastric tissues. The expression of these novel miRNAs was highly specific to the gastric samples, 143 of which were significantly deregulated between tumor and nonmalignant contexts (p-adjusted < 0.05; fold change > 1.5). Multivariate survival analyses showed that the combined expression of one previously annotated miRNA and two novel miRNA candidates was significantly predictive of patient outcome. Further, the expression of these three miRNAs was able to stratify patients into three distinct prognostic groups (p = 0.00003). These novel miRNAs were also present in the independent cohort (43 sequences detected in both cohorts). Our findings uncover novel miRNA transcripts in gastric tissues that may have implications in the biology and management of gastric adenocarcinoma.

Background Though much is known about the benefits attributed to medical scribes documenting patient visits (e.g., reducing documentation time for the provider, increasing patient-care time, expanding the roles of licensed and non-licensed personnel), little attention has been paid to how care workers enact scribing as a part of their existing practice. The purpose of this study was to perform an ethnographic process evaluation of an innovative medical scribing practice with primary care teams in Veterans Health Administration (VHA) clinics across the United States. The aim of our study was to understand barriers and facilitators to implementing a scribing practice in primary care. Methods At three to six months after medical scribing was introduced, we used semi-structured interviews and direct observations during site visits to five sites to describe the intervention, understand if the intervention was implemented as planned, and to record the experience of the teams who implemented the intervention. This manuscript only reports on semi-structured interview data collected from providers and scribes. Initial matrix analysis based on categories outlined in the evaluation plan informed subsequent deductive coding using the social-shaping theory Normalization Process Theory. Results Through illustrating the slow accumulation of interactions and knowledge that fostered cautious momentum of teams working to normalize scribing practice in VHA primary care clinics, we show how the practice had 1) an organizing effect, as it centered a shared goal (the creation of the note) between the provider, scribe, and patient, and 2) a generative effect, as it facilitated care workers developing relationships that were both interpersonally and inter-professionally valuable. Based on our findings, we suggest that a scribing practice emphasizes the complementarity of existing professional roles, which thus leverage the interactional possibilities already present in the primary care team. Scribing, as a skill, forged moments of interprofessional fit. Scribing, in practice, created opportunities for interpersonal connection. Conclusions Our research suggests that individuals will notice different benefits to scribing based on their professional expectations and organizational roles related to documenting patient visits. Electronic supplementary material The online version of this article (10.1186/s12913-019-4355-z) contains supplementary material, which is available to authorized users.

Teams are a basic building block of organizations. Over the past twenty-five years, a great deal of research has focused on what can be done to improve team effectiveness. Team design characteristics represent inputs that can be manipulated by organizational leaders and can be grouped into three broad classifications: Team Composition, Team Task Design Characteristics, and Team Leadership. The first team design characteristic—composition—focuses on the attributes of individuals who are team members and is generally captured either as the average standing on a particular trait such as mental ability or as a pattern of a characteristic such as the variability in team member conscientiousness. Teams composed of members with desirable traits generally outperform teams composed of members who do not possess desirable individual characteristics. Members with negative individual characteristics harm cooperation and are often rejected by teammates. The impact of some team members—frequently labeled the strategic core—is, however, greater than the impact of others. Team Member Diversity of individual characteristics also corresponds with team processes and outcomes, although the effect is positive in some instances and negative in others. A particularly difficult methodological issue associated with team composition research concerns missing data that occurs when some team members fail to complete survey measures. The second team design feature—team task characteristics—arises from the work itself and how the team accomplishes its prescribed tasks. Some teams have a high level of collective autonomy whereas others work under strict hierarchical control. Teams vary in interdependence with some operating such that members work together very closely and others allowing members to work primarily as individuals. Differences in reward structure also vary from teams that are rewarded collectively to teams with individual-based rewards that result in some members being rewarded more than others. Moreover, an increasingly important task feature of teams is the degree of virtuality, with some teams interacting primarily face-to-face and others interacting mostly through electronic means. The third team design feature is leadership. Teams are facilitated by Empowering Leadership that encourages the team to collectively lead itself, by Shared Leadership that exists when leadership functions are dispersed throughout the team, and by Transformational Leadership that provides teams with a vision that transcends individual interests.

Transcriptome sequencing has led to the widespread identification of long non-coding RNAs (lncRNAs). Subsequently, these genes have been shown to hold functional importance in human cellular biology, which can be exploited by tumors to drive the hallmarks of cancer. Due to the complex tertiary structure and unknown binding motifs of lncRNAs, there is a growing disparity between the number of lncRNAs identified and those that have been functionally characterized. As such, lncRNAs deregulated in cancer may represent critical components of cancer pathways that could serve as novel therapeutic intervention points. Pseudogenes are non-coding DNA sequences that are defunct relatives of their protein-coding parent genes but retain high sequence similarity. Interestingly, certain lncRNAs expressed from pseudogene loci have been shown to regulate the protein-coding parent genes of these pseudogenes in trans particularly because of this sequence complementarity. We hypothesize that this phenomenon occurs more broadly than previously realized, and that aberrant expression of lncRNAs overlapping pseudogene loci provides an alternative mechanism of cancer gene deregulation. Using RNA-sequencing data from two cohorts of lung adenocarcinoma, each paired with patient-matched non-malignant lung samples, we discovered 104 deregulated pseudogene-derived lncRNAs. Remarkably, many of these deregulated lncRNAs (i) were expressed from the loci of pseudogenes related to known cancer genes, (ii) had expression that significantly correlated with protein-coding parent gene expression, and (iii) had lncRNA protein-coding parent gene expression that was significantly associated with survival. Here, we uncover evidence to suggest the lncRNA-pseudogene-protein-coding gene axis as a prominent mechanism of cancer gene regulation in lung adenocarcinoma, and highlights the clinical utility of exploring the non-coding regions of the cancer transcriptome.

Cancer care delivery is highly complex. Treatment involves coordination within oncology health-care teams and across other teams of referring primary and specialty providers (a team of teams). Each team interfaces with patients and caregivers to offer component parts of comprehensive care. Because patients frequently obtain specialty care from divergent health-care systems resulting in cross-system health-care use, oncology teams need mechanisms to coordinate and collaborate within and across health-care systems to optimize clinical outcomes for all cancer patients. Transactive memory is one potential strategy that can help improve comprehensive patient care delivery. Transactive memory is a process by which two or more team professionals develop a shared system for encoding, storing, and retrieving information. Each professional is responsible for retaining only part of the total information. Applying this concept to a team of teams results in system benefits wherein all teams share an understanding of specialized knowledge held by each component team. The patient’s role as the unifying member of the team of teams is central to successful treatment delivery. This clinical case presents a patient who is receiving oral treatment for advanced prostate cancer within two health systems. The case emphasizes the potential for error when multiple teams function without a point team (the team coordinating efforts of all other primary and specialty teams) and when the specialty knowledge of providers and patients is not well integrated into all phases of the care delivery process.

While considerable research has been conducted on understanding why individuals are perceived as leaders in traditional work contexts, much less is known about how individual difference variables influence leader perceptions in a virtual environment. In this study, we examine this issue by investigating the effects of two communication-related constructs (communication apprehension [CA] and text-based communication ability [TBCA]) on leadership emergence in virtual teams. We also examine how leadership emergence is affected by team dispersion: specifically, overall team configuration and dyadic team member co-location. Predicated on adaptive structuration theory (DeSanctis & Poole, 1994), we propose a theoretical model that outlines the effects of the individual difference attributes and team dispersion variables on leadership emergence. Results of an experiment testing the model with 84 four-person teams of varying levels of team member dispersion suggest that CA and TBCA have significant relationships with leadership emergence, as well as team configuration and team member co-location.

International implementation of the patient-centered medical home (PCMH) model for delivering primary care has dramatically increased in the last decade. A majority of research on PCMH's impact has emphasized the care provided by clinically trained staff. In this article, we report our ethnographic analysis of data collected from Department of Veterans Affairs staff implementing PACT, the VA version of PCMH. Teams were trained to use within-team delegation, largely accomplished through attention to clinical licensure, to differentiate staff in providing efficient, patient-centered care. In doing so, PACT may reinforce a clinically defined culture of care that countermands PCMH ideals. Such competing rubrics for care are brought into relief through a focus on the care work performed by clerks. Ethnographic analysis identifies clerks' care as a kind of emotional dirty work, signaling important areas for future anthropological study of the relationships among patient-centered care, stigma, and clinical authority.

BACKGROUND: Physician burnout is associated with deleterious effects for physicians and their patients and might be exacerbated by practice transformation. OBJECTIVE: Assess the effect of the Comprehensive Primary Care (CPC) initiative on primary care physician experience. DESIGN: Prospective cohort study conducted with about 500 CPC and 900 matched comparison practices. Mail surveys of primary care physicians, selected using cross-sectional stratified random selection 11 months into CPC, and a longitudinal design with sample replacement 44 months into CPC. PARTICIPANTS: Primary care physicians in study practices. INTERVENTION: A multipayer primary care transformation initiative (October 2012–December 2016) that required care delivery changes and provided enhanced payment, data feedback, and learning support. MAIN MEASURES: Burnout, control over work, job satisfaction, likelihood of leaving current practice within 2 years. KEY RESULTS: More than 1000 physicians responded (over 630 of these in CPC practices) in each round (response rates 70–81%, depending on round and research group). Physician experience outcomes were similar for physicians in CPC and comparison practices. About one third of physician respondents in CPC and comparison practices reported high levels of burnout in each round (32 and 29% in 2013 [P = 0.59], and 34 and 36% in 2016 [P = 0.63]). Physicians in CPC and comparison practices reported some to moderate control over work, with an average score from 0.50 to 0.55 out of 1 in 2013 and 2016 (CPC-comparison differences of − 0.04 in 2013 [95% CI − 0.08–0.00, P = 0.07], and − 0.03 in 2016 [95% CI − 0.03–0.02, P = 0.19]). In 2016, roughly three quarters of CPC and comparison physicians were satisfied with their current job (77 and 74%, P = 0.77) and about 15% planned to leave their practice within 2 years (14 and 15%, P = 0.17). CONCLUSIONS: Despite requiring substantial practice transformation, CPC did not affect physician experience. Research should track effects of other transformation initiatives on physicians and test new ways to address burnout. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02320591 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-018-4545-0) contains supplementary material, which is available to authorized users.

Background: It is a truism that children are our future and yet is only recently that science has come to understand the significant impact that child and youth development has on later adult health and wellbeing. This includes not only prevention of disease, injury and disability, but also inclusion in education, employment and social relationships. Important during these early years is the interaction of a child’s genetic inheritance with the family and home environment, and later the peer-relationships, school and community environment. There are also critical historical and intergenerational influences that have a profound impact on the genetic-environment interaction. Adverse childhood experiences (ACE) of parents and caregivers can continue to have an impact. Local and state communities seek to mitigate these adverse impacts. The proverb “it takes a village to raise a child” provides the underlying ethos whereby all members of society work together to raise healthy and resilient children and young people. To do so it is necessary support and nurture, mothers, fathers, families, children and young people along an ever changing life-course trajectory that may require inputs from maternity services, childcare, schools, primary care, welfare and housing, income support, mental health, police, and hospitals. The provision of this support to families, children and young people can be complex and for some it will require a number of simultaneous inputs. It could be argued that the potential complexity of inputs is not realised at any other stage of the life-course. Each stage of child and youth development has its own unique complexity, be it: pregnancy and childbirth; early childhood; school; adolescence and early adulthood. Thus the integration of system-wide policies and services has long provided the foundation for promoting and protecting the health, development and wellbeing of children, young people and their families. The United Nations Convention on the Rights of Children and the Sustainable Development Goals (SDGs) provide the global platform to addressing the needs of children young people and families. The challenges are global. Integration of services for families, children and young people, for example, is important in low-income countries, countries affected by war, among refugee and migrant populations, and within rich countries as highlighted by the recent Innocenti Report. Aims and Objectives: 1) Discuss definitions and scope for Integrating Health and Social Care as it applies to Children, Young People and their Families 2) Discuss the scope and purpose of a Integrating Care for Children Youth People and Their Families Special Interest Group (IC-CYF SIG) 3) Modify the Scope and Purpose Document for the Integrating Care for Children Youth People and Their Families, Special Interest Group (IC-CYF SIG) Format: Timing 60 minutes, One Speaker, Group work at tables, Feed-back from tables, Discussion and Summation Target Audience: Health, education and social care practitioners and researchers who are interested in aspects of integrated health and social care as it applies to children, young people and their families. Learnings and Takeaway: The workshop will define the scope and purpose of a SIG for Integrating Care for Children Youth People and Their Families.

Made available in DSpace on 2019-10-06T15:22:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-26 Canada Foundation for Innovation Canadian Institutes of Health Research University of British Columbia MicroRNAs (miRNAs) are crucial regulators of gene expression in normal development and cellular homeostasis. While miRNA repositories contain thousands of unique sequences, they primarily contain molecules that are conserved across several tissues, largely excluding lineage and tissue-specific miRNAs. By analyzing small non-coding RNA sequencing data for abundance and secondary RNA structure, we discovered 103 miRNA candidates previously undescribed in liver tissue. While expression of some of these unannotated sequences is restricted to non-malignant tissue, downregulation of most of the sequences was detected in liver tumors, indicating their importance in the maintenance of liver homeostasis. Furthermore, target prediction revealed the involvement of the unannotated miRNA candidates in fatty-acid metabolism and tissue regeneration, which are key pathways in liver biology. Here, we provide a comprehensive analysis of the undiscovered liver miRNA transcriptome, providing new resources for a deeper exploration of organ-specific biology and disease. Department of Integrative Oncology British Columbia Cancer Research Centre Krembil Research Institute University Health Network Faculty of Medicine São Paulo State University (UNESP) Faculty of Medicine São Paulo State University (UNESP) Canada Foundation for Innovation: 225404 Canada Foundation for Innovation: 30865

Introduction: Health Justice Partnerships (HJPs) are local collaborations between legal assistance, health, and social care organisations. They seek to meet the legal needs of clients who would otherwise not seek legal assistance, and to provide timely intervention in legal issues. Because each partnership is localised, HJPs serve different populations in different service arrangements. A challenge for HJPs is to develop a robust evidence base to support their development, which requires evaluation of HJPs’ impact individually and collectively. This presentation describes a program logic that was developed with HJPs in New South Wales (NSW), as an initial step towards examining their impact and effectiveness in the Australian context. Policy context and objective: HJPs in NSW have evolved at the local level, and each local partnership between services is governed through individual memoranda of understanding. Clients’ legal needs and organisational arrangements vary between individual HJPs. Targeted population: Vulnerable people experiencing complex, interrelated, and compounding legal and health problems. Highlights: A program logic that was developed, based on a series of workshops that were undertaken with representatives of NSW HJPs. It sets out sets out the principles that underpin HJPs’ operation, assumptions, inputs, activities, outcomes and impacts. It differentiates outcomes for clients, workers, partnerships, and for the justice and health systems. Comments on transferability: This program logic provides a starting point for planning and evaluating local partnerships that integrate health and social care. By describing key components of multi-site partnerships with a focus on integration, the program logic develops a shared terminology. Conclusions: A tension in evaluating disparate but related initiatives is accurately describing their activities, and how these individually and collectively contribute to change. Further work: is required to test and adapt the logic, and to use it to develop more robust evaluation, monitoring and performance frameworks.

The experiences of RNs and licensed practical nurses (LPNs) implementing a patient-centered medical home (PCMH) in the Department of Veterans Affairs (VA) primary care clinics were examined to understand model implications for nursing practice and professional identity.National implementation of the PCMH model, called patient-aligned care teams (PACTs) in VA, emphasizes areas of nursing expertise, yet little is known about the effect of medical homes on the day-to-day work of nurses.As part of a formative evaluation to identify barriers and facilitators to PACT implementation, we interviewed 18 nurses implementing PACT.Challenges to nurse's organizational and professional roles were experienced differently by RNs and LPNs in the following areas: (1) diversified modes of care and expanded clinical duties, (2) division of labor among PACT nurses, and (3) interprofessional status in the team.Healthcare managers implementing PCMH should consider its inherent cultural and practice transformations.

Implementation of TeamSTEPPS for improving patient safety is examined via descriptive qualitative analysis of semistructured interviews with 21 informants at 12 hospitals. Implementation approaches fit 3 strategies: top-down, bottom-up, and combination. The top-down approach failed to develop enough commitment to spread implementation. The bottom-up approach was unable to marshal the resources necessary to spread implementation. Combining top-down and bottom-up processes best facilitated the implementation and spread of the TeamSTEPPS safety initiative.

Purpose – Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) is being widely promoted in healthcare settings to train staff in evidence-based approaches that promote patient safety. It involves a comprehensive curriculum that spells out key principles and actionable tools for a culture change toward patient-safety-focussed teamwork. Activities begin with selected personnel attending TeamSTEPPS Master Trainer Training (MTT) and then organizing and providing TeamSTEPPS training for staff in their organization. The authors conducted interviews with respondents at community hospitals conducting TeamSTEPPS staff training. To structure the interviews, the authors used 11 key questions identified by Weaver et al. in their in-depth team training literature review. The purpose of this paper is to examine approaches taken by community hospital personnel and compare those to the best practices recommended by Weaver et al. Design/methodology/approach – The authors interviewed 57 staff and administrators at 22 community hospitals sending teams to TeamSTEPPS MTT. Findings – The authors find that training implementation in community hospitals differs significantly from the established, research-based principles for effective team training described in the research literature, which is largely based in academic medical centers. Originality/value – The current findings suggest that several TeamSTEPPS training features could be enhanced in community hospitals including: choosing staff who have the skills to be effective trainers in this train-the-trainer model; emphasizing active learning; and sustaining lessons through on-the-job application, practice and feedback. These principles apply to many training approaches employed in small healthcare organizations.

Research evaluating the effectiveness, function, and implementation of patient-centered medical homes (PCMHs) has found major socioprofessional transformations and contributions of primary care physicians and, to a lesser degree, nurses. Our longitudinal ethnographic research with teams implementing PCMH in Veterans Health Administration (VHA) primary care identifies the important but largely underutilized contributions of clerks to PCMH outcomes. Although the relationship of high-performing clerical staff to patient satisfaction is widely acknowledged, PCMH can be further enhanced by enabling clerks to use administrative tasks as conduits for investing in long-term personalized relationships with patients that foster trust in the PCMH and the broader health care organization. Such relationships are engendered through the care-coordination activities clerks perform, which may be bolstered by organizational investment in clerks as skilled health care team members.

The patient-centered medical home (PCMH) relies on a team approach to patient care. For organizations engaged in transitioning to a PCMH model, identifying and providing the resources needed to promote team functioning is essential.To describe team-level resources required to support PCMH team functioning within the Veterans Health Administration (VHA), and provide insight into how the presence or absence of these resources facilitates or impedes within-team delegation.Semi-structured interviews with members of pilot teams engaged in PCMH implementation in 77 primary care clinics serving over 300,000 patients across two VHA regions covering the Mid-Atlantic and Midwest United States.A purposive sample of 101 core members of pilot teams, including 32 primary care providers, 42 registered nurse care managers, 15 clinical associates, and 12 clerical associates.Investigators from two evaluation sites interviewed frontline primary care staff separately, and then collaborated on joint analysis of parallel data to develop a broad, comprehensive understanding of global themes impacting team functioning and within-team delegation.We describe four themes key to understanding how resources at the team level supported ability of primary care staff to work as effective, engaged teams. Team-based task delegation was facilitated by demarcated boundaries and collective identity; shared goals and sense of purpose; mature and open communication characterized by psychological safety; and ongoing, intentional role negotiation.Our findings provide a framework for organizations to identify assets already in place to support team functioning, as well as areas in need of improvement. For teams struggling to make practice changes, our results indicate key areas where they may benefit from future support. In addition, this research sheds light on how variation in medical home implementation and outcomes may be associated with variation in team-based task delegation.