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Expert recommendations on treatment sequencing and challenging clinical scenarios in human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer.
No full textHuman epidermal growth factor receptor 2 (HER2) overexpression and/or ERBB2 gene amplification occurs in approximately 15-20% of breast cancers and is associated with poor prognosis. While the introduction of HER2-targeted therapies has significantly improved survival in patients with HER2-positive metastatic breast cancer, the incidence of brain metastases has increased due to patients living longer. Current recommendations sequence treatments by line of therapy, as well as by the status of brain metastases in patients with HER2-positive breast cancer. However, in the third-line treatment setting and beyond, there is a lack of clarity of the preferred choice of therapy. In clinical practice, clinicians may also encounter challenging scenarios where the optimal therapeutic approach has not been defined by clinical studies, so there is a need for clarity in such situations. Two consensus meetings of expert oncologists (12 from Europe and one from Canada) were convened to discuss these scenarios. We subsequently developed this article to present an overview of current treatment recommendations for HER2-positive metastatic breast cancer and give practical guidance on addressing challenging scenarios in a real-world setting. Based on our clinical experience, we provide a unanimous consensus concerning the treatment of elderly patients as well as those with brain-only metastases, leptomeningeal disease, oligometastatic disease, central nervous system oligo-progressive disease or ERBB2-mutant disease. We also discuss how to combine HER2-targeted therapy with endocrine therapy in patients with HER2-positive/hormone-receptor-positive disease, considerations for potential discontinuation of HER2-targeted therapy in patients with long-term remission and how to treat patients whose metastatic biopsy no longer confirms their HER2-positive status
Hypoxia and post-hepatectomy liver failure : a double-edged sword post-extended hepatectomy
No full textLiver resection is the only curative treatment for liver tumors but is associated with a significant risk of post-hepatectomy liver failure (PHLF), marked by high mortality. The lack of mechanistic understanding limits treatment options. Discrepancies exist about the role of tissue hypoxia after extended hepatectomy. Once considered as a key driver of PHLF pathophysiology, recent studies reported a protective effect of early hypoxia. In this study, we investigated how hypoxia modulates regeneration after PHLF-inducing hepatectomy. Our work reveals a timing-dependent role of hypoxia in liver regeneration. While early hypoxia prevents vascular damage, stimulates vasculogenesis, preserves liver architecture, and promotes hepatocyte function, prolonged hypoxia causes hepatocyte cell cycle arrest and hinders recovery, reversible upon oxygenation of the liver remnant. Our findings identify hypoxia as a critical modulator of liver regeneration after extended hepatectomy.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202
Entre la educación y el trabajo en minas informales: las expectativas y la trayectoria educativa de los jóvenes rurales en los Andes del sur de Perú (Ocongate, Cusco)
No full textEste artículo examina las expectativas y decisiones de las familias campesinas frente a la educación en la comunidad campesina de Huacatinco del distrito de Ocongate en la región de Cusco (Andes del sur del Perú) en un contexto de cambios acelerados. Las madres y los padres quechua hablantes utilizan la expresión metafórica ñawiyuq (con ojos) para referirse a la educación que quisieran que sus hijas e hijos tengan. La investigación muestra que la mayor aspiración enunciada por las madres, padres de familia, las y los estudiantes del colegio es alcanzar la educación secundaria; y posteriormente seguir el proceso educativo superior que, se espera, les permita obtener empleo y bienestar económico. Sin embargo, en la práctica, muchos jóvenes no continúan con sus estudios superiores, optando por trabajar lo antes posible, sobre todo, en el sector minero informal. Este texto también indaga sobre la brecha entre el discurso, las prácticas y las condiciones socioeconómicas estructurales que la explican
Productivity Labour Adjustment Costs. How do new hires and leavers (incl. retirees) compare?
No full textLabour turnover is a crucial element of contemporary economic life. It can improve productivity if more productive workers replace less productive ones. However, in the short run, it generates sizeable labour adjustment costs (LACs), including productivity losses. This paper sheds new light on the turnover-productivity relationship focusing on productivity LACs. We use firm-level 2014-2022 Belgian data with information on stayers, new hires and leavers: those who are fired, those leaving voluntarily, and those who are about to retire. We use the Hellerstein-Neumark (HN) framework to quantify the productivity of these different labour types, using stayers as a benchmark. We posit that evidence of significant productivity handicaps is a good indicator of productivity LACs. Results suggest no productivity LACs for new hires. By contrast, for leavers, they point to significant ones. What is more, findings for prospective (early) retirees indicate a very sizeable drop in productivity during their last year of employment
L’anthropocentrisme face à l’émergence du droit à un environnement sain en République Démocratique du Congo
No full textDepuis plusieurs décennies, la destruction de l’environnement est la genèse des problèmes majeurs de la santé humaine. Avec la tenue de deux grandes conférences des Nations Unies vers les années soixante-dix, la question est devenue alarmante.Il a été constaté que l’homme ne pourrait vivre que dans un environnement d’une certaine qualité. L’inscription de l’environnement au menu des biens pouvant être protégé a au fur du temps préoccupé les Etats. La question a eu un succès et actuellement, il n’existe plus de controverse sur la nécessité de protéger l’environnement. L’animus des décideurs était de protéger non pas l’environnement, mais plutôt l’homme via son environnement. Cette politique est une émanation anthropocentrique. D’autant que cela ne suffisait pas, les Nations Unies sont allées loin en reconnaissant que pour le bienêtre de la vie humaine, l’homme avait le droit de vivre dans un environnement sain dépourvu de tout risque pour sa santé. La République Démocratique du Congo a adhéré à cette option en constitutionnalisant ce droit. Cette constitutionnalisation nous permet de nous interroger sur ses effets et son animus. C’est autour de la question que la réflexion se concentre
A limitation on black-box dynamics approaches to Reinforcement Learning
No full textWe prove a fundamental limitation on the computational efficiency of a large class of Reinforcement Learning (RL) methods. This limitation applies to model-free RL methods as well as some model-based methods, such as AlphaZero. We provide a formalism that describes this class and present a family of RL problems provably intractable for these methods. Conversely, the problems in the family can be efficiently solved by toy methods. We identify several types of algorithms proposed in the literature that can avoid our limitation, including algorithms that construct an inverse dynamics model, and planning algorithms that leverage an explicit model of the dynamics
Studying keywords in discourse: contrasting different theories and methods
No full textThis article aims at contributing to the recent development of corpus-based research which tries to account for the different features that make specific words play a ‘key’ role in discourse. It proposes to approach this ‘keyness’ in terms of sociopolitical (vs statistical) significance and hence discusses the defining properties of what Jeffries & Walker (2018, p. 4) call ‘sociopolitical keywords’ from a more qualitative perspective. Since there are different labels and different understandings of these qualitatively defined keywords, we review different works on sociopolitical keywords (or related notions) and we discuss them with the aim of offering a general theoretical framework for this concept. In order to introduce the special issue of the Journal of Corpora and Discourse Studies about keywords in sociopolitical debates which includes works on different languages using quantitative and qualitative methods, we also discuss the context-specificness of sociopolitical keywords and highlight the diverse methodologies that have been used to approach this particular discursive phenomenon
Comparison of predictors’ performance in insurance pricing: testing for Bregman dominance based on Murphy diagrams
No full textEhm et al. (2016) defined forecast dominance, or Bregman dominance as dominance for every Bregman loss function. This letter explores Bregman dominance to compare competing candidate pure premiums. An effective testing procedure for Bregman dominance is proposed based on Murphy diagrams and its performance is evaluated through a simulation study. An application to a Swiss motor insurance data set demonstrates the potential of the proposed procedure
Drought and High Temperatures Impact the Plant–Pollinator Interactions in Fagopyrum esculentum
No full textAs a result of climate change, temperate regions are facing the simultaneous increase in water and heat stress. These changes may affect the interactions between plants and pollinators, which will have an impact on entomophilous crop yields. Here, we investigated the consequences of high temperatures and water stress on plant growth, floral biology, flower-reward production, and insect visitation of five varieties of common buckwheat (Fagopyrum esculentum), an entomophilous crop of growing interest for sustainable agriculture. The plants were grown under two temperature regimes (21 °C/19 °C and 28 °C/26 °C, day/night) and two watering regimes (well-watered and water-stressed). Our results showed that the reproductive growth was more affected by drought and high temperatures than was the vegetative growth, and that combined stress had more detrimental effects. However, the impact of drought and high temperatures was variety-dependent. Drought and/or high temperatures reduced the number of open flowers per plant, as well as the floral resources (nectar and pollen), resulting in a decrease in pollinator visits, mainly under combined stress. Although the proportion of Hymenoptera visiting the flowers decreased with high temperatures, the proportion of Diptera remained stable. The insect visiting behavior was not strongly affected by drought and high temperatures. In conclusion, the modification of floral display and floral resources induced by abiotic stresses related to climate change alters plant–pollinator interactions in common buckwheat