Antoinette, an Opera in One Act

Antoinette is a chamber opera in one act. It is a dramatization of the events leading to the execution of Marie Antoinette and is 30 minutes in length. The narrative of the opera was developed together with Vancouver based poet Ray Hsu, who wrote the libretto. Antoinette is intended to address modern societal issues through musical drama. These issues represent the biographical reality of the characters but are intended to resonate with modern audiences. Themes will include overconsumption, the dangers of so-called “Strong-man Politics”, mortality, and feminism. Antoinette is written for five principle vocalists (soprano, mezzo-soprano, tenor, baritone, bass) accompanied by a chamber orchestra which consists of a flute, clarinet, percussion (snare drum, bass drum, vibraphone), piano, violin, viola, violoncello, and contrabass

Congenital Heart Disease in Down Syndrome

Down syndrome remains the most common chromosomal abnormality in live-born infants in the world today. The association between Down syndrome and congenital heart disease (CHD) is well known, and it is widely recognized that CHD contributes significantly to the morbidity of children with Down syndrome. The reported incidence of CHD in Down syndrome patients is between 40 and 60%. The most commonly described defect is complete atrioventricular septal defect (AVSD), which comprises 30–40% of all cardiac defects. Complex genetic factors are involved. Routine cardiac screening of all newborn babies with Down syndrome is recommended. Expert groups suggest that the cardiac status of all children with Down syndrome should be established by 6 weeks of age to permit appropriate and timely treatment avoiding the establishment of irreversible pulmonary vascular disease that would make corrective surgery impossible

Storm Clouds on the Horizon—Challenges and Recommendations for Military Recruiting and Retention

In light of current Department of Defense (DoD) priorities to increase the size of the military forces, new strategies must be developed to recruit and retain high-quality personnel with the right expertise to fill the expanding number of open billets. DoD should consider modifying existing policies to address this need, lest serious personnel issues overtake other force priorities

Quarantining the past : commemorating the Great Irish Famine on Grosse-Île

Grosse-Île, Canada's main quarantine station from 1832 to 1937, was a required stopover for immigrants on their voyage up the St. Lawrence River to the Port of Quebec. Though most passed through the inspection process with little delay, during the spring and summer of 1847, the deadliest year of the Great Famine (1845-50), 100 000, predominantly Catholic, Irish made their way to the island aboard 'coffin ships'. Their already weakened state worsened by the inhumane crossing, some succumbed to typhus en route, others while in quarantine. Despite the efforts of the island's medical staff and the ministrations of members of Quebec's Catholic and Anglican clergy, over five thousand Irish were buried that summer on Grosse-Ile in mass graves. Thousands more died after leaving the island for Quebec City, Montreal, Kingston, Toronto, and Hamilton. In commemorations organized on the island at the beginning and the end of the twentieth century, Irish-Canadians have memorialized this Irish episode in Grosse-Île's history. In 1909, eight thousand commemorators made the journey to the island to witness the unveiling of a Celtic Cross and hear an assortment of historical, political, and religious orations. Almost ninety years later, amidst controversy and debate over the extent to which the island's Irishness would be emphasized, Parks Canada renamed the national historic site, Grosse-Île and the Irish Memorial , and opened an exhibition marking the Famine sesquicentennial. These acts of public remembrance were multivocal orchestrations, incorporating a variety of historical perspectives. Examining Grosse-Île's commemorative discourses reveals much about the socio-political context in which they were formulated and affords the opportunity to consider how we as a society choose to approach the past in the public sphere

HDAC inhibitors increase NRF2-signaling in tumour cells and blunt the efficacy of co-adminstered cytotoxic agents

The NRF2 signalling cascade provides a primary response against electrophilic chemicals and oxidative stress. The activation of NRF2-signaling is anticipated to have adverse clinical consequences; NRF2 is activated in a number of cancers and, additionally, its pharmacological activation by one compound can reduce the toxicity or efficiency of a second agent administered concomitantly. In this work, we have analysed systematically the ability of 152 research, pre-clinical or clinically used drugs to induce an NRF2 response using the MCF7-AREc32 NRF2 reporter. Ten percent of the tested drugs induced an NRF2 response. The NRF2 activators were not restricted to classical cytotoxic alkylating agents but also included a number of emerging anticancer drugs, including an IGF1-R inhibitor (NVP-AEW541), a PIM-1 kinase inhibitor (Pim1 inhibitor 2), a PLK1 inhibitor (BI 2536) and most strikingly seven of nine tested HDAC inhibitors. These findings were further confirmed by demonstrating NRF2-dependent induction of endogenous AKR genes, biomarkers of NRF2 activity. The ability of HDAC inhibitors to stimulate NRF2-signalling did not diminish their own potency as antitumour agents. However, when used to pre-treat cells, they did reduce the efficacy of acrolein. Taken together, our data suggest that the ability of drugs to stimulate NRF2 activity is common and should be investigated as part of the drug-development process

Paediatric and adult congenital cardiology education and training in Europe

Background:Limited data exist on training of European paediatric and adult congenital cardiologists.Methods:A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries.Results:Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87–9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63–10.72 million), and one training centre per 4.29 million population (range 1.63–10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1–17), and duration of training was 3 years (range 2–5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R$^{2}$ = 0.41).Conclusion:Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists

Potential of in vivo stress reporter models to reduce animal use and provide mechanistic insights in toxicity studies

Chemical risk assessment ensures protection from the toxic effects of drugs and manmade chemicals. To comply with regulatory guidance, studies in complex organisms are required, as well as mechanistic studies to establish the relevance of any toxicities observed to man. Although in vitro toxicity models are improving, in vivo studies remain central to this process. Such studies are invariably time-consuming and often involve large numbers of animals. New regulatory frameworks recommend the implementation of “smart” in vivo approaches to toxicity testing that can effectively assess safety for humans and comply with societal expectations for reduction in animal use. A major obstacle in reducing the animals required is the time-consuming and complexity of the pathological endpoints used as markers of toxicity. Such endpoints are prone to inter-animal variability, subjectivity and require harmonisation between testing sites. As a consequence, large numbers of animals per experimental group are required. To address this issue, we propose the implementation of sophisticated stress response reporter mice that we have developed. These reporter models provide early biomarkers of toxic potential in a highly reproducible manner at single-cell resolution, which can also be measured non-invasively and have been extensively validated in academic research as early biomarkers of stress responses for a wide range of chemicals at human-relevant exposures. In this report, we describe a new and previously generated models in our lab, provide the methodology required for their use and discuss how they have been used to inform on toxic risk. We propose our in vivo approach is more informative (refinement) and reduces the animal use (reduction) compared to traditional toxicity testing. These models could be incorporated into tiered toxicity testing and used in combination with in vitro assays to generate quantitative adverse outcome pathways and inform on toxic potential

Editorial Board Composition Among Pediatric Cardiology Journals:Time to Cast the Net Wider

Background: No data currently exist on the diversity of editorial board members (EBMs) of pediatric cardiology journals. Objectives: The objective was to investigate the editorial boards of 5 pediatric cardiology journals to assess the composition of these boards in terms of the geographical, gender, and economic representation of their members. Methods: Information on EBMs was collected directly from 5 journal websites accessed in February 2022. The following data were collected: country of practice (including World Bank geographical and income classification), institution of practice, role on editorial board, and whether an individual held a role on 1 or more of the boards included. Results: A total of 455 EBMs were identified. A total of 369 (81%) were male. All editors-in-chief were male, and 4 were from the United States. EBMs practicing in North America accounted for 278 individuals (61%) of the editorial boards reviewed. The next majority of EBMs are practicing within Europe and Central Asia (23%, n = 103), East Asia and Pacific (7%, n = 31), Middle East and North Africa (4%, n = 18), and Latin America and Caribbean (4%, n = 16). Less than 2% (n = 9) practice in Sub-Saharan Africa and South Asia. Over 90% (n = 415) practice in high-income countries. There was no representation from low-income countries. Conclusions: Women and pediatric cardiologists practicing in countries outside of Europe and North America were underrepresented on the editorial boards of the journals studied. Diversifying composition of editorial boards may provide greater representation of underserved areas and encourage broader avenues of investigation and research