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Contrary to common belief, effective communication is not only achieved via verbal exchanges of information. It requires a thoughtful combination of verbal and non-verbal cues since, in some circumstances, verbal communication in healthcare may be impossible, unfavourable or ineffective. The semiotics literature suggests that effective non-verbal communication goes beyond body language and gestures. It also includes the use of objects (i.e. traces) to transmit a message. We call this trace-based communication (TBC). In this perspective paper, we offer some reflections from our experience researching and using trace-based communication for training purposes. Our intention was to bring further awareness to the opportunities that trace-based communication might enable, including opportunities to enhance trainee-supervisor interactions, and consequently inform curriculum design.

Background: Although speaking up is lauded as a critical patient safety strategy, it remains exceptionally challenging for team members to enact. Existing efforts to address the problem of silence among interprofessional teams involve training low-authority members to use direct language and unambiguous challenge scripts. The role or value of indirect communication in preventing medical error remains largely unexplored despite its pervasiveness among interprofessional teams. This study explores the role of indirect challenges in the face of medical error and professionalism lapses., Methods: Obstetricians at one academic center participated in an interprofessional simulation as a partial actor. Thirteen iterations were completed with 39 participants (13 obstetrician consultants, 11 obstetric residents, 2 family medicine consultants, 5 midwives, and 8 obstetrical nurses). Thirty participants completed a subsequent semi-structured interview. Five challenge moments were scripted for the obstetrician involving deliberate clinical judgment errors or professionalism infractions. Other participants were unaware of the obstetrician's partial actor role. Scenarios were videotaped; debriefs and interviews were audio-recorded and transcribed verbatim and analyzed using a constructivist qualitative approach., Results: Low-authority team members primarily relied on indirect challenge scripts to promote patient safety during simulation. Faculty participants were highly receptive to indirect challenges from low-authority team members, particularly in front of awake patients. In the context of obstetric care, direct challenges were actually viewed by participants as threatening to patient trust and disruptive to the interprofessional team. Instead of exclusively focusing our efforts on encouraging low-authority team members to speak up through direct challenges, it may be fruitful to expand our attention toward teaching faculty to identify, listen for, and respond to the indirect, subtle challenges that are already prolific among interprofessional teams., (© 2024. The Author(s).)

Background: Bilateral Wilms tumor (BWT) is a rare entity. The goal of this study is to report outcomes (overall and event-free survival, OS/EFS) of BWT in a large cohort representative of the Canadian population since 2000. We focused on the occurrence of late events (relapse or death beyond 18 months), as well as outcomes of patients treated following the only protocol specifically designed for BWT to date, AREN0534, compared to patients treated following other therapeutic schemes., Methods: Data was obtained for patients diagnosed with BWT between 2001 and 2018 from the Cancer in Young People in Canada (CYP-C) database. Demographics, treatment protocols, and dates for events were collected. Specifically, we examined outcomes of patients treated according to the Children's Oncology Group (COG) protocol AREN0534 since 2009. Survival analysis was performed., Results: 57/816 (7%) of patients with Wilms tumor had BWT during the study period. Median age at diagnosis was 2.74 years (IQR 1.37-4.48) and 35 (64%) were female; 8/57 (15%) had metastatic disease. After a median follow-up of 4.8 years (IQR 2.8-5.7 years, range 0.2-18 years), OS and EFS were 86% (CI 73-93%) and 80% (CI 66-89%), respectively. Less than 5 events were recorded after 18 months from diagnosis. Since 2009, patients treated according to the AREN0534 protocol had a statistically significant higher OS compared to patients treated with other protocols., Conclusions: In this large Canadian cohort of patients with BWT, OS and EFS compared favorably to the published literature. Late events were rare. Patients treated according to a disease-specific protocol (AREN0534) had improved overall survival., Type of Study: Original article., Level of Evidence: Level IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The stimulus-secretion coupling of the pancreatic beta cell is particularly complex, as it integrates the availability of glucose and other nutrients with the neuronal and hormonal input to generate rates of insulin secretion that are appropriate for the entire organism. It is beyond dispute however, that the cytosolic Ca 2+ concentration plays a particularly prominent role in this process, as it not only triggers the fusion of insulin granules with the plasma membrane, but also regulates the metabolism of nutrient secretagogues and affects the function of ion channels and transporters. In order to obtain a better understanding of the interdependence of these processes and, ultimately, of the entire beta cell as a working system, models have been developed based on a set of nonlinear ordinary differential equations, and were tested and parametrized on a limited set of experiments. In the present investigation, we have used a recently published version of the beta cell model to test its ability to describe further measurements from our own experimentation and from the literature. The sensitivity of the parameters is quantified and discussed; furthermore, the possible influence of the measuring technique is taken into account. The model proved to be powerful in correctly describing the depolarization pattern in response to glucose and the reaction of the cytosolic Ca 2+ concentration to stepwise increases of the extracellular K + concentration. Additionally, the membrane potential during a KATP channel block combined with a high extracellular K + concentration could be reproduced. In some cases, however, a slight change of a single parameter led to an abrupt change in the cellular response, such as the generation of a Ca 2+ oscillation with high amplitude and high frequency. This raises the question as to whether the beta cell may be a partially unstable system or whether further developments in modeling are needed to achieve a generally valid description of the stimulus-secretion coupling of the beta cell.

Background: Simulation research that seeks to solve the problem of silence among interprofessional teams has focused almost exclusively on training subordinate team members to be more courageous and to speak up to team leaders using direct challenge scripts despite the great interpersonal cost. Consequently, the existing literature overemphasizes the responsibility of subordinate team members for speaking up and fails to consider the role and responsibilities of team leaders in sustaining silence. The purpose of this study is to identify and describe the subtle behaviors and actions of team leaders that both promote and discourage speaking up., Methods: This study used a simulation-primed qualitative inquiry approach. Obstetricians (OB) at one academic center participated in an interprofessional simulation as an embedded participant. Five challenge moments (CM) were scripted for the OB involving deliberate clinical judgment errors or professionalism infractions. Other participants were unaware of the OB embedded participant role. Thirteen iterations were completed with 39 participants. Twelve faculty members completed a subsequent semi-structured interview. Scenarios were videotaped; debriefs and interviews were audio-recorded and transcribed verbatim. Data were analyzed using an inductive thematic approach., Results: After participating in an interprofessional simulation, faculty participants reflected that being an approachable team leader requires more than simply avoiding disruptive behaviors. We found that approachability necessitates that team leaders actively create the conditions in which team members perceive that speaking up is welcomed, rather than an act of bravery. In practice, this conceptualization of approachability involves the tangible actions of signaling availability through presence, uncertainty through thinking aloud, and vulnerability through debriefing., Conclusions: By using faculty as embedded participants with scripted errors, our simulation design provided an ideal learning opportunity to prompt discussion of the subtle behaviors and actions of team leaders that both promote and discourage speaking up. Faculty participants gained a new appreciation that their actions create the conditions for speaking up to occur before critical incidents through their verbal and non-verbal communication., (© 2022. The Author(s).)

The antimalarial agent, mefloquine, inhibits the function of connexin Cx36 gap junctions and hemichannels and has thus become a tool to investigate their physiological relevance in pancreatic islets. In view of earlier reports on a K ATP channel-block by mefloquine, the specificity of mefloquine as a pharmacological tool was investigated. Mouse pancreatic islets and single beta cells were used to measure membrane potential, whole cell currents, Ca 2+ channel activity, cytosolic Ca 2+ concentration ([Ca 2+ ] i ) and insulin secretion. Mefloquine was tested in the concentration range of 5-50 μM 25 μM mefloquine was as effective as 500 μM tolbutamide to depolarize the plasma membrane of beta cells, but did not induce action potentials. Rather, it abolished tolbutamide-induced action potentials and the associated increase of [Ca 2+ ] i . In the range of 5-50 μM mefloquine inhibited voltage-dependent Ca 2+ currents in primary beta cells as effectively as 1 μM nisoldipine, a specific blocker of L-type Ca 2+ channels. The Ca 2+ channel opening effect of Bay K8644 was completely antagonized by mefloquine. Likewise, the increase of [Ca 2+ ] i and of insulin secretion stimulated by 40 mM KCl, but not that by 30 mM glucose was antagonized by 50 μM mefloquine. Neither at 5 μM nor at 50 μM did mefloquin stimulate insulin secretion at basal glucose. In conclusion, mefloquine blocks K ATP channels and L-type Ca 2+ channels in pancreatic beta cells in the range from 5 to 50 μM. Thus it inhibits depolarization-induced insulin secretion, but in the presence of a stimulatory glucose concentration additional effects of mefloquine, possibly on intracellular Ca 2+ mobilization, and the metabolic amplification by glucose permit a sustained rate of secretion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The metabolic amplification of insulin secretion is the sequence of events which enables the secretory response to a fuel secretagogue to exceed the secretory response to a purely depolarizing stimulus. The signals in this pathway are incompletely understood. Here, we have characterized an experimental procedure by which the amplifying response to glucose is reversibly desensitized, while the response to α-ketoisocaproic acid (KIC) is unchanged., Materials/methods: Insulin secretion, NAD(P)H- and FAD-autofluorescence, Fura-2 fluorescence and oxygen consumption were measured in perifused NMRI mouse islets. The ATP- and ADP-contents were measured in statically incubated mouse islets. All islets were freshly isolated., Results: While the original observation on the dissociation between glucose- and KIC-amplification was obtained with islets that had been exposed to a high concentration of the sulfonylurea glipizide in the absence of glucose, we now show that in the absence of exogenous fuel a moderate depolarization, irrespective of its mechanism, progressively decreased the amplification in response to both glucose and KIC. However, the amplification in response to glucose declined faster, so a time window exists where glucose was already inefficient, whereas KIC was of unimpaired efficiency. Measurements of adenine nucleotides, NAD(P)H- and FAD-autofluorescence, and oxygen consumption point to a central role of the mitochondrial metabolism in this process. The desensitization could be quickly reversed by increasing oxidative deamination of glutamate and consequently anaplerosis of the citrate cycle., Conclusion: Depolarization in the absence of exogenous fuel may be a useful model to identify those signals which are indispensable for the generation of metabolic amplification., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The number of women in surgery has steadily increased, yet their numbers in academic surgery positions and in high-ranking leadership roles remain low. To create strategies to address and improve this problem, it is essential to examine how gender plays into the advancement of a woman's career in academic surgery., Methods: Focus group (1) and one-on-one qualitative interviews (8) were conducted with women academic surgeons from various subspecialties in a large university setting. Interviews examined women surgeons' accounts of their experiences as women in surgery. Audio-recorded data were transcribed verbatim and coded thematically. NVivo10 software was used for cross-referencing of data and categorization of data into themes., Results: Focus group data suggested that gender discrimination was pervasive in academic surgery. However, in interviews, most interviewees strongly disavowed the possibility that their gender had any bearing on their professional lives. These surgeons attempted to distance themselves from the possibility of discrimination by suggesting that differences in men and women surgeons' experiences are due to personality issues and personal choices. However, their narratives highlighted deep contradiction; they both affirmed and denied the relevance of gender for their experience as surgeons., Conclusions: As overt acts of discrimination become less acceptable in society, it does not necessarily disappear but rather manifests itself in covert forms. By disavowing and distancing themselves from discrimination, these women exposed the degree to which these issues continue to be pervasive in surgery. Women surgeons' ability to both identify and resist discrimination was hobbled by narratives of individualism, gender equality, and normative ideas of gender difference., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To explore surgeons' perceptions of and potential concerns about coaching., Background: There is growing recognition that the traditional model of continuing professional development is suboptimal. This has led to increasing interest in alternative strategies that take place within the actual practice environment such as coaching. However, if coaching is to be a successful strategy for continuing professional development, it will need to be accepted by surgeons., Methods: This was a qualitative interview-based study using a constructivist grounded theory approach. Participants included 14 surgeons from University of Toronto-affiliated hospitals., Results: Participants expressed 3 main concerns about coaching: questioning the value of technical improvement ("As you get older if you don't have the stimulation from surgery to get better or to do things that are different and you are so good at so much, why bother [with coaching]?" P009), worry about appearing incompetent ("I think it would be perceived as either a sign of weakness or a sign of inability" P532), and concern about losing autonomy ("To me that would be real coaching where it's self-identified, I'm motivated, I find the person and then they coach me" P086)., Conclusions and Relevance: Coaching faces unique challenges in the context of a powerful surgical culture that values the portrayal of competency and instills the value of surgical autonomy. This study suggests that hanging on to these tightly held values of competency and autonomy is actually limiting the ways, and extent to which, surgeons can improve their practice.

Although manifesting female carriers of dystrophinopathies have been documented in adults, there are few reports of females presenting with symptomatic dystrophinopathies during childhood. The Canadian Pediatric Neuromuscular Group identified and characterized nine cases of female children 16 years or younger with genetically and/or histologically confirmed symptomatic dystrophinopathy, with an age range of 2-10 years at presentation. Presenting symptoms included proximal muscle weakness (6/9), calf pseudohypertrophy (5/9), abnormal gait (5/9) and myalgias (5/9). Five patients were noted to have significant behavioural and learning issues. The patients had a delay in diagnosis of 4 years from symptom onset. Skewed X inactivation was noted in 5/9 patients, while one patient had X inactivation levels in the normal range. Two of the patients were found to have X/autosome translocation, one of whom also had skewed X-inactivation. Increased awareness of manifesting females with dystrophinopathies will allow for earlier diagnosis and appropriate management for this rare group of patients., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The perception of dyspnea shows many similarities to the perception of pain. Both are multidimensional processes, which are not only influenced by sensory input but also by nonsensory factors like attention. Recent research has suggested that attentional distraction might reduce the perception of dyspnea but results are conflicting. Furthermore, the specific impact of attentional distraction on the distinct dimensions of perceived dyspnea has not been studied yet. Therefore, the present study examined the specific impact of changes in the attentional focus on the sensory and affective dimension of perceived dyspnea. Dyspnea was induced in forty-four healthy volunteers (mean age: 27.7 years, range: 18-47 years) by breathing through an inspiratory resistive load (3.57 kPa/L/s), while attention was directed either to breathing or distracted by reading texts. Inspiratory time (T(i)) and breathing frequency (f) were measured continuously. After each condition the experienced intensity (i.e., sensory dimension) and unpleasantness (i.e., affective dimension) of dyspnea were rated on separate visual analog scales (VAS), presented in randomized order. ANOVAs showed that attentional distraction during loaded breathing reduced the perceived unpleasantness of dyspnea (P<0.05), while the perceived intensity of dyspnea as well as T(i) and f remained unchanged. The results show that attentional distraction reduces the affective, but not the sensory dimension of induced dyspnea in healthy volunteers. Future studies are needed to clarify whether attentional distraction can effectively be used as intervention technique for reducing the unpleasant aspects of dyspnea in different patients groups.

Cutaneous leiomyosarcomas (LMS) originating from smooth muscle of the skin are rare malignant neoplasms. Preferential sites are hair-bearing areas, especially the legs. We report two patients in their 5th and 7th decade, in whom leiomyosarcomas were encountered in the lower leg and the capillitium, respectively. Histologically, the former was found to be a dermal leiomyosarcoma with subcutaneous infiltration, the latter an exclusively dermal tumor. The LMS of the lower leg had been excised three years previously in a different institution and had been diagnosed as a leiomyoma. Both lesions were excised with adequate safety margins in our institution and within a two-year postoperative observation period no recurrences were encountered. Dermal leiomyosarcomas have a 33% recurrence rate while that of subcutaneous leiomyosarcomas show is 50%. In contrast to exclusively dermal tumors, subcutaneous LMS show a tendency for hematogenic and lymphogenic metastases. Therapy of choice is excision with wide safety margins.

p16 (CDKN2A, MTS1, INK4A) status at genomic and protein levels was analysed and correlated with clinico-pathological features in 72 pituitary adenomas. Methylation of CpG islands of promoter/exon 1 sequences was found in most gonadotroph, lactotroph, plurihormonal, and null cell adenomas (36 of 44, 82%), but it was rare in somatotroph (1 of 13 cases, 8%) and corticotroph adenomas (1 of 15 cases, 7%). Homozygous CDKN2A deletion was restricted to rare somatotroph (15%) and corticotroph adenomas (13%). Immunohistochemical p16 protein expression was observed in the normal adenohypophysis, whereas it was absent in 60 of 72 (83%) tumours and reduced in another ten (14%) tumours. Staining for p16 was only seen in 5 of 15 (33%) corticotroph, 3 of 13 (23%) somatotroph, 3 of 5 (60%) plurihormonal, and 1 of 19 (5%) null cell adenomas. p16 immunonegativity without CDKN2A methylation or deletion occurred in 22 tumours, including most somatotroph and corticotroph adenomas (15 of 28, 54%). Both CDKN2A alterations and p16 negativity were related to larger tumour size. Patients with p16-negative tumours were older than patients with p16-positive tumours. These data suggest that p16 down-regulation is common in all adenoma types. The mechanisms of p16 down-regulation probably involve CDKN2A methylation in most types, but remain to be determined in somatotroph and corticotroph adenomas. These findings also suggest that p16 down-regulation is usually not an initial event, but is acquired during adenoma progression., (Copyright 2001 John Wiley & Sons, Ltd.)