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Introduction: Selecting appropriate patients for hospitalization following emergency department (ED) evaluation of syncope is critical for serious adverse event (SAE) identification. The primary objective of this study is to determine the association of hospitalization and SAE detection using propensity score (PS) matching. The secondary objective was to determine if SAE identification with hospitalization varied by the Canadian Syncope Risk Score (CSRS) risk-category. Methods: This was a secondary analysis of two large prospective cohort studies that enrolled adults (age ≥ 16 years) with syncope at 11 Canadian EDs. Patients with a serious condition identified during index ED evaluation were excluded. Outcome was a 30-day SAE identified either in-hospital for hospitalized patients or after ED disposition for discharged patients and included death, ventricular arrhythmia, non-lethal arrhythmia and non-arrhythmic SAE (myocardial infarction, structural heart disease, pulmonary embolism, hemorrhage). Patients were propensity matched using age, sex, blood pressure, prodrome, presumed ED diagnosis, ECG abnormalities, troponin, heart disease, hypertension, diabetes, arrival by ambulance and hospital site. Multivariable logistic regression assessed the interaction between CSRS and SAE detection and we report odds ratios (OR). Results: Of the 8183 patients enrolled, 743 (9.0%) patients were hospitalized and 658 (88.6%) were PS matched. The OR for SAE detection for hospitalized patients in comparison to those discharged from the ED was 5.0 (95%CI 3.3, 7.4), non-lethal arrhythmia 5.4 (95%CI 3.1, 9.6) and non-arrhythmic SAE 6.3 (95%CI 2.9, 13.5). Overall, the odds of any SAE identification, and specifically non-lethal arrhythmia and non-arrhythmia was significantly higher in-hospital among hospitalized patients than those discharged from the ED (p < 0.001). There were no significant differences in 30-day mortality (p = 1.00) or ventricular arrhythmia detection (p = 0.21). The interaction between ED disposition and CSRS was significant (p = 0.04) and the probability of 30-day SAEs while in-hospital was greater for medium and high risk CSRS patients. Conclusion: In this multicenter prospective cohort, 30-day SAE detection was greater for hospitalized compared with discharged patients. CSRS low-risk patients are least likely to have SAEs identified in-hospital; out-patient monitoring for moderate risk patients requires further study.
The short allele of the serotonin transporter gene 5’ promoter region polymorphism (5-HTTLPR) is reported by A. Caspi and others to be associated with susceptibility to depression and suicidality in response to stressful life events. We examined the relationship of a triallelic 5-HTTLPR polymorphism to stressful life events (SLE) and severity of major depression and suicidality.
Mood disorder subjects (N=191) and healthy volunteers (N=125), all Caucasians of European origin, were genotyped for the triallelic 5-HTTLPR polymorphism, two low expressing alleles (LG, S) and a higher expressing LA allele. All subjects underwent structured clinical interviews for DSM IV diagnoses, ratings of psychopathology, stressful life events, developmental history and suicidal behavior. Cerebrospinal fluid (CSF) 5-HIAA was assayed in a sub-sample.
Lower expressing alleles independently predicted greater depression severity and predicted greater severity of major depression with moderate-severe life events compared with the LA allele. No associations with suicidal behavior and CSF 5-HIAA were found.
Low expression transporter alleles explain 31% of the variance in major depression severity and increase the impact of stressful life events on severity. The biological phenotype responsible for these effects remains to be elucidated
We evaluated the efficacy of eszopiclone (ESZ) and concurrent escitalopram oxalate (EO) in patients with insomnia and co-morbid GAD.
Patients meeting DSM-IV-TR criteria for GAD and insomnia received 10 weeks of EO 10mg and co-therapy with ESZ 3mg or placebo (PBO) for 8 weeks. For the last 2 weeks, ESZ was replaced with single-blind PBO to evaluate discontinuation effects. Sleep, daytime functioning and anxiety measures were captured during the study.
ESZ+EO improved sleep and daytime functioning at each week and the double-blind period average (p<0.05). At Week 8, significantly more ESZ+EO patients had no clinically meaningful insomnia based on ISI</=7. Significant improvements with ESZ+EO (relative to PBO+EO) were observed in HAM-A total scores each week, and Weeks 4-10 excluding the insomnia item. ESZ+EO was significantly better at every timepoint on CGI-I (p<0.02); CGI-S was not different between treatments after Week 1. Median time to anxiolytic response was reduced with ESZ+EO based on HAM-A and CGI-I. HAM-A response and remission rates at Week 8 were higher with ESZ+EO, and HAM-D17 scores were improved at all timepoints (p<0.004). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and no treatment differences in sleep or daytime function. Significant treatment differences in anxiety and mood were maintained after discontinuation.
In this study, ESZ+EO was well tolerated and associated with improved sleep and daytime function without evidence of tolerance. Improvements in anxiety and mood were observed with ESZ+EO.
Support for this study provided by Sepracor Inc., Marlborough, MA.
Tuberculosis (TB) is the leading cause of death among infectious diseases. China has a high burden of TB and accounted for almost 13% of the world's cases of multi-drug resistant (MDR) TB. Spinal TB is one reason for the resurgence of TB in China. Few large case studies of MDR spinal TB in China have been conducted. The aim of this research was to observe the epidemiological characteristics of inpatients with MDR spinal TB in six provinces and cities of China from 1999–2015. This is a multicentre retrospective observational study. Patients' information was collected from the control disease centre and infectious disease database of hospitals in six provinces and cities in China. A total of 3137 patients with spinal TB and 272 patients with MDR spinal TB were analysed. The result showed that MDR spinal TB remains a public health concern and commonly affects patients 15–30 years of age (34.19%). The most common lesions involved the thoracolumbar spine (35.66%). Local pain was the most common symptom (98.53%). Logistic analysis showed that for spinal TB patients, reside in rural district (OR 1.79), advanced in years (OR 1.92) and high education degree (OR 2.22) were independent risk factors for the development of MDR spinal TB. Women were associated with a lower risk of MDR spinal TB (OR 0.48). The most common first-line and second-line resistant drug was isoniazid (68.75%) and levofloxacin (29.04%), respectively. The use of molecular diagnosis resulted in noteworthy clinical advances, including earlier initiation of MDR spinal TB treatment, improved infection control and better clinical outcome. Chemotherapy and surgery can yield satisfactory outcomes with timely diagnosis and long-term treatment. These results enable a better understanding of the MDR spinal TB in China among the general public.
We aimed to provide comprehensive estimates of laboratory-confirmed respiratory syncytial virus (RSV)-associated hospitalisations. Between 2012 and 2015, active surveillance of acute respiratory infection (ARI) hospitalisations during winter seasons was used to estimate the seasonal incidence of laboratory-confirmed RSV hospitalisations in children aged <5 years in Auckland, New Zealand (NZ). Incidence rates were estimated by fine age group, ethnicity and socio-economic status (SES) strata. Additionally, RSV disease estimates determined through active surveillance were compared to rates estimated from hospital discharge codes. There were 5309 ARI hospitalisations among children during the study period, of which 3923 (73.9%) were tested for RSV and 1597 (40.7%) were RSV-positive. The seasonal incidence of RSV-associated ARI hospitalisations, once corrected for non-testing, was 6.1 (95% confidence intervals 5.8–6.4) per 1000 children <5 years old. The highest incidence was among children aged <3 months. Being of indigenous Māori or Pacific ethnicity or living in a neighbourhood with low SES independently increased the risk of an RSV-associated hospitalisation. RSV hospital discharge codes had a sensitivity of 71% for identifying laboratory-confirmed RSV cases. RSV infection is a leading cause of hospitalisation among children in NZ, with significant disparities by ethnicity and SES. Our findings highlight the need for effective RSV vaccines and therapies.
The device standardized infection ratio (SIR) is used to compare unit and hospital performance for different publicly reported infections. Interventions to reduce unnecessary device use may select a higher-risk population, leading to a paradoxical increase in SIR for some high-performing facilities. The standardized utilization ratio (SUR) adjusts for device use for different units and facilities.
We calculated the device SIR (calculated based on actual device days) and population SIR (defined as Σ observed events divided by Σ predicted events based on predicted device days), adjusting for the facility SUR for both central-line–associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) in 84 hospitals from a single system for calendar years 2016 and 2017.
The central-line SUR was 1.02 for 801,172 central-line days, with a device SIR of 0.76 and a population SIR of 0.78, a 1.6% relative increase. On the other hand, the urinary catheter SUR was 0.90 for 757,504 urinary catheter days, with a device SIR of 0.84 and a population SIR of 0.76, a 10.0% relative decrease. The cumulative attributable difference for CAUTI to a target SIR of 1 was −135.4 for the device SIR compared to −203.66 for the population SIR, a 50.8% increase in prevented events.
Population SIR accounts for predicted device utilization; thus, it is an attractive metric with which to address overall risk of infection or harm to a patient population. It also reduces the risk of selection bias that may impact the device SIR with interventions to reduce device use.
Salvia daiguii Y.K.Wei & Y.B.Huang, a new species from China, is described. Salvia daiguii belongs to Salvia subg. Glutinaria (Raf.) G.X.Hu, C.L.Xiang & B.T.Drew, sect. Sobiso (Raf.) G.X.Hu, A.Takano & B.T.Drew, and is distinguished from morphologically similar species by differences in its habit, leaves, inflorescences and flowers. It has a narrow distribution in a karst region of Yongding District, Hunan Province, central China. A key to the Chinese species of section Sobiso is also presented.
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.
Employing atomic-scale simulations, the response of a high-angle grain boundary (GB), the soft/hard GB, against external loading was systematically investigated. Under tensile loading close to the hard orientation, strain-induced dynamic recrystallization was observed to initiate through direct soft-to-hard grain reorientation, which was triggered by stress mismatch, inhibited by surface tension from the soft-hard GB, and proceeded by interface ledges. Such grain reorientation corresponds with expansion and contraction of the hard grain along and perpendicular to the loading direction, respectively, accompanied by local atomic shuffling, providing relatively large normal strain of 8.3% with activation energy of 0.04 eV per atom. Tensile strain and residual dislocations on the hard/soft GB facilitate the initiation of dynamic recrystallization by lowering the energy barrier and the critical stress for grain reorientation, respectively.
Guangxi, a province in southwestern China, has the second highest reported number of HIV/AIDS cases in China. This study aimed to develop an accurate and effective model to describe the tendency of HIV and to predict its incidence in Guangxi. HIV incidence data of Guangxi from 2005 to 2016 were obtained from the database of the Chinese Center for Disease Control and Prevention. Long short-term memory (LSTM) neural network models, autoregressive integrated moving average (ARIMA) models, generalised regression neural network (GRNN) models and exponential smoothing (ES) were used to fit the incidence data. Data from 2015 and 2016 were used to validate the most suitable models. The model performances were evaluated by evaluating metrics, including mean square error (MSE), root mean square error, mean absolute error and mean absolute percentage error. The LSTM model had the lowest MSE when the N value (time step) was 12. The most appropriate ARIMA models for incidence in 2015 and 2016 were ARIMA (1, 1, 2) (0, 1, 2)12 and ARIMA (2, 1, 0) (1, 1, 2)12, respectively. The accuracy of GRNN and ES models in forecasting HIV incidence in Guangxi was relatively poor. Four performance metrics of the LSTM model were all lower than the ARIMA, GRNN and ES models. The LSTM model was more effective than other time-series models and is important for the monitoring and control of local HIV epidemics.
An algorithm for Global Navigation Satellite System satellite atomic clock integrity monitoring based on an extended measurement model is proposed. A detection statistic achieved by parity transformation is used to detect clock anomalies, and the concept of the optimal accumulation number, with a method to find it, is provided. Numerical simulations are adopted to verify the validity of detecting two typical anomalies.
This study investigates the stability and transition of Görtler vortices in a hypersonic boundary layer using linear stability theory and direct numerical simulations. In the simulations, Görtler vortices are separately excited by wall blowing and suction with spanwise wavelengths of 3, 6 and 9 mm. In addition to primary streaks with the same wavelength as the blowing and suction, secondary streaks with half the wavelength also emerge in the 6 and 9 mm cases. The streaks develop into mushroom structures before breaking down. The breakdown processes of the three cases are dominated by a sinuous-mode instability, a varicose-mode instability and a combination of the two, respectively. Both fundamental and subharmonic instabilities are relevant in all cases. Multiple modes are identified in the secondary-instability stage, some of which originate from the primary instabilities (first and second Mack modes). We demonstrate that the first Mack mode can be destabilized to either a varicose-mode or sinuous-mode streak instability depending on its frequency and wavelength, whereas the second Mack mode undergoes a stabilizing stage before turning into a varicose mode in the 6 and 9 mm cases. An energy analysis reveals the stabilizing and destabilizing mechanisms of the primary instabilities under the influence of Görtler vortices, highlighting the role played by the spanwise production based on the spanwise gradient of the streamwise velocity in both varicose and sinuous modes. The effects introduced by the secondary streaks are examined by filtering the secondary streaks in two new simulations with nominally identical conditions to those of the 6 and 9 mm cases. Remarkably, the secondary streaks can destabilize the Görtler vortices, therefore advancing the transition. The stability theory results are in good agreement with those from direct numerical simulations.
In order to understand the transport of fast electrons within solid density targets driven by an optical high power laser, we have numerically investigated the dynamics and structure of strong self-generated magnetic fields in such experiments. Here we present a systematic study of the bulk magnetic field generation due to the ponderomotive current, Weibel-like instability and resistivity gradient between two solid layers. Using particle-in-cell simulations, we observe the effect of varying the laser and target parameters, including laser intensity, focal size, incident angle, preplasma scale length, target thickness and material and experimental geometry. The simulation results suggest that the strongest magnetic field is generated with laser incident angles and preplasma scale lengths that maximize laser absorption efficiency. The recent commissioning of experimental platforms equipped with both optical high power laser and X-ray free electron laser (XFEL), such as European XFEL-HED, LCLS-MEC and SACLA beamlines, provides unprecedented opportunities to probe the self-generated bulk magnetic field by X-ray polarimetry via Faraday rotation with simultaneous high spatial and temporal resolution. We expect that this systematic numerical investigation will pave the way to design and optimize near future experimental setups to probe the magnetic fields in such experimental platforms.
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.
With the increase in long-term survival of post-transplant children, there is a paradigm shift in the emphasis of post-transplant care. We describe de novo cardiovascular abnormalities, which occurred in otherwise asymptomatic paediatric liver transplant recipients, who received liver allografts between 1991 and 2014 at the National University Hospital, Singapore, detected during routine post-transplant monitoring. A total of 96 paediatric liver transplants were performed in 90 children. After transplant, 7/90 (7.8%) recipients were identified with new-onset aortopathy. Glycogen storage disease type I (42.9% versus 2.4%; p<0.001) and recipient Epstein-Barr virus seropositivity (85.7 versus 31.0%, p=0.004) were significant risk factors for aortopathy on univariate analysis. On multivariate analysis, only glycogen storage disease type I remained as the significant risk factor (odds ratio 51.3 [95% confidence intervals: 1.1–2498.1, p=0.047]). Liver transplant is a double-edged sword that reverses certain cardiopulmonary complications of end-stage liver disease but may induce de novo structural cardiac injury in the form of aortic dilation.
This paper presents a simple and highly visual approach for the type synthesis of a family of overconstrained parallel mechanisms that have one translational and two rotational movement capabilities. It considers, especially, mechanisms offering the accuracy and dynamic response needed for machining applications. This family features a spatial limb plus a member of a class of planar symmetrical linkages, the latter connected by a revolute joint either to the machine frame at its base link or to the platform at its output link. Criteria for selecting suitable structures from among numerous candidates are proposed by considering the realistic practical requirements for reconfigurability, movement capability, rational component design and so on. It concludes that a few can simultaneously fulfil the proposed criteria, even though a variety of structures have been presented in the literature. Exploitation of the proposed structures and evaluation criteria then leads to a novel five degrees of freedom hybrid module named TriMule. A significant potential advantage of the TriMule over the Tricept arises because all the joints connecting the base link and the machine frame can be integrated into one single, compact part, leading to a lightweight, cost effective and flexible design particularly suitable for configuring various robotized manufacturing cells.