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Parasites cause harm to their hosts and represent pervasive causal agents of natural selection. Understanding host proximate responses during interactions with parasites can help predict which genes and molecular pathways are targets of this selection. In the current study, we examined transcriptional changes arising from interactions between Drosophila melanogaster and their naturally occurring ectoparasitic mite, Gamasodes queenslandicus. Shifts in host transcript levels associated with behavioural avoidance revealed the involvement of genes underlying nutrient metabolism. These genetic responses were reflected in altered body lipid and glycogen levels in the flies. Mite infestation triggered a striking immune response, while male accessory gland protein transcript levels were simultaneously reduced, suggesting a trade-off between host immune responses to parasite challenge and reproduction. Comparison of transcriptional analyses during mite infestation to those during nematode and parasitoid attack identified host genes similarly expressed in flies during these interactions. Validation of the involvement of specific genes with RNA interference lines revealed candidates that may directly mediate fly–ectoparasite interactions. Our physiological and molecular characterization of the Drosophila–Gamasodes interface reveals new proximate mechanisms underlying host–parasite interactions, specifically host transcriptional shifts associated with behavioural avoidance and infestation. The results identify potential general mechanisms underlying host resistance and evolutionarily relevant trade-offs.
Nanosized, well-dispersed titania particles were synthesized via a hydrothermal method using multiwalled carbon nanotubes (MWCNTs) as structural modifiers during the nucleation process to decrease aggregation. Synthesized TiO2/MWCNT composites containing different amounts of MWCNTs were characterized using N2 physisorption, XRD, spectroscopic techniques (Raman, UV-visible, and X-ray photoelectron), and electron microscopy to illuminate the morphology, crystal structure, and surface chemistry of the composites. Photocatalytic performance was evaluated by measuring the degradation of acetaldehyde in a batch reactor under UV illumination. Average rate constants decrease in the following order: TiO2/MWCNT-1% > TiO2 > TiO2/MWCNT-5%. Addition of MWCNTs beyond the optimum loading ratio of 1:100 (MWCNT:TiO2) diminishes the effectiveness of the photocatalyst and the synergistic effect between MWCNTs and TiO2. The primary mechanism for photocatalytic activity enhancement in TiO2/MWCNT-1% is thought to be due to increased porosity, hydroxyl enrichment on the surface, and high dispersion of TiO2 particles.
Introduction: Lacerations are common in children presenting to the emergency department (ED). They are often uncooperative when sutures are needed and may require procedural sedation. Few studies have evaluated intranasal (IN) ketamine for procedural sedation in children, with doses from 3 to 9 mg/kg used mostly for dental procedures. In a previous dose escalation trial, DosINK-1, 6 mg/kg was found to be the optimal IN ketamine dose for procedural sedation for sutures in children. In this trial, we aim to further evaluate the efficacy of this dose. Methods: We conducted a multicentre single-arm clinical trial. A convenience sample of 30 uncooperative children between 1 and 12 years (10 to 30 kg) with no cardiac or kidney disease, active respiratory infection, prior administration of opioid or sedative agents received 6 mg/kg of IN ketamine using an atomizer for their laceration repair with sutures in the ED. The primary outcome was defined as the proportion (95% CI) of patients who achieved an adequate procedural sedation evaluated with the PERC/PECARN consensus criteria. Results: Thirty patients were recruited from April 2018 to November 2019 in 2 pediatric ED. The median age was 3.2 (interquartile range(IQR), 1.9 to 4.7) years-old with laceration of more than 2 cm in 20 (67%) patients and in the face in 21 (70%) cases. Sedation was effective in 18 out of 30 children 60% (95%CI, 45 to 80), was suboptimal in 6 patients (20%) with a procedure completed with minimal difficulties, and unsuccessful in the remaining 6 (20%), all without serious adverse event. Similarly, 21/30 (70%) physicians were willing to reuse IN ketamine at the same doses and 25 parents (83%) would agree to the same sedation in the future. Median time to return to baseline status was 58 min (IQR, 33 to 73). One patient desaturated during the procedure and required transitory oxygen and repositioning. After the procedure, 1 (3%) patient had headache, 1 (3%) patient had nausea, and 2 (7%) patients vomited. Conclusion: A single dose of 6 mg/kg of IN Ketamine for laceration repair with sutures in uncooperative children is safe and facilitated the procedure in 60% (95%CI, 45 to 80) of patients, was suboptimal in 20% and unsuccessful in 20% of patients. As seen with IV ketamine, an available additional dose of IN ketamine for some children if needed could potentially increase proportion of successful sedation. However, the safety and efficacy of repeated doses needs to be addressed.
Introduction: Venipuncture is a frequent cause of pain and distress in the pediatric emergency department (ED). Distraction, which can improve patient experience, remains the most studied psychological intervention. Virtual reality (VR) is a method of immersive distraction that can contribute to the multi-modal management of procedural pain and distress. Methods: The main objectives of this study were to determine the feasibility and acceptability of Virtual Reality (VR) distraction for pain management associated with venipunctures and to examine its preliminary effects on pain and distress in the pediatric ED. Children 7-17 years requiring a venipuncture in the pediatric ED were recruited. Participants were randomized to either a control group (standard care) or intervention group (standard of care + VR). Principal clinical outcome was the mean level of procedural pain, measured by the verbal numerical rating scale (VNRS). Distress was also measured using the Child Fear Scale (CFS) and the Procedure Behavior Check List (PBCL) and memory of pain using the VNRS. Side effects were documented. Results: A total of 63 patients were recruited. Results showed feasibility and acceptability of VR in the PED and overall high satisfaction levels (79% recruitment rate of eligible families, 90% rate of VR game completion, and overall high mean satisfaction levels). There was a significantly higher level of satisfaction among healthcare providers in the intervention group, and 93% of those were willing to use this technology again for the same procedure. Regarding clinical outcomes, no significant difference was observed between groups on procedural pain. Distress evaluated by proxy (10/40 vs 13.2/40, p = 0.007) and memory of pain at 24 hours (2.4 vs 4.2, p = 0.027) were significantly lower in the VR group. Venipuncture was successful on first attempt in 23/31 patients (74%) in the VR group and 15/30 (50%) patients in the control group (p = 0.039). Five of the 31 patients (16%) in the VR group reported side effects Conclusion: The addition of VR to standard care is feasible and acceptable for pain and distress management during venipunctures in the pediatric ED. There was no difference in self-reported procedural pain between groups. Levels of procedural distress and memory of pain at 24 hours were lower in the VR group.
Introduction: Emergency department (ED) buprenorphine/naloxone inductions for opioid use disorder are an effective and safe way to initiate addictions care in the ED. Kelowna General Hospital's ED buprenorphine/naloxone (KEDSS) program was implemented in September 2018 in order to respond to a community need for accessible and evidence-based addictions care. The objective of our program evaluation study was to examine the implementation of the first five months of the KEDSS program through evaluating patient characteristics and service outcomes. Methods: The KEDSS treatment pathway consists of a standardized protocol (pre-printed order set) to facilitate buprenorphine/naloxone induction and stabilization in the acute care setting (ED and inpatient wards) at Kelowna General Hospital, a community academic hospital. All patients referred to the outpatient addictions clinic via the order set during September 2018-January 2019 (the first 5 months) were included in the study population. A retrospective descriptive chart review was completed. Outcome measures included population characteristics (sociodemographic information, clinical characteristics) and service outcomes (number of patients initiated, patient follow-up). Descriptive statistics and bivariate analyses using t-tests or Pearson's χ2 statistic, as appropriate, were conducted to compare the ED-initiated group with the inpatient-initiated group. Results: During the first five months of the KEDSS program, a total of 35 patients (26% female, mean age 36.6 years, 54% homeless) were started on the treatment pathway, 16 (46%) in the ED. Compared to the inpatient-initiated group, the ED-initiated group were less likely to have psychiatric comorbidities (ED 1.0 vs. inpatient 1.5, p = 0.002), require methadone or sustained-release oral morphine (ED 13% vs. inpatient 37%, p = 0.048), and have attended follow-up (ED 56% vs. inpatient 84%, p = 0.004). Conclusion: This study provides a preliminary look at a new opioid agonist therapy (OAT) treatment pathway (KEDSS) at Kelowna General Hospital, and provides insight into the population that is accessing the program. We found that the majority of patients who are started on buprenorphine/naloxone in the ED are seen in follow-up at the addictions clinic. Future work will examine ongoing follow-up and OAT adherence rates in the study population to quantify the program's impact on improving access to addictions treatment within this community hospital setting.
Introduction: The ways in which Emergency Medicine (EM) physicians interact with the medical literature has been transformed with the rise of Free Open Access Medical Education (FOAM). Although nearly all residents use FOAM resources, some criticize the lack of universal quality assurance. This problem is a particular risk for trainees who have many time constraints and incompletely developed critical appraisal skills. One potential safeguard is journal club, which is used by virtually all EM residency programs in North America to review new literature. However, EM resident perspectives have not been studied. Our research objective was to describe how residents perceive journal club to influence how they translate the medical literature into their clinical practice. Our research question was whether FOAM has influenced residents’ goals and perceived value of journal club. Methods: We developed a semi-structured interview script in conjunction with a methods expert and refined it via pilot testing. Following constructivist grounded theory, and using both purposive and theoretical sampling, we conducted a focus group (n = 7) and 18 individual interviews with EM residents at the 4 training sites of the University of British Columbia. In total, we analyzed 920 minutes of recorded audio. Two authors independently coded each transcript, with discrepancies reconciled by discussion and consensus. Constant comparative analysis was performed. We conducted return of findings through public presentations. Results: We found evidence that journal club works as a community of practice with a progression of roles from junior to senior residents. Participants described journal club as a safe venue to compare practice patterns and to gain insight into the practical wisdom of their peers and mentors. The social and academic activities present at journal club interacted positively to foster this environment. In asking residents about ways that journal club accelerates knowledge translation, we actually found that residents cite journal club as a quality check to prevent premature adoption of new research findings. Residents are hesitant to adopt new literature into their practice without positive validation, which can occur during journal club. Conclusion: Journal club functions as a community of practice that is valued by residents. Journal club is a primary way that new evidence can be validated before being put into practice, and may act as quality assurance in the era of FOAM.
Selenium (Se) is an essential element for human health. However, our knowledge of the prevalence of Se deficiency is less than for other micronutrients of public health concern such as iodine, iron and zinc, especially in sub-Saharan Africa (SSA). Studies of food systems in SSA, in particular in Malawi, have revealed that human Se deficiency risks are widespread and influenced strongly by geography. Direct evidence of Se deficiency risks includes nationally representative data of Se concentrations in blood plasma and urine as population biomarkers of Se status. Long-range geospatial variation in Se deficiency risks has been linked to soil characteristics and their effects on the Se concentration of food crops. Selenium deficiency risks are also linked to socio-economic status including access to animal source foods. This review highlights the need for geospatially-resolved data on the movement of Se and other micronutrients in food systems which span agriculture–nutrition–health disciplinary domains (defined as a GeoNutrition approach). Given that similar drivers of deficiency risks for Se, and other micronutrients, are likely to occur in other countries in SSA and elsewhere, micronutrient surveillance programmes should be designed accordingly.
Twelve evidence-based profiles of roles across the translational workforce and two patients were made available through clinical and translational science (CTS) Personas, a project of the Clinical and Translational Science Awards (CTSA) Program National Center for Data to Health (CD2H). The persona profiles were designed and researched to demonstrate the key responsibilities, motivators, goals, software use, pain points, and professional development needs of those working across the spectrum of translation, from basic science to clinical research to public health. The project’s goal was to provide reliable documents that could be used to inform CTSA software development projects, educational resources, and communication initiatives. This paper presents the initiative to create personas for the translational workforce, including the methodology, engagement strategy, and lessons learned. Challenges faced and successes achieved by the project may serve as a roadmap for others searching for best practices in the creation of Persona profiles.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Introduction: Needle-related procedures are considered the most important source of pain and distress in children in hospital settings. Time constraints, heavy workload, busy and noisy environment represent barriers to the use of available interventions for pain management during needle-related procedures. Therefore, the use of a rapid, easy-to-use intervention could improve procedural pain management practices. The objective was to determine if a device combining cold and vibration (Buzzy) is non-inferior (no worse) to a topical anesthetic (Maxilene) for pain management in children undergoing needle-related procedures in the Emergency Department (ED). Methods: This study was a randomized, controlled, non-inferiority trial. We enrolled children aged between 4-17 years presenting to the ED and requiring a needle-related procedure. Participants were randomly assigned to the Buzzy or Maxilene group. The primary outcome was the mean difference in pain intensity during the procedure, as measured with the CAS (0-10). Secondary outcomes were procedural distress, success of the procedure at first-attempt and satisfaction of parents. Results: A total of 352 participants were enrolled and 346 were randomized (Buzzy = 172; Maxilene = 174). Mean difference in procedural pain scores between groups was 0.64 (95%CI -0.1 to 1.3), showing that the Buzzy device was not non-inferior to Maxilene according to a non-inferiority margin of 0.70. No significant differences were observed for procedural distress (p = .370) and success of the procedure at first attempt (p = .602). Parents of both groups were very satisfied with both interventions (Buzzy = 7.8 ±2.66; Maxilene = 8.1 ±2.4), but there was no significant difference between groups (p = .236). Conclusion: Non-inferiority of the Buzzy device over a topical anesthetic was not demonstrated for pain management of children during a needle-related procedure in the ED. However, considering that topical anesthetics are underused in the ED setting and require time, the Buzzy device seems to be a promising alternative as it is a rapid, low-cost, easy-to-use and reusable intervention.
Atom probe tomography (APT) is a powerful technique to characterize buried three-dimensional nanostructures in a variety of materials. Accurate characterization of those nanometer-scale clusters and precipitates is of great scientific significance to understand the structure–property relationships and the microstructural evolution. The current widely used cluster analysis method, a variant of the density-based spatial clustering of applications with noise algorithm, can only accurately extract clusters of the same atomic density, neglecting several experimental realities, such as density variations within and between clusters and the nonuniformity of the atomic density in the APT reconstruction itself (e.g., crystallographic poles and other field evaporation artifacts). This clustering method relies heavily on multiple input parameters, but ideal selection of those parameters is challenging and oftentimes ambiguous. In this study, we utilize a well-known cluster analysis algorithm, called ordering points to identify the clustering structures, and an automatic cluster extraction algorithm to analyze clusters of varying atomic density in APT data. This approach requires only one free parameter, and other inputs can be estimated or bounded based on physical parameters, such as the lattice parameter and solute concentration. The effectiveness of this method is demonstrated by application to several small-scale model datasets and a real APT dataset obtained from an oxide-dispersion strengthened ferritic alloy specimen.
Introduction: Despite revolutionary changes in the medical education landscape, journal club (JC) continues to be a ubiquitous pedagogical tool and is a primary way that residency programs review new evidence and teach evidence-based medicine. JC is a community of practice among physicians, which may help translate research findings into practice. Program representatives state that JC should have a goal of translating novel research into changes in clinical care, but there has been minimal evaluation of the success of JC in achieving this goal. Specifically, emergency medicine resident perspectives on the utility of JC remain unknown. Methods: We designed a multi-centre qualitative study for three distinct academic environments at the University of British Columbia (Vancouver, Victoria and Kelowna). Pilot testing was performed to generate preliminary themes and to finalize the interview script. An exploratory, semi-structured focus group was performed, followed by multiple one-on-one interviews using snowball sampling. Iterative thematic analysis directed data collection until thematic sufficiency was achieved. Analysis was conducted using a constructivist Grounded Theory method with communities of practice as a theoretical lens. Themes were compared to the existing literature to corroborate or challenge existing educational theory. Results: Pilot testing has revealed the following primary themes: (1) Only select residents are able to increase their participation in JC over the course of residency and navigate the transition from peripheral participant to core member; (2) These residents use their increased clinical experience to perceive relevance in JC topics, and; (3) Residents who remain peripheral participants identify a lack time to prepare for journal club and a lack of staff physician attendance as barriers to resident engagement. We will further develop these themes during the focus group and interview phases of our study. Conclusion: JC is a potentially valuable educational resource for residents. JC works as a community of practice only for a select group of residents, and many remain peripheral participants for the duration of their residency. Incorporation of Free Open-Access Medical Education resources may also decrease preparation time for residents and staff physicians and increase buy-in. To augment clinical impact, the JC community of practice may need to expand beyond emergency medicine and include other specialties.
Introduction: Laceration is common in children presenting to the emergency department (ED). They are often uncooperative related to pain and distressed during repair. Currently, there are wide variations regarding sedation and analgesia practices when sutures are required. There is a growing interest in the intranasal (IN) route for procedural sedation and pain control because of its effectiveness potential and ease of administration. Few studies have evaluated IN ketamine for procedural sedation in children with reported doses ranging from 3 to 9 mg/kg. The objective is to evaluate the optimal IN ketamine dose for effective and safe procedural sedation for laceration repair in children aged 1 to 12 years. Methods: A dose escalation clinical trial with an initial dose of 3 mg/kg of IN ketamine up to a maximum dose of 9 mg/kg in children 1 to 12 years old, using a 3+3 trial design. For each tested dose, 3 patients are enrolled. Escalation to the next dose is permitted if sedation is unsuccessful in at least one patient without serious adverse event (SAE). Regression to prior dose is warranted in the occurrence of two or more SEAs. This process is repeated until effective sedation for 6 patients at two consecutive doses is achieved with a maximum of 1 SAE or if regression occurs. The primary outcome is the optimal dose for successful procedural sedation as per the PERC/PECARN consensus criteria. Secondary outcome, namely, pain and anxiety levels, parent, patient and provider satisfaction, recovery time, length of stay in the ED, side effects and adverse event are recorded. Results: Nine patients have been recruited from March to December 2017 with median age of 2.9 years-old and with laceration length of 2 to 5 cm and with facial involvement in 55% of cases, respectively. Sedation was successful in 1/3, 1/3 and 3/3 of patients at doses of 3, 4, 5 mg/kg respectively, without any SAE. Median time from ketamine administration to return to baseline status and discharge were 35 and 98 min, respectively. We expect to complete patient recruitment in March 2018. Conclusion: The results from our trial is a groundwork for future dose-finding study. Pending study completion, a multicentric dose validation trial, is set up to further validate the optimal dose from dosINK1 trial. IN ketamine has the potential to improve the field of procedural sedation for children by introducing an effective IN agent with respiratory stability but without the need for an IV line insertion not otherwise needed.
To investigate the effectiveness and usability of automated procedural guidance during virtual temporal bone surgery.
Two randomised controlled trials were performed to evaluate the effectiveness, for medical students, of two presentation modalities of automated real-time procedural guidance in virtual reality simulation: full and step-by-step visual presentation of drillable areas. Presentation modality effectiveness was determined through a comparison of participants’ dissection quality, evaluated by a blinded otologist, using a validated assessment scale.
While the provision of automated guidance on procedure improved performance (full presentation, p = 0.03; step-by-step presentation, p < 0.001), usage of the two different presentation modalities was vastly different (full presentation, 3.73 per cent; step-by-step presentation, 60.40 per cent).
Automated procedural guidance in virtual temporal bone surgery is effective in improving trainee performance. Step-by-step presentation of procedural guidance was engaging, and therefore more likely to be used by the participants.
Co-Phenylcaine Forte is a nasal spray routinely prescribed by otolaryngologists in Australia. The taste of Co-Phenylcaine Forte is typically described as unpleasant. This study sought to improve the overall patient experience associated with Co-Phenylcaine Forte by generating a Co-Phenylcaine Forte formulation, referred to as Co-Phenylcaine Zest, which contains an added vanilla flavour and masking agent.
Participants were randomised to receive two actuations of Co-Phenylcaine Forte in each nostril followed by two actuations of Co-Phenylcaine Zest, or vice versa. There was a 6–36-hour washout period between each treatment. After the administration of each spray, participants completed a questionnaire to rate various sensory attributes of each formulation on seven-point ordinal scales. Patients reported their overall formulation preference after receiving both treatments.
A total of 86 participants completed the trial. Seventy-four per cent of patients preferred Co-Phenylcaine Zest, 21 per cent preferred Co-Phenylcaine Forte and 5 per cent had no preference (p < 0.001). The satisfaction score associated with Co-Phenylcaine Zest was 1.22 points greater than with Co-Phenylcaine Forte (p < 0.001).
A novel formulation of Co-Phenylcaine Forte was created by adding a flavour and a masking agent; this formulation was preferred by most patients.
Accurate models of X-ray absorption and re-emission in partly stripped ions are necessary to calculate the structure of stars, the performance of hohlraums for inertial confinement fusion and many other systems in high-energy-density plasma physics. Despite theoretical progress, a persistent discrepancy exists with recent experiments at the Sandia Z facility studying iron in conditions characteristic of the solar radiative–convective transition region. The increased iron opacity measured at Z could help resolve a longstanding issue with the standard solar model, but requires a radical departure for opacity theory. To replicate the Z measurements, an opacity experiment has been designed for the National Facility (NIF). The design uses established techniques scaled to NIF. A laser-heated hohlraum will produce X-ray-heated uniform iron plasmas in local thermodynamic equilibrium (LTE) at temperatures
eV and electron densities
. The iron will be probed using continuum X-rays emitted in a
diameter source from a 2 mm diameter polystyrene (CH) capsule implosion. In this design,
of the NIF beams deliver 500 kJ to the
mm diameter hohlraum, and the remaining
directly drive the CH capsule with 200 kJ. Calculations indicate this capsule backlighter should outshine the iron sample, delivering a point-projection transmission opacity measurement to a time-integrated X-ray spectrometer viewing down the hohlraum axis. Preliminary experiments to develop the backlighter and hohlraum are underway, informing simulated measurements to guide the final design.
This report describes the unique challenges of managing potential exposure to bats in a neonatal intensive care unit. The outcome demonstrates that rabies post-exposure prophylaxis can be safely administered to preterm infants with evidence that preterm infants are able to develop adequate titers post vaccination.