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Introduction: Emergency department (ED) crowding is a major problem across Canada. We studied the ability of artificial intelligence methods to improve patient flow through the ED by predicting patient disposition using information available at triage and shortly after patients’ arrival in the ED. Methods: This retrospective study included all visits to an urban, academic, adult ED between May 2012 and June 2019. For each visit, 489 variables were extracted including triage data that had been collected for use in the Canadian Triage Assessment Scale (CTAS) and information regarding laboratory tests, radiological tests, consultations and admissions. A training set consisting of all visits from April 2012 up to December 2018 was used to train 5 classes of machine learning models to predict admission to the hospital from the ED. The models were trained to predict admission at the time of the patient's arrival in the ED and every 30 minutes after arrival until 6 hours into their ED stay. The performance of models was compared using the area under the ROC curve (AUC) on a test set consisting of all visits from January 2019 to June 2019. Results: The study included 536,332 visits and the admission rate was 15.0%. Gradient boosting models generally outperformed other machine learning models. A gradient boosting model using all available data at 2 hours after patient arrival in the ED yielded a test set AUC 0.92 [95% CI 0.91-0.93], while a model using only data available at triage yielded an AUC 0.90 [95% CI 0.89-0.91]. The quality of predictions generally improved as predictions were made later in the patient's ED stay leading to an AUC 0.95 [95% CI 0.93-0.96] at 6 hours after arrival. A gradient boosting model with 20 variables available at 2 hours after patient arrival in the ED yielded an AUC 0.91 [95% CI 0.89-0.93]. A gradient boosting model that makes predictions at 2 hours after arrival in ED using only variables that are available at all EDs in the province of Quebec yielded an AUC 0.91 [95% 0.89-0.92]. Conclusion: Machine learning can predict admission to a hospital from the ED using variables that area collected as part of routine ED care. Machine learning tools may potentially be used to help ED physicians to make faster and more appropriate disposition decisions, to decrease unnecessary testing and alleviate ED crowding.
Imprinting, characterized by unequal expression of the offspring's genes in a parent-of-origin dependent manner, has been functionally implicated in brain development and in psychiatric disorders. In this study, unambiguous distortion in paternal but not maternal transmission of the disease-associated single-nucleotide polymorphism (SNP) rs6556547 (T/G) clearly indicated the presence of parent-of-origin effect (POE) in the GABAA receptor β2 subunit gene (GABRB2). ‘Flipping’ of allelic mRNA expression in heterozygotes of SNP rs2229944 (C/T) and the observed two-tiered distribution of mRNA expression levels in heterozygotes of the disease-associated SNP rs1816071 (G/A) furnished important support for the occurrence of imprinting at GABRB2. Imprinting in effect introduced heterozygotes from different parents-of-origin endowed with dissimilar mRNA expression capabilities. The deficit of upper-tiered expressions accounted for the lowered mRNA expression levels in the schizophrenic heterozygotes. This pointed to the necessity of differentiating between two kinds of heterozygotes of different parental origins in disease association studies on GABRB2. Bisulfite sequencing revealed hypermethylation in the neighborhood of SNP rs1816071, and methylation differences between controls and schizophrenia patients. Notably, allele-specific methylation was observed at the disease-associated SNPs rs6556547 and rs1816071. These findings raised the possibility that CpG methylation status of these sites could have an impact on the expression of GABRB2 and the risk of schizophrenia. Furthermore, the occurrence of imprinting and allele-specific methylation in the schizophrenia candidate gene GABRB2 was compatible with the epigenetic hypothesis for schizophrenia pathophysiology, thereby calling for the need to explore the role of epigenetic factors in mediating susceptibility to schizophrenia.
Previously the GABA(A) receptor beta-2 subunit gene GABRB2 was found to be associated with schizophrenia (SCZ). for SNPs and haplotypes in GRBRB2, the associations with bipolar disorder (BPD), the functional consequences on GABRB2 expression and their relationship to demographic and clinical characteristics in BPD and SCZ remain to be elucidated.
Case-control analysis was performed for association study of GABRB2 with BPD, and its mRNA expression in postmortem BPD brains was examined using quantitative real-time PCR. Quantitative trait analysis was subsequently employed to assess the covariate effects of demographic and clinical characteristics on genotypic correlation of GABRB2 expression in SCZ and BPD.
Significant association of GABRB2 with BPD and reduction in GABRB2 mRNA expression in BPD brains were observed in the present study. Duration of illness (DOI) was found to be a significant covariate for the correlation of the disease-associated SNPs rs1816071, rs1816072 and rs187269 with GABRB2 expression in both SCZ and BPD. for individuals with homozygous major genotypes of these SNPs, while GABRB2 expression increased with age in the controls, it decreased with DOI and age in SCZ, and with DOI in BPD. with age of onset as covariate, these three SNPs were significantly correlated with antipsychotic dosage in SCZ.
These results have thus revealed correlations of GABRB2 SNPs and expression not only with the occurrence of SCZ and BPD, but also with the clinical characteristics of patients, therefore providing support for a shared etiological role played by the gene in both diseases.
Insecticide resistance is an increasing problem in citrus production. The Asian citrus psyllid, Diaphornia citri Kuwayama, is recognized as one of the most important citrus pests worldwide and it has developed resistance in areas where insecticides have been overused. The development of insecticide resistance is often associated with fitness costs that only become apparent in the absence of selection pressure. Here, the fitness costs associated with resistance to thiamethoxam and imidacloprid were investigated in three agricultural populations of D. citri as compared with susceptible laboratory colonies. Results showed that all field populations had greater resistance than laboratory susceptible colonies. For both thiamethoxam and imidacloprid, a Candidatus Liberibacter asiaticus-positive (CLas+) colony was more susceptible than the CLas− colony. Resistance ratios ranged from 7.65–16.11 for imidacloprid and 26.79–49.09 for thiamethoxam in field populations as compared with a susceptible, CLas− laboratory strain. Among three resistant field populations, a significantly reduced net reproductive rate and finite rate of population increase were observed in a population from Lake Wales, FL as compared to both susceptible strains. The fecundity of field populations from Lake Wales, FL was statistically lower than both laboratory susceptible populations. Certain changes in morphological characteristics were observed among resistant, as compared, with susceptible strains. Our data suggest fitness disadvantages associated with insecticide resistance in D. citri are related to both development and reproduction. The lower fitness of D. citri populations that exhibit resistance to neonicotinoid insecticides should promote recovery of sensitivity when those populations are no longer exposed to thiamethoxam and/or imidacloprid in the field. The results are congruent with a strategy of insecticide rotation for resistance management.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
In this paper, a novel continuous fiber reinforced piezoelectric composite (CFRPC) actuator is proposed to improve the stability and reliability of piezoelectric actuators. A piezoelectric driving structure composed of a cantilever beam and the CFRPC actuator is utilized to research the actuation performance of the CFRPC actuator. The expression of the equivalent moment for the CFRPC actuator is obtained using the equivalent load method and electro-mechanical coupling theory. Based on Euler-Bernoulli beam theory, the analytical expression of the deflection for the cantilever beam is derived. The accuracy of the obtained analytical expressions is demonstrated by finite element simulation as well as published experimental results. The actuation performance of the CFRPC actuator is investigated through the analytical expressions of the equivalent moment and deflection. The results show that the key parameters such as driving voltage, fiber volume fraction, cantilever beam height, actuator height, actuator length and actuator position have great influence on the actuation performance of the CFRPC actuator. The CFRPC actuator has good mechanical and electrical properties, and has a wide application prospect in the field of structural shape control.
This paper focus on the mechanical and martensitic transformation behaviors of axially functionally graded shape memory alloy (AFG SMA) beams. It is taken into consideration that material properties, such as austenitic elastic modulus, martensitic elastic modulus, critical transformation stresses and maximum transformation strain vary continuously along the longitudinal direction. According to the simplified linear SMA constitutive equations and Bernoulli-Euler beam theory, the formulations of stress, strain, martensitic volume fraction and governing equations of the deflection, height and length of transformed layers are derived. Employing the Galerkin’s weighted residual method, the governing differential equation of the deflection is solved. As an example, the bending behaviors of an AFG SMA cantilever beam subjected to an end concentrated load are numerically analyzed using the developed model. Results show that the mechanical and martensitic transformation behaviors of the AFG SMA beam are complex after the martensitic transformation of SMA occurs. The influences of FG parameter on the mechanical behaviors and geometrical shape of transformed regions are obvious, and should be considered in the design and analysis of AFG SMA beams in the related regions.
Polarimetric studies of pulsars at low radio frequencies provide important observational insights into the pulsar emission mechanism and beam models, and probe the properties of the magneto-ionic interstellar medium (ISM). Aperture arrays are the main form of next-generation low-frequency telescopes, including the Murchison Widefield Array (MWA). These require a distinctly different approach to data processing (e.g. calibration and beamforming) compared to traditional dish antennas. As the second paper of this series, we present a verification of the MWA’s pulsar polarimetry capability, using two bright southern pulsars, PSRs J0742–2822 and J1752–2806. Our observations simultaneously cover multiple frequencies (76–313 MHz) and were taken at multiple zenith angles (ZA) during a single night for each pulsar. We show that the MWA can be reliably calibrated for ZA ≲45° and frequencies ≲270 MHz. We present the polarimetric profiles for PSRs J0742–2822 and J1752–2806 at frequencies lower than 300 MHz for the first time, along with an analysis of the linear polarisation degree and pulse profile evolution with frequency. For PSR J0742–2822, the measured degree of linear polarisation shows a rapid decrease at low frequencies, in contrast with the generally expected trend, which can be attributed to depolarisation effects from small-scale, turbulent, magneto-ionic ISM components. This effect has not been widely explored for pulsars in general and will be further investigated in future work.
Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the disruption of lipid metabolism. The present study aimed to explore the underlying mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total, 10 pregnant ewes were fed normally (control group) whereas another 10 were subjected to 70% level feed restriction for 15 days to establish a pathological model of PT. Results showed that, as compared with the controls, the levels of blood β-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes than those of the controls. For ewes with PT, excessive fat vacuoles were observed in liver sections stained with hematoxylin–eosin; furthermore, inner structures of hepatocytes including nuclei, mitochondria and endoplasmic reticulum were damaged seriously according to the results of transmission electron microscope. Real-time PCR data showed that compared with the controls, the expression of hepatic genes involved in fatty acid oxidation (FAO) and triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl-CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results showed that negative energy balance altered the expression of genes involved in FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting in PT of ewes. Our findings may provide the molecular basis for novel therapeutic strategies against this systemic metabolic disease in sheep.
Increasing evidence has demonstrated that the environmental conditions experienced by parents can shape offspring phenotypes. Here, we examined the effects of the photoperiod and temperature experienced by parents on the incidence of diapause in their progeny in the cabbage beetle, Colaphellus bowringi, using three experiments. The first experiment examined parental diapause incidence under different photoperiods at 25°C and the incidence of diapause in progeny from both non-diapausing and diapausing parents under the same rearing conditions. The results revealed that the incidence of diapause among progeny was exactly opposite to that of their parents, i.e., higher parental diapause incidence led to lower progeny diapause incidence, showing a negative relationship in diapause incidence between the parental generation and the progeny generation. The incidence of diapause among progeny produced by diapausing parents was higher than that in progeny produced by non-diapausing parents. The second experiment examined parental diapause incidence at different temperatures under LD 12:12 and the incidence of diapause in progeny from both non-diapausing and diapausing parents under the same rearing conditions. Similarly, the incidence of diapause in progeny was also opposite to that of their parents. However, the incidence of diapause in progeny produced by non-diapausing parents was different from that in progeny produced by diapausing parents. In the third experiment, naturally diapausing adults were maintained at a constant temperature of 9, 28°C or the mean daily summer temperature of 27.84°C under continuous darkness for 3 months of dormancy. After dormancy, the progeny of these post-diapause parents were reared under different photoperiods at 25°C. The results showed that the incidence of diapause among progeny was higher when their parents experienced high temperatures than when they experienced low temperatures. All results demonstrate that the photoperiod and temperature experienced by parents may significantly affect the diapause incidence among progeny.
The Murchison Widefield Array, and its recently developed Voltage Capture System, facilitates extending the low-frequency range of pulsar observations at high-time and -frequency resolution in the Southern Hemisphere, providing further information about pulsars and the ISM. We present the results of an initial time-resolved census of known pulsars using the Murchison Widefield Array. To significantly reduce the processing load, we incoherently sum the detected powers from the 128 Murchison Widefield Array tiles, which yields ~10% of the attainable sensitivity of the coherent sum. This preserves the large field-of-view (~450 deg2 at 185 MHz), allowing multiple pulsars to be observed simultaneously. We developed a WIde-field Pulsar Pipeline that processes the data from each observation and automatically folds every known pulsar located within the beam. We have detected 50 pulsars to date, 6 of which are millisecond pulsars. This is consistent with our expectation, given the telescope sensitivity and the sky coverage of the processed data (~17 000 deg2). For 10 pulsars, we present the lowest frequency detections published. For a subset of the pulsars, we present multi-frequency pulse profiles by combining our data with published profiles from other telescopes. Since the Murchison Widefield Array is a low-frequency precursor to the Square Kilometre Array, we use our census results to forecast that a survey using the low-frequency component of the Square Kilometre Array Phase 1 can potentially detect around 9 400 pulsars.
Studying the polarised properties of pulsars has a rich history giving unique geometric information about pulsars as well as testing the theories of pulsar emission physics. Performing such studies with the MWA has the attraction that the percentage of linear polarisation of many pulsars increases as the observing frequency decreases. Here we discuss the strategies being employed to verify the polarimetric response of the MWA’s high time resolution data.
Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.
As biomarkers of dietary intake or disease risk factor, n-3 fatty acid (FA) can be measured in plasma phospholipids (PL), total lipids (TL) or erythrocytes. However, the numeric relationships between n-3 FA in these lipid pools are not clear. Our goal was to derive conversion ratios for plasma and erythrocyte n-3 FA. Potential studies were identified through systematic literature search in PubMed, Embase and the Cochrane Library of Systematic reviews (1950 to October 2014). In all, fifty-six studies reporting n-3 in healthy individuals were included, of which thirty-four articles reported plasma PL and erythrocytes, and twenty-two reported plasma TL and erythrocytes. Meta-regressions were performed to quantify the ratio between plasma and erythrocyte n-3 FA weight percentages, controlling for covariates including age, sex and study design. The conversion ratios from plasma PL to erythrocytes for EPA, DHA, DPA and total n-3 PUFA are 0·75, 1·16, 2·32 and 1·22; the corresponding conversion ratios from plasma TL to erythrocytes are 1·00, 2·10, 3·85 and 2·08, respectively. The conversion ratios were validated using reported values from the literature and measured data from fifty individuals. The relative error of the predicted results were within 10 % of the mean reported values except for EPA, and the individual measured data except for DPA, in plasma TL. The conversion ratios between plasma PL and erythrocytes were more stable compared with plasma TL. Such conversion ratios will be useful for nutritionists or public health professionals to assess FA profiles of different populations using data collected with different methodologies.
The fruit of Ligustrum lucidum (FLL, Nuzhenzi in Chinese) is an important traditional medicine, and have attracted significant research attention because of their various biological activities. However, there are few research reports available on the use of FLL as a feed additive in livestock nutrition, particularly in layers. This study was conducted to determine the effects of supplementation of the diet of laying hens with FLL on laying performance, egg quality and blood metabolites. A total of 360 72-week-old hens were allocated to three dietary treatments (eight replications of 15 hens/treatment group) and were fed either a control diet or a diet supplemented with an inclusion level of 0.25% or 0.50% of FLL powder in the final feed, until 78 weeks of age. Hens were housed in a three-tier cage system. Feed and water were provided ad libitum. Blood samples and eggs were collected at the end of the experiment. The results showed that dietary supplementation with FLL did not affect egg weight, feed conversion ratio, eggshell thickness, albumen height, egg yolk color, eggshell breaking strength or egg shape index. However, FLL supplementation significantly decreased (P<0.001) mortality, cracked-egg rate and blood serum levels of cholesterol, low-density lipoprotein cholesterol, triglycerides and alanine aminotransferase, and increased (P<0.001) blood serum levels of high-density lipoprotein cholesterol. No differences in serum levels of total protein, albumin, glucose, calcium, aspartate aminotransferase or alkaline phosphatase were observed in hens fed FLL compared with the control group. It can be concluded that FLL, at a supplementation level of 0.25% final feed, can be used as an effective feed additive to improve the performance of laying hens during the late laying period.
Determining what external stimuli influence cell differentiation, morphology, and growth continues to be a focus on many research groups to meet the healthcare Grand Challenges. While prior work has shown the influence of stiffness, surface chemistry and topography, these parameters often change in tandem, making it difficult to delineate the role of an individual component. This study examined the possible incorporation of microelectronic processing to produce reusable substrates for cell guidance studies. Subsequent plating of substrates cleaned with methods common in a microelectronic fabrication process showed complex responses including migration. Optical characterization of surfaces after cleaning showed remaining cellular debris that could be removed through the incorporation of a piranha solution. The micro patterned substrates did allow controlled comparison between dental pulp stem cells and osteoblast cells. The dental pulp cells did not show any cell alignment or cell proliferation (as indicated by cell density) with the isotropic or anisotropic micropatterns on the initial plating. The osteoblast cells (control) only aligned with the lines and not any of the other patterns (dots, holes or hexagons).
Historically, alloy development with better radiation performance has been focused on traditional alloys with one or two principal element(s) and minor alloying elements, where enhanced radiation resistance depends on microstructural or nanoscale features to mitigate displacement damage. In sharp contrast to traditional alloys, recent advances of single-phase concentrated solid solution alloys (SP-CSAs) have opened up new frontiers in materials research. In these alloys, a random arrangement of multiple elemental species on a crystalline lattice results in disordered local chemical environments and unique site-to-site lattice distortions. Based on closely integrated computational and experimental studies using a novel set of SP-CSAs in a face-centered cubic structure, we have explicitly demonstrated that increasing chemical disorder can lead to a substantial reduction in electron mean free paths, as well as electrical and thermal conductivity, which results in slower heat dissipation in SP-CSAs. The chemical disorder also has a significant impact on defect evolution under ion irradiation. Considerable improvement in radiation resistance is observed with increasing chemical disorder at electronic and atomic levels. The insights into defect dynamics may provide a basis for understanding elemental effects on evolution of radiation damage in irradiated materials and may inspire new design principles of radiation-tolerant structural alloys for advanced energy systems.
A large-scale network named the default mode network (DMN) dynamically cooperates and competes with an external attention system (EAS) to facilitate various cognitive functioning that is prominently impaired in schizophrenia. However, it is unclear whether the cognitive deficit in schizophrenia is related to the disrupted competition and/or cooperation between these two networks.
A total of 35 schizophrenia patients and 30 healthy controls were scanned using gradient-echo echo-planar imaging during n-back working memory (WM) processing. Brain activities of the DMN and EAS were measured using general linear modelling of the functional magnetic resonance imaging data. Dynamic interaction between the DMN and EAS was decomposed into two directions using Granger causality analysis.
We observed a significant failure of DMN suppression in patients with schizophrenia, which was significantly related to WM/attentional deficit. Granger causality modelling showed that in healthy controls, while the EAS inhibitorily influenced the DMN, the DMN exerted an ‘excitatory’ or cooperative influence back on the EAS, especially in those with lower WM accuracy. In schizophrenia, this ‘excitatory’ DMN→EAS influence within the reciprocal EAS–DMN loop was significantly reduced, especially in patients with WM/attentional deficit.
The dynamic interaction between the DMN and EAS is likely to be comprised of both competitive and cooperative influences. In healthy controls, both the ‘inhibitory’ EAS→DMN interaction and ‘excitatory’ DMN→EAS interaction are correlated with WM performance. In schizophrenia, reduced ‘cooperative’ influence from the DMN to dorsal nodes of the EAS occurs in the context of non-suppression of the DMN and may form a possible pathophysiological substrate of WM deficit and attention disorder.
While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).
Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology – Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾50% MADRS score reduction) was the primary outcome.
By 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01–0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02–0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days–2 weeks; effect size (ES) = 1.08–1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.
Single-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.