Communicative Practices Clinicians Use to Correct Patient Misconceptions in Primary Care Visits.

To investigate how clinicians correct patient misconceptions, we analyzed 23 video recordings of primary care visits. Analysis focused on operationalizing, identifying, and characterizing clinician corrections, integrating two inductive approaches: microanalysis of clinical interaction and conversation analysis. According to our definition, patient misconception-clinician correction episodes met three essential criteria: (1) the clinician refuted something the patient had said, (2) which the patient had presented without uncertainty, and (3) which contained a proposition that was factually incorrect. We identified 59 such episodes; the patient misconceptions most commonly related to medication issues; fewer than half had foreseeable implications for patients' future actions. We identified seven clinician correction practices: Three direct practices (displaying surprise, marking disagreement, contradicting the patient) and four indirect practices (presenting the correct proposition, providing explanations, invoking an outside authority, demonstrating with evidence). We found an almost equal distribution of these direct and indirect practices.

Making Conversation Analysis Accessible: A Conceptual Guide for Health Services Researchers.

The quality of healthcare communication can impact both experiences and outcomes. We highlight aspects of communication that can be systematically examined using Conversation Analysis (CA) and provide guidance about how researchers can incorporate CA into healthcare studies. CA is a qualitative method for studying naturally occurring communication by analyzing recurrent, systematic practices of verbal and nonverbal behavior. CA involves examining audio- or video-recorded conversations and their transcriptions to identify practices speakers use to communicate and interpret behavior. We explain what distinguishes CA from other methods that study communication and highlight three accessible CA approaches that researchers can use in their research design, analysis, or implementation of communication interventions. Specifically, these approaches focus on how talk is produced (specific words, framing, and syntax), by whom, and when it occurs in the conversation. These approaches can be leveraged to generate hypotheses and to identify patterns of behavior that inform empirically driven communication interventions.

Agenda setting and visit openings in primary care visits involving patients taking opioids for chronic pain.

BACKGROUND: Agenda setting is associated with more efficient care and better patient experience. This study develops a taxonomy of visit opening styles to assess use of agenda and non-agenda setting visit openings and their effects on participant experience. METHODS: This observational study analyzed 83 video recorded US primary care visits at a single academic medical center in California involving family medicine and internal medicine resident physicians (n = 49) and patients (n = 83) with chronic pain on opioids. Using conversation analysis, we developed a coding scheme that assessed the presence of agenda setting, distinct visit opening styles, and the number of total topics, major topics, surprise patient topics, and returns to prior topics discussed. Exploratory quantitative analyses were conducted to assess the relationship of agenda setting and visit opening styles with post-visit measures of both patient experience and physician perception of visit difficulty. RESULTS: We identified 2 visit opening styles representing agenda setting (agenda eliciting, agenda reframing) and 3 non-agenda setting opening styles (open-ended question, patient launch, physician launch). Agenda setting was only performed in 11% of visits and was associated with fewer surprise patient topics than visits without agenda setting (mean (SD) 2.67 (1.66) versus 4.28 (3.23), p = 0.03). CONCLUSIONS: In this study of patients with chronic pain, resident physicians rarely performed agenda setting, whether defined in terms of "agenda eliciting" or "agenda re-framing." Agenda setting was associated with fewer surprise topics. Understanding the communication context and outcomes of agenda setting may inform better use of this communication tool in primary care  practice.

"It Sometimes Doesn't Even Work": Patient Opioid Assessments as Clues to Therapeutic Flexibility in Primary Care.

BACKGROUND: Physicians' fear of difficult patient interactions is an important barrier to discontinuing long-term opioid therapy. OBJECTIVE: To identify patient statements about opioids that indicate potential openness to tapering opioids or trying non-opioid pain treatments DESIGN: This is an observational study of regularly scheduled primary care visits involving discussion of chronic pain management. A coding system to characterize patient assessments about opioids, physician responses to assessments, and patient-endorsed opioid side effects was developed and applied to transcripts of video-recorded visits. All visits were independently coded by 2 authors. PARTICIPANTS: Eighty-six established adult patients taking opioids for chronic pain; 49 physicians in 2 academic primary care clinics MAIN MEASURES: Frequency and topic of patients' opioid assessments; proportion of opioid assessments classified as clues (assessments indicating potential willingness to consider non-opioid pain treatments or lower opioid doses); physician responses to patient clues; frequency and type of patient-endorsed side effects KEY RESULTS: Patients made a mean of 3.2 opioid assessments (median 2) per visit. The most common assessment topics were pain relief (51%), effect on function (21%), and opioid safety (14%). Forty-seven percent of opioid assessments (mean 1.5 per visit) were classified as clues. Fifty-three percent of visits included ≥ 1 clue; 21% of visits contained ≥ 3 clues. Physicians responded to patient clues with no/minimal response 43% of the time, sympathetic/empathetic statements 14% of the time, and further explored clues 43% of the time. Fifty-eight percent of patients endorsed ≥ 1 opioid-related side effect; 10% endorsed ≥ 3 side effects. The most commonly endorsed side effects were constipation (15% of patients), sedation (15%), withdrawal symptoms (13%), and nausea (12%). CONCLUSIONS: Patient statements suggesting openness to non-opioid pain treatments or lower opioid doses are common during routine primary care visits. Listening for and exploring these clues may be a patient-centered strategy for broaching difficult topics with patients on long-term opioid therapy.

Irradiated recycled plastic as a concrete additive for improved chemo-mechanical properties and lower carbon footprint.

Concrete production contributes heavily to greenhouse gas emissions, thus a need exists for the development of durable and sustainable concrete with a lower carbon footprint. This can be achieved when cement is partially replaced with another material, such as waste plastic, though normally with a tradeoff in compressive strength. This study discusses progress toward a high/medium strength concrete with a dense, cementitious matrix that contains an irradiated plastic additive, recovering the compressive strength while displacing concrete with waste materials to reduce greenhouse gas generation. Compressive strength tests showed that the addition of high dose (100kGy) irradiated plastic in multiple concretes resulted in increased compressive strength as compared to samples containing regular, non-irradiated plastic. This suggests that irradiating plastic at a high dose is a viable potential solution for regaining some of the strength that is lost when plastic is added to cement paste. X-ray Diffraction (XRD), Backscattered Electron Microscopy (BSE), and X-ray microtomography explain the mechanisms for strength retention when using irradiated plastic as a filler for cement paste. By partially replacing Portland cement with a recycled waste plastic, this design may have a potential to contribute to reduced carbon emissions when scaled to the level of mass concrete production.

Architecture of the human interactome defines protein communities and disease networks.

The physiology of a cell can be viewed as the product of thousands of proteins acting in concert to shape the cellular response. Coordination is achieved in part through networks of protein-protein interactions that assemble functionally related proteins into complexes, organelles, and signal transduction pathways. Understanding the architecture of the human proteome has the potential to inform cellular, structural, and evolutionary mechanisms and is critical to elucidating how genome variation contributes to disease. Here we present BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust affinity purification-mass spectrometry methodology to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein-coding genes from the human genome, and constitutes, to our knowledge, the largest such network so far. With more than 56,000 candidate interactions, BioPlex 2.0 contains more than 29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins while enhancing network-based analyses of domain associations, subcellular localization, and co-complex formation. Unsupervised Markov clustering of interacting proteins identified more than 1,300 protein communities representing diverse cellular activities. Genes essential for cell fitness are enriched within 53 communities representing central cellular functions. Moreover, we identified 442 communities associated with more than 2,000 disease annotations, placing numerous candidate disease genes into a cellular framework. BioPlex 2.0 exceeds previous experimentally derived interaction networks in depth and breadth, and will be a valuable resource for exploring the biology of incompletely characterized proteins and for elucidating larger-scale patterns of proteome organization.

Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP.

YAP is a transcriptional coactivator that controls organ expansion and differentiation and is inhibited by the Hippo pathway in cells in interphase. Here, we demonstrated that, during mitosis, YAP localized to the midbody and spindle, subcellular structures that are involved in cytokinesis, the process by which contraction of the cytoskeleton produces two daughter cells. Furthermore, YAP was phosphorylated by CDK1, a kinase that promotes cell cycle progression. Knockdown of YAP by shRNA or expression of a nonphosphorylatable form of YAP delayed the separation of daughter cells (called abscission) and induced a cytokinesis phenotype associated with increased contractile force, membrane blebbing and bulges, and abnormal spindle orientation. Consequently, these defects led to an increased frequency of multinucleation, micronuclei, and aneuploidy. YAP was required for proper localization of proteins that regulate contraction during cytokinesis, including ECT2, MgcRacGap, Anillin, and RHOA. In addition, depletion of YAP increased the phosphorylation of myosin light chain, which would be expected to activate the contractile activity of myosin II, the molecular motor involved in cytokinesis. The polarity scaffold protein PATJ coprecipitated with YAP and colocalized with YAP at the cytokinesis midbody, and knockdown of PATJ phenocopied the cytokinetic defects and spindle orientation alterations induced by either YAP depletion or expression of a nonphosphorylatable YAP mutant. Together, these results reveal an unanticipated role for YAP in the proper organization of the cytokinesis machinery during mitosis through interaction with the polarity protein PATJ.

Identification of TRIM27 as a novel degradation target of herpes simplex virus 1 ICP0.

UNLABELLED: The herpes simplex virus 1 (HSV-1) immediate early protein ICP0 performs many functions during infection, including transactivation of viral gene expression, suppression of innate immune responses, and modification and eviction of histones from viral chromatin. Although these functions of ICP0 have been characterized, the detailed mechanisms underlying ICP0's complex role during infection warrant further investigation. We thus undertook an unbiased proteomic approach to identifying viral and cellular proteins that interact with ICP0 in the infected cell. Cellular candidates resulting from our analysis included the ubiquitin-specific protease USP7, the transcriptional repressor TRIM27, DNA repair proteins NBN and MRE11A, regulators of apoptosis, including BIRC6, and the proteasome. We also identified two HSV-1 early proteins involved in nucleotide metabolism, UL39 and UL50, as novel candidate interactors of ICP0. Because TRIM27 was the most statistically significant cellular candidate, we investigated the relationship between TRIM27 and ICP0. We observed rapid, ICP0-dependent loss of TRIM27 during HSV-1 infection. TRIM27 protein levels were restored by disrupting the RING domain of ICP0 or by inhibiting the proteasome, arguing that TRIM27 is a novel degradation target of ICP0. A mutant ICP0 lacking E3 ligase activity interacted with endogenous TRIM27 during infection as demonstrated by reciprocal coimmunoprecipitation and supported by immunofluorescence data. Surprisingly, ICP0-null mutant virus yields decreased upon TRIM27 depletion, arguing that TRIM27 has a positive effect on infection despite being targeted for degradation. These results illustrate a complex interaction between TRIM27 and viral infection with potential positive or negative effects of TRIM27 on HSV under different infection conditions. IMPORTANCE: During productive infection, a virus must simultaneously redirect multiple cellular pathways to replicate itself while evading detection by the host's defenses. To orchestrate such complex regulation, viruses, including herpes simplex virus 1 (HSV-1), rely on multifunctional proteins such as the E3 ubiquitin ligase ICP0. This protein regulates various cellular pathways concurrently by targeting a diverse set of cellular factors for degradation. While some of these targets have been previously identified and characterized, we undertook a proteomic screen to identify additional targets of this activity to further characterize ICP0's role during infection. We describe a set of candidate interacting proteins of ICP0 identified through this approach and our characterization of the most statistically significant result, the cellular transcriptional repressor TRIM27. We present TRIM27 as a novel degradation target of ICP0 and describe the relationship of these two proteins during infection.

Drosophila histone locus bodies form by hierarchical recruitment of components.

Nuclear bodies are protein- and RNA-containing structures that participate in a wide range of processes critical to genome function. Molecular self-organization is thought to drive nuclear body formation, but whether this occurs stochastically or via an ordered, hierarchical process is not fully understood. We addressed this question using RNAi and proteomic approaches in Drosophila melanogaster to identify and characterize novel components of the histone locus body (HLB), a nuclear body involved in the expression of replication-dependent histone genes. We identified the transcription elongation factor suppressor of Ty 6 (Spt6) and a homologue of mammalian nuclear protein of the ataxia telangiectasia-mutated locus that is encoded by the homeotic gene multisex combs (mxc) as novel HLB components. By combining genetic manipulation in both cell culture and embryos with cytological observations of Mxc, Spt6, and the known HLB components, FLICE-associated huge protein, Mute, U7 small nuclear ribonucleoprotein, and MPM-2 phosphoepitope, we demonstrated sequential recruitment and hierarchical dependency for localization of factors to HLBs during development, suggesting that ordered assembly can play a role in nuclear body formation.

The Drosophila U7 snRNP proteins Lsm10 and Lsm11 are required for histone pre-mRNA processing and play an essential role in development.

Metazoan replication-dependent histone mRNAs are not polyadenylated, and instead terminate in a conserved stem-loop structure generated by an endonucleolytic cleavage of the pre-mRNA involving U7 snRNP. U7 snRNP contains two like-Sm proteins, Lsm10 and Lsm11, which replace SmD1 and SmD2 in the canonical heptameric Sm protein ring that binds spliceosomal snRNAs. Here we show that mutations in either the Drosophila Lsm10 or the Lsm11 gene disrupt normal histone pre-mRNA processing, resulting in production of poly(A)+ histone mRNA as a result of transcriptional read-through to cryptic polyadenylation sites present downstream from each histone gene. This molecular phenotype is indistinguishable from that which we previously described for mutations in U7 snRNA. Lsm10 protein fails to accumulate in Lsm11 mutants, suggesting that a pool of Lsm10-Lsm11 dimers provides precursors for U7 snRNP assembly. Unexpectedly, U7 snRNA was detected in Lsm11 and Lsm1 mutants and could be precipitated with anti-trimethylguanosine antibodies, suggesting that it assembles into a snRNP particle in the absence of Lsm10 and Lsm11. However, this U7 snRNA could not be detected at the histone locus body, suggesting that Lsm10 and Lsm11 are necessary for U7 snRNP localization. In contrast to U7 snRNA null mutants, which are viable, Lsm10 and Lsm11 mutants do not survive to adulthood. Because we cannot detect differences in the histone mRNA phenotype between Lsm10 or Lsm11 and U7 mutants, we propose that the different terminal developmental phenotypes result from the participation of Lsm10 and Lsm11 in an essential function that is distinct from histone pre-mRNA processing and that is independent of U7 snRNA.

Developmental and cell cycle regulation of the Drosophila histone locus body.

Cyclin E/Cdk2 is necessary for replication-dependent histone mRNA biosynthesis, but how it controls this process in early development is unknown. We show that in Drosophila embryos the MPM-2 monoclonal antibody, raised against a phosphoepitope from human mitotic cells, detects Cyclin E/Cdk2-dependent nuclear foci that colocalize with nascent histone transcripts. These foci are coincident with the histone locus body (HLB), a Cajal body-like nuclear structure associated with the histone locus and enriched in histone pre-mRNA processing factors such as Lsm11, a core component of the U7 small nuclear ribonucleoprotein. Using MPM-2 and anti-Lsm11 antibodies, we demonstrate that the HLB is absent in the early embryo and occurs when zygotic histone transcription begins during nuclear cycle 11. Whereas the HLB is found in all cells after its formation, MPM-2 labels the HLB only in cells with active Cyclin E/Cdk2. MPM-2 and Lsm11 foci are present in embryos lacking the histone locus, and MPM-2 foci are present in U7 mutants, which cannot correctly process histone pre-mRNA. These data indicate that MPM-2 recognizes a Cdk2-regulated protein that assembles into the HLB independently of histone mRNA biosynthesis. HLB foci are present in histone deletion embryos, although the MPM-2 foci are smaller, and some Lsm11 foci are not associated with MPM-2 foci, suggesting that the histone locus is important for HLB integrity.

Supervised teaching practice: a system for teacher support and quality assurance.

Supervised teaching practice is practical supervision of teaching under the tutelage of an established teacher. It is proposed as a cost-effective integrated approach to linking the support and development of teachers with quality assurance. In modern undergraduate medical curricula increasing value is placed on teaching and teacher-training. The response to the General Medical Council's demand for a new style of undergraduate medical education requires a system of practical and continuous training which will ensure the highest standard among teachers. Supervised teaching practice offers such a system.