The 67P/Churyumov-Gerasimenko observation campaign in support of the Rosetta mission.

We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit. Comparison between this large collection of telescopic observations and the in situ results from Rosetta will allow us to better understand comet coma chemistry and structure. This work is just beginning as the mission ends-in this paper, we present a summary of the ground-based observations and early results, and point to many questions that will be addressed in future studies.This article is part of the themed issue 'Cometary science after Rosetta'.

Surface changes on comet 67P/Churyumov-Gerasimenko suggest a more active past.

The Rosetta spacecraft spent ~2 years orbiting comet 67P/Churyumov-Gerasimenko, most of it at distances that allowed surface characterization and monitoring at submeter scales. From December 2014 to June 2016, numerous localized changes were observed, which we attribute to cometary-specific weathering, erosion, and transient events driven by exposure to sunlight and other processes. While the localized changes suggest compositional or physical heterogeneity, their scale has not resulted in substantial alterations to the comet's landscape. This suggests that most of the major landforms were created early in the comet's current orbital configuration. They may even date from earlier if the comet had a larger volatile inventory, particularly of CO or CO2 ices, or contained amorphous ice, which could have triggered activity at greater distances from the Sun.

Rosetta's comet 67P/Churyumov-Gerasimenko sheds its dusty mantle to reveal its icy nature.

The Rosetta spacecraft has investigated comet 67P/Churyumov-Gerasimenko from large heliocentric distances to its perihelion passage and beyond. We trace the seasonal and diurnal evolution of the colors of the 67P nucleus, finding changes driven by sublimation and recondensation of water ice. The whole nucleus became relatively bluer near perihelion, as increasing activity removed the surface dust, implying that water ice is widespread underneath the surface. We identified large (1500 square meters) ice-rich patches appearing and then vanishing in about 10 days, indicating small-scale heterogeneities on the nucleus. Thin frosts sublimating in a few minutes are observed close to receding shadows, and rapid variations in color are seen on extended areas close to the terminator. These cyclic processes are widespread and lead to continuously, slightly varying surface properties.

Images of asteroid 21 Lutetia: a remnant planetesimal from the early Solar System.

Images obtained by the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras onboard the Rosetta spacecraft reveal that asteroid 21 Lutetia has a complex geology and one of the highest asteroid densities measured so far, 3.4 ± 0.3 grams per cubic centimeter. The north pole region is covered by a thick layer of regolith, which is seen to flow in major landslides associated with albedo variation. Its geologically complex surface, ancient surface age, and high density suggest that Lutetia is most likely a primordial planetesimal. This contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.

E-type asteroid (2867) Steins as imaged by OSIRIS on board Rosetta.

The European Space Agency's Rosetta mission encountered the main-belt asteroid (2867) Steins while on its way to rendezvous with comet 67P/Churyumov-Gerasimenko. Images taken with the OSIRIS (optical, spectroscopic, and infrared remote( )imaging system) cameras on board Rosetta show that Steins is an oblate body with an effective spherical diameter of 5.3 kilometers. Its surface does not show color variations. The morphology of Steins is dominated by linear faults and a large 2.1-kilometer-diameter crater near its south pole. Crater counts reveal a distinct lack of small craters. Steins is not solid rock but a rubble pile and has a conical appearance that is probably the result of reshaping due to Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) spin-up. The OSIRIS images constitute direct evidence for the YORP effect on a main-belt asteroid.

Drug concentration effect relationship of estradiol from two matrix transdermal delivery systems: Menorest and Climara.

OBJECTIVES: To relate the pharmacokinetics of estradiol to pharmacological effects. METHODS: Drug concentration effect relationship of estradiol from two matrix transdermal delivery systems, Menorest and Climara, was studied in a single centre, open, randomised, comparative crossover study. The trial consisted of two treatment periods, 14 days for each patch separated by a 4-week washout period. Blood hormone levels were followed during the second week of each treatment. Estradiol levels during treatments were related to three concentration levels previously proposed as efficacy or safety limits. The effect of treatment on FSH-levels was examined and the relationship between the levels of estradiol and FSH was described using an inhibitory sigmoidal I(max) model. Estrone levels and estradiol/estrone before and during treatment were followed. RESULTS: The C(average) of FSH during treatment was 38% lower than baseline plasma levels. Estradiol had an inhibitory effect on FSH with an I(max) of 0.68 and an IC(50) of 19 pg/ml. The fraction of time above the minimum concentration for therapeutic effect and the tolerability limit did not differ between the two treatments, whereas the fraction of time above the suggested threshold for osteoporosis prophylaxis was significantly larger for Menorest than for Climara (P<0.05). The low baseline estradiol/estrone ratios increased towards pre-menopausal levels during treatment. CONCLUSIONS: The drug concentration effect relationship of estradiol may be of use in evaluation of the effects of prophylactic estrogen therapy and to facilitate comparisons between different forms of estrogen treatments.

Bioavailability of estradiol from two matrix transdermal delivery systems: Menorest and Climara.

OBJECTIVES: To compare two estradiol transdermal matrix systems with regard to bioavailability, pharmacokinetics and tolerability. METHODS: A single centre, open, randomized, comparative cross-over study in 20 healthy postmenopausal women. Menorest with 3 or 4 days of suggested use and Climara with 7 days of suggested use (both 50 microg/24 h) were compared at steady state. Two 14-day treatment periods were separated by a 4 week washout. Plasma levels of estradiol were monitored during the second week of each treatment. Tolerability was assessed by open questions and inspection of the application site. RESULTS: There were no differences between the two treatments with regards to AUC, Cmax, Cmin, Caverage or fluctuations of plasma estradiol. Tmax was significantly shorter for Menorest than Climara. Cmax and Cmin were significantly higher for the second Menorest patch during the monitoring period compared to the first. All local reactions were mild and there were three cases of erythema with Menorest and a total of 21 skin reactions in 15 subjects with Climara. Systemic tolerability was similar between treatments with eight estrogen-related adverse events in eight subjects (period pains, uterine bleeding, mastodynia, headache and vaginal discharge) with Menorest and 13 events in ten subjects with Climara. CONCLUSIONS: The bioavailability of estradiol from the two matrix transdermal delivery systems Menorest and Climara was similar, but the products were not bioequivalent because Tmax was significantly shorter for Menorest than for Climara. Tolerability of treatment was good for both patches but with a higher number of local reactions and estrogen related adverse events for Climara.

Quantitation of protein A in human plasma is possible after heat inactivation of the samples.

Quantitative determination of staphylococcal protein A in plasma is often hampered by the interaction between protein A and immunoglobulins. In human plasma, these interactions may not only involve the non-immune binding to the Fc or Fab regions of Ig but also antigen/antibody interaction by specific antibodies directed against protein A. In this paper we describe a method which can be used to quantitate nanogram amounts of protein A in the presence of human plasma. The ELISA used for the quantification of protein A is based on a double antibody solid-phase assay utilizing chicken anti-protein A as both capture and detector antibody. Protein A may be measured down to 5 ng/ml in plasma and 0.5 ng/ml in buffer. The plasma samples were heat-inactivated before analysis and this eliminated interference in the assay caused by interaction of protein A with an excess of immunoglobulins. This assay provides a reliable and convenient method for the detection and quantitation of soluble protein A in human plasma.

Model of pulmonary extravasation as an effect of neutropenia in endotoxic shock in guinea pigs.

A guinea pig model was developed to document the association of polymorphonuclear neutrophils (PMN) decrease with pulmonary leakage after a sublethal infusion of endotoxin (LPS Escherichia coli 0111:B4, 5 micrograms/min/kg). A control group was prepared in the same manner and given an infusion of vehicle alone. Severe leukopenia developed, mostly expressed in the neutrophil population. There was a decrease in RBC catalase and fibronectin. Plasma leakage in the lung followed the endotoxin infusion, which could indicate endothelial cell damage. The results from the present study suggest an activation of PMN in endotoxin-infused animals, degranulation and release of toxic oxygen species, resulting in pulmonary plasma extravasation.

Nitroglycol and nitroglycerine exposure in a dynamite industry 1958-1978.

An excess mortality from chronic cardio-cerebrovascular diseases among dynamite workers has recently been reported from two Swedish explosives industries. This study summarizes the exposure situation with regard to nitroglycol and nitroglycerine during the last two decades in one of these factories. The manufacturing process is described as well as the sampling and analytic procedures. The mean 8-hour TWA concentrations of nitrate esters for different job types during three seven-year periods 1958-1978 have been calculated from a large number of simi-annually measured short-time samples. The concentrations are estimated to have been in the range of 0.2 - 1.1 mg/m3, with the highest levels for cartridge fillers and mix house workers. The representativeness of short-time samples was found to be comparatively good in relation to 8-1/2 hour personal air sampling. The presented exposure calculations could be used for international comparison and dose-response discussions in future epidemiological studies on chronic effects of nitrate esters.