Search

We describe the clinical course of 4 infants infected with severe acute respiratory syndrome coronavirus 2. All were admitted to our tertiary care neonatal intensive care unit during the Omicron variant wave in our region. All 4 infants, who were less than 3 months of age, including three born prematurely, presented with critical illness. However, their clinical presentation varied considerably. Of them, two infants presented with apnea, one with respiratory distress, and one with gastrointestinal manifestation. Our experience with these four infants provides evidence for a severe form of disease and varied clinical presentation in neonates and young infants speculated to be infected with Omicron variant.

Acute Critical Event Debriefing (ACED) after cardiopulmonary arrests should be the standard of care. However, little literature exists on how to implement performance-focused ACED in healthcare. Based on a series of successful ACED implementations in a variety of our settings, we describe key learnings and propose best practices to aid clinicians and organizations in establishing a successful ACED program. Within this practical guide, we also present a novel, standardized debriefing tool (Hotwash) that has been adapted for a variety of clinical settings.

To examine the synergetic effects of ocean acidification (OA) and light intensity on the photosynthetic performance of marine diatoms, the marine centric diatom Thalassiosira weissflogii was cultured under ambient low CO2 (LC, 390 μatm) and elevated high CO2 (HC, 1000 μatm) levels under low-light (LL, 60 μmol m−2 s−1) or high-light (HL, 220 μmol m−2 s−1) conditions for over 20 generations. HL stimulated the growth rate by 128 and 99% but decreased cell size by 9 and 7% under LC and HC conditions, respectively. However, HC did not change the growth rate under LL but decreased it by 9% under HL. LL combined with HC decreased both maximum quantum yield (FV/FM) and effective quantum yield (ΦPSII), measured under either low or high actinic light. When exposed to UV radiation (UVR), LL-grown cells were more prone to UVA exposure, with higher UVA and UVR inducing inhibition of ΦPSII compared with HL-grown cells. Light use efficiency (α) and maximum relative electron transport rate (rETRmax) were inhibited more in the HC-grown cells when UVR (UVA and UVB) was present, particularly under LL. Our results indicate that the growth light history influences the cell growth and photosynthetic responses to OA and UVR.

1. Diatoms of the Arctic Ocean annually experience extreme changes of light environment linked to photoperiodic cycles and seasonal variations of the snow and sea-ice cover extent and thickness which attenuate light penetration in the water column. Arctic diatom communities exploit this complex seasonal dynamic through a well-documented species succession during spring, beginning in sea-ice and culminating in massive phytoplankton blooms underneath sea-ice and in the marginal ice zone. The pattern of diatom taxa sequentially dominating this succession is relatively well conserved interannually, and taxonomic shifts seem to align with habitat transitions. 2. To understand whether differential photoadaptation strategies among diatom taxa explain these recurring succession sequences, we coupled lab experiments with field work in Baffin Bay at 67.5°N. Based on field data, we selected five diatom species typical of different ecological niches and measured their growth rates under light intensity ranges representative of their natural habitats. To characterize their photoacclimative responses, we sampled pigments and total particulate carbon, and conducted 14C-uptake photosynthesis response curves and variable fluorescence measurements. 3. We documented a gradient in species respective light intensity for maximal growth suggesting divergent light response plasticity, which for the most part align with species sequential dominance. Other photophysiological parameters supported this ecophysiological framing, although contrasts were always clear only between succession endmembers, Nitzschia frigida and Chaetoceros neogracilis. To validate that these photoacclimative responses are representative of in situ dynamics, we compared them to the chlorophyll a-specific light-limited slope (α*) and saturated rate of photosynthesis (P*M), monitored in Baffin Bay on sea-ice and planktonic communities. This complementary approach confirmed that unusual responses in α* and P*M as a function of light history intensity are similar between sentinel sympagic species N. frigida and natural ice-core communities. While no light-history-dependent trends were observed in planktonic communities, their α* and P*M values were in the range of measurements from our monospecific cultures. 4. Synthesis. Our results suggest that Arctic diatoms species photoadaptation strategy is tuned to the light environment of the habitats in which they dominate and indeed drives the seasonal taxonomic succession.

To enable rapid propagation of action potentials, axons are ensheathed by myelin, a multilayered insulating membrane formed by oligodendrocytes. Most of the myelin is generated early in development, resulting in the generation of long-lasting stable membrane structures. Here, we explored structural and dynamic changes in central nervous system myelin during development. To achieve this, we performed an ultrastructural analysis of mouse optic nerves by serial block face scanning electron microscopy (SBF-SEM) and confocal time-lapse imaging in the zebrafish spinal cord. We found that myelin undergoes extensive ultrastructural changes during early postnatal development. Myelin degeneration profiles were engulfed and phagocytosed by microglia using exposed phosphatidylserine as one “eat me” signal. In contrast, retractions of entire myelin sheaths occurred independently of microglia and involved uptake of myelin by the oligodendrocyte itself. Our findings show that the generation of myelin early in development is an inaccurate process associated with aberrant ultrastructural features that require substantial refinement.

ImportanceWearing a face mask in school can reduce SARS-CoV-2 transmission but it may also lead to increased hand-to-face contact, which in turn could increase infection risk through self-inoculation.ObjectiveTo evaluate the effect of wearing a face mask on hand-to-face contact by children while at school.Design, Setting, and ParticipantsThis prospective randomized clinical trial randomized students from junior kindergarten to grade 12 at 2 schools in Toronto, Ontario, Canada, during August 2020 in a 1:1 ratio to either a mask or control class during a 2-day school simulation. Classes were video recorded from 4 angles to accurately capture outcomes.InterventionsParticipants in the mask arm were instructed to bring their own mask and wear it at all times. Students assigned to control classes were not required to mask at any time (grade 4 and lower) or in the classroom where physical distancing could be maintained (grade 5 and up).Main Outcomes and MeasuresThe primary outcome was the number of hand-to-face contacts per student per hour on day 2 of the simulation. Secondary outcomes included hand-to-mucosa contacts and hand-to-nonmucosa contacts. A mixed Poisson regression model was used to derive rate ratios (RRs), adjusted for age and sex with a random intercept for class with bootstrapped 95% CIs.ResultsA total of 174 students underwent randomization and 171 students (mask group, 50.6% male; control group, 52.4% male) attended school on day 2. The rate of hand-to-face contacts did not differ significantly between the mask and the control groups (88.2 vs 88.7 events per student per hour; RR, 1.00; 95% CI, 0.78-1.28; P = >.99). When compared with the control group, the rate of hand-to-mucosa contacts was significantly lower in the mask group (RR, 0.12; 95% CI, 0.07-0.21), while the rate of hand-to-nonmucosa contacts was higher (RR, 1.40; 95% CI, 1.08-1.82).Conclusions and RelevanceIn this clinical trial of simulated school attendance, hand-to-face contacts did not differ among students required to wear face masks vs students not required to wear face masks; however, hand-to-mucosa contracts were lower in the face mask group. This suggests that mask wearing is unlikely to increase infection risk through self-inoculation.Trial RegistrationClinicalTrials.gov Identifier: NCT04531254

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide with high mortality, which is mainly due to the lack of reliable biomarkers for PDAC diagnosis/prognosis in the early stages and effective therapeutic strategies for the treatment. Cancer-derived small extracellular vesicles (sEVs), which carry various messages and signal biomolecules (e.g. RNAs, DNAs, proteins, lipids, and glycans) to constitute the key features (e.g. genetic and phenotypic status) of cancer cells, are regarded as highly competitive non-invasive biomarkers for PDAC diagnosis/prognosis. Additionally, new insights on the biogenesis and molecular functions of cancer-derived sEVs pave the way for novel therapeutic strategies based on cancer-derived sEVs for PDAC treatment such as inhibition of the formation or secretion of cancer-derived sEVs, using cancer-derived sEVs as drug carriers and for immunotherapy. This review provides a comprehensive overview of the most recent scientific and clinical research on the discovery and involvement of key molecules in cancer-derived sEVs for PDAC diagnosis/prognosis and strategies using cancer-derived sEVs for PDAC treatment. The current limitations and emerging trends toward clinical application of cancer-derived sEVs in PDAC diagnosis/prognosis and treatment have also been discussed.

Background Helping Babies Breathe (HBB) is a newborn resuscitation training program designed to reduce neonatal mortality in low- and middle-income countries. However, skills decay after initial training is a significant barrier to sustained impact. Objective To test whether a mobile app, HBB Prompt, developed with user-centred design, helps improve skills and knowledge retention after HBB training. Methods HBB Prompt was created during Phase 1 of this study with input from HBB facilitators and providers from Southwestern Uganda recruited from a national HBB provider registry. During Phase 2, healthcare workers (HCWs) in two community hospitals received HBB training. One hospital was randomly assigned as the intervention hospital, where trained HCWs had access to HBB Prompt, and the other served as control without HBB Prompt (NCT03577054). Participants were evaluated using the HBB 2.0 knowledge check and Objective Structured Clinical Exam, version B (OSCE B) immediately before and after training, and 6 months post-training. The primary outcome was difference in OSCE B scores immediately after training and 6 months post-training. Results Twenty-nine HCWs were trained in HBB (17 in intervention, 12 in control). At 6 months, 10 HCW were evaluated in intervention and 7 in control. In intervention and control respectively, the median OSCE B scores were: 7 vs. 9 immediately before training, 17 vs. 21 immediately after training, and 12 vs. 13 at 6 months after training. Six months after training, the median difference in OSCE B scores was -3 (IQR -5 to -1) in intervention and -8 (IQR -11 to -6) in control (p = 0.02). Conclusion HBB Prompt, a mobile app created by user-centred design, improved retention of HBB skills at 6 months. However, skills decay remained high 6 months after training. Continued adaptation of HBB Prompt may further improve maintenance of HBB skills.

Introduction Rh sensitization occurs when Rh(D)-negative women develop anti-Rh(D) antibodies following exposure through pregnancy or transfusion. Rh disease may cause jaundice, anemia, neurological impairment, and death. It is rare in countries where Rh Immune Globulin (RhIg) is used. Canadian Rh sensitization and disease rates are unknown. Methods This survey-based study was conducted using a Canadian Paediatric Surveillance Program questionnaire sent to Canadian paediatricians and paediatric subspecialists to solicit Rh disease cases from May 2016 to June 2018. Paediatricians reported Rh-positive infants ≤ 60 days of age, born to Rh-negative mothers with RhD sensitization. Results Sixty-two confirmed cases of infants affected by Rh(D) sensitization were reported across Canada. The median gestational age of neonates was term, age at presentation was 2 hours, and hemoglobin at presentation was 137.5 g/L (33 to 203 g/L). The median peak bilirubin and phototherapy duration were 280 µmol/L (92 to 771 µmol/L), and 124 hours, respectively. Thirty (48%) infants received Intravenous immune globulin (IVIG) (median two doses). Seventeen (27%) received one to three simple transfusions; 10 (16%) required exchange transfusions. Six (10%) infants presented with acute bilirubin encephalopathy, and less than five presented with seizures. Fourteen mothers with affected infants were born outside of Canada. Discussion Rh disease continues to exist in Canada. Additional efforts are needed to raise awareness of Rh disease, prevent disease, and minimize sequelae when it does occur. The ongoing global burden of Rh Disease, as well as the possibility of emerging Rh immunoglobulin refusal are among factors that could be taken into consideration in future prevention efforts.

A sealed abdominal interface was positioned below the diaphragm (the "NeoVest") to apply synchronized and proportional negative pressure ventilation (NPV) and was compared to positive pressure ventilation (PPV) using neurally adjusted ventilatory assist (NAVA). Both modes were controlled by the diaphragm electrical activity (Edi).Eleven rabbits (mean weight 2.9 kg) were instrumented, tracheotomized, and ventilated with either NPV or PPV (sequentially) with different loads (resistive, dead space, acute lung injury). Assist with either PPV or NPV was titrated to reduce Edi by 50%.In order to achieve a 50% reduction in Edi, NPV required slightly more negative pressure (-8 to -12 cm HIt is feasible to apply NPV sub-diaphragmatically in synchrony and in proportion to Edi in an animal model of respiratory distress.Negative pressure ventilation (NPV), for example, the "Iron Lung," may offer advantages over positive pressure ventilation. In the present work, we describe the "NeoVest," a system consisting of a sealed abdominal interface and a ventilator that applies NPV in synchrony and in proportion to the diaphragm electrical activity (Edi).

Extremely preterm infants are prone to hyperbilirubinemia and its sequelae. Currently recommended thresholds for initiating phototherapy in these newborns are consensus-based (CB).A multi-site retrospective cohort study of 642 infants born at 24Among infants born 24We provide statistically derived pre-phototherapy TSB levels that may clarify patterns of pre-phototherapy TSB levels in extremely preterm infants.We present statistically derived pre-phototherapy total serum bilirubin levels in a cohort of extremely preterm infants. Most of these preterm infants received phototherapy-some at below currently published thresholds. There are notable differences between our statistically derived pre-phototherapy TSB levels and currently published lower limit TSB thresholds for phototherapy. Our study results assist in the understanding of pre-phototherapy TSB levels in extremely preterm infants.

The nosocomial spread of Mycobacterium tuberculosis from a healthcare worker with infectious pulmonary tuberculosis disease to patients remains a risk in the healthcare environment, including neonatal intensive care units. In this paper, we outlined a protocol for neonates exposed to tuberculosis in a neonatal intensive care unit that includes skin testing, chest X-ray imaging, and prophylactic isoniazid. Neonatal patients were followed up with tuberculosis skin testing at both three months corrected age and two months postexposure. To our knowledge, this is the first Canadian study to illustrate a protocol following tuberculosis exposure in a neonatal intensive care unit for exposed neonates.

Prenatal opioid use is increasingly common and can have adverse impacts on maternal and child health. In Ontario, there are no clear guidelines or universal programs to support the healthy development of children with prenatal opioid exposure. We present the epidemiology of prenatal opioid exposure in Ontario, summarize research examining child health outcomes with a focus on child development, review emerging guidelines for child health and developmental surveillance and highlight promising programs. We emphasize the need to strengthen current Canadian recommendations for routine enhanced developmental and vision screening and ensure funding for evidence-based integrated maternal/child services.

Background Opioid overdose epidemic is a public health crisis that is impacting communities around the world. Overdose education and naloxone distribution programs equip and train lay people to respond in the event of an overdose. We aimed to design an open-access naloxone kit and ultra-brief education session for use in point-of-care settings. Methods We hosted a multi-stakeholder co-design workshop to elicit suggestions for the kit and education session. We recruited people with lived experience of opioid overdose, community representatives, and other stakeholders from family practice, emergency medicine, addictions medicine, and public health to participate in a one-day facilitated co-design discussion wherein large and small group discussions were audio-recorded, transcribed and analysed using thematic approaches. Results A total of twenty four participants participated in the multi-stakeholder workshop from five stakeholder groups including geographic and setting diversity. Collaborative dialogue and shared storytelling which revealed seven design considerations: recognizing overdose, how much naloxone, impact of stigma, legal risk of responding, position as conventional first aid, friends and family as responders, support to call 911. Conclusion To create an open access kit and ultra-brief education session for distribution in emergency departments, family practice and substance use treatment services, stigma is a central design consideration. Design choices that reference the iconography, type, and form of materials associated with first aid have the potential to satisfy the need to de-stigmatize overdose response.

In this methodological intersection article, we describe how we developed a new variation of the established tabletop simulation modality, inspired by institutional ethnography (IE)-informed principles. We aimed to design and conduct pilot implementations of this innovative tabletop simulation modality, which focused uniquely on everyday and everynight work, along with the factors that govern that work. In so doing, we aimed to develop a modality and preliminary findings that researchers and educators can use to simulate healthcare practices across longer episodes of care (i.e., time scales of hours or an entire day) and to detect the ‘latent social threats’ that can emerge during interprofessional clinical care.An interprofessional team designed tabletop simulation scenarios of interprofessional challenges during transfers of care on a labour and delivery (L&D) unit. Within each scenario, participants provided real-time explanations for their work and associated drivers, both independently and as a team. Thus, we combined ‘think-aloud’ and simulation principles to design tabletop simulation scenarios to elicit healthcare professionals’ descriptions of how they collaborate in their work on the L&D unit. We completed a total of five tabletop simulations with eight participants (obstetricians, N = 2; midwives, N = 2; nurses, N = 5).The conversations stimulated by the tabletop simulation scenarios and debriefs allowed us to generate a preliminary understanding of the texts that govern and organize clinicians’ everyday work processes. We generated data about longitudinal, multi-hour work processes in a condensed timeline, with opportunities to pause and probe, and with reduced focus on individual practitioner’s competence.We believe our innovative tabletop simulation approach allowed us to examine clinical work in ways no other simulation permits. Participants described how the scenarios opened a productive dialogue between professional groups and suggested this simulation-based approach might contribute to enhanced interprofessional understanding and cultural change. We suggest that others can adapt our low-resource approach to understand clinicians’ everyday work and to map how this work is governed by documents, like policies, with the end goal of facilitating system change and managing latent social threats.

Primary Subject area Developmental Paediatrics Background The incidence of Fetal Alcohol Spectrum Disorder (FASD) is estimated to be 1 in 100 live births. Caused by prenatal exposure to alcohol, FASD is the leading cause of developmental and cognitive disabilities among Ontario’s children. No study has conducted a comparison of the costs associated with FASD among Indigenous children, and Non-Indigenous children. Objectives To calculate and compare an estimate of direct and indirect costs associated with FASD at the patient level among Indigenous children and Non-Indigenous children living in Ontario. Design/Methods A cross-sectional study design was used. Eight-hundred and thirty (830) participants completed the study tool. Participants included caregivers of children aged 3 months to 17.5 years, living in urban and rural communities throughout Ontario. Four-hundred and twelve (412) participants were Indigenous Ontarians, and 418 participants were Non-Indigenous Ontarians. Participants completed the Health Services Utilization Inventory (HSUI). Key cost components were elicited: direct costs (medical, education, social services, out-of-pocket costs); and indirect costs (productivity losses). Total average costs per child with FASD were calculated by summing the costs for each, in each cost component, and dividing by the sample size. Costs were extrapolated to one year. A t-test was used to compare costs associated with FASD in the two groups. A stepwise multiple regression analysis was used to identify significant determinants of costs. Results Total adjusted annual costs associated with FASD at the individual level was $51,543 (95% CI $46,825; $56,642) among Indigenous children compared to $36,435 (95% CI $31,935; $42,245), among Non-Indigenous children (p Conclusion Study results demonstrated the cost associated with FASD in Ontario was significantly greater among Indigenous children compared to Non-Indigenous children. Implications for practice, policy, and research are discussed.

The opioid crisis is a growing public health emergency and increasing resources are being directed towards overdose education. Simulation has emerged as a novel strategy for training overdose response, yet little is known about training non-clinicians in bystander resuscitation. Understanding the perspectives of individuals who are likely to experience or witness opioid overdose is critical to ensure that emergency response is effective. The Surviving Opioid Overdose with Naloxone Education and Resuscitation (SOONER) study evaluates the effectiveness of a novel naloxone education and distribution tool among people who are non-clinicians and likely to witness opioid overdose. Participants’ resuscitation skills are evaluated using a realistic overdose simulation as the primary outcome of the trial. The purpose of our study is to describe the experience of participants with the simulation process in the SOONER study. We employed a semi-structured debriefing interview and a follow up qualitative interview to understand the experience of participants with simulation. A qualitative content analysis was performed using data from 21 participants who participated in the SOONER study. Our qualitative analysis identified 5 themes and 17 subthemes which described the experience of participants within the simulation process. These themes included realism, valuing practical experience, improving self-efficacy, gaining new perspective and bidirectional learning. Our analysis found that simulation was a positive and empowering experience for participants in the SOONER trial, most of whom are marginalized in society. Our study supports the notion that expanding simulation-based education to non-clinicians may offer an acceptable and effective way of supplementing current opioid overdose education strategies. Increasing the accessibility of simulation-based education may represent a paradigm shift whereby simulation is transformed from a primarily academic practice into a patient-based community resource.

We plan to conduct a randomised clinical trial among people likely to witness opioid overdose to compare the educational effectiveness of point-of-care naloxone distribution with best-available care, by observing participants' resuscitation skills in a simulated overdose. This mixed methods feasibility study aims to assess the effectiveness of recruitment and retention strategies and acceptability of study procedures.We implemented candidate-driven recruitment strategies with verbal consent and destigmatizing study materials in a family practice, emergency department, and addictions service. People ≥16 years of age who are likely to witness overdose were randomized to point-of-care naloxone distribution or referral to an existing program. We evaluated participant skills as a responder to a simulated overdose 3-14 days post-recruitment. Retention strategies included flexible scheduling, reminders, cash compensation and refreshments. The primary outcome was recruitment and retention feasibility, defined as the ability to recruit 28 eligible participants in 28 days, with50% attrition at the outcome simulation. Acceptability of study procedures and motivations for participation were assessed in a semi-structured interview.We enrolled 30 participants over 24 days, and retained 21 participants (70%, 95%CI 56.7-100). The most common motivation for participation was a desire to serve the community or loved ones in distress. Participants reported that study procedures were acceptable and that the outcome simulation provided a supportive and affirming environment.The planned trial is ready for implementation. Recruitment and retention is feasible and study processes are acceptable for people who are likely to witness overdose. (Registration: NCT03821649).

BACKGROUND Stress, anxiety, distress, and depression are high among health care workers during the COVID-19 pandemic, and they have reported acting in ways that are contrary to their moral values and professional commitments that degrade their integrity. This creates moral distress and injury due to constraints they have encountered, such as limited resources. OBJECTIVE The purpose of this study is to develop and show the feasibility of digital platforms (a virtual reality and a mobile platform) to understand the causes and ultimately reduce the moral distress of health care providers during the COVID-19 pandemic. METHODS This will be a prospective, single cohort, pre- and posttest study examining the effect of a brief informative video describing moral distress on perceptual, psychological, and physiological indicators of stress and decision-making during a scenario known to potentially elicit moral distress. To accomplish this, we have developed a virtual reality simulation that will be used before and after the digital intervention for monitoring short-term impacts. The simulation involves an intensive care unit setting during the COVID-19 pandemic, and participants will be placed in morally challenging situations. The participants will be engaged in an educational intervention at the individual, team, and organizational levels. During each test, data will be collected for (1) physiological measures of stress and after each test, data will be collected regarding (2) thoughts, feelings and behaviors during a morally challenging situation, and (3) perceptual estimates of psychological stress. In addition, participants will continue to be monitored for moral distress and other psychological stresses for 8 weeks through our Digital intervention/intelligence Group mobile platform. Finally, a comparison will be conducted using machine learning and biostatistical techniques to analyze the short- and long-term impacts of the virtual reality intervention. RESULTS The study was funded in November 2020 and received research ethics board approval in March 2021. The study is ongoing. CONCLUSIONS This project is a proof-of-concept integration to demonstrate viability over 6 months and guide future studies to develop these state-of-the-art technologies to help frontline health care workers work in complex moral contexts. In addition, the project will develop innovations that can be used for future pandemics and in other contexts prone to producing moral distress and injury. This project aims to demonstrate the feasibility of using digital platforms to understand the continuum of moral distress that can lead to moral injury. Demonstration of feasibility will lead to future studies to examine the efficacy of digital platforms to reduce moral distress. CLINICALTRIAL ClinicalTrials.gov NCT05001542; https://clinicaltrials.gov/ct2/show/NCT05001542 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/32240

Background Stress, anxiety, distress, and depression are high among health care workers during the COVID-19 pandemic, and they have reported acting in ways that are contrary to their moral values and professional commitments that degrade their integrity. This creates moral distress and injury due to constraints they have encountered, such as limited resources. Objective The purpose of this study is to develop and show the feasibility of digital platforms (a virtual reality and a mobile platform) to understand the causes and ultimately reduce the moral distress of health care providers during the COVID-19 pandemic. Methods This will be a prospective, single cohort, pre- and posttest study examining the effect of a brief informative video describing moral distress on perceptual, psychological, and physiological indicators of stress and decision-making during a scenario known to potentially elicit moral distress. To accomplish this, we have developed a virtual reality simulation that will be used before and after the digital intervention for monitoring short-term impacts. The simulation involves an intensive care unit setting during the COVID-19 pandemic, and participants will be placed in morally challenging situations. The participants will be engaged in an educational intervention at the individual, team, and organizational levels. During each test, data will be collected for (1) physiological measures of stress and after each test, data will be collected regarding (2) thoughts, feelings and behaviors during a morally challenging situation, and (3) perceptual estimates of psychological stress. In addition, participants will continue to be monitored for moral distress and other psychological stresses for 8 weeks through our Digital intervention/intelligence Group mobile platform. Finally, a comparison will be conducted using machine learning and biostatistical techniques to analyze the short- and long-term impacts of the virtual reality intervention. Results The study was funded in November 2020 and received research ethics board approval in March 2021. The study is ongoing. Conclusions This project is a proof-of-concept integration to demonstrate viability over 6 months and guide future studies to develop these state-of-the-art technologies to help frontline health care workers work in complex moral contexts. In addition, the project will develop innovations that can be used for future pandemics and in other contexts prone to producing moral distress and injury. This project aims to demonstrate the feasibility of using digital platforms to understand the continuum of moral distress that can lead to moral injury. Demonstration of feasibility will lead to future studies to examine the efficacy of digital platforms to reduce moral distress. Trial Registration ClinicalTrials.gov NCT05001542; https://clinicaltrials.gov/ct2/show/NCT05001542 International Registered Report Identifier (IRRID) DERR1-10.2196/32240

Aim: We plan to conduct a randomised clinical trial among people likely to witness opioid overdose to compare the educational effectiveness of point-of-care naloxone distribution with best-available care, by observing participants’ resuscitation skills in a simulated overdose. This mixed methods feasibility study aims to assess the effectiveness of recruitment and retention strategies and acceptability of study procedures. Methods: We implemented candidate-driven recruitment strategies with verbal consent and destigmatizing study materials in a family practice, emergency department, and addictions service. People ≥16 years of age who are likely to witness overdose were randomized to point-of-care naloxone distribution or referral to an existing program. We evaluated participant skills as a responder to a simulated overdose 3–14 days post-recruitment. Retention strategies included flexible scheduling, reminders, cash compensation and refreshments. The primary outcome was recruitment and retention feasibility, defined as the ability to recruit 28 eligible participants in 28 days, with

ObjectiveTo evaluate trends in organisms causing early-onset neonatal sepsis (EONS). Congruent with recent reports, we hypothesized there would be an increase in EONS caused by Escherichia coli.Study DesignNational data on infants admitted to neonatal intensive care units from 2009 to 2014 were compared to previously reported data from 2003 to 2008. We report 430 cases of EONS from 2009 to 2014. Bivariate analyses were used to analyze the distribution of causative organisms over time and differences by gestational age. Linear regression was used to estimate trends in causative organisms.ResultsSince 2003, there has been a trend of increasing numbers of cases caused by E coli (PConclusionsWith the majority of EONS cases now caused by E coli, our findings emphasize the importance of continued surveillance of causative organism patterns and developing approaches to reduce cases caused by E coli.

The counterfactual account of physical computation is simple and, for the most part, very attractive. However, it is usually thought to trivialize the notion of physical computation insofar as it implies ‘limited pancomputationalism’, this being the doctrine that every deterministic physical system computes some function. Should we bite the bullet and accept limited pancomputationalism, or reject the counterfactual account as untenable? Jack Copeland would have us do neither of the above. He attempts to thread a path between the two horns of the dilemma by buttressing the counterfactual account with extra conditions intended to block certain classes of deterministic physical systems from qualifying as physical computers. His theory is called the ‘algorithm execution account’. Here we show that the algorithm execution account entails limited pancomputationalism, despite Copeland’s argument to the contrary. We suggest, partly on this basis, that the counterfactual account should be accepted as it stands, pancomputationalist warts and all.

Despite standardized neonatal resuscitation program (NRP) training, retention and adherence to the NRP algorithm remain a challenge. Cognitive aids can potentially improve acquisition and application of NRP knowledge and skills. The objective of this study was to determine whether an interactive mobile application providing audiovisual prompts, NRP Prompt, can help novice NRP providers learn the NRP algorithm more effectively and therefore improve their NRP performance.First- and second-year residents from family medicine and obstetrics and gynecology attending NRP training were randomized into intervention and control groups. Resident pairs used standard visual aids with NRP Prompt (intervention) or visual aids only (control) in two simulated neonatal resuscitation training sessions with each resident taking turns as a team leader. Pairs were then evaluated in a third simulation that was video recorded, where neither group used cognitive aids. The primary outcome was comparing resuscitation performance. Secondary outcomes included the following: times to positive-pressure ventilation, intubation, and chest compressions.Thirty-nine residents participated, of which 18 received the intervention. Neonatal resuscitation program performance scores did not significantly differ (P = 0.69). Wilcoxon rank-sum tests showed no significant differences in secondary outcomes of times to positive-pressure ventilation (P = 0.43), intubation (P = 0.44), or chest compressions (P = 0.35).Training using NRP Prompt did not improve performance scores in simulated neonatal resuscitations immediately after training. Potential reasons include voice prompts in their current format being distracting and lack of customizability to user preferences. Future development of prompting applications should apply a user-centered design approach to optimize the ability to meet end-user needs.

We study the impact of large real exchange rate shocks on workers in sectors initially more exposed to international trade using the Current Population Survey’s (CPS) Merged Outgoing Rotation Group (MORG) from 1979 to 2010 combined with new annual measures of imported inputs, a proxy for offshoring. We find that in periods when US relative prices are high, and imports surge relative to exports, workers in sectors with greater initial exposure to international trade were more likely to be unemployed or exit the labor force a year later, but did not experience significant declines in wages conditional on being employed. Contrary to the usual narrative, we find negative wage effects for higher-wage, but not lower-wage workers, particularly for those who are less-educated.

Objective To evaluate the relationship between the timing of infant cereal introduction between 4 and 6 months of age and growth and dietary intake in later childhood. Study design A longitudinal cohort study was conducted among healthy children 0-10 years of age participating in The Applied Research Group for Kids cohort study between June 2008 and August 2019 in Toronto, Canada. Results Of 8943 children included, the mean (SD) age of infant cereal introduction was 5.7 (2.1) months. In the primary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.17 greater body mass index z score (95% CI 0.06-0.28; P = .002) and greater odds of obesity (OR 1.82; 95% CI 1.18-2.80; P = .006) at 10 years of age. In the secondary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.09 greater height-for-age z score (95% CI 0.04-0.15; P = .002) at 1 year of age, an association that was not observed at 5 or 10 years of age. Children who were introduced to infant cereal at 4 vs 6 months had greater nutrition risk which was primarily determined by a less-favorable eating behavior score at 18 months to 5 years of age (0.18 units higher; 95% CI 0.07-0.29; P = .001). Conclusions Introduction of infant cereal at 4 vs 6 months was associated with greater body mass index z score, greater odds of obesity, similar height-for-age z score, and less favorable eating behavior. These findings support recommendations for introducing solid food around 6 months of age.

Summary • The lichen Lobaria pulmonaria survives large seasonal environmental changes through physiological acclimation to ambient conditions. • We quantitated algal cell population, cell division and key macromolecular levels associated with photosynthesis and nitrogen metabolism in L. pulmonaria sampled from four seasons with contrasting environmental conditions in a deciduous forest. • The algal symbiont population did not vary seasonally and cell division was restricted to the newest thallus margins. Nevertheless the symbiont concentrations of chlorophyll, PsbS, PsbA, and RbcL changed significantly through the seasons in the nondividing algal cells from older thallus regions. • L. pulmonaria reversibly allocated resources toward photochemical electron generation and carbohydrate production through the spring, summer and fall, and towards photoprotective dissipation in the cold, high-light winter. Our study shows that large seasonal molecular acclimation in L. pulmonaria occurs within a nearly stable, nondividing algal cell population that maintains photosynthetic capacity through many years of changing environmental cues.

Unicellular nitrogen fixing cyanobacteria (UCYN) are abundant members of phytoplankton communities in a wide range of marine environments, including those with rapidly changing nitrogen (N) concentrations. We hypothesized that differences in N availability (N2 vs. combined N) would cause UCYN to shift strategies of intracellular N and C allocation. We used transmission electron microscopy and nanoscale secondary ion mass spectrometry imaging to track assimilation and intracellular allocation of 13C-labeled CO2 and 15N-labeled N2 or NO3 at different periods across a diel cycle in Cyanothece sp. ATCC 51142. We present new ideas on interpreting these imaging data, including the influences of pre-incubation cellular C and N contents and turnover rates of inclusion bodies. Within cultures growing diazotrophically, distinct subpopulations were detected that fixed N2 at night or in the morning. Additional significant within-population heterogeneity was likely caused by differences in the relative amounts of N assimilated into cyanophycin from sources external and internal to the cells. Whether growing on N2 or NO3, cells prioritized cyanophycin synthesis when N assimilation rates were highest. N assimilation in cells growing on NO3 switched from cyanophycin synthesis to protein synthesis, suggesting that once a cyanophycin quota is met, it is bypassed in favor of protein synthesis. Growth on NO3 also revealed that at night, there is a very low level of CO2 assimilation into polysaccharides simultaneous with their catabolism for protein synthesis. This study revealed multiple, detailed mechanisms underlying C and N management in Cyanothece that facilitate its success in dynamic aquatic environments.

Background Helping Babies Breathe (HBB) is a life-saving program that has helped reduce neonatal morbidity and mortality, but knowledge and skills retention after training remains a significant challenge for sustainability of impact. User-centred design (UCD) can be used to develop solutions to target knowledge and skills maintenance. Methods We applied a process of UCD beginning with understanding the facilitators of, and barriers to, learning and retaining HBB knowledge and skills. HBB Master Trainers and frontline HBB providers participated in a series of focus group discussions (FGDs) to uncover the processes of skills acquisition and maintenance to develop a mobile application called “HBB Prompt”. Themes derived from each FGD were identified and implications for development of the HBB Prompt app were explored, including feasibility of incorporating strategies into the format of an app. Data analysis took place after each iteration in Phase 1 to incorporate feedback and improve subsequent versions of HBB Prompt. Results Six HBB trainers and seven frontline HBB providers participated in a series of FGDs in Phase 1 of this study. Common themes included lack of motivation to practise, improving confidence in ventilation skills, ability to achieve the Golden Minute, fear of forgetting knowledge or skills, importance of feedback, and peer-to-peer learning. Themes identified that were not feasible to address pertained to health system challenges. Feedback about HBB Prompt was generally positive. Based on initial and iterative feedback, HBB Prompt was created with four primary functions: Training Mode, Simulation Mode, Quizzes, and Dashboard/Scoreboard. Conclusions Developing HBB Prompt with UCD to help improve knowledge and skills retention was feasible and revealed key concepts, including drivers for successes and challenges faced for learning and maintaining HBB skills. HBB Prompt will be piloted in Phase 2 of this study, where knowledge and skills retention after HBB training will be compared between an intervention group with HBB Prompt and a control group without the app. Trial registration Clinicaltrials.gov (NCT03577054). Retrospectively registered July 5, 2018, https://clinicaltrials.gov/ct2/show/study/NCT03577054.

Background Insertion of an umbilical venous catheter (UVC) is a required skill for pediatric residents to learn and perform effectively. However, there is known variability in the ability of residents to perform this essential neonatal skill. Objective The objective of our study was to create a competency-based curriculum for umbilical vein catheter insertion using a human umbilical tissue simulated model, and to assess the feasibility of the curriculum on resident learners during their neonatology rotations. Methods We evaluated the curriculum by assessment of resident learning, reactions, and behaviours. Performance was assessed using the Ottawa Surgical Competency Operating Room Evaluation (O-SCORE). Results A total of 14 residents were included for analysis. The majority were 'senior' residents (postgraduate year (PGY)-3 and PGY-4 n = 10; PGY-1 n =4), and they reported a wide range of previous experience with UVC insertion prior to this curriculum implementation. The residents' reaction to the curriculum was overwhelmingly positive. All residents maintained or improved in their knowledge assessment. O-SCORE results showed improvement in UVC insertion before and after curriculum completion for both junior (2.5 +/- 0.71 to 4.5 +/- 0.41) and senior (3.55 +/- 0.42 to 4.95 +/- 0.15, p < 0.001) residents. The mean improvement in O-SCORE was greater for junior residents than senior residents. Conclusion The results of this study demonstrate the feasibility and emerging impact of a competency-based curriculum using simulation for procedural skills.

A limitation to the wider introduction of personalised dosimetry in theranostics is the relative paucity of imaging radionuclides with suitable physical and chemical properties to be paired with a long-lived therapeutic partner. As most of the beta-emitting therapeutic radionuclides emit gamma radiation as well they could potentially be used as the imaging radionuclide as well as the therapeutic radionuclide. However, the downsides are that the beta radiation will deliver a significant radiation dose as part of the treatment planning procedure, and the gamma radiation branching ratio is often quite low. Gallium-67 has been in use in nuclear medicine for over 50 years. However, the tremendous interest in gallium imaging in theranostics in recent times has focused on the PET radionuclide gallium-68. In this article it is suggested that the longer-lived gallium-67, which has desirable characteristics for imaging with the gamma camera and a suitably long half-life to match biological timescales for drug uptake and turnover, has been overlooked, in particular, for treatment planning with radionuclide therapy. Gallium-67 could also allow non-PET facilities to participate in theranostic imaging prior to treatment or for monitoring response after therapy. Gallium-67 could play a niche role in the future development of personalised medicine with theranostics.

Simulation's benefits in medical education are well established. However, its use for pandemic preparedness in obstetrics is lacking. Management of obstetrical patients with suspected COVID-19 infection is a complex task with safety considerations for mother, fetus and healthcare workers. Implementation of new workflow algorithms to ensure safety is critical but is challenging to implement in real-time. We sought to improve pandemic preparedness by designing and deploying a high-fidelity simulation exercise involving the admission of a labouring obstetrical patient with suspected COVID-19 into a labour room, urgent transfer to the operating room and neonatal resuscitation. The creation of the simulation scenario was a multi-disciplinary effort with input from a focus group of key clinical stakeholders from within and outside of our centre to ensure clinical validity. Simulations were performed on the clinical unit during regular work hours so workflow could be observed in real-time with access to the equipment and personnel in which this clinical scenario would occur. We completed a total of 11 simulation sessions involving 42 participants. Feedback, obtained from debrief sessions and anonymous surveys, was categorized based on the human factors framework, and used as part of an iterative process to adapt, revise and improve the simulation scenario. The result of this iterative process was the creation of validated departmental infection control protocols that continue to be implemented through the second wave of the COVID-19 pandemic.

Humans have overloaded the world’s nutrient fluxes. Formerly clear waters are now dominated by a variety of photosynthesizing microorganisms instead of underwater plants. With insights into the diverse metabolism of these microorganisms, the chances for restoration can be improved. We summarize here the developments of recent years., Phytoplankton growth depends not only upon external factors that are not strongly altered by the presence of phytoplankton, such as temperature, but also upon factors that are strongly influenced by activity of phytoplankton, including photosynthetically active radiation, and the availability of the macronutrients carbon, nitrogen, phosphorus and, for some, silicate. Since phytoplankton therefore modify, and to an extent create, their own habitats, established phytoplankton communities can show resistance and resilience to change, including managed changes in nutrient regimes. Phytoplankton blooms and community structures can be predicted from the overall biogeochemical setting and inputs, but restorations may be influenced by the physiological responses of established phytoplankton taxa to nutrient inputs, temperature, second-order changes in illumination and nutrient recycling. In this review we discuss the contributions of phytoplankton ecophysiology to biogeochemical hysteresis and possible effects on community composition in the face of management, conservation or remediation plans.

Introduction: Transcutaneous bilirubin (TcB) measurement offers a noninvasive approach for bilirubin screening; however, its accuracy in preterm infants is unclear. This study determined the agreement between TcB and total serum bilirubin (TSB) among preterm infants. Methods: A multisite prospective cohort study was conducted at 3 NICUs in Ontario, Canada, September 2016 to June 2018. Among 296 preterm infants born at 240/7 to 356/7 weeks, 856 TcB levels were taken at the forehead, sternum, and before and after the initiation of phototherapy with TSB measurements. Bland-Altman plots and 95% limits of agreement (LOA) expressed agreement between TcB and TSB. Results: The overall mean TcB-TSB difference was −24.5 μmol/L (95% LOA −103.3 to 54.3), 1.6 μmol/L (95% LOA −73.4 to 76.5) before phototherapy, and −31.1 μmol/L (95% LOA −105.5 to 43.4) after the initiation of phototherapy. The overall mean TcB-TSB difference was −15.2 μmol/L (95% LOA −86.8 to 56.3) at the forehead and −24.4 μmol/L (95% LOA −112.9 to 64.0) at the sternum. The mean TcB-TSB difference was −31.4 μmol/L (95% LOA −95.3 to 32.4) among infants born 24–28 weeks, −25.5 μmol/L (95% LOA −102.7 to 51.8) at 29–32 weeks, and −15.9 μmol/L (95% LOA −107.4 to 75.6) at 33–35 weeks. Measures did not differ by maternal ethnicity. Conclusion: Among preterm infants, TcB may offer a noninvasive, immediate approach to screening for hyperbilirubinemia with more careful use in preterm infants born at

Introduction For many training programs, including hematology, there are limited structured opportunities to practice collaboration as a competency. Training is often limited to ad hoc interactions during clinical rotations. Accordingly, there is further need for immersive and standardized collaboration educational programs. This pilot study explored simulation for developing and assessing collaboration competency among hematology residents. Methods Two standardized simulation center scenarios were developed that required residents to work in interprofessional teams. The objectives were to develop collaboration competence and confidence through experiential learning and facilitated reflection. Team members included education and simulation experts as well as hematology nurses as embedded participants. Case 1 presented a 72-year-old male with stage 4 lymphoma experiencing shortness of breath during a rituximab infusion. Case 2 presented a 68-year-old male who suffered a provoked pulmonary embolism. Both cases utilized a simulated clinic space. Pre, post, and 3-month questionnaires (self-assessed collaboration competency and simulation evaluation) were completed. Each session included structured debriefing with facilitated reflection focused on collaboration. Results Seven senior hematology subspecialty residents participated. Despite residents entering the simulation cases with confidence in collaboration, higher collaboration confidence ratings were observed on postsimulation questionnaires (8.2 vs. 7.6 on a 10-point Likert scale). Residents demonstrated awareness of appropriate collaboration skills, but at times failed to implement knowledge into action. Facilitated reflection during the debrief helped residents critique their collaboration performance and develop improvement plans. Discussion Simulation is a promising tool for teaching and assessing collaboration within hematology training.

Oxygenic photoautotrophs are, paradoxically, subject to photoinhibition of their photosynthetic apparatus, in particular one of its major components, the Photosystem II (PSII). Photoinhibition is generalized across species, light conditions and habitats, imposing substantial metabolic costs that lower photosynthetic productivity and constrain the niches of photoautotrophy. As a process driven by light reaching PSII, light attenuation in optically thick samples influences both the actual extent, and the detection, of photoinhibition. Chlorophyll fluorescence is widely used to measure photoinhibition, but fluorescence-based parameters are affected by light attenuation of both downwelling incident radiation traversing the sample to reach PSII, and emitted fluorescence upwelling through the sample. We used modelling, experimental manipulation of within-sample light attenuation, and meta-analysis of published data, to show substantial, differential effects of light attenuation and depth-integration of emitted fluorescence upon measurements of photoinhibition. Numerical simulations and experimental manipulation of light attenuation indicated that PSII photoinactivation tracked using chlorophyll fluorescence can appear to be over three times lower than the inherent cellular susceptibility to photoinactivation, in optically-dense samples such as leaves or biofilms. The meta-analysis of published data showed that this general trend was unknowingly present in the literature, revealing an overall difference of more than five times between optically thick leaves and optically thin cell suspensions. Although fluorescence-based parameters may provide ecophysiologically relevant information for characterizing the sample as a whole, light attenuation and depth integration can vary between samples independently of their intrinsic physiology. They should be used with caution when aiming to quantify in absolute terms inherent photoinhibition-related parameters in optically thick samples.

Marine diazotrophs are a diverse group with key roles in biogeochemical fluxes linked to primary productivity. The unicellular, diazotrophic cyanobacterium Cyanothece is widely found in coastal, subtropical oceans. We analyze the consequences of diazotrophy on growth efficiency, compared to NO3–-supported growth in Cyanothece, to understand how cells cope with N2-fixation when they also have to face carbon limitation, which may transiently affect populations in coastal environments or during blooms of phytoplankton communities. When grown in obligate diazotrophy, cells face the double burden of a more ATP-demanding N-acquisition mode and additional metabolic losses imposed by the transient storage of reducing potential as carbohydrate, compared to a hypothetical N2 assimilation directly driven by photosynthetic electron transport. Further, this energetic burden imposed by N2-fixation could not be alleviated, despite the high irradiance level within the cultures, because photosynthesis was limited by the availability of dissolved inorganic carbon (DIC), and possibly by a constrained capacity for carbon storage. DIC limitation exacerbates the costs on growth imposed by nitrogen fixation. Therefore, the competitive efficiency of diazotrophs could be hindered in areas with insufficient renewal of dissolved gases and/or with intense phytoplankton biomass that both decrease available light energy and draw the DIC level down.