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Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
The term “Antarctic ambassadorship” is increasingly used to represent an individual’s connection to Antarctica and their subsequent advocacy. However, there is little clarity regarding the concept. To address this, we combined a literature review with an expert elicitation workshop. We argue that (i) the concept of Antarctic ambassador has been understood in myriad ways; (ii) Antarctic ambassadors have a connection to, knowledge of and passion for Antarctica; (iii) they also have a commitment to defending and advancing Antarctic values and (iv) Antarctic ambassadorship is about more than advocacy. We propose the first comprehensive definition of Antarctic ambassadorship. We hope this will provide a cornerstone upon which future research, and a more informed governance of Antarctic tourism, can be built.
The contribution of mental health to the risk of smoking is increasingly acknowledged but still insufficiently studied during the key period of student life. In particular, the simultaneous action of stress and Attention Deficit Hyperactivity Disorder (ADHD) symptoms on the risk of smoking remains poorly understood.
To assess the effects of stress and ADHD symptoms on tobacco smoking.
Multivariate modeling was conducted on the French i-Share study (n = 8110, median age 20.3 years, 74.8% females, 32.9% regular/occasional smokers) to evaluate the associations between stress, ADHD symptoms and tobacco smoking, adjusting for potential family/socio-demographic confounders.
Students with high levels of stress were more likely to smoke > 10 cigarettes/day (adjusted odds ratio (aOR): 1.48, 95% CI: 1.12–1.96) than those with low levels of stress. Students with high levels of ADHD symptoms were more likely to smoke > 10 cigarettes/day (aOR: 2.08, 95% CI: 1.58–2.75) than those with low levels of ADHD symptoms.
Stress and ADHD contribute independently to the risk of smoking. Interventions targeting each condition are likely to reduce the burden of tobacco use in students.
Malnutrition is a serious condition that is frequent in hospitalized patients even in countries with high healthcare standards, and may affect up to 30% of all hospitalized patients in tertiary hospitals. Malnutrition or risk of malnutrition (hereafter referred to as malnutrition) strongly relate to clinical outcomes and mortality, even after adjustment for age and co-morbidities. There is a great need for improved methods for detecting and treating malnutrition in this population.
Investigate factors that are associated with malnutrition at hospitalization, and provide data on specific nutrient deficiencies that are associated with malnutrition. Analyse the association of malnutrition with nutritional biomarkers, quality of life, disease-related functions and re-hospitalization, morbidity and mortality.
The study is s a prospective case-control study including patients from different Departments of a tertiary hospital (Haukeland University Hospital, Bergen, Norway). As part of the patients security programme, all hospitalized patients are routinely screened for nutritional risk using NRS-2002. The result allocates the patient to either the case- or the control group. Included patients undergo extensive examinations; standardized assessments of quality of life, socio-economic status, lifestyle habits, dietary habits and food intake, and anthropometric measurements (mid-upper arm circumference, waist circumference and body composition by bioelectrical impedance analysis). Blood and urine samples are collected to assess nutritional biomarkers related to malnutrition.
The study recruitment is ongoing and up to April 2019, 220 patients have been recruited (n = 90 (41%) at nutritional risk, n = 130 (59%) not at nutritional risk. Most of the patients are recruited from the Department of Heart Disease, n = 69 (31%) and Thoracic Medicine, n = 98 (45%). The recruitment of patients faces many challenges, including a high degree of non-participation (about one in four patients), and a high degree of misclassification (patients falsely categorized as ‘not at nutritional risk’).
The study is unique due to the integration of patient-derived data on quality of life, food intake, and socio-economic factors with multiple and complementary nutritional biomarkers. A first result from the recruitment period is the need for specification of the specificity and sensitivity of screening tools for malnutrition in hospitals under realistic circumstances. This should ideally be tested in a multicentre study
Patients with bipolar disorder (BD) experience persistent impairments in both affective and non-affective cognitive function, which is associated with a worse course of illness and poor functional outcomes. Nevertheless, the temporal progression of cognitive dysfunction in BD remains unclear and the identification of objective endophenotypes can inform the aetiology of BD.
The present study is a cross-sectional investigation of cognitive baseline data from the longitudinal Bipolar Illness Onset-study. One hundred seventy-two remitted patients newly diagnosed with BD, 52 of their unaffected relatives (UR), and 110 healthy controls (HC) were compared on a large battery of behavioural cognitive tasks tapping into non-affective (i.e. neurocognitive) and affective (i.e. emotion processing and regulation) cognition.
Relative to HCs, patients with BD exhibited global neurocognitive deficits (ps < 0.001), as well as aberrant emotion processing and regulation (ps ⩽ 0.011); including decreased emotional reactivity to positive social scenarios, impaired ability to down-regulate positive emotion, as well as a specific deficit in the ability to recognise surprised facial expressions. Their URs also showed a trend towards difficulties identifying surprised faces (p = 0.075). No other differences in cognitive function were found for URs compared to HCs.
Neurocognitive deficits and impairments within emotion processing and regulation may be illness-related deficits of BD that present after illness-onset, whereas processing of emotional faces may represent an early risk marker of BD. However, longitudinal studies are needed to examine the association between cognitive impairments and illness progression in BD.
Surface mass balance (SMB) is the net input of mass on a glacier's upper surface, composed of snow deposition, melt and erosion processes, and is a major contributor to the overall mass balance. Pine Island Glacier (PIG) in West Antarctica has been dynamically imbalanced since the early 1990s, indicating that discharge of solid ice into the oceans exceeds snow deposition. However, observations of the SMB pattern on the fast flowing regions are scarce, and are potentially affected by the firn's strain history. Here, we present new observations from radar-derived stratigraphy and a relatively dense network of firn cores, collected along a ~900 km traverse of PIG. Between 1986 and 2014, the SMB along the traverse was 0.505 m w.e. a−1 on average with a gradient of higher snow deposition in the South-West compared with the North-East of the catchment. We show that along ~80% of the traverse the strain history amounts to a misestimation of SMB below the nominal uncertainty, but can exceed it by a factor 5 in places, making it a significant correction to the SMB estimate locally. We find that the strain correction changes the basin-wide SMB by ~0.7 Gt a−1 and thus forms a negligible (1%) correction to the glacier's total SMB.
Introduction: Emergency Department (ED) visits related to substance use are rapidly increasing. Despite this, few Canadian EDs have immediate access to addiction medicine specialists or on-site addiction medicine clinics. This study characterized substance-related ED presentations to an urban tertiary care ED and assessed need for an on-site rapid-access addiction clinic (RAAC). Methods: This prospective enrollment, retrospective chart review was conducted from June to August 2018. Adult patients presenting to the ED with a known or suspected substance use disorder were enrolled by any member of their ED care team using a 1-page form. Retrospective chart review of the index ED visit was conducted and the Emergency Department Information System was used to extract information related to the visit. A multivariable logistic regression model was fit to examine factors associated with recommendation for referral to a hypothetical on-site RAAC.This prospective enrollment, retrospective chart review was conducted from June to August 2018. Adult patients presenting to the ED with a known or suspected substance use disorder were enrolled by any member of their ED care team using a 1-page form. Retrospective chart review of the index ED visit was conducted and the Emergency Department Information System was used to extract information related to the visit. A multivariable logistic regression model was fit to examine factors associated with recommendation for referral to a hypothetical on-site RAAC. Results: Of the 557 enrolment forms received, 458 were included in the analysis. 64% of included patients were male and 36% were female, with a median age of 35.0 years. Polysubstance use was seen in 23% of patients, and alcohol was the most common substance indicated (60%), followed by stimulants (32%) and opioids (16%). The median ED length of stay for included patients was 483 minutes, compared to 354 minutes for all-comers discharged from the ED during the study period. 28% of patients had a previous ED visit within 7 days of the index visit, and an additional 17% had a visit in the preceding 30 days. The ED care team indicated ‘Yes’ for RAAC referral from the ED for 66% of patients, for a mean of 4.3 patients referred per day during the study period. Multivariable analysis showed that all substances (except cannabis) correlated to a statistically significant increase in likelihood for indicating ‘Yes’ for RAAC referral from the ED (alcohol, stimulants, opioids, polysubstance; p < 0.05). Patients presenting to the ED with a chief complaint related to substance use were also more likely to be referred (p = 0.01). Conclusion: This retrospective chart review characterized substance-related presentations at a Canadian urban tertiary care ED. Approximately four patients per day would have been referred to an on-site RAAC had one been available. The RAAC model has been implemented in other Canadian hospitals, and collaborating with these sites to begin developing this service would be an important next step.
The Association of Polar Early Career Scientists (APECS) is an important legacy of the International Polar Year (IPY). APECS continues to foster engagement in education, outreach and communication (EOC) activities relating to the polar regions and provide training for early career researchers (ECRs). We highlight opportunities for training, leadership and skills development, such as the annual Polar Weeks and Antarctica Day celebrations. Participation and engagement in EOC activities actively contributes to career development by enabling ECRs to develop valuable soft skills such as networking, communication and interdisciplinary knowledge. A pilot survey on EOC engagement highlighted that those who organise events also gain leadership skills such as team management. We discuss several factors contributing to the success of APECS in training the next generation of polar leaders. These include the geographical rather than discipline-specific focus of the organisation, utilisation of online resources, including social media, and the strong links with partner organisations. These examples demonstrate how the EOC legacy of IPY has continued due to APECS’ targeted efforts to create EOC opportunities and provide skills and leadership training for ECRs.
Collaborative care can support the treatment of depression in people with long-term conditions, but long-term benefits and costs are unknown.
To explore the long-term (24-month) effectiveness and cost-effectiveness of collaborative care in people with mental-physical multimorbidity.
A cluster randomised trial compared collaborative care (integrated physical and mental healthcare) with usual care for depression alongside diabetes and/or coronary heart disease. Depression symptoms were measured by the symptom checklist-depression scale (SCL-D13). The economic evaluation was from the perspective of the English National Health Service.
191 participants were allocated to collaborative care and 196 to usual care. At 24 months, the mean SCL-D13 score was 0.27 (95% CI, −0.48 to −0.06) lower in the collaborative care group alongside a gain of 0.14 (95% CI, 0.06-0.21) quality-adjusted life-years (QALYs). The cost per QALY gained was £13 069.
In the long term, collaborative care reduces depression and is potentially cost-effective at internationally accepted willingness-to-pay thresholds.
West Antarctic climate and surface mass balance (SMB) records are sparse. To fill this gap, regional atmospheric climate modelling is useful, providing that such models are employed at sufficiently high horizontal resolution and coupled with a snow model. Here we present the results of a high-resolution (5.5 km) regional atmospheric climate model (RACMO2) simulation of coastal West Antarctica for the period 1979–2015. We evaluate the results with available in situ weather observations, remote-sensing estimates of surface melt, and SMB estimates derived from radar and firn cores. Moreover, results are compared with those from a lower-resolution version, to assess the added value of the resolution. The high-resolution model resolves small-scale climate variability invoked by topography, such as the relatively warm conditions over ice-shelf grounding zones, and local wind speed accelerations. Surface melt and SMB are well reproduced by RACMO2. This dataset will prove useful for picking ice core locations, converting elevation changes to mass changes, for driving ocean, ice-sheet and coupled models, and for attributing changes in the West Antarctic Ice Sheet and shelves to changes in atmospheric forcing.
Seabird bycatch is widely regarded as the greatest threat globally to procellariiform seabirds. Although measures to reduce seabird–fishery interactions have been in existence for many years, uptake in fleets with high risk profiles remains variable. We recorded seabird bycatch and other interactions in the Namibian demersal longline fishery. Interaction rates were estimated for seasonal and spatial strata and scaled up to fishing effort data. Bycatch rates were 0.77 (95% CI 0.24–1.39) and 0.37 (95% CI 0.11–0.72) birds per 1,000 hooks in winter and summer, respectively. Scaling up to 2010, the most recent year for which complete data are available, suggests 20,567 (95% CI 6,328–37,935) birds were killed in this fishery that year. We compared bycatch rates to those from experimental fishing sets using mitigation measures (one or two bird-scaring lines and the replacement of standard concrete weights with 5 kg steel weights). All mitigation measures significantly reduced the bycatch rate. This study confirms the Namibian longline fishery has some of the highest known impacts on seabirds globally, but implementing simple measures could rapidly reduce those impacts. In November 2015 the Ministry of Fisheries and Marine Resources introduced regulations requiring the use of bird-scaring lines, line weighting and night setting in this fishery. A collaborative approach between NGOs, industry and government was important in achieving wide understanding and acceptance of the proposed mitigation measures in the lead up to the introduction of new fishery regulations.
Introduction: Emergency department visits related to substance use are becoming more serious and increasingly costly in Canada. Emergency physicians must be able to effectively screen, manage, refer, and advocate for these complex patients. This study sought to describe the current state of addiction medicine training in Canadian emergency medicine (EM) residency programs and to assess the need for a formal curriculum. Methods: All Royal College and College of Family Physicians EM Program Directors (PDs) were asked to participate in a ten-question needs assessment survey on addiction medicine training for residents. Questions were developed through consensus after reviewing the relevant literature and conducting a formal pilot survey with staff physicians experienced in survey methodology. Responses were collected securely using the Research Electronic Data Capture (REDCap) database. Results: 19 out of 31 (62%) eligible PDs completed the survey. The importance of addiction medicine training received a median score of 69.5 (IQR=74.0) on a scale of 1-100. Most programs devoted two hours or less per year of formalized teaching on individual topics (such as opioids, alcohol, harm reduction) over the past two academic years. The two most common teaching modalities used were didactic lectures (15/19, 78.9%) and case-based tutorials (12/19, 63.2%). Case-based tutorials were identified as the most effective teaching method (12/19, 63.2%). Topics highlighted as most important to include in a curriculum were: screening for substance use disorders and referral for further treatment (14/19, 73.7%), social determinants of health (14/19, 73.7%), alcohol, opioid, and stimulant intoxication and/or withdrawal (14/19, 73.7% each), and management of patients on opioid agonist therapy (14/19, 73.7%). The most commonly perceived barriers to implementing such a curriculum were insufficient curriculum time (10/19, 52.6%) and lack of qualified teaching staff (7/19, 36.8%). Conclusion: This needs assessment provides an understanding of the current state of addiction medicine training for EM residents in Canada. A case-based addiction medicine workshop is currently being developed to address identified curriculum gaps. Integrating this curriculum longitudinally into a time-constrained academic schedule is an important next step.
The Numeniini is a tribe of 13 wader species (Scolopacidae, Charadriiformes) of which seven are Near Threatened or globally threatened, including two Critically Endangered. To help inform conservation management and policy responses, we present the results of an expert assessment of the threats that members of this taxonomic group face across migratory flyways. Most threats are increasing in intensity, particularly in non-breeding areas, where habitat loss resulting from residential and commercial development, aquaculture, mining, transport, disturbance, problematic invasive species, pollution and climate change were regarded as having the greatest detrimental impact. Fewer threats (mining, disturbance, problematic native species and climate change) were identified as widely affecting breeding areas. Numeniini populations face the greatest number of non-breeding threats in the East Asian-Australasian Flyway, especially those associated with coastal reclamation; related threats were also identified across the Central and Atlantic Americas, and East Atlantic flyways. Threats on the breeding grounds were greatest in Central and Atlantic Americas, East Atlantic and West Asian flyways. Three priority actions were associated with monitoring and research: to monitor breeding population trends (which for species breeding in remote areas may best be achieved through surveys at key non-breeding sites), to deploy tracking technologies to identify migratory connectivity, and to monitor land-cover change across breeding and non-breeding areas. Two priority actions were focused on conservation and policy responses: to identify and effectively protect key non-breeding sites across all flyways (particularly in the East Asian- Australasian Flyway), and to implement successful conservation interventions at a sufficient scale across human-dominated landscapes for species’ recovery to be achieved. If implemented urgently, these measures in combination have the potential to alter the current population declines of many Numeniini species and provide a template for the conservation of other groups of threatened species.
Marginal stability arguments are used to describe the rotation number dependence of torque in Taylor–Couette (TC) flow for radius ratios
and shear Reynolds number
. With an approximate representation of the mean profile by piecewise linear functions, characterised by the boundary-layer thicknesses at the inner and outer cylinder and the angular momentum in the centre, profiles and torques are extracted from the requirement that the boundary layers represent marginally stable TC subsystems and that the torque at the inner and outer cylinder coincide. This model then explains the broad shoulder in the torque as a function of rotation number near
. For rotation numbers
the TC stability conditions predict boundary layers in which the shear Reynolds numbers are very large. Assuming that the TC instability is bypassed by some shear instability, a second narrower maximum in torque appears, in very good agreement with numerical simulations. The results show that marginal stability theory, despite its shortcomings in other cases, can explain quantitatively the non-monotonic torque variation with rotation number for both the broad maximum as well as the narrow maximum.
A floating air bag, ballasted in water, expands and contracts as it heaves under wave action. Connecting the bag to a secondary volume via a turbine transforms the bag into a device capable of generating useful energy from the waves. Small-scale measurements of the device reveal some interesting properties, which are successfully predicted numerically. Owing to its compressibility, the device can have a heave resonance period longer than that of a rigid device of the same shape and size, without any phase control. Furthermore, varying the amount of air in the bag is found to change its shape and hence its dynamic response, while varying the turbine damping or the air volume ratio changes the dynamic response without changing the shape.
We numerically study turbulent Taylor–Couette flow (TCF) between two independently rotating cylinders and the transition to rotating plane Couette flow (RPCF) in the limit of infinite radii. By using the shear Reynolds number
and rotation number
as dimensionless parameters, the transition from TCF to RPCF can be studied continuously without singularities. Already for radius ratios
we find that the simulation results for various radius ratios and for RPCF collapse as a function of
, indicating a turbulent behaviour common to both systems. We observe this agreement in the torque, mean momentum transport, mean profiles and turbulent fluctuations. Moreover, in TCF and RPCF for
, the profiles in the central region are found to conform with inviscid neutral stability. Intermittent bursts, that have been observed in the outer boundary layer and have been linked to the formation of a torque maximum for counter-rotation, are shown to disappear as
. The corresponding torque maximum disappears as well. Instead, two new maxima of different origin appear for
and RPCF, a broad and a narrow one, in contrast to the results for smaller
. The broad maximum at
is connected with a strong vortical flow and can be reproduced by streamwise-invariant simulations. The narrow maximum at
only emerges with increasing
and is accompanied by an efficient and correlated momentum transport by the mean flow. Since the narrow maximum is of larger amplitude for
, our simulations suggest that it will dominate at even higher