Errata for Stochastic calculus for symmetric Markov processes

This erratum corrects the article arXiv:0806.2044 published in Ann. Probab. 36 (2008) 931--970Comment: Published in at http://dx.doi.org/10.1214/11-AOP684 the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org

6′,7′‐Dihydroxybergamottin in grapefruit juice and Seville orange juice: Effects on cyclosporine disposition, enterocyte CYP3A4, and P‐glycoprotein

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109869/1/cptclpt1999363.pd

Physical properties of near-Earth asteroid (2102) Tantalus from multiwavelength observations

Between 2010 and 2017 we have collected new optical and radar observations of the potentially hazardous asteroid (2102) Tantalus from the ESO NTT and Danish telescopes at the La Silla Observatory and from the Arecibo planetary radar. The object appears to be nearly spherical, showing a low amplitude light-curve variation and limited large-scale features in the radar images. The spin-state is difficult to constrain with the available data; including a certain light-curve subset significantly changes the spin-state estimates, and the uncertainties on period determination are significant. Constraining any change in rotation rate was not possible, despite decades of observations. The convex lightcurve-inversion model, with rotational pole at λ = 210 ± 41○ and β = −30 ± 35○, is more flattened than the two models reconstructed by including radar observations: with prograde (λ = 36 ± 23○, β = 30 ± 15○), and with retrograde rotation mode (λ = 180 ± 24○, β = −30 ± 16○). Using data from WISE we were able to determine that the prograde model produces the best agreement in size determination between radar and thermophysical modelling. Radar measurements indicate possible variation in surface properties, suggesting one side might have lower radar albedo and be rougher at centimetre-to-decimetre scale than the other. However, further observations are needed to confirm this. Thermophysical analysis indicates a surface covered in fine-grained regolith, consistent with radar albedo and polarisation ratio measurements. Finally, geophysical investigation of the spin-stability of Tantalus shows that it could be exceeding its critical spin-rate via cohesive forces

Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents: Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins

Grapefruit juice increases the oral availability of a variety of CYP3A4 substrates. It has been shown that recurrent grapefruit juice ingestion results in a loss of CYP3A4 from the small bowel epithelium. We now show that the reduction in intestinal CYP3A4 concentration is rapid; a 47% decrease occurred in a healthy volunteer within 4 hr after consuming grapefruit juice. To identify the specific components of the juice responsible for this effect, we used a recently developed Caco-2 cell culture model of human intestinal epithelium that expresses catalytically active CYP3A4. We found that grapefruit oil and two furanocoumarin constituents (6*,7*-dihydroxybergamottin and a closely related dimer) caused a dose-dependent fall in CYP3A4 catalytic activity and immunoreactive CYP3A4 concentration. The effect was selective in that concentrations of CYP1A1 and CYP2D6 did not fall, consistent with previous results obtained in vivo. Assays of various juices confirmed that 6*,7*-dihydroxybergamottin is the major furanocoumarin present and, although its concentration varies significantly among types and brands of grapefruit juice, it is consistently present in concentrations exceeding the IC50 (1 mM) for loss of midazolam 1*-hydroxylase activity determined in the Caco-2 cells. Studies with recombinant CYP3A4 revealed that 6*,7*-dihydroxybergamottin is a mechanism-based inactivator, which supports the idea that loss of CYP3A4 results from accelerated degradation of the enzyme. We conclude that the effect of grapefruit juice on oral availability of CYP3A4 substrates can be largely accounted for by the presence of 6*,7*-dihydroxybergamottin although other furanocoumarins probably also contribute

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

The ESA Hera Mission : Detailed Characterization of the DART Impact Outcome and of the Binary Asteroid (65803) Didymos

Funding Information: To achieve these objectives, Milani is carrying two scientific payloads, the ASPECT visual and near-infrared (Vis-NIR) imaging spectrometer and the VISTA thermogravimeter aimed at collecting and characterizing volatiles and dust particles below 10 μm. Additionally, navigation payloads include a visible navigation camera and lidar. The Milani consortium is composed of entities and institutions from Italy, the Czech Republic, and Finland. The consortium Prime is Tyvak International, responsible for the whole program management and platform design, development, integration, testing, and final delivery to the customer. Politecnico di Torino is tasked with defining requirements and performing thermal, radiation, and debris analysis. Politecnico di Milano is responsible for mission analysis and GNC. Altec will support the Ground Segment architecture and interface definition. Centro Italiano per la Ricerca Aerospaziale (CIRA) is responsible for the execution of the vehicle environmental campaign. HULD contributes to developing the mission-specific software. VTT is the main payload (ASPECT hyperspectral imager) provider and is supported by the following entities dealing with ASPECT-related development: University of Helsinki (ASPECT calibration); Reaktor Space Lab (ASPECT Data Processing Unit development), Institute of Geology of the Czech Academy of Sciences (ASPECT scientific algorithms requirements and testing); and Brno University of Technology (ASPECT scientific algorithms development). INAF-IAPS is the secondary Payload (VISTA, dust detector) provider. Funding Information: The Mission PI is appointed by ESA and is the primary interface to ESA. The Hera SMB consists of the ESA Hera Project Scientist (ESA PS), the Mission PI, and the Hera Advisory Board, consisting of four mission advisors. The Mission PI chairs the HIT and is supported by the Hera Advisory Board. The tasks of the Hera SMB are 1. advising the Hera mission project team on all aspects related to the Hera mission objectives; 2. ensuring that the WGs’ activities cover the needs of the Hera mission; 3. providing recommendations to ESA concerning the membership in the HIT; and 4. implementing the Publication Policy. Funding Information: Hera is the ESA contribution to the AIDA collaboration. Hera, Juventas, Milani, and their instruments are developed under ESA contract supported by national agencies. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 870377 (project NEO-MAPP), the CNRS through the MITI interdisciplinary programs, ASI, CNES, JAXA, the Academy of Finland project no. 335595, and was conducted with institutional support RVO 67985831 of the Institute of Geology of the Czech Academy of Sciences. M.L., E.P., P.T .and E.D. are grateful to the Italian Space Agency (ASI) for financial support through Agreement No. 2022-8-HH.0 in the context of ESA’s Hera mission. We are grateful to the whole Hera team, including Working Group core members and other contributors for their continuous efforts and support. Their names can be found on the following website: https:// www.heramission.space/team. Publisher Copyright: © 2022. The Author(s). Published by the American Astronomical Society.Hera is a planetary defense mission under development in the Space Safety and Security Program of the European Space Agency for launch in 2024 October. It will rendezvous in late 2026 December with the binary asteroid (65803) Didymos and in particular its moon, Dimorphos, which will be impacted by NASA’s DART spacecraft on 2022 September 26 as the first asteroid deflection test. The main goals of Hera are the detailed characterization of the physical properties of Didymos and Dimorphos and of the crater made by the DART mission, as well as measurement of the momentum transfer efficiency resulting from DART’s impact. The data from the Hera spacecraft and its two CubeSats will also provide significant insights into asteroid science and the evolutionary history of our solar system. Hera will perform the first rendezvous with a binary asteroid and provide new measurements, such as radar sounding of an asteroid interior, which will allow models in planetary science to be tested. Hera will thus provide a crucial element in the global effort to avert future asteroid impacts at the same time as providing world-leading science.Peer reviewe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial)

BACKGROUND: Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. METHODS/DESIGN: Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). DISCUSSION: The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor