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Aims: The associations between potassium level and outcomes, the effect of sacubitril–valsartan on potassium level, and whether potassium level modified the effect of sacubitril–valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM‐HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non‐cardiovascular death and heart failure hospitalization, were examined. Methods and results: A total of 8399 patients were randomized to either enalapril or sacubitril–valsartan. Potassium level at randomization and follow‐up was examined as a continuous and categorical variable (≤3.5, 3.6–4.0, 4.1–4.9, 5.0–5.4 and ≥5.5 mmol/L) in various statistical models. Hyperkalaemia was defined as K+ ≥5.5 mmol/L and hypokalaemia as K+ ≤3.5 mmol/L. Compared with potassium 4.1–4.9 mmol/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84–3.14] and hyperkalaemia (HR 1.42, 95% CI 1.10–1.83) were associated with a higher risk for cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non‐cardiovascular death and heart failure hospitalization. Sacubitril–valsartan had no effect on potassium overall. The benefit of sacubitril–valsartan over enalapril was consistent across the range of baseline potassium levels. Conclusions: Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.

10 Background: For men with mCRPC, systemic therapies such as docetaxel and cabazitaxel improve survival, but more effective treatments are needed. KEYNOTE-365 (NCT02861573) is a phase 1b/2 study to examine the safety and efficacy of pembro in combination with 4 different study medications (cohorts A, B, C, D) in mCRPC. Previous data from cohort B with a median of 20 months of follow-up showed that pembro + docetaxel and prednisone was well tolerated and had antitumor activity in patients (pts) with mCRPC previously treated with abi or enza. New efficacy and safety data after an additional year of follow-up are presented. Methods: Cohort B enrolled pts who did not respond to or were intolerant to ≥4 weeks of abi or enza in the prechemotherapy mCRPC state and whose disease progressed within 6 months of screening (determined by PSA progression or radiologic bone/soft tissue progression). Pts received pembro 200 mg IV every 3 weeks (Q3W), docetaxel 75 mg/m2 IV Q3W, and oral prednisone 5 mg twice daily. Primary end points were safety, PSA response rate (PSA decrease >50% from baseline), and ORR per RECIST v1.1 by blinded independent central review. Efficacy and safety were assessed in all pts as treated. Results: Of the 104 treated pts, median age was 68.0 years (range, 50-86), 23.1% had PD-L1–positive tumors (combined positive score ≥1), 25.0% had visceral disease, and 50.0% had measurable disease. Median time from enrollment to data cutoff was 32.4 months (range 13.9-40.3); 101 pts discontinued, primarily because of disease progression (77.9%). Efficacy outcomes are reported in the table below. Treatment-related adverse events (TRAEs) occurred in 100 pts (96.2%); the most frequent (≥30%) were diarrhea (41.3%), fatigue (41.3%), and alopecia (40.4%). Grade 3-5 TRAEs occurred in 46 pts (44.2%). Five pts (4.8%) died of AEs; 2 were treatment-related pneumonitis. Conclusions: After another year of follow-up, pembro + docetaxel and prednisone showed improved ORR and PSA response rates compared to the prior dataset in pts with mCRPC previously treated with abi or enza. Safety was consistent with known profiles of each agent and will be further evaluated in a phase 3 study (KEYNOTE-921). Clinical trial information: NCT02861573. [Table: see text]

Background: The diagnosis of solitary cutaneous mastocytoma is mainly clinical, based on lesion morphology, the presence of a positive Darier sign, and the absence of systemic involvement. Knowledge of this condition is important so that an accurate diagnosis can be made. Objective: To familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of a solitary cutaneous mastocytoma. Methods: A PubMed search was completed in Clinical Queries using the key term "solitary cutaneous mastocytoma". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in English language were included. The information retrieved from the above search was used in the compilation of the present article. Results: Typically, a solitary cutaneous mastocytoma presents as an indurated, erythematous, yellow- brown or reddish-brown macule, papule, plaque or nodule, usually measuring up to 5 cm in diameter. The lesion often has a peau d'orange appearance and a leathery or rubbery consistency. A solitary cutaneous mastocytoma may urticate spontaneously or when stroked or rubbed (Darier sign). Organomegaly and lymphadenopathy are characteristically absent. The majority of patients with skin lesions that erupt within the first two years of life have spontaneous resolution of the lesions before puberty. Treatment is mainly symptomatic. Reassurance and avoidance of triggering factors suffice in most cases. Conclusion: The diagnosis is mainly clinical, based on the morphology of the lesion, the presence of a positive Darier sign, and the absence of systemic involvement. A skin biopsy is usually not necessary unless the diagnosis is in doubt.

Abstract With an increasing number of coastal issues associated with human pressure and exacerbated by climate change, this study examines how residents of coastal communities perceive their living environment and how they perceive risks in this environment and more particularly coastal risks (marine erosion and flooding). An international (Canada-France) questionnaire study was conducted among 190 people, approximately half of whom lived on New Brunswick's Acadian Coast and half on France's west coast. The results highlight, on the one hand, the residents' strong relationship with their coastal living environment and, on the other, a representation of coastal risks as an important area of concern for them. That said, the worry concerning these risks varied among the participants. The local and cultural context (media coverage of this issue and the country-specific risk management strategies) may explain the differences in attitude between the two countries.

We report on an all-sky search for continuous gravitational waves in the frequency band 20-2000 Hz and with a frequency time derivative in the range of [-1.0,+0.1]×10-8 Hz/s. Such a signal could be produced by a nearby, spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. This search uses the LIGO data from the first six months of Advanced LIGO's and Advanced Virgo's third observational run, O3. No periodic gravitational wave signals are observed, and 95% confidence-level (C.L.) frequentist upper limits are placed on their strengths. The lowest upper limits on worst-case (linearly polarized) strain amplitude h0 are ∼1.7×10-25 near 200 Hz. For a circularly polarized source (most favorable orientation), the lowest upper limits are ∼6.3×10-26. These strict frequentist upper limits refer to all sky locations and the entire range of frequency derivative values. For a population-averaged ensemble of sky locations and stellar orientations, the lowest 95% C.L. upper limits on the strain amplitude are ∼1.4×10-25. These upper limits improve upon our previously published all-sky results, with the greatest improvement (factor of ∼2) seen at higher frequencies, in part because quantum squeezing has dramatically improved the detector noise level relative to the second observational run, O2. These limits are the most constraining to date over most of the parameter space searched. This work was supported by MEXT, JSPS Leading-edge Research Infrastructure Program, JSPS Grant-in-Aid for Specially Promoted Research 26000005, JSPS Grant-in-Aid for Scientific Research on Innovative Areas 2905: JP17H06358, JP17H06361 and JP17H06364, JSPS Core-to-Core Program A. Advanced Research Networks, JSPS Grant-in-Aid for Scientific Research (S) 17H06133, the joint research program of the Institute for Cosmic Ray Research, University of Tokyo, National Research Foundation (NRF) and Computing Infrastructure Project of KISTI-GSDC in Korea, Academia Sinica (AS), AS Grid Center (ASGC) and the Ministry of Science and Technology (MoST) in Taiwan under grants including ASCDA-105-M06, Advanced Technology Center (ATC) of NAOJ, and Mechanical Engineering Center of KEK Abbott, R. (LIGO Scientific Collaboration, Virgo Collaboration, KAGRA Collaboration)

Multimarginal Optimal Transport (MOT) has attracted significant interest due to applications in machine learning, statistics, and the sciences. However, in most applications, the success of MOT is severely limited by a lack of efficient algorithms. Indeed, MOT in general requires exponential time in the number of marginals k and their support sizes n. This paper develops a general theory about what "structure" makes MOT solvable in poly(n,k) time. We develop a unified algorithmic framework for solving MOT in poly(n,k) time by characterizing the "structure" that different algorithms require in terms of simple variants of the dual feasibility oracle. This framework has several benefits. First, it enables us to show that the Sinkhorn algorithm, which is currently the most popular MOT algorithm, requires strictly more structure than other algorithms do to solve MOT in poly(n,k) time. Second, our framework makes it much simpler to develop poly(n,k) time algorithms for a given MOT problem. In particular, it is necessary and sufficient to (approximately) solve the dual feasibility oracle -- which is much more amenable to standard algorithmic techniques. We illustrate this ease-of-use by developing poly(n,k) time algorithms for three general classes of MOT cost structures: (1) graphical structure; (2) set-optimization structure; and (3) low-rank plus sparse structure. For structure (1), we recover the known result that Sinkhorn has poly(n,k) runtime; moreover, we provide the first poly(n,k) time algorithms for computing solutions that are exact and sparse. For structures (2)-(3), we give the first poly(n,k) time algorithms, even for approximate computation. Together, these three structures encompass many -- if not most -- current applications of MOT. v4: to appear in Mathematical Programming, improved exposition and refs, no changes to technical results

Atmospheric ammonia (NH3) is a precursor to fine particulate matter formation and contributes to nitrogen (N) deposition, with potential implications for the health of humans and ecosystems. Agricultural soils and animal excreta are the primary source of atmospheric NH3, but natural soils can also be an important emitter. In regions with distinct dry and wet seasons such as the Sahel, the start of the rainy season triggers a pulse of biogeochemical activity in surface soils known as the Birch effect, which is often accompanied by emissions of microbially produced gases such as carbon dioxide and nitric oxide. Field and lab studies have sometimes, but not always, observed pulses of NH3 after the wetting of dry soils; however, the potential regional importance of these emissions remains poorly constrained. Here we use satellite retrievals of atmospheric NH3 using the Infrared Atmospheric Sounding Interferometer (IASI) regridded at 0.25∘ resolution, in combination with satellite-based observations of precipitation, surface soil moisture, and nitrogen dioxide concentrations, to reveal substantial precipitation-induced pulses of NH3 across the Sahel at the onset of the rainy season in 2008. The highest concentrations of NH3 occur in pulses during March and April when NH3 biomass burning emissions estimated for the region are low. For the region of the Sahel spanning 10 to 16∘ N and 0 to 30∘ E, changes in NH3 concentrations are weakly but significantly correlated with changes in soil moisture during the period from mid-March through April when the peak NH3 concentrations occur (r=0.28, p=0.02). The correlation is also present when evaluated on an individual pixel basis during April (r=0.16, p<0.001). Average emissions for the entire Sahel from a simple box model are estimated to be between 2 and 6 mg NH3 m−2 d−1 during peaks of the observed pulses, depending on the assumed effective NH3 lifetime. These early season pulses are consistent with surface observations of monthly concentrations, which show an uptick in NH3 concentration at the start of the rainy season for sites in the Sahel. The NH3 concentrations in April are also correlated with increasing tropospheric NO2 concentrations observed by the Ozone Monitoring Instrument (r=0.78, p<0.0001), which have previously been attributed to the Birch effect. Box model results suggest that pulses occurring over a 35-day period in March and April are responsible for roughly one-fifth of annual emissions of NH3-N from the Sahel. We conclude that precipitation early in the rainy season is responsible for substantial NH3 emissions in the Sahel, likely representing the largest instantaneous fluxes of gas-phase N from the region during the year.

Avec la crise du coronavirus, les destinations lointaines de nature comme la Patagonie chilienne sont inquiètes d’un effondrement du tourisme. Les communautés locales, apeurées par les risques liés à l’accueil de visiteurs, se replient et se protègent. Les entrepreneurs espèrent un rapide retour à la « normalité » d’une zone relativement épargnée par la COVID-19, mais craignent la fin du boom touristique, car prendre l’avion restera anxiogène dans un contexte de pandémie. Ces destinations devraient recentrer leur offre afin de capter une clientèle de proximité, mais cela semble un défi peu rentable pour les zones isolées. Alors que les entrepreneurs affinent leur plan marketing et les services d’État leurs protocoles d’accueil sécurisés, les animateurs de projets touristiques écologiques, axés sur la conservation, le tourisme rural et les migrations d’agrément, font valoir leurs atouts. L’actuelle crise pourrait mettre fin au tourisme de masse, à l’hypermobilité vers des hauts lieux et aux projets basés sur la rentabilité. La crise socioenvironnementale globale est l’occasion de repenser les rapports à la nature et de renforcer les systèmes touristiques locaux, pensés comme des lieux de vie, basés sur des économies rurales respectueuses de l’environnement, les échanges culturels, scientifiques et traditionnels, attirants autant pour les clientèles nationales qu’étrangères. With the coronavirus crisis, remote nature destinations like Chilean Patagonia are worried of a possible collapse of tourism. Local communities, frightened by the risks of welcoming visitors, are withdrawing and protecting themselves. Entrepreneurs hope for a rapid return to “normality” in an area relatively untouched by COVID-19 but they fear the end of the tourism boom, as flying will remain an anxiety-provoking issue in a post-pandemic situation. These destinations have to refocus their offer in order to capture a national clientele, but this seems an unprofitable challenge for isolated areas. While entrepreneurs are refining their marketing plans and government services are establishing their secure reception protocols, leaders of ecological and conservation tourism projects along with rural tourism and leisure migration stakeholders are highlighting their assets. The current crisis could put an end to mass tourism, hypermobilities, projects based on high profitability and overtourism in iconic places. In that sense, the present global socioenvironmental crisis is an opportunity to rethink our relationship with nature and seek ways to strengthen local tourism systems, conceived as places to live and based on environmentally friendly rural economies, cultural, scientific, and traditional exchanges, attractive both to national and foreign visitors.

The beaches of the Caribbean Islands are regularly affected by the stranding of plant debris (algae, phanerogams, etc.) at the tide mark line, which becomes mixed with sand at the top of the beach, along with deadwood and other waste of anthropogenic origin. This situation has worsened since 2011 as a result of the stranding of sargassum seaweed, which significantly reduces beach access and produces emanations of harmful gases. This is damaging for the Caribbean islands of the Lesser Antilles, since their economies are heavily dependant on tourism. These deposits also play a complex role in the sedimentary dynamics of beaches by favouring the trapping or, alternatively, the re-mobilization of sands. Does this accumulation of drift reinforce the erosion of beaches or, on the contrary, does it contribute to their growth? What are the impacts of the manual or mechanical collection of these drift materials on the sediment budget and dynamics of beaches? In an attempt to address these questions, an in-situ experimental study was carried out on the beaches of the Anse Caffard (Le Diamant) and the Anse au Bois (Sainte-Anne) on Martinique. The pocket beach of the Anse au Bois was divided into three sectors. In the first sector, the drift was completely removed by collection, while a second sector was treated by spreading the stranded debris and a third sector was left in a natural state, without any collection. Topographic and hydrodynamic measurements were carried out on the three sectors to characterize the sedimentary response of the beach according to these three methods of managing the stranded drift. Measurements were also carried out on the Anse Caffard beach, which was managed by mechanical collection. These experiments reveal morphodynamic trends which need to be taken into account in the framework of the management of sargassum seaweed crises. Les plages des Antilles sont régulièrement concernées par des échouages de laisses de mer végétales (algues, phanérogames…) qui viennent se mélanger en haut de plage au sable, au bois mort et autres déchets d’origine anthropique. Cette situation est renforcée depuis 2011 par de massifs échouages d’algues sargasses, qui réduisent significativement l’accès à la mer et produisent des émanations de gaz nocifs. Cette situation est préjudiciable pour l’économie des îles antillaises lourdement dépendantes du tourisme. Ces dépôts jouent également un rôle complexe sur la dynamique sédimentaire des plages par des facteurs de piégeage ou, à l’inverse, de remobilisation des sables. Les laisses végétales sont-elles des facteurs de renforcement de l’érosion des plages ou contribuent-elles, au contraire, à leur engraissement? Quels sont les impacts des ramassages manuels ou mécaniques de ces laisses sur le bilan sédimentaire et la dynamique des plages? Pour tenter de répondre à ces questions, une expérimentation in-situ a été réalisée sur les plages de l’Anse Caffard (Le Diamant) et l’Anse au Bois (Ste Anne) en Martinique. La plage de poche de l’Anse au Bois a été divisée en trois tronçons. Un premier, concerné par un ramassage total des laisses ; un second avec un épandage des échouages végétaux ; un troisième à l’état naturel, sans ramassage. Des mesures topographiques et hydrodynamiques ont été réalisées sur les trois secteurs afin de caractériser la réaction sédimentaire de la plage face à ces trois méthodes de gestion des échouages. Des mesures ont également été réalisées sur la plage de l’Anse Cafard, concernée par un ramassage mécanique. Ces expérimentations montrent des tendances morphodynamiques qu’il sera nécessaire de prendre en compte dans le cadre de la gestion des crises d’échouages d’algues sargasses.