Genetically programmed retinoic acid deficiency during gastrulation phenocopies most known developmental defects due to acute prenatal alcohol exposure in FASD.

Fetal Alcohol Spectrum Disorder (FASD) arises from maternal consumption of alcohol during pregnancy affecting 2%-5% of the Western population. In Xenopus laevis studies, we showed that alcohol exposure during early gastrulation reduces retinoic acid (RA) levels at this critical embryonic stage inducing craniofacial malformations associated with Fetal Alcohol Syndrome. A genetic mouse model that induces a transient RA deficiency in the node during gastrulation is described. These mice recapitulate the phenotypes characteristic of prenatal alcohol exposure (PAE) suggesting a molecular etiology for the craniofacial malformations seen in children with FASD. Gsc +/Cyp26A1 mouse embryos have a reduced RA domain and expression in the developing frontonasal prominence region and delayed HoxA1 and HoxB1 expression at E8.5. These embryos also show aberrant neurofilament expression during cranial nerve formation at E10.5 and have significant FASD sentinel-like craniofacial phenotypes at E18.5. Gsc +/Cyp26A1 mice develop severe maxillary malocclusions in adulthood. Phenocopying the PAE-induced developmental malformations with a genetic model inducing RA deficiency during early gastrulation strongly supports the alcohol/vitamin A competition model as a major molecular etiology for the neurodevelopmental defects and craniofacial malformations seen in children with FASD.

Measurement of Magnetic Cavitation Driven by Heat Flow in a Plasma.

We describe the direct measurement of the expulsion of a magnetic field from a plasma driven by heat flow. Using a laser to heat a column of gas within an applied magnetic field, we isolate Nernst advection and show how it changes the field over a nanosecond timescale. Reconstruction of the magnetic field map from proton radiographs demonstrates that the field is advected by heat flow in advance of the plasma expansion with a velocity v_{N}=(6±2)×10^{5} m/s. Kinetic and extended magnetohydrodynamic simulations agree well in this regime due to the buildup of a magnetic transport barrier.

Colorectal cancer care in the COVID-19 era: outcomes from a 'mixed site' model.

INTRODUCTION: The COVID-19 pandemic has presented many challenges to colorectal cancer (CRC) care. Many organisations opted to perform CRC resections in 'cold' sites. Infrastructure in Northumbria Healthcare NHS Foundation Trust (NHCT) necessitated co-locating CRC care with 'hot' COVID streams but with additional precautions. This study aimed to evaluate that approach for a consecutive series of CRC cases, diagnosed before and during the COVID-19 pandemic. METHODS: A prospectively populated data set of CRC patients diagnosed between 1 April 2019 and 30 September 2020 was used. Patients presenting before 1 April 2020 were considered 'pre-COVID' and those presenting subsequently as 'COVID era'. RESULTS: Some 344 cases were diagnosed in the 12 months 'pre-COVID' and 166 in the 6 months of the 'COVID era'. The median numbers of days from referral to diagnosis (21 vs 20, p=0.373) and operation (63 vs 61, p=0.208) were unchanged. The 'COVID era' saw an increase in the proportion of radiological diagnoses (39.5% vs 53.0%, p=0.004) with an associated decrease in endoscopic diagnoses (56.7% vs 45.8%, p=0.021). Rates of inoperable (1.5% vs 1.2%, p=0.821), obstructing (11.0% vs 16.2%, p=0.272) and perforated tumours (0.6% vs 1.5%, p=0.492) remained the same. One patient developed COVID-19 perioperatively. Rates of laparoscopic operation (59.5% vs 61.8%, p=0.751), anastomotic leak (6.4% vs 5.9%, p=0.891), re-operative surgery (10.4% vs 4.4%, p=0.138), primary stoma (40.5% vs 32.4%, p=0.244) and 90-day mortality (0.6% vs 1.5%, p=0.492) did not change. CONCLUSIONS: With appropriate infection control measures, it may be safe to continue providing standard elective and urgent CRC care without access to a 'COVID clean' site.

Selective Ion Acceleration by Intense Radiation Pressure.

We report on the selective acceleration of carbon ions during the interaction of ultrashort, circularly polarized and contrast-enhanced laser pulses, at a peak intensity of 5.5×10^{20} W/cm^{2}, with ultrathin carbon foils. Under optimized conditions, energies per nucleon of the bulk carbon ions reached significantly higher values than the energies of contaminant protons (33 MeV/nucleon vs 18 MeV), unlike what is typically observed in laser-foil acceleration experiments. Experimental data, and supporting simulations, emphasize different dominant acceleration mechanisms for the two ion species and highlight an (intensity dependent) optimum thickness for radiation pressure acceleration; it is suggested that the preceding laser energy reaching the target before the main pulse arrives plays a key role in a preferential acceleration of the heavier ion species.

The diagnostic accuracy of the faecal immunochemical test for colorectal cancer in risk-stratified symptomatic patients.

INTRODUCTION: The faecal immunochemical test detects blood in the faeces, reporting faecal haemoglobin quantitatively in micrograms of haemoglobin per gram of faeces. The aim of this pilot study was to determine the feasibility of using the faecal immunochemical test as a rule-out test in symptomatic patients at low and high risk of colorectal cancer. MATERIAL AND METHODS: Between November 2016 and October 2017, consecutive symptomatic patients within a multicultural part of London were recruited to perform a faecal immunochemical test prior to colonoscopy. Analysis was performed on the HM-JACKarc analyser. RESULTS: Faecal immunochemical test samples were returned by 298 patients who underwent colonoscopy. There was no significant variation in faecal haemoglobin levels by age, sex, ethnicity or deprivation. The overall detection rate for colorectal cancer was 100% at 2 µg/g and 92% at 10 µg/g. If a faecal haemoglobin threshold for investigation of 2 µg/g (ie detectable) or 10 µg/g had been employed, the number of colonoscopies would have been reduced by 70% and 84%, respectively, in all symptomatic patients. For low-risk patients, the sensitivity of the faecal immunochemical test for colorectal cancer at both thresholds of 2 µg/g or 10 µg/g remained 100%, with the number of colonoscopies reduced by 80% and 91%, respectively. CONCLUSION: This study shows that the faecal immunochemical test is a promising technology that detected colorectal cancer in all high- or low-risk symptomatic patients in our cohort at a threshold of detectable faecal haemoglobin. Data from adequately powered cohort studies will elucidate the true diagnostic accuracy of the test and the rate and patterns of undetected colorectal cancer.

Outcomes of inflammatory bowel disease surgery in obese versus non-obese patients: a meta-analysis.

BACKGROUND: Obesity is considered a risk factor for many chronic diseases and obese patients are often considered higher risk surgical candidates. The aim of this meta-analysis was to evaluate the outcomes of obese (body mass index ≥ 30 kg/m2) versus non-obese patients undergoing surgery for inflammatory bowel disease (IBD). METHODS: PubMed, Scopus, and Embase libraries were searched up to March 2019 for studies comparing outcomes of obese with non-obese patients undergoing surgery for IBD. A meta-analysis was conducted using Review Manager software to create forest plots and calculate odds ratios and mean differences. RESULTS: Four thousand three hundred and eleven patients from five observational studies were included. Obese patients were older at the time of surgery and more likely to have diabetes. Obese patients had longer operative times (MD 23.28, 95% CI 14.63-31.93, p < 0.001), higher intra-operative blood loss (MD 45.32, 95% CI 5.89-84.76, p = 0.02), longer length of stay (MD 0.90, 95% CI 0.60-1.20, p < 0.001), higher wound infection rates (OR 1.76, 95% CI 1.39-2.23, p < 0.001), and higher total postoperative complication rates (OR 1.33, 95% CI 1.04-1.70, p = 0.02). CONCLUSIONS: Obesity is associated with significantly worse outcomes following IBD-specific surgery, including longer operative times, greater blood loss, longer length of stay, higher wound infection rates, and higher total postoperative complication rates. Clinicians should be mindful of these increased risks when counselling patients and consider weight reduction strategies where possible.

Lysosomal dysfunction induced by changes in albumin's tertiary structure: Potential key factor in protein toxicity during diabetic nephropathy.

AIMS: Increased amounts of protein, in particular albumin within renal tubular cells (TBCs), induce the expression of inflammatory and fibrogenic mediators, which are adverse prognostic factors in tubulointerstitial fibrosis and diabetic nephropathy (DN). We sought to assess the participation of the thiol-linked tertiary structure of albumin in the mechanism of protein toxicity in a model of TBCs. MATERIALS AND METHODS: Cultured human renal proximal tubular cells, HK-2, were exposed to isolated albumin from patients with and without DN (Stages 0, 1 and 4). The magnitude of change of the albumin tertiary structure, cell viability (LDH leakage), apoptosis (Annexin V), transdifferentiation and reticulum endoplasmic stress (Western blot and flow cytometry) and lysosomal enzyme activity were assessed. KEY FINDINGS: We found that albumin from Stage 4 patients presented >50% higher thiol-dependent changes of tertiary structure compared to Stages 0 and 1. Cells incubated with Stage 4 albumin displayed 5 times less viability, accompanied by an increased number of apoptotic cells; evidence of profibrogenic markers E-cadherin and vimentin and higher expression of epithelial-to-mesenchymal transition markers α-SMA and E-cadherin and of endoplasmic reticulum stress protein GRP78 were likewise observed. Moreover, we found that cathepsin B activity in isolated lysosomes showed a significant inhibitory effect on albumin from patients in advanced stages of DN and on albumin that was intentionally modified. SIGNIFICANCE: Overall, this study showed that thiol-dependent changes in albumin's tertiary structure interfere with the lysosomal proteolysis of renal TBCs, inducing molecular changes associated with interstitial fibrosis and DN progression.

Generation of intense quasi-electrostatic fields due to deposition of particles accelerated by petawatt-range laser-matter interactions.

We demonstrate here for the first time that charge emitted by laser-target interactions at petawatt peak-powers can be efficiently deposited on a capacitor-collector structure far away from the target and lead to the rapid (tens of nanoseconds) generation of large quasi-static electric fields over wide (tens-of-centimeters scale-length) regions, with intensities much higher than common ElectroMagnetic Pulses (EMPs) generated by the same experiment in the same position. A good agreement was obtained between measurements from a classical field-probe and calculations based on particle-flux measurements from a Thomson spectrometer. Proof-of-principle particle-in-cell simulations reproduced the measurements of field evolution in time, giving a useful insight into the charging process, generation and distribution of fields. The understanding of this charging phenomenon and of the related intense fields, which can reach the MV/m order and in specific configurations might also exceed it, is very important for present and future facilities studying laser-plasma-acceleration and inertial-confinement-fusion, but also for application to the conditioning of accelerated charged-particles, the generation of intense electric and magnetic fields and many other multidisciplinary high-power laser-driven processes.

Differences between morphological and electrophysiological retinal ganglion cell classes.

Retinal prostheses work by delivering electrical pulses to the surviving retinal neurons. A pattern of electrical stimulation can generate a perception of vision in blind patients. To improve efficacy of retinal implants, it is important to understand how different classes of retinal neurons respond to electrical stimulation and if a classification can be made based on the electrophysiological properties of neurons. We use previously recorded patch clamp data from retinal ganglion cells classified into morphological classes (A,B,C, D) and functional types (ON, OFF, ON-OFF). We use a machine learning technique to separate data based on the recorded electrophysiological parameters. Results show that the clusters discovered using the machine learning technique do not correspond to the morphological or functional classes used by neuroscientists.

Examining Differences in Recovery Outcomes between Male and Female Hip Fracture Patients: Design and Baseline Results of a Prospective Cohort Study from the Baltimore Hip Studies.

BACKGROUND: Incidence of hip fractures in men is expected to increase, yet little is known about consequences of hip fracture in men compared to women. It is important to investigate differences at time of fracture using the newest technologies and methodology regarding metabolic, physiologic, neuromuscular, functional, and clinical outcomes, with attention to design issues for recruiting frail older adults across numerous settings. OBJECTIVES: To determine whether at least moderately-sized sex differences exist across several key outcomes after a hip fracture. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study (Baltimore Hip Studies 7th cohort [BHS-7]) was designed to include equal numbers of male and female hip fracture patients to assess sex differences across various outcomes post-hip fracture. Participants were recruited from eight hospitals in the Baltimore metropolitan area within 15 days of admission and were assessed at baseline, 2, 6 and 12 months post-admission. MEASUREMENTS: Assessments included questionnaire, functional performance evaluation, cognitive testing, measures of body composition, and phlebotomy. RESULTS: Of 1709 hip fracture patients screened from May 2006 through June 2011, 917 (54%) were eligible and 39% (n=362) provided informed consent. The final analytic sample was 339 (168 men and 171 women). At time of fracture, men were sicker (mean Charlson score= 2.4 vs. 1.6; p<0.001) and had worse cognition (3MS score= 82.3 vs. 86.2; p<0.05), and prior to fracture were less likely to be on bisphosphonates (8% vs. 39%; p<0.001) and less physically active (2426 kilocalories/week vs. 3625; p<0.001). CONCLUSIONS: This paper provides the study design and methodology for recruiting and assessing hip fracture patients and evidence of baseline and pre-injury sex differences which may affect eventual recovery one year later.

Is gestational diabetes mellitus in obese women predicted by oxidative damage in red blood cells?

Obesity in pregnant women has been associated with an increased risk of maternal complications, including gestational diabetes mellitus (GDM), a process that is related to oxidative stress (OS). To evaluate the biomarkers of OS in red blood cells (RBCs), we assigned 80 pregnant women to one of three groups: control (n = 28), overweight (n = 26) and obese (n = 26). Then, we measured in plasma, the levels of glucose, triacylglycerol (TAG), insulin, free fatty acids (FFAs), leptin and cytokines (e.g. interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-alpha]) and OS biomarkers, such as lipohydroperoxides (LHP), malondialdehyde (MDA) and protein carbonylation (PC) in RBCs. We found significant positive correlations between OS biomarkers, body mass index (BMI) and pregnancy progression. Seven (26.9%) obese women who were diagnosed with GDM at 24-28 weeks of pregnancy showed significantly increased concentrations of FFAs, insulin, leptin, TNF-alpha and biomarkers of OS measured at 12-13 weeks of gestation. We propose to quantify LHP, MDA and PC in membranes of erythrocytes as possible markers to diagnose GDM from weeks 12-14.

Oxidative modifications of foetal LDL-c and HDL-c lipoproteins in preeclampsia.

BACKGROUND: Oxidative modifications have been observed in lipids and proteins in lipoproteins isolated from women with preeclampsia. Thus, newborns could also be susceptible to this damage directly through their mothers. In this study, we evaluated the oxidative profile of LDL-c and HDL-c lipoproteins isolated from the umbilical cord from newborns born to women with preeclampsia. METHODS: Thirty newborns born to women with preeclampsia and thirty newborns born to women with healthy pregnancies were included. Lipid-damage biomarkers, including conjugated dienes, lipohydroperoxides and malondialdehyde, were measured. The reduction of nitroblue tetrazolium, formation of dityrosines, and carbonylation of proteins were assessed as indicators of protein damage. The protective activity of paraoxonase-I on HDL-c particles was evaluated. The total antioxidant capacity and lipid profiles were quantified in plasma. Data were analysed using Student's t-tests and Pearson correlation coefficients. RESULTS: Compared with the control group, the preeclampsia group had an increase in the percentage of lipid damage in both lipoproteins. There was an increase of 23.3 and 19.9% for conjugated dienes, 82.4 and 21.1% for lipohydroperoxides, and 103.8 and 51.5% for malondialdehyde in LDL-c and HDL-c, respectively. However, these infants did not show evident damage in protein oxidation. The activity of the enzyme paraoxonase-I was decreased by 36.2%; by contrast, the total antioxidant capacity was increased by 40% (protein) and 28.8% (non-protein). CONCLUSIONS: The oxidative modifications that occur in HDL-c and LDL-c isolated from newborns from women with preeclampsia are mainly caused by lipoperoxidation processes related to evident paraoxonase-I inactivation. The absence of protein damage is likely linked to an increase in total antioxidant capacity. Therefore, antioxidant support could be helpful in reducing oxidative stress in mother/newborn dyads.

Association of pretreatment neutrophil-lymphocyte ratio and outcome in emergency colorectal cancer care.

Introduction The association between the neutrophil-lymphocyte ratio (NLR) and outcome in elective colorectal cancer surgery is well established; the relationship between NLR and the emergency colorectal cancer patient is, as yet, unexplored. This paper evaluates the predictive quality of the NLR for outcome in the emergency colorectal cancer patient. Materials and Methods A total of 187 consecutive patients who underwent emergency surgery for colorectal cancer were included in the study. NLR was calculated from the haematological tests done on admission. Receiver operating characteristic analyses were used to determine the most suitable cut-off for NLR. Outcomes were assessed by mortality at 30 and 90 days using stepwise Cox proportional hazards regression. Results An NLR cut-off of 5 was found to have the highest sensitivity and specificity. At 30 days, age and time from admission to surgery were associated with increased mortality; a high NLR was associated with an increased risk of mortality in univariate but not multivariate analysis. At 90 days, age, NLR, time from admission to surgery and nodal status were all significantly associated with increased mortality on multivariate analysis. Conclusions Pre-operative NLR is a cheap, easily performed and useful clinical tool to aid prediction of outcome in the emergency colorectal cancer patient.

Older men who sustain a hip fracture experience greater declines in bone mineral density at the contralateral hip than non-fractured comparators.

Men experience declining bone mineral density (BMD) after hip fracture; however, changes attributable to fracture are unknown. This study evaluated the excess BMD decline attributable to hip fracture among older men. Older men with hip fracture experienced accelerated BMD declines and are at an increased risk of secondary fractures. INTRODUCTION: The objective was to determine whether bone mineral density (BMD) changes in men after hip fracture exceed that expected with aging. METHODS: Two cohorts were used: Baltimore Hip Studies 7th cohort (BHS-7) and Baltimore Men's Osteoporosis Study (MOST). BHS-7 recruited older adults (N = 339) hospitalized for hip fracture; assessments occurred within 22 days of admission and at 2, 6, and 12 months follow-up. MOST enrolled age-eligible men (N = 694) from population-based listings; data were collected at a baseline visit and a second visit that occurred between 10 and 31 months later. The combined sample (n = 452) consisted of Caucasian men from BHS-7 (n = 89) and MOST (n = 363) with ≥ 2 dual-energy X-ray absorptiometry scans and overlapping ranges of age, height, and weight. Mixed-effect models estimated rates of BMD change, and generalized linear models evaluated differences in annual bone loss at the total hip and femoral neck between cohorts. RESULTS: Adjusted changes in total hip and femoral neck BMD were - 4.16% (95% CI, - 4.87 to - 3.46%) and - 4.90% (95% CI, - 5.88 to - 3.92%) in BHS-7 participants; - 1.57% (95% CI, - 2.19 to - 0.96%) and - 0.99% (95% CI, - 1.88 to - 0.10%) in MOST participants; and statistically significant (P < 0.001) between-group differences in change were - 2.59% (95% CI, - 3.26 to - 1.91%) and - 3.91% (95% CI, - 4.83 to - 2.98%), respectively. CONCLUSION: Hip fracture in older men is associated with accelerated BMD declines at the non-fractured hip that are greater than those expected during aging, and pharmacological interventions in this population to prevent secondary fractures may be warranted.

Low-noise time-resolved optical sensing of electromagnetic pulses from petawatt laser-matter interactions.

We report on the development and deployment of an optical diagnostic for single-shot measurement of the electric-field components of electromagnetic pulses from high-intensity laser-matter interactions in a high-noise environment. The electro-optic Pockels effect in KDP crystals was used to measure transient electric fields using a geometry easily modifiable for magnetic field detection via Faraday rotation. Using dielectric sensors and an optical fibre-based readout ensures minimal field perturbations compared to conductive probes and greatly limits unwanted electrical pickup between probe and recording system. The device was tested at the Vulcan Petawatt facility with 1020 W cm-2 peak intensities, the first time such a diagnostic has been used in this regime. The probe crystals were located ~1.25 m from target and did not require direct view of the source plasma. The measured signals compare favourably with previously reported studies from Vulcan, in terms of the maximum measured intra-crystal field of 10.9 kV/m, signal duration and detected frequency content which was found to match the interaction chamber's horizontal-plane fundamental harmonics of 76 and 101 MHz. Methods for improving the diagnostic for future use are also discussed in detail. Orthogonal optical probes offer a low-noise alternative for direct simultaneous measurement of each vector field component.

The association of waist circumference with walking difficulty among adults with or at risk of knee osteoarthritis: the Osteoarthritis Initiative.

OBJECTIVE: Excess weight is a known risk factor for functional limitation and common in adults with knee osteoarthritis (OA). We asked to what extent high waist circumference was linked with developing difficulty with walking speed and distance over 4 years in adults with or at risk of knee OA. METHOD: Using data from the Osteoarthritis Initiative (OAI), we employed World Health Organization (WHO) categories for Body Mass Index (BMI) and waist circumference (small/medium and large). Difficulty with speed was defined by slow gait: <1.2 m/s during a 20-m walk, and difficulty with distance was defined by an inability to walk 400 m. We calculated risk ratios (RR) to examine the likelihood of developing difficulty with distance and speed using obesity and waist circumference as predictors with RRs adjusted for potential confounders (i.e., age, sex, race, education, physical activity, and OA status). RESULTS: Participants with obesity and large waists were 2.2 times more likely to have difficulty with speed at 4 years compared to healthy weight and small/medium waisted participants (Adjusted RR 2.2 [95% Confidence interval (CI) 1.6, 3.1], P < .0001). Participants with obesity and a large waist circumference had 2.4 times the risk of developing the inability to walk 400 m compared with those with a healthy BMI and small/medium waist circumference (Adjusted RR 0.9 [95% CI 1.6, 3.7], P < .0001). CONCLUSIONS: Waist circumference may be a main risk factor for developing difficulty with speed in adults with or at risk of knee OA.

The immediate effect of dry needling on multifidus muscles' function in healthy individuals.

BACKGROUND: Dry needling of muscles is mainly used for the management of pain in musculoskeletal disorders. Yet, the association between dry needling and motor performance of muscles is still unclear. OBJECTIVE: To investigate the immediate effect of dry needling on lumbar multifidus muscles' function in healthy subjects. METHODS: Twenty-eight volunteers were divided randomly into: study group (13 subjects) and control group (15 subjects) who underwent no intervention. Study group received dry needling to the lumbar multifidus muscles using a deep insertion technique with 4 needles (2 on each side of the spine). The needles were left in situ for 10 minutes. Ultrasound imaging was used to measure multifidus muscles' thickness, pre and post-procedure during rest in a prone position and during contralateral active straight leg extension. RESULTS: Significant difference was found in the percentage of change of muscle activation post needling between groups on the right side at level L4-5. A slight increase in the percentage of muscle activity, post procedure was observed in the dry needling group compared with the control group, although not significant in other segments examined. CONCLUSION: An improvement of back muscle function following dry needling procedure in healthy individuals was found. This implies that dry needling might stimulate motor nerve fibers and as such increase muscle activity.

Older Adults with Chronic Low Back Pain: A Clinical Population Vulnerable to Frailty?

The purpose of this secondary analysis was to explore the differences in proportions of frailty criteria, pre-frailty, and frailty in older adults with and without chronic low back pain (CLBP). Among individuals with CLBP, we also explored whether the proportions of these outcomes differed based on pain intensity status. Using measures to determine weakness, slowness, and exhaustion, we determined that older adults with CLBP had higher proportions of frailty criteria and were more likely to be classified as pre-frail or frail. Older adults with high intensity CLBP had greater proportions of weakness, exhaustion, and pre-frailty/frailty compared to those with low intensity CLBP. These preliminary findings suggest older adults with CLBP may be at a higher risk for frailty than those without pain; pain intensity may be an important factor in assessing risk of frailty in this population.

Lack of association between prehospital response times and patient outcomes.

BACKGROUND: Limited data exist that examine the relationship between prehospital response times (RTs) and improved patient outcomes. Objective. We tested the hypothesis that patient outcomes do not differ substantially based on an explicitly chosen advanced life support (ALS) RT upper limit of 10 minutes 59 seconds (10:59 minutes). METHODS: This case-control retrospective study was conducted in a metropolitan county with a population of 750,000 for the calendar year 2004. The emergency medical services (EMS) system is a single-tiered, ALS paramedic service that includes basic life support (BLS) first responders. The 90% fractile RT specification required by contractual agreement is 10:59 minutes or less for emergency, life-threatening (Priority 1) calls. Cases (study patients), defined as Priority 1 transports with RTs exceeding 10:59 minutes, were compared with controls, which comprised a random sample of Priority 1 calls with RTs of 10:59 minutes or less. Prehospital run reports and hospital outcomes were evaluated using explicit criteria by one observer for the primary outcome of in-hospital death and secondary outcomes of critical interventions performed in the field. We tested the hypothesis of equivalence using the 95% confidence intervals (CIs) for difference in proportions with alpha = 0.05 and beta = 0.2 to show Delta = +/- 5%. RESULTS: Of the 3,270 emergency transports in 2004, we identified 373 study patients (RT > 10:59 min) and a random sample of 373 controls (RT < or = 10:59 min). Survival to hospital discharge was 80% (76% to 84%) for study patients vs. 82% (77% to 85%) for controls, yielding a 95% CI for the difference of -6 to +4%. ALS procedures were performed in 47.7% (95% CI: 43% to 53%) of study patients vs. 45.4% (40% to 51%) of controls (95% difference in proportions -10 to +5%). The most frequently performed procedures were administration of nitroglycerine and endotracheal intubation. CONCLUSIONS: Compared with patients who wait 10:59 minutes or less for ALS response, Priority 1 patients who wait longer than 10:59 minutes could experience between a 6% increase and a 4% decrease in mortality, and do not have an increase in critical procedures performed in the field. Our data are most consistent with the inference that neither the mortality nor the frequency of critical procedural interventions varies substantially based on this prespecified ALS RT.