Regionalist themes in 'Breton' Operas, 1850-1954: Four case studies

This thesis aims to challenge the suggestion that couleur locale, in nineteenth-century French operas which incorporated Breton themes, was merely a convenient vehicle for spectacle. It seeks to demonstrate that the deployment of regional symbolism served a variety of complex personal, psychological and socio-political needs and was complicit in the establishment of new regional and national musical identities. Four case studies are at the heart of the enquiry: Édouard Lalo's Le Roi d'Ys (1888), Joseph-Guy Ropartz's Le Pays (1912) and Sylvio Lazzari's La Lepreuse (1912) and La Tour de feu (1928). Two additional works, Giacomo Meyerbeer's Le Pardon de Ploermel (1859) and Paul Le Flem's Magicienne de la mer (1954) frame the main study and define it aesthetically and chronologically. These works were all selected to facilitate the comparison of specific regionalist responses by both non-Breton and native Breton composers. The evaluation of the ways in which regional symbols and themes were deployed in those Breton operas refers to current identity theories and makes extensive use of relevant iconography. Whilst the musical scores are central to the enquiry, close reference is equally made to the literary sources which informed the libretti of the operas. The links between these sources, the significant folklore of the region and the regionally-canonical works of Hersart de la Villemarqué, Émile Souvestre and Anatole Le Braz are assiduously traced. The case studies reveal hitherto undetected or unacknowledged libretti sources; however the interrogation of the operas by Sylvio Lazzari also records previously-undiscovered musical borrowings which have significance for the regional symbolism which his works project. Finally, the conclusion sets the evidence from the case studies in the context of the role of Breton symbolism in the active preservation or invention of a unique regional heritage and, paradoxically, in the affirmation of an overarching national identity. It demonstrates conclusively that operas which consciously deployed Breton couleur locale thereby achieved distinct artistic and psychological goals and continued to evolve in response to their shifting socio-political contexts

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death

BACKGROUND: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. METHODS: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. RESULTS: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. CONCLUSIONS: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40635-021-00425-4

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The effect of direct instruction and writer’s workshop on the early writing skills of children who use augmentative and alternative communication

A single subject multiple probe across subjects research design was used to evaluate a writing instructional program for children who use augmentative and alternative communication (AAC). Specifically, the effect of instruction on the selection of initial letters of words by 3 children with developmental disabilities who used AAC was evaluated. The writing instructional program comprised direct instruction in letter-sound correspondence and selection of initial letters of words, and a writing workshop-type task to provide instruction in literacy activities. Two of the 3 children were successful in the acquisition of the target skill, maintained use of the skill at least 1 month following instruction, and demonstrated some generalization of the skill to less structured tasks. The third child required a simplified instructional program to accommodate transient episodes of hemiplegia and to increase his time on task. The results of the study suggest that an instructional program that combines a direct instruction approach and a writing workshop-type activity may facilitate the development and application of phonemic awareness skills with children who use AAC

Uncovering hidden footprints: revision of the Lower Jurassic (Sinemurian) Razorback Beds – home to Australia’s earliest reported dinosaur trackway

This investigation uses archival data (circa 1954) to elucidate new details on Australia’s first scientifically described dinosaur trackway, located at the Fireclay Caverns-Site A, Mount Morgan, Queensland. A high-resolution archival photograph reveals two additional prints, extending the known sequence from four to six tracks. Leveraging this extended dataset, we have quantified temporospatial variations to assess the trackmaker’s locomotion. Our findings reveal a decrease in stride and step lengths towards the end of the trackway, accompanied by a slight directional shift from east-southeast to east and a reduction in walking speed from a maximum of 3.8–1.8 km/hr. The life reconstruction animation of the Fireclay Caverns-Site A trackmaker supports the walking gait calculated from the relative stride data and demonstrates biomechanically plausible limb movements. By incorporating non-traditional methods, such as temporal trackway analysis and its translation as a trackmaker animation, we establish a broader framework for conventional ichnological studies. This approach enhances our interpretation of the dynamic record encapsulated in fossil trackways, enabling us to visualise and scientifically scrutinise the behaviour of extinct trackmakers.</p

<b>Uncovering Hidden Footprints: Revision of the Lower Jurassic (Sinemurian) Razorback Beds – Home to Australia's Earliest Reported Dinosaur Trackway</b>

This investigation uses archival data (circa 1954) to elucidate new details on Australia's first scientifically described dinosaur trackway, located at the Fireclay Caverns-Site A, Mount Morgan, Queensland. A high-resolution archival photograph reveals two additional prints, extending the known sequence from four to six tracks. Leveraging this extended dataset, we have quantified temporospatial variations to assess the trackmaker's locomotion. Our findings reveal a decrease in stride and step lengths towards the end of the trackway, accompanied by a slight directional shift from east-southeast to east and a reduction in walking speed from a maximum of 3.8 km/hr to 1.8 km/hr. The life reconstruction animation of the Fireclay Caverns-Site A trackmaker supports the walking gait calculated from the relative stride data and demonstrates biomechanically plausible limb movements. By incorporating non-traditional methods, such as temporal trackway analysis and its translation as a trackmaker animation, we establish a broader framework for conventional ichnological studies. This approach enhances our interpretation of the dynamic record encapsulated in fossil trackways, enabling us to visualise and scientifically scrutinise the behaviour of extinct trackmakers.</p

The nucleotidase/phosphatase SAL1 is a negative regulator of drought tolerance in Arabidopsis

An Arabidopsis thaliana drought-tolerant mutant, altered expression of APX2 (alx8), has constitutively increased abscisic acid (ABA) content, increased expression of genes responsive to high light stress and is reported to be drought tolerant. We have identified alx8 as a mutation in SAL1, an enzyme that can dephosphorylate dinucleotide phosphates or inositol phosphates. Previously identified mutations in SAL1, including fiery (fry1-1), were reported as being more sensitive to drought imposed by detachment of rosettes. Here we demonstrate that alx8, fry1-1 and a T-DNA insertional knockout allele all have markedly increased resistance to drought when water is withheld from soil-grown intact plants. Microarray analysis revealed constitutively altered expression of more than 1800 genes in both alx8 and fry1-1. The up-regulated genes included some characterized stress response genes, but few are inducible by ABA. Metabolomic analysis revealed that both mutants exhibit a similar, dramatic reprogramming of metabolism, including increased levels of the polyamine putrescine implicated in stress tolerance, and the accumulation of a number of unknown, potential osmoprotectant carbohydrate derivatives. Under well-watered conditions, there was no substantial difference between alx8 and Col-0 in biomass at maturity; plant water use efficiency (WUE) as measured by carbon isotope discrimination; or stomatal index, morphology or aperture. Thus, SAL1 acts as a negative regulator of predominantly ABA-independent and also ABA-dependent stress response pathways, such that its inactivation results in altered osmoprotectants, higher leaf relative water content and maintenance of viable tissues during prolonged water stress