Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

Radial Velocities of Six OB Stars

We present new results from a radial velocity study of six bright OB stars with little or no prior measurements. One of these, HD 45314, may be a long-period binary, but the velocity variations of this Be star may be related to changes in its circumstellar disk. Significant velocity variations were also found for HD 60848 (possibly related to nonradial pulsations) and HD 61827 (related to wind variations). The other three targets, HD 46150, HD 54879, and HD 206183, are constant velocity objects, but we note that HD 54879 has H$\alpha$ emission that may originate from a binary companion. We illustrate the average red spectrum of each target.Comment: Accepted for publication in PASP July 2007 issu

Thirty Meter Telescope Site Testing I: Overview

As part of the conceptual and preliminary design processes of the Thirty Meter Telescope (TMT), the TMT site testing team has spent the last five years measuring the atmospheric properties of five candidate mountains in North and South America with an unprecedented array of instrumentation. The site testing period was preceded by several years of analyses selecting the five candidates, Cerros Tolar, Armazones and Tolonchar in northern Chile; San Pedro Martir in Baja California, Mexico and the 13 North (13N) site on Mauna Kea, Hawaii. Site testing was concluded by the selection of two remaining sites for further consideration, Armazones and Mauna Kea 13N. It showed that all five candidates are excellent sites for an extremely large astronomical observatory and that none of the sites stands out as the obvious and only logical choice based on its combined properties. This is the first article in a series discussing the TMT site testing project.Comment: Accepted for publication in PASP, April 2009 issu

Mass and Angular Momentum Transfer in the Massive Algol Binary RY Persei

We present an investigation of H-alpha emission line variations observed in the massive Algol binary, RY Per. We give new radial velocity data for the secondary based upon our optical spectra and for the primary based upon high dispersion UV spectra. We present revised orbital elements and an estimate of the primary's projected rotational velocity (which indicates that the primary is rotating 7 times faster than synchronous). We use a Doppler tomography algorithm to reconstruct the individual primary and secondary spectra in the region of H-alpha, and we subtract the latter from each of our observations to obtain profiles of the primary and its disk alone. Our H-alpha observations of RY Per show that the mass gaining primary is surrounded by a persistent but time variable accretion disk. The profile that is observed outside-of-eclipse has weak, double-peaked emission flanking a deep central absorption, and we find that these properties can be reproduced by a disk model that includes the absorption of photospheric light by the band of the disk seen in projection against the face of the star. We developed a new method to reconstruct the disk surface density distribution from the ensemble of H-alpha profiles observed around the orbit, and this method accounts for the effects of disk occultation by the stellar components, the obscuration of the primary by the disk, and flux contributions from optically thick disk elements. The resulting surface density distribution is elongated along the axis joining the stars, in the same way as seen in hydrodynamical simulations of gas flows that strike the mass gainer near trailing edge of the star. This type of gas stream configuration is optimal for the transfer of angular momentum, and we show that rapid rotation is found in other Algols that have passed through a similar stage.Comment: 39 pages, 12 figures, ApJ in press, 2004 June 20 issu

New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs:a randomized controlled trial (EDITION 3)

AIMS: To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of glargine 100 U/ml (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs. METHODS: The EDITION 3 study was a multicentre, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6 months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4–5.6 mmol/l (80–100 mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month 6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia from week 9 to month 6. Other measures of glycaemia and hypoglycaemia, weight change and insulin dose were assessed. RESULTS: Randomized participants (n = 878) had a mean (standard deviation) age of 57.7 (10.1) years, diabetes duration 9.8 (6.4) years, body mass index 33.0 (6.7) kg/m(2) and HbA1c 8.54 (1.06) % [69.8 (11.6) mmol/mol]. HbA1c levels decreased by equivalent amounts with the two treatments; the least squares mean difference in change from baseline was 0.04 [95% confidence interval (CI) −0.09 to 0.17] % or 0.4 (−1.0 to 1.9) mmol/mol. Numerically fewer participants reported ≥1 nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia from week 9 to month 6 [relative risk (RR) 0.89 (95% CI 0.66 to 1.20)] with Gla-300 versus Gla-100; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [RR 0.76 (95% CI 0.59 to 0.99)]. No between-treatment differences in adverse events were identified. CONCLUSIONS: Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower hypoglycaemia risk

Characterizing the Cool KOIs. VI. H- and K-band Spectra of Kepler M Dwarf Planet-Candidate Hosts

We present H- and K-band spectra for late-type Kepler Objects of Interest (the "Cool KOIs"): low-mass stars with transiting-planet candidates discovered by NASA's Kepler Mission that are listed on the NASA Exoplanet Archive. We acquired spectra of 103 Cool KOIs and used the indices and calibrations of Rojas-Ayala et al. to determine their spectral types, stellar effective temperatures and metallicities, significantly augmenting previously published values. We interpolate our measured effective temperatures and metallicities onto evolutionary isochrones to determine stellar masses, radii, luminosities and distances, assuming the stars have settled onto the main-sequence. As a choice of isochrones, we use a new suite of Dartmouth predictions that reliably include mid-to-late M dwarf stars. We identify five M4V stars: KOI-961 (confirmed as Kepler 42), KOI-2704, KOI-2842, KOI-4290, and the secondary component to visual binary KOI-1725, which we call KOI-1725 B. We also identify a peculiar star, KOI-3497, which has a Na and Ca lines consistent with a dwarf star but CO lines consistent with a giant. Visible-wavelength adaptive optics imaging reveals two objects within a 1 arc second diameter; however, the objects' colors are peculiar. The spectra and properties presented in this paper serve as a resource for prioritizing follow-up observations and planet validation efforts for the Cool KOIs, and are all available for download online using the "data behind the figure" feature.Comment: Accepted for publication in the Astrophysical Journal Supplement Series (ApJS). Data and table are available in the sourc

Wind Accretion and State Transitions in Cygnus X-1

We present the results of a spectroscopic monitoring program (from 1998 to 2002) of the H-alpha emission strength in HDE 226868, the optical counterpart of the black hole binary, Cyg X-1. The H-alpha profiles consist of (1) a P Cygni component associated with the wind of the supergiant, (2) emission components that attain high velocity at the conjunctions and that probably form in enhanced outflows both towards and away from the black hole, and (3) an emission component that moves in anti-phase with the supergiant's motion. We argue that the third component forms in accreted gas near the black hole, and the radial velocity curve of the emission is consistent with a mass ratio of M_X / M_opt = 0.36 +/- 0.05. We find that there is a general anti-correlation between the H-alpha emission strength and X-ray flux in the sense that when the H-alpha emission is strong (W_\lambda < -0.5 Angstroms) the X-ray flux is weaker and the spectrum harder. On the other hand, there is no correlation between H-alpha emission strength and X-ray flux when H-alpha is weak. During the low/hard X-ray state, the strong wind is fast and the accretion rate is relatively low, while in the high/soft state the weaker, highly ionized wind attains only a moderate velocity and the accretion rate increases. We argue that the X-ray transitions from the normal low/hard to the rare high/soft state are triggered by episodes of decreased mass loss rate in the supergiant donor star.Comment: 45 pages, 16 figures, ApJ, in pres

Standing with our American Indian and Alaska Native Women, Girls, and Two-Spirit People: Exploring the Impact of and Resources for Survivors of Human Trafficking

Despite the violence against Indigenous women, girls, and two-spirit people occurring at epidemic levels there is little national visibility and data pertaining to the lived experiences of American Indian/Alaska Native (AI/AN) individuals and communities. The purpose of this manuscript is to specifically focus on violence regarding the missing and murdered Indigenous women, girls, and two-spirit people with a concentration on human trafficking. AI/AN leaders have identified human trafficking as a major contributor to the disappearance of AI/AN women, girls, and two-spirit people (Department of Justice, 2018). In a trauma-informed intersectional approach we review available data discussing the negative impacts on the brain, the role of complex trauma, and behavioral outcomes while highlighting cultural strengths and resilience. We conclude with culturally relevant and research-informed recommendations to continue to help raise awareness and action to end human trafficking