Operationalising generalism in medical education: a narrative review of international policy and mission documents.

INTRODUCTION: Despite moves across medical education to increase learning of generalist principles, a lack of clarity about what generalism means and how we should train doctors as 'generalists', has remained. This study explores how international, undergraduate and postgraduate, policy and educational mission documents characterise the practice and learning of generalism and how this can inform physician training. METHODS: A narrative literature review was conducted based on policy and mission documents identified through grey literature searches and a wider systematic review looking at empirical texts. Texts published between 1999 and present and related to 'generalism' were eligible for inclusion. Texts were coded and codes were reviewed and grouped into key themes. RESULTS: Thirty-four documents were included. Definitions vary: some described generalism as a basic skill, whilst others emphasised expertise. Factors which support learning generalism include: favourable financial outcomes; ageing populations; coordination of multidisciplinary care; demand for doctors with transferable skills; and patient expectations. Barriers to learning about generalism include: preference for specialisation; structure of undergraduate teaching and assessment; and the hidden curriculum. Solutions may include re-imagining generalists and specialists as being on a continuum as well as increasing exposure throughout medical education. DISCUSSION: Whilst generalism is consistently positioned as valuable, less clarity exists about how best to operationalise this in medical education. Fundamental ideological and structural changes within teaching curricula and assessment, are necessary to improve generalist learning and to promote sustainable practice. Medical education needs careful, considered planning to ensure workforce expertise is meeting population needs.

Management of sleep disorder by preceptors in a family medicine residency program in Calgary, Alberta: a mixed-methods study.

BACKGROUND: Most prescriptions for sedative-hypnotics are written by family physicians. Given the influence of preceptors on residents' prescribing, this study explored how family physician preceptors manage sleeping problems. METHODS: Family physician preceptors affiliated with a postgraduate training program in Alberta were invited to participate in this mixed-methods study, conducted from January to October 2021. It included a quantitative survey of preceptors' attitudes to treatment options for sleep disorder, perceptions of patient expectations and self-efficacy beliefs. Participants indicated their responses on a 5-point Likert scale ranging from "strongly disagree" to "strongly agree." Respondents were then asked whether they were interested in participating in a semistructured qualitative interview that elicited preceptors' management of sleep disorder in response to a series of vignettes. We analyzed the quantitative data using descriptive statistics and the qualitative interviews using thematic analysis. RESULTS: Of the 76 preceptors invited to participate, 47 (62%) completed the survey, and 10 were interviewed. Thirty-two survey respondents (68%) were in academic teaching clinics, and 15 (32%) were from community clinics. The majority of participants (34 [72%]) agreed they had sufficient expertise to use nondrug treatment. Most (43 [91%]) had made efforts to reduce prescribing, and 45 (96%) felt able to support patients empathically when not using sleeping medication. The qualitative data showed that management of sleeping disorder was emotionally challenging. Participants hesitated to prescribe sedatives and reported "exceptions" to prescribing, many of which included indications within guideline recommendations. Participants were reluctant to change a colleague's management. INTERPRETATION: Preceptors were confident using nonpharmacologic management to treat sleep disorder and hesitant to use sedative-hypnotics, presenting legitimate use of sedatives as exceptional behaviour. Acknowledging social norms and affective aspects involved in prescribing may support balanced prescribing of sedative-hypnotics for sleep disorder and reduce physician anxiety.

The own-voice benefit for word recognition in early bilinguals.

The current study examines the self-voice benefit in an early bilingual population. Female Cantonese-English bilinguals produced words containing Cantonese contrasts. A subset of these minimal pairs was selected as stimuli for a perception task. Speakers' productions were grouped according to how acoustically contrastive their pronunciation of each minimal pair was and these groupings were used to design personalized experiments for each participant, featuring their own voice and the voices of others' similarly-contrastive tokens. The perception task was a two-alternative forced-choice word identification paradigm in which participants heard isolated Cantonese words, which had undergone synthesis to mask the original talker identity. Listeners were more accurate in recognizing minimal pairs produced in their own (disguised) voice than recognizing the realizations of speakers who maintain similar degrees of phonetic contrast for the same minimal pairs. Generally, individuals with larger phonetic contrasts were also more accurate in word identification for self and other voices overall. These results provide evidence for an own-voice benefit for early bilinguals. These results suggest that the phonetic distributions that undergird phonological contrasts are heavily shaped by one's own phonetic realizations.

Characterising generalism in clinical practice: a systematic mixed studies review protocol.

BACKGROUND: Generalist physician care is associated with improved patient outcomes. Despite initiatives to promote generalism in educational settings, recruitment to generalist disciplines remains less than required to serve societal needs. Increasingly this impacts not just general practice but also generalist specialties such as internal medicine, surgery, and paediatrics. One potential factor for this deficit is a lack of explicit attention to generalism as a praxis, including clarifying key aspects of generalist expertise. AIM: To examine empirical clinical literature on generalism, and characterise how generalism is described and delivered by physicians in primary and secondary care. DESIGN & SETTING: A systematic mixed studies review (SMSR) including quantitative, qualitative, mixed-methods studies, and systematic reviews of physician generalist practice. METHOD: MEDLINE, Psycinfo, SocINDEX, Embase, Ovid HealthSTAR, Scopus, and Web of Science will be searched for English language studies from 1999 to present, using a structured search. Given study heterogeneity, quality appraisal will not be performed. Two reviewers will perform study selection for each study. Data extraction will focus on how generalism is defined and characterised, including the clinical care provided by generalists and patient experiences of generalist care. Quantitative and qualitative data will be summarised in tabular and narrative form. Convergent synthesis design will then be used to synthesise quantitative and qualitative data. CONCLUSION: Findings will characterise generalism and generalist practice from a grassroots clinical perspective. By identifying similarities and differences across generalist disciplines, this work will inform more focused educational initiatives on generalism at undergraduate and postgraduate level, including collaborations between generalist disciplines.

Microenvironmental topographic cues influence migration dynamics of nasopharyngeal carcinoma cells from tumour spheroids.

Tumour metastasis is a complex process that strongly influences the prognosis and treatment of cancer. Apart from intracellular factors, recent studies have indicated that metastasis also depends on microenvironmental factors such as the biochemical, mechanical and topographical properties of the surrounding extracellular matrix (ECM) of tumours. In this study, as a proof of concept, we conducted tumour spheroid dissemination assay on engineered surfaces with micrograting patterns. Nasopharyngeal spheroids were generated by the 3D culture of nasopharyngeal carcinoma (NPC43) cells, a newly established cell line that maintains a high level of Epstein-Barr virus, a hallmark of NPC. Three types of collagen I-coated polydimethylsiloxane (PDMS) substrates were used, with 15 µm deep "trenches" that grated the surfaces: (a) 40/10 µm ridges (R)/trenches (T), (b) 18/18 µm (R/T) and (c) 50/50 µm (R/T). The dimensions of these patterns were designed to test how various topographical cues, different with respect to the size of tumour spheroids and individual NPC43 cells, might affect dissemination behaviours. Spreading efficiencies on all three patterned surfaces, especially 18/18 µm (R/T), were lower than that on flat PDMS surface. The outspreading cell sheets on flat and 40/10 µm (R/T) surfaces were relatively symmetrical but appeared ellipsoid and aligned with the main axes of the 18/18 µm (R/T) and 50/50 µm (R/T) grating platforms. Focal adhesions (FAs) were found to preferentially formed on the ridges of all patterns. The number of FAs per spheroid was strongly influenced by the grating pattern, with the least FAs on the 40/10 µm (R/T) and the most on the 50/50 µm (R/T) substrate. Taken together, these data indicate a previously unknown effect of surface topography on the efficiency and directionality of cancer cell spreading from tumour spheroids, suggesting that topography, like ECM biochemistry and stiffness, can influence the migration dynamics in 3D cell culture models.

Use of Human Intestinal Enteroids to Detect Human Norovirus Infectivity.

Tools to detect human norovirus infectivity have been lacking. Using human intestinal enteroid cultures inoculated with GII.Pe-GII.4 Sydney-infected fecal samples, we determined that a real-time reverse transcription PCR cycle threshold cutoff of 30 may indicate infectious norovirus. This finding could be used to help guide infection control.

Current and Common Definitions of Treatment-Resistant Depression: Findings from a Systematic Review and Qualitative Interviews.

OBJECTIVE: No universal definition for treatment-resistant depression (TRD) exists. This lack of consensus reduces the generalizability of study findings and limits the ability to study TRD. In addition, anecdotally, there may be a difference between the definitions of TRD within research and those applied in practice. Thus, the objective of this work was to identify current common definitions of TRD used in both research and clinical practice. METHOD: A systematic review of published literature was conducted to document TRD definitions. Extracted data were grouped based on patient cohort and method of defining TRD. Validation studies were narratively summarized. Interviews with 6 key informants were conducted to understand how definitions are applied in practice. RESULTS: In total, 155 definitions for TRD were identified in the published literature, and 48.4% of all definitions specified requirement of at least 2 treatment failures. Key informant interviews indicated the concept of TRD is rarely employed in clinical practice. Instead, concepts like "complex needs," "struggling with their disease," and "chronic" are used. When asked directly about how they would define TRD, interview participants said an adequate trial of psychotherapy as well as an adequate trial of at least 2 to 3 antidepressant medications. CONCLUSIONS: There is no universally accepted definition of TRD, and substantial heterogeneity exists. This study indicates discordance between the use of the term in research and clinical practice, with several key informants emphasizing that the terminology is rarely used in their clinical experience. Development of a shared, common definition across practice and research is required.

Higher Viral Load of Emerging Norovirus GII.P16-GII.2 than Pandemic GII.4 and Epidemic GII.17, Hong Kong, China.

We compared viral load of emerging recombinant norovirus GII.P16-GII.2 with those for pandemic GII.Pe-GII.4 and epidemic GII.P17-GII.17 genotypes among inpatients in Hong Kong. Viral load of GII.P16-GII.2 was higher than those for other genotypes in different age groups. GII.P16-GII.2 is as replication competent as the pandemic genotype, explaining its high transmissibility and widespread circulation.

From Misperception to Social Connection: Correlates and Consequences of Overestimating Others' Social Connectedness.

Two studies document the existence and correlates of a widespread social belief, wherein individuals who have recently moved to a new social environment see their peers as more socially connected than they themselves are. In Study 1, the prevalence of this belief was documented in a large sample of first-year students ( N = 1,099). In Study 2, the prevalence of this social belief was replicated in a targeted sample of university students ( N = 389). Study 2 also documented both positive and negative implications of this belief. Specifically, at any given time, students who believed that their peers were more socially connected reported lower well-being and belonging. Over time, however, the belief that one's peers are moderately more socially connected than oneself was associated with more friendship formation.

FhCaBP1 (FH22): A Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains.

FH22 has been previously identified as a calcium-binding protein from the common liver fluke, Fasciola hepatica. It is part of a family of at least four proteins in this organism which combine an EF-hand containing N-terminal domain with a C-terminal dynein light chain-like domain. Here we report further biochemical properties of FH22, which we propose should be renamed FhCaBP1 for consistency with other family members. Molecular modelling predicted that the two domains are linked by a flexible region and that the second EF-hand in the N-terminal domain is most likely the calcium ion binding site. Native gel electrophoresis demonstrated that the protein binds both calcium and manganese ions, but not cadmium, magnesium, strontium, barium, cobalt, copper(II), iron (II), nickel, zinc, lead or potassium ions. Calcium ion binding alters the conformation of the protein and increases its stability towards thermal denaturation. FhCaBP1 is a dimer in solution and calcium ions have no detectable effect on the protein's ability to dimerise. FhCaBP1 binds to the calmodulin antagonists trifluoperazine and chlorpromazine. Overall, the FhCaBP1's biochemical properties are most similar to FhCaBP2 a fact consistent with the close sequence and predicted structural similarity between the two proteins.

Stage-specific embryonic antigen-3 (SSEA-3) and ß3GalT5 are cancer specific and significant markers for breast cancer stem cells.

The discovery of cancer stem cells (CSCs), which are responsible for self-renewal and tumor growth in heterogeneous cancer tissues, has stimulated interests in developing new cancer therapies and early diagnosis. However, the markers currently used for isolation of CSCs are often not selective enough to enrich CSCs for the study of this special cell population. Here we show that the breast CSCs isolated with CD44(+)CD24(-/lo)SSEA-3(+) or ESA(hi)PROCR(hi)SSEA-3(+) markers had higher tumorigenicity than those with conventional markers in vitro and in vivo. As few as 10 cells with CD44(+)CD24(-/lo)SSEA-3(+) formed tumor in mice, compared with more than 100 cells with CD44(+)CD24(-/lo). Suppression of SSEA-3 expression by knockdown of the gene encoding ß-1,3-galactosyltransferase 5 (ß3GalT5) in the globo-series pathway, led to apoptosis in cancer cells specifically but had no effect on normal cells. This finding is further supported by the analysis of SSEA-3 and the two related globo-series epitopes SSEA4 and globo-H in stem cells (embryonic stem cells and induced pluripotent stem cells) and various normal and cancer cells, and by the antibody approach to target the globo-series glycans and the late-stage clinical trials of a breast cancer vaccine.

Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer.

Globo H (GH) is a hexasaccharide specifically overexpressed on a variety of cancer cells and therefore, a good candidate for cancer vaccine development. To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked GH to a carrier protein, including keyhole limpet hemocyanion, diphtheria toxoid cross-reactive material (CRM) 197 (DT), tetanus toxoid, and BSA, and combined with an adjuvant, and it was administered to mice for the study of immune response. Glycan microarray analysis of the antiserum obtained indicated that the combination of GH-DT adjuvanted with the α-galactosylceramide C34 has the highest enhancement of anti-GH IgG. Compared with the phase III clinical trial vaccine, GH-keyhole limpet hemocyanion/QS21, the GH-DT/C34 vaccine elicited more IgG antibodies, which are more selective for GH and the GH-related epitopes, stage-specific embryonic antigen 3 (SSEA3) and SSEA4, all of which were specifically overexpressed on breast cancer cells and breast cancer stem cells with SSEA4 at the highest level (>90%). We, therefore, further developed SSEA4-DT/C34 as a vaccine candidate, and after immunization, it was found that the elicited antibodies are also IgG-dominant and very specific for SSEA4.

In situ labeling of transcription sites in marine medaka.

Transcription factories have been characterized in cultured mammalian cells, but little is known about the regulation of these nuclear structures in different primary cell types. Using marine medaka, we observed transcription sites labeled by the metabolic incorporation of 5-fluorouridine (5-FU) into nascent RNA. Medaka was permeable to 5-FU in ambient water and became fully labeled within 4 hr of incubation. The incorporation of 5-FU was inhibited by the transcription inhibitor actinomycin D. The 5-FU incorporation sites were detected in the cell nucleus, and could be abolished by RNase digestion. The tissue distribution of 5-FU incorporation was visualized by immunocytochemistry on whole-mount specimens and histological sections. The 5-FU labeling appeared highly cell type specific, suggesting a regulation of the overall transcription activities at tissue level. Mapping of transcription factories by 5-FU incorporation in fish provides a useful and physiologically relevant model for studying the control of gene expression in the context of the functional organization of the cell nucleus. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.