Designing fit-for-purpose indicators to connect nature and people’s well-being in New Zealand

Recognizing the value of nature for people’s wellbeing is key to ensuring protection of the environment for current and future generations. However, data to demonstrate the connection between nature and wellbeing, are needed for environmental reporting, to inform policy development and evaluate progress toward outcomes. While many indicators exist, they are mostly derived from available data collected for other purposes and there is limited, if any, description of how these indicators were designed. Based on a conceptualization of nature–well-being connections, we propose a participatory process to identify fit-for-purpose indicators linking nature to human wellbeing. The process uses a series of targeted questions to explore how different aspects of wellbeing rely on nature, enabling more fitting indicators to be identified by the participatory group. The process was refined and tested in workshops with stakeholders in a New Zealand context

Multicellular tumor spheroid model to evaluate spatio-temporal dynamics effect of chemotherapeutics: application to the gemcitabine/CHK1 inhibitor combination in pancreatic cancer

International audienceUNLABELLED: ABSTRACT: BACKGROUND: The multicellular tumor spheroid (MCTS) is an in vitro model associating malignant-cell microenvironment and 3D organization as currently observed in avascular tumors. METHODS: In order to evaluate the relevance of this model for pre-clinical studies of drug combinations, we analyzed the effect of gemcitabine alone and in combination with the CHIR-124 CHK1 inhibitor in a Capan-2 pancreatic cell MCTS model. RESULTS: Compared to monolayer cultures, Capan-2 MCTS exhibited resistance to gemcitabine cytotoxic effect. This resistance was amplified in EGF-deprived quiescent spheroid suggesting that quiescent cells are playing a role in gemcitabine multicellular resistance. After a prolonged incubation with gemcitabine, DNA damages and massive apoptosis were observed throughout the spheroid while cell cycle arrest was restricted to the outer cell layer, indicating that gemcitabine-induced apoptosis is directly correlated to DNA damages. The combination of gemcitabine and CHIR-124 in this MCTS model, enhanced the sensitivity to the gemcitabine antiproliferative effect in correlation with an increase in DNA damage and apoptosis. CONCLUSIONS: These results demonstrate that our pancreatic MCTS model, suitable for both screening and imaging analysis, is a valuable advanced tool for evaluating the spatio-temporal effect of drugs and drug combinations in a chemoresistant and microenvironment-depending tumor model

New insights on the mechanism of quinoline-based DNA methyltransferase inhibitors

Among the epigenetic marks, DNA methylation is one of the most studied. It is highly deregulated in numerous diseases, including cancer. Indeed, it has been shown that hypermethylation of tumor suppressor genes promoters is a common feature of cancer cells. Because DNA methylation is reversible, the DNA methyltransferases (DNMTs), responsible for this epigenetic mark, are considered promising therapeutic targets. Several molecules have been identified as DNMT inhibitors and, among the non-nucleoside inhibitors, 4-aminoquinoline-based inhibitors, such as SGI-1027 and its analogs, showed potent inhibitory activity. Here we characterized the in vitro mechanism of action of SGI-1027 and two analogs. Enzymatic competition studies with the DNA substrate and the methyl donor cofactor, S-adenosyl-L-methionine (AdoMet), displayed AdoMet non-competitive and DNA competitive behavior. In addition, deviations from the Michaelis-Menten model in DNA competition experiments suggested an interaction with DNA. Thus their ability to interact with DNA was established; although SGI-1027 was a weak DNA ligand, analog 5, the most potent inhibitor, strongly interacted with DNA. Finally, as 5 interacted with DNMT only when the DNA duplex was present, we hypothesize that this class of chemical compounds inhibit DNMTs by interacting with the DNA substrate

Implications of albedo changes following afforestation on the benefits of forests as carbon sinks

Increased carbon storage with afforestation leads to a decrease in atmospheric carbon dioxide concentration and thus decreases radiative forcing and cools the Earth. However, afforestation also changes the reflective properties of the surface vegetation from more reflective pasture to relatively less reflective forest cover. This increase in radiation absorption by the forest constitutes an increase in radiative forcing, with a warming effect. The net effect of decreased albedo and carbon storage on radiative forcing depends on the relative magnitude of these two opposing processes. <br></br> We used data from an intensively studied site in New Zealand's Central North Island that has long-term, ground-based measurements of albedo over the full short-wave spectrum from a developing <i>Pinus radiata</i> forest. Data from this site were supplemented with satellite-derived albedo estimates from New Zealand pastures. The albedo of a well-established forest was measured as 13 % and pasture albedo as 20 %. We used these data to calculate the direct radiative forcing effect of changing albedo as the forest grew. <br></br> We calculated the radiative forcing resulting from the removal of carbon from the atmosphere as a decrease in radiative forcing of −104 GJ tC<sup>−1</sup> yr<sup>−1</sup>. We also showed that the observed change in albedo constituted a direct radiative forcing of 2759 GJ ha<sup>−1</sup> yr<sup>−1</sup>. Thus, following afforestation, 26.5 tC ha<sup>−1</sup> needs to be stored in a growing forest to balance the increase in radiative forcing resulting from the observed albedo change. Measurements of tree biomass and albedo were used to estimate the net change in radiative forcing as the newly planted forest grew. Albedo and carbon-storage effects were of similar magnitude for the first four to five years after tree planting, but as the stand grew older, the carbon storage effect increasingly dominated. Averaged over the whole length of the rotation, the changes in albedo negated the benefits from increased carbon storage by 17–24 %

Etude des connaissances, attitudes et pratiques en matière de réintégration sociale des femmes victimes de fistule obstétricale: Région de l’Extrême-nord, Cameroun

Introduction: la fistule obstétricale est un orifice entre le vagin et la vessie ou le rectum, voire les deux. Ses impacts sont des conséquencesanatomo-fonctionnelles et sociales. On estime à plus de 19 000 le nombre de femmes qui souffrent de fistule obstétricale au Cameroun.Méthodes: il s'agissait d'une étude transversale descriptive conduite dans trois districts de santé de la région de l'Extrême-nord. Vingt-huit femmes victimes de fistules obstétricales, quarante-deux membres de leur  entourage et vingt-quatre agents de santé ont été interviewés entre Novembre et Décembre 2013. Trois types de questionnaires ont été  utilisés. Les données ont été analysées dans Epi Info version 7.1.4.0. Lesmoyennes et les fréquences ont été calculées avec un intervalle de  confiance à 95%. Résultats: 46,4% des femmes victimes de fistule obstétricales  interviewées avaient subi une intervention chirurgicale réparatrice parmi lesquelles, 61,5% bénéficiaient de la réintégration. Le fonds de commerce (62,5%) était l'aide la plus reçue. Vingt-deux membres de l'entourage savaient pourquoi on fait la réintégration. Selon eux, les considérations socioculturelles (68,2%), sont la principale barrière de la réintégration.  D'après les agents de santé, le suivi psychosocial (58,3%) est la principale activité de la réintégration dans les centres de prise en charge de la fistule. Conclusion: la prise en charge des fistules obstétricales au Cameroun souffre de manque de réintégration sociale. Ceci expliquerait en partie la persistance de cette pathologie. Un accent devrait être mis sur l'appui matériel, financier et sur le suivi psychosocial des femmes victimes de fistule obstétricale

Dynamic Optimization in Peer-To-Peer Transportation with Acceptance Probability Approximation

Crowdsourced transportation by independent suppliers (or drivers) is central to urban delivery and mobility platforms. While utilizing crowdsourced resources has several advantages, it comes with the challenge that suppliers are not bound to assignments made by the platforms. In practice, suppliers often decline offered service requests, e.g., due to the required travel detour, the expected tip, or the area a request is located. This leads to inconveniences for the platform (ineffective assignments), the corresponding customer (delayed service), and also the suppliers themselves (non-fitting assignment, less revenue). In this work, we show how approximating suppliers’ acceptance behavior by analyzing their past decision making can alleviate these inconveniences. To this end, we propose a dynamic matching problem where suppliers’ acceptances or rejections of offers are uncertain and depend on a variety of request attributes. Suppliers who accept an offered request from the platform are assigned and reenter the system after service looking for another offer. Suppliers declining an offer stay idle to wait for another offer, but leave after a limited time if no acceptable offer is made. Every supplier decision reveals partial information about the suppliers’ acceptance behavior, and in this paper, we present a corresponding mathematical model and a solution approach that translates supplier responses into the probability of a specific supplier to accept a specific future offer and uses this information to optimize subsequent offering decisions. We show that our approach leads to overall more successful assignments, more revenue for the platform and most of the suppliers, and less waiting for the customers to be served. We also show that considering individual supplier behavior can lead to unfair treatment of more agreeable suppliers