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Water utilities provide water, sewerage and sanitation services. Yet, they have failed worldwide to provide safely managed water services to at least 2.2 billion people and safely managed sanitation services to between 3.5 and 4.4 billion. Following 70 years of experience in different modes of water services provision, this paper addresses the question: What lessons can be learnt from the scholarship on the policy and practice of water service provision, and how can these inform and be integrated into a justice framework? This paper examines the literature through the lens of Water System Justice, charting how an early stage of state water and sanitation provision gave way to an increase in private sector participation and eventually hybrid services provision. Neither the state, private nor hybrid models have been able to provide water and sanitation services to all. Combining a Water System Justice approach with a purpose-led market-shaping approach, we argue that the state must take responsibility for a purpose-based approach that puts the furthest behind first – in line with the Agenda 2030. This includes using water within water system boundaries (quantity) and standards (quality), through collaboration with other actors, using patient and local finance, contextual modular systems and ensuring accountability.

The Paris Agreement has seen the adoption of a 1.5° to 2 °C climate target, based on the belief that climate change becomes ‘dangerous’ above this level. Since then, the scientific community and the countries most affected by global warming have reiterated that the maximum limit to be reached should be 1.5 °C. This paper goes one step further by questioning the reasoning behind the adoption of these targets, arguing that the fossil fuel-dependent political context in which they were adopted has undermined justice concerns. We highlight the political influence of the fossil fuels industry within target-setting negotiations, analyzing the evolution of climate targets and fossil fuel lobbying. We then harness published scientific evidence and the Earth System Justice framework to analyze the impacts of the 1.5 °C target, and the injustices that have so far been implicitly deemed acceptable. We argue that 1 °C would have been a far more just target and was undermined by vested interests and status quo maintenance. Finally, we propose just supply-side policies to ensure an adequate placement of responsibility on the fossil fuel industry. This way we (a) identify political influences and scientific blind spots that have and could continue to hinder climate action, (b) reveal how these influences delayed more ambitious climate objectives, contributing to the adoption of an unjust climate target, and (c) promote a focus on supply-side measures and polluting industries in order to break free from the impasse in the energy transition and foster more just outcomes.

This study simulates carbon dioxide (CO 2 ) sequestration in 300 major world river basins (about 70% of global surface area) through carbonates dissolution and silicate hydrolysis. For each river basin, the daily timescale impacts under the RCP 2.6 and RCP 8.5 climate scenarios were assessed relative to a historical baseline (1969–1999) using a cascade of models accounting for the hydrological evolution under climate change scenarios. Here we show that the global temporal evolution of the CO 2 uptake presents a general increase in the annual amount of CO 2 consumed from 0.247 ± 0.045 Pg C year −1 to 0.261 and 0.273 ± 0.054 Pg C year −1 , respectively for RCP 2.6 and RCP 8.5. Despite showing a general increase in the global daily carbon sequestration, both climate scenarios show a decrease between June and August. Such projected changes have been mapped and evaluated against changes in hydrology, identifying hot spots and moments for the annual and seasonal periods.

Southern Iceland is one of the main outlets of the Icelandic ice sheet and is subject to seismicity of both tectonic and volcanic origins along the South Iceland Seismic Zone (SISZ). A sedimentary complex spanning Marine Isotopic Stage 6 (MIS 6) to the present includes evidence of both activities. It includes a continuous sedimentary record since the Eemian interglacial period, controlled by a rapid deglaciation, followed by two marine glacioisostasy-forced transgressions, separated by a regression phase connected to an intra-MIS 5e glacial advance. This record has been constrained by tephrostratigraphy and dating. Analysis of this record has provided better insights into the interconnectedness of hydrology and volcanic and tectonic activity during deglaciations and glaciations. Low-intensity earthquakes recurrently affected the water-laid sedimentation during the early stages of unloading, accompanying rifting events, dyke injection, and fault reactivations. During full interglacial periods, earthquakes were significantly less frequent but of higher magnitude along the SISZ, due to stress accumulation, favored by low groundwater levels and more limited magma production. Occurrence of volcanism and seismicity in Iceland is commonly related to rifting events. Subglacial volcanic events seem moreover to have been related to stress unlocking related to limited or full unloading/deglaciation events. Major eruptions were mostly located at the melting margin of the ice sheet.

Valvular heart disease is observed in approximately 2% of the general population 1 . Although the initial observation is often localized (for example, to the aortic or mitral valve), disease manifestations are regularly observed in the other valves and patients frequently require surgery. Despite the high frequency of heart valve disease, only a handful of genes have so far been identified as the monogenic causes of disease 2 – 7 . Here we identify two consanguineous families, each with two affected family members presenting with progressive heart valve disease early in life. Whole-exome sequencing revealed homozygous, truncating nonsense alleles in ADAMTS19 in all four affected individuals. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype. Expression analysis using a lacZ reporter and single-cell RNA sequencing highlight Adamts19 as a novel marker for valvular interstitial cells; inference of gene regulatory networks in valvular interstitial cells positions Adamts19 in a highly discriminatory network driven by the transcription factor lymphoid enhancer-binding factor 1 downstream of the Wnt signaling pathway. Upregulation of endocardial Krüppel-like factor 2 in Adamts19 knockout mice precedes hemodynamic perturbation, showing that a tight balance in the Wnt–Adamts19–Klf2 axis is required for proper valve maturation and maintenance. Mutations in ADAMTS19 lead to progressive heart valve disease in humans. Analysis of mice lacking Adamts19 highlights the role of a Wnt–Adamts19–Klf2 axis in proper valve function.

Abstract This study simulates carbon dioxide (CO 2 ) sequestration in 300 major world river basins (about 70% of global surface area) through carbonates dissolution and silicate hydrolysis. For each river basin, the daily timescale impacts under the RCP 2.6 and RCP 8.5 climate scenarios were assessed relative to a historical baseline (1969–1999) using a cascade of models accounting for the hydrological evolution under climate change scenarios. Here we show that the global temporal evolution of the CO 2 uptake presents a general increase in the annual amount of CO 2 consumed from 0.247 ± 0.045 Pg C year −1 to 0.261 and 0.273 ± 0.054 Pg C year −1 , respectively for RCP 2.6 and RCP 8.5. Despite showing a general increase in the global daily carbon sequestration, both climate scenarios show a decrease between June and August. Such projected changes have been mapped and evaluated against changes in hydrology, identifying hot spots and moments for the annual and seasonal periods.

Background & Aims: Epithelial tumors generally resemble the cellular architecture of their tissue of origin. However, this link remains largely unexplored in the pancreas. Methods: Using Nanostring GeoMx DSP®, Resolve Molecular Cartography® and Nanostring CosMx®, and integration with single cell RNAseq datasets, we mapped the human pancreatic ductal epithelium in non-neoplastic pancreas, and compared it to pancreatic cancer subtypes. Results: Groups of Keratin-5+ cells among the Pan-Cytokeratin+ cells in the duct have a gene signature reminiscent of stem cells and (supra)basal cells from other tissues. In spatial analysis at single cell resolution, the pancreatic duct manifests as a stratified epithelium comprising a basal and four luminal populations; In large ducts, KRT5+ basal (BAS) cells express ∆Np63 while KRT5+ luminal (LUM)-B cells reside supra-basally and are distinct from the common KRT5- LUM-A cells. LUM-C and LUM-D cells pertain to intercalated ducts and ductal glands, respectively. LUM-A and -C cells express gel-forming mucins while LUM-B cells have membrane-bound MUC4 and MUC16. In cancer, BAS and LUM-B signatures associate with the basal-like pancreatic ductal adenocarcinoma (PDAC) and correlate with lower survival but exhibit a mixed spatial pattern with a diffracted gene signature. In contrast, adenosquamous cancers of the pancreas (ASCP) preserve the normal spatially unmixed identity of LUM-B cells and BAS cells that is regulated by ∆Np63. Next to ∆Np63, conserved drug targets were identified for both populations. Conclusion: This study offers a refined pancreatic tumor classification based on the native ductal architecture, with better preservation of the LUM-B and BAS cell population identity in ASCP than in PDAC, including the conserved drug targets.Competing Interest StatementThe authors have declared no competing interest.

Le gisement d'Hénin-sur-Cojeul (Pas-de-Calais) est contenu dans une couverture loessique correspondant au Pléniglaciaire moyen du Weichsélien (stade isotopique 3). Les niveaux d'occupation sont inclus dans un pédocomplexe attribuable aux interstades d'Hengelo et de Denekamp. L'analyse pollinique montre un développement du Bouleau dans une végétation steppique. La date 14C la plus ancienne est 37900 ± 1800 ans BP. Les restes osseux appartiennent surtout au Bison. Les séries lithiques sont attribuées au Moustérien typique. The site of Hénin-sur-Cojeul (Pas-de-Calais) includes loessic deposits corresponding to the Middle Pleniglacial (Weichselian) (isotopic stage 3). Occupation levels are preserved in a fossil soil complex interpreted as Hengelo and Denekamp interstadials. Pollen analysis shows the development of Betula in a steppe-like vegetation. The oldest 14C date gives 37900 ± 1800 years BP. The faunal remains are dominated by Bison. The lithics series are attributed to the typical Mousterian.