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Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children <2 years, with a focus on the interactions between virus and age. Statistical interactions between age and respiratory syncytial virus (RSV), influenza, adenovirus (ADV) and rhinovirus on the risk of ALRI outcomes were investigated. Of 1780 hospitalisations, 228 (12.8%) were admitted to the intensive care unit (ICU). The median (range) length of stay (LOS) in hospital was 3 (1–27) days. An increase of 1 month of age was associated with a decreased risk of ICU admission (rate ratio (RR) 0.94; 95% confidence intervals (CI) 0.91–0.98) and with a decrease in LOS (RR 0.96; 95% CI 0.95–0.97). Associations between RSV, influenza, ADV positivity and ICU admission and LOS were significantly modified by age. Children <5 months old were at the highest risk from RSV-associated severe outcomes, while children >8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.
Introduction: Understanding the spatial distribution of opioid abuse at the local level may facilitate community intervention strategies. The purpose of this analysis was to apply spatial analytical methods to determine clustering of opioid-related emergency medical services (EMS) responses in the City of Calgary. Methods: Using opioid-related EMS responses in the City of Calgary between January 1st through October 31st, 2017, we estimated the dissemination area (DA) specific spatial randomness effects by incorporating the spatial autocorrelation using intrinsic Gaussian conditional autoregressive model and generalized linear mixed models (GLMM). Global spatial autocorrelation was evaluated by Morans I index. Both Getis-Ord Gi and the LISA function in Geoda were used to estimate the local spatial autocorrelation. Two models were applied: 1) Poisson regression with DA-specific non-spatial random effects; 2) Poisson regression with DA-specific G-side spatial random effects. A pseudolikelihood approach was used for model comparison. Two types of cluster analysis were used to identify the spatial clustering. Results: There were 1488 opioid-related EMS responses available for analysis. Of the responses, 74% of the individuals were males. The median age was 33 years ( IQR: 26-42 years) with 65% of individuals between 20 and 39 years, and 27% between 40 and 64 years. In 62% of EMS responses, poisoning/overdose was the chief complaint. The global Morans Index implied the presence of global spatial autocorrelation. Comparing the two models applied suggested that the spatial model provided a better fit for the adjusted opioid-related EMS response rate. Calgary Center and East were identified as hot spots by both types of cluster analysis. Conclusion: Spatial modeling has a better predictability to assess potential high risk areas and identify locations for community intervention strategies. The clusters identified in Calgarys Center and East may have implications for future response strategies.
Introduction: The GridlockED game is a serious game aimed at teaching junior learners about flow and organization in the emergency department(ED). With serious games, the mechanism of learning is thought to be via the gameplay experience. Objectives built into gameplay are aimed at teaching players about a specific concept; in this case, we hoped to teach players about interprofessional collaboration and basic mechanics that drive flow in the ED. However, before a player can be taught, he or she must be engaged and have a positive gameplay experience. From the GridlockED gameplay, we aim to explore how a players gameplay experience related to observed actions while playing the game, including participating in decision making and keeping the team organized. Methods: From April-August 2017, participants were invited to play 4 turns of a GridlockED game session. They were video recorded during gameplay. After playing the game, they were surveyed using the previously derived Game Experience Questionnaire (GEQ) to measure their gameplay experience. The videos were reviewed by two research team members (SH, EJ), tallying various observed game actions. We conducted Pearson correlation between players GEQ total score and their observed actions. Results: A total of 32 participants (13 attendings, 5 senior residents, 10 junior residents, and 4 nurses) played the game. The average total GEQ was 67.2/132 (SD=10.7), suggesting most players had a moderately good gameplay experience. The total GEQ score correlated with component subscores within the questionnaire. Overall observed activity correlated well with each observed action subtype. However, the GEQ total score did not correlate significantly with the total observed action (Pearsons r=0.18,p=0.32). GEQ total score was found to be moderately correlated to an observation that a player participated in determining strategy during gameplay (r=0.36,p=0.04). There was a moderate negative correlation between determining strategy during gameplay and teaching about the game (r=-0.37,p=0.04) or emergency medicine concepts (r=-0.47,p<0.01). Conclusion: The GEQ is internally consistent, but does not have a strong relationship to observed actions, suggesting that game experience does not necessarily correlate with observable actions. This suggests that players may be intellectually stimulated or engaged without necessarily completing any observable actions during gameplay.
Introduction: The management of patient flow in the emergency department (ED) is crucial for the practice of emergency medicine (EM). However, this skill is difficult to teach didactically and is learned implicitly in the latter half of residency training. To help expedite the learning process, we developed the GridlockED board game as an educational tool to simulate ED patient flow. By having junior medical trainees play this game, we believe that they will develop a greater understanding of patient flow and resource management in the ED. Additionally, since GridlockED is a cooperative game, players may also benefit by improving their communication and teamwork skills. Methods: GridlockED was developed over twenty months of iterative gameplay and review. Feedback from attending emergency physicians, residents, and medical students was integrated into the game through a Plan-Do-Study-Act (PDSA) model. Emergency medicine nurses, physicians and residents at McMaster University were recruited to play GridlockED. Each player completed a pre-survey to collect demographic data and to assess their prior experience with playing board games. All play sessions were recorded for data collection purposes. Following each game session, a member of the research team conducted an exit interview with the players to gather information about their play experience and the educational value of the game. A post-survey was also sent to each participant for further feedback. Results: Eighteen gameplay sessions were conducted from June to August 2017. A total of thirty-two participants played the game (13 emergency physicians, 15 residents, and four nurses). Overall responses to the post-gameplay survey showed that players endorsed GridlockED as a useful potential teaching tool (75%, n=24/32) and the majority felt that it had the potential to improve patient flow in the ED (56%, n=18/32). Most participants found that the game was easy to play (91%, n=27/29), and that the instructions were clear (87.5%, n=28/32). Respondents also felt that the game reflected real life scenarios (56%, n=18) and that cases reflected the types of patients that they saw in the ED (78%, n=25). Conclusion: Our results have shown an overall positive response to GridlockED, with most participants supporting it as both an engaging board game and potential teaching tool. We believe that future studies with larger sample sizes and medical students will further validate the use of serious games in medical education.
Introduction: With the increasing volume of medical literature published each year, it is difficult for clinicians to translate the latest research into practice. Awareness is the first step of knowledge translation and journals have begun using social media to increase the dissemination and awareness of their publications. Infographics can describe research findings visually, are shared broadly on social media, and may be a more effective way to convey information. We hypothesized that infographic abstracts would increase the social media dissemination and online readership of research articles relative to traditional abstracts. Methods: In this randomized controlled trial, 24 original research articles were chosen from the six issues of the Canadian Journal of Emergency Medicine (CJEM) published between July 2016 and May 2017 (4 articles per issue). Half were randomized to the infographic and control groups within each issue. Infographic articles were promoted using a visual infographic outlining the findings of the article. Control articles were promoted using a screen capture image of each articles abstract. Both were disseminated through the journals social media accounts (Twitter and Facebook) along with the link to the selected article. Infographics were also published on CanadiEM.org. Abstract views, full text views, and the change in Altmetric score were tracked for 30 days and compared between groups. Unpaired two-tailed t-tests were used to detect significant differences. Results: Abstract views (mean, SD) were significantly higher for infographic articles (378.9, 162.0) than control articles (175.5, 69.2, p<0.001). Mean Altmetric scores were significantly higher for infographic articles (26.4, 13.8) than control articles (3.4, 1.7, p<0.0001). There was no statistically significant difference in full-text views between infographic (49.7, 90.4) and control articles (25.3, 12.3). Conclusion: CJEM articles promoted on social media using infographics had higher abstract viewership and Altmetric scores than those promoted with traditional abstracts. Although there was no difference in full-text readership, our results suggest that infographic abstracts may have a role in increasing the dissemination of medical literature.
While previous work showed that the Centers for Disease Control and Prevention toolkit for carbapenem-resistant Enterobacteriaceae (CRE) can reduce spread regionally, these interventions are costly, and decisions makers want to know whether and when economic benefits occur.
Orange County, California
Using our Regional Healthcare Ecosystem Analyst (RHEA)-generated agent-based model of all inpatient healthcare facilities, we simulated the implementation of the CRE toolkit (active screening of interfacility transfers) in different ways and estimated their economic impacts under various circumstances.
Compared to routine control measures, screening generated cost savings by year 1 when hospitals implemented screening after identifying ≤20 CRE cases (saving $2,000–$9,000) and by year 7 if all hospitals implemented in a regional coordinated manner after 1 hospital identified a CRE case (hospital perspective). Cost savings was achieved only if hospitals independently screened after identifying 10 cases (year 1, third-party payer perspective). Cost savings was achieved by year 1 if hospitals independently screened after identifying 1 CRE case and by year 3 if all hospitals coordinated and screened after 1 hospital identified 1 case (societal perspective). After a few years, all strategies cost less and have positive health effects compared to routine control measures; most strategies generate a positive cost-benefit each year.
Active screening of interfacility transfers garnered cost savings in year 1 of implementation when hospitals acted independently and by year 3 if all hospitals collectively implemented the toolkit in a coordinated manner. Despite taking longer to manifest, coordinated regional control resulted in greater savings over time.
Litter size has a great impact on the profit of swine producers. Uterine development is an important determinant of reproduction efficiency and could hence affect litter size. Chinese Erhualian pig is one of the most prolific breeds in the world, even though large phenotypic variation in litter size was observed within Erhualian sows. To dissect the genetic basis of the phenotypic variation, we herein conducted genome-wide association studies for total number born and number born alive (NBA) of Erhualian sows. In total, one significant single nucleotide polymorphism (SNP) (P<1.78e−06) and 11 suggestive SNPs (P<3.57e−05) were identified on 10 chromosomes, confirming seven previously reported quantitative trait loci (QTL) and uncovering six QTL for litter size or uterus length. One locus on Sus scrofa chromosome (SSC) 13 (79.28 to 90.43 Mb) harbored a cluster of suggestive SNPs associated with multiparous NBA. The SNP (rs81447100) within this region was confirmed to be significantly (P<0.05) associated with litter size in Erhualian (n=313), Sutai (n=173) and Yorkshire (n=488) populations. Retinol binding protein 2 and retinol binding protein 1 functionally related to the development of uterus were located in a region of 2 Mb around rs81447100. Moreover, four genes related to embryo implantation and development were also detected around other significant SNPs. Taken together, our findings provide a potential marker (rs81447100) for the genetic improvement of litter size not only in Chinese Erhualian pigs but also in European commercial pig breeds like Yorkshire, and would facilitate the final identification of causative variant(s) underlying the effect of SSC13 QTL on litter size.
Characterisation of genetic diversity in a large number of European pig populations has been undertaken with EC support. The populations sampled included local (rare) breeds, national varieties of the major international breeds, commercial lines and the Chinese Meishan breed. A second phase of the project will sample a further 50 Chinese breeds. Neutral genetic markers (AFLP and microsatellites), with individual or bulk typing, were used and compared.
DNA from 59 European pig populations was extracted on samples of about 50 individuals per population. Individuals were typed for 50 microsatellites and for 148 AFLP bands. A subset of 25 populations was typed for 20 microsatellites on pools of DNA. Allele frequencies were estimated by direct allele counting for the co-dominant markers. Frequencies of AFLP negative alleles (absent bands) were obtained by taking the square root of absent band frequencies. Within-breed variability was summarised using standard statistics: expected and observed heterozygosity, mean observed and effective numbers of alleles, and F statistics. Between-breed diversity analysis was based on a bootstrapped Neighbor-Joining (NJ) tree derived from Reynolds distances (DR). The standard distance of Nei (DS) was also calculated.
Four complete platysiagid fish specimens are described from the Luoping Biota, Anisian (Middle Triassic), Yunnan Province, southwest China. They are small fishes with bones and scales covered with ganoine. All characters observed, such as nasals meeting in the midline, a keystone-like dermosphenotic, absence of post-rostral bone, two infraorbitals between dermosphenotic and jugal, large antorbital, and two postcleithra, suggest that the new materials belong to a single, new Platysiagum species, P. sinensis sp. nov. Three genera are ascribed to Platysiagidae: Platysiagum, Helmolepis and Caelatichthys. However, most specimens of the first two genera are imprints or fragmentary. The new, well-preserved specimens from the Luoping Biota provide more detailed anatomical information than before, and thus help amend the concept of the Platysiagidae. The Family Platysiagidae was previously classed in the Perleidiformes. Phylogenetic analysis indicates that the Platysiagidae is a member of basal Neopterygii, and its origin seems to predate that of Perleidiformes. Moreover, platysiagid fishes are known from the Middle Triassic of the western Tethys region. The newly found specimens of platysiagids from Luoping provide additional evidence that both eastern and western sides of the Tethys Ocean were biogeographically more connected than previously thought.
A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders.
In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18–100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction.
An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6–17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both.
CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.
TAOS II is a next-generation occultation survey with the goal of measuring the size distribution of the small end of the Kuiper Belt (objects with diameters 0.5–30 km). Such objects have magnitudes r > 30, and are thus undetectable by direct imaging. The project will operate three telescopes at San Pedro Mártir Observatory in Baja California, México. Each telescope will be equipped with a custom-built camera comprised of a focal-plane array of CMOS imagers. The cameras will be capable of reading out image data from 10,000 stars at a cadence of 20 Hz. The telescopes will monitor the same set of stars simultaneously to search for coincident occultation detections, thus minimising the false-positive rate. This talk described the project, and reported on the progress of the development of the survey infrastructure.
In rock engineering, evaluating the post-peak strength and deformation of rock is necessary. To explore the elasto-plastic behavior of sandstone in the post-peak stage, a series of strain-controlled triaxial tests were conducted under different confining pressures. According to the post-peak characteristics, a constitutive model based on nonlinear elasticity and generalized plasticity is proposed. This proposed model is characterized by the following features: (1) Nonlinear elasticity is observed under hydrostatic and shear loading; (2) the associated flow rule is followed; (3) substantial plastic deformation occurs during shear loading; and (4) post-peak softening behavior is accurately predicted. This model requires twelve material parameters, three for elasticity and nine for plasticity. The proposed model was validated by comparing the triaxial test results of Mushan sandstone at different hydrostatic pressures under dry and saturated conditions. In addition, the model is versatile; it can simulate the deformational behavior of two other sandstones. In summary, the proposed model can reasonably predict the complete stress–strain curve of sandstone.
Scholars continue to argue about whether bipolar disorders (BD) and unipolar depression (UD) are distinguishable with regard to neurocognitive function. This study aims to explore the cognitive profiles of UD and BD by applying the Brief Assessment of Cognition in Affective Disorders (BAC-A) for neuropsychological assessment.
This cross-sectional study included 68 patients with UD, 67 patients with BD, and 135 healthy control subjects. We evaluated the participants’ cognitive functions at euthymic status using the BAC-A, which is made up of six traditional cognitive subtests and the Affective Processing Test. We then used a discriminant function analysis (DFA) to determine whether cognitive performance can be used to distinguish these participant groups.
Healthy controls demonstrated better performance in all subtests of the BAC-A than both the UD and BD patients, with the exception of delayed recognition of affective interference. Compared with the BD group, the UD group exhibited better performance in working memory and emotion inhibition. Furthermore, using all BAC-A indexes, a total of 70% of participants could be correctly classified using a DFA model, and the discriminating validity between UD and BD was superior to using either the traditional cognitive domains or the Affective Processing Test alone.
We have found that UD patients may exhibit an intermediate performance between healthy subjects and BD patients in working memory and emotional inhibition tests. The BAC-A can potentially assist in differentiating BD patients from UD patients at euthymic status in clinical settings.
We have examined the global properties of 250 galaxies and galaxy pairs observed as part of the Five College Radio Astronomy Observatory (FCRAO) Extragalactic CO Survey with respect to bar type and arm type, and we have compared the results with the global properties of the same galaxies as a function of morphological type. The bar types of the galaxies were taken from RC2, and the arm types for 48% of the sample were taken from Elmegreen and Elmegreen (1987). We find the following:
1) There is little dependence of the star formation efficiency, as measured by the global FIR luminosity to molecular gas mass ratio, on bar type. Similarly, we find no obvious correlation between the global ratio of molecular to atomic gas mass and the bar type.
2) Variations of up to a factor of 6 are seen in the mean star formation efficiency with arm type, where flocculent galaxies appear to have slightly higher global star formation efficiencies than spirals with clearly delineated arms. Variations in the mean molecular to atomic gas mass ratio of a factor of 5 are seen as a function of arm type, but there is no apparent trend from flocculent to grand design spirals.
3) The decrease of a factor of 20 in the molecular to atomic gas mass ratio observed as a function of morphological type (Young and Knezek 1989) is more pronounced than the same ratio as a function of bar or arm type.
A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities.
Contact precautions are a traditional strategy to prevent transmission of methicillin-resistant Staphylococcus aureus (MRSA). Chlorhexidine bathing is increasingly used to decrease MRSA burden and transmission in intensive care units (ICUs). We sought to evaluate a hospital policy change from routine contact precautions for MRSA compared with universal chlorhexidine bathing, without contact precautions. We measured new MRSA acquisition in ICU patients and surveyed for MRSA environmental contamination in common areas and non-MRSA patient rooms before and after the policy change. During the baseline and chlorhexidine bathing periods, the number of patients (453 vs. 417), ICU days (1999 vs. 1703) and MRSA days/1000 ICU days (109 vs. 102) were similar. MRSA acquisition (2/453 vs. 2/457, P = 0·93) and environmental MRSA contamination (9/474 vs. 7/500, P = 0·53) were not significantly different between time periods. There were 58% fewer contact precaution days in the ICU during the chlorhexidine period (241/1993 vs. 102/1730, P < 0·01). We found no evidence that discontinuation of contact precautions for patients with MRSA in conjunction with adoption of daily chlorhexidine bathing in ICUs is associated with increased MRSA acquisition among ICU patients or increased MRSA contamination of ICU fomites. Although underpowered, our findings suggest this strategy, which has the potential to reduce costs and improve patient safety, should be assessed in similar but larger studies.