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High-intensity laser–plasma interactions produce a wide array of energetic particles and beams with promising applications. Unfortunately, the high repetition rate and high average power requirements for many applications are not satisfied by the lasers, optics, targets, and diagnostics currently employed. Here, we aim to address the need for high-repetition-rate targets and optics through the use of liquids. A novel nozzle assembly is used to generate high-velocity, laminar-flowing liquid microjets which are compatible with a low-vacuum environment, generate little to no debris, and exhibit precise positional and dimensional tolerances. Jets, droplets, submicron-thick sheets, and other exotic configurations are characterized with pump–probe shadowgraphy to evaluate their use as targets. To demonstrate a high-repetition-rate, consumable, liquid optical element, we present a plasma mirror created by a submicron-thick liquid sheet. This plasma mirror provides etalon-like anti-reflection properties in the low field of 0.1% and high reflectivity as a plasma, 69%, at a repetition rate of 1 kHz. Practical considerations of fluid compatibility, in-vacuum operation, and estimates of maximum repetition rate are addressed. The targets and optics presented here demonstrate a potential technique for enabling the operation of laser–plasma interactions at high repetition rates.
Introduction: 9-1-1 telecommunicators receive minimal education on agonal breathing, often resulting in unrecognized out-of-hospital cardiac arrest (OHCA). We successfully piloted an educational intervention that significantly improved telecommunicators’ OHCA recognition and bystander CPR rates in Ottawa. We sought to better understand the operations of Canadian 9-1-1 communications centers (CC) in preparation for a multi-centre study of this intervention. Methods: We conducted a National survey of all Canadian CCs. Survey domains included information on organizational structure, dispatch system used, education curriculum, and performance monitoring. It was peer-reviewed, translated in French, pilot-tested, and distributed electronically using a modified Dillman method. We designated respondents in each CC before distribution and used targeted follow-up and small incentives to increase response rate. Respondents also described functioning of neighboring CCs if known. Results: We received information from 51/51 provincial and 1/25 territorial CCs, representing 99.7% of the Canadian population. CCs largely utilize the Medical Dispatch Priority System (MPDS) platform (93%), many are Province/Ministry regulated (50%) and most require a High School diploma as minimum entry level education (78%). Telecommunicators receive initial in-class training (median 1.3 months, IQR 0.3-1.9; range 0.1-2.2), often followed by a preceptorship (84.4%) (median 1.0 months, IQR 0.7-1.7; range 0.4-6.0). Educational curriculum includes information on agonal breathing in 41% of CC, without audio examples in 34%. Among responding CCs, over 39,000 suspected OHCA 9-1-1 calls are received annually. Few CCs maintain local performance statistics on OHCA recognition (25%), bystander CPR rates (25%) or survival rates (50%). Most (97%) expressed interest in future research collaborations. Conclusion: Most Canadian telecommunicators receive no or minimal education in recognizing agonal breathing. Further training and improved OHCA monitoring may assist recognition and enhance outcomes.
Emergency physicians are using bolus-dose vasopressors to temporize hypotensive patients until more definitive blood pressure support can be established. Despite a paucity of clinical outcome data, emergency department applications are expanding into the prehospital setting. This series presents two cases of field expedient vasopressor use by emergency medicine providers for preflight stabilization during aeromedical evacuation to a hospital ship as part of the United States Navy disaster response in Puerto Rico. A critical approach and review of the literature are discussed.
Two critically ill patients were managed in an austere environment as a result of the devastation from Hurricane Maria (Yabucoa, Puerto Rico; 2017). They both exhibited signs of respiratory distress, hemodynamic instability, and distributive shock requiring definitive airway management and hemodynamic support prior to aeromedical evacuation.
The novel use of field expedient vasopressors prior to induction for rapid sequence intubation was successfully and safely employed in both cases. Both patients had multiple risk factors for peri-induction cardiac arrest given their presenting hemodynamics. Despite their illness severity, both patients were induced, transported, and ultimately admitted to the intensive care unit (ICU) in stable condition following administration of the field expedient vasopressors.
Field expedient vasopressors were safely and effectively employed in an austere field environment during a disaster response. This case series contributes to the growing body of literature of safe bolus-dose vasopressor use by emergency physicians to temporize hypotensive patients in resource-constrained situations.
HardwickJM, MurnanSD, Morrison-PonceDP, DevlinJJ. Field Expedient Vasopressors During Aeromedical Evacuation: A Case Series from the Puerto Rico Disaster Response. Prehosp Disaster Med. 2018;33(6):668–672.
The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH MB using immunohistochemical analysis as well as transcriptome data across 763 primary tumors. Characterization of CD271+ and CD271- cells by RNA sequencing revealed that these two subpopulations are molecularly distinct, co-existing cellular subsets both in vitro and in vivo. MAPK/ERK signaling is upregulated in the CD271+ population and inhibiting this pathway reduced CD271 levels, stem/progenitor cell proliferation and cell survival as well as cell migration in vitro. Importantly, the MEK inhibitor selumetinib extends survival and reduces CD271 levels in vivo. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH MB tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH MB cells.
Hamiltonian extended magnetohydrodynamics (XMHD) is restricted to respect helical symmetry by reducing the Poisson bracket for the three-dimensional dynamics to a helically symmetric one, as an extension of the previous study for translationally symmetric XMHD (Kaltsas et al., Phys. Plasmas, vol. 24, 2017, 092504). Four families of Casimir invariants are obtained directly from the symmetric Poisson bracket and they are used to construct Energy–Casimir variational principles for deriving generalized XMHD equilibrium equations with arbitrary macroscopic flows. The system is then cast into the form of Grad–Shafranov–Bernoulli equilibrium equations. The axisymmetric and the translationally symmetric formulations can be retrieved as geometric reductions of the helically symmetric one. As special cases, the derivation of the corresponding equilibrium equations for incompressible plasmas is discussed and the helically symmetric equilibrium equations for the Hall MHD system are obtained upon neglecting electron inertia. An example of an incompressible double-Beltrami equilibrium is presented in connection with a magnetic configuration having non-planar helical magnetic axis.
Introduction: Medical journals are an essential venue for knowledge translation. Skilled reviewers and editors are required to ensure quality standards in research publications and yet postgraduate programs rarely include this training in their curricula. Imparting appropriate skills and developing capacity in journalship has thus proved challenging. The Canadian Journal of Emergency Medicine (CJEM) is the national journal for Emergency Medicine (EM) in Canada. The CJEM editorial board recently decided to provide longitudinal mentorship for junior academic faculty members and trainees through an editorial internship. The internship had three goals for participants: (1) introduce and develop the responsibilities and skills of a good editor; (2) enhance a career in academic EM; and, (3) galvanize future participation as a reviewer or editor in scientific publications. Methods: The senior editorial board of CJEM and the inaugural intern developed a one-year Editorial Internship that was launched in June 2017. The curricular framework was designed by current and prior CJEM senior editors from four Canadian universities, and was informed by similar programs in the United States. The curriculum was refined iteratively based on feedback and discussion between the senior editors and intern. The internship was designed for a single individual in the Canadian EM community, including residents, pediatric fellows and practicing emergency physicians. Results: To develop the responsibilities and skills of being a good editor, the intern performed six mentored reviews of manuscripts either under current review at CJEM or previous submissions identified as difficult peer review decisions. In addition, the intern learned about CJEM values and norms by participating in monthly videoconference meetings and quarterly editorial board meetings. To enhance an academic career, the intern was assigned two writing projects under the guidance of senior editors for publication in CJEM, and completed an online critical appraisal course. Conclusion: The inaugural editorial intern gained experience as an editor and produced scholarly work. We feel the internship met its first two goals, and CJEM has committed to continue the internship annually. The ultimate determination of whether the internship achieved its third goal will only be known after longitudinal tracking of participants career involvement in academic publishing and editing.
With increasing Holsteinisation of the dairy herd, the milk production potential of dairy cows has increased substantially over the past two decades. This development presents new challenges for managing dairy cows during grazing, particularly where the objective is to maximise the proportion of energy in the diet derived from forage (Mayne and Peyraud, 1996). The objective of the current study was to explore forage supplementation strategies to maintain high milk yields from grass and forage in dairy cows during the grazing season. A second objective of the study was to examine the effect of concentrates of contrasting degradability on milk production.
An outbreak of mumps within a student population in Scotland was investigated to assess the effect of previous vaccination on infection and clinical presentation, and any genotypic variation. Of the 341 cases, 79% were aged 18–24. Vaccination status was available for 278 cases of whom 84% had received at least one dose of mumps containing vaccine and 62% had received two. The complication rate was 5·3% (mainly orchitis), and 1·2% were admitted to hospital. Genetic sequencing of mumps virus isolated from cases across Scotland classified 97% of the samples as genotype G. Two distinct clusters of genotype G were identified, one circulating before the outbreak and the other thereafter, suggesting the virus that caused this outbreak was genetically different from the previously circulating virus. Whilst the poor vaccine effectiveness we found may be due to waning immunity over time, a contributing factor may be that the current mumps vaccine is less effective against some genotypes. Although the general benefits of the measles–mumps–rubella (MMR) vaccine should continue to be promoted, there may be value in reassessing the UK vaccination schedule and the current mumps component of the MMR vaccine.
Complications related to methamphetamine use and abuse are common presentations seen in the emergency department. Standard management focuses on addressing the central nervous system and cardiovascular effects with the use of sedation and hemodynamic support. We describe a case report of a patient with methamphetamine toxicity and subsequent severe cardiomyopathy refractory to conventional management that responded to cardiovascular support with extracorporeal membrane oxygenation therapy (ECMO). A 22-year-old female was admitted in severe cardiogenic shock following intravenous administration of methamphetamine and oral fentanyl use. Despite aggressive treatment with benzodiazepines, intravenous fluids, vasopressors, vasodilators, antibiotics and inotropes, the patient’s clinical status deteriorated, and she suffered a cardiac arrest. The patient was successfully resuscitated, and following the return of spontaneous circulation, ECMO was initiated. After 82 hours the patient was successfully weaned from ECMO with the recovery of her left ventricular function and no neurologic sequelae. The patient developed leg ischemia requiring embolectomy and open repair as a complication of ECMO cannulation. In our case, ECMO was used successfully in treating severe cardiac dysfunction from acute methamphetamine-induced cardiomyopathy and was used as a bridge to recovery. The complications seen in this patient emphasize the potential risks associated with this intervention and highlight the need for careful patient selection.
Cardiometabolic diseases exhibit changes in lipid biology, which is important as lipids have critical roles in membrane architecture, signalling, hormone synthesis, homoeostasis and metabolism. However, Developmental Origins of Health and Disease studies of cardiometabolic disease rarely include analysis of lipids. This short review highlights some examples of lipid pathology and then explores the technology available for analysing lipids, focussing on the need to develop imaging modalities for intracellular lipids. Analytical methods for studying interactions between the complex endocrine and intracellular signalling pathways that regulate lipid metabolism have been critical in expanding our understanding of how cardiometabolic diseases develop in association with obesity and dietary factors. Biochemical methods can be used to generate detailed lipid profiles to establish links between lifestyle factors and metabolic signalling pathways and determine how changes in specific lipid subtypes in plasma and homogenized tissue are associated with disease progression. New imaging modalities enable the specific visualization of intracellular lipid traffic and distribution in situ. These techniques provide a dynamic picture of the interactions between lipid storage, mobilization and signalling, which operate during normal cell function and are altered in many important diseases. The development of methods for imaging intracellular lipids can provide a dynamic real-time picture of how lipids are involved in complex signalling and other cell biology pathways; and how they ultimately regulate metabolic function/homoeostasis during early development. Some imaging modalities have the potential to be adapted for in vivo applications, and may enable the direct visualization of progression of pathogenesis of cardiometabolic disease after poor growth in early life.
To assess the impact of farm management on herd fertility, a survey of 105 beef farms in Northern Ireland was conducted to establish the relationship between management variables and fertility. Each herd's average calving interval (CI) and the proportion of cows with a CI > 450 days (extended calving interval, ECI) was calculated to establish herd fertility. The relationship between each response variable (CI and proportion ECI) and each explanatory variable (respondents’ answers to questionnaire) was examined using univariate linear regression analyses. All response variables found to be associated with the explanatory variables were modelled against each group in turn using a fully automated multivariate stepwise regression algorithm employing the method of forward selection with backward elimination. The optimum 365-day CI and a proportion of 0 cows per hundred calved ECI targets were not widely attained in the current study. The distribution of CI and proportion ECI in the current study suggests more realistic targets would be a 379-day CI and 5 cows per hundred calved with ECI in commercial beef breeding herds. Six management factors were found to be associated with herd fertility: herd vaccination, bull selection, fertility management, breeding female management, perception of extension service (rural education provided by the government) and record keeping. It was found that respondents who vaccinated cows had a reduction of 5 cows per hundred calved in the proportion of cows with ECI, and as the number of vaccines administered to a cow increased, the CI decreased. Regular vaccination of breeding bulls was associated with a 9-day reduction in CI. Bull selection strategy had several associations with herd fertility; most notable was that respondents who used visual selection rather than estimated breeding values (EBVs) to select bulls were found to have a 15-day longer CI and 7 cows per hundred calved higher proportion of cows with ECI. For each 0·01 increase in the proportion of cows served by artificial insemination, CI increased by 0·16 days. Respondents who rated their beef breeding herd fertility as ‘very good’ had lower ECI and CI than those who rated beef breeding herd fertility as poor or satisfactory. Condition scoring of cows at weaning lowered ECI by 5 cows per hundred calved. Those who perceived the extension service to be very useful had the lowest CI and lowest ECI. Respondents who did not keep a record of CI to assess herd fertility had an 11-day longer CI and 6 cows per hundred calved higher proportion ECI than those who did not. In conclusion, the survey found a number of important variables linked to improved fertility including selecting sires based on EBVs and using a robust vaccination programme.
Epidemiology formed the basis of ‘the Barker hypothesis’, the concept of ‘developmental programming’ and today’s discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.
Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia.
This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 (clinicaltrials.gov identifier: NCT02176044). Twenty patients with schizophrenia aged 18–60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 μg/kg per min for 4 h) or placebo and were re-assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later.
SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo.
Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms.
A specific feature of three-dimensional bluff body wakes, flow bistability, is a subject of particular recent interest. This feature consists of a random flipping of the wake between two asymmetric configurations and is believed to contribute to the pressure drag of many bluff bodies. In this study we apply the modelling approach recently suggested for axisymmetric bodies by Rigas et al. (J. Fluid Mech., vol. 778, 2015, R2) to the reflectional symmetry-breaking modes of a rectilinear bluff body wake. We demonstrate the validity of the model and its Reynolds number independence through time-resolved base pressure measurements of the natural wake. Further, oscillating flaps are used to investigate the dynamics and time scales of the instability associated with the flipping process, demonstrating that they are largely independent of Reynolds number. The modelling approach is then used to design a feedback controller that uses the flaps to suppress the symmetry-breaking modes. The controller is successful, leading to a suppression of the bistability of the wake, with concomitant reductions in both lateral and streamwise forces. Importantly, the controller is found to be efficient, the actuator requiring only 24 % of the aerodynamic power saving. The controller therefore provides a key demonstration of efficient feedback control used to reduce the drag of a high-Reynolds-number three-dimensional bluff body. Furthermore, the results suggest that suppression of large-scale structures is a fundamentally efficient approach for bluff body drag reduction.
We sought to conduct a major objective of the CAEP Academic Section, an environmental scan of the academic emergency medicine programs across the 17 Canadian medical schools.
We developed an 84-question questionnaire, which was distributed to academic heads. The responses were validated by phone by the lead author to ensure that the questions were answered completely and consistently. Details of pediatric emergency medicine units were excluded from the scan.
At eight of 17 universities, emergency medicine has full departmental status and at two it has no official academic status. Canadian academic emergency medicine is practiced at 46 major teaching hospitals and 13 specialized pediatric hospitals. Another 69 Canadian hospital EDs regularly take clinical clerks and emergency medicine residents. There are 31 full professors of emergency medicine in Canada. Teaching programs are strong with clerkships offered at 16/17 universities, CCFP(EM) programs at 17/17, and RCPSC residency programs at 14/17. Fourteen sites have at least one physician with a Master’s degree in education. There are 55 clinical researchers with salary support at 13 universities. Sixteen sites have published peer-reviewed papers in the past five years, ranging from four to 235 per site. Annual budgets range from $200,000 to $5,900,000.
This comprehensive review of academic activities in emergency medicine across Canada identifies areas of strengths as well as opportunities for improvement. CAEP and the Academic Section hope we can ultimately improve ED patient care by sharing best academic practices and becoming better teachers, educators, and researchers.
The Medium-l Program of the Michelson Doppler Imager (MDI) instrument on board SOHO provides continuous observations of oscillation modes of angular degree, l, from 0 to ∼ 300. The initial results show that the noise in the Medium-l oscillation power spectrum is substantially lower than in ground-based measurements. This enables us to detect lower amplitude modes and, thus, to extend the range of measured mode frequencies. The MDI observations also reveal the asymmetry of oscillation spectral lines. The line asymmetries agree with the theory of mode excitation by acoustic sources localized in the upper convective boundary layer. The sound-speed profile inferred from the mean frequencies gives evidence for a sharp variation at the edge of the energy-generating core. In a thin layer just beneath the convection zone, helium appears to be less abundant than predicted by theory. Inverting the multiplet frequency splittings from MDI, we detect significant rotational shear in this thin layer.
Mathematical models are important tools to estimate nutritional requirements and animal growth. Very few calf models generated from other countries with different feeding programs, environment and production systems have been evaluated. The objective of this paper is to evaluate two calf models: (i) the National Research Council (NRC) in 2001 and (ii) the updates published by Van Amburgh and Drackley in 2005 and inputted into Agricultural Modeling and Training Systems (AMTS, version 3.5.8). Data from 16 previous studies involving 51 diets for dairy calves under tropical conditions (n=485 calves, initial BW 37.5±4.35 kg and weaning weight of 62.0±10.16 kg) were used. The calves were fed with whole milk, milk replacer or fermented colostrum, plus starter (20.9±1.78% of CP). The accuracy of the average daily gain (ADG) prediction was evaluated by mean bias, mean square prediction error (MSPE), concordance correlation coefficient, bias correction factor (Cb), and regression between the observed and predicted values. The ADG observed from birth to weaning was 0.452±0.121 kg/day. Calves fed with whole milk had greater ADG compared with calves fed milk replacer (0.477 v. 0.379 kg/day) during the milk-feeding period. When all data were pooled (n=51 diets), predictions had a mean bias of −0.019 and 0.068 kg/day for energy-allowable gain using NRC and AMTS models, respectively. The regression equation between observed and predicted values obtained from energy of diets showed an intercept different from zero (P<0.0001) and slope that differed from unity (P<0.0001). In a second evaluation, when calves were fed only milk replacer, the energy-allowable gain from AMTS showed the lowest mean bias (0.008 kg/day) and 82.1% of the MSPE value originated from random errors. The lowest MSPE, the higher Cb value and no significant slope bias (P>0.05) indicate that the AMTS growth model resulted in accurate predictions for calves fed with milk replacer. However, within these latter two approaches, the goodness of fit (R2) was low, representing low precision. The weight gain estimated by the energy available from the diet was overestimated by 19 g/day when calculated by the NRC and underestimated by 68 g/day when calculated by AMTS. The reasons for this discrepancy need to be understood, for only then new models could be developed and parameterized to estimate animal performance in tropical conditions more accurately and precisely.