Exploring formal and informal learning opportunities during morning report: a qualitative study.

BACKGROUND: Morning reports are an essential component of physicians' daily work. Attending morning reports is prioritized by junior doctors as it provides them with an opportunity to learn diagnostic reasoning through discussion of cases. While teaching formats during morning reports have previously been reported, an in-depth analysis of what learning opportunities exist, e.g., how teaching is enacted during morning reports, is lacking. This qualitative study explores learning opportunities during morning reports. METHODS: We used an explorative design based on video-recordings of 23 morning reports from two surgical departments, an internal medicine department and an emergency department. We used thematic analysis combined with and inspired by Eraut's theoretical framework of workplace learning. RESULTS: Both formal and informal learning opportunities were identified. Formal learning opportunities had the character of planned teaching activities, and we identified four themes: (1) modes of teaching, (2) structure, (3) presenter role, and (4) participant involvement. Informal learning, on the other hand, was often implicit and reactive, while deliberate learning opportunities were rare. The data showed many missed opportunities for learning. CONCLUSION: Both formal and informal learning opportunities are present during morning reports. However, a prevalent focus on medical topics exists, leaving other important aspects of the medical role under-discussed. Pedagogical methods could be employed more optimally, and harnessing the potential of missed opportunities should be encouraged.

How doctors build community and socialize into a clinical department through morning reports. A positioning theory study.

PHENOMENON: The morning report is one of the longest surviving hospital practices. Most studies of the morning report focus on the effectiveness of formal medical training, while focus on social and communicative aspects is rarer. This study explores the social interactions and communication in morning reports, examining the ways in which they contribute to the construction of professional identity and socialization into the community of the clinical department. APPROACH: We used a qualitative explorative design with video observations of morning reports. Our data consisted of 43 video-recorded observations (in all, 15.5 hours) from four different hospital departments in Denmark. These were analyzed using the theoretical framework of positioning theory. FINDINGS: A key finding was that each department followed its own individual structure. This order was not articulated as such but played out implictly. Two alternative storylines unfolded in the elements of the morning report: 1) being equal members of the specialty and department, and 2) preserving the hierarchical community and its inherent positions. INSIGHTS: The morning report can be seen as playing an important role in community making. It unfolds as a "dance" of repeated elements in a complex collegial space. Within this complexity, the morning report is a space for positioning oneself and others as a collegial "we", i.e., equal members of a department and specialty, at the same time as "having a place" in a hierarchal community. Thus, morning reports contribute to developing professional identity and socialization into the medical community.

What works in appraisal meetings for newly graduated doctors? - and what doesn't?

BACKGROUND: In Denmark a national formal advisory program (NFAP) is mandatory in Postgraduate Medical Education (PGME). According to this, an educational advisor is assigned to each doctor in every clinical rotation to guide and oversee the work and learning progress of the trainee. This study explores why newly graduated trainees evaluated the appraisal meetings in the advisory program as either beneficial (successes) or not beneficial (non-successes). METHODS: Inspired by the Success Case Method, a survey was conducted among all 129 doctors employed in their first six-month clinical rotation of postgraduate medical education (PGY1) in the Central Denmark Region. A cluster analysis resulted in a group with eight successes respectively seven non-successes. Semi-structured interviews were conducted with six successes and five non-successes. RESULTS: In contrast to non-successes, the successes had longer appraisal meetings and their advisor introduced them to purpose and process of meetings including use of the personal learning plan. Successes received feedback on clinical skills, overall global performance and career plans. The successes perceived their advisors as prepared, skilled and motivated and the advisor acted as a contact person. To the successes, the appraisal meetings fostered clarification of and reflections on educational goals, progress and career as well as self-confidence and a sense of security. CONCLUSION: Success with appraisal meetings seemed to depend on advisor's skills and motivation including willingness to prioritize time for this task. The results from this study indicate the importance of faculty development. It also raises the question if all doctors should serve as advisors or if this task should be assigned to the most motivated candidates.

Attitude and Barriers in Palliative Care and Advance Care Planning in Nonmalignant Chronic Lung Disease: Results From a Danish National Survey.

INTRODUCTION: Patients with chronic obstructive pulmonary disease and interstitial lung disease have a significant burden of symptoms. Many are not offered palliative care (PC). Our aim was to investigate the attitudes to and barriers for PC among physicians. METHOD: A web-based survey was conducted among members of the Danish Respiratory Society. The questionnaire included contextual (gender, age, clinical experience, type of center, patient caseload) and outcome questions (knowledge and use of statements for PC and advance care planning [ACP], practice of communication about end-of-life decisions, practice for referral to PC, barriers regarding structural surroundings, clinical skills, and organization). RESULTS: One hundred fifty-six (45%) physicians responded. Median age was 40 - 49 years and 55% were female. Fifty-two percent were specialists; 71% worked at a university hospital. The majority of physicians (60%) reported barriers for discussions about PC and ACP; 63% reported lack of time, 52% lack of multidisciplinary staff settings, 63% reported the unpredictability of the prognosis, and 20% insufficient awareness of patient's culture, religion, or spirituality. Fewer specialists than nonspecialists reported barriers toward ACP. The majority had knowledge of guidelines in PC and ACP, but only a minority used these in daily clinical practice. CONCLUSION: The attitude toward PC and ACP conversations was positive and implementation was regarded as important, but only a minority performed these conversations in practice. Main barriers were lack of time and staff. Palliative care guidelines were known but only scarcely used. Structural changes at the organizational level to improve access to palliation for patients with nonmalignant chronic lung diseases are needed.

[Palliative care is for everyone, even for patients with life-threatening medical organ failure].

Healthcare authorities have emphasised the need to develop palliative care for everybody suffering from life-threatening diseases, including people suffering from medical organ failure. In 2011, the Danish Health Authority requested that all medical associations developed guidelines for palliative care. Until now, this has been fulfilled by only four associations. The aim of this review is to summarise the status of the palliative care needs and palliative care across diagnosis for patients suffering from life-threatening medical organ failure and to draw attention to the lack of care and the importance of guidelines.

[Treatment limitations or discontinuation in patients with benign pulmonary diseases].

The decision to limit or discontinue treatment is a difficult issue, which all physicians will face. Timely communication with information on treatment possibilities and limitations, respectful listening to patients' and informal caregivers' wishes and early palliation is recommended in a stable phase. In some situations, it is better to stop life-prolonging treatment and optimise quality of life in patients with benign pulmonary diseases. Decision on treatment limitations or discontinuation is best taken at a conference and should be based on the patient's wishes, the disease stage and progression and potential reversible components.

Danish respiratory society position paper: palliative care in patients with chronic progressive non-malignant lung diseases.

Background:  Chronic non-malignant lung diseases such as chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD) result in reduced quality of life (QoL), a high symptom burden and reduced survival. Patients with chronic non-malignant lung disease often have limited access to palliative care. The symptom burden and the QoL of these patients resembles patients with cancer and the general palliative approach is similar. However, the disease trajectory is often slow and unpredictable, and the palliative effort must be built on accessibility, continuity and professional competences. The Danish Health Authority as well as the WHO recommends that there is access to palliative care for all patients with life-threatening diseases regardless of diagnosis. In 2011, the Danish Health Authority requested that the national medical societies would to formulate guidelines for palliation. Methods: In 2015, a group of members of the Danish Respiratory Society (DRS) was appointed for this purpose. It was composed of experienced ILD and COPD researchers as well as clinicians from different parts of Denmark. A literature review was made, a draft was prepared, and all recommendations were agreed upon unanimously. Results: The Danish version of the position paper was finally submitted for review and accepted by all members of DRS. Conclusion: In this position paper we provide recommendations on the terminology of chronic and terminal lung failure, rehabilitation and palliative care, advanced care planning, informal caregivers and bereavement, symptom management, the imminently dying patient, and organization of palliative care for patients with chronic non-malignant lung diseases.

A SWOT analysis of how the youngest doctors perceive the formal Danish educational advisory programme.

INTRODUCTION: A national formal advisory programme (NFAP) was introduced in Denmark in 1998. This study investigates the implementation of the NFAP and identifies areas to improve. METHODS: In March 2017, a survey was conducted among all 129 doctors employed in the first rotation of postgraduate medical education in the Central Denmark Region. A priority chart was created to appoint strengths, weaknesses, op-portunities and threats (SWOT). RESULTS: The response rate was 67%. The questionnaire showed good reliability and discriminant validity. Almost all respondents had completed the recommended appraisal meetings and a personal learning plan, both of which - in contrast to the NFAP's coherence to everyday clinical practice - showed to have much influence on the overall value of the NFAP. Strengths found were that appraisal meetings and learning plans support the development of clinical competencies, the latter identifying learning objectives and how to achieve them. Threats identified included learning plans that were not prepared sufficiently early, were not regularly adjusted and that did not describe when each learning objective is to be achieved, or when, by whom or how assessment will take place. CONCLUSIONS: Appraisal meetings and learning plans seem to be well implemented and to support the development of clinical competencies. Even so, improvements are needed, particularly to ensure an earlier preparation, inclusion of plans for assessment and regular adjustment of the learning plans. FUNDING: The study was funded by the Central Denmark Region. TRIAL REGISTRATION: Data collection was approved by the Danish Health Data Authority.

Lamin A, Chromatin and FPLD2: Not Just a Peripheral Ménage-à-Trois.

At the nuclear periphery, the genome is anchored to A- and B-type nuclear lamins in the form of heterochromatic lamina-associated domains. A-type lamins also associate with chromatin in the nuclear interior, away from the peripheral nuclear lamina. This nucleoplasmic lamin A environment tends to be euchromatic, suggesting distinct roles of lamin A in the regulation of gene expression in peripheral and more central regions of the nucleus. The hot-spot lamin A R482W mutation causing familial partial lipodystrophy of Dunnigan-type (FPLD2), affects lamin A association with chromatin at the nuclear periphery and in the nuclear interior, and is associated with 3-dimensional (3D) rearrangements of chromatin. Here, we highlight features of nuclear lamin association with the genome at the nuclear periphery and in the nuclear interior. We address recent data showing a rewiring of such interactions in cells from FPLD2 patients, and in adipose progenitor and induced pluripotent stem cell models of FPLD2. We discuss associated epigenetic and genome conformation changes elicited by the lamin A R482W mutation at the gene level. The findings argue that the mutation adversely impacts both global and local genome architecture throughout the nucleus space. The results, together with emerging new computational modeling tools, mark the start of a new era in our understanding of the 3D genomics of laminopathies.

A lipodystrophy-causing lamin A mutant alters conformation and epigenetic regulation of the anti-adipogenic MIR335 locus.

Mutations in the Lamin A/C (LMNA) gene-encoding nuclear LMNA cause laminopathies, which include partial lipodystrophies associated with metabolic syndromes. The lipodystrophy-associated LMNA p.R482W mutation is known to impair adipogenic differentiation, but the mechanisms involved are unclear. We show in this study that the lamin A p.R482W hot spot mutation prevents adipogenic gene expression by epigenetically deregulating long-range enhancers of the anti-adipogenic MIR335 microRNA gene in human adipocyte progenitor cells. The R482W mutation results in a loss of function of differentiation-dependent lamin A binding to the MIR335 locus. This impairs H3K27 methylation and instead favors H3K27 acetylation on MIR335 enhancers. The lamin A mutation further promotes spatial clustering of MIR335 enhancer and promoter elements along with overexpression of the MIR355 gene after adipogenic induction. Our results link a laminopathy-causing lamin A mutation to an unsuspected deregulation of chromatin states and spatial conformation of an miRNA locus critical for adipose progenitor cell fate.

Chrom3D: three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts.

Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells. Chrom3D reveals unexpected spatial features of LAD regulation in cells from patients with a laminopathy-causing lamin mutation. Chrom3D is freely available on github.

Genome-wide analysis of DNA methylation and gene expression patterns in purified, uncultured human liver cells and activated hepatic stellate cells.

BACKGROUND & AIMS: Liver fibrogenesis - scarring of the liver that can lead to cirrhosis and liver cancer - is characterized by hepatocyte impairment, capillarization of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cell (HSC) activation. To date, the molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. Here, we assess the transcriptome and the genome-wide promoter methylome specific for purified, non-cultured human hepatocytes, LSECs and HSCs, and investigate the nature of epigenetic changes accompanying transcriptional changes associated with activation of HSCs. MATERIAL AND METHODS: Gene expression profile and promoter methylome of purified, uncultured human liver cells and culture-activated HSCs were respectively determined using Affymetrix HG-U219 genechips and by methylated DNA immunoprecipitation coupled to promoter array hybridization. Histone modification patterns were assessed at the single-gene level by chromatin immunoprecipitation and quantitative PCR. RESULTS: We unveil a DNA-methylation-based epigenetic relationship between hepatocytes, LSECs and HSCs despite their distinct ontogeny. We show that liver cell type-specific DNA methylation targets early developmental and differentiation-associated functions. Integrative analysis of promoter methylome and transcriptome reveals partial concordance between DNA methylation and transcriptional changes associated with human HSC activation. Further, we identify concordant histone methylation and acetylation changes in the promoter and putative novel enhancer elements of genes involved in liver fibrosis. CONCLUSIONS: Our study provides the first epigenetic blueprint of three distinct freshly isolated, human hepatic cell types and of epigenetic changes elicited upon HSC activation.

Promoter DNA methylation patterns of differentiated cells are largely programmed at the progenitor stage.

Mesenchymal stem cells (MSCs) isolated from various tissues share common phenotypic and functional properties. However, intrinsic molecular evidence supporting these observations has been lacking. Here, we unravel overlapping genome-wide promoter DNA methylation patterns between MSCs from adipose tissue, bone marrow, and skeletal muscle, whereas hematopoietic progenitors are more epigenetically distant from MSCs as a whole. Commonly hypermethylated genes are enriched in signaling, metabolic, and developmental functions, whereas genes hypermethylated only in MSCs are associated with early development functions. We find that most lineage-specification promoters are DNA hypomethylated and harbor a combination of trimethylated H3K4 and H3K27, whereas early developmental genes are DNA hypermethylated with or without H3K27 methylation. Promoter DNA methylation patterns of differentiated cells are largely established at the progenitor stage; yet, differentiation segregates a minor fraction of the commonly hypermethylated promoters, generating greater epigenetic divergence between differentiated cell types than between their undifferentiated counterparts. We also show an effect of promoter CpG content on methylation dynamics upon differentiation and distinct methylation profiles on transcriptionally active and inactive promoters. We infer that methylation state of lineage-specific promoters in MSCs is not a primary determinant of differentiation capacity. Our results support the view of a common origin of mesenchymal progenitors.

Chromatin environment of histone variant H3.3 revealed by quantitative imaging and genome-scale chromatin and DNA immunoprecipitation.

In contrast to canonical histones, histone variant H3.3 is incorporated into chromatin in a replication-independent manner. Posttranslational modifications of H3.3 have been identified; however, the epigenetic environment of incorporated H3.3 is unclear. We have investigated the genomic distribution of epitope-tagged H3.3 in relation to histone modifications, DNA methylation, and transcription in mesenchymal stem cells. Quantitative imaging at the nucleus level shows that H3.3, relative to replicative H3.2 or canonical H2B, is enriched in chromatin domains marked by histone modifications of active or potentially active genes. Chromatin immunoprecipitation of epitope-tagged H3.3 and array hybridization identified 1649 H3.3-enriched promoters, a fraction of which is coenriched in H3K4me3 alone or together with H3K27me3, whereas H3K9me3 is excluded, corroborating nucleus-level imaging data. H3.3-enriched promoters are predominantly CpG-rich and preferentially DNA methylated, relative to the proportion of methylated RefSeq promoters in the genome. Most but not all H3.3-enriched promoters are transcriptionally active, and coenrichment of H3.3 with repressive H3K27me3 correlates with an enhanced proportion of expressed genes carrying this mark. H3.3-target genes are enriched in mesodermal differentiation and signaling functions. Our data suggest that in mesenchymal stem cells, H3.3 targets lineage-priming genes with a potential for activation facilitated by H3K4me3 in facultative association with H3K27me3.

Lineage-specific promoter DNA methylation patterns segregate adult progenitor cell types.

Mesenchymal stem cells (MSCs) can differentiate into multiple mesodermal cell types in vitro; however, their differentiation capacity is influenced by their tissue of origin. To what extent epigenetic information on promoters of lineage-specification genes in human progenitors influences transcriptional activation and differentiation potential remains unclear. We produced bisulfite sequencing maps of DNA methylation in adipogenic, myogenic, and endothelial promoters in relation to gene expression and differentiation capacity, and unravel a similarity in DNA methylation profiles between MSCs isolated from human adipose tissue, bone marrow (BM), and muscle. This similarity is irrespective of promoter CpG content. Methylation patterns of MSCs are distinct from those of hematopoietic progenitor cells (HPCs), pluripotent human embryonic stem cells (hESCs), and multipotent hESC-derived mesenchymal cells (MCs). Moreover, in vitro MSC differentiation does not affect lineage-specific promoter methylation states, arguing that these methylation patterns in differentiated cells are already established at the progenitor stage. Further, we find a correlation between lineage-specific promoter hypermethylation and lack of differentiation capacity toward that lineage, but no relationship between weak promoter methylation and capacity of transcriptional activation or differentiation. Thus, only part of the restriction in differentiation capacity of tissue-specific stem cells is programmed by promoter DNA methylation: hypermethylation seems to constitute a barrier to differentiation, however, no or weak methylation has no predictive value for differentiation potential.

Immunoprecipitation of methylated DNA.

DNA methylation contributes to the regulation of long-term gene repression by enabling the recruitment of transcriptional repressor complexes to methylated cytosines. Several methods for detecting DNA methylation at the gene-specific and genome-wide levels have been developed. Methylated DNA immunoprecipitation, or MeDIP, consists of the selective immunoprecipitation of methylated DNA fragments using antibodies to 5-methylcytosine. The genomic site of interest can be detected by PCR, hybridization to DNA arrays, or by direct sequencing. This chapter describes the MeDIP protocol and quality control tests that should be performed throughout the procedure.

Epigenetic Basis for the Differentiation Potential of Mesenchymal and Embryonic Stem Cells.

SUMMARY: Stem cells have the ability to self-renew, and give rise to one or more differentiated cell types. Embryonic stem cells can differentiate into all cell types of the body and have unlimited self-renewal capacity. Somatic stem cells are found in many adult tissues. They have an extensive but finite lifespan and can differentiate into a more restricted range of cell types. Increasing evidence indicates that the multilineage differentiation ability of stem cells is defined by the potential for expression of developmentally regulated transcription factors and of lineage specification genes. Gene expression, or as emphasized here, the potential for gene expression, is largely controlled by epigenetic modifications of DNA (DNA methylation) and chromatin (such as post-translational histone modifications) in the regulatory regions of specific genes. Epigenetic modifications can also influence the timing of DNA replication. We highlight here how mechanisms by which genes are poised for transcription in undifferentiated stem cells are being uncovered through the mapping of DNA methylation profiles on differentiation-regulated promoters and at the genome-wide level, histone modifications, and transcription factor binding. Epigenetic marks on developmentally regulated and lineage specification genes in stem cells seem to define a state of pluripotency.

Risk of lung cancer according to mild steel and stainless steel welding.

OBJECTIVES: Whether the elevated risk of lung cancer observed among welders is caused by welding emissions or by confounding from smoking or asbestos exposure is still not resolved. This question was addressed in a cohort with a long follow-up and quantified estimates of individual exposure to welding fume particulates. METHODS: Male metal workers employed at least 1 year at one or more Danish stainless or mild steel industrial companies from 1964 through 1984 were enrolled in a cohort. Data on occupational and smoking history were obtained by questionnaire in 1986. Welders in the cohort who started welding in 1960 or later (N=4539) were followed from April 1968 until December 2003, when information on cancer diagnosis was obtained from the Danish Cancer Registry. During the follow-up, 75 cases of primary lung cancer were identified. Lifetime accumulated exposure to welding fume particulates was estimated by combining questionnaire information and more than 1000 welding-process-specific measurements of fume particulates in the Danish welding industry. RESULTS: The standardized incidence ratio (SIR) for lung cancer was increased among the welders [SIR 1.35, 95% confidence interval (95% CI) 1.06-1.70)]. Among the stainless steel welders, the risk increased significantly with increasing accumulative welding particulate exposure, while no exposure-response relation was found for mild steel welders, even after adjustment for tobacco smoking and asbestos exposure. CONCLUSIONS: The study corroborates earlier findings that welders have an increased risk of lung cancer. While exposure-response relations indicate carcinogenic effects related to stainless steel welding, it is still unresolved whether the mild steel welding process carries a carcinogenic risk.

CpG methylation profiles of endothelial cell-specific gene promoter regions in adipose tissue stem cells suggest limited differentiation potential toward the endothelial cell lineage.

In vivo endothelial commitment of adipose stem cells (ASCs) has scarcely been reported, and controversy remains on the contribution of ASCs to vascularization. We address the epigenetic commitment of ASCs to the endothelial lineage. We report a bisulfite sequencing analysis of CpG methylation in the promoters of two endothelial-cell-specific genes, CD31 and CD144, in freshly isolated and in cultures of ASCs before and after induction of endothelial differentiation. In contrast to adipose tissue-derived endothelial (CD31(+)) cells, freshly isolated ASCs display a heavily methylated CD31 promoter and a mosaically methylated CD144 promoter despite basal transcription of both genes. Methylation state of both promoters remains globally stable upon culture. Endothelial stimulation of ASCs in methylcellulose elicits phenotypic changes, marginal upregulation of CD31, and CD144 expression and restrictive induction of a CD31(+)CD144(+) immunophenotype. These events are accompanied by discrete changes in CpG methylation in CD31 and CD144 promoters; however, no global demethylation that marks CD31(+) cells and human umbilical vein endothelial cells occurs. Immunoselection of CD31(+) cells after endothelial stimulation reveals consistent demethylation of one CpG immediately 3' of the transcription start site of the CD31 promoter. Adipogenic or osteogenic differentiation maintains CD31 and CD144 methylation patterns of undifferentiated cells. Methylation profiles of CD31 and CD144 promoters suggest a limited commitment of ASCs to the endothelial lineage. This contrasts with the reported hypomethylation of adipogenic promoters, which reflects a propensity of ASCs toward adipogenic differentiation. Analysis of CpG methylation at lineage-specific promoters provides a robust assessment of epigenetic commitment of stem cells to a specific lineage.