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Animals navigate by learning the spatial layout of their environment. We investigated spatial learning of mice in an open maze where food was hidden in one of a hundred holes. Mice leaving from a stable entrance learned to efficiently navigate to the food without the need for landmarks. We developed a quantitative framework to reveal how the mice estimate the food location based on analyses of trajectories and active hole checks. After learning, the computed ‘target estimation vector’ (TEV) closely approximated the mice’s route and its hole check distribution. The TEV required learning both the direction and distance of the start to food vector, and our data suggests that different learning dynamics underlie these estimates. We propose that the TEV can be precisely connected to the properties of hippocampal place cells. Finally, we provide the first demonstration that, after learning the location of two food sites, the mice took a shortcut between the sites, demonstrating that they had generated a cognitive map.

ABSTRACT The detection of Clostridioides difficile infections (CDI) relies on testing the stool of patients by toxin antigen detection or PCR methods. Although PCR and antigenic methods have significantly reduced the time to results, delays in stool collection can significantly add to the turnaround time. The use of rectal swabs to detect C. difficile could considerably reduce the time to diagnosis of CDI. We developed a new rapid PCR assay for the detection of C. difficile and evaluated this PCR assay on both stool and rectal swab specimens. We recruited a total of 623 patients suspected of C. difficile infection. Stool samples and rectal swabs were collected from each patient and tested by our PCR assay. Stool samples were also tested by the cell cytotoxicity neutralization assay (CCNA) as a reference. The PCR assay detected C. difficile in 60 stool specimens and 61 rectal swabs for the 64 patients whose stool samples were positive for C. difficile by CCNA. The PCR assay detected an additional 35 and 36 stool and rectal swab specimens positive for C. difficile, respectively, for sensitivity with stools and rectal swabs of 93.8% and 95.3%, specificity of 93.7% and 93.6%, positive predictive values of 63.2% and 62.9%, and negative predictive values of 99.2% and 99.4%. Detection of C. difficile using PCR on stools or rectal swabs yielded reliable and similar results. The use of PCR tests on rectal swabs could reduce turnaround time for CDI detection, thus improving CDI management and control of C. difficile transmission.IMPORTANCEClostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, resulting in high morbidity, mortality, and economic burden. In clinical laboratories, CDI testing is currently performed on stool samples collected from patients with diarrhea. However, the diagnosis of CDI can be delayed by the time required to collect stool samples. Barriers to sample collection could be overcome by using a rectal swab instead of a stool sample. Our study showed that CDI can be identified rapidly and reliably by a new PCR assay developed in our laboratory on both stool and rectal swab specimens. The use of PCR tests on rectal swabs could reduce the time for the detection of CDI and improve the management of this infection. It should also provide a useful alternative for infection-control practitioners to better control the spread of C. difficile.

Background: The molecular and epidemiological landscape of C. difficile infection (CDI) has evolved markedly in the last decade; however, limited information is available contrasting differences between adult and pediatric populations. We describe a multicenter study evaluating healthcare-associated (HA) and community-associated (CA) adult and pediatric-CDI identified in the Canadian Nosocomial Infection Surveillance Program (CNISP) network from 2015 to 2022. Methods: Hospitalized patients with CDI were identified from up to 84 hospitals between 2015–2022 using standardized case definitions. Cases were confirmed by PCR, cultured, and further characterized using ribotyping and E-test. We used two-tailed tests for significance (p≤0.05). Results: Of 30,817 cases reported, 29,245 were adult cases [HA-CDI (73.2%), CA-CDI (26.8%)] and 1,572 were pediatric cases [HA-CDI (77.7%), CA-CDI (22.3%)]. From 2015 to 2022, HA-CDI rates decreased 19.7% (p=0.007) and 29.4% (p=0.004) in adult and pediatric populations, respectively (Figure 1). CA-CDI rates remained relatively stable in the adult population (p=0.797), while decreasing 60.7% in the pediatric population (p=0.013). Median ages of adult and pediatric patients were 70 (interquartile range (IQR), 58–80) and seven (IQR, 3–13) years, respectively. Thirty-day all-cause mortality was significantly higher among adult vs. Pediatric CDI patients (11.0% vs 1.4%, p < 0.0001). No significant differences in other severe outcomes were found. Ribotyping and susceptibility data were available for 4,620 samples: 3,558 adult (77.0%) and 1,062 pediatric (23.0%). The predominant adult and pediatric ribotypes (RT) were 106 (12.2/16.2%), 027 (11.4/3.2%), and 014 (8.8/8.2%). Overall, RT027 prevalence significantly decreased from 17.9% in 2015 to 3.2% in 2022 (p=0.003), while RT106 increased from 8.5% to 14.4%. Resistance rates among adult and pediatric isolates were similar for all antimicrobials tested except moxifloxacin (16.2% vs. 6.2%, p < 0.0001, respectively). Adult moxifloxacin resistance decreased from 30% to 6.3% from 2015 to 2022 (p=0.006). Adults with moxifloxacin-resistant CDI were older (median: 74 vs. 69 years, p < 0.001) and had higher thirty-day all-cause mortality (13% vs. 9.8%, p=0.041) and recurrence (10% vs. 5.7%, p < 0.001) compared to those with moxifloxacin non-resistant CDI, while these trends were not observed in pediatric patients. Among RT027 strains, moxifloxacin resistance decreased from 91.0% in 2015 to 7.1% in 2022. There was one metronidazole-resistant pediatric sample in 2018 and no resistance to vancomycin or tigecycline in either population. Conclusion: We have found differences in the epidemiological and molecular characteristics of adult and pediatric CDI, with higher thirty-day all-cause mortality among adults. Overall, RT106 has replaced RT027 as the predominant ribotype with a concomitant decrease in fluoroquinolone resistance.

Background: Patients colonized with Clostridioides difficile are at risk of transmitting C. difficile to other patients, and of developing C. difficile infection (CDI). Known risk factors for carriage include previous hospitalization, gastric acid suppression and previous CDI. Data regarding duration of carriage and its predictors are lacking but could be useful to better understand the natural evolution of carriage and better estimate the likelihood of transmission or progression to CDI. Methods: We performed a retrospective cohort study of C. difficile colonized patients with > = 1 admission to a tertiary academic institution between November 2013 and January 2017. Colonization status was determined upon hospital admission by detection of TcdB gene by polymerase chain reaction on a rectal screening swab, as part of a systematic screening program. Overall duration of carriage and predictors of prolonged carriage were explored using Kaplan-Meier methods and Cox regression. Results: There were 134 patients, who after having a positive initial screening test (and therefore identified as colonized with C. difficile), had subsequent testing. The median age was 77 years (IQR, 66 to 85), and 53.6% of the patients were female. After hospital discharge, 26 (19.4%) colonized patients progressed to CDI. Mean duration of follow up was 269 days, with a median of 179 days. Median duration of carriage was 211 days, (95% confidence interval (CI) [157, 264]). Predictors associated with decreased duration of C. difficile colonization included younger age (HR per unit decrease (year), 1.013; 95% CI, 1.025 to 1.001; p=0.03), and receipt of antibiotics in the 3 months prior to first admission (mean days to clearance of patients with and without recent antibiotic use, 252 days vs 372 days, respectively; HR, 1.55; 95% CI, 1.01 to 2.36; p < 0 .04). By contrast, the presence of comorbidities (e.g. heart failure, diabetes, cancer, and chronic kidney disease), the use of proton-pump inhibitors (PPIs), the receipt of antibiotics during the first admission, and the duration of first hospitalization were not associated with significant differences in duration of carriage. Conclusion: This study is the largest cohort of C. difficile carriers with longitudinal follow up of their colonization status. It highlights the extended duration of carrier status especially in older patients and identifies predictors of prolonged carriage. Further studies are needed to understand the underlying relationship with the predictors identified in this study.

Graduate student socialization has been studied in multiple disciplines, including communication. As their career trajectories change, faculty must consider how to socialize students into the field and their subsequent careers. Using a modified Delphi survey, we examined the differences in faculty and students' perceptions regarding the content of a graduate professional seminar in communication. Results indicate that students would prefer a focus on implicit norms and the hidden curriculum, while faculty would prefer to focus on disciplinary content. We offer recommendations for developing a course that addresses both needs and, thus, simultaneously attends to the changing job market.

Abstract Analysis of patterns of variation of time-series, termed variability analysis, represents a rapidly evolving discipline with increasing applications in different fields of science. In medicine and in particular critical care, efforts have focussed on evaluating the clinical utility of variability. However, the growth and complexity of techniques applicable to this field have made interpretation and understanding of variability more challenging. Our objective is to provide an updated review of variability analysis techniques suitable for clinical applications. We review more than 70 variability techniques, providing for each technique a brief description of the underlying theory and assumptions, together with a summary of clinical applications. We propose a revised classification for the domains of variability techniques, which include statistical, geometric, energetic, informational, and invariant. We discuss the process of calculation, often necessitating a mathematical transform of the time-series. Our aims are to summarize a broad literature, promote a shared vocabulary that would improve the exchange of ideas, and the analyses of the results between different studies. We conclude with challenges for the evolving science of variability analysis.

The past decade has brought increased focus on STEM learning (Bell, Lewenstein, Shouse, & Feder, 2009; NGSS Lead States, 2013; U.S. Department of Education, 2015). The growth of STEM-related industries and the power associated with STEM fields make access to STEM careers an equity issue (Buechley, 2016). Despite gains in educational achievement, women and individuals from nondominant cultures remain underrepresented in STEM majors and careers (National Science Foundation, 2017). Afterschool programs offer a promising context for engaging diverse students: African American and Latinx children attend afterschool programs at rates twice that of White students (Afterschool Alliance, 2015). STEM programs at youth-centered sites capitalize on the resources of spaces children find welcoming and accessible. The natural curricular flexibility of afterschool programs enables immersive exploration and experimentation in STEM as well as authentic opportunities for building skills and developing relationships helpful to STEM careers (Afterschool Alliance, 2015; Krishnamurthi, Ballard, & Noam, 2014). Afterschool science programs naturally blur disciplinary boundaries and incorporate diverse ways of knowing (Calabrese Barton, Birmingham, Sato, Tan, & Calabrese Barton, 2013). These factors can be leveraged to broaden young people's definition of science and to foster "productive hybrid STEM identity work for underrepresented youth" (Calabrese Barton, Tan, & Greenberg, 2017, p. 21). Science education in youth-centered sites can value the cultures of underrepresented students while encouraging them to explore new science-related interests and identities (Calabrese Barton & Tan, 2010). Despite widespread acceptance of the benefits of afterschool STEM, more research is needed on how program factors affect student engagement and learning (Laursen, Thiry, Archie, & Crane, 2013). Coburn and Penuel (2016) call for more studies on program processes, collaboration strategies, and productive responses to challenges. The STEMinist Program, created by the authors, was a research-practice collaboration between university researchers and an afterschool program for female students in grades 4 to 6. This article describes how the program's ongoing design transformations increased girls' understanding of and interest in STEM. Design-based framing (Barab & Squire, 2009) enabled ongoing adjustments to the program while also identifying best practices for afterschool STEM learning. To understand the program's progression and outcomes, the authors examined the features of the learning environment and the relationships among design components by analyzing qualitative data collected before, during, and after program implementation. Participants' perceptions of science and scientists helped them understand the impact of the program and ways to improve it.

The introduction to interpersonal communication course (IPC) is popular for both communication majors and nonmajors alike, and as such, many departments have designed online versions of the course. Teaching IPC in this format has challenges, given its dual emphasis on theoretical understanding and skill-building. This reflection essay explores the efficacy of providing audio feedback on essays in the online IPC course, as a way to create a positive online presence, manage the grading load, and encourage students to implement the feedback. The rationale for this approach to feedback and implementation strategies are provided, as well as a discussion of outcomes from the intervention. A review of course data and perceptions indicated gains in student application of course material and satisfaction with the audio feedback mechanism.

In a variety of neurons, action potentials (APs) initiate at the proximal axon, within a region called the axon initial segment (AIS), which has a high density of voltage-gated sodium channels (NaVs) on its membrane. In pyramidal neurons, the proximal AIS has been reported to exhibit a higher proportion of NaVs with gating properties that are "right-shifted" to more depolarized voltages, compared to the distal AIS. Further, recent experiments have revealed that as neurons develop, the spatial distribution of NaV subtypes along the AIS can change substantially, suggesting that neurons tune their excitability by modifying said distribution. When neurons are stimulated axonally, computational modelling has shown that this spatial separation of gating properties in the AIS enhances the backpropagation of APs into the dendrites. In contrast, in the more natural scenario of somatic stimulation, our simulations show that the same distribution can impede backpropagation, suggesting that the choice of orthodromic versus antidromic stimulation can bias or even invert experimental findings regarding the role of NaV subtypes in the AIS. We implemented a range of hypothetical NaV distributions in the AIS of three multicompartmental pyramidal cell models and investigated the precise kinetic mechanisms underlying such effects, as the spatial distribution of NaV subtypes is varied. With axonal stimulation, proximal NaV availability dominates, such that concentrating right-shifted NaVs in the proximal AIS promotes backpropagation. However, with somatic stimulation, the models are insensitive to availability kinetics. Instead, the higher activation threshold of right-shifted NaVs in the AIS impedes backpropagation. Therefore, recently observed developmental changes to the spatial separation and relative proportions of NaV1.2 and NaV1.6 in the AIS differentially impact activation and availability. The observed effects on backpropagation, and potentially learning via its putative role in synaptic plasticity (e.g. through spike-timing-dependent plasticity), are opposite for orthodromic versus antidromic stimulation, which should inform hypotheses about the impact of the developmentally regulated subcellular localization of these NaV subtypes.

A 38-year-old pregnant patient was managed by the cardio-obstetrics multidisciplinary team for severe degenerative bioprosthetic aortic valve failure. She was medically managed utilizing echocardiogram and brain natriuretic peptide until she demonstrated worsening heart failure. A valve and cardio-obstetrics team evaluation led to valve-in-valve transcatheter aortic valve replacement at 30 weeks’ gestation.

Abstract Objective: To describe the epidemiology of healthcare-associated Clostridioides difficile infection (HA-CDI) in two Québec hospitals in Canada following the 2003 epidemic and to evaluate the impact of antibiotic stewardship on the incidence of HA-CDI and the NAP1/027 strain. Design: Time-series analysis. Setting: Two Canadian tertiary care hospitals based in Montréal, Québec. Patients: Patients with a positive assay for toxigenic C. difficile were identified through infection control surveillance. All cases of HA-CDI, defined as symptoms occurring after 72 hours of hospital admission or within 4 weeks of hospitalization, were included. Methods: The incidence of HA-CDI and antibiotic utilization from 2003 to 2020 were analyzed with available C. difficile isolates. The impact of antibiotic utilization on HA-CDI incidence was estimated by a dynamic regression time-series model. Antibiotic utilization and the proportion of NAP1/027 strains were compared biannually for available isolates from 2010 to 2020. Results: The incidence of HA-CDI decreased between 2003 and 2020 at both hospitals from 26.5 cases per 10,000 patient-days in 2003 to 4.9 cases per 10,000 patient-days in 2020 respectively. Over the study period, there were an increase in the utilization of third-generation cephalosporins and a decrease in usage of fluoroquinolones and clindamycin. A decrease in fluoroquinolone utilization was associated with a significant decrease in HA-CDI incidence as well as decrease in the NAP1/027 strain by approximately 80% in both hospitals. Conclusions: Decreased utilization of fluoroquinolones in two Québec hospitals was associated with a decrease in the incidence of HA-CDI and a genotype shift from NAP1/027 to non-NAP1/027 strains.

BackgroundThe COVID-19 pandemic has had a profound impact on emergency department (ED) care in Canada and around the world. To prevent transmission of COVID-19, personal protective equipment (PPE) was required for all ED care providers in contact with suspected cases. With mass vaccination and improvements in several infection prevention components, our hypothesis is that the risks of transmission of COVID-19 will be significantly reduced and that current PPE use will have economic and ecological consequences that exceed its anticipated benefits. Evidence is needed to evaluate PPE use so that recommendations can ensure the clinical, economic, and environmental efficiency (ie, eco-efficiency) of its use. ObjectiveTo support the development of recommendations for the eco-efficient use of PPE, our research objectives are to (1) estimate the clinical effectiveness (reduced transmission, hospitalizations, mortality, and work absenteeism) of PPE against COVID-19 for health care workers; (2) estimate the financial cost of using PPE in the ED for the management of suspected or confirmed COVID-19 patients; and (3) estimate the ecological footprint of PPE use against COVID-19 in the ED. MethodsWe will conduct a mixed method study to evaluate the eco-efficiency of PPE use in the 5 EDs of the CHU de Québec-Université Laval (Québec, Canada). To achieve our goals, the project will include four phases: systematic review of the literature to assess the clinical effectiveness of PPE (objective 1; phase 1); cost estimation of PPE use in the ED using a time-driven activity-based costing method (objective 2; phase 2); ecological footprint estimation of PPE use using a life cycle assessment approach (objective 3; phase 3); and cost-consequence analysis and focus groups (integration of objectives 1 to 3; phase 4). ResultsThe first 3 phases have started. The results of these phases will be available in 2023. Phase 4 will begin in 2023 and results will be available in 2024. ConclusionsWhile the benefits of PPE use are likely to diminish as health care workers’ immunity increases, it is important to assess its economic and ecological impacts to develop recommendations to guide its eco-efficient use. Trial RegistrationPROSPERO CRD42022302598; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=302598 International Registered Report Identifier (IRRID)DERR1-10.2196/50682

Introduction: The Measures Associated to PrognoStic (MAPS) tool is a standardized questionnaire that integrates validated prognostic tools to detect the presence of biopsychosocial prognostic factors in patients consulting for musculoskeletal disorders. Purpose: The objectives were to assess the: 1) feasibility of implementation of the MAPS tool, 2) clinicians' acceptability of the dashboard, and 3) patients' acceptability of the MAPS tool. Methods: Twenty physiotherapists and two occupational therapists from seven outpatient musculoskeletal clinics were recruited to implement the MAPS tool during a 3-month timeframe, where new patients completed the questionnaire upon initial assessment. The results were presented to the clinicians via a dashboard. Surveys and semi-structured interviews were conducted to measure feasibility and acceptability. Results: Six out of 11 feasibility criteria (55%) and 21 out of 24 acceptability criteria (88%) reached the a priori threshold for success. The interviews allowed us to identify three main themes to facilitate implementation: 1) limiting the burden, 2) ensuring patients' understanding of the tool's purpose, and 3) integrating the dashboard as a clinical information tool. Conclusion: Our quantitative and qualitative results support the feasibility of implementation and acceptability of the MAPS tool pending minor adjustments. Depicting the patients' prognostic profile has the potential to help clinicians optimize their interventions for patients presenting with musculoskeletal disorders. [ABSTRACT FROM AUTHOR]

Clostridioides difficile is a major cause of infectious nosocomial diarrhea in high-income countries (1). Disease severity ranges from asymptomatic colonization to fulminant colitis, sometimes leading to colectomy and death (2). [...]