Comparative Effectiveness of Step-up Therapies in Children with Asthma Prescribed Inhaled Corticosteroids : A Historical Cohort Study

This work was supported by the Respiratory Effectiveness Group. Acknowledgments We thank the Respiratory Effectiveness Group for funding this work, Annie Burden for assistance with statistics, and Simon Van Rysewyk and Lisa Law for assistance with medical writing.Peer reviewedPostprin

Direct shock compression experiments on premolten forsterite and progress toward a consistent high-pressure equation of state for CaO-MgO-Al_2O_3-SiO_2-FeO liquids

We performed shock compression experiments on preheated forsterite liquid (Mg_2SiO_4) at an initial temperature of 2273 K and have revised the equation of state (EOS) that was previously determined by shock melting of initially solid Mg_2SiO_4 (300 K). The linear Hugoniot, U_S = 2.674 ± 0.188 + 1.64 ± 0.06 u_p km/s, constrains the bulk sound speed within a temperature and composition space as yet unexplored by 1 bar ultrasonic experiments. We have also revised the EOS for enstatite liquid (MgSiO_3) to exclude experiments that may have been only partially melted upon shock compression and also the EOS for anorthite (CaAl_2SiO_6) liquid, which now excludes potentially unrelaxed experiments at low pressure. The revised fits and the previously determined EOS of fayalite and diopside (CaMg_2SiO_6) were used to produce isentropes in the multicomponent CaO-MgO-Al_2O_3-SiO_2-FeO system at elevated temperatures and pressures. Our results are similar to those previously presented for peridotite and simplified “chondrite” liquids such that regardless of where crystallization first occurs, the liquidus solid sinks upon formation. This process is not conducive to the formation of a basal magma ocean. We also examined the chemical and physical plausibility of the partial melt hypothesis to explain the occurrence and characteristics of ultra-low velocity zones (ULVZ). We determined that the ambient mantle cannot produce an equilibrium partial melt and residue that is sufficiently dense to be an ultra-low velocity zone mush. The partial melt would need to be segregated from its equilibrium residue and combined with a denser solid component to achieve a sufficiently large aggregate density

Estimates of genetic parameters of distal limb fracture and superficial digital flexor tendon injury in UK Thoroughbred racehorses

A retrospective cohort study of distal limb fracture and superficial digital flexor tendon (SDFT) injury in Thoroughbred racehorses was conducted using health records generated by the British Horseracing Authority (BHA) between 2000 and 2010. After excluding records of horses that had both flat and jump racing starts, repeated records were reduced to a single binary record per horse (<i>n</i> = 66,507, 2982 sires), and the heritability of each condition was estimated using residual maximum likelihood (REML) with animal logistic regression models. Similarly, the heritability of each condition was estimated for the flat racing and jump racing populations separately. Bivariate mixed models were used to generate estimates of genetic correlations between SDFT injury and distal limb fracture. The heritability of distal limb fracture ranged from 0.21 to 0.37. The heritability of SDFT injury ranged from 0.31 to 0.34. SDFT injury and distal limb fracture were positively genetically correlated. These findings suggest that reductions in the risk of the conditions studied could be attempted using targeted breeding strategies

Applying UK real world primary care data to predict asthma attacks in 3776 well-characterised children : a retrospective cohort study

FUNDING This analysis was funded by Respiratory Effectiveness Group DATA AVAILABILITY STATEMENT Data are available from Clinical Practice Research Datalink (https://www.cprd.com/home/) and Optimum Patient Care (http://optimumpatientcare.org/about-us/).Peer reviewedPublisher PD

Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions.

ObjectiveTo determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk.MethodsBreast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18-21 days after rituximab infusion in 4 patients. Five additional patients provided 1-2 samples at various times after rituximab infusion.ResultsThe median average rituximab concentration in mature breast milk was low at 0.063 μg/mL (range 0.046-0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%-0.10%). Most patients had a maximum concentration at 1-7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 μg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion.ConclusionsWe determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding

Preheated shock experiments in the molten CaAl_2Si_2O_8-CaFeSi_2O_6-CaMgSi_2O_6 ternary: A test for linear mixing of liquid volumes at high pressure and temperature

We performed 17 new shock wave experiments on preheated (1673 K) hedenbergite liquid (CaFeSi_2O_6) and two model basalt liquids (an equimolar binary mix of CaAl_2Si_2O_8 + CaFeSi_2O_6 and an equimolar ternary mix of CaAl_2Si_2O_8 + CaFeSi_2O_6 +CaMgSi_2O_6) in order to determine their equations of state (EOS). Ambient pressure density measurements on these and other Fe-bearing silicate liquids indicate that FeO has a partial molar volume that is highly dependent on composition, which leads to large errors in estimates of the densities of Fe-bearing liquids at ambient pressure based on an ideal mixing of any fixed set of end-member liquids. We formulated a series of mixing tests using the EOS determined in this study to examine whether ideal mixing of volumes might nevertheless suffice to describe the ternary system CaAl_2Si_2O_8-CaFeSi_2O_6-CaMgSi_2O_6 at high temperature and pressure. The ideal mixing null hypothesis is rejected; compositional variations in partial molar volume of FeO appear to extend to high pressure. Only densities of Fe-bearing liquid mixtures with oxide mole fraction of FeO less than 0.06 can be adequately approximated using an ideal solution

Multi-technique equation of state for Fe_(2)SiO_4 melt and the density of Fe-bearing silicate melts from 0 to 161 GPa

We have conducted new equation of state measurements on liquid Fe_(2)SiO_4 in a collaborative, multi-technique study. The liquid density (ρ), the bulk modulus (K), and its pressure derivative (K′) were measured from 1 atm to 161 GPa using 1-atm double-bob Archimedean, multi-anvil sink/float, and shock wave techniques. Shock compression results on initially molten Fe_(2)SiO_4 (1573 K) fitted with previous work and the ultrasonically measured bulk sound speed (C_o) in shock velocity (U_S)-particle velocity (u_p) space yields the Hugoniot: U_S = 1.58(0.03) u_p + 2.438(0.005) km/s. Sink/float results are in agreement with shock wave and ultrasonic data, consistent with an isothermal K_T = 19.4 GPa and K′ = 5.33 at 1500°C. Shock melting of initially solid Fe_(2)SiO_4 (300 K) confirms that the Grüneisen parameter (γ) of this liquid increases upon compression where γ = γ_o(ρ_(o)/ρ)^q yields a q value of –1.45. Constraints on the liquid fayalite EOS permit the calculation of isentropes for silicate liquids of general composition in the multicomponent system CaO-MgO-Al_(2)O_3-SiO_2-FeO at elevated temperatures and pressures. In our model a whole mantle magma ocean would first crystallize in the mid-lower mantle or at the base of the mantle were it composed of either peridotite or simplified “chondrite” liquid, respectively. In regards to the partial melt hypothesis to explain the occurrence and characteristics of ultra-low velocity zones, neither of these candidate liquids would be dense enough to remain at the core mantle boundary on geologic timescales, but our model defines a compositional range of liquids that would be gravitationally stable

Multi‐technique equation of state for Fe 2 SiO 4 melt and the density of Fe‐bearing silicate melts from 0 to 161 GPa

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95366/1/jgrb17308.pd

Supporting Online Learning for Advanced Placement Students in Small Rural Schools: Conceptual Foundations and Intervention Components of the Facilitator Preparation Program

This paper examines the need for interventions to support students who are taking advanced placement courses in small rural districts and describes the Facilitator Preparation Program (FPP) as a strategy to address this need. Issues in the delivery of Online Distance Education (ODE) in small rural schools are summarized and the conceptual foundations and service delivery considerations of the FPP are outlined. Future research needs are also considered

The impact of streetlights on an aquatic invasive species: artificial light at night alters signal crayfish behaviour

Artificial light at night (ALAN) can significantly alter the behaviour, communication and orientation of animals, and will potentially interact with other stressors to affect biodiversity. Invasive, non-native species are one of the largest threats to freshwater biodiversity; however, the impact of ALAN on such species is unknown. This study assessed the effects of ALAN at ecologically relevant levels on the behaviour of a globally widespread invasive species, the signal crayfish (Pacifastacus leniusculus). In experimental aquaria, crayfish were exposed to periods of daylight, control (<0.1 lx) and street-lit nights to test two hypotheses: (1) signal crayfish under natural conditions are nocturnal animals, spending more time in shelter during the day, whilst active and interacting during the night, and (2) ALAN reduces crayfish activity and intraspecific interactions, whilst increasing their propensity to use shelter. Our results confirm that signal crayfish are largely nocturnal, showing peak activity and interaction levels during control nights, whilst taking refuge during daylight hours. When exposed to short-term simulated light pollution from a streetlight at night however, activity and interactions with conspecifics were significantly reduced compared to control nights, whilst time spent in shelters increased. By altering crayfish behaviour, ALAN may change the ecosystem impacts of invasive crayfish in the wild. This study is the first to show an impact of ALAN on the behaviour of an invasive, non-native species, and provides information for the management of invasive crayfish in areas where ALAN is prevalent