To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Introduction: Emergency Department (ED) health care professionals are responsible for providing team-based care to critically ill patients. Given this complex responsibility, simulation training is paramount. In situ simulation (ISS) has many cited benefits as a training strategy that targets on-duty staff and occurs in the actual patient environment. Several evidence-based frameworks identify staff buy-in as essential for successful ISS implementation, however, the attitudes of interdisciplinary front-line ED staff in this regard are unknown. The purpose of this study is to identify contextual trends in interdisciplinary opinions on routine ISS in the ED. Methods: Qualitative and quantitative review, exploring the self-reported attitudes of interdisciplinary ED staff: before, during and after the implementation of a routine ISS pilot program (5 sessions in 5 months) at the Charles V Keating Emergency and Trauma Center in Halifax from Feb-Nov, 2018. Results: 149 surveys were received. Baseline support for ISS was high; 83% of respondents believed that the advantages of ISS outweigh the challenges and 47% favoured simulation in the ED, relative the sim bay (26%) and 28% were indifferent. The attitudes of direct participants in ISS were very positive, with 88% believing that the benefits outweighed the challenges after participation and 91% believing that they personally benefited from participating. A department wide post-ISS pilot survey suggested a slight decrease in support. Support for ISS dropped from 83% to 67%, a statistically insignificant reduction (p = 0.098) but a sizeable change that warrants further investigation. Most notably respondents reported increased support for simulation training in a simulation bay relative to ISS in the ED. Respondents still regarded simulation highly overall. Interestingly, when the results were stratified by position, staff physicians were the least positive. Conclusion: Pre-pilot or baseline opinions of ISS were very positive, and participants all responded positively to the simulations. This study generates valuable insight into the perceptions of interdisciplinary ED staff regarding the implementation and perceived impact of routine ISS. This evidence can be used to inform future programming, though further investigation is warranted into why opinions post-intervention may have changed at the department level.
Synchrotron radiation was used to obtain a high-resolution powder diffraction pattern of the high-density form of BeH2, a material whose unit-cell dimensions have not previously been determined. The observed d-spacing values were presented to three different computer indexing programs. All three programs returned as best solution a body-centered orthorhombic unit cell with a = 9.082, b = 4.160, c = 7.707 Å and V = 292 Å3. Interpretation of the three-dimensional Patterson led to 12 BeH2 molecules per unit cell; thus, the theoretical density is 0.755 g/cm3. The molecular structure is based on a network of corner-sharing BeH4 tetrahedra rather than flat, infinite chains with hydrogen bridges previously assumed.
In June 2012, the Botswana Ministry of Health and Wellness (MOHW; Gaborone, Botswana) initiated a national Emergency Medical Services (EMS) system in response to significant morbidity and mortality associated with prehospital emergencies. The MOHW requested external expertise to train its developing workforce. Simulation-based training was planned to equip these health care providers with clinical knowledge, procedural skills, and communication techniques.
The objective of this study was to assess the educational needs of the pioneer Botswana MOHW EMS providers based on retrospective EMS logbook review and EMS provider feedback to guide development of a novel educational curriculum.
Data were abstracted from a representative sample of the Gaborone, Botswana MOHW EMS response log from 2013-2014 and were quantified into the five most common call types for both adults and children. Informal focus groups with health professionals and EMS staff, as well as surveys, were used to rank common response call types and self-perceived educational needs.
Based on 1,506 calls, the most common adult response calls were for obstetric emergencies, altered mental status, gastrointestinal/abdominal pain, trauma, gynecological emergencies, and cardiovascular and respiratory distress-related emergencies. The most common pediatric response calls were for respiratory distress, gastrointestinal complaints/dehydration, trauma and musculoskeletal injuries, newborn delivery, seizures, and toxic ingestion/exposure. The EMS providers identified these same chief complaints as priorities for training using the qualitative approach. A locally relevant, simulation-based curriculum for the Botswana MOHW EMS system was developed and implemented based on these data.
: Trauma, respiratory distress, gastrointestinal complaints, and puerperal/perinatal emergencies were common conditions for all age groups. Other age-specific conditions were also identified as educational needs based on epidemiologic data and provider feedback. This needs assessment may be useful when designing locally relevant EMS curricula in other low-income and middle-income countries.GlombNW, KosokoAA, DoughtyCB, RusMC, ShahMI, CoxM, GalapiC, ParkesPS, KumarS, LabaB.Needs Assessment for Simulation Training for Prehospital Providers in Botswana. Prehosp Disaster Med. 2018;33(6):621–626.
Deutetrabenazine is approved for treating Huntington disease (HD) chorea and is being evaluated for tardive dyskinesia (TD).
To assess the effect of deutetrabenazine on cardiac repolarization.
A QT interval study was performed to evaluate effects of deutetrabenazine 12 and 24 mg on cardiac repolarization, as assessed by time-matched change from baseline, placebo-adjusted, in Fridericia-corrected QT interval (ΔΔQTcF). Moxifloxacin (400 mg) and tetrabenazine (50 mg) were the positive control and comparator, respectively. An exposure–response analysis was developed from this study to predict maximal effects on QTcF at maximum recommended dosing based on CYP2D6 status, an approach consistent with regulatory guidance at predicting QT interval effects.
Maximal ΔΔQTcF between the least-squares mean (90% two-sided confidence interval) of deutetrabenazine 12 and 24 mg (n=45 in each group) were 2.8 (0.7–4.8) ms and 4.5 (2.4–6.5) ms, respectively. The ΔΔQTcF increase with tetrabenazine (n=45) was 7.6 (5.6–9.5) ms. Assay sensitivity was verified with moxifloxacin (n=47), which produced a maximal effect on ΔΔQTcF of 14.0 (11.9–16.0) ms. A linear model was developed that described a correlation between plasma concentrations from pivotal HD andTD trials (n=101) and QT interval prolongation. Using that model and the individual predicted Cmax for HD and TD patients, the placebo-adjusted change from baseline inQTcF for deutetrabenazine at maximal recommended daily doses was found to be 5.4 (2.5–9.5) ms.
Patients receiving the maximal recommended doses of deutetrabenazine are predicted to have a QTcF increase below the level of regulatory concern.
Presented at: Psych Congress; September 16–19, 2017; New Orleans, Louisiana, USA.
This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel
Moving mesh methods provide an efficient way of solving partial differential equations for which large, localised variations in the solution necessitate locally dense spatial meshes. In one-dimension, meshes are typically specified using the arclength mesh density function. This choice is well-justified for piecewise polynomial interpolants, but it is only justified for spectral methods when model solutions include localised steep gradients. In this paper, one-dimensional mesh density functions are presented which are based on a spatially localised measure of the bandwidth of the approximated model solution. In considering bandwidth, these mesh density functions are well-justified for spectral methods, but are not strictly tied to the error properties of any particular spatial interpolant, and are hence widely applicable. The bandwidth mesh density functions are illustrated in two ways. First, by applying them to Chebyshev polynomial approximation of two test functions, and second, through use in periodic spectral and finite-difference moving mesh methods applied to a number of model problems in acoustics. These problems include a heterogeneous advection equation, the viscous Burgers’ equation, and the Korteweg-de Vries equation. Simulation results demonstrate solution convergence rates that are up to an order of magnitude faster using the bandwidth mesh density functions than uniform meshes, and around three times faster than those using the arclength mesh density function.
Although World Glacier Inventory (WGI) data for 241 local glaciers (>1 km2 in area) in Svalbard show a mean aspect of 014˚ ± 24˚, their mid-altitudes are lowest for an aspect of 109˚ ± 46˚, which is inconsistent. Further data are generated here for the altitude, length and source aspect of 205 local glaciers (0.3–6.0 km long) in the main area of local glaciation in Svalbard, Nordenskiöld Land. All four mountain blocks have mean glacier source aspects of 356˚ to 018˚; the overall mean is 011˚ ± 8˚. Mid-altitudes are lowest at 042˚ ±21˚, predicted to be 53 m lower than on opposite aspects. Lowest altitudes are predicted at 009˚ to 030˚, averaging 157 m lower than on opposite aspects. These results show that local, land-terminating glaciers around 78˚ N are affected more by north-south radiation receipt contrasts than by wind effects, consistent with the trend found across most other Arctic regions. It is concluded that, although weaker than in mid-latitudes, contrasts due to slope climates are substantial even in Arctic glaciers. This is apparent only when small, steep glaciers are inventoried: WGI data are incomplete and users need to check the thresholds of coverage.
North–south and east–west differences in firn-line altitude, equilibrium-line altitude or middle altitudes of glaciers can be separated by regression on the cosine and sine of glacier aspect (accumulation area azimuth). Allowing for regional trends in altitude, the north–south differences expected from radiation and shade effects can be reliably quantified from World Glacier Inventory (WGI) data. The north–south differences are greater in sunnier climates, mid-latitudes and steeper relief. Local altitude differences between north- and south-facing glaciers are commonly 70–320 m. Such asymmetry is near-universal, although weak in the Arctic and tropics. East–west contrasts are less, and found mainly in the tropics and areas most exposed to strong winds. Altitude, latitude, glacier gradient and height range, calculable from most of the WGI data, are potential controls on the degree of north–south contrast, as well as surrogates for climatic controls (temperature, precipitation, radiation and cloudiness). An asymmetric sine–cosine power model is developed to describe the variation of north–south contrast with latitude. Multiple regression over 51 regions shows altitude and latitude to be the strongest controls of this contrast. Aspect–altitude analysis for former glaciers provides new evidence of cloudiness.
The net mass balance on Gulkana Glacier, Alaska, U.S.A., has been measured since 1966 by the glaciological method, in which seasonal balances are measured at three index sites and extrapolated over large areas of the glacier. Systematic errors can accumulate linearly with time in this method. Therefore, the geodetic balance, in which errors are less time-dependent, was calculated for comparison with the glaciological method. Digital elevation models of the glacier in 1974, 1993 and 1999 were prepared using aerial photographs, and geodetic balances were computed, giving – 6.0 ± 0.7 m w.e. from 1974 to 1993 and -11.8 ± 0.7 m w.e. from 1974 to 1999. These balances are compared with the glaciological balances over the same intervals, which were – 5.8 ± 0.9 and -11.2 ± 1.0 m w.e. respectively; both balances show that the thinning rate tripled in the 1990s. These cumulative balances differ by <6%. For this close agreement, the glaciologically measured mass balance of Gulkana Glacier must be largely free of systematic errors and be based on a time-variable area-altitude distribution, and the photography used in the geodetic method must have enough contrast to enable accurate photogrammetry.
We report here a systematic study of the molecular content in the neutral envelope of NGC 7027. The measurements were done in September 1991 with the 30-meter IRAM telescope on Pico Veleta (Spain). The frequencies and transitions covered are given in Table 1. Long integrations were performed in each transitions toward the central position of NGC 7027, and for the strongest lines we obtained detailed maps. The results of the observation are given in Table 1 (in units of main beam temperature).
Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features. Today, long-read PacBio and chromatin conformation technologies are overcoming such obstacles. Here, based on the use of these technologies, we present a highly refined de novo P. knowlesi genome sequence of the Pk1(A+) clone. This sequence and annotation, referred to as the ‘MaHPIC Pk genome sequence’, includes manual annotation of the SICAvar gene family with 136 full-length members categorized as type I or II. This sequence provides a framework that will permit a better understanding of the SICAvar repertoire, selective pressures acting on this gene family and mechanisms of antigenic variation in this species and other pathogens.
Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi – macaque model systems and summarizing exciting new progress in this area of research.
In the face of shifting demographics and an increase in human longevity, it is important to examine carefully what is known about cognitive ageing, and to identify and promote possibly malleable lifestyle and health-related factors that might mitigate age-associated cognitive decline. The Lothian Birth Cohorts of 1921 (LBC1921, n = 550) and 1936 (LBC1936, n = 1091) are longitudinal studies of cognitive and brain ageing based in Scotland. Childhood IQ data are available for these participants, who were recruited in later life and then followed up regularly. This overview summarises some of the main LBC findings to date, illustrating the possible genetic and environmental contributions to cognitive function (level and change) and brain imaging biomarkers in later life. Key associations include genetic variation, health and fitness, psychosocial and lifestyle factors, and aspects of the brain's structure. It addresses some key methodological issues such as confounding by early-life intelligence and social factors and emphasises areas requiring further investigation. Overall, the findings that have emerged from the LBC studies highlight that there are multiple correlates of cognitive ability level in later life, many of which have small effects, that there are as yet few reliable predictors of cognitive change, and that not all of the correlates have independent additive associations. The concept of marginal gains, whereby there might be a cumulative effect of small incremental improvements across a wide range of lifestyle and health-related factors, may offer a useful way to think about and promote a multivariate recipe for healthy cognitive and brain ageing.
Introduction: Gun related injuries were last reported by the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) in 2005. Since that time, Canadian gun control is less stringent and non-powder guns are increasingly popular. We aim to describe trends in pediatric gun related injuries and deaths since 2005. Methods: This is a retrospective review of CHIRPP data. The dataset included pediatric (age 0-19 years) gun-related injuries and deaths reported by participating CHIRPP emergency departments (ED) from 2005-2013. Variables were tested using Fisher’s exact test and simple linear regression. Results: There were 421 records of gun-related injuries in the database. Three hundred and twenty-nine occurred from use of non-powder guns, 85 occurred from use of powder-guns, and in 7 cases the type of gun was not clear. The number of gun-related injuries per 100 000 ED visits remained stable from 2005-2013 with a male predominance (n=366, 87%). Most injuries resulted from non-powder guns and were unintentional. Injuries most often occurred in the context of recreation (n=181) and sport (n=51). One hundred fifty four eye injuries were reported, 98% of which were from a non-powder gun. Forty-six individuals required admission to hospital and 2 died in the ED. Nine of 10 intentional self-harm injuries were inflicted with a powder gun. Conclusion: This study describes the injuries and circumstances in which pediatric gun-related injury and death occur in Canada. Unintentional injuries caused by non-powder guns were most common. Though less fatal than powder guns, non-powder guns can still cause life-altering eye injuries. This evidence can inform injury prevention programs to target specific circumstances in which the pediatric population is most vulnerable.
Introduction: Point of care ultrasonography (PoCUS) is an established tool in the initial management of hypotensive patients in the emergency department (ED). It has been shown rule out certain shock etiologies, and improve diagnostic certainty, however evidence on benefit in the management of hypotensive patients is limited. We report the findings from our international multicenter RCT assessing the impact of a PoCUS protocol on diagnostic accuracy, as well as other key outcomes including mortality, which are reported elsewhere. Methods: Recruitment occurred at 4 North American and 3 Southern African sites. Screening at triage identified patients (SBP<100 mmHg or shock index >1) who were randomized to either PoCUS or control groups. Scans were performed by PoCUS-trained physicians. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. Final chart review was blinded to initial impressions and PoCUS findings. Categorical data was analyzed using Fishers two-tailed test. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. The perceived shock category changed more frequently in the PoCUS group 20/127 (15.7%) vs. control 7/125 (5.6%); RR 2.81 (95% CI 1.23 to 6.42; p=0.0134). There was no significant difference in change of diagnostic impression between groups PoCUS 39/123 (31.7%) vs control 34/124 (27.4%); RR 1.16 (95% CI 0.786 to 1.70; p=0.4879). There was no significant difference in the rate of correct category of shock between PoCUS (118/127; 93%) and control (113/122; 93%); RR 1.00 (95% CI 0.936 to 1.08; p=1.00), or for correct diagnosis; PoCUS 90/127 (70%) vs control 86/122 (70%); RR 0.987 (95% CI 0.671 to 1.45; p=1.00). Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We found that the use of PoCUS did change physicians’ perceived shock category. PoCUS did not improve diagnostic accuracy for category of shock or diagnosis.
Introduction: Point of care ultrasound (PoCUS) is an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). While PoCUS protocols have been shown to improve early diagnostic accuracy, there is little published evidence for any mortality benefit. We report the findings from our international multicenter randomized controlled trial, assessing the impact of a PoCUS protocol on survival and key clinical outcomes. Methods: Recruitment occurred at 7 centres in North America (4) and South Africa (3). Scans were performed by PoCUS-trained physicians. Screening at triage identified patients (SBP<100 or shock index>1), randomized to PoCUS or control (standard care and no PoCUS) groups. Demographics, clinical details and study findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. The primary outcome measure was 30-day/discharge mortality. Secondary outcome measures included diagnostic accuracy, changes in vital signs, acid-base status, and length of stay. Categorical data was analyzed using Fishers test, and continuous data by Student T test and multi-level log-regression testing. (GraphPad/SPSS) Final chart review was blinded to initial impressions and PoCUS findings. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no difference between groups for the primary outcome of mortality; PoCUS 32/129 (24.8%; 95% CI 14.3-35.3%) vs. Control 32/129 (24.8%; 95% CI 14.3-35.3%); RR 1.00 (95% CI 0.869 to 1.15; p=1.00). There were no differences in the secondary outcomes; ICU and total length of stay. Our sample size has a power of 0.80 (α:0.05) for a moderate effect size. Other secondary outcomes are reported separately. Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We did not find any mortality or length of stay benefits with the use of a PoCUS protocol, though a larger study is required to confirm these findings. While PoCUS may have diagnostic benefits, these may not translate into a survival benefit effect.
Introduction: Point of Care Ultrasound (PoCUS) protocols are commonly used to guide resuscitation for emergency department (ED) patients with undifferentiated non-traumatic hypotension. While PoCUS has been shown to improve early diagnosis, there is a minimal evidence for any outcome benefit. We completed an international multicenter randomized controlled trial (RCT) to assess the impact of a PoCUS protocol on key resuscitation markers in this group. We report diagnostic impact and mortality elsewhere. Methods: The SHoC-ED1 study compared the addition of PoCUS to standard care within the first hour in the treatment of adult patients presenting with undifferentiated hypotension (SBP<100 mmHg or a Shock Index >1.0) with a control group that did not receive PoCUS. Scans were performed by PoCUS-trained physicians. 4 North American, and 3 South African sites participated in the study. Resuscitation outcomes analyzed included volume of fluid administered in the ED, changes in shock index (SI), modified early warning score (MEWS), venous acid-base balance, and lactate, at one and four hours. Comparisons utilized a T-test as well as stratified binomial log-regression to assess for any significant improvement in resuscitation amount the outcomes. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no significant difference in mean total volume of fluid received between the control (1658 ml; 95%CI 1365-1950) and PoCUS groups (1609 ml; 1385-1832; p=0.79). Significant improvements were seen in SI, MEWS, lactate and bicarbonate with resuscitation in both the PoCUS and control groups, however there was no difference between groups. Conclusion: SHOC-ED1 is the first RCT to compare PoCUS to standard of care in hypotensive ED patients. No significant difference in fluid used, or markers of resuscitation was found when comparing the use of a PoCUS protocol to that of standard of care in the resuscitation of patients with undifferentiated hypotension.