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The downsizing of disperser assemblages by selective defaunation is a worldwide phenomenon thought to have important consequences in animal‐dispersed plants. Numerous large‐seeded Neotropical plants currently depend on the last megafaunal survivors, the large tapirs Tapirus spp., and medium‐sized frugivores. The extent to which medium frugivores are functionally equivalent to tapirs remains unresolved. We combined feeding trials, seed dispersal kernel modeling based on seed retention times and animal movement simulation (Levy walks), and germination experiments in a large‐seeded palm to assess the dispersal quality provided by the largest (tapirs) and two medium (foxes and howler monkeys) frugivore species in terms of dispersal distances and gut passage effects on germination. Tapirs retained the seeds in the gut for much longer (mean = 221 hours) than howlers (43 h) and foxes (22 h). Median dispersal distance by tapirs (1252 m) was 14 and 40 times larger than that by foxes (88 m) and howlers (31 m), respectively. The seed dispersal kernel of tapirs showed a 5th percentile value (291 m) larger than the 95th percentiles of foxes (285 m) and howlers (108 m). Manually depulped and gut‐passed seeds germinated in similar proportions, showing, respectively, 3.5 and 2.5–2.9 times higher values than intact fruits. Germination probability and seed viability decreased with retention time in howlers' and tapirs' gut, with howlers showing a steeper negative relationship. Such detrimental effect implies a trade‐off between germination success and dispersal distance. We conclude that tapirs may not play a unique role in germination enhancement but move seeds much further than medium frugivores, thus playing a critical role as long‐distance dispersers of many plants. This study provides important insights on palm–frugivore interactions and the potential consequences for large‐seeded plants of losing the last megafaunal representatives in the Neotropics. [ABSTRACT FROM AUTHOR]

We use 26×106 galaxies from the Dark Energy Survey (DES) Year 1 shape catalogs over 1321 deg2 of the sky to produce the most significant measurement of cosmic shear in a galaxy survey to date. We constrain cosmological parameters in both the flat ΛCDM and the wCDM models, while also varying the neutrino mass density. These results are shown to be robust using two independent shape catalogs, two independent photo-z calibration methods, and two independent analysis pipelines in a blind analysis. We find a 3.5% fractional uncertainty on σ8(Ωm/0.3)0.5=0.782-0.027+0.027 at 68% C.L., which is a factor of 2.5 improvement over the fractional constraining power of our DES Science Verification results. In wCDM, we find a 4.8% fractional uncertainty on σ8(Ωm/0.3)0.5=0.777-0.038+0.036 and a dark energy equation-of-state w=-0.95-0.39+0.33. We find results that are consistent with previous cosmic shear constraints in σ8 - Ωm, and we see no evidence for disagreement of our weak lensing data with data from the cosmic microwave background. Finally, we find no evidence preferring a wCDM model allowing w≠-1. We expect further significant improvements with subsequent years of DES data, which will more than triple the sky coverage of our shape catalogs and double the effective integrated exposure time per galaxy.

We present galaxy-galaxy lensing measurements from 1321 sq. deg. of the Dark Energy Survey (DES) Year 1 (Y1) data. The lens sample consists of a selection of 660,000 red galaxies with high-precision photometric redshifts, known as redMaGiC, split into five tomographic bins in the redshift range 0.15

We present cosmological results from a combined analysis of galaxy clustering and weak gravitational lensing, using 1321 deg2 of griz imaging data from the first year of the Dark Energy Survey (DES Y1). We combine three two-point functions: (i) the cosmic shear correlation function of 26 million source galaxies in four redshift bins, (ii) the galaxy angular autocorrelation function of 650,000 luminous red galaxies in five redshift bins, and (iii) the galaxy-shear cross-correlation of luminous red galaxy positions and source galaxy shears. To demonstrate the robustness of these results, we use independent pairs of galaxy shape, photometric-redshift estimation and validation, and likelihood analysis pipelines. To prevent confirmation bias, the bulk of the analysis was carried out while "blind" to the true results; we describe an extensive suite of systematics checks performed and passed during this blinded phase. The data are modeled in flat ΛCDM and wCDM cosmologies, marginalizing over 20 nuisance parameters, varying 6 (for ΛCDM) or 7 (for wCDM) cosmological parameters including the neutrino mass density and including the 457×457 element analytic covariance matrix. We find consistent cosmological results from these three two-point functions and from their combination obtain S8≡σ8(Ωm/0.3)0.5=0.773-0.020+0.026 and Ωm=0.267-0.017+0.030 for ΛCDM; for wCDM, we find S8=0.782-0.024+0.036, Ωm=0.284-0.030+0.033, and w=-0.82-0.20+0.21 at 68% C.L. The precision of these DES Y1 constraints rivals that from the Planck cosmic microwave background measurements, allowing a comparison of structure in the very early and late Universe on equal terms. Although the DES Y1 best-fit values for S8 and Ωm are lower than the central values from Planck for both ΛCDM and wCDM, the Bayes factor indicates that the DES Y1 and Planck data sets are consistent with each other in the context of ΛCDM. Combining DES Y1 with Planck, baryonic acoustic oscillation measurements from SDSS, 6dF, and BOSS and type Ia supernovae from the Joint Lightcurve Analysis data set, we derive very tight constraints on cosmological parameters: S8=0.802±0.012 and Ωm=0.298±0.007 in ΛCDM and w=-1.00-0.04+0.05 in wCDM. Upcoming Dark Energy Survey analyses will provide more stringent tests of the ΛCDM model and extensions such as a time-varying equation of state of dark energy or modified gravity.

We describe the derivation and validation of redshift distribution estimates and their uncertainties for the populations of galaxies used as weak-lensing sources in the Dark Energy Survey (DES) Year 1 cosmological analyses. The Bayesian Photometric Redshift (BPZ) code is used to assign galaxies to four redshift bins between z ≈ 0.2 and ≈1.3, and to produce initial estimates of the lensing-weighted redshift distributions nPZi(z) ∝ dni/dz for members of bin i. Accurate determination of cosmological parameters depends critically on knowledge of ni, but is insensitive to bin assignments or redshift errors for individual galaxies. The cosmological analyses allow for shifts ni (z) = nPZi(z - Δzi) to correct themean redshift of ni(z) for biases in nPZi. The Δzi are constrained by comparison of independently estimated 30-band photometric redshifts of galaxies in the Cosmic Evolution Survey (COSMOS) field to BPZ estimates made from the DES griz fluxes, for a sample matched in fluxes, pre-seeing size, and lensing weight to the DES weak-lensing sources. In companion papers, the Δzi of the three lowest redshift bins are further constrained by the angular clustering of the source galaxies around red galaxies with secure photometric redshifts at 0.15 < z < 0.9. This paper details the BPZ and COSMOS procedures, and demonstrates that the cosmological inference is insensitive to details of the ni(z) beyond the choice of Δzi. The clustering and COSMOS validation methods produce consistent estimates of Δzi in the bins where both can be applied, with combined uncertainties of σΔzi = 0.015, 0.013, 0.011, and 0.022 in the four bins. Repeating the photo-z procedure instead using the Directional Neighbourhood Fitting algorithm, or using the ni(z) estimated from the matched sample in COSMOS, yields no discernible difference in cosmological inferences.

We use numerical simulations to characterize the performance of a clustering-based method to calibrate photometric redshift biases. In particular, we cross-correlate the weak lensing source galaxies from the Dark Energy Survey Year 1 sample with redMaGiC galaxies (luminous red galaxies with secure photometric redshifts) to estimate the redshift distribution of the former sample. The recovered redshift distributions are used to calibrate the photometric redshift bias of standard photo-z methods applied to the same source galaxy sample.We apply the method to two photo-z codes run in our simulated data: Bayesian Photometric Redshift and Directional Neighbourhood Fitting. We characterize the systematic uncertainties of our calibration procedure, and find that these systematic uncertainties dominate our error budget. The dominant systematics are due to our assumption of unevolving bias and clustering across each redshift bin, and to differences between the shapes of the redshift distributions derived by clustering versus photo-zs. The systematic uncertainty in the mean redshift bias of the source galaxy sample is Δz ≲ 0.02, though the precise value depends on the redshift bin under consideration. We discuss possible ways to mitigate the impact of our dominant systematics in future analyses.

Milo Gatti,1,2 Massimo Andreoni,3,4 Federico Pea,1,2 Pierluigi Viale1,5 1Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; 2SSD Clinical Pharmacology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy; 4Infectious Diseases Clinic, University Hospital “Tor Vergata”, Rome, Italy; 5Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyCorrespondence: Milo GattiDepartment of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Via Massarenti 9, Bologna, 40138, ItalyTel +39 051 214 3627Email milo.gatti2@unibo.itAbstract: Dalbavancin is a novel, long-acting lipoglycopeptide characterized by a long elimination half-life coupled with excellent in vitro activity against multidrug-resistant Gram-positives. Although it is currently approved only for the treatment of acute bacterial skin and skin structure infections, an ever-growing amount of evidence supports the efficacy of dalbavancin as a long-term therapy in osteomyelitis, prosthetic joint infections, endocarditis, and bloodstream infections. This article provides a critical reappraisal of real-world use of dalbavancin for off-label indications. A search strategy using specific keywords (dalbavancin, osteomyelitis, endocarditis, long-term suppressive therapy, bloodstream infection, pharmacokinetic/pharmacodynamic profile) until April 2021 was performed on the PubMed-MEDLINE database. As for other novel antibiotics, a conundrum between approved indications and potential innovative therapeutic uses has emerged for dalbavancin as well. The promising efficacy in challenging scenarios (i.e., osteomyelitis, endocarditis, prosthetic joint infections), coupled with the unique pharmacokinetic/pharmacodynamic properties, makes dalbavancin a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections. This makes dalbavancin valuable in the current COVID-19 scenario, in which hospitalization and territorial medicine empowerment are unavoidable.Keywords: dalbavancin, osteomyelitis, endocarditis, long-term suppressive therapy, PK/PD properties, COVID-19

Nicolina Conti,1 Milo Gatti,2,3 Emanuel Raschi,2 Igor Diemberger,1,4 Luciano Potena4 1Cardiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum - University of Bologna, Bologna, Italy; 2Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy; 3SSD Clinical Pharmacology, IRCSS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; 4Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyCorrespondence: Emanuel RaschiPharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, via Irnerio 48, Bologna, 40126, ItalyTel +39-051-2091802Email emanuel.raschi@unibo.itAbstract: Levosimendan is a distinctive inodilator combing calcium sensitization, phosphodiesterase inhibition and vasodilating properties through the opening of adenosine triphosphate-dependent potassium channels. It was first approved in Sweden in 2000 for the short-term treatment of acutely decompensated severe chronic heart failure when conventional therapy is not sufficient, and in cases where inotropic support is considered appropriate. After more than 20 years, clinical applications have considerably expanded across critical care and emergency medicine, and levosimendan is now under investigation in different cardiac settings (eg, septic shock, pulmonary hypertension) and for non-cardiac applications (eg, amyotrophic lateral sclerosis). This narrative review outlines key milestones in levosimendan history, by addressing regulatory issues, pharmacological peculiarities and clinical aspects (efficacy and safety) of a drug that did not receive great attention in the heart failure guidelines. A brief outlook to the ongoing clinical trials is also offered.Keywords: levosimendan, heart failure, cardiogenic shock, cardiac surgery, amyotrophic lateral sclerosis

Milo Gatti,1,2 Bruno Viaggi,3 Gian Maria Rossolini,4– 6 Federico Pea,1,2 Pierluigi Viale1,7 1Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy; 2SSD Clinical Pharmacology, IRCCS Azienda Ospedaliero Universitaria Sant’Orsola, Bologna, Italy; 3Neurointensive Care Unit, Department of Anesthesiology, Careggi, University Hospital, Florence, Italy; 4Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 5Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy; 6IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy; 7Infectious Diseases Unit, IRCCS Azienda Ospedaliero Universitaria Sant’Orsola, Bologna, ItalyCorrespondence: Federico PeaDepartment of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti, 9, Bologna, 40138, ItalyTel +39 051 214 3199Email federico.pea@unibo.itAbstract: Prompt implementation of appropriate targeted antibiotic therapy represents a valuable approach in improving clinical and ecological outcome in critically septic patients. This multidisciplinary opinion article focused at developing evidence-based algorithms for targeted antibiotic therapy of bloodstream (BSIs), complicated urinary tract (cUTIs), and complicated intrabdominal infections (cIAIs) caused by Enterobacterales. The aim was to provide a guidance for intensive care physicians either in appropriately placing novel antibiotics or in considering strategies for sparing the broadest-spectrum antibiotics. A multidisciplinary team of experts (one intensive care physician, one infectious disease consultant, one clinical microbiologist and one MD clinical pharmacologist), performed several rounds of assessment to reach agreement in developing six different algorithms according to the susceptibility pattern (one each for multi-susceptible, extended-spectrum beta-lactamase-producing, AmpC beta-lactamase-producing, Klebsiella pneumoniae carbapenemase (KPC)-producing, OXA-48-producing, and Metallo-beta-lactamase (MBL)-producing Enterobacterales). Whenever multiple therapeutic options were feasible, a hierarchical scale was established. Recommendations on antibiotic dosing optimization were also provided. In order to retrieve evidence-based support for the therapeutic choices proposed in the algorithms, a comprehensive literature search was performed by a researcher on PubMed-MEDLINE from inception until March 2021. Quality and strength of evidence was established according to a hierarchical scale of the study design. Only articles published in English were included. It is expected that these algorithms, by allowing prompt revision of antibiotic regimens whenever feasible, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens, may be helpful either in improving clinical outcome or in containing the spread of antimicrobial resistance.Keywords: critically ill patients, targeted antibiotic therapy, antimicrobial stewardship, Enterobacterales, multidisciplinary taskforce, PK/PD dosing optimization

We present an alternative calibration of the MagLim lens sample redshift distributions from the Dark Energy Survey (DES) first 3 yr of data (Y3). The new calibration is based on a combination of a self-organizing-map-based scheme and clustering redshifts to estimate redshift distributions and inherent uncertainties, which is expected to be more accurate than the original DES Y3 redshift calibration of the lens sample. We describe in detail the methodology, and validate it on simulations and discuss the main effects dominating our error budget. The new calibration is in fair agreement with the fiducial DES Y3 n(z) calibration, with only mild differences (<3σ) in the means and widths of the distributions. We study the impact of this new calibration on cosmological constraints, analysing DES Y3 galaxy clustering and galaxy–galaxy lensing measurements, assuming a Lambda cold dark matter cosmology. We obtain Ωm = 0.30 ± 0.04, σ8 = 0.81 ± 0.07, and S 8 = 0.81 ± 0.04, which implies a ∼0.4σ shift in the Ω − S 8 plane compared to the fiducial DES Y3 results, highlighting the importance of the redshift calibration of the lens sample in multiprobe cosmological analyses. [ABSTRACT FROM AUTHOR]