Co-évolution des paysages urbain et agraire à Ouidah (Sud-ouest du Bénin) : entre urbanisation et déprise agricole

Les dynamiques foncières dues principalement à l’urbanisation ont profondément modifié l’occupation et l’organisation des espaces urbain et rural. La présente recherche vise à analyser la double évolution du paysage urbain et des espaces cultivables en vue d’une contribution à la maîtrise du phénomène d’urbanisation et ses impacts sur l’agriculture. Les données utilisées sont relatives à l’évolution démographique de la Commune de Ouidah et son influence sur les terres agricoles et aux unités d’occupation du sol de 1995 et de 2010. En plus de la recherche documentaire, les investigations de terrain ont été faites. A cet effet, un effectif de 212 chefs d’exploitation agricole répartis dans cinq (5) arrondissements, a été pris en compte suivant un choix raisonné. Le calcul de l’Indice d’Evolution (IE) et quelques paramètres de la statistique descriptive combinés avec l’approche cartographique ont permis de traiter les données collectées. Il ressort des résultats que la location (49 %) reste le mode d’accès à la terre le plus dominant suivi de l’héritage (38,2 %). Les modes d’accès tels que le don (2,80 %), l’achat (9,90 %) sont d’une proportion très faible. Entre 1995 et 2010, l’agglomération est passée de 6,1 km² à 15,14 km² soit une augmentation de 148,19 % au détriment de la plantation, des champs et jachères sous palmeraie, des champs et jachères, de la formation marécageuse et de la plage sablonneuse. Le mouvement d’urbanisation dans la Commune de Ouidah prend alors de l’ampleur au fil des années et les superficies cultivables s’amenuisent de plus en plus. Face à cette accélération de l’urbanisation des espaces ruraux périphériques, il s’avère indispensable que les pouvoirs publics adoptent des politiques de planification spatiale en vue d’une cohabitation équilibrée des paysages urbain et agraire dans la Commune de Ouidah. Land tenure dynamics mainly caused by urbanization have deeply modified the occupation and organization of urban and rural areas. The present study aims to analyze the development of both the urban landscape and the cultivated areas, in order to help control the urbanization phenomenon and its impacts on agriculture. The data used are based on the demographic growth of Ouidah Township, and its influence on the cultivated areas as well as soil occupation, in 1995 and 2010. In addition to the review of literatures, field investigation was also carried out. To achieve this, 212 farmers from 5 districts were interviewed. Growth index (GI), and some descriptive statistical parameters, combined with mapping approach were used to analyze the collected data. The obtained results show that the lease of lands (49 %) was the most dominant mode of land acquisition, followed by inheritance (38.2 %). The other modes of land acquisition were donation (2.80 %) and purchase (9.90 %). Between 1995 and 2010, the urban area ranged from 6.1 km² to 15.14 km², which represents 148.19 % increase, to the detriment of plantations, farms, palm trees, fallows, swamp and sandy beaches. The urbanization growth in Ouidah Township has gained momentum over the years, while cultivated areas have decreased. With such high speed in urbanization of the peripheral rural areas, it is crucial that official authorities plan the management of the lands, for proper balanced cohabitation of urban and agrarian lands in the Township of Ouidah

Comprehensive Molecular and Clinicopathologic Analysis of 200 Pulmonary Invasive Mucinous Adenocarcinomas Identifies Distinct Characteristics of Molecular Subtypes

PURPOSE: Invasive mucinous adenocarcinoma (IMA) is a unique subtype of lung adenocarcinoma, characterized genomically by frequent KRAS mutations or specific gene fusions, most commonly involving NRG1. Comprehensive analysis of a large series of IMAs using broad DNA- and RNA-sequencing methods is still lacking, and it remains unclear whether molecular subtypes of IMA differ clinicopathologically. EXPERIMENTAL DESIGN: A total of 200 IMAs were analyzed by 410-gene DNA next-generation sequencing (MSK-IMPACT; n = 136) or hotspot 8-oncogene genotyping (n = 64). Driver-negative cases were further analyzed by 62-gene RNA sequencing (MSK-Fusion) and those lacking fusions were further tested by whole-exome sequencing and whole-transcriptome sequencing (WTS). RESULTS: Combined MSK-IMPACT and MSK-Fusion testing identified mutually exclusive driver alterations in 96% of IMAs, including KRAS mutations (76%), NRG1 fusions (7%), ERBB2 alterations (6%), and other less common events. In addition, WTS identified a novel NRG2 fusion (F11R-NRG2). Overall, targetable gene fusions were identified in 51% of KRAS wild-type IMAs, leading to durable responses to targeted therapy in some patients. Compared with KRAS-mutant IMAs, NRG1-rearranged tumors exhibited several more aggressive characteristics, including worse recurrence-free survival (P \u3c 0.0001). CONCLUSIONS: This is the largest molecular study of IMAs to date, where we demonstrate the presence of a major oncogenic driver in nearly all cases. This study is the first to document more aggressive characteristics of NRG1-rearranged IMAs, ERBB2 as the third most common alteration, and a novel NRG2 fusion in these tumors. Comprehensive molecular testing of KRAS wild-type IMAs that includes fusion testing is essential, given the high prevalence of alterations with established and investigational targeted therapies in this subset

HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

Amplification and oncogenic mutations of ERBB2, the gene encoding the HER2 receptor tyrosine kinase, promote receptor hyperactivation and tumor growth. Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody-drug conjugates (ADCs) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models. These data translated into a 51% response rate in a clinical trial of T-DM1 in 49 patients with ERBB2/HER2-amplified or mutant lung cancers. We show that co-treatment with irreversible pan-HER inhibitors enhances receptor ubiquitination and consequent ADC internalization and efficacy. We also demonstrate that ADC switching to T-DXd, which harbors a different cytotoxic payload, achieves durable responses in a patient with lung cancer and corresponding xenograft model developing resistance to T-DM1. Our findings may help guide future clinical trials and expand the field of ADC as cancer therapy

Phase II, open-label study of encorafenib plus binimetinib in patients with BRAFV600-mutant metastatic non-small-cell lung cancer

PURPOSE The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with BRAF(V600E/K)-mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC).METHODS In this ongoing, open-label, single-arm, phase II study, patients with BRAF(V600E)-mutant metastatic NSCLC received oral encorafenib 450 mg once daily plus binimetinib 45 mg twice daily in 28-day cycles. The primary end point was confirmed objective response rate (ORR) by independent radiology review (IRR). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival, time to response, and safety.RESULTS At data cutoff, 98 patients (59 treatment-naive and 39 previously treated) with BRAF(V600E)-mutant metastatic NSCLC received encorafenib plus binimetinib. Median duration of treatment was 9.2 months with encorafenib and 8.4 months with binimetinib. ORR by IRR was 75% (95% CI, 62 to 85) in treatment-naive and 46% (95% CI, 30 to 63) in previously treated patients; median DOR was not estimable (NE; 95% CI, 23.1 to NE) and 16.7 months (95% CI, 7.4 to NE), respectively. DCR after 24 weeks was 64% in treatment-naive and 41% in previously treated patients. Median PFS was NE (95% CI, 15.7 to NE) in treatment-naive and 9.3 months (95% CI, 6.2 to NE) in previously treated patients. The most frequent treatment-related adverse events (TRAEs) were nausea (50%), diarrhea (43%), and fatigue (32%). TRAEs led to dose reductions in 24 (24%) and permanent discontinuation of encorafenib plus binimetinib in 15 (15%) patients. One grade 5 TRAE of intracranial hemorrhage was reported. Interactive visualization of the data presented in this article is available at the PHAROS dashboard ().CONCLUSION For patients with treatment-naive and previously treated BRAF(V600E)-mutant metastatic NSCLC, encorafenib plus binimetinib showed a meaningful clinical benefit with a safety profile consistent with that observed in the approved indication in melanoma.Pathogenesis and treatment of chronic pulmonary disease