Le Page Research Articles

The short-lived verdict in Le Page v Center for Reproductive Medicine: why 'personhood' matters in the regulation of assisted reproductive technologies.

The short-lived verdict in Le Page v Center for Reproductive Medicine: why 'personhood' matters in the regulation of assisted reproductive technologies.

Marie de Bourgogne/ Mary of Burgundy: figure, principat et postérité d’une duchesse tardo-médiévale/ ‘Persona’, Reign, and Legacy of a Late Medieval Duchess. Sous la direction de Michael Depreter, Jonathan Dumont, Elizabeth L’Estrange et Samuel Mareel

Duchess Mary of Burgundy (1457–1482) can rightly be called a princess in the shadow. Only very few authentic images of her survive and little research has been undertaken so far to shed light on this important historical figure. This edited volume with its twenty-four individual contributions aims at filling this deplorable gap. The only daughter of Charles the Bold (1433–1477), she was heir to the powerful conglomerate of territories called Burgundy. Mary died at the age of only twenty-five, leaving her little time to develop a public image. She thus left few traces as an active patron of the arts. Several representations of the young duchess can be found in contemporary manuscripts, the window miniature in the Vienna Book of Hours being the most famous. However, no mention is made here of the duchess’s portrait in the Berlin Book of Hours; this manuscript was passed by her husband, Emperor Maximilian I to their daughter, Margaret of Austria, in 1483. In Part One, the emphasis is on the authority of Mary of Burgundy as a legitimate heir to Burgundy, being a princesse naturelle. Several suitors tried to incorporate the rich Netherlands into their territory by securing a union with the young sovereign. ­Inherent legal issues are discussed from different angles by Jonathan Dumont, Élodie Lecuppre-Desjardin, and Kathleen Daly; meanwhile, iconographic models such as the concept of a ‘City Maiden’ are studied by Lisa Demets in contemporary texts. The 1477 Bruges tableau vivant with Queen Penthesilea demonstrates for Olga Karaskova the difficulty of finding suitable symbols to represent a young female sovereign. The discussion of how to visualize the power of a female head of state is discussed further in Andrea Pearson’s close analysis of Mary’s equestrian seals. Part Two is concerned with Mary’s household, her councillors, the court as an institution, and the economic situation. In this context, Federica Veratelli investigates the presence of Italian administrators at the Burgundian court and the significance of Italian luxury goods. In Part Three, five essays discuss the afterlife of Mary of Burgundy as a historical figure in later centuries, from the funerary rites in 1482 up to the twentieth century. Pierre-Gilles Girault argues that Margaret of Austria’s response to the premature death of her mother was to play an active political role as Countess of Bresse and regent of the Netherlands, instrumentalizing the Brou Church to express her aspirations. Dominique Le Page studies the ways in which Mary was viewed in the old Duchy of Burgundy across four centuries. To balance the emphasis on French and Netherlandish history, an essay on the visual and textual examples of sixteenth-century Habsburg propaganda (Der Weißkunig, Theuerdank, and The Triumphal Procession) would have been ­worthwhile. In the conclusions by Éric Bousmar and Jelle Haemers, a brief reference is made to ­Maximilian’s use of art for the purpose of propaganda. In all, this is a ­high-calibre collection of essays that critically investigate Mary of Burgundy and provide ­numerous new insights into her life and her reputation through the centuries.

Last shot

We have had years of missed opportunities to hit our climate goals, and with a fossil fuel gold rush triggered by Russia's invasion of Ukraine, the situation looks bleak. But ahead of COP27, there are still positives to reach for, finds Michael Le Page

Comment on "Sutured Versus Mesh-augmented Hiatus Hernia Repair: A Systematic Review and Meta-analysis of Randomized Controlled Trials".

Comment on "Sutured Versus Mesh-augmented Hiatus Hernia Repair: A Systematic Review and Meta-analysis of Randomized Controlled Trials".

Abstract 6325: Identification of genes responsible for osteosarcomas metastatic evolution by active super enhancers profiling

Abstract Super enhancers are strong spatiotemporal transcriptional regulators. They can be mapped on genomes thanks to their astounding enrichment for well-known enhancers markers, such as acetylation of the lysine 27 of type 3 histones (H3K27Ac). Their target genes, confined in their so-called topologically associated domains, present exceptionally high expression levels, depending on associated super enhancers activation status, and are responsible for defining cells identity whether physiological or pathological. Osteosarcomas are the most common primary malignant bone tumors. Patients suffering from osteosarcomas, on average 15 years old, mostly develop pulmonary metastasis, responsible for drastic decrease in their survival. We have conducted chromatin immunoprecipitation sequencing against H3K27Ac and RNA sequencing experiments on osteosarcoma cells presenting high propensity to metastatic dissemination or devoid of this capacity, in order to unveil genes implicated in metastasis development through super enhancers genomic mapping. We have highlighted exclusive active super enhancers profiles between metastatic and non-metastatic osteosarcoma cells. Among target genes of spotted super enhancers, three of them caught our attention. Implication of these genes in metastatic development have already been demonstrated in various cancers evolution, except in osteosarcomas. Osteosarcoma cells having high capacity for metastatic development present identified genes over expressions compared to cells incompetent in this pathological process. Artificial down expressions of identified genes decrease osteosarcoma cells metastatic capacity in vitro. In vivo experiments, that correspond to paratibial implantation of modified osteosarcoma cells and analysis of primary tumor metastatic development, are currently under way. Our strategy may allow identification of new therapeutic targets to fight against osteosarcoma metastatic evolution and open new perspectives to improve patients prognostic. This work is funded by Ligue contre le cancer, ANR, SFCE and Région Pays de la Loire. Citation Format: Mélanie Lavaud, Robel Tesfaye, Céline Charrier, Rose Anne Thépault, Maxime Golias, Sarah Le Page, Mathilde Mullard, Bénédicte Brounais, Franck Verrecchia, Marc Baud'huin, François Lamoureux, Steven Georges, Benjamin Ory. Identification of genes responsible for osteosarcomas metastatic evolution by active super enhancers profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6325.

The future of medicine unlocked

When the covid-19 pandemic finally showcased the power of mRNA therapies, it opened the door to a medical revolution, finds Michael Le Page

The world is warming, and we know why. We also know how to stop it. To stave off the worst effects, we must wean ourselves off greenhouse gas-producing fossil fuels – and fast, hitting “net zero” carbon emissions by mid-century.

Doing that requires a huge transformation in how we produce and consume energy. That will profoundly change the world, says Michael Le Page

Historical and future global burned area with changing climate and human demography

Summary Wildfires influence terrestrial carbon cycling and represent a safety risk, and yet a process-based understanding of their frequency and spatial distributions remains elusive. We combine satellite-based observations with an enhanced dynamic global vegetation model to make regionally resolved global assessments of burned area (BA) responses to changing climate, derived from 34 Earth system models and human demographics for 1860–2100. Limited by climate and socioeconomics, recent BA has decreased, especially in central South America and mesic African savannas. However, future simulations predict increasing BA due to changing climate, rapid population density growth, and urbanization. BA increases are especially notable at high latitudes, due to accelerated warming, and over the tropics and subtropics, due to drying and human ignitions. Conversely, rapid urbanization also limits BA via enhanced fire suppression in the immediate vicinity of settlements, offsetting the potential for dramatic future increases, depending on warming extent. Our analysis provides further insight into regional and global BA trends, highlighting the importance of including human demographic change in models for wildfire under changing climate.

“Make or break” is hardly hyperbole for the climate negotiations due to reach their climax in November in Glasgow, UK. At the COP26 meeting, nations will have a last chance to really rev up the stuttering motor of climate action and come good on commitments made in Paris in 2015 to limit global warming to a “safe” level of 1.5°C.

The facts aren't waiting. Global temperature has already risen by more than 1°C. Melting ice caps, rising sea levels and weather extremes from hurricanes to heatwaves are already showing us some of what a warmed world looks like. Meanwhile, the latest research into climate feedback effects underscores the need to cut emissions deeply and fast, and adapt to a changing world. But it's not – quite – yet too late to do that, as Michael Le Page reports

How climate change hits nature

A warming world is piling pressure on already struggling biodiversity. We need to tackle both problems together, finds Michael Le Page

Rama Kant Agnihotri, Mahendra Kishore Verma and Vandana Puri (Eds.), Language and Identity: Selected Papers of Robert B. Le Page

Rama Kant Agnihotri, Mahendra Kishore Verma and Vandana Puri (Eds.), Language and Identity: Selected Papers of Robert B. Le Page

NLRC5 promotes transcription of BTN3A1-3 genes and Vγ9Vδ2 Tcell-mediated killing.

SummaryBTN3A molecules—BTN3A1 in particular—emerged as important mediators of Vγ9Vδ2 T cell activation by phosphoantigens. These metabolites can originate from infections, e.g. with Mycobacterium tuberculosis, or by alterations in cellular metabolism. Despite the growing interest in the BTN3A genes and their high expression in immune cells and various cancers, little is known about their transcriptional regulation. Here we show that these genes are induced by NLRC5, a regulator of MHC class I gene transcription, through an atypical regulatory motif found in their promoters. Accordingly, a robust correlation between NLRC5 and BTN3A gene expression was found in healthy, in M. tuberculosis-infected donors' blood cells, and in primary tumors. Moreover, forcing NLRC5 expression promoted Vγ9Vδ2 T-cell-mediated killing of tumor cells in a BTN3A-dependent manner. Altogether, these findings indicate that NLRC5 regulates the expression of BTN3A genes and hence open opportunities to modulate antimicrobial and anticancer immunity.

Characteristics of temperature evolution from 1960 to 2015 in the Three Rivers\u2019 Headstream Region, Qinghai, China

The cumulative anomaly analysis, the ensemble empirical mode decomposition (EEMD), the Bernaola Galvan heuristic segmentation algorithm (BGSA), the Le Page test, the moving t test at different sub-series scales, and the quasi-periodic oscillations (QPOs) were used to demonstrate the statistical characteristics of the temperature changes in the study area from 1960 to 2015. The results were as follows: the temperatures varied obviously among subregions and seasons and they generally increased; the climate tendency rates of autumn mean temperatures were higher than those of summer and spring; additionally, the temperatures in the three subregions of the Three Rivers’ Headstream Region (THRHR) were relatively low in the 1960s, especially in the early 1960s, followed by those in the 1970s, and the annual mean temperature has been increasing since the mid-late 1980s, especially in the middle 1990s. The results of EEMD showed that the QPOs of the annual mean temperature series in the study area were mainly quasi-3 years, quasi-5–8 years, quasi-12–15 years, and quasi-35–38 years. The results of the annual mean temperature series mutational sites showed that a significant warming mutation began in approximately 1997; and the mutational sites of seasonal mean temperature series in the three subregions of the THRHR all began in the middle and late 1990s. The prediction result of the temperature series trend based on multiple methods showed that the warming persistence of annual and seasonal mean temperature series would be stronger, and their seasonal and regional differences were obvious.

MONOCLONAL ANTIBODY GONE ROGUE: ALEMTUZUMAB CAUSING ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Anti-Glomerular basement membrane disease (anti-GBM), is a rare autoimmune process that can cause irreversible renal or lung injury. Here we discuss a case of Alemtuzumab induced anti-GBM. CASE PRESENTATION: A 46 year-old caucasian female with history of Multiple Sclerosis presented with flu-like symptoms, dizziness, nausea and vomiting ongoing for two weeks. Her physical exam was significant for dry mucous membranes and tachycardia. Her labs were significant for a BUN of 48 mg/dL and a creatinine of 6.8 mg/dL without any history of prior kidney disease. Renal biopsy revealed more than 90% glomerular involvement with necrotizing and crescentic proliferation, as well as positive linear staining along the glomerular basement membranes for IgG, Kappa, Lambda and C3. Anti-glomerular basement membrane antibodies were 189 units; thereby, Anti-GBM disease was diagnosed. Patient reported being on Alemtuzumab eight months prior to presentation. She was started on plasmapheresis, high dose prednisone and cyclophosphamide but therapy was stopped early due to nightly agitation and confusion likely related to sundowning, but the patient's family attributed it to the new therapy. Patient was discharged to inpatient rehab where she developed a right internal jugular vein thrombosis and was started on rivaroxaban. She later developed hemoptysis and had to be readmitted. Computed tomography scan of her lungs showed bi-apical and basilar dense airspace opacities with air bronchograms suggesting hemorrhagic infiltrates, findings were most consistent with diffuse alveolar hemorrhage. [Images A-C] Anti-GBM antibodies were elevated at 217 units. Patient was then restarted on plasmapheresis, steroids and cyclophosphamide and was able to complete therapy with slow but definite improvement. DISCUSSION: Alemtuzumab is a humanized monoclonal antibody that binds to CD52 (a cell-surface antigen present on T and B cells) and can be associated with anti-GBM disease that may present up to 40 months after the last dose.[1] Our case illustrates this lingering side effect and highlights the importance of taking a thorough history including previous and current medications. Our case shows the second reported case of Alemtuzumab induced anti-GBM with both renal and lung involvement [2] and the seventh case with renal involvement.[3-6] Our case is unique in the timing and course of development of kidney and lung injury, with about a month in between, while the first reported case showed a more rapid succession of kidney and lung injury. CONCLUSIONS: Alemtuzumab can be associated with autoimmune syndromes but clear screening tools and monitoring is not currently available. Further investigation is needed to identify a possible role for antibody monitoring in patients on Alemtuzumab. Reference #1: [1] Devonshire, V et al. Monitoring and management of autoimmunity in multiple sclerosis patients treated with alemtuzumab: practical recommendations. J Neurol 2018. Reference #2: [2] Lapointe, E., Moghaddam, B., Barclay, K., Traboulsee, A., & Neufeld, P. (2018). Goodpasture’s Syndrome Following Alemtuzumab Therapy in Multiple Sclerosis. Canadian Journal of Neurological Sciences / Journal Canadien Des Sciences Neurologiques, 45(6), 712-714. Reference #3: [3] Coles, AJ, Cox, A, Le Page, E, et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006;253(1):98-108 [4] Meyer, D, Coles, A, Oyuela, P, et al. Case report of anti-glomerular basement membrane disease following alemtuzumab treatment of relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2013;2(1):60-63. [5] Phelps, R. Autoimmune events: nephropathies. Scientific exchange forum 2013. [6] Singer, BA, Alroughani, R, Brassat, D, et al. Durable improvements in clinical outcomes with alemtuzumab in patients with active RRMS in the absence of continuous treatment: 7-year follow-up of CARE-MS II patients (TOPAZ study). Poster 736. 7th joint ACTRIMS-ECTRIMS meeting, Paris. 2017. DISCLOSURES: No relevant relationships by Youssef Abouleish, source=Web Response No relevant relationships by Paul Marik, source=Web Response

Sweden's virus response analysed

The Scandinavian country avoided compulsory lockdowns as the coronavirus spread. It isn't clear if this was a wise choice, says Michael Le Page

Inside the race for a vaccine

Sarah Gilbert, the driving force behind the much-publicised Oxford vaccine, tells Michael Le Page what her life is like right now, and why we should be optimistic

Vaccine immune boost.

An early trial of a vaccine candidate from the University of Oxford has produced a promising immune response, reports Michael Le Page

Covid risk or just hot air?

As people return to public buildings, there is disagreement over the risk of airborne spread of the coronavirus, reports Michael Le Page

Should I get an antibody test?

Antibody testing can reveal if you have had covid-19. Michael Le Page asks if it is worth paying for a test

The problems with so-called immunity tests.

Initial antibody testing surveys suggest more people have been infected than we thought. But we need to be cautious about these results, reports Michael Le Page