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The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
To evaluate the association between novel pre- and post-operative biomarker levels and 30-day unplanned readmission or mortality after paediatric congenital heart surgery.
Children aged 18 years or younger undergoing congenital heart surgery (n = 162) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Collected novel pre- and post-operative biomarkers include soluble suppression of tumorgenicity 2, galectin-3, N-terminal prohormone of brain natriuretic peptide, and glial fibrillary acidic protein. A model based on clinical variables from the Society of Thoracic Surgery database was developed and evaluated against two augmented models.
Unplanned readmission or mortality within 30 days of cardiac surgery occurred among 21 (13%) children. The clinical model augmented with pre-operative biomarkers demonstrated a statistically significant improvement over the clinical model alone with a receiver-operating characteristics curve of 0.754 (95% confidence interval: 0.65–0.86) compared to 0.617 (95% confidence interval: 0.47–0.76; p-value: 0.012). The clinical model augmented with pre- and post-operative biomarkers demonstrated a significant improvement over the clinical model alone, with a receiver-operating characteristics curve of 0.802 (95% confidence interval: 0.72–0.89; p-value: 0.003).
Novel biomarkers add significant predictive value when assessing the likelihood of unplanned readmission or mortality after paediatric congenital heart surgery. Further exploration of the utility of these novel biomarkers during the pre- or post-operative period to identify early risk of mortality or readmission will aid in determining the clinical utility and application of these biomarkers into routine risk assessment.
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.
Few studies have investigated the patterns of posttraumatic stress disorder (PTSD) symptom change in prolonged exposure (PE) therapy. In this study, we aimed to understand the patterns of PTSD symptom change in both PE and present-centered therapy (PCT).
Participants were active duty military personnel (N = 326, 89.3% male, 61.2% white, 32.5 years old) randomized to spaced-PE (S-PE; 10 sessions over 8 weeks), PCT (10 sessions over 8 weeks), or massed-PE (M-PE; 10 sessions over 2 weeks). Using latent profile analysis, we determined the optimal number of PTSD symptom change classes over time and analyzed whether baseline and follow-up variables were associated with class membership.
Five classes, namely rapid responder (7–17%), steep linear responder (14–22%), gradual responder (30–34%), non-responder (27–33%), and symptom exacerbation (7–13%) classes, characterized each treatment. No baseline clinical characteristics predicted class membership for S-PE and M-PE; in PCT, more negative baseline trauma cognitions predicted membership in the non-responder v. gradual responder class. Class membership was robustly associated with PTSD, trauma cognitions, and depression up to 6 months after treatment for both S-PE and M-PE but not for PCT.
Distinct profiles of treatment response emerged that were similar across interventions. By and large, no baseline variables predicted responder class. Responder status was a strong predictor of future symptom severity for PE, whereas response to PCT was not as strongly associated with future symptoms.
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.
The objective of this panel was to generate recommendations to promote the engagement of front-line emergency department (ED) clinicians in clinical and implementation research.
Panel members conducted semi-structured interviews with 37 Canadian adult and pediatric emergency medicine researchers to elicit barriers and facilitators to clinician engagement in research activities, and to glean strategies for promoting clinician engagement.
Responses were organized by themes, and, based on these responses, recommendations were developed and refined in an iterative fashion by panel members.
We offer eight recommendations to promote front-line clinician engagement in clinical research activities. Recommendations to promote clinician engagement specifically address the creation of a research-friendly culture in the ED, minimizing the burden of data collection on clinical staff through the careful design of data collection tools and the use of research staff, and communication between researchers and clinical staff to promote adherence to study protocols.
The objective of Panel 2b was to present an overview of and recommendations for the conduct of implementation trials and multicentre studies in emergency medicine.
Panel members engaged methodologists to discuss the design and conduct of implementation and multicentre studies. We also conducted semi-structured interviews with 37 Canadian adult and pediatric emergency medicine researchers to elicit barriers and facilitators to conducting these kinds of studies.
Responses were organized by themes, and, based on these responses, recommendations were developed and refined in an iterative fashion by panel members.
We offer eight recommendations to facilitate multicentre clinical and implementation studies, along with guidance for conducting implementation research in the emergency department. Recommendations for multicentre studies reflect the importance of local study investigators and champions, requirements for research infrastructure and staffing, and the cooperation and communication between the coordinating centre and participating sites.
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.
Virginia Woolf 's engagements with artistic and feminist history were often shadowed by the problem of ephemeral contemporaneity. While figures like T. S. Eliot were able to envision the literary tradition existing within a timeless and autotelic simultaneity, Woolf 's own understanding of the continued presence of the past was constantly challenged by her awareness of the material inequalities that defined that past and the forms of female cultural production that remained invisible and fleeting, resistant to the ossification and enduring life of print. This awareness dominates an essay Woolf wrote in December 1940, a meditation on the life and work of acclaimed Victorian actor Ellen Terry (D5: 329).
Few subjects could have better served Woolf 's reflection on the vagaries of historical consciousness and the peculiar values of contemporaneity. Born in 1847 to a family of actors, Terry grew up in the theater, identifying fully with the stage from an early age. In the latter decades of the nineteenth century, she rose to the pinnacle of her craft and her profession at the Lyceum Theatre, where her Shakespearean performances alongside the actor-manager Henry Irving inspired adoring missives from such Victorian luminaries as Lewis Carroll and Oscar Wilde (Terry 140). She was—in her own words and those of her admirers—“the Terry of the age” (56), an ambivalent, multifaceted icon of Victorianism in art, politics, and culture. Woolf may have seen Terry when she appeared at the Court Theatre as Lady Cicely in Bernard Shaw's Captain Brassbound's Conversion in 1906. But soon thereafter, Terry's career began a gradual close. As many have remarked, Terry's mode of acting and the overwhelming force of her celebrity could find no place on the modern stages of the twentieth century. She died in 1928, seemingly left behind by the medium she once defined.
It is therefore unsurprising to note in Woolf 's belated retrospective unique evasions of the historical record and a tone of benign nostalgia for the effervescence of Terry's luminous personality. Indeed, Woolf 's prose swiftly enacts a sort of transubstantiation in which the actor's conception is loosed from her body and thence unites with the immaterial ideal of the role itself.
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.
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.