ALMA high-frequency long-baseline campaign in 2017: an investigation of phase-referencing cycle times and effective baseline lengths using band-to-band and in-band phase calibration techniques

Interstellar matter and star formatio

Phase correction for ALMA. Investigating water vapour radiometer scaling: The long-baseline science verification data case study

Instrumentatio

ALMA high-frequency long baseline campaign in 2021: highest angular resolution submillimeter wave images for the carbon-rich Star R Lep

Instrumentatio

ALMA high-frequency long baseline campaign in 2017: Band-to-band phase referencing in submillimeter waves

Instrumentatio

Evaluating the Clinical Impact and Feasibility of Therapeutic Drug Monitoring of Pazopanib in a Real-World Soft-Tissue Sarcoma Cohort

Introduction and Objective:Pazopanib is registered for metastatic renal cell carcinoma and soft-tissue sarcoma (STS). Its variable pharmacokinetic (PK) characteristics and narrow therapeutic range provide a strong rationale for therapeutic drug monitoring (TDM). Prior studies have defined target levels of drug exposure (≥ 20.5 mg/L) linked to prolonged progression-free survival (PFS), but the added value of using TDM remains unclear. This study investigates the effect of TDM of pazopanib in patients with STS on survival outcomes and dose-limiting toxicities (DLTs) and evaluates the feasibility of TDM-guided dosing. Methods: A TDM-guided cohort was compared to a non-TDM-guided cohort for PFS, overall survival (OS) and DLTs. PK samples were available from all patients, though not acted upon in the non-TDM-guided cohort. We evaluated the feasibility of TDM by comparing the proportion of underdosed patients in our TDM cohort with data from previous publications.Results: A total of 122 STS patients were included in the TDM-guided cohort (n = 95) and non-TDM-guided cohort (n = 27). The average exposure in the overall population was 30.5 mg/L and was similar in both groups. Median PFS and OS did not differ between the TDM-guided cohort and non-TDM-guided cohort (respectively 5.5 vs 4.4 months, p = 0.3, and 12.6 vs 10.1 months, p = 0.8). Slightly more patients in the non-TDM-guided cohort experienced DLTs (54%) compared to the TDM-guided cohort (44%). The proportion of underdosed patients (13.3%) was halved compared to historical data (26.7%). Conclusion: TDM reduced the proportion of patients with subtherapeutic exposure levels by ~ 50%. Nonetheless, the added value of TDM for achieving target trough levels of ≥ 20.5 mg/L for pazopanib on survival outcomes could not be confirmed in STS patients.</p

Kinematics and stability of high-mass protostellar disk candidates at sub-arcsecond resolution

Context. The fragmentation mode of high-mass molecular clumps and the accretion processes that form the most massive stars (M & 8 M) are still not well understood. A growing number of case studies have found massive young stellar objects (MYSOs) to harbour disk-like structures, painting a picture that the formation of high-mass stars may proceed through disk accretion, similar to that of lower mass stars. However, the properties of such structures have yet to be uniformly and systematically characterised. Massive disks are prone to fragmentation via gravitational instabilities due to high gas densities and accretion rates. Therefore, it is important to study the stability of such disks in order to put into context the role of disk fragmentation in setting the final stellar mass distribution in high-mass star forming regions. Aims. The aim of this work is to uniformly study the kinematic properties of a large sample of MYSOs and characterise the stability of possible circumstellar disks against gravitational fragmentation. Methods. We have undertaken a large observational program (CORE) making use of interferometric observations from the Northern Extended Millimetre Array (NOEMA) for a sample of 20 luminous (L > 104 L) protostellar objects in the 1.37 mm wavelength regime in both continuum and spectral line emission, reaching 0.400 resolution (800 au at 2 kpc). Results. We present the gas kinematics of the full sample and detect dense gas emission surrounding 15 regions within the CORE sample. Using the dense gas tracer CH3CN, we find velocity gradients across 13 cores perpendicular to the directions of bipolar molecular outflows, making them excellent disk candidates. The extent of the CH3CN emission tracing the disk candidates varies from 1800 − 8500 au. Analysing the free-fall to rotational timescales, we find that the sources are rotationally supported. The rotation profiles of some disk candidates are well described by differential rotation while for others the profiles are poorly resolved. Fitting the velocity profiles with a Keplerian model, we find protostellar masses in the range of ∼ 10 − 25 M. Modelling the level population of CH3CN (12K − 11K) K = 0 − 6 lines we present temperature maps and find median temperature in the range 70–210 K with a diversity in distributions. Radial profiles of the specific angular momentum (j) for the best disk candidates span a range of 1–2 orders of magnitude, on average ∼ 10−3 km s−1 pc, and follow j ∝ r 1.7, consistent with a poorly resolved rotating and infalling envelope/disk model. Studying the Toomre stability of the disk candidates, we find almost all (11 out of 13) disk candidates to be prone to fragmentation due to gravitational instabilities at the scales probed by our observations, as a result of their high disk to stellar mass ratio. In particular, disks with masses greater than ∼ 10 − 20% of the mass of their host (proto)stars are Toomre unstable, and more luminous YSOs tend to have disks that are more massive compared to their host star and hence more prone to fragmentation. Conclusions. In this work, we show that most disk structures around high-mass YSOs are prone to disk fragmentation early in their formation due to their high disk to stellar mass ratio. This impacts the accretion evolution of high-mass protostars which will have significant implications for the formation of the most massive stars

Evaluating the Clinical Impact and Feasibility of Therapeutic Drug Monitoring of Pazopanib in a Real-World Soft-Tissue Sarcoma Cohort

Introduction and Objective: Pazopanib is registered for metastatic renal cell carcinoma and soft-tissue sarcoma (STS). Its variable pharmacokinetic (PK) characteristics and narrow therapeutic range provide a strong rationale for therapeutic drug monitoring (TDM). Prior studies have defined target levels of drug exposure (≥ 20.5 mg/L) linked to prolonged progression-free survival (PFS), but the added value of using TDM remains unclear. This study investigates the effect of TDM of pazopanib in patients with STS on survival outcomes and dose-limiting toxicities (DLTs) and evaluates the feasibility of TDM-guided dosing. Methods: A TDM-guided cohort was compared to a non-TDM-guided cohort for PFS, overall survival (OS) and DLTs. PK samples were available from all patients, though not acted upon in the non-TDM-guided cohort. We evaluated the feasibility of TDM by comparing the proportion of underdosed patients in our TDM cohort with data from previous publications. Results: A total of 122 STS patients were included in the TDM-guided cohort (n = 95) and non-TDM-guided cohort (n = 27). The average exposure in the overall population was 30.5 mg/L and was similar in both groups. Median PFS and OS did not differ between the TDM-guided cohort and non-TDM-guided cohort (respectively 5.5 vs 4.4 months, p = 0.3, and 12.6 vs 10.1 months, p = 0.8). Slightly more patients in the non-TDM-guided cohort experienced DLTs (54%) compared to the TDM-guided cohort (44%). The proportion of underdosed patients (13.3%) was halved compared to historical data (26.7%). Conclusion: TDM reduced the proportion of patients with subtherapeutic exposure levels by ~ 50%. Nonetheless, the added value of TDM for achieving target trough levels of ≥ 20.5 mg/L for pazopanib on survival outcomes could not be confirmed in STS patients

Chemical and physical characterization of the isolated protostellar source CB68: FAUST IV

Interstellar matter and star formatio

Zur genetischen Fundierung des Sommerekzems beim Islandpferd

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