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The COVID-19 pandemic prompted the development and implementation of hundreds of clinical trials across the USA. The Trial Innovation Network (TIN), funded by the National Center for Advancing Translational Sciences, was an established clinical research network that pivoted to respond to the pandemic.
The TIN’s three Trial Innovation Centers, Recruitment Innovation Center, and 66 Clinical and Translational Science Award Hub institutions, collaborated to adapt to the pandemic’s rapidly changing landscape, playing central roles in the planning and execution of pivotal studies addressing COVID-19. Our objective was to summarize the results of these collaborations and lessons learned.
The TIN provided 29 COVID-related consults between March 2020 and December 2020, including 6 trial participation expressions of interest and 8 community engagement studios from the Recruitment Innovation Center. Key lessons learned from these experiences include the benefits of leveraging an established infrastructure, innovations surrounding remote research activities, data harmonization and central safety reviews, and early community engagement and involvement.
Our experience highlighted the benefits and challenges of a multi-institutional approach to clinical research during a pandemic.
Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
Several grass and broadleaf weed species around the world have evolved multiple-herbicide resistance at alarmingly increasing rates. Research on the biochemical and molecular resistance mechanisms of multiple-resistant weed populations indicate a prevalence of herbicide metabolism catalyzed by enzyme systems such as cytochrome P450 monooxygenases and glutathione S-transferases and, to a lesser extent, by glucosyl transferases. A symposium was conducted to gain an understanding of the current state of research on metabolic resistance mechanisms in weed species that pose major management problems around the world. These topics, as well as future directions of investigations that were identified in the symposium, are summarized herein. In addition, the latest information on selected topics such as the role of safeners in inducing crop tolerance to herbicides, selectivity to clomazone, glyphosate metabolism in crops and weeds, and bioactivation of natural molecules is reviewed.
Objectives: The objective of this study was to evaluate the feasibility and implementation of a standardized medically supervised concussion protocol established between a city-wide AAA hockey league and a multi-disciplinary concussion program. Methods: We conducted a retrospective review of injury surveillance, clinical and healthcare utilization data from all athletes evaluated and managed through the Winnipeg AAA Hockey concussion protocol during the 2016-2017 season. We also conducted post-season email surveys of head coaches and parents responsible for athletes who competed in the same season. Results: During the 2016-2017 season, 28 athletes were evaluated through the medically supervised concussion protocol, with two athletes undergoing evaluation for repeat injuries (a total of 30 suspected injuries and consultations). In all, 96.7% of the athletes managed through the concussion protocol were captured by the league-designated Concussion Protocol Coordinator and 100% of eligible athletes underwent complete medical follow-up and clearance to return to full hockey activities. Although 90% of responding head coaches and 91% of parents were aware of the concussion protocol, survey results suggest that some athletes who sustained suspected concussions were not managed through the protocol. Head coaches and parents also indicated that athlete education and communication between medical and sport stakeholders were other elements of the concussion protocol that could be improved. Conclusion: Successful implementation of a medically supervised concussion protocol for youth hockey requires clear communication between sport stakeholders and timely access to multi-disciplinary experts in traumatic brain and spine injuries. Standardized concussion protocols for youth sports may benefit from periodic evaluations by sport stakeholders and incorporation of national guideline best practices and resources.
Purpose: To examine the safety and tolerability of clinical graded aerobic treadmill testing in recovering adolescent moderate and severe traumatic brain injury (TBI) patients referred to a multidisciplinary pediatric concussion program. Methods: We completed a retrospective case series of two moderate and five severe TBI patients (mean age, 17.3 years) who underwent initial Buffalo Concussion Treadmill Testing at a mean time of 71.6 days (range, 55-87) postinjury. Results: Six patients completed one graded aerobic treadmill test each and one patient underwent initial and repeat testing. There were no complications. Five initial treadmill tests were completely tolerated and allowed an accurate assessment of exercise tolerance. Two initial tests were terminated early by the treatment team because of neurological and cardiorespiratory limitations. As a result of testing, two patients were cleared for aerobic exercise as tolerated and four patients were treated with individually tailored submaximal aerobic exercise programs resulting in subjective improvement in residual symptoms and/or exercise tolerance. Repeat treadmill testing in one patient performed after 1 month of treatment with submaximal aerobic exercise prescription was suggestive of improved exercise tolerance. One patient was able to tolerate aerobic exercise following surgery for posterior glottic stenosis. Conclusions: Preliminary results suggest that graded aerobic treadmill testing is a safe, well tolerated, and clinically useful tool to assess exercise tolerance in appropriately selected adolescent patients with TBI. Future prospective studies are needed to evaluate the effect of tailored submaximal aerobic exercise prescription on exercise tolerance and patient outcomes in recovering adolescent moderate and severe TBI patients.
Objectives: To summarize the clinical characteristics and outcomes of pediatric sports-related concussion (SRC) patients who were evaluated and managed at a multidisciplinary pediatric concussion program and examine the healthcare resources and personnel required to meet the needs of this patient population. Methods: We conducted a retrospective review of all pediatric SRC patients referred to the Pan Am Concussion Program from September 1st, 2013 to May 25th, 2015. Initial assessments and diagnoses were carried out by a single neurosurgeon. Return-to-Play decision-making was carried out by the multidisciplinary team. Results: 604 patients, including 423 pediatric SRC patients were evaluated at the Pan Am Concussion Program during the study period. The mean age of study patients was 14.30 years (SD: 2.32, range 7-19 years); 252 (59.57%) were males. Hockey (182; 43.03%) and soccer (60; 14.18%) were the most commonly played sports at the time of injury. Overall, 294 (69.50%) of SRC patients met the clinical criteria for concussion recovery, while 75 (17.73%) were lost to follow-up, and 53 (12.53%) remained in active treatment at the end of the study period. The median duration of symptoms among the 261 acute SRC patients with complete follow-up was 23 days (IQR: 15, 36). Overall, 25.30% of pediatric SRC patients underwent at least one diagnostic imaging test and 32.62% received referral to another member of our multidisciplinary clinical team. Conclusion: Comprehensive care of pediatric SRC patients requires access to appropriate diagnostic resources and the multidisciplinary collaboration of experts with national and provincially-recognized training in TBI.
Various medications and devices are available for facilitation of emergent endotracheal intubations (EETIs). The objective of this study was to survey which medications and devices are being utilized for intubation by Canadian physicians.
A clinical scenario-based survey was developed to determine which medications physicians would administer to facilitate EETI, their first choice of intubation device, and backup strategy should their first choice fail. The survey was distributed to Canadian emergency medicine (EM) and intensive care unit (ICU) physicians using web-based and postal methods. Physicians were asked questions based on three scenarios (trauma; pneumonia; heart failure) and responded using a 5-point scale ranging from “always” to “never” to capture usual practice.
The survey response rate was 50.2% (882/1,758). Most physicians indicated a Macintosh blade with direct laryngoscopy would “always/often” be their first choice of intubation device in the three scenarios (mean 85% [79%-89%]) followed by video laryngoscopy (mean 37% [30%-49%]). The most common backup device chosen was an extraglottic device (mean 59% [56%-60%]). The medications most physicians would “always/often” administer were fentanyl (mean 45% [42%-51%]) and etomidate (mean 38% [25%-50%]). EM physicians were more likely than ICU physicians to paralyze patients for EETI (adjusted odds ratio 3.40; 95% CI 2.90-4.00).
Most EM and ICU physicians utilize direct laryngoscopy with a Macintosh blade as a primary device for EETI and an extraglottic device as a backup strategy. This survey highlights variation in Canadian practice patterns for some aspects of intubation in critically ill patients.
This study tests competing models of the relation between depression and polysubstance use over the course of adolescence. Participants included a nationwide sample of adolescents (N = 3,604), ages 12 to 17 at study Wave 1, assessed annually for 3 years. Models were tested using cohort-sequential latent growth curve modeling to determine whether depressive symptoms at baseline predicted concurrent and age-related changes in drug use, whether drug use at baseline predicted concurrent and age-related changes in depressive symptoms, and whether initial levels of depression predicted changes in substance use significantly better than vice versa. The results suggest a transactional model such that early polysubstance use promotes early depressive symptoms, which in turn convey elevated risk for increasing polysubstance use over time, which in turn conveys additional risk for future depressive symptoms, even after accounting for gender, ethnicity, and household income. In contrast, early drug use did not portend risk for future depressive symptoms. These findings suggest a complicated pattern of interrelations over time and indicate that many current models of co-occurring polysubstance use and depressive symptoms may not fully account for these associations. Instead, the results suggest a developmental cascade, in which symptoms of one disorder promote symptoms of the other across intrapersonal domains.
Silicon carbide power devices are purported to be capable of operating at very high temperatures. Current commercially available SiC MOSFETs from a number of manufacturers have been evaluated to understand and quantify the aging processes and temperature dependencies that occur when operated up to 350°C. High temperature constant positive bias stress tests demonstrated a two times increase in threshold voltage from the original value for some device types, which was maintained indefinitely but could be corrected with a long negative gate bias. The threshold voltages were found to decrease close to zero and the on-state resistances increased quite linearly to approximately five or six times their room temperature values. Long term thermal aging of the dies appears to demonstrate possible degradation of the ohmic contacts. This appears as a rectifying response in the I-V curves at low drain-source bias. The high temperature capability of the latest generations of these devices has been proven independently; provided that threshold voltage management is implemented, the devices are capable of being operated and are free from the effects of thermal aging for at least 70 hours cumulative at 300°C.
The forests of the Angolan highlands are the smallest and most isolated of the Afromontane centres of endemism. Despite their high biodiversity value and small, fragmented extent of less than 200 ha, they remain entirely unprotected. Here we draw attention to their uniqueness and the threats to their conservation. We specifically highlight the importance of Mt Moco to bird conservation and describe current forest cover and condition. Sixty-four endemic/near-endemic species/subspecies and taxa with isolated populations are associated with the highlands of western Angola. All 19 forest-dependent taxa are among the 233 species recorded at Mt Moco, which include a rich diversity of montane specialists. Swierstra’s Francolin Pternistis swierstrai is the only threatened endemic. In 2009, 10 of 30 forest patches at Mt Moco larger than 0.5 ha were surveyed for this species. It occurred in seven of these surveyed patches, at a mean minimum density of 0.95 pair ha−1 in forest patches > 1 ha. Based on extrapolations of this figure, we estimate a minimum of 75 pairs of Swierstra’s Francolin at Mt Moco, and 185–420 pairs worldwide. Due to both limited range and small population size, we propose the species be up-listed from ‘Vulnerable’ to ‘Endangered’. Total forest cover at Mount Moco in forest patches > 0.5 ha in size is currently 85 ha. This is c.40% of the total cover of Afromontane forest estimated for Angola in 1974. Remaining forest cover at Mt Moco is being eroded by bush fires, removal of wood for fire and construction material, and clearance for subsistence agriculture by the c.330 inhabitants of Kanjonde village. In order to preserve the forest of Mt Moco, we propose the implementation of a protected area and define its boundaries. A similar proposal was made in 1974 for the creation of the Mount Moco Special Reserve.
Infiltration of T cells is a key step in the pathogenesis of the inflammatory skin diseases atopic dermatitis, allergic contact dermatitis and psoriasis. Understanding the mechanisms of T cell recruitment to the skin is therefore of fundamental importance for the discovery and application of novel therapies for these conditions. Studies of both clinical samples and experimental models of skin inflammation have implicated specific adhesion molecules and chemokines in lymphocyte recruitment. In particular, recent studies using advanced in vivo imaging techniques have greatly increased our understanding of the kinetics and molecular basis of this process. In this review, we summarise the current understanding of the cellular immunology of antigen-driven dermal inflammation and the roles of adhesion molecules and chemokines. We focus on results obtained using intravital microscopy to examine the dermal microvasculature and interstitium to determine the mechanisms of T cell recruitment and migration in experimental models of T-cell-mediated skin inflammation.