Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.

Despite decades of trials, the prognosis for diffuse intrinsic pontine gliomas (DIPG) remains dismal. DIPG is inoperable and standard treatment is radiation alone, as the addition of chemotherapeutic agents, such as temozolomide, have not improved survival. In addition to inherent chemoresistance, treatment of DIPG is impeded by an intact blood-brain barrier (BBB). VAL-083 is a structurally unique bi-functional DNA-targeting agent that readily crosses the BBB. VAL-083 forms interstrand DNA crosslinks at N7-guanine, resulting in DNA double-strand breaks (DSB), S/G2-phase cell-cycle arrest, and ultimately cancer cell death. We have previously demonstrated that VAL-083 is able to overcome temozolomide-resistance in vitro and in vivo, and that its cytotoxicity is independent of the DNA-repair enzyme O6-methylguanine DNA-methyltransferase (MGMT). MGMT is almost universally expressed in DIPG and its expression is strongly correlated with temozolomide-resistance. VAL-083’s distinct mechanism-of-action suggests the potential for combination with inhibitors of DNA DSB repair or S/G2 cell-cycle progression (e.g. Wee1 inhibitor AZD1775). Here, we investigated the effects of VAL-083 in combination with radiation, AZD1775 or irinotecan (topoisomerase inhibitor) in three DIPG cell-lines: SF10693 (H3.1), SF8628 (H3.3) and NEM157 (H3.3). VAL-083 showed activity at low uM-concentration in all three cell-lines. In addition, VAL-083 showed synergy with AZD1775 in all three cell-lines. Combined with its ability to cross the BBB, accumulate in brain tumor tissue and overcome MGMT-related chemoresistance, these results suggest VAL-083 as a potentially attractive treatment option for DIPG as single agent or in combination with AZD1775. Combination studies with radiation are ongoing and will be presented at the meeting.

The vogue for the philosophy of Henri Bergson, and the popularity of vitalist ideas more generally, periodically claims the attention of historians of early twentieth-century American thought and culture. There is little appreciation, however, for either the broad epistemic significance of these ideas or for their profound ethical and political implications. This essay explores the activity of Bergsonian vitalism, particularly as applied by Bergson's radical compatriot, Georges Sorel, within the fractious conversation that attended the emergence of revolutionary syndicalism as a significant force in the pre-war 1910s. Understanding the ways in which this seemingly unprecedented menace to the status quo was understood facilitates a rethinking of the relationship between ideas and experience in the rise of the Industrial Workers of the World, and illuminates the attraction of radically empiricist approaches to interpreting social phenomena in the Progressive Era. Here, as elsewhere, Bergsonism challenged dominant materialistic and mechanistic explanations in the name of “life,” a seductive alternative for those alienated by, or suffering under, the juggernaut of urban-industrial modernization.

As a global language, English is taken up and used in local contexts in ways that cannot be accounted for by limited World Englishes (WE) paradigm. This can be illustrated through an analysis of the performative agency of individuals’ language usage in specific contact contexts. After a brief overview of the WE paradigm, this article offers a consideration of the Malaysian linguistic context and Malaysian English from a ‘post-WE’ perspective. The conclusion is that, rather than think of the respective WE and post-WE approaches as opposed to one another, it is more useful to characterize them as distinctive theoretical prisms that illuminate divergent issues.

We argue that the appropriate discount rate for pension liabilities depends on the objective. In particular, if the objective is to measure pension under- or overfunding, a default-free discount rate should always be used, even if the liabilities are themselves not default-free. If, instead, the objective is to determine the market value of pension benefits, then it is appropriate that discount rates incorporate default risk. We also discuss the choice of a default-free discount rate. Finally, we show how cost-of-living adjustments that are common in public pensions can be accounted for and valued in this framework.

We report on a large, multi-wavelength campaign to observe variability across the electromagnetic spectrum in the M dwarf flare star EV Lacertae, in 2001 September. The campaign involved X-ray (Chandra ACIS-S+HETG), UV (HST/STIS), and optical (McDonald) spectra, as well as optical photometry and multi-frequency radio (VLA) observations. EV Lac demonstrated both frequent and extreme variability during the course of the two day intensive recordings. Dispersed X-ray spectra confirm the metal underabundance seen in other active stars. The increase in continuum fluxes at short X-ray wavelengths during flare intervals compared to quiescent intervals signals the creation of high temperature plasma, a signature of the flare process. Multi-wavelength comparisons reveal interesting trends: X-ray flare frequencies are within the range predicted by optical observations, yet there is no correspondence between X-ray flares and optical flares in our data. Two UV flares occur during the rise stages of X-ray flares; a major radio flare is accompanied by a large optical flare, which has no apparent counterpart in the X-ray. The results give conflicting evidence for the applicability of the Neupert effect interpretation in stellar coronae.

The mechanism responsible for driving the ubiquitous winds of cool giant and supergiant stars remains to be established. To this end, we are constructing semi-empirical models of the extended outer atmospheres (‘chromospheres’) and winds of selected red supergiants. These models are constrained by analyses of the UV line spectra of single stars, and of red supergiants in binaries that eclipse their main-sequence companions: the ζ Aur and VV Cep stars. These detached binaries are well-separated, with no evidence of mass transfer. The C II] 2325 Å line profiles of the binaries are similar to those of comparable single stars, suggesting that the chromospheres remain relatively unperturbed by binarity. However, it is unclear how much binarity disturbs the wind: binary observations suggest a gradual acceleration (β ∼ 3), but line profile analyses of single red supergiants imply a rapid acceleration (β < 1). To date, we have obtained extensive series of HST/GHRS and STIS observations of three eclipsing red supergiant binaries: ζ Aur, HR 2554 and VV Cep. In this paper, we focus on ζ Aur, and present observations and modelling results for this eclipsing binary.

In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.

Imidazoles present a tunable, versatile and economical platform for the development of novel liquid solvents and polymer membranes for CO2 capture. An overview of our studies in this area is presented, with emphasis on characterization of structure-property relationships in imidazole-based materials through both experimental and computational studies. To this end, a growing library of systematically varied imidazole compounds has been synthesized using only commercial available starting materials and straightforward reactions. Using this library of compounds, we have sought to understand and develop predictive models for thermophysical properties relating to process design, including: density, viscosity, vapor pressure, pKa and CO2 absorption capacity. Furthermore, we have discovered that imidazoles are stable in the presence of SO2 and can form reversible 1:1 adducts, which can be beneficial as SO2 is typically present at ppm levels alongside CO2 in flue gas from coal-fired power plants.