A recurrent nova super-remnant in the Andromeda galaxy.

The accretion of hydrogen onto a white dwarf star ignites a classical nova eruption1,2-a thermonuclear runaway in the accumulated envelope of gas, leading to luminosities up to a million times that of the Sun and a high-velocity mass ejection that produces a remnant shell (mainly consisting of insterstellar medium). Close to the upper mass limit of a white dwarf3 (1.4 solar masses), rapid accretion of hydrogen (about 10-7 solar masses per year) from a stellar companion leads to frequent eruptions on timescales of years4,5 to decades6. Such binary systems are known as recurrent novae. The ejecta of recurrent novae, initially moving at velocities of up to 10,000 kilometres per second7, must 'sweep up' the surrounding interstellar medium, creating cavities in space around the nova binary. No remnant larger than one parsec across from any single classical or recurrent nova eruption is known8-10, but thousands of successive recurrent nova eruptions should be capable of generating shells hundreds of parsecs across. Here we report that the most frequently recurring nova, M31N 2008-12a in the Andromeda galaxy (Messier 31 or NGC 224), which erupts annually11, is indeed surrounded by such a super-remnant with a projected size of at least 134 by 90 parsecs. Larger than almost all known remnants of even supernova explosions12, the existence of this shell demonstrates that the nova M31N 2008-12a has erupted with high frequency for millions of years.

Sourcebook update: using near-infrared spectroscopy to assess skeletal muscle oxygen uptake.

Monitoring the metabolic cost or oxygen consumption associated with rest and exercise is crucial to understanding the impact of disease or physical training on the health of individuals. Traditionally, measuring the skeletal muscle oxygen cost associated with exercise/muscle contractions can be rather expensive or invasive (i.e., muscle biopsies). More recently, specific protocols designed around the use of near-infrared spectroscopy (NIRS) have been shown to provide a quick, noninvasive easy-to-use tool to measure skeletal muscle oxygen consumption ([Formula: see text]). However, the data and results from NIRS devices are often misunderstood. Thus the primary purpose of this sourcebook update is to provide several experimental protocols students can utilize to improve their understanding of NIRS technology, learn how to analyze results from NIRS devices, and better understand how muscle contraction intensity and type (isometric, concentric, or eccentric) influence the oxygen cost of muscle contractions.NEW & NOTEWORTHY Compared to traditional methods, near-infrared spectroscopy (NIRS) provides a relatively cheap and easy-to-use noninvasive technique to measure skeletal muscle oxygen uptake following exercise. This laboratory not only enables students to learn about the basics of NIRS and muscle energetics but also addresses more complex questions regarding skeletal muscle physiology.

Evaluating the performance of Bayesian geostatistical prediction with physical barriers in the Chesapeake Bay.

The Chesapeake Bay is one of the most widely studied bodies of water in the United States and around the world. Routine monitoring of water quality indicators (e.g., salinity) relies on fixed sampling stations throughout the Bay. Utilizing this rich monitoring data, various methods produce surface predictions of water quality indicators to further characterize the health of the Bay as well as to support wildlife and human health research studies. Bayesian approaches for geostatistical modelling are becoming increasingly popular and can be preferred over frequentist approaches because full and exact inference can be computed, along with more accurate characterization of uncertainty. Traditional geostatistical prediction methods assume a Euclidean distance between two points when characterizing spatial dependence as a function of distance. However, Euclidean approaches may not be appropriate in estuarine environments when water-land boundaries are crossed during the modelling process. In this study, we compare stationary and barrier INLA geostatistical models with a classic kriging geostatistical model to predict salinity in the Chesapeake Bay during 4 months in 2019. Cross-validation is conducted for each approach to evaluate model performance based on prediction accuracy and precision. The results provide evidence that the two Bayesian-based models outperformed ordinary kriging, especially when examining prediction accuracy (most notably in the tributaries). We also suggest that the non-Euclidean model accounts for the appropriate water-based distances between sampling locations and is likely better at characterizing the uncertainty. However, more complex bodies of water may better showcase the capabilities and efficacy of the physical barrier INLA model.

Analysis of electrical stimulation and voluntary muscle contraction on skeletal muscle oxygen uptake and mitochondrial recovery using near-infrared spectroscopy.

PURPOSE: This investigation was to compare differences in skeletal muscle oxygen consumption ([Formula: see text]) and mitochondrial recovery between voluntary (VOL) and electrically stimulated (ES) plantarflexion contractions. METHODS: Twelve men and women (26 ± 4.0 years; 171.8 ± 5.1 cm; 74.0 ± 13.7 kg) were seated in a chair with their right knee fully extended and right foot secured to a force transducer. ES electrodes and a near-infrared spectroscopy device were placed on the gastrocnemius. Participants performed ES plantarflexion contractions across a range of stimulation intensities at frequencies of 1 and 2 Hz and similar VOL contractions. Cuff occlusion occurred immediately following each series of contractions to measure [Formula: see text]. A standardized mitochondrial function assessment protocol was also performed to calculate K-constants between work-matched ES and VOL contractions. RESULTS: For mitochondrial assessments, there were no significant differences between ES and VOL rate constants (2.03 ± 0.98 vs. 1.25 ± 1.35 min-1, p = 0.266). ES resulted in a significantly greater workrate-[Formula: see text] slope at 1 Hz (0.007 ± 0.007 vs. 0.001 ± 0.002% [Formula: see text]/s/N, p = 0.014) and 2 Hz (0.010 ± 0.010 vs. 0.001 ± 0.001% [Formula: see text]/s/N, p = 0.012), as well as a significantly greater workrate-[Formula: see text] Y-intercept at 2 Hz (1.603 ± 1.513 vs. 0.556 ± 0.564% [Formula: see text]/s, p = 0.035) but not 1 Hz (0.579 ± 0.448 vs. 0.442 ± 0.357% mV̇O2/s, p = 0.535) when compared to VOL. CONCLUSION: ES results in a significantly greater [Formula: see text] at similar work rates compared to VOL, however, the mitochondrial recovery rate constants were similar. The greater mVO2 with ES may partially contribute to the increased rate of fatigue during ES exercise in individuals with muscle paralysis.

Hemodynamic Changes in an Actively Rupturing Abdominal Aortic Aneurysm.

Computational fluid dynamics were used to assess hemodynamic changes in an actively rupturing abdominal aortic aneurysm (AAA) over a 9-day period. Active migration of contrast from the lumen into the thickest region of intraluminal thrombus (ILT) was demonstrated until it ultimately breached the adventitial layer. Four days after symptom onset, there was a discrete disruption of adventitial calcium with bleb formation at the site of future rupture. Rupture occurred in a region of low wall shear stress and was associated with a marked increase in AAA diameter from 6.6 to 8.4 cm. The cross-sectional area of the flow lumen increased across all time points from 6.28 to 12.08 cm2. The increase in luminal area preceded the increase in AAA diameter and was characterized by an overall deceleration in recirculation flow velocity with a coinciding increase in flow velocity penetrating the ILT. We show that there are significant hemodynamic and structural changes in the AAA flow lumen in advance of any appreciable increase in aortic diameter or rupture. The significant increase in AAA diameter with rupture suggests that AAA may actually rupture at smaller sizes than those measured on day of rupture. These findings have implications for algorithms the predict AAA rupture risk.

The association between carotid disease, arterial stiffness and diabetic retinopathy in type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIM: To determine whether macrovascular disease assessed by carotid ultrasonography and arterial stiffness by pulse wave velocity are independently associated with diabetic retinopathy in type 2 diabetes. METHODS: A random subgroup of surviving participants with type 2 diabetes from the Fremantle Diabetes Study Phase II were invited to take part in this sub-study in 2018-2019. In addition to standardized questionnaires, a physical examination and fasting biochemical tests, each underwent dilated colour fundus photography, carotid arterial ultrasonography with measurement of the intima-media thickness (IMT) and quantification of the degree of stenosis, and pulse wave analysis calculation of the carotid-femoral pulse wave velocity (cfPWV). The cross-sectional association between arterial disease parameters and diabetic retinopathy was assessed using generalized estimating equation models which enabled both eyes to be included in the analysis. RESULTS: Some 270 participants [mean ± sd age 72 ± 9 years, 153 (57%) men and median (IQR) diabetes duration 15 (11-22) years] were included in analysis. Of 524 assessable eyes, 82 (16%) had diabetic retinopathy. In multivariable analysis, significant independent associates of diabetic retinopathy were age at diabetes diagnosis (inversely), HbA1c , insulin treatment and urinary albumin to creatinine ratio (all P ≤ 0.022), as well as cfPWV [odds ratio (OR) 1.13, 95% confidence interval (CI) 1.03, 1.23 per 1 m/s increase; P = 0.008] and common carotid artery (CCA) IMT ≥1 mm (OR 2.95, 95% CI 1.21, 7.23; P = 0.018). CONCLUSIONS: The association between diabetic retinopathy and CCA IMT suggests that carotid disease may share cardiovascular risk factors with diabetic retinopathy. The association between diabetic retinopathy and cfPWV may reflect the consequences of altered intravascular haemodynamics.

Dilatational rheology of water-in-diesel fuel interfaces: effect of surfactant concentration and bulk-to-interface exchange.

Micrometer-sized water droplets dispersed in diesel fuel are stabilized by the fuel's surface-active additives, such as mono-olein and poly(isobutylene)succinimide (PIBSI), making the droplets challenging for coalescing filters to separate. Dynamic material properties found from interfacial rheology are known to influence the behavior of microscale droplets in coalescing filters. In this work, we study the interfacial dilatational properties of water-in-fuel interfaces laden with mono-olein and PIBSI, with a fuel phase of clay-treated ultra-low sulphur diesel (CT ULSD). First, the dynamic interfacial tension (IFT) is measured using pendant drop tensiometry, and a curvature-dependent form of the Ward and Tordai diffusion equation is applied for extracting the diffusivity of the surfactants. Additionally, Langmuir kinetics are applied to the dynamic IFT results to obtain the maximum surface concentration (Γ∞) and ratio of adsorption to desorption rate constants (κ). We then use a capillary pressure microtensiometer to measure the interfacial dilatational modulus, and further extract the characteristic frequency of surfactant exchange (ω0) by fitting a model assuming diffusive exchange between the interface and bulk. In this measurement, 50-100 µm diameter water droplets are pinned at the tip of a glass capillary in contact with the surfactant-containing fuel phase, and small amplitude capillary pressure oscillations over a range of frequencies from 0.45-20 rad s-1 are applied to the interface, inducing changes in interfacial tension and area to yield the dilatational modulus, E*(ω). Over the range of concentrations studied, the dilatational modulus of CT ULSD with either mono-olein or PIBSI increases with a decrease in bulk concentration and plateaus at the lowest concentrations of mono-olein. Characteristic frequency (ω0) values extracted from the fit are compared with those calculated using equilibrium surfactant parameters (κ and Γ∞) derived from pendant drop tensiometry, and good agreement is found between these values. Importantly, the results imply that diffusive exchange models based on the equilibrium relationships between surfactant concentration and interfacial tension can be used to infer the dynamic dilatational behavior of complex surfactant systems, such as the water-in-diesel fuel interfaces in this study.

DEVELOPING twin-specific 75-g oral glucose tolerance test diagnostic thresholds for gestational diabetes based on the risk of future maternal diabetes: a population-based cohort study.

OBJECTIVE: To develop twin-specific outcome-based oral glucose tolerance test (OGTT) diagnostic thresholds for GDM based on the risk of future maternal type-2 diabetes. DESIGN: A population-based retrospective cohort study (2007-2017). SETTING: Ontario, Canada. METHODS: Nulliparous women with a live singleton (n = 55 361) or twin (n = 1308) birth who underwent testing for gestational diabetes mellitus (GDM) using a 75-g OGTT in Ontario, Canada (2007-2017). We identified the 75-g OGTT thresholds in twin pregnancies that were associated with similar incidence rates of future type-2 diabetes to those associated with the standard OGTT thresholds in singleton pregnancies. RESULTS: For any given 75-g OGTT value, the incidence rate of future maternal type-2 diabetes was lower for women with a twin than women with a singleton pregnancy. Using women with a negative OGTT as reference, the risk of future maternal type-2 diabetes in twin pregnancies with a positive OGTT based on the standard OGTT thresholds (9.86 per 1000 person years, adjusted hazard ratio (aHR) 4.79, 95% CI 2.69-8.51) was lower than for singleton pregnancies with a positive OGTT (18.74 per 1000 person years, aHR 8.22, 95% CI 7.38-9.16). The twin-specific OGTT fasting, 1-hour and 2-hour thresholds identified in the current study based on correlation with future maternal type-2 diabetes were 5.8 mmol/l (104 mg/dl), 11.8 mmol/l (213 mg/dl) and 10.4 mmol/l (187 mg/dl), respectively. CONCLUSIONS: We identified potential twin-specific OGTT thresholds for GDM that are associated with a similar risk of future type-2 diabetes to that observed in women diagnosed with GDM in singleton pregnancies based on standard OGTT thresholds. TWEETABLE ABSTRACT: Potential twin-specific OGTT thresholds for GDM were identified.

Insights into the Microscale Coalescence Behavior of Surfactant-Stabilized Droplets Using a Microfluidic Hydrodynamic Trap.

Coalescence of micrometer-scale droplets is impacted by several parameters, including droplet size, viscosities of the two phases, droplet velocity, angle of approach, as well as interfacial tension and surfactant coverage. The thinning dynamics of films between coalescing droplets can be particularly complex in the presence of surfactants, due to the generation of Marangoni stresses and reduced film mobility. Here, a microfluidic hydrodynamic "Stokes" trap is used to gently steer and trap surfactant-laden micrometer-sized droplets at the center of a cross-slot. Water droplets are formed upstream of the cross-slot using a microfluidic T-junction, in heavy and light mineral oils and stabilized using SPAN 80, an oil-soluble surfactant. Incoming droplets are made to coalesce with the trapped droplet, yielding measurements of the film drainage time. Film drainage times are measured as a function of continuous phase viscosity, incoming droplet speed, trapped droplet size, and surfactant concentrations above and below the critical micelle concentration (CMC). As expected, systems with higher surfactant concentrations and slower incoming droplet speed exhibit longer film drainage times. At low surfactant concentrations, the drainage time is longer for the more viscous heavy mineral oil in the continuous phase, whereas at high surfactant concentrations, the dependence on continuous phase viscosity vanishes. Perhaps more surprisingly, larger droplets and high confinement also result in longer film drainage times, potentially due to deformation of the droplet interfaces. The results are used here to determine critical conditions for coalescence, including both an upper and a lower critical capillary number. Moreover, it is shown that induced surfactant concentration gradient effects enable coalescence events after the droplets had originally flocculated, at surfactant concentrations above the CMC. The microfluidic hydrodynamic trap provides new insights into the role of surfactants in film drainage and opens avenues for controlled coalescence studies at micrometer length scales and millisecond time scales.

Addressing embodied inequities in health: how do we enable improvement in women's diet in pregnancy?

OBJECTIVE: To disrupt cycles of health inequity, traceable to dietary inequities in the earliest stages of life, public health interventions should target improving nutritional wellbeing in preconception/pregnancy environments. This requires a deep engagement with pregnant/postpartum people (PPP) and their communities (including their health and social care providers, HSCP). We sought to understand the factors that influence diet during pregnancy from the perspectives of PPP and HSCP, and to outline intervention priorities. DESIGN: We carried out thematic network analyses of transcripts from ten focus group discussions (FGD) and one stakeholder engagement meeting with PPP and HSCP in a Canadian city. Identified themes were developed into conceptual maps, highlighting local priorities for pregnancy nutrition and intervention development. SETTING: FGD and the stakeholder meeting were run in predominantly lower socioeconomic position (SEP) neighbourhoods in the sociodemographically diverse city of Hamilton, Canada. PARTICIPANTS: All local, comprising twenty-two lower SEP PPP and forty-three HSCP. RESULTS: Salient themes were resilience, resources, relationships and the embodied experience of pregnancy. Both PPP and HSCP underscored that socioeconomic-political forces operating at multiple levels largely determined the availability of individual and relational resources constraining diet during pregnancy. Intervention proposals focused on cultivating individual and community resilience to improve early-life nutritional environments. Participants called for better-integrated services, greater income supports and strengthened support programmes. CONCLUSIONS: Hamilton stakeholders foregrounded social determinants of inequity as main factors influencing pregnancy diet. They further indicated a need to develop interventions that build resilience and redistribute resources at multiple levels, from the household to the state.

Improving systems of care during and after a pregnancy complicated by hyperglycaemia: A protocol for a complex health systems intervention.

BACKGROUND: Many women with hyperglycaemia in pregnancy do not receive care during and after pregnancy according to standards recommended in international guidelines. The burden of hyperglycaemia in pregnancy falls disproportionately upon Indigenous peoples worldwide, including Aboriginal and Torres Strait Islander women in Australia. The remote and regional Australian context poses additional barriers to delivering healthcare, including high staff turnover and a socially disadvantaged population with a high prevalence of diabetes. METHODS: A complex health systems intervention to improve care for women during and after a pregnancy complicated by hyperglycaemia will be implemented in remote and regional Australia (the Northern Territory and Far North Queensland). The Theoretical Domains Framework was used during formative work with stakeholders to identify intervention components: (1) increasing workforce capacity, skills and knowledge and improving health literacy of health professionals and women; (2) improving access to healthcare through culturally and clinically appropriate pathways; (3) improving information management and communication; (4) enhancing policies and guidelines; (5) embedding use of a clinical register as a quality improvement tool. The intervention will be evaluated utilising the RE-AIM framework at two timepoints: firstly, a qualitative interim evaluation involving interviews with stakeholders (health professionals, champions and project implementers); and subsequently a mixed-methods final evaluation of outcomes and processes: interviews with stakeholders; survey of health professionals; an audit of electronic health records and clinical register; and a review of operational documents. Outcome measures include changes between pre- and post-intervention in: proportion of high risk women receiving recommended glucose screening in early pregnancy; diabetes-related birth outcomes; proportion of women receiving recommended postpartum care including glucose testing; health practitioner confidence in providing care, knowledge and use of relevant guidelines and referral pathways, and perception of care coordination and communication systems; changes to health systems including referral pathways and clinical guidelines. DISCUSSION: This study will provide insights into the impact of health systems changes in improving care for women with hyperglycaemia during and after pregnancy in a challenging setting. It will also provide detailed information on process measures in the implementation of such health system changes.

Revealing Color Forces with Transverse Polarized Electron Scattering.

The Spin Asymmetries of the Nucleon Experiment measured two double spin asymmetries using a polarized proton target and polarized electron beam at two beam energies, 4.7 and 5.9 GeV. A large-acceptance open-configuration detector package identified scattered electrons at 40° and covered a wide range in Bjorken x (0.3

Population-based mortality data suggests remediation is modestly effective in two Montana Superfund counties.

The health effects of living in proximity to Superfund sites with ongoing remediation were evaluated for residents of two contiguous Montana counties, Deer Lodge and Silver Bow. Deer Lodge and Silver Bow are home to the Anaconda Smelter and Silver Bow Creek/Butte Area Superfund sites, respectively. Established by the Environmental Protection Agency in 1983, both sites have had ongoing remediation for decades. Employing county level death certificate data obtained from the Centers for Disease Control and Prevention WONDER site, sex and age-adjusted standardized mortality ratios (SMRs) for composite targeted causes of death were calculated using observed versus expected mortality for both counties, and compared to the expected mortality from the remaining Montana counties. Cancers, cerebro- and cardiovascular diseases (CCVD), and organ failure were elevated for the two counties during the study period, 2000-2016, with SMRs of 1.19 (95% CI 1.10, 1.29); 1.36 (95% CI 1.29, 1.43); and 1.24 (95% CI 1.10, 1.38), respectively. Neurological conditions were not elevated for the two counties (SMR = 1.01; 95% CI 0.89, 1.14). Time trend analyses performed using Cox regression models indicate that deaths from cancers (HR = 0.97; p = 0.0004), CCVDs (HR = 0.95; p ≤ 0.0001), and neurological conditions (HR = 0.97; p = 0.01) decreased over the study period. While the ecological approach applied limits the interpretation of our results, our study suggests that while mortality is elevated, it is also decreasing over time for these two Superfund sites.

Analysis of water sports injuries admitted to a pediatric trauma center: a 13 year experience.

BACKGROUND: Unintentional injury is the leading cause of death in children and adolescents. Injuries occurring during boating and recreational water sports are poorly described in the literature. Herein, we compare injuries from water sports to those resulting from motor vehicle collisions, which are better described in existing literature. METHODS: A retrospective review of 1935 consecutive pediatric trauma patients, as defined by age < 18 years, admitted to a single level-1 pediatric trauma center between January 2000 and August 2013 was performed. Patients were divided into two cohorts based on the mechanism of injury: water sports injury (WSI) or motor vehicle collision (MVC). Demographics, injury descriptors, and outcomes were reviewed for each patient. Categorical variables were compared by Chi square or Fisher's exact test, and continuous by t test or Mann-Whitney U test. Parametric data are reported as mean ± standard deviation and nonparametric as median (interquartile range). Significance was set at alpha level 0.05. RESULTS: A total of 18 pediatric patients were admitted for WSI and 615 for MVC during the study period. Among those with WSI, mean age was 12 ± 4 years, mean Injury Severity Score (ISS) was 11 ± 10, and mean Revised Trauma Score (RTS) was 7.841(IQR 6.055-7.841). 44% of WSI occurred by personal watercraft (Jet Ski, WaveRunner), 39% by boat, and 17% by other means (e.g., diving, tubing, kite surfing). Overall, the most common WSI included skin/soft-tissue lacerations (59%), head injury/concussion (33%), tendon/ligament lacerations (28%), and extremity fractures (28%). Compared to 615 patients admitted for MVC, age, sex, race, Glasgow Coma Scale, ISS, RTS, spleen and liver laceration rates, neurosurgical consultation, ICU admission, ICU and total length of stay, and mortality were similar. Patients with WSI were more likely to be tourists (44% vs. 5%, p < 0.001). Those with WSI showed a significantly higher requirement for any surgical intervention (61% vs. 15%, p = 0.001). The rate of open fracture (28% vs. 6%, p = 0.006) and, subsequently, orthopedic procedures (39% vs. 17%, p = 0.027) were also higher in the WSI group. CONCLUSION: Overall, water sports injuries are similar in in-hospital mortality to motor vehicle collisions. They are more likely to result in penetrating trauma and more likely to require surgical intervention. Primary and secondary prevention strategies should specifically target personal watercraft usage and tourist populations.

Fischer-Tropsch synthesis. Evaluation of an aluminum small channel reactor.

Fischer-Tropsch synthesis was conducted in a small channel compact heat exchange reactor that was constructed of aluminum. While limited to lower temperature-pressure regions of the Fischer-Tropsch synthesis, the reactor could be operated in an isothermal mode with nearly a constant temperature along the length of the channel. The results obtained with the compact heat exchange reactor were similar to those obtained in the isothermal continuous stirred tank reactor, with respect to both activity and selectivity. Following a planned or unplanned shutdown, the reactor could be restarted to produce essentially the same catalytic activity and selectivity as before the shutdown.

Electron-transfer sensitization of H2 oxidation and CO2 reduction catalysts using a single chromophore.

Energy-storing artificial-photosynthetic systems for CO2 reduction must derive the reducing equivalents from a renewable source rather than from sacrificial donors. To this end, a homogeneous, integrated chromophore/two-catalyst system is described that is thermodynamically capable of photochemically driving the energy-storing reverse water-gas shift reaction (CO2 + H2 → CO + H2O), where the reducing equivalents are provided by renewable H2. The system consists of the chromophore zinc tetraphenylporphyrin (ZnTPP), H2 oxidation catalysts of the form [Cp(R)Cr(CO)3](-), and CO2 reduction catalysts of the type Re(bpy-4,4'-R2)(CO)3Cl. Using time-resolved spectroscopic methods, a comprehensive mechanistic and kinetic picture of the photoinitiated reactions of mixtures of these compounds has been developed. It has been found that absorption of a single photon by broadly absorbing ZnTPP sensitizes intercatalyst electron transfer to produce the substrate-active forms of each. The initial photochemical step is the heretofore unobserved reductive quenching of the low-energy T1 state of ZnTPP. Under the experimental conditions, the catalytically competent state decays with a second-order half-life of ∼15 µs, which is of the right magnitude for substrate trapping of sensitized catalyst intermediates.

A dual CysLT1/2 antagonist attenuates allergen-induced airway responses in subjects with mild allergic asthma.

BACKGROUND: The cysteinyl leukotrienes (cysLTs) play a key role in the pathophysiology of asthma. In addition to functioning as potent bronchoconstrictors, cysLTs contribute to airway inflammation through eosinophil and neutrophil chemotaxis, plasma exudation, and mucus secretion. We tested the activity of the dual cysLT1/2 antagonist, ONO-6950, against allergen-induced airway responses. METHODS: Subjects with documented allergen-induced early (EAR) and late asthmatic response (LAR) were randomized in a three-way crossover study to receive ONO-6950 (200 mg) or montelukast (10 mg) or placebo q.d. on days 1-8 of the three treatment periods. Allergen was inhaled on day 7 two hours postdose, and forced expiratory volume in 1 s (FEV1 ) was measured for 7 h following challenge. Sputum eosinophils and airway hyperresponsiveness were measured before and after allergen challenge. The primary outcome was the effect of ONO-6950 vs placebo on the EAR and LAR. RESULTS: Twenty-five nonsmoking subjects with mild allergic asthma were enrolled and 20 subjects completed all three treatment periods per protocol. ONO-6950 was well tolerated. Compared to placebo, ONO-6950 significantly attenuated the maximum % fall in FEV1 and area under the %FEV1 /time curve during the EAR and LAR asthmatic responses (P < 0.05) and allergen-induced sputum eosinophils. There were no significant differences between ONO-6950 and montelukast. CONCLUSIONS: Attenuation of EAR, LAR, and airway inflammation is consistent with cysLT1 blockade. Whether dual cysLT1/2 antagonism offers additional benefit for treatment of asthma requires further study.

Predictors of mortality in pediatric trauma: experiences of a level 1 trauma center and an assessment of the International Classification Injury Severity Score (ICISS).

OBJECTIVES: Injury severity scoring tools allow systematic comparison of outcomes in trauma research and quality improvement by indexing an expected mortality risk for certain injuries. This study investigated the predictive value of the empirically derived ICD9-derived Injury Severity Score (ICISS) compared to expert consensus-derived scoring systems for trauma mortality in a pediatric population. METHODS: 1935 consecutive trauma patients aged <18 years from 1/2000 to 12/2012 were reviewed. Mechanism of injury (MOI), Injury Severity Score (ISS), Revised Trauma Score (RTS), Trauma Score ISS (TRISS), and ICISS were compared using univariate and multivariate logistic regression analysis and receiver operator characteristic analysis. RESULTS: The population was a median age of 11 ± 6 year, 70 % male, and 76 % blunt injury. Median ISS 13 ± 12 and overall mortality 3.5 %. Independent predictors of mortality were initial hematocrit [odds ratio (OR) 0.83 (0.73-0.95)], HCO3 [OR 0.82 (0.67-0.98)], Glasgow Coma Scale score [OR 0.75 (0.62-0.90)], and ISS [OR 1.10 (1.04-1.15)]. TRISS was superior to ICISS in predicting survival [area under receiver operator curve: 0.992 (0.982-1.000) vs 0.888 (0.838-0.938)]. CONCLUSIONS: ICISS was inferior to existing injury scoring tools at predicting mortality in pediatric trauma patients.

Airway responsiveness to mannitol 24 h after allergen challenge in atopic asthmatics.

BACKGROUND: Airway responsiveness to indirect stimuli correlates positively with airway inflammation. In atopic asthmatics, allergen inhalation is associated with an influx of inflammatory cells and increased responsiveness to the direct-acting stimuli methacholine at 3 and 24 h after exposure. We have shown mannitol responsiveness decreases 3 h after allergen inhalation. The current investigation assessed mannitol responsiveness 24 h after allergen challenge. METHODS: Eleven mild atopic asthmatics completed allergen challenges on two separate occasions. In random order, methacholine or mannitol challenges were performed 24 h pre- and post-allergen challenge. Levels of fractional exhaled nitric oxide were also measured. RESULTS: Allergen challenge increased airway responsiveness to methacholine 24 h postchallenge; the geometric mean (95% CI) methacholine PC20 decreased from 5.9 mg/ml (1.8-19.4) to 2.2 mg/ml (0.81-5.89); P = 0.01. This coincided with a significant increase (P = 0.02) in FeNO levels. Conversely, allergen challenge decreased airway responsiveness to mannitol; geometric mean (95% CI) dose-response ratio was significantly higher after allergen exposure (57 mg/% FEV1 fall [27-121] to 147 mg/% FEV1 fall [57-379]; P = 0.03), and FeNO levels were not significantly increased (P = 0.054). CONCLUSION: Allergen-induced changes in airway responsiveness to direct and indirect stimuli are markedly different. The loss in responsiveness to mannitol is likely not explainable by a refractory state. The effect(s) of allergen exposure on airway responsiveness to indirect-acting stimuli require further investigation.