Thoracolumbar spine trauma: a guide for the FRCS examination.

Thoracolumbar spine injuries are commonly seen in trauma settings and have a high risk of causing serious morbidity. There can be controversy when it comes to classifying thoracolumbar injuries within the spinal community, but there remains a need to classify, evaluate and manage thoracolumbar fractures. This article aims to provide a guide on classification of thoracolumbar spine injuries using the AO Spine Thoracolumbar Injury Classification System (AO TLICS).

Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia.

PURPOSE: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. METHODS: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. RESULTS: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). CONCLUSION: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.

Predicting the periodic risk of anthrax in livestock in Victoria, Australia, using meteorological data.

Cases of anthrax in livestock are infrequently and irregularly reported in the state of Victoria, Australia; however, their impact on individual livestock, farming communities and the government agencies tasked with containing these outbreaks is high. This infrequency has been anecdotally associated with differences in annual and local weather patterns. In this study, we used historical anthrax cases and meteorological data from weather stations throughout Victoria to train a generalized linear mixed effects model to predict the daily odds of a case of anthrax occurring in each shire in the coming 30 days. Meteorological variables were transformed to deviations from the mean values for temperature or cumulative values for rainfall in the shire across all years. Shire was incorporated as a random effect to account for meteorological variation between shires. The model incorporated a post hoc weighting for the frequency of historic cases within each shire and the spatial contribution of each shire to the recently redefined Australian Anthrax Belt. Our model reveals that anthrax cases were associated with drier summer conditions (OR 0.96 (95% CI 0.95-0.97) and OR 0.98 (95% CI 0.97-0.99) for every mm increase in rainfall during September and December, respectively) and cooler than average spring (OR 0.20 (95% CI 0.11-0.52) for every °C increase in minimum daily temperature during November and warmer than average summer temperatures (OR 1.45 (95% CI 1.29-1.61) for every °C increase in maximum daily temperature during January. Cases were also preceded by a 40-day period of cooler, drier temperatures (OR 0.5 (95% CI 0.27-0.74) for every °C increase in maximum daily temperature and OR 0.96 (95% CI 0.95-0.97) for every mm increase in rainfall followed by a warmer than average minimum (or nightly) temperature 10 days immediately before the case (OR 1.46 (95% CI 1.35-1.58) for every °C increase in maximum daily temperature). These coefficients of this training model were then applied daily to meteorological data for each shire, and output of these models was presented as a choropleth and timeline plot in a Shiny web application. The application builds on previous spatial modelling and provides Victorian agencies with a tool to engage at-risk farmers and guide discussions towards anthrax control. This application can contribute to the wider rejuvenation of anthrax knowledge and control in Victoria and corroborates the anecdote that increased odds of disease can be linked to meteorological events.

Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Using bivariate linear mixed models to monitor the change in spatial distribution of heavy metals at the site of a historic landfill.

To improve accuracy and efficiency of monitoring remediated sites, the current study proposed the use of bivariate linear mixed modelling and subsequent hypothesis testing to determine significant change in contaminant concentrations over time. The modelling method integrated soil heavy metal (arsenic-As, lead-Pb and zinc-Zn) concentrations obtained from Bicentennial Park, Sydney, Australia, in the years 1990 (n = 144) and 2015 (n = 60), alongside potential influencing factors as predictor variables. Following variable selection, significant predictors included As (1990)-plan curvature, land cover change; As (2015)-multi-resolution ridge top flatness (MRRTF); Pb (1990)-elevation, MRRTF, type of nearest road; Pb (2015)-land cover change; Zn (1990)-distance to the nearest road and road type; and for Zn (2015)-aspect and land cover change. Model quality statistics (standardised squared prediction error; SSPE) indicated relatively good estimates of the prediction variance (mean ~ 1.0 for all metals, median = 0.512 for As (1990), 0.420 for As (2015), 0.417 for Pb (1990), 0.388 for Pb (2015), 0.342 for Zn (1990) and 0.263 for Zn (2015)), however Lin's concordance correlation coefficient indicated poor prediction of point estimates (LCCC = 0.263 for As (1990), 0.414 for As (2015), 0.250 for Pb (1990), 0.166 for Pb (2015), 0.233 for Zn (1990) and 0.408 for Zn (2015)). Pb in 1990 exceeded the Australian guide value of 600 mg kg-1 in small, isolated areas of the park, and by 2015, these 'hotspots' had significantly diminished (P < 0.05). Concentrations of As were low in both 1990 and 2015, not exceeding the 300 mg kg-1 guide; yet, in 2015, As had significantly increased in the south of the study area (P < 0.2). Zn concentrations in 1990 were elevated but did not exceed the guide value of 30,000 mg kg-1. Overall, the models exhibited good estimation of prediction variance and therefore are suitable for hypothesis testing; however, they exhibited poor prediction quality at times. Despite this, bivariate linear mixed modelling is worth exploring as it provides an advantage over modelling single time points and can assist with tracking potential contaminant sources before they cause harm.

Feasibility of a text-based smoking cessation intervention in rural older adults.

Text-based interventions are effective for smoking cessation, but have not been tested in rural older adults. The purpose of this study was to compare the feasibility, acceptability and preliminary efficacy of a text-based Scheduled Gradual Reduction (SGR) program to a non-SGR text messaging support condition among rural older adults. Adults over 60 years were randomized to either: (i) the SGR program (n = 20), a text-based program to reduce smoking over 4-weeks plus text-based support messages; or (ii) control (n = 20), receipt of text-based support messages only. Participants completed surveys at baseline and end of program to assess feasibility and acceptability of the intervention, and biochemically validated 7-day point prevalence cessation was assessed at end of treatment. Most participants (81%) reported reading all the messages they received. Participants found both interventions useful in quitting smoking (SGR = 57%, Control = 63%) and would recommend it to a friend (SGR = 72%, Control = 79%). Although not statically significant, the SGR group had a higher rate of biochemically validated cessation (SGR = 15%, Control = 5%, Cohen d = 0.67). Among those still smoking, the median percent reduction in cigarettes was 33.3% for both groups. Text-based cessation interventions are feasible, acceptable and can be easily disseminated to rural older adult tobacco users.

Sagnac Interferometry with a Single Atomic Clock.

The Sagnac effect enables interferometric measurements of rotation with high precision. Using matter waves instead of light promises resolution enhancement by orders of magnitude that scales with particle mass. So far, the paradigm for matter wave Sagnac interferometry relies on de Broglie waves and thus on free propagation of atoms either in free fall or within waveguides. However, the Sagnac effect can be expressed as a proper time difference experienced by two observers moving in opposite directions along closed paths and has indeed been measured with atomic clocks flown around Earth. Inspired by this, we investigate an interferometer comprised of a single atomic clock. The Sagnac effect manifests as a phase shift between trapped atoms in different internal states after transportation along closed paths in opposite directions, without any free propagation. With analytic models, we quantify limitations of the scheme arising from atomic dynamics and finite temperature. Furthermore, we suggest an implementation with previously demonstrated technology.

A multi-country Salmonella Enteritidis phage type 14b outbreak associated with eggs from a German producer: 'near real-time' application of whole genome sequencing and food chain investigations, United Kingdom, May to September 2014.

We report an outbreak of Salmonella Enteritidis phage type 14b (PT14b) in the United Kingdom (UK) between May and September 2014 where Public Health England launched an investigation to identify the source of infection and implement control measures. During the same period, outbreaks caused by a Salmonella Enteritidis strain with a specific multilocus variable-number tandem repeat analysis (MLVA) profile occurred in other European Union Member States. Isolates from a number of persons affected by the UK outbreak, who had initially been tested by MLVA also shared this particular profile. Cases were defined as any person infected with S. Enteritidis PT14b, resident in England or Wales and without history of travel outside of this geographical area during the incubation period, reported from 1 June 2014 onwards, with a MLVA profile of 2­11­9-7­4-3­2-8­9 or a single locus variant thereof. In total, 287 cases met the definition. Food traceback investigations in the UK and other affected European countries linked the outbreaks to chicken eggs from a German company. We undertook whole genome sequencing of isolates from UK and European cases, implicated UK premises, and German eggs: isolates were highly similar. Combined with food traceback information, this confirmed that the UK outbreak was also linked to a German producer.

Pteropox infection in a juvenile grey-headed flying fox (Pteropus poliocephalus).

A juvenile grey-headed flying fox (GHFF) (Pteropus poliocephalus) presented to the Australia Zoo Wildlife Hospital after a wildlife carer found the animal hanging on the outside of an aviary. On presentation, the animal was emaciated and moribund with disseminated, multifocal, depigmented and proliferative lesions on the wing membranes and skin of the neck. Histopathology revealed multiple, well-circumscribed proliferative epidermal lesions with intracytoplasmic inclusion bodies. A poxvirus was identified via transmission electron microscopy and next-generation sequencing (NGS). Analysis of sequences obtained demonstrated 99% nucleotide identity to Pteropox virus strain Australia (GenBank KU980965). To the authors' knowledge, this paper describes the first case of Pteropox virus infection in a GHFF.

Reducing radiation exposure and cancer risk for children with scoliosis: EOS the new gold standard.

PURPOSE: Children are exposed to significant radiation doses during the investigation and treatment phases of scoliosis. EOS is a new form of low-dose radiation scan which also yields great image quality. However, currently its use is discouraged in the UK due to higher costs. We aimed to quantify the additional radiation dose and cancer risk. METHODS: We retrospectively reviewed all paediatric cases who received both standing whole spine roentgenograms and EOS scans as part of their investigations for scoliosis during a six-month period. We compared the radiation doses between the two modalities and estimated the additional mean lifetime cancer risk per study. RESULTS: We identified 206 children (mean age 14.4) who met the criteria of having both scans. Dose area products (dGycm2) were converted to estimated effective doses (mSv). The total mean doses were 0.68 mSv (PA 0.49 + Lat 0.19) for plain films, and 0.13 mSv (PA 0.08 + Lat 0.04) for EOS scans (p < 0.001). Additional lifetime cancer risk of a plain film was 543% greater than EOS for both sexes (1/10727 versus 1/5827 in males, 1/34483 versus 1/6350 in females). CONCLUSION: There is approximately 5.4-fold increase in risk of cancer for both boys and girls with roentgenograms over EOS, with girls being the most impacted. This carries a significant impact when considering the need for repeat imaging on additional lifetime malignancy risk in children. In our opinion, EOS dual planar scanning is the new gold standard when X-ray of the whole spine is required. LEVEL OF EVIDENCE: III.

The impact of increased chest compression fraction on survival for out-of-hospital cardiac arrest patients with a non-shockable initial rhythm.

OBJECTIVE: We evaluated the effect of chest compression fraction (CCF) on survival to hospital discharge and return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythms. METHODS: This is a retrospective analysis (completed in 2016) of a prospective cohort study which included OHCA patients from ten U.S. and Canadian sites (Resuscitation Outcomes Consortium Epistry and PRIMED study (2007-2011)). We included all OHCA victims of presumed cardiac aetiology, not witnessed by emergency medical services (EMS), without automated external defibrillator shock prior to EMS arrival, receiving > 1 min of CPR with CPR process measures available, and initial non-shockable rhythm. We measured CCF using the first 5 min of electronic CPR records. RESULTS: Demographics of 12,928 adult patients were: mean age 68; male 59.9%; public location 8.5%; bystander witnessed 35.2%; bystander CPR 39.3%; median interval from 911 to defibrillator turned on 10 min:04 s; initial rhythm asystole 64.8%, PEA 26.0%, other non-shockable 9.2%; compression rate 80-120/min (69.1%); median CCF 74%; ROSC 25.6%; survival to hospital discharge 2.4%. Adjusted odds ratio (OR); 95% confidence intervals (95%CI) of survival for each CCF category were: 0-40% (2.00; 1.16, 3.32); 41-60% (0.83; 0.54, 1.24); 61-80% (1.02; 0.77, 1.35); and 81-100% (reference group). Adjusted (OR; 95%CI) of ROSC for each CCF category were: 0-40% (1.02; 0.79, 1.30); 41-60% (0.83; 0.72, 0.95); 61-80% (0.85; 0.77, 0.94); and 81-100% (reference group). CONCLUSIONS: We observed an incremental benefit from higher CCF on the incidence of ROSC, but not survival, among non-shockable OHCA patients with CCF higher than 40%.

The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism.

The minor histocompatibility antigen (mHag) HA-1 is the only known mHag for which mismatching is correlated with the development of severe graft versus host disease (GvHD) after human leukocyte antigen-identical bone marrow transplantation. HA-1 was found to be a nonapeptide derived from an allele of the KIAA0223 gene. The HA-1-negative allelic counterpart encoded by KIAA0223 had one amino acid difference from HA-1. Family analysis with HA-1 allele-specific polymerase chain reaction showed an exact correlation between this allelic polymorphism and the HA-1 phenotype. HA-1 allele typing of donor and recipient should improve donor selection and allow the determination of bone marrow transplantation recipients with high risk for HA-1-induced GvHD development.

Agnostic particle tracking for three-dimensional motion of cellular granules and membrane-tethered bead dynamics.

The ability to detect biological events at the single-molecule level provides unique biophysical insights. Back-focal-plane laser interferometry is a promising technique for nanoscale three-dimensional position measurements at rates far beyond the capability of standard video. We report an in situ calibration technique for back-focal-plane, low-power (nontrapping) laser interferometry. The technique does not rely on any a priori model or calibration knowledge, hence the name "agnostic". We apply the technique to track long-range (up to 100 microm) motion of a variety of particles, including magnetic beads, in three-dimensions with high spatiotemporal resolution ( approximately 2 nm, 100 micros). Our tracking of individual unlabeled vesicles revealed a previously unreported grouping of mean-squared displacement curves at short timescales (<10 ms). Also, tracking functionalized magnetic beads attached to a live cell membrane revealed an anchorage-dependent nonlinear response of the membrane. The software-based technique involves injecting small perturbations into the probe position by driving a precalibrated specimen-mounting stage while recording the quadrant photodetector signals. The perturbations and corresponding quadrant photodetector signals are analyzed to extract the calibration parameters. The technique is sufficiently fast and noninvasive that the calibration can be performed on-the-fly without interrupting or compromising high-bandwidth, long-range tracking of a particle.

Selectivity of dobutamine for adrenergic receptor subtypes: in vitro analysis by radioligand binding.

The cardiovascular responses elicited by dobutamine are distinctly different from those produced by other adrenergic or dopaminergic agonists. To test the hypothesis that dobutamine could have differential affinities for adrenergic receptor subtypes, and that such subtype selectivity could be related to its relatively unique pharmacologic properties, we assessed the ability of dobutamine to displace adrenergic radioligands from membrane receptors in a number of tissues of previously characterized adrenergic receptor subtype. For beta adrenergic receptors identified by (-) [(3)H]dihydroalprenolol (DHA), dobutamine had significantly greater affinity for the beta(1) subtype (K(D) = 2.5 muM in rat heart and 2.6 muM in turkey erythrocyte) than for the beta(2) subtype (K(D) = 14.8 muM in frog heart and 25.4 muM in rat lung) (P < 0.001). For alpha adrenergic receptors, dobutamine had markedly greater affinity for the alpha(1)-subtype identified by [(3)H]prazosin (K(D) = 0.09 muM in rat heart and 0.14 muM in rabbit uterus) than for the alpha(2)-subtype identified by [(3)H]dihydroergocryptine (DHE) (K(D) = 9.3 muM in human platelet) or by [(3)H]yohimbine (K(D) = 5.7 muM in rabbit uterus) (P < 0.001). Like other beta(1)-agonists, in the absence of guanine nucleotide, dobutamine competition curves for DHA binding in rat heart demonstrated two classes of binding sites, with one site of significantly higher affinity (K(D) = 0.5 muM, P = 0.008) than the single class of binding sites (K(D) = 5.2 muM) identified in the presence of guanine nucleotide. However, unlike beta(2)- or alpha(2)-agonists, dobutamine displacement of DHA binding in rat lung or of DHE binding in human platelets demonstrated only a single class of binding sites, and guanine nucleotide had only minimal effects. We conclude that dobutamine is selective for beta(1) as opposed to beta(2), and for alpha(1) as opposed to alpha(2) adrenergic receptors. Furthermore, guanine nucleotide effects on dobutamine binding, and biochemical response data in vitro suggest that dobutamine is a beta(1)-agonist, but has little intrinsic activity at beta(2) and alpha(2)-receptors. This selectivity for adrenergic receptor subtypes may be part of the basis for dobutamine's distinctive pharmacologic properties in vivo.

Mouse beta-globin DNA-binding protein B1 is identical to a proto-oncogene, the transcription factor Spi-1/PU.1, and is restricted in expression to hematopoietic cells and the testis.

The hematopoietic-specific DNA-binding protein B1 binds to the DNA consensus sequence AAAGRGGAARYG located twice in intervening sequence 2 of both of the mouse beta-globin genes (D. L. Galson and D.E. Housman, Mol. Cell. Biol. 8:381-392, 1988). B1 was cloned by expression of a murine erythroleukemia (MEL) cell cDNA library in transfected COS cells and screening by electrophoretic mobility shift analysis. B1 is identical to the proto-oncogene Spi-1/PU.1 (Spi-1), an ets family member. Protein-DNA contacts are shown to resemble those of the helix-turn-helix homeodomain proteins. By Northern (RNA) analysis, we found that Spi-1 mRNA is present at low levels during murine CFU-E maturation and is at least 20-fold higher in uninduced MEL, a transformed proerythroblast-like cell line which contains an activating/transforming insertion of spleen focus-forming virus at the Spi-1 locus. Dimethyl sulfoxide-induced MEL cell differentiation decreases Spi-1 mRNA to approximately 20% of the uninduced level before commitment occurs. In addition to erythroid cells, Spi-1 mRNA is present in B cells, myelomonocytes, and mast cells but not in T cells and nonhematopoietic cell types. In situ hybridization demonstrated Spi-1 mRNA expression in bone marrow, spleen, interstitial nonhepatocytes of the liver, and interstitial nontubular cells of the testis. The Spi-1 locus was mapped on human chromosome 11 to the same interval as ACP2 (lysosomal acid phosphatase), between the anonymous DNA markers D11S33 and D11S14. This region has not yet been found to be associated with a human malignancy.

Modelling drivers and distribution of lead and zinc concentrations in soils of an urban catchment (Sydney estuary, Australia).

The human population is increasing globally and land use is changing to accommodate for this growth. Soils within urban areas require closer attention as the higher population density increases the chance of human exposure to urban contaminants. One such example of an urban area undergoing an increase in population density is Sydney, Australia. The city also possesses a notable history of intense industrial activity. By integrating multiple soil surveys and covariates into a linear mixed model, it was possible to determine the main drivers and map the distribution of lead and zinc concentrations within the Sydney estuary catchment. The main drivers as derived from the model included elevation, distance to main roads, main road type, soil landscape, population density (lead only) and land use (zinc only). Lead concentrations predicted using the model exceeded the established guideline value of 300mgkg-1 over a large portion of the study area with concentrations exceeding 1000mgkg-1 in the south of the catchment. Predicted zinc did not exceed the established guideline value of 7400mgkg-1; however concentrations were higher to the south and west of the study area. Unlike many other studies we considered the prediction uncertainty when assessing the contamination risk. Although the predictions indicate contamination over a large area, the broadness of the prediction intervals suggests that in many of these areas we cannot be sure that the site is contaminated. More samples are required to determine the contaminant distribution with greater precision, especially in residential areas where contamination was highest. Managing sources and addressing areas of elevated lead and zinc concentrations in urban areas has the potential to reduce the impact of past human activities and improve the urban environment of the future.

Hydrocephalus secondary to obstruction of the lateral apertures in two dogs.

BACKGROUND: Traditionally, hydrocephalus is divided into communicating or non-communicating (obstructive) based on the identification of a blockage of cerebrospinal fluid (CSF) flow through the ventricular system. Hydrocephalus ex vacuo refers to ventricular enlargement as a consequence of neuroparenchymal loss. Hydrocephalus related to obstruction of the lateral apertures of the fourth ventricles has rarely been described. CASE REPORT: The clinicopathologic findings in two dogs with hydrocephalus secondary to obstruction of the lateral apertures of the fourth ventricle are reported. Signs were associated with a caudal cervical spinal cord lesion in one dog and a caudal brain stem lesion in the other dog. Magnetic resonance imaging (MRI) disclosed dilation of the ventricular system, including the lateral recesses of the fourth ventricle. In one dog, postmortem ventriculography confirmed obstruction of the lateral apertures. Microscopic changes were identified in the choroid plexus in both dogs, yet a definitive cause of the obstructions was not identified. The MRI findings in both dogs are similar to membranous occlusion of the lateral and median apertures in human patients. CONCLUSION: MRI detection of dilation of the entire ventricular system in the absence of an identifiable cause should prompt consideration of an obstruction of the lateral apertures. In future cases, therapeutic interventions aimed at re-establishing CSF flow or ventriculoperitoneal catheterisation should be considered.

Prospective Validation of the National Field Triage Guidelines for Identifying Seriously Injured Persons.

BACKGROUND: The national field trauma triage guidelines have been widely implemented in US trauma systems, but never prospectively validated. We sought to prospectively validate the guidelines, as applied by out-of-hospital providers, for identifying high-risk trauma patients. STUDY DESIGN: This was an out-of-hospital prospective cohort study from January 1, 2011 through December 31, 2011 with 44 Emergency Medical Services agencies in 7 counties in 2 states. We enrolled injured patients transported to 28 acute care hospitals, including 7 major trauma centers (Level I and II trauma hospitals) and 21 nontrauma hospitals. The primary exposure term was Emergency Medical Services' use of one or more field triage criteria in the national field triage guidelines. Outcomes included Injured Severity Score ≥16 (primary) and critical resource use within 24 hours of emergency department arrival (secondary). RESULTS: We enrolled 53,487 injured children and adults transported by Emergency Medical Services to an acute care hospital, 17,633 of which were sampled for the primary analysis; 13.9% met field triage guidelines, 3.1% had Injury Severity Score ≥16, and 1.7% required early critical resources. The sensitivity and specificity of the field triage guidelines were 66.2% (95% CI, 60.2-71.7%) and 87.8% (95% CI, 87.7-88.0%) for Injury Severity Score ≥16 and 80.1% (95% CI, 65.8-89.4%) and 87.3% (95% CI 87.1-87.4%) for early critical resource use. Triage guideline sensitivity decreased with age, from 87.4% in children to 51.8% in older adults. CONCLUSIONS: The national field triage guidelines are relatively insensitive for identifying seriously injured patients and patients requiring early critical interventions, particularly among older adults.

Sequential activation of genes for heme pathway enzymes during erythroid differentiation of mouse Friend virus-transformed erythroleukemia cells.

Changes in the level of transcripts encoding enzymes of the heme biosynthetic pathway as well as those encoding ubiquitous proteins were examined in murine Friend virus-transformed erythroleukemia cells during erythroid cell differentiation induced by chemicals including dimethyl sulfoxide (DMSO). Early changes following DMSO treatment were marked decreases in mRNAs for three ubiquitous proteins, i.e., a 70 kDa heat shock protein (less than 6 h), heme oxygenase and nonspecific delta-aminolevulinate synthase (ALAS) (less than 12 h). These changes were followed by sequential increases in mRNAs for enzymes in the heme biosynthetic pathway. Namely, mRNAs for the erythroid-specific ALAS, delta-aminolevulinate dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase started to increase at 12, 18, 18-24 and 24 h, respectively. Nuclear runoff studies revealed that these changes are largely transcriptional. Treatments with other inducers of erythroid differentiation, e.g., hexamethylene bisacetamide, n-butyric acid and N'-methylnicotinamide, also showed similar effects on mRNAs as those following DMSO. These findings suggest that both suppression of ubiquitous genes and activation of heme pathway enzyme genes are associated with erythroid differentiation, and the former occurs preceding changes in the latter.