Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab

Background: Pertuzumab, a human epidermal growth factor receptor (HER) 2 dimerization inhibitor, has demonstrated promising efficacy in combination with trastuzumab in patients with metastatic breast cancer. As HER signaling pathways are not only involved in oncogenesis, but also in myocardial homeostasis, an analysis of cardiac safety data was undertaken in a large group of patients treated with pertuzumab. Patients and methods: A complete database of patients treated with full-dose pertuzumab was used to describe the incidence of asymptomatic left ventricular systolic dysfunction (LVSD) and symptomatic heart failure (HF). Results: Information for 598 unique patients was available for the current analysis. Of the patients treated with pertuzumab alone (n = 331) or pertuzumab in combination with a non-anthracycline-containing cytotoxic (n = 175) or trastuzumab (n = 93), 23 (6.9%), 6 (3.4%), and 6 (6.5%), respectively, developed asymptomatic LVSD and 1 (0.3%), 2 (1.1%), and 1 (1.1%), respectively, displayed symptomatic HF. None of the 15 patients receiving both pertuzumab and erlotinib demonstrated LVSD. Conclusions: Patients treated with pertuzumab experienced relatively low levels of asymptomatic LVSD or symptomatic HF. There was no notable increase in cardiac side-effects when pertuzumab was given in combination with other anticancer agent

Bright galaxies at Hubble's redshift detection frontier: Preliminary results and design from the redshift z~9-10 BoRG pure-parallel HST survey

We present the first results and design from the redshift z~9-10 Brightest of the Reionizing Galaxies {\it Hubble Space Telescope} survey BoRG[z9-10], aimed at searching for intrinsically luminous unlensed galaxies during the first 700 Myr after the Big Bang. BoRG[z9-10] is the continuation of a multi-year pure-parallel near-IR and optical imaging campaign with the Wide Field Camera 3. The ongoing survey uses five filters, optimized for detecting the most distant objects and offering continuous wavelength coverage from {\lambda}=0.35{\mu}m to {\lambda}=1.7{\mu}m. We analyze the initial ~130 arcmin$^2$ of area over 28 independent lines of sight (~25% of the total planned) to search for z>7 galaxies using a combination of Lyman break and photometric redshift selections. From an effective comoving volume of (5-25) $times 10^5$ Mpc$^3$ for magnitudes brighter than $m_{AB}=26.5-24.0$ in the $H_{160}$-band respectively, we find five galaxy candidates at z~8.3-10 detected at high confidence (S/N>8), including a source at z~8.4 with mAB=24.5 (S/N~22), which, if confirmed, would be the brightest galaxy identified at such early times (z>8). In addition, BoRG[z9-10] data yield four galaxies with $7.3 \lesssim z \lesssim 8$. These new Lyman break galaxies with m$\lesssim26.5$ are ideal targets for follow-up observations from ground and space based observatories to help investigate the complex interplay between dark matter growth, galaxy assembly, and reionization.Comment: Accepted for publication on ApJ. 21 pages, 11 figures, 4 table

Photometric Constraints on the Redshift of z~10 candidate UDFj-39546284 from deeper WFC3/IR+ACS+IRAC observations over the HUDF

Ultra-deep WFC3/IR observations on the HUDF from the HUDF09 program revealed just one plausible z~10 candidate UDFj-39546284. UDFj-39546284 had all the properties expected of a galaxy at z~10 showing (1) no detection in the deep ACS+WFC3 imaging data blueward of the F160W band, exhibiting (2) a blue spectral slope redward of the break, and showing (3) no prominent detection in deep IRAC observations. The new, similarly deep WFC3/IR HUDF12 F160W observations over the HUDF09/XDF allow us to further assess this candidate. These observations show that this candidate, previously only detected at ~5.9 sigma in a single band, clearly corresponds to a real source. It is detected at ~5.3 sigma in the new H-band data and at ~7.8 sigma in the full 85-orbit H-band stack. Interestingly, the non-detection of the source (<1 sigma) in the new F140W observations suggests a higher redshift. Formally, the best-fit redshift of the source utilizing all the WFC3+ACS (and IRAC+K-band) observations is 11.8+/-0.3. However, we consider the z~12 interpretation somewhat unlikely, since the source would either need to be ~20x more luminous than expected or show very high-EW Ly-alpha emission (which seems improbable given the extensive neutral gas prevalent early in the reionization epoch). Lower-redshift solutions fail if only continuum models are allowed. Plausible lower-redshift solutions require that the H-band flux be dominated by line emission such as Halpha or [OIII] with extreme EWs. The tentative detection of line emission at 1.6 microns in UDFj-39546284 in a companion paper suggests that such emission may have already been found.Comment: 6 pages, 4 figures, 1 table, accepted for publication in ApJ Letters, updated to match the version in pres

Neural responses to facial and vocal expressions of fear and disgust

Neuropsychological studies report more impaired responses to facial expressions of fear than disgust in people with amygdala lesions, and vice versa in people with Huntington's disease. Experiments using functional magnetic resonance imaging (fMRI) have confirmed the role of the amygdala in the response to fearful faces and have implicated the anterior insula in the response to facial expressions of disgust. We used fMRI to extend these studies to the perception of fear and disgust from both facial and vocal expressions. Consistent with neuropsychological findings, both types of fearful stimuli activated the amygdala. Facial expressions of disgust activated the anterior insula and the caudate-putamen; vocal expressions of disgust did not significantly activate either of these regions. All four types of stimuli activated the superior temporal gyrus. Our findings therefore (i) support the differential localization of the neural substrates of fear and disgust; (ii) confirm the involvement of the amygdala in the emotion of fear, whether evoked by facial or vocal expressions; (iii) confirm the involvement of the anterior insula and the striatum in reactions to facial expressions of disgust; and (iv) suggest a possible general role for the perception of emotional expressions for the superior temporal gyrus

The KMOS^3D Survey: design, first results, and the evolution of galaxy kinematics from 0.7<z<2.7

We present the KMOS^3D survey, a new integral field survey of over 600 galaxies at 0.7<z<2.7 using KMOS at the Very Large Telescope (VLT). The KMOS^3D survey utilizes synergies with multi-wavelength ground and space-based surveys to trace the evolution of spatially-resolved kinematics and star formation from a homogeneous sample over 5 Gyrs of cosmic history. Targets, drawn from a mass-selected parent sample from the 3D-HST survey, cover the star formation-stellar mass ($M_*$) and rest-frame $(U-V)-M_*$ planes uniformly. We describe the selection of targets, the observations, and the data reduction. In the first year of data we detect Halpha emission in 191 $M_*=3\times10^{9}-7\times10^{11}$ Msun galaxies at z=0.7-1.1 and z=1.9-2.7. In the current sample 83% of the resolved galaxies are rotation-dominated, determined from a continuous velocity gradient and $v_{rot}/\sigma>1$, implying that the star-forming 'main sequence' (MS) is primarily composed of rotating galaxies at both redshift regimes. When considering additional stricter criteria, the Halpha kinematic maps indicate at least ~70% of the resolved galaxies are disk-like systems. Our high-quality KMOS data confirm the elevated velocity dispersions reported in previous IFS studies at z>0.7. For rotation-dominated disks, the average intrinsic velocity dispersion decreases by a factor of two from 50 km/s at z~2.3 to 25 km/s at z~0.9 while the rotational velocities at the two redshifts are comparable. Combined with existing results spanning z~0-3, disk velocity dispersions follow an approximate (1+z) evolution that is consistent with the dependence of velocity dispersion on gas fractions predicted by marginally-stable disk theory.Comment: 20 pages, 11 figures, 1 Appendix; Accepted to ApJ November 2

Not In Our Backyard: Spectroscopic Support for the CLASH z=11 Candidate MACS0647-JD

We report on our first set of spectroscopic Hubble Space Telescope observations of the z~11 candidate galaxy strongly lensed by the MACSJ0647.7+7015 galaxy cluster. The three lensed images are faint and we show that these early slitless grism observations are of sufficient depth to investigate whether this high-redshift candidate, identified by its strong photometric break at ~1.5 micron, could possibly be an emission line galaxy at a much lower redshift. While such an interloper would imply the existence of a rather peculiar object, we show here that such strong emission lines would clearly have been detected. Comparing realistic, two-dimensional simulations to these new observations we would expect the necessary emission lines to be detected at >5 sigma while we see no evidence for such lines in the dispersed data of any of the three lensed images. We therefore exclude that this object could be a low redshift emission line interloper, which significantly increases the likelihood of this candidate being a bona fide z~11 galaxy.Comment: 14 Pages. 6 Figures. 2nd revised version. Accepted. To appear in ApJ. Please contact [email protected] for comments on this pape