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The high rate of planet detection among solar-type stars argues that planet formation is common. It is also generally assumed that planets form in protoplanetary discs like those observed in nearby star-forming regions. On what time-scale does the transformation from discs to planets occur? Here, we show that current inventories of planets and protoplanetary discs are sensitive enough to place basic constraints on the time-scale and efficiency of the planet formation process. A comparison of planet detection statistics and the measured solid reservoirs in T Tauri discs suggests that planet formation is likely already underway at the few Myr age of the discs in Taurus–Auriga, with a large fraction of solids having been converted into large objects with low millimetre opacity and/or sequestered at small disc radii where they are difficult to detect at millimetre wavelengths. [ABSTRACT FROM AUTHOR]

Background A multicenter NCI-sponsored phase II study was conducted to analyze the safety and efficacy of the combination of ixabepilone with trastuzumab in patients with metastatic HER2-positive breast cancer. Patients and methods Two cohorts were enrolled: cohort 1 had received no prior chemotherapy or trastuzumab for metastatic disease and cohort 2 had received 1–2 prior trastuzumab-containing regimens for metastatic disease. Patients in both cohorts received ixabepilone 40 mg/m2 as a 3-h infusion and trastuzumab on day 1 of a 21-day cycle. Tumor biomarkers that may predict response to trastuzumab were explored. Results Thirty-nine women entered the study with 15 patients in cohort 1 and 24 patients in cohort 2. Across both cohorts, the overall RR was 44%, with a clinical benefit rate (CR + PR + SD for at least 24 weeks) of 56%. Treatment-related toxic effects included neuropathy (grade ≥2, 56%), leukopenia (grade ≥2, 26%), myalgias (grade ≥2, 21%), neutropenia (grade ≥2, 23%), and anemia (grade ≥2, 18%). Conclusions This represents the first study of the combination of ixabepilone with trastuzumab for the treatment of metastatic HER2-positive breast cancer. These results suggest that the combination has encouraging activity as first and subsequent line therapy for metastatic breast cancer. [ABSTRACT FROM PUBLISHER]

Background Research studies involving human tissue are increasingly common. However, patients' attitudes toward research biopsies are not well characterized, particularly when the biopsies are carried out outside the context of therapeutic trials. Patients and methods One hundred sixty patients with metastatic breast cancer (MBC) from two academic (n = 80) and two community (n = 80) hospitals completed a 29-item self-administered survey to evaluate their willingness to consider providing research purposes only biopsies (RPOBs) (as a stand-alone procedure) and additional biopsies (ABs) (additional needle passes at the time of a clinically indicated biopsy). Results Eighty-two (51%) of 160 patients would consider having RPOBs, of which 42 (53%) and 40 (50%) patients were from academic and community hospitals, respectively. Patients who had more prior biopsies were less likely to consider RPOBs (RR = 0.6, 95% CI: 0.4–1.0, P = 0.03). Of 160 patients, 115 (72%) patients would consider having ABs. Of these, 64 (80%) and 51 (64%) patients from academic and community hospitals, respectively, would consider ABs (RR = 1.2, 95% CI: 1.0–1.5, P = 0.03). Conclusions Many patients with MBC in both academic and community settings report willingness to consider undergoing biopsies for research. Further research is needed to understand ethical, logistical and provider-based barriers to broader participation in such studies. [ABSTRACT FROM PUBLISHER]

We compare line emission calculated from theoretical disk models with optical to submillimeter wavelength observational data of the gas disk surrounding TW Hya and infer the spatial distribution of mass in the gas disk. The model disk that best matches observations has a gas mass ranging from ~10-4 to 10-5 M ☉ for 0.06 AU < r < 3.5 AU and ~0.06 M ☉ for 3.5 AU < r < 200 AU. We find that the inner dust hole (r < 3.5 AU) in the disk must be depleted of gas by ~1-2 orders of magnitude compared with the extrapolated surface density distribution of the outer disk. Grain growth alone is therefore not a viable explanation for the dust hole. CO vibrational emission arises within r ~ 0.5 AU from thermal excitation of gas. [O I] 6300 Å and 5577 Å forbidden lines and OH mid-infrared emission are mainly due to prompt emission following UV photodissociation of OH and water at r lsim 0.1 AU and at r ~ 4 AU. [Ne II] emission is consistent with an origin in X-ray heated neutral gas at r lsim 10 AU, and may not require the presence of a significant extreme-ultraviolet (hν > 13.6 eV) flux from TW Hya. H2 pure rotational line emission comes primarily from r ~ 1 to 30 AU. [O I] 63 μm, HCO+, and CO pure rotational lines all arise from the outer disk at r ~ 30-120 AU. We discuss planet formation and photoevaporation as causes for the decrease in surface density of gas and dust inside 4 AU. If a planet is present, our results suggest a planet mass ~4-7 MJ situated at ~3 AU. Using our photoevaporation models and the best surface density profile match to observations, we estimate a current photoevaporative mass loss rate of 4 × 10-9 M ☉ yr-1 and a remaining disk lifetime of ~5 million years. [ABSTRACT FROM AUTHOR]

Background: In the era of molecularly targeted therapy, developing an understanding of the molecular basis of cancer is a principal or secondary goal of many research studies. For this reason, studies collecting tissue for research purposes are increasingly common. Understanding patients' attitudes towards research biopsies may lead to improvement in accrual to research biopsy studies. Methods: Patients with metastatic breast cancer from two academic and two community hospitals completed a self-administered paper survey consisting of 29 questions in clinic to evaluate their willingness to consider providing additional biopsies (additional biopsy performed with a clinically indicated biopsy) and research purposes only biopsies (RPOB) (research biopsy performed as a stand alone procedure). Results: 160 patients (n = 80 academic, n=80 community) completed the survey, with a response rate of 98%. As expected, demographic variables differed between sites, with patients from academic sites likely to be younger (p = 0.01), more educated (p = 0.002), employed (p = 0.01), have prior trial participation (P <0.001) and have a longer travel time (P <0.0001). 64 (80%) academic patients and 51 (64%) community patients would definitely or probably consider additional biopsies. 42 (53%) academic patients and 40 (50%) community patients would consider RPOB. In univariate analyses of patients' willingness to have additional biopsies, patients in academic sites were more likely to agree to additional biopsies than those at community sites (RR = 1.2, 95% CI 1.0-1.5, p = 0.03). Statistically significant differences based on demographic characteristics such as age, education, marital status, prior trial participation, number of prior biopsies, and travel time were not observed. For RPOB, patients having had more prior biopsies were less likely to consider research biopsies (RR = 0.6, 95% CI 0.4-1.0, p = 0.03). The following variables did not reach statistical significance: type of practice, age, education, marital status, prior trial participation, and travel time. Patients' willingness in both academic and community sites to consider RPOB declined with more invasive biopsies. Although differences were observed, none were statistically significant between academic and community; skin (56%, 65%), bone marrow (30%, 27%), breast (43%, 49%) or liver (24%, 19%). Of the 13/160 (8%) patients who would not consider additional biopsies, the most common reasons cited included pain or discomfort (n = 8/13, 62%), risk of biopsy (n = 8/13, 62%) and anxiety related to the biopsy (n = 6/13, 46%). Of the 37/160 (23%) patients who would not consider RPOB, the most common reasons cited included pain or discomfort (n = 23/37, 62%), risk of biopsy (n = 15/37, 41%) and inconvenience of the procedure to the patient (n = 13/37, 35%). Conclusions: The majority of patients in this study indicated they would consider research biopsies, with a larger proportion willing to consider additional biopsies; patients seen at academic hospitals were more likely to consider additional biopsies compared to those seen at community hospitals. Breast cancer patients' willingness to undergo research biopsies may be higher than generally expected by clinicians and may not be the primary barrier to obtaining research biopsies. [ABSTRACT FROM AUTHOR]

We present far-infrared (50-200 μm) spectroscopic observations of young pre-main-sequence stars taken with Herschel/PACS as part of the DIGIT key project. The sample includes 16 Herbig AeBe and 4 T Tauri sources observed in SED mode covering the entire spectral range. An additional 6 Herbig AeBe and 4 T Tauri systems have been observed in SED mode with a limited spectral coverage. Multiple atomic fine structure and molecular lines are detected at the source position: [O I], [C II], CO, OH, H2O, CH+. The most common feature is the [O I] 63 μm line detected in almost all of the sources, followed by OH. In contrast with CO, OH is detected toward both Herbig AeBe groups (flared and non-flared sources). An isothermal LTE slab model fit to the OH lines indicates column densities of 1013 < NOH < 1016 cm-2, emitting radii 15 < r < 100AU and excitation temperatures 100 < Tex < 400 K. We used the non-LTE code RADEX to verify the LTE assumption. High gas densities (n ⩾ 1010 cm-3) are needed to reproduce the observations. The OH emission thus comes from a warm layer in the disk at intermediate stellar distances. Warm H2O emission is detected through multiple lines toward the T Tauri systems AS 205, DG Tau, S CrA and RNO 90 and three Herbig AeBe systems HD 104237, HD 142527, HD 163296 (through line stacking). Overall, Herbig AeBe sources have higher OH/H2O abundance ratios across the disk than do T Tauri disks, from near- to far-infrared wavelengths. Far-infrared CH+ emission is detected toward HD 100546 and HD 97048. The slab model suggests moderate excitation (Tex ~ 100K) and compact (r ~ 60AU) emission in the case of HD 100546. Off-source [O I] emission is detected toward DG Tau, whose origin is likely the outflow associated with this source. The [CII] emission is spatially extended in all sources where the line is detected. This suggests that not all [CII] emission is associated with the disk and that there is a substantial contribution from diffuse material around the young stars. The flux ratios of the atomic fine structure lines ([O I] 63 μm, [O I] 145 μm, [CII]) are analyzed with PDR models and require high gas density (n ⩾ 105 cm-3) and high UV fluxes (Go ~ 103-107), consistent with a disk origin for the oxygen lines for most of the sources. [ABSTRACT FROM AUTHOR]

Background: Women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) can respond to multiple lines of anti-HER2 therapy. It is unknown whether these patients will derive further clinical benefit following treatment with trastuzumab-MCC-DM1 (T-DM1).Patients and methods: We retrospectively identified HER2-positive MBC patients treated with T-DM1 and characterized outcomes during subsequent lines of anti-HER2 therapy. Response was determined by a blinded radiology review. Time-dependent analyses were carried out using Kaplan–Meier estimates.Results: We identified 23 patients treated with single-agent T-DM1 and report on the 20 patients who discontinued protocol therapy. All patients received trastuzumab-based metastatic therapy before initiation of T-DM1 [median 7 regimens (range 3–14)]. Of these 20 patients, 75% (15 of 20) received further therapy with or without anti-HER2 agents after discontinuing T-DM1. Partial response to either first- or second-subsequent line(s) of therapy was seen in 5 of 15 (33%) treated patients, including 33% (4 of 12) who received a regimen containing trastuzumab and/or lapatinib. Median durations of therapy to first- and second-subsequent regimens after T-DM1 were 5.5 and 6.4 months, respectively.Conclusions: In heavily pretreated HER2-positive MBC patients, prior exposure to T-DM1 does not exhaust the potential benefit of ongoing anti-HER2 therapy with trastuzumab- and/or lapatinib-based regimens. [ABSTRACT FROM AUTHOR]

Class 0 protostars, the youngest type of young stellar objects, show many signs of rapid development from their initial, spheroidal configurations, and therefore are studied intensively for details of the formation of protoplanetary disks within protostellar envelopes. At millimetre wavelengths, kinematic signatures of collapse have been observed in several such protostars, through observations of molecular lines that probe their outer envelopes. It has been suggested that one or more components of the proto-multiple system NGC 1333–IRAS 4 (refs 1, 2) may display signs of an embedded region that is warmer and denser than the bulk of the envelope. Here we report observations that reveal details of the core on Solar System dimensions. We detect in NGC 1333–IRAS 4B a rich emission spectrum of H2O, at wavelengths 20–37 μm, which indicates an origin in extremely dense, warm gas. We can model the emission as infall from a protostellar envelope onto the surface of a deeply embedded, dense disk, and therefore see the development of a protoplanetary disk. This is the only example of mid-infrared water emission from a sample of 30 class 0 objects, perhaps arising from a favourable orientation; alternatively, this may be an early and short-lived stage in the evolution of a protoplanetary disk. [ABSTRACT FROM AUTHOR]

In this paper we investigate the origin of the mid-infrared (IR) hydrogen recombination lines for a sample of 114 disks in different evolutionary stages (full, transitional, and debris disks) collected from the Spitzer archive. We focus on the two brighter H I lines observed in the Spitzer spectra, the H I (7-6) at 12.37 μm and the H I (9-7) at 11.32 μm. We detect the H I (7-6) line in 46 objects, and the H I (9-7) in 11. We compare these lines with the other most common gas line detected in Spitzer spectra, the [Ne II] at 12.81 μm. We argue that it is unlikely that the H I emission originates from the photoevaporating upper surface layers of the disk, as has been found for the [Ne II] lines toward low-accreting stars. Using the H I (9-7)/H I (7-6) line ratios we find these gas lines are likely probing gas with hydrogen column densities of 1010-1011 cm–3. The subsample of objects surrounded by full and transitional disks show a positive correlation between the accretion luminosity and the H I line luminosity. These two results suggest that the observed mid-IR H I lines trace gas accreting onto the star in the same way as other hydrogen recombination lines at shorter wavelengths. A pure chromospheric origin of these lines can be excluded for the vast majority of full and transitional disks. We report for the first time the detection of the H I (7-6) line in eight young (<20 Myr) debris disks. A pure chromospheric origin cannot be ruled out in these objects. If the H I (7-6) line traces accretion in these older systems, as in the case of full and transitional disks, the strength of the emission implies accretion rates lower than 10–10M☼ yr–1. We discuss some advantages of extending accretion indicators to longer wavelengths, and the next steps required pinning down the origin of mid-IR hydrogen lines. [ABSTRACT FROM AUTHOR]

HD 142527 is a young pre-main-sequence star with properties indicative of the presence of a giant planet and/or a low-mass stellar companion. We have analyzed an X-Shooter/Very Large Telescope spectrum to provide accurate stellar parameters and accretion rate. The analysis of the spectrum, together with constraints provided by the spectral energy distribution fitting, the distance to the star (140 ± 20 pc), and the use of evolutionary tracks and isochrones, led to the following set of parameters: Teff = 6550 ± 100 K, log g = 3.75 ± 0.10, L*/L☼ = 16.3 ± 4.5, M*/M☼ = 2.0 ± 0.3, and an age of 5.0 ± 1.5 Myr. This stellar age provides further constraints to the mass of the possible companion estimated by Biller et al., being between 0.20 and 0.35 M☼. Stellar accretion rates obtained from UV Balmer excess modeling and optical photospheric line veiling, and from the correlations with several emission lines spanning from the UV to the near-IR, are consistent with each other. The mean value from all previous tracers is 2 (±1) × 10–7M☼ yr–1, which is within the upper limit gas flow rate from the outer to the inner disk recently provided by Cassasus et al.. This suggests that almost all gas transferred between both components of the disk is not trapped by the possible planet(s) in between but fall onto the central star, although it is discussed how the gap flow rate could be larger than previously suggested. In addition, we provide evidence showing that the stellar accretion rate of HD 142527 has increased by a factor ∼7 on a timescale of 2 to 5 yr. [ABSTRACT FROM AUTHOR]