Search

Abstract Antenatal hydronephrosis (HN) impacts up to 5% of pregnancies and requires close, frequent follow-up monitoring to determine who may benefit from surgical intervention. To create an automated HN Severity Index (HSI) that helps guide clinical decision-making directly from renal ultrasound images. We applied a deep learning model to paediatric renal ultrasound images to predict the need for surgical intervention based on the HSI. The model was developed and studied at four large quaternary free-standing paediatric hospitals in North America. We evaluated the degree to which HSI corresponded with surgical intervention at each hospital using area under the receiver-operator curve, area under the precision-recall curve, sensitivity, and specificity. HSI predicted subsequent surgical intervention with > 90% AUROC, > 90% sensitivity, and > 70% specificity in a test set of 202 patients from the same institution. At three external institutions, HSI corresponded with AUROCs ≥ 90%, sensitivities ≥ 80%, and specificities > 50%. It is possible to automatically and reliably assess HN severity directly from a single ultrasound. The HSI stratifies low- and high-risk HN patients thus helping to triage low-risk patients while maintaining very high sensitivity to surgical cases. HN severity can be predicted from a single patient ultrasound using a novel image-based artificial intelligence system.

Abstract Storytelling is a powerful means to evoke empathy and understanding among people. When patient partners, which include patients, family members, caregivers and organ donors, share their stories with health professionals, this can prompt listeners to reflect on their practice and consider new ways of driving change in the healthcare system. However, a growing number of patient partners are asked to ‘share their story’ within health care and research settings without adequate support to do so. This may ultimately widen, rather than close, the gap between healthcare practitioners and people affected by chronic disease in this new era of patient and public involvement in research. To better support patient partners with storytelling in the context of a patient-oriented research network, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) Network adapted an existing in-person storytelling workshop for patient educators within a hospital setting. The result is a 6-week virtual program called Storytelling for Impact, which guides patients, family members, caregivers and organ donors in developing impactful stories and sharing them at health care and research events, e.g., conferences. The online series of synchronous workshops is co-facilitated by story coaches, who are program alumni and Can-SOLVE CKD staff with trained storytelling experience. Each story follows a structure that includes a call to action, which aims to positively impact the priority-setting and delivery of care and research in Canada. The program has been a transformational process for many who have completed it, and numerous other health organizations have expressed interest in sharing this tool with their own patient partners. As result, we have also created an asynchronous online program that can be used by other interested parties outside our network. Patient partners who share their stories can be powerful mediators for inspiring changes in the health care and research landscape, with adequate structured support. We describe two novel programs to support patient partners in impactful storytelling, which are applicable across all health research disciplines. Additional resources are required for sustainability and scale up of training, by having alumni train future storytellers.

CAKUT is the leading cause of end-stage kidney disease in children and comprises a broad spectrum of phenotypic abnormalities in kidney and ureter development. Molecular mechanisms underlying the pathogenesis of CAKUT have been elucidated in genetic models, predominantly in the mouse, a paradigm for human renal development. Hedgehog (Hh) signaling is critical to normal embryogenesis, including kidney development. Hh signaling mediates the physiological development of the ureter and stroma and has adverse pathophysiological effects on the metanephric mesenchyme, ureteric, and nephrogenic lineages. Further, disruption of Hh signaling is causative of numerous human developmental disorders associated with renal malformation; Pallister-Hall Syndrome (PHS) is characterized by a diverse spectrum of malformations including CAKUT and caused by truncating variants in the middle-third of the Hh signaling effector GLI3. Here, we outline the roles of Hh signaling in regulating murine kidney development, and review human variants in Hh signaling genes in patients with renal malformation.

Congenital anomalies of the urinary tract are a major cause of chronic kidney disease in both adults and children. Ureteropelvic junction obstruction, usually detected as urinary tract dilatation in utero, is one of the most common forms of CAKUT. As antenatal ultrasound technology advances and screening becomes more widespread, increasing numbers of infants with this UPJO will be detected. Management of these infants presents a clinical conundrum, as distinguishing mild benign cases from those who may develop severe renal impairment is challenging. Herein we propose that an understanding of normal developmental and pathological mechanisms involved in UPJO is important in the armamentarium for tackling this challenging condition.

Antecedentes: El departamento del Cauca en Colombia es multiétnico, multicultural y biodiverso, también con grandes diferencias en bajo peso al nacer (BPN), mortalidad perinatal y mortalidad neonatal tardía entre municipios. Objetivo: Determinar la relación de costo-efectividad del control prenatal (CPN) cuando ha tenido buena calidad frente al que ha tenido calidad deficiente con respecto al BPN en el departamento del Cauca entre 2018 y 2020. Método: Evaluación económica con diseño epidemiológico de una cohorte histórica desde la perspectiva de la institución pagadora. Se calculó la razón incremental de costo-efectividad (RICE), análisis de sensibilidad e impacto presupuestal. Resultados: La incidencia de BPN fue del 8,3% (348/4182). La calidad deficiente en el CPN incrementó el riesgo de BPN (OR: 3,38; IC95%: 1,05-8,2) y la buena calidad tuvo una mejor relación de costo-efectividad (RICE: USD 2727,75), con posición dominante frente a la calidad deficiente (6,14 veces el PIB per cápita de ahorro) y con un impacto presupuestal de USD 2.904.392. Conclusiones: La buena calidad del CPN en el departamento del Cauca durante 2018-2020 fue costo-efectiva y dominante por ser de menor costo y mayor efectividad.

Eczema herpeticum (EH), also known as Kaposi's varicelliform eruption, is a disseminated herpes simplex virus infection seen in patients with underlying skin conditions, most commonly atopic dermatitis. Monomorphic vesicles and ''punched-out'' erosions with hemorrhagic crusts over eczematous regions are the hallmarks of EH's presentation. Here, we discuss a first reported case of eczema herpeticum in a patient living with well controlled HIV with prior steroid use. A 30-year-old male patient living with HIV presented to the hospital with a generalized rash involving the face, neck, arms, hands, low back region, and both feet. Herpes simplex 1 and 2 by PCR DNA were detected from external auditory ear canal drainage. The patient was treated with intravenous acyclovir and responded well. He had long term history of eczema and required acyclovir prophylaxis later.

Purpose of program: Given the growing interest in patient-oriented research (POR) initiatives, there is a need to provide relevant training and education on how to engage with patients as partners on research teams. Sources of information: As part of its mandate to develop appropriate training materials, the patient-oriented renal research network, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD), established a training and Mentorship Committee (TMC). Methods: The committee brings together a unique combination of Indigenous and non-Indigenous patient partners (including caregivers, family members, and living donors), researchers, as well as patient engagement and knowledge translation experts, combining a multitude of perspectives and expertise. Following an assessment of training needs within the network, the TMC undertook the co-development of 5 learning modules to address the identified gaps. Subsequently, the committee divided into working groups tasked with developing content using a consultive and iterative approach informed by the DoTTI framework for building web-based tools for patients. In addition, the TMC embodied the guiding principles of inclusiveness, support, mutual respect, and co-building as set out by the Patient Engagement Framework through the Strategy for Patient-Oriented Research (SPOR) of the Canadian Institutes of Health Research. Key findings: The 5 new modules include: A Patient Engagement Toolkit, Storytelling for Impact, Promoting Kidney Research in Canada (KidneyPRO), Wabishki Bizhiko Skaanj Learning Pathway, and Knowledge Translation. The TMC’s approach to developing these modules demonstrates how a diverse group of stakeholders working together can create tools to support high-quality POR. This also provides a roadmap for other health research entities interested in developing similar tools within their unique domains. Limitations: The landscape of patient engagement in research is constantly evolving. This underscores the need for sustained resources to keep POR tools and training relevant and up-to-date. Sustaining such resources may not be feasible for all research entities. Implications: Collaborative approaches integrating patients in the development of POR tools ensure the content is relevant and meaningful to patients. Broader adoption of such approaches has great potential to address existing gaps and enhance the Canadian POR landscape.

The intricate anatomy and physiology of cranial nerves have inspired clinicians and scientists to study their roles in the nervous system. Damage to motor cranial nerves may result from a variety of organic or iatrogenic insults and causes devastating functional impairment and disfigurement. Surgical innovations directed towards restoring function to injured motor cranial nerves and their associated organs have evolved to include nerve repair, grafting, substitution, and muscle transposition. In parallel with this progress, research on tissue-engineered constructs, development of bioelectrical interfaces, and modulation of the regenerative milieu through cellular, immunomodulatory, or neurotrophic mechanisms has proliferated to enhance the available repertoire of clinically applicable reconstructive options. Despite these advances, patients continue to suffer from functional limitations relating to inadequate cranial nerve regeneration, aberrant reinnervation, or incomplete recovery of neuromuscular function. These shortfalls have profound quality of life ramifications and provide an impetus to further elucidate mechanisms underlying cranial nerve denervation and to improve repair. In this review, we summarize the literature on reconstruction and regeneration of motor cranial nerves following various injury patterns. We focus on seven cranial nerves with predominantly efferent functions and highlight shared patterns of injuries and clinical manifestations. We also present an overview of the existing reconstructive approaches, from facial reanimation, laryngeal reinnervation, to variations of interposition nerve grafts for reconstruction. We discuss ongoing endeavors to promote nerve regeneration and to suppress aberrant reinnervation and the development of synkinesis. Insights from these studies will shed light on recent progress and new horizons in understanding the biomechanics of peripheral nerve neurobiology, with emphasis on promising strategies for optimizing neural regeneration and identifying future directions in the field of motor cranial neuron research.

Summary: Induced pluripotent stem cells (iPSC) derived from healthy individuals are important controls for disease-modeling studies. Here we apply precision health to create a high-quality resource of control iPSCs. Footprint-free lines were reprogrammed from four volunteers of the Personal Genome Project Canada (PGPC). Multilineage-directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users demonstrated versatility by generating kidney organoids, T lymphocytes, and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited the expected hypertrophic phenotype. Whole-genome sequencing-based annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harbored at least one pre-existing or acquired variant with cardiac, neurological, or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cells from six tissues for disease modeling, and variant-preferred healthy control lines were identified for specific disease settings. : Ellis, Scherer, and colleagues apply precision health to upgrade iPSC quality for disease modeling. The resource provides control lines from four healthy individuals, clinical annotation of whole-genome variants, and identification of variant-preferred lines for neurologic and cardiac disease. Resource users demonstrated versatile differentiation into functional cells from six tissues, and CRISPR-edited cells phenocopied a cardiomyopathy model. Keywords: Personal Genome Project Canada, control iPSCs, whole-genome sequencing, gene editing, cellular phenotyping, disease modeling

Objectives In-office serial intralesional steroid injections (SILSIs) have become a commonly used treatment for subglottic stenosis. We characterized the impact of SILSIs on the time between operating room visits and incidence of glucocorticoid systemic side effects. Study Design Retrospective case series. Setting Academic tertiary care center. Methods All patients with subglottic stenosis receiving SILSIs at 1 institution from 2016 to 2020 were included. Surgery-free interval was compared using paired t tests. Side effect incidence was calculated with Kaplan-Meier methodology for visualization. Results Nineteen patients and 207 procedures were included. The majority of patients were White (95%) and female (95%) and had idiopathic subglottic stenosis (53%). Mean surgery-free interval for all patients was 8.7 months (95% CI, 5.6-11.8) before initiating SILSIs. Of 11 patients with calculable surgery-free interval, 10 experienced improvement, with a mean surgery-free interval increase of 4.6 months (95% CI, 2.4-6.7). Seven patients have not required surgery since initiation of SILSIs, with a mean follow-up time of 28 months (95% CI, 25-31). Noncutaneous systemic side effects occurred at a mean 3.2 months (95% CI, 2.4-4.0) from first injection and included Cushing’s syndrome, increased intraocular pressure, central serous chorioretinopathy, and new insulin requirement in the setting of diabetes. Conclusions Ninety-one percent of patients who initiated SILSIs and had a subsequent return to the operating room experienced a mean 4.6-month increase in surgery-free interval. Systemic side effects of glucocorticoids occurred in 32% of patients after initiating SILSIs. This should be considered in preprocedure counseling and side effect monitoring during treatment.

Background: Women scientists are less likely to obtain Assistant Professorship and achieve promotion, and obtain less grant funding than men. Scientist/clinician-scientist training programs which provide salary awards as well as training and mentorship are a potential intervention to improve outcomes among women scientists. We hypothesized whether a programmatic approach to scientist/clinician-scientist training is associated with improved outcomes for women scientists in Canada when compared with salary awards alone. Trainees within the Kidney Research Scientist Core Education and National Training Program (KRESCENT), Canadian Child Health Clinician Scientist Program (CCHCSP), and the Canadian Institutes of Health Research (CIHR) salary award programs were evaluated. Objective: To examine whether the structured KRESCENT training program with salary support improves academic success for women scientists relative to salary awards alone. Design: Retrospective cohort study. Setting: Canadian national research scientist and clinician-scientist training programs and salary awards. Participants: KRESCENT cohort (n = 59, 2005-2017), CCHCSP cohort (n = 58, 2002-2015), and CIHR (n = 571, 2005-2015) Salary Awardees for postdoctoral fellows (PDF) and new investigators (NI). Measurements: National operating grant funding success, achieving an academic position as an Assistant Professor for PDF, or achieving promotion to Associate Professor for NI. Methods: The gender distribution of each cohort was determined using first name and NamepediA and was examined for PDF and NI, followed by a description of trainee outcomes by gender and training level. Results: KRESCENT and CIHR PDF were balanced (12/27, 44% men and 55/116, 47% women) while CCHCSP had a higher proportion of women (13/20, 65%). KRESCENT and CCHCSP NI retained women scientists (19/32, 59% and 22/38, 58% women), whereas CIHR NI had fewer women (165/455, 36% women vs 290/455, 64% men, P = 0.01). There was a high rate of NI operating grant success (91%-95%) with no gender differences in each cohort. There was a high proportion of CCHCSP PDF who achieved an Assistant Professorship (18/20, 90%) that may be due in part to a longer follow-up period (9.3 ± 3 years) compared with KRESCENT PDF (7/27, 26%, 0.88 ± 4.5 years), and these data were not available for CIHR PDF. Women KRESCENT NI showed increased promotion to Associate Professor ( P = 0.02, 0.25 ± 3.2 years follow-up) and CCHCSP NI had high promotion rates (37/38, 97%, 6.9 ± 3.6 years follow-up) irrespective of gender. There was an overall trend toward more men pursuing biomedical research. Limitations: KRESCENT and CCHCSP training program cohort size and heterogeneity; assigning gender by first name may result in misclassification; lack of data on the respective applicant pools; and inability to examine intersectionality with gender, ethnicity, and sexual orientation. Conclusion: Overall trainee performance across programs is remarkable by community standards regardless of gender. KRESCENT and CCHCSP training programs demonstrated balanced success in their PDF and NI, whereas the CIHR awardees had reduced representation of women scientists from PDF to NI. This exploratory study highlights the utility of programmatic training approaches like the KRESCENT program as potential tools to support and retain women scientists in the academic pipeline during the challenging PDF to NI transition period.

Objective Patients with COVID-19 are at risk for laryngeal injury and dysfunction secondary to respiratory failure, prolonged intubation, and other unique facets of this illness. Our goal is to report clinical features and treatment for patients presenting with voice, airway, and/or swallowing concerns postacute COVID-19. Study Design Case series. Setting Academic tertiary care center. Methods Patients presenting with laryngeal issues following recovery from COVID-19 were included after evaluation by our laryngology team. Data were collected via retrospective chart review from March 1, 2020, to April 1, 2021. This included details of the patient’s COVID-19 course, initial presentation to laryngology, and subsequent treatment. Results Twenty-four patients met inclusion criteria. Twenty (83%) patients were hospitalized, and 18 required endotracheal intubation for a median (range) duration of 14 days (6-31). Ten patients underwent tracheostomy. Patients were evaluated at a median 107 days (32-215) after their positive SARS-CoV-2 test result. The most common presenting concerns were dysphonia (n = 19, 79%), dyspnea (n = 17, 71%), and dysphagia (n = 6, 25%). Vocal fold motion impairment (50%), early glottic injury (39%), subglottic/tracheal stenosis (22%), and posterior glottic stenosis (17%) were identified in patients who required endotracheal intubation. Patients who did not need intubation were most frequently treated for muscle tension dysphonia (67%). Conclusion Patients may develop significant voice, airway, and/or swallowing issues postacute COVID-19. These complications are not limited to patients requiring intubation or tracheostomy. Multidisciplinary laryngology clinics will continue to play an integral role in diagnosing and treating patients with COVID-19–related laryngeal sequelae.

One possible solution to the recent decline of calcium (Ca) concentrations in Canadian Shield forests and lakes in eastern North America is the addition of Ca-rich wood ash to watersheds. We investigated the feasibility of using small, mainly residential sources of non-industrial wood ash (NIWA) for this purpose by quantifying concentrations of its major nutrients and metals, its toxicity to Daphnia in aqueous extracts, and estimating the amount of NIWA available in the District of Muskoka in central Ontario. Locally collected NIWA averaged 30% Ca, and also contained smaller but significant amounts of K, Mg, Na, and P. Of these, K was so soluble that it was toxic to Daphnia over 48 h in the concentrate and 10-fold dilution; however, sedimented ash was not toxic over 15 d. Most metal levels in NIWA were below targets permitting unrestricted land application. However, Cu and Zn were just above these targets, but well below those for conditional use. Muskoka residents generate about 235 000 kg of NIWA annually, not enough to treat all central Ontario areas affected; however, a NIWA recycling programme implemented across southern Ontario could generate enough ash to solve the Ca decline problem in Muskoka’s forests and lakes.

Objective: Emergency medicine program directors (PD) value the standardized letter of evaluation (SLOE) as the most important aspect of a residency application when making both invitation and ranking decisions. This study aims to determine whether the presence of any lower-third in either SLOE global assessment (GA) question impacted the ability of an applicant to match into EM. We hypothesized that any lower-third ranking would be associated with increased odds of not matching into EM. Methods: We conducted a retrospective cohort study evaluating allopathic applicants from medical schools in the United States (US allopathic applicants) to a single EM residency program during the 2018/2019 match cycles. GA SLOE rankings from all applications were tabulated and compared to the applicant’s National Resident Matching Program (NRMP) match outcome. Comparative analyses were conducted between SLOE groupings and odds ratios (OR) were calculated. Results: A total of 2,017 SLOEs from 781 US allopathic applicants were analyzed during the study period. Of the total, 277 (35%) applicants in our sample had any lower-third GA ranking, which significantly decreased an applicant’s odds of matching in EM by 79% (OR 0.21, 95% CI, 0.12-0.34). Having more than one lower-third GA ranking did not further statistically decrease the odds of a successful EM match (OR 0.60, 95% CI 0.31-1.17). As a secondary finding of the study, results demonstrate that those applicants having no lower-third GA rankings had a nearly 5 times increased odds of an EM match (OR 4.84, 95% CI, 2.91-8.03). Conclusion: Having any lower-third GA ranking significantly reduced an applicant’s chances of matching into an EM program. Faculty advisors should be aware of the increased risk of not matching for any applicant with any lower-third GA ranking and advise students appropriately, while maintaining the integrity of the SLOE and not divulging the confidential information contained within.

Purpose of program: Traditionally, peer review was a closed process conducted only by individuals working in the research field. To establish a more integrated and patient-centered approach, one of Canada’s largest kidney research networks (Can-SOLVE CKD) has created a Research Operations Committee (ROC) that includes patients as key members. The ROC represents one way for achieving meaningful patient-oriented research (POR). Source of information: Can-SOLVE CKD, a network created as part of the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR). Methods: The ROC consists of patients, physicians, scientists, Indigenous partners, experts in research methodology, and a member of Can-SOLVE CKD’s operational team. On an annual basis, Can-SOLVE CKD’s research teams provide the ROC with a review package, which incorporates information from patient engagement check-in calls and surveys, the project’s knowledge translation plan and products, and a progress report written by the project team. The ROC evaluates the review package and provides feedback and recommendations accordingly. Key findings: The transparent nature of the process, regular feedback and review, along with an overt accountability and scoring system, has been embraced by both patients and researchers. As a result of the ROC process, the number of patient leads for each project has grown over a 3-year period and more researchers have received POR and cultural sensitivity training. Limitations: While anecdotal evidence suggests this approach is beneficial for achieving POR, formal mechanisms of evaluation are currently lacking. Implications: This ROC framework ensures patients are active contributors throughout the research process and could be adopted by other organizations to achieve a more patient-centered approach to research.

COVID‐19 has halted research around the globe and forced researchers out of their laboratories. Non‐emergency medical appointments were canceled. Ongoing clinical trials were challenged to create new modes of operation while public pressure mounted to find therapeutic options against COVID‐19. Yet, the inability to conduct research during COVID‐19 was overcome with cooperation, resource sharing, and compassion, which provides important lessons on how to improve health related research as we enter a new normal.

Biomedical scientists aim to contribute to further understanding of disease pathogenesis and to develop new diagnostic and therapeutic tools that relieve disease burden. Yet the majority of biomedical scientists do not develop their academic career or professional identity as “translational scientists,” and are not actively involved in the continuum from scientific concept to development of new strategies that change medical practice. The collaborative nature of translational medicine and the lengthy process of bringing innovative findings from bench to bedside conflict with established pathways of building a career in academia. This collaborative approach also poses a problem for evaluating individual contributions and progress. The traditional evaluation of scientific success measured by the impact and number of publications and grants scientists achieve is inadequate when the product is a team effort that may take decades to complete. Further, where scientists are trained to be independent thinkers and to establish unique scientific niches, translational medicine depends on combining individual insights and strengths for the greater good. Training programs that are specifically geared to prepare scientists for a career in translational medicine are not widespread. In addition, the legal, regulatory, scientific and clinical infrastructure and support required for translational research is often underdeveloped in academic institutions and funding organizations, further discouraging the development and success of translational scientists in the academic setting. In this perspective we discuss challenges and potential solutions that could allow for physicians, physician scientists and basic scientists to develop a professional identity and a fruitful career in translational medicine.

Background. Burnout and depression among physician trainees is increasing at an alarming rate. Promoting well-being is of utmost importance for graduate medical education. The primary objective was to determine if spiritual care staff/chaplaincy can assist in building emotional well-being and resiliency within medical residency education. Methods. For the academic year of July 2017 through June 2018, all graduate medical trainees in our institution were given the option of attending either an individual or group spiritual care session as part of a universal “Call to Wellness” curriculum. A Post-Wellness Survey was administered to measure perceptions about the program. Results. 49% (N = 258) of residents chose to participate in a spiritual care session. Prior to the session, 51% (N = 132) rated their overall well-being as neutral and 25% (N = 64) rated their overall well-being as slightly positive, positive, or very positive. After their spiritual care session, significant improvement was seen. 25% (N = 64) rated their overall well-being as neutral, and 51% (N = 132) rated their overall well-being as slightly positive, positive, or very positive (p

Far too much biomedical research is wasted and ends in the so called “Valley of Death”: the gap that exists between biomedical research and its clinical application. While the translational process requires collaboration between many disciplines, current translational medicine focuses on single disciplines. Therefore, educational pathways that integrate clinical and research skills in interdisciplinary and interprofessional contexts are needed. The Eureka institute (http://www.eurekainstitute.org/) was founded to address these issues. The institute organizes an annual 1-week international certificate course to educate professionals in the domains of translational medicine.Study design: This study set out to investigate the impact of the Eureka certificate course on the alumni, focusing on their ability to engage in translational activities and thus become more proficient translational professionals. An explanatory, mixed-methods study was executed.Data collection: A questionnaire was distributed to collect quantitative data on the number of alumni who were able to apply what they learned during the Eureka course and engage in translational activities. Questionnaire data were also used to inform the semi-structured interviews that were conducted subsequently.Results: Fifty-one percent of the alumni reported that participating in the Eureka course played a role in their decision to change to a different job or in the way they were accomplishing their everyday work. Ten conditions for change that either hampered or supported the Eureka alumni's engagement in translational research activities were identified. Further, the learning outcomes of the Eureka course that impacted the alumni's professional activities were explored using Personal Professional Theory (PPT). The insight that alumni gained in the full translational spectrum and stakeholders involved stimulated reflection on their own role within that pathway. Further, according to the alumni, the course provided them with the skills and confidence to pursue a career as translational professional. These learning outcomes, in combination with conditions that supported alumni's engagement in translational activities, such as supportive professional partners, opportunities to network or collaborate, and a translational work environment, contributed to the large number of alumni that were able to engage in translational activities.

This article is intended to collect some results of the several studies that have been made concerning Bullying and Harassment among boys and girls who attend basic education institutions in the central part of Santa Cruz province, in Argentina. It encloses theoretical framework about the problem of bullying and violence among children at school. It presents information about the region, some common aggressive behaviors as well as different ways and places in which those violent habits might be produced, according to children. Describes school populations suffering from such practices and analyzes some differences from school years, gender and zonal characteristics. It also shows samples of Victimization Rate and General Aggression Rate got in the area. Open to further discussion, this work provides certain description about some bullying phenomenon in the area, such as the case of the “Round-up Effect”, produced by the lack of anonymity in barely populated places. This article presents new emerging issues in the research field, like the appearance of new ways of violence, related to digital communication technologies such as instant messaging, e-mail, chat, blog, photoblog and social networks. To conclude, it offers some ideas about the construction of Early Warning Devices and Early Intervention Devices.

Empirical evidence is reviewed indicating that the extraordinary aspects of the human mind are due to our species’ ability to go beyond simple “dyadic associations” and to process the relations among three items of information simultaneously. Classic explanations of the “triadic” nature of human skills have been advocated by various scholars in the context of the evolution of human cognition. Here I summarize the core processes as found in (i) the syntax of language, (ii) tool-usage, and (iii) joint attention. I then review the triadic foundations of two perceptual phenomena of great importance in human aesthetics: (iv) harmony perception and (v) pictorial depth perception. In all five subfields of human psychology, most previous work has emphasized the recursive, hierarchical complexity of such “higher cognition,” but a strongly reductionist approach indicates that the core mechanisms are triadic. It is concluded that the cognitive skills traditionally considered to be “uniquely” human require three-way associational processing that most non-Primate animal species find difficult or impossible, but all members of Homo sapiens – regardless of small cultural differences – find easy and inherently intriguing.

This paper describes a library-based project involving the library staff at the Institute of Technology Carlow (ITC), in a collaboration led by the European Cooperation in Science and Technology (COST), Action MP1302 Nanospectroscopy. The project uses a comprehensive scoping methodology, an Advanced Scoping Meta-Review (ASMR), to identify significant topics in an emergent subject area; Optical Nanospectroscopy. An agreed mapping of the subject is derived in order to deliver a pedagogically coherent structure for a three-volume textbook set intended primarily for Early Stage Researchers (ESR). The review process is based on some earlier scoping methodologies, but is devised for a project involving a large number of individuals collaborating in authorship of the textbooks. A description of the scoping process is given, noting both the specific work in searching for and retrieving the appropriate literature, the qualitative and quantitative analysis and ordering of the search results, and placing the meta-review in the wider context of the editorial process to develop the Nanospectroscopy textbooks. The meta-review is employed in a special way in order to map an emergent subject area for the purpose of textbook development, rather than the more traditional use of such reviews to answer specific research questions. The importance of the library-led searching which underpinned this activity is emphasised. The successful outcome of this process resulting in agreement on the detailed content of three volumes is discussed. The paper ends with a critical evaluation of the lessons that can be drawn from this project.

Purpose of review This article serves to describe the Can-SOLVE CKD network, a program of research projects and infrastructure that has excited patients and given them hope that we can truly transform the care they receive. Issue Chronic kidney disease (CKD) is a complex disorder that affects more than 4 million Canadians and costs the Canadian health care system more than $40 billion per year. The evidence base for guiding care in CKD is small, and even in areas where evidence exists, uptake of evidence into clinical practice has been slow. Compounding these complexities are the variations in outcomes for patients with CKD and difficulties predicting who is most likely to develop complications over time. Clearly these gaps in our knowledge and understanding of CKD need to be filled, but the current state of CKD research is not where it needs to be. A culture of clinical trials and inquiry into the disease is lacking, and much of the existing evidence base addresses the concerns of the researchers but not necessarily those of the patients. Program overview The Canadian Institutes of Health Research (CIHR) has launched the national Strategy for Patient-Oriented Research (SPOR), a coalition of federal, provincial, and territorial partners dedicated to integrating research into care. Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) is one of five pan-Canadian chronic kidney disease networks supported through the SPOR. The vision of Can-SOLVE CKD is that by 2020 every Canadian with or at high risk for CKD will receive the best recommended care, experience optimal outcomes, and have the opportunity to participate in studies with novel therapies, regardless of age, sex, gender, location, or ethnicity. Program objective The overarching objective of Can-SOLVE CKD is to accelerate the translation of knowledge about CKD into clinical research and practice. By focusing on the patient’s voice and implementing relevant findings in real time, Can-SOLVE CKD will transform the care that CKD patients receive, and will improve kidney health for future generations.

In-person interviewing is the norm during the medical school application process, but it is not always possible due to reasons such as exorbitant cost of travel, work or residence outside the country and adverse travel conditions. In January 2016 during Winter Storm Jonas in the eastern United States of America, officials at the West Virginia University School of Medicine (WVU SOM) mandated a closure of the campus resulting in the cancellation of twenty on-site medical school interviews. The impromptu solution to overcoming this obstacle to in-person interviewing is described here as a case study. The successful use of digital interviewing has already been described at the residency and fellowship level; we believe this is the first reported case study about the successful use of FaceTime interviewing at the medical school level, and it may encourage admissions officials to expand the use of this modality in medical student recruitment.

Recently, quantum contextuality has been proved to be the source of quantum computation’s power. That, together with multiple recent contextual experiments, prompts improving the methods of generation of contextual sets and finding their features. The most elaborated contextual sets, which offer blueprints for contextual experiments and computational gates, are the Kochen⁻Specker (KS) sets. In this paper, we show a method of vector generation that supersedes previous methods. It is implemented by means of algorithms and programs that generate hypergraphs embodying the Kochen⁻Specker property and that are designed to be carried out on supercomputers. We show that vector component generation of KS hypergraphs exhausts all possible vectors that can be constructed from chosen vector components, in contrast to previous studies that used incomplete lists of vectors and therefore missed a majority of hypergraphs. Consequently, this unified method is far more efficient for generations of KS sets and their implementation in quantum computation and quantum communication. Several new KS classes and their features have been found and are elaborated on in the paper. Greechie diagrams are discussed.

Since 1926, the fishes in Lake Orta, one of Italy’s deepest natural lakes, were heavily damaged by profundal hypoxia and acidification linked to oxidation of ammonia from industrial effluents and by industrial metal pollution. Of the original 28 fish species, only perch survived the lake’s contamination. Recently, the water quality of the lake has been largely restored by reductions in pollutant inputs, and a massive liming intervention. These interventions restored fish habitat, but it is unclear whether the recent fish reintroductions were successful, and the present status of the fish community is unknown. Here we reviewed the history of the Lake Orta fish assemblage. Using an extensive 2014 sampling campaign, we compared the present fish community to both its pre-pollution composition and to the assemblages of nearby un-polluted, but otherwise similar lakes, Lake Mergozzo and Lake Maggiore. While nearshore fish density now appears normal in lake Orta, the open water community remains impoverished both in numbers and in species. Epilimnetic and hypolimnetic benthic nets were dominated by perch and roach in all the three lakes, but the catch of pelagic nets differed among lakes. Perch (Perca fluviatilis), rudd (Scardinius erythrophthalmus) and brown trout (Salmo trutta) dominated in Lake Orta while shad (Alosa fallax lacustris) and coregonids (Coregonus spp.) were dominant in the open waters of the other two lakes, but missing from Lake Orta. Many fully or partially migratory species, including marble trout (Salmo trutta marmoratus), eel (Anguilla Anguilla) and barbel (Barbus plebejus) were also missing from Lake Orta, a consequence of their initial extirpation and blocked re-colonization routes along the River Strona. In comparison with both pre-pollution and contemporary reference data, the fish community of Lake Orta has not been rehabilitated. The recovery of the littoral community is complete, but cold water species such as burbot (Lota lota), Arctic charr (Salvelinus alpinus) and bullhead (Cottus gobio) are still lacking, as are the pelagic zooplanktivores European whitefish (Coregonus lavaretus) and shad, which dominate offshore communities in the reference lakes, as they did a century ago in Lake Orta. To propose priorities for fish community rehabilitation in Lake Orta, we categorized the conservation, ecological and fishing values of each missing fish species in the lake, and evaluated the cost and probability of success of the needed intervention for each species. This analysis indicated that rehabilitation of shad and European whitefish should receive highest priority.

The goal of this study was to improve the understanding of the large-scale mechanisms underlying the recovery of the zooplankton of Lake Orta from historical contamination, following reduced input of ammonia and metals and the subsequent 1989/90 liming intervention. The industrial pollution had been severe and long-lasting (1929-1990). Zooplankton biodiversity has improved, but most of the new taxa appearing in our counts are rotifers, while many calanoids and the large cladoceran predators (Bythotrephes and Leptodora) that are common in the nearby Lake Maggiore, were still absent from Lake Orta 17 years after liming. To aid understanding of the large-scale mechanisms controlling changes in annual richness, we assessed the annual persistence (P) of Crustacea and Rotifera taxa as an estimator of whether propagules that survived introduction, as result of the natural recolonization process, also thrived. We found that the rate of introduction of zooplankton colonists and their persistence in the water column of Lake Orta changed from 1971 to 2007. New rotifer taxa appeared in the lake after the mid-1980s, when discharge of toxic substances decreased, but their annual persistence was low (P

The recovery of lakes from severe, historical acid and metal pollution requires that colonists of extirpated species arrive, survive and subsequently thrive. We employed 40 year records from weekly to monthly crustacean zooplankton samples from Middle and Clearwater lakes near Sudbury, Canada, to identify the main mechanistic bottlenecks in this recovery process. While both lakes now have circum-neutral pH, acidity decreased more rapidly in Middle Lake because of past liming interventions, while Clearwater Lake, being larger and supporting more housing, likely receives more zooplankton colonists than Middle Lake. Community richness increased much faster in Middle Lake than in Clearwater Lake, at 1.6 vs 0.9 species decade-1, respectively. Richness has recovered in Middle Lake, when assessed against a target of 9-16 species collection-1 determined from regional reference lakes, but it has not yet recovered in Clearwater Lake. Species accumulation curves and a metric of annual persistence show that this difference is a product not of greater rates of species introduction into Middle Lake, but rather to their greater annual persistence once introduced. Greater annual persistence was associated with better habitat quality (i.e., lower acid and metal toxicity) in Middle Lake, particularly early in the record, and lower planktivore abundance, more recently. These results support a growing consensus that ecological recovery of zooplankton from acidification and metal pollution does not depend strongly on propagule introduction rates which are adequate, but rather on propagule persistence, in lake-rich, suburban landscapes such as those near Sudbury.

Smelting of sulphur-rich metallic ores in Sudbury, Ontario, Canada, has caused acidification and metal contamination of thousands of lakes in the region. Recent reductions in smelter emissions have resulted in much ecological recovery, but the recovery of Daphnia species has been poor. To determine if Cu and Ni toxicity could explain differences in daphniid recovery among lakes, we compared results of 14 d static with renewal bioassays in waters from Blue Chalk Lake, an uncontaminated reference lake 200 km from Sudbury, and from five Sudbury lakes ranging in distance from the smelters and varying in metal and cation concentrations. We spiked Blue Chalk Lake water with Cu and Ni to levels resembling those of the Sudbury lakes and also tested the lake waters for toxicity. Survival of Daphnia pulex, D. pulicaria and D. mendotae decreased monotonically with increasing metal concentrations in the spiked Blue Chalk Lake treatments, falling from 90% in the controls to 0% at the two highest Cu and Ni levels, reflecting levels of Middle and Hannah lakes. In contrast, survival in waters collected from the actual Sudbury lakes did not monotonically track their total metal concentrations. Rather, survival fell to 0% in Clearwater Lake water, a lake with intermediate metal contamination (8.9 and 79.9 μg L–1 of Cu and Ni, respectively) vs 70-100% in the other lakes. We performed an additional assay with Clearwater Lake waters increasing its Ca and Na concentrations, singly and in combination to levels that reflected the levels in Middle Lake. The survival of the four daphniid species increased from 0% up to 80-100% with added Ca and from 0% to 60-90% with added Na. Lipid-ovarian indices had a similar trend to survival for D. mendotae and D. pulicaria in Bioassay 1, varying with the cation concentrations in the lakes for the daphniids in Bioassay 2. The bioassays results imply that regional recovery patterns of daphniids in Sudbury lakes cannot be understood without as a minimum considering both metal and base cation concentration differences among lakes, and give an indication of differences among Daphnia species to cope with metal stress.

The idea of launching another special issue of the Journal of limnology on Lake Orta was born in 2014, on the 25th anniversary of its liming intervention, during an International symposium on Lake Orta organized and hosted by the Pallanza Institute (http://www.ise.cnr.it/vb). The conference did not simply celebrate the past. While the liming of Lake Orta was undoubtedly a great national and international success, the speakers at the conference, instead sought to enlarge and deepen knowledge of patterns and mechanisms of lake ecosystem responses to the water quality improvements, or chemical recovery, that accompanied Lake Orta’s liming.

Group B streptococcal (GBS) infection of a native joint in a nonpregnant adult is uncommon. While many women are colonized with this flora, it rarely becomes pathogenic in its adult host. GBS associated joint infections have been reported, most of which have been related to hematogenous seeding from unknown sources. To our knowledge, there are no published case reports of a GBS joint infection in association with a pelvic exam and Papanicolaou (PAP) smear. In this case report, we present a case of GBS sepsis of a native shoulder, possibly resulting from a routine pelvic exam and PAP smear.

Glenoid loosening is the most common cause of failure in primary total shoulder arthroplasty (TSA) and often occurs years after the initial surgery. It is rare for a glenoid component to fail acutely. Several case reports of complete glenoid dissociation appear in the literature. It is important to report these failures to identify technical errors or component design flaws to improve outcomes in TSA. In this case report, we present an unrecognized acute failure of a cemented hybrid glenoid component at the time of surgery.

This study discusses the justifiability of item parameter estimation in incomplete testing designs in item response theory. Marginal maximum likelihood (MML) as well as conditional maximum likelihood (CML) procedures are considered in three commonly used incomplete designs: random incomplete, multistage testing and targeted testing designs. Mislevy and Sheenan (1989) have shown that in incomplete designs the justifiability of MML can be deduced from Rubin's (1976) general theory on inference in the presence of missing data. Their results are recapitulated and extended for more situations. In this study it is shown that for CML estimation the justification must be established in an alternative way, by considering the neglected part of the complete likelihood. The problems with incomplete designs are not generally recognized in practical situations. This is due to the stochastic nature of the incomplete designs which is not taken into account in standard computer algorithms. For that reason, incorrect uses of standard MML- and CML-algorithms are discussed.

Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis.

The relative consonance/dissonance of 2-tone intervals is well understood both experimentally and theoretically and provides a strong foundation for explaining why diatonic scales or their subsets are used in most musical cultures. Frequent textbook assertions notwithstanding, however, the consonance of intervals fails to account for the basic facts of harmony (3 or more tone combinations). We have recently shown (Cook & Fujisawa, 2006) how consideration of 3-tone psychophysics can explain the fundamental regularities of diatonic harmony. Distinct from the dissonance of 2-tone intervals, 3-tone combinations introduce an effect described by Leonard Meyer (1956) as harmonic “tension”: when a third tone is located midway between an upper and a lower tone, the chord takes on an unresolved, unstable, tense character – a psychoacoustical property inherent to the diminished and augmented chords. If the effects of the upper partials are included in a formal model that includes both 2-tone and 3-tone effects, the perceived sonority of the triads (major>minor> diminished>augmented) is easily explained.

Voluntary medical male circumcision (VMMC) is a priority HIV preventive intervention. Current adult circumcision methods need improvement.Field trial in 3 primary care centres. Minimally invasive VMMC using the Unicirc instrument following topical lidocaine/prilocaine anesthetic. Men were followed up at 1 and 4 weeks.We circumcised 110 healthy volunteers. Two men complained of transient burning pain during circumcision, but none required injectable anaesthesia. Median blood loss was 1ml and median procedure time was 9.0 min. There were 7 (6.3%) moderate complications (5 (4.5%) post-operative bleeds requiring suture and 2 (1.8%) post-operative infections) affecting 7 men. No men experienced significant wound dehiscence. 90.4% of men were fully healed at 4 weeks of follow-up and all were highly satisfied.Use of topical anaesthesia obviates the need for injectable anesthetic and makes the Unicirc procedure nearly painless. Unicirc is rapid, easy to learn, heals by primary intention with excellent cosmetic results, obviates the need for a return visit for device removal, and is potentially cheaper and safer than other methods. Use of this method will greatly facilitate scale-up of mass circumcision programs.ClinicalTrials.gov NCT02091726.

Too few women are aware of the very high efficacy of intrauterine copper devices (IUDs) to prevent pregnancy after unprotected intercourse. Women who frequently engage in unprotected intercourse or seek emergency contraception (EC) are at high risk of unplanned pregnancy and possible abortion. It is therefore important that these women receive precise and accurate information about intrauterine devices as they may benefit from using an IUD for EC as continuing contraception. Copper IUDs should be used as first choice options given their rapid onset of action and their long-term contraceptive action which require minimal thought or intervention on the part of the user. In the United States, there is only one copper IUD presently available which limits treatment options. There are numerous copper IUDs available for use in EC, however, their designs and size are not always optimal for use in nulliparous women or women with smaller or narrower uteruses. Utilization of frameless IUDs which do not require a larger transverse arm for uterine retention may have distinct advantages, particularly in young women, as they will be suitable for use in all women irrespective of uterine size. This paper provides practical information on EC use with emphasis on the use of the frameless IUD.

In line with musical “common sense” (but contrary to the century-old tradition of musical psychophysics), we show that harmony is an inherently three-tone phenomenon. Previous attempts at explaining the affective response to major/minor chords and resolved/unresolved chords on the basis of the summation of interval dissonance have been notably unsuccessful, but consideration of the relative size of the intervals contained in triads leads directly to solutions to these historical problems. At the heart of our model is Leonard Meyer’s idea from 1956 concerning “intervallic equidistance” – i.e., the perception of “tension” inherent to any three-tone combination that has two intervals of equivalent size (e.g., the augmented chord). By including the effects of the upper partials, a psychophysical explanation of the perceived sonority of the triads (major>minor>diminished>augmented) and the affective valence of major and minor chords is easily achieved. We conclude that the perceptual regularities of traditional diatonic harmony are neither due to the summation of interval effects nor simply arbitrary, learned cultural artifacts, but rather that harmony has a psychophysical basis dependent on three-tone combinations.

The primary cilium is required during early embryo patterning, epithelial tubulogenesis, and growth factor-dependent signal transduction. The requirement for primary cilia during renal epithelial-mesenchymal tissue interactions that give rise to nephrons is undefined. Here, we used Cre-mediated recombination to generate mice with Kif3a deficiency targeted to the ureteric and/or metanephric mesenchyme cell lineages in the embryonic kidney. Gradual loss of primary cilia in either lineage leads to a phenotype of reduced nephron number. Remarkably, in addition to cyst formation, loss of primary cilia in the ureteric epithelial cell leads to decreased expression of Wnt11 and Ret and reduced ureteric branching. Constitutive expression of GLI3 repressor (Gli3(Δ699/+) ) rescues these abnormalities. In embryonic metanephric mesenchyme cells, Kif3a deficiency limits survival of nephrogenic progenitor cells and expression of genes required for nephron formation. Together, our data demonstrate that Kif3a controls nephron number via distinct cell lineage-specific mechanisms.

Coniopterygidae material collected in two northwestern provinces of Argentina contained six described and one hitherto undescribed species. A list of the determined coniopterygids and the description of a new Incasemidalis species is given. Distinctive features of the species belonging to subgenus Stangesemidalis also are discussed.

The reverse perspective (RP) illusion is classified as a motion illusion due to inverted depth perception, similar to the Mach book and hollow mask illusions. Distortional motion of a rigid object surface is observed when an observer moves in front of the object which has a texture pattern giving inverted perspective cues (RP object). In this research, we studied the influence of the background pattern of the RP objects on the strength of the illusion. To perform quantitative evaluation, a stereo computer-graphics technique was used. Computer generated right- and left-eye images of an RP object were shown separately to the subjects' eyes through a haploscope. Using a computer key board, they adjusted the binocular disparity of the stereo images so that depth inversion due to the surface texture occurs. We evaluated the strength of the illusion by the critical value of the disparity and found that the background texture is an important factor determining the strength of the RP illusion. Especially, the texture in the horizontal direction creates stronger depth inversion effect compared to the vertical pattern. Using our experimental system, the influences of various pictorial cues on the RP illusion can be studied quantitatively.

Truncating GLI3 mutations in Pallister-Hall Syndrome with renal malformation suggests a requirement for Hedgehog signaling during renal development. HH-dependent signaling increases levels of GLI transcriptional activators and decreases processing of GLI3 to a shorter transcriptional repressor. Previously, we showed that Shh-deficiency interrupts early inductive events during renal development in a manner dependent on GLI3 repressor. Here we identify a novel function for GLI3 repressor in controlling nephron number. During renal morphogenesis, HH signaling activity, assayed by expression of Ptc1-lacZ, is localized to ureteric cells of the medulla, but is undetectable in the cortex. Targeted inactivation of Smo, the HH effector, in the ureteric cell lineage causes no detectable abnormality in renal morphogenesis. The functional significance of absent HH signaling activity in cortical ureteric cells was determined by targeted deletion of Ptc1, the SMO inhibitor, in the ureteric cell lineage. Ptc1(-/-UB) mice demonstrate ectopic Ptc1-lacZ expression in ureteric branch tips and renal hypoplasia characterized by reduced kidney size and a paucity of mature and intermediate nephrogenic structures. Ureteric tip cells are remarkable for abnormal morphology and impaired expression of Ret and Wnt11, markers of tip cell differentiation. A finding of renal hypoplasia in Gli3(-/-) mice suggests a pathogenic role for reduced GLI3 repressor in the Ptc1(-/-UB) mice. Indeed, constitutive expression of GLI3 repressor via the Gli3(Delta699) allele in Ptc1(-/-UB) mice restores the normal pattern of HH signaling, and expression of Ret and Wnt11 and rescued the renal phenotype. Thus, GLI3 repressor controls nephron number by regulating ureteric tip cell expression of Wnt11 and Ret.