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.

We present new far-IR and submillimeter broad-band and spectroscopic results on the dense and very luminous cores of massive star formation regions. The best-studied region, W51, contains one core around the source IRS2 and another around W51 MAIN. Our earlier submillimeter continuum mapping has shown that these two cores are very massive (2-4 × 104 M⊙) and have average densities of nH2 ∼ 105 over their inner parsec. New far-IR maps show that both cores are very luminous (L(MAIN) ∼2 × 106 L⊙; L(IRS2) ∼4x106 L⊙). Observations of the (1,1) and (2,1) transitions of NH3, indicate high kinetic temperatures (200-400 K) for the quiescent gas in the inner several arc seconds (0.1 pc) of both cores. Spectroscopy of the 370 μm J = 7 → 6 and 163 μm J = 16 → 15 transitions of CO toward the cores allows us to characterize the hot high velocity material seen previously on the H2O maser transitions and not readily visible in the low J transitions of CO. The high velocity flow in IRS2 is ∼ 60 times more massive than the very similar outflow in the ∼ 30 times less luminous Orion/KL core. The mass loss rate is ∼ 30 times greater than in Orion. Additional observations of W49 allow us to draw a few general conclusions about the most luminous star formation regions in our galaxy: (1) The luminous cores are 102-103 more massive than the Orion core with the same density. (2) Outflows and warm regions in these cores have physical conditions similar to those in their less luminous counterparts but far more mass is involved in the flows.

The young stellar object SVS 13 has been proposed as the powering source of the HH 7-11 objects. Recent observations have revealed that in the radio continuum (3.6-cm) the source is a binary separated by about 0.3 in the east-west direction. We present Very Large Array observations, made in the highest angular resolution A configuration, of H2O maser emission toward this source. Our data show that the H2O spots appear to be segregated in two velocity groups: a group with radial velocity similar to that of the ambient cloud (V LSR ⋍ 8 km s−1) that is associated with the western radio source, and a blueshifted (by ∼20 km s−1) velocity group that is associated with the eastern radio source. We discuss the possible implications of this observation.

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.

Experiments on the National Ignition Facility show that multi-dimensional effects currently dominate the implosion performance. Low mode implosion symmetry and hydrodynamic instabilities seeded by capsule mounting features appear to be two key limiting factors for implosion performance. One reason these factors have a large impact on the performance of inertial confinement fusion implosions is the high convergence required to achieve high fusion gains. To tackle these problems, a predictable implosion platform is needed meaning experiments must trade-off high gain for performance. LANL has adopted three main approaches to develop a one-dimensional (1D) implosion platform where 1D means measured yield over the 1D clean calculation. A high adiabat, low convergence platform is being developed using beryllium capsules enabling larger case-to-capsule ratios to improve symmetry. The second approach is liquid fuel layers using wetted foam targets. With liquid fuel layers, the implosion convergence can be controlled via the initial vapor pressure set by the target fielding temperature. The last method is double shell targets. For double shells, the smaller inner shell houses the DT fuel and the convergence of this cavity is relatively small compared to hot spot ignition. However, double shell targets have a different set of trade-off versus advantages. Details for each of these approaches are described.

A 3′ × 6′ field centered ~4′ south of the Galactic center and a ~2′ × 4′ field east of the Galactic center have been mapped using the 4–1 → 30 E line (36.169 GHz) of methanol (CH3OH). Line profiles typically consist of broad (~10–20 km s−1) components, as well as narrow (~1 km s−1), spike-like components. The narrow features are bright and unresolved with 60″ resolution, and are probably due to maser activity. We found maser activity immediately adjacent to the non-thermal “wisp” (SgrA-E) ~4′ south of SgrA-West, the secondary knot at SgrA-F, and the eastern edge of SgrA-East. Position-velocity diagrams suggest that the molecular material has been shocked to a higher velocity in the same vicinities. We propose that the maser activity, and the shift in velocity south of the Galactic center, heretofore interpreted as an increasingly steep velocity gradient toward the Galactic center, may be due to the impact of a SNR and the resulting shock of the ambient molecular material. The dynamical effects on the molecular gas of such a shock may have implications on gas feeding toward the nucleus.

The inner few hundred parsecs of the Milky Way, the Central Molecular Zone (CMZ), is our closest laboratory for understanding star formation in the extreme environments (hot, dense, turbulent gas) that once dominated the universe. We present an update on the first large-area survey to expose the sites of star formation across the CMZ at high-resolution in submillimeter wavelengths: the CMZoom survey with the Submillimeter Array (SMA). We identify the locations of dense cores and search for signatures of embedded star formation. CMZoom is a three-year survey in its final year and is mapping out the highest column density regions of the CMZ in dust continuum and a variety of spectral lines around 1.3 mm. CMZoom combines SMA compact and subcompact configurations with single-dish data from BGPS and the APEX telescope, achieving an angular resolution of about 4″ (0.2 pc) and good image fidelity up to large spatial scales.

Hair diameter and curvature are two characteristics of human scalp hair used in forensic contexts. While previous data show that subjective categorization of hair curvature is highly heritable, the heritability of objectively measured curvature and diameter, and variability of hair characteristics within each individual have not yet been studied. The present study measured hair diameter and curvature using an optical fiber diameter analyzer in a sample of 2,332 twins and siblings. Heritability was estimated using maximum likelihood structural equation modeling. Results show sex differences in the magnitude of genetic influence for mean diameter and curvature, with the vast majority of the variance accounted for by genetic effects in males (diameter = 86%, curvature = 53%) and females (diameter = 77%, curvature = 61%). The consistency of diameter (variance within an individual) was also highly heritable, but did not show sex limitation, with 68% of the variance accounted for by genetic factors. Moderate phenotypic correlations were seen between diameter and consistency (r = 0.3) but there was little correlation between diameter and curvature (r = -0.13). A bivariate Cholesky analysis was used to estimate the genetic and environmental correlations between hair diameter and consistency, yielding genetic correlations of r gF = 0.27 for females and r gM = 0.25 for males.