Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials

Background: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk.
Methods: We undertook a meta-analysis of individual patient data for 10?801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease.
Findings: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7–17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6–6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2–17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8–5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (=20%), intermediate (10–19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8% (95% CI 3·1–12·5), 1·1% (–2·0 to 4·2), and 0·1% (–7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5–27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8–15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease.
Interpretation: After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made.
Funding: Cancer Research UK, British Heart Foundation, and UK Medical Research Council.

The Kepler-10 Planetary System Revisited by HARPS-N: A Hot Rocky World and a Solid Neptune-Mass Planet

Kepler-10b was the first rocky planet detected by the Kepler satellite and confirmed with radial velocity follow-up observations from Keck-HIRES. The mass of the planet was measured with a precision of around 30%, which was
insufficient to constrain models of its internal structure and composition in detail. In addition to Kepler-10b, a second planet transiting the same star with a period of 45 days was statistically validated, but the radial velocities were only
good enough to set an upper limit of 20 M⊕ for the mass of Kepler-10c. To improve the precision on the mass for planet b, the HARPS-N Collaboration decided to observe Kepler-10 intensively with the HARPS-N spectrograph
on the Telescopio Nazionale Galileo on La Palma. In total, 148 high-quality radial-velocity measurements were obtained over two observing seasons. These new data allow us to improve the precision of the mass determination for Kepler-10b to 15%. With a mass of 3.33 ± 0.49 M⊕ and an updated radius of 1.47+0.03 −0.02 R⊕, Kepler-10b has a density of 5.8 ± 0.8 g cm−3, very close to the value predicted by models with the same internal structure and composition as the Earth. We were also able to determine a mass for the 45-day period planet Kepler-10c, with an even better precision of 11%. With a mass of 17.2 ± 1.9 M⊕ and radius of 2.35+0.09 −0.04 R⊕, Kepler-10c has a density of 7.1 ± 1.0 g cm−3. Kepler-10c appears to be the first strong evidence of a class of more massive solid planets with longer orbital periods

Absolute Magnitudes of Pan-STARRS 1 Asteroids

It is well known that the absolute magnitudes (H) in the MPCORB and ASTORB orbital element catalogs suffer from a systematic offset. Juric at al. (2002) found 0.4 mag offset in the SDSS data and detailed light curve studies of WISE asteroids by Pravec et al. (2012) revealed size-dependent offsets of up to 0.5 mag. The offsets are thought to be caused by systematic errors introduced by earlier surveys using different photometric catalogs and filters. The next generation asteroid surveys provide an order of magnitude more asteroids and well-defined and calibrated magnitudes. The Pan-STARRS 1 telescope (PS1) has observed hundreds of thousands asteroids, submitted more than 2 million detections to the Minor Planet Center (MPC) and discovered almost 300 NEOs since the beginning of operations in late 2010. We transformed the observed apparent magnitudes of PS1-detected asteroids from the gP1,rP1,iP1,yP1,zP1 and wP1-bands into Johnson photometric system by assuming the mean S and C-type asteroid color (Fitzsimmons 2011 - personal communication, Schlafly et al. 2012, Magnier et al. 2012 - in preparation) and calculated the absolute magnitude (H) in the V-band and its uncertainty (Bowell et al., 1989) for more than 200,000 known asteroids having on average 6.7 detections per object. The H error with respect to the MPCORB catalog revealed a mean offset of -0.49+0.30 mag in good agreement with published values. We will also discuss the statistical and systematical errors in H and slope parameter G.

1.° Richardi, Anglici, tractatus de anatomia. — 2.° Ejusdem summa de diebus criticis. — 3.° Ejusdem practica. — 4.° Rogerii, Cancellarii Studii Montispessulani, summa, sive, Rogerina major, minor et media. — 5.° Summa secundùm Trotulam. — 6.° Cleopatrae ad Deodatam liber de morbis mulierum. — 7.° Gilberti, Cancellarii Studii Montispessulani, experimenta. — 8.° Anonymus de mulierum aegritudinibus. — 9.° Anonymi antidotarium. — 10.° Anonymus de ponderibus et mensuris. — 11.° Synonyma medica. — 12.° Galeni antibalomena. — 13.° Nicolai antidotarium.

DD. de Bethune

Developmental and individual differences in novelty and error detection in 10-year-old children and young adults /

Event-related potentials were recorded from 10-year-old children and young adults in order to examine the developmental dififerences in two frontal lobe functions: detection of novel stimuli during an auditory novelty oddball task, and error detection during a visual flanker task. All participants showed a parietally-maximal P3 in response to auditory stimuli. In children, novel stimuli generated higher P3 amplitudes at the frontal site compared with target stimuli, whereas target stimuli generated higher P3 amplitudes at the parietal site compared with novel stimuli. Adults, however, had higher P3 amplitude to novel tones compared with target tones at each site. Children also had greater P3 amplitude at more parietal sites than adults during the novelty oddball and flanker tasks. Furthermore, children and adults did not show a significant reduction in P3 amplitude from the first to second novel stimulus presentation. No age differences were found with respect to P3 latency to novel and target stimuli. These findings suggest that the detection of novel and target stimuli is mature in 10-year-olds. Error trials typically elicit a negative ERP deflection (the ERN) with a frontal-central scalp distribution that may reflect response monitoring. There is also evidence of a positive ERP peak (the Pe) with a posterior scalp distribution which may reflect subjective recognition of a response. Both children and adults showed an ERN and Pe maximal at frontal-central sites. Children committed more errors, had smaller ERN across sites, and had a larger Pe at the parietal site than adults. This suggests that response monitoring is still immature in 10-year-olds whereas recognition of and emotional responses to errors may be similar in children and adults.

Incorporation of cis-9, trans-11 or trans-10, cis-12 conjugated linoleic acid into human erythrocytes in vivo

The purpose of this study was to determine the incorporation into erythrocytes of cis (c)-9,trans (t)-11 conjugated linoleic acid (CLA) and t10,c12 CLA consumed as supplements highly enriched in these isomers. Healthy men (31 8 years) consumed 1, 2, and 4 capsules containing approximately 80 g/100 g of either c9,t11 CLA or t10,c12 CLA for sequential 8-week periods. Fatty acid concentrations in erythrocyte total lipids were determined at baseline and after consumption of the highest dose. The increase in c9,t11 CLA concentration (0.31 g/100 g) was significantly greater than that in t10,c12 CLA (0.19 g/100 g). This was associated with minor changes in concentrations of some fatty acids of chain length greater than 20 carbons. These data suggest selective assimilation of individual CLA isomers into erythrocyte lipids and partial substitution for specific saturated and polyunsaturated fatty acids. (C) 2005 Elsevier Inc. All rights reserved.

Gravitational Capture of Asteroids by Gas Drag

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Collisions with the Earth: the Moon's contribution

In the present work is analyzed the contribution of the Moon on the collisional process of the Earth with asteroids (NEOs). The dynamical system adopted is the restricted four-body problem Sun-Earth-Moon-particle. Using a simple analytical approach one can verify that, the orbit of an object can be significantly affected by the Moon's gravitational field when their relative velocity is smaller than 5 km/s. Therefore, the present work is based on hypothetical asteroids whose velocities relative to Moon are of the order of 1 km/s. In fact, there are several real objects (NEOs) with such velocities at the point they cross the Earth's orbit. The net results obtained indicate that the Moon helps to avoid collisions (2.6%) more than it contributes to extra collisions (0.6%). (C) 2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

Effects of the planetary migration on some primordial satellites of the outer planets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Isoflurane and propofol contribute to increasing the antioxidant status of patients during minor elective surgery: a randomized clinical study

Isoflurane is a volatile halogenated anesthetic used especially for anesthesia maintenance whereas propofol is a venous anesthetic utilized for anesthesia induction and maintenance, and reportedly an antioxidant. However, there are still controversies related to isoflurane-induced oxidative stress and it remains unanswered whether the antioxidant effects occur in patients under propofol anesthesia.Taking into account the importance of better understanding the role of anesthetics on oxidative stress in anesthetized patients, the present study was designed to evaluate general anesthesia maintained with isoflurane or propofol on antioxidant status in patients who underwent minimally invasive surgeries.We conducted a prospective randomized trial in 30 adult patients without comorbidities who underwent elective minor surgery (septoplasty) lasting at least 2 h admitted to a Brazilian tertiary hospital.The patients were randomly allocated into 2 groups, according to anesthesia maintenance (isoflurane, n = 15 or propofol, n = 15). Peripheral blood samples were drawn before anesthesia (baseline) and 2-h after anesthesia induction.The primary outcomes were to investigate the effect of either isoflurane or propofol anesthesia on aqueous plasma oxidizability and total antioxidant performance (TAP) by fluorometry as well as several individual antioxidants by high-performance liquid chromatography. As secondary outcome, oxidized genetic damage (7,8-dihydro-8-oxoguanine, known as 8-oxo-Gua) was investigated by the comet assay.Both anesthesia techniques (isoflurane or propofol) for a 2-h period resulted in a significant decrease of plasma α-tocopherol, but not other antioxidants including uric acid, carotenoids, and retinol (P > 0.05). Propofol, in contrast to isoflurane anesthesia, significantly increased (P < 0.001) anti-inflammatory/antioxidant plasma γ-tocopherol concentration in patients. Both anesthesia types significantly enhanced hydrophilic antioxidant capacity and TAP, with no significant difference between them, and 8-oxo-Gua remained unchanged during anesthesia in both groups. In addition, both anesthetics showed antioxidant capacity in vitro.This study shows that anesthesia maintained with either propofol or isoflurane increase both hydrophilic and total antioxidant capacity in plasma, but only propofol anesthesia increases plasma γ-tocopherol concentration. Additionally, both types of anesthetics do not lead to oxidative DNA damage in patients without comorbidities undergoing minimally invasive surgery.

Effects of high-energy astrophysical events on habitable planets

With the possible exception of meteor impacts, high-energy astrophysical events such as supernovae, gamma-ray bursts (GRB) and flares are usually not taken into account for biological and evolutionary studies due to their low rates of occurrence. We show that a class of these events may occur at distances and time scales in which their biological effects are non-negligible, maybe more frequent than the impacts of large asteroids. We review the effects of four transient astrophysical sources of ionizing radiation on biospheres - stellar flares, giant flares from soft gamma repeaters (SGR), supernovae and GRB. The main damaging features of them are briefly discussed and illustrated. We point out some open problems and ongoing work. Received 28 February 2012, accepted 6 July 2012, first published online 10 August 2012

The Gemini NICI planet-finding campaign: the frequency of giant planets around young B and A stars

We have carried out high contrast imaging of 70 young, nearby B and A stars to search for brown dwarf and planetary companions as part of the Gemini NICI Planet-Finding Campaign. Our survey represents the largest, deepest survey for planets around high-mass stars (≈1.5-2.5 M ☉) conducted to date and includes the planet hosts β Pic and Fomalhaut. We obtained follow-up astrometry of all candidate companions within 400 AU projected separation for stars in uncrowded fields and identified new low-mass companions to HD 1160 and HIP 79797. We have found that the previously known young brown dwarf companion to HIP 79797 is itself a tight (3 AU) binary, composed of brown dwarfs with masses 58$^{+21}_{-20}$ M Jup and 55$^{+20}_{-19}$ M Jup, making this system one of the rare substellar binaries in orbit around a star. Considering the contrast limits of our NICI data and the fact that we did not detect any planets, we use high-fidelity Monte Carlo simulations to show that fewer than 20% of 2 M ☉ stars can have giant planets greater than 4 M Jup between 59 and 460 AU at 95% confidence, and fewer than 10% of these stars can have a planet more massive than 10 M Jup between 38 and 650 AU. Overall, we find that large-separation giant planets are not common around B and A stars: fewer than 10% of B and A stars can have an analog to the HR 8799 b (7 M Jup, 68 AU) planet at 95% confidence. We also describe a new Bayesian technique for determining the ages of field B and A stars from photometry and theoretical isochrones. Our method produces more plausible ages for high-mass stars than previous age-dating techniques, which tend to underestimate stellar ages and their uncertainties.

Is a black eye a useful sign of facial fractures in patients with minor head injuries? A retrospective analysis in a level I trauma centre over 10 years

Orbital blunt trauma is common, and the diagnosis of a fracture should be made by computed tomographic (CT) scan. However, this will expose patients to ionising radiation. Our objective was to identify clinical predictors of orbital fracture, in particular the presence of a black eye, to minimise unnecessary exposure to radiation. A 10-year retrospective study was made of the medical records of all patients with minor head trauma who presented with one or two black eyes to our emergency department between May 2000 and April 2010. Each of the patients had a CT scan, was over 16 years old, and had a Glasgow Coma Score (GCS) of 13-15. The primary outcome was whether the black eye was a valuable predictor of a fracture. Accompanying clinical signs were considered as a secondary outcome. A total of 1676 patients (mean (SD) age 51 (22) years) and minor head trauma with either one or two black eyes were included. In 1144 the CT scan showed a fracture of the maxillofacial skeleton, which gave an incidence of 68.3% in whom a black eye was the obvious symptom. Specificity for facial fractures was particularly high for other clinical signs, such as diminished skin sensation (specificity 96.4%), diplopia or occulomotility disorders (89.3%), fracture steps (99.8%), epistaxis (95.5%), subconjunctival haemorrhage (90.4%), and emphysema (99.6%). Sensitivity for the same signs ranged from 10.8% to 22.2%. The most striking fact was that 68.3% of all patients with a black eye had an underlying fracture. We therefore conclude that a CT scan should be recommended for every patient with minor head injury who presents with a black eye.