All planetary materials sampled thus far vary in their relative abundance of the major isotope of oxygen, 16 O, such that it has not been possible to define a primordial solar system composition. We ...measured the oxygen isotopic composition of solar wind captured and returned to Earth by NASA's Genesis mission. Our results demonstrate that the Sun is highly enriched in 16 O relative to the Earth, Moon, Mars, and bulk meteorites. Because the solar photosphere preserves the average isotopic composition of the solar system for elements heavier than lithium, we conclude that essentially all rocky materials in the inner solar system were enriched in 17 O and 18 O, relative to 16 O, by ∼7%, probably via non—mass-dependent chemistry before accretion of the first planetesimals.
Owing to the heritage of previous missions such as the Pioneer Venus Orbiter and Venus Express, the typical global plasma environment of Venus is relatively well understood. On the other hand, this ...is not true for more extreme driving conditions such as during passages of interplanetary coronal mass ejections (ICMEs). One of the outstanding questions is how do ICMEs, either the ejecta or sheath portions, impact (1) the Venusian magnetic topology and (2) escape rates of planetary ions? One of the main issues encountered when addressing these problems is the difficulty of inferring global dynamics from single spacecraft obits; this is where the benefits of simulations become apparent. In the present study, we present a detailed case study of an ICME interaction with Venus on 5 November 2011 in which the magnetic barrier reached over 250 nT. We use both Venus Express observations and hybrid simulation runs to study the impact on the field draping pattern and the escape rates of planetary O+ ions. The simulation showed that the magnetic field line draping pattern around Venus during the ICME is similar to that during typical solar wind conditions and that O+ ion escape rates are increased by approximately 30% due to the ICME. Moreover, the atypically large magnetic barrier appears to manifest from a number of factors such as the flux pileup, dayside compression, and the driving time from the ICME ejecta.
Key Points
Response of Venus magnetosphere to an ICME has been studied by data analysis and hybrid model simulations
Atypically large magnetic barrier (>250 nT) and magnetization of the ionosphere were observed
Simulation resulted in a relatively nominal magnetic field draping pattern and about 30% increase of O+ escape in the ICME run
Background. The standard treatment for septic arthritis in children is antimicrobials for several weeks (initially administered intravenously) and arthrotomy (at least for the hip and shoulder ...joints). No sufficiently powered study has examined the true need for these treatments. Methods. In a randomized, multicenter prospective trial in Finland, children aged 3 months to 15 years who had culture-positive septic arthritis were randomized to receive clindamycin or a first-generation cephalosporin for 10 days or 30 days (intravenously for the first 2–4 days). The number of surgical procedures was kept to a minimum. Illness was monitored with preset criteria. Antimicrobial therapy was discontinued when the clinical response was good and the C-reactive protein level decreased to ⩽20 mg/L. The primary end point was full recovery without need for further administration of antimicrobial therapy because of an osteoarticular indication during the 12 months after therapy. Results. Of the total 130 cases, 88% were caused by Staphylococcus aureus, Haemophilus influenzae, or Streptococcus pyogenes; 63 patients were in the short-term treatment group, and 67 were in the long-term treatment group. The median durations of antimicrobial treatment were 10 days and 30 days, respectively. Surgical procedures that were more extensive than percutaneous joint aspiration were performed for 12% of patients, with no preponderance to hip or shoulder arthritis. Two late-onset infections occurred in 1 child in the long-term treatment group; however, all patients recovered without sequelae. Conclusions. Large doses of well-absorbed antimicrobials for <2 weeks (initially administered intravenously) and only 1 joint aspiration are sufficient for treatment of most cases of childhood septic arthritis, regardless of the infecting pathogen or anatomical site, if the clinical response is good and the C-reactive protein level normalizes shortly after initiation of treatment.
No sufficiently powered trial has examined two antimicrobials in acute osteoarticular infections of childhood. We conducted a prospective, multicentre, quasi-randomized trial in Finland, comparing ...clindamycin with first-generation cephalosporins. The age of patients ranged between 3 months and 15 years, and all cases were culture-positive. We assigned antibiotic treatment intravenously for the first 2–4 days, and continued oral treatment with clindamycin 40 mg/kg/24 h or first-generation cephalosporin 150 mg/kg/24 h in four doses. Surgery was kept to a minimum. Subsiding symptoms and signs and normalization of C-reactive protein (CRP) level were preconditions for the discontinuation of antimicrobials. The main outcome was full recovery without further antimicrobials because of an osteoarticular indication during 12 months after therapy. The intention-to-treat analysis comprised 252 children, 169 of whom were analysed per-protocol: 82 cases of osteomyelitis, 80 of septic arthritis, and seven of osteomyelitis–arthritis. Staphylococcus aureus strains (all methicillin-sensitive) caused 84% of the cases. Except for one non-serious sequela during convalescence in both groups, and two late infections caused by dissimilar agents in one child, all patients recovered. The entire courses (medians) of clindamycin and cephalosporin lasted for 23 and 24 days, respectively. CRP normalized in both groups in 9 days. The patients were discharged, on average, on day 10. Loose stools were reported less often (1%) in the clindamycin group than in the cephalosporin group (7%), but two clindamycin recipients developed rash. Clindamycin or a first-generation cephalosporin, administered mostly orally, perform equally well in childhood osteoarticular infections, provided that high doses and administration four times daily are used. As most methicillin-resistant staphylococci remain clindamycin-sensitive, clindamycin remains an option instead of costly alternatives.
Activation of androgen receptor (AR) is crucial for prostate cancer growth. Remarkably, also castration-resistant prostate cancer (CRPC) is dependent on functional AR, and several mechanisms have ...been proposed to explain the addiction. Known causes of CRPC include gene amplification and overexpression as well as point mutations of AR. We report here the pharmacological profile of ODM-201, a novel AR inhibitor that showed significant antitumor activity and a favorable safety profile in phase 1/2 studies in men with CRPC. ODM-201 is a full and high-affinity AR antagonist that, similar to second-generation antiandrogens enzalutamide and ARN-509, inhibits testosterone-induced nuclear translocation of AR. Importantly, ODM-201 also blocks the activity of the tested mutant ARs arising in response to antiandrogen therapies, including the F876L mutation that confers resistance to enzalutamide and ARN-509. In addition, ODM-201 reduces the growth of AR-overexpressing VCaP prostate cancer cells both in vitro and in a castration-resistant VCaP xenograft model. In contrast to other antiandrogens, ODM-201 shows negligible brain penetrance and does not increase serum testosterone levels in mice. In conclusion, ODM-201 is a potent AR inhibitor that overcomes resistance to AR-targeted therapies by antagonizing both overexpressed and mutated ARs. ODM-201 is currently in a phase 3 trial in CRPC.
PDF
