Ruelle predicted that the maximal amplification of perturbations in homogeneous isotropic turbulence is exponential $\exp ({\sigma \sqrt {Re} \,t})$ (where $\sigma \sqrt {Re}$ is the maximal Lyapunov exponent). In our earlier works, we predicted that the maximal amplification of perturbations in fully developed turbulence is faster than exponential and is given by $\exp ({\sigma \sqrt {Re} \sqrt {t} +\sigma _1 t})$ where $\sigma \sqrt {Re} \sqrt {t}$ is much larger than $\sigma \sqrt {Re} \, t$ for small $t$ . That is, we predicted superfast initial amplification of perturbations. Built upon our earlier numerical verification of our prediction, here, we conduct a large numerical verification with resolution up to $2048^3$ and Reynolds number up to $6210$ . Our direct numerical simulation here confirms our analytical prediction. Our numerical simulation also demonstrates that such superfast amplification of perturbations leads to superfast nonlinear saturation. We conclude that such superfast amplification and superfast nonlinear saturation of ever existing perturbations suggest a mechanism for the generation, development and persistence of fully developed turbulence.

Despite consistent public health efforts, the burden of viral disease in India remains high. The present study was undertaken to understand the aetiology, frequency and distribution of viral disease outbreaks in the state of Odisha between 2010 and 2019. This was a prospective study conducted at the Virology Research and Diagnostic Laboratory located at ICMR-Regional Medical Research Centre, Bhubaneswar, Odisha, wherein all the outbreaks of viral aetiologies were investigated and analysed to provide a comprehensive picture of the state of viral disease outbreaks in the region. A total of 191 suspected viral outbreaks were investigated by the team from VRDL during September 2010 and September 2019 reported from all the 30 districts of Odisha. Annual number of suspected cases ranged from 185 to 1002. The most commonly suspected outbreaks were of viral hepatitis (55 outbreaks; 1223 cases) followed by dengue (45 outbreaks; 1185 cases), chickenpox (30 outbreaks; 421 cases), viral encephalitis (27 outbreaks; 930 cases), measles (23 outbreaks; 464 cases), chikungunya (10 outbreaks; 593 cases) and rubella (1 outbreak; 60). The outbreaks peaked in frequency and intensity during the months of July and September. The epidemiology of viral disease outbreaks in the region is presented in the study. Health system preparedness based on evidence is essential for early detection and adequate response to such viral outbreaks.

We read with interest the recent editorial, “The Hennepin Ketamine Study,” by Dr. Samuel Stratton commenting on the research ethics, methodology, and the current public controversy surrounding this study.1 As researchers and investigators of this study, we strongly agree that prospective clinical research in the prehospital environment is necessary to advance the science of Emergency Medical Services (EMS) and emergency medicine. We also agree that accomplishing this is challenging as the prehospital environment often encounters patient populations who cannot provide meaningful informed consent due to their emergent conditions. To ensure that fellow emergency medicine researchers understand the facts of our work so they may plan future studies, and to address some of the questions and concerns in Dr. Stratton’s editorial, the lay press, and in social media,2 we would like to call attention to some inaccuracies in Dr. Stratton’s editorial, and to the lay media stories on which it appears to be based.

Ho JD, Cole JB, Klein LR, Olives TD, Driver BE, Moore JC, Nystrom PC, Arens AM, Simpson NS, Hick JL, Chavez RA, Lynch WL, Miner JR. The Hennepin Ketamine Study investigators’ reply. Prehosp Disaster Med. 2019;34(2):111–113

OBJECTIVES/SPECIFIC AIMS: Characterize the expression kinetics of HIV-1 Envelope and their relationship to virus production at the cellular level. METHODS/STUDY POPULATION: In vitro and ex vivo laboratory analyses. RESULTS/ANTICIPATED RESULTS: Initial studies addressing the kinetics of cell surface. Envelope (Env) expression reveal that Env expression to peaks on day 2 post infection. Next steps include a series of experiments to compare the kinetics of Env cell surface expression with broadly neutralizing antibody (bNAb)-mediated ADCC and the characterization of virus production kinetics in this same context. To be maximally effective, ADCC elimination of infected cells should occur before peak Env expression. DISCUSSION/SIGNIFICANCE OF IMPACT: Potent bNAbs to HIV-1 recognize vulnerable sites on the HIV-1 Envelope (Env) protein and are of great clinical interest due to their potential use in the prevention and treatment of HIV-1 infection. Their effectiveness depends not only on the neutralization of viral infectivity, but also on the elimination of productively infected cells via antibody-dependent cellular cytotoxicity (ADCC). On a cellular level, ADCC dynamics are determined by the timing and level of Env expression on the surface of HIV-infected cells. This study aims to delineate the expression kinetics of HIV-1 Envelope and their relationship to virus production. We expect that it will provide new insights into the utility of bNAb-mediated ADCC in treating and possibly curing HIV-1 infection; therefore results might have substantial impact on future HIV treatment strategies.

Introduction: In many rural and remote communities in BC, family physicians who are providing excellent primary and emergency care would like to access useful, timely, and collegial support to ensure the highest quality of health services for their patients. We undertook a real-time virtual support project in Robson Valley, located in northern BC, to evaluate the use of digital technologies such as videoconferencing for on demand consultation between family physicians at rural sites and emergency physicians at a regional site. Telehealth consults also occurred between rural sites with nurses at community emergency rooms consulting with local on-call physicians. Our aim was to use telehealth to facilitate timely access to high quality, comprehensive, coordinated team-based care. An evaluation framework, based on the Triple Aim sought to: 1) Identify telehealth use cases and assess impact on patient outcomes, patient and health professional experience, and cost of health care delivery; and 2) Assess the role of relationships among care team members in progressing from uptake to normalization of telehealth into routine usage. Methods: Using a participatory approach, all members of the pilot project were involved in shaping the pilot including the co-development of the evaluation itself. Evaluation was used iteratively throughout implementation for ongoing quality improvement via regular team meetings, sharing and reflecting on findings, and adjusting processes as required. Mixed methods were used including: interviews with family physicians, nurses, and patients at rural sites, and emergency physicians at regional site; review of records such as technology use statistics; and stakeholder focus groups. Results: From November 2016 to July 2017, 26 cases of telehealth use were captured and evaluated. Findings indicate that telehealth has positively impacted care team, patients, and health system. Benefits for care team at the rural sites included confidence in diagnoses through timely access to advice and support, while emergency physicians at the regional site gained deeper understanding of the practice settings of rural colleagues. Nevertheless, telehealth has complicated the emergency department work flow and increased physician workload. Findings demonstrated efficiencies for the health system, including reducing the need for patient transfer. Patients expressed confidence in the physicians and telehealth system; by receiving care closer to home, they experienced personal cost savings. Implementation saw a move away from scheduled telehealth visits to real use of technology for timely access. Conclusion: Evidence of the benefits of telehealth in emergency settings is needed to support stakeholder engagement to address issues of workflow and capacity. This pilot has early indications of significant local impact and will inform the expansion of emergency telehealth in all emergency settings in BC.

Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.

The structural integrity of nuclear fission and fusion power plant components is the focus of this research. The state of the art is using micro scale specimens milled with a focussed ion beam (FIB). Because of their very low volume such specimens can be lab tested, even when irradiated to low or medium level of activity. This offers a possibility of testing multiple specimens to investigate stochastic effects, e.g. effects of irradiation on the shift of the ductile to brittle transition. However, FIB milled specimens suffer from Ga contamination, to the degree that the validity of fracture data obtained on such specimens is questionable. We propose to use nano-additive manufacturing as an alternative to FIB for making micro scale fracture specimens. A combination of two-photon polymerization and electrodeposition and sputtering was used to manufacture micro-scale Brazilian disk fracture specimens (CBD), which are free from Ga and thus better suited for the study of irradiation effects on structural integrity. In this study Ni CBD specimens were made with 30 µm diameter and up to 13 µm thickness. The slot width varied between 1 µm to 2.9 µm width the corresponding slot length of between 7.5 µm and 8 µm. Consecutive FIB characterization shows that the specimens have polycrystalline microstructure with sub-µm grains. The work is ongoing making W CBD specimens and on reducing the slot width and using chemical vapor deposition fabrication.

Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.

Introduction: Medication discrepancies are unintended differences between a patient’s outpatient and inpatient medication regimens, and occur in up to 60% of hospital admissions. Canadian emergency departments (EDs) have implemented medication reconciliation forms that are pre-populated with outpatient medication dispensing data in order to reduce medication discrepancies and resultant adverse drug events. However, these forms may introduce errors of commission by prompting prescribers to reorder discontinued or potentially harmful medications. Our objective was to evaluate the incidence of medication discrepancies and errors of commission after the implementation of pre-populated medication reconciliation forms. Methods: This chart review included admitted patients who were enrolled in a parent study in which a research pharmacist prospectively collected best-possible medication histories (BPMHs) in the ED using all available information sources. Following discharge, research assistants uninvolved with the parent study compared medication orders documented within 48 h of admission with the BPMH to identify medication discrepancies and errors of commission. Errors of commission were defined as inappropriate continuations of medications and reordering discontinued medications. An independent panel adjudicated the clinical significance of the errors. We used regression methods to identify factors associated with errors. The sample size was limited by enrolment into the parent study. Results: Of 151 patients, 71 (47%; 95%CI 39.2-54.9) were exposed to 112 medication errors. Of these errors, 75.9% (85/112; 95%CI 67.1-82.9) were discrepancies, of which 18.8% (16/85; 95%CI 12.0-28.4) were clinically significant. Errors of commission made up 24.1% (27/112; 95%CI 17.3-32.8) of all errors, of which 37.0% (10/27; 95%CI 18.8-55.2) were clinically significant. Taking 8 or more medications was associated with a 5-fold greater odds of experiencing a medication error after controlling for confounders (OR 5.00; 95%CI 2.45-10.17; p<0.001). Conclusion: Clinically significant medication discrepancies and errors of commission remain common despite the implementation of electronically pre-populated medication reconciliation forms. Prospective studies are needed to evaluate whether using pre-populated medication reconciliation forms increases the risk of introducing errors of commission.