Although advanced cutaneous squamous cell carcinoma (CSCC) is quite common, there are few prospective trials regarding its optimal management. This study evaluated the efficacy and safety of ...single-agent panitumumab in the treatment of patients with CSCC not suitable for local therapy.
Sixteen patients received single-agent panitumumab at a dose of 6 mg/kg repeated every 2 weeks for a minimum of three cycles and continued until progression, a maximum of nine cycles or dose-limiting toxicity. The primary end point was the best overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) criteria. Secondary end points included evaluation of safety, toxicity and progression-free survival (PFS).
Between May 2010 and May 2012, 16 patients were recruited. Fourteen patients were male and the median age was 68 years. Fifteen patients had locoregionally advanced or recurrent disease with 14 patients receiving previous radiotherapy and 7 receiving previous cytotoxic chemotherapy. The best ORR partial (PR) or complete response (CR) was 31% (3/16 PR, 2/16 CR) with a further 6 of 16 patients achieving SD. The median PFS and overall survival were 8 and 11 months respectively. Grade 3 or 4 events were observed in five patients (four being skin toxicity) with one patient ceasing due to skin toxicity. With a median follow-up of 24 months, 10 patients died due to progressive disease, 6 are alive, one patient with no evidence of disease at the time of analysis.
Single-agent panitumumab is safe and effective in the management of patients with advanced CSCC even in a previously extensively pre-treated cohort.
Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for ...severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.
The intrinsic heterogeneity of many nanoformulations is currently challenging to characterize on both the single particle and population level. Therefore, there is great opportunity to develop ...advanced techniques to describe and understand nanomedicine heterogeneity, which will aid translation to the clinic by informing manufacturing quality control, characterization for regulatory bodies, and connecting nanoformulation properties to clinical outcomes to enable rational design. Here, we present an analytical technique to provide such information, while measuring the nanocarrier and cargo simultaneously with label-free, nondestructive single particle automated Raman trapping analysis (SPARTA). We first synthesized a library of model compounds covering a range of hydrophilicities and providing distinct Raman signals. These compounds were then loaded into model nanovesicles (polymersomes) that can load both hydrophobic and hydrophilic cargo into the membrane or core regions, respectively. Using our analytical framework, we characterized the heterogeneity of the population by correlating the signal per particle from the membrane and cargo. We found that core and membrane loading can be distinguished, and we detected subpopulations of highly loaded particles in certain cases. We then confirmed the suitability of our technique in liposomes, another nanovesicle class, including the commercial formulation Doxil. Our label-free analytical technique precisely determines cargo location alongside loading and release heterogeneity in nanomedicines, which could be instrumental for future quality control, regulatory body protocols, and development of structure–function relationships to bring more nanomedicines to the clinic.
Abstract
HESS J0632+057 belongs to a rare subclass of binary systems that emit gamma rays above 100 GeV. It stands out for its distinctive high-energy light curve, which features a sharp “primary” ...peak and broader “secondary” peak. We present the results of contemporaneous observations by NuSTAR and VERITAS during the secondary peak between 2019 December and 2020 February, when the orbital phase (
ϕ
) is between 0.55 and 0.75. NuSTAR detected X-ray spectral evolution, while VERITAS detected TeV emission. We fit a leptonic wind-collision model to the multiwavelength spectra data obtained over the four NuSTAR and VERITAS observations, constraining the pulsar spin-down luminosity and the magnetization parameter at the shock. Despite long-term monitoring of the source from 2019 October to 2020 March, the MDM observatory did not detect significant variation in H
α
and H
β
line equivalent widths, an expected signature of Be-disk interaction with the pulsar. Furthermore, fitting folded Swift-XRT light-curve data with an intrabinary shock model constrained the orbital parameters, suggesting two orbital phases (at
ϕ
D
= 0.13 and 0.37), where the pulsar crosses the Be-disk, as well as phases for the periastron (
ϕ
0
= 0.30) and inferior conjunction (
ϕ
IFC
= 0.75). The broadband X-ray spectra with Swift-XRT and NuSTAR allowed us to measure a higher neutral hydrogen column density at one of the predicted disk-passing phases.
Context.
The response of imaging atmospheric Cherenkov telescopes to incident
γ
-ray-initiated showers in the atmosphere changes as the telescopes age due to exposure to light and weather. These ...aging processes affect the reconstructed energies of the events and
γ
-ray fluxes.
Aims.
This work discusses the implementation of signal calibration methods for the Very Energetic Radiation Imaging Telescope Array System (VERITAS) to account for changes in the optical throughput and detector performance over time.
Methods.
The total throughput of a Cherenkov telescope is the product of camera-dependent factors, such as the photomultiplier tube gains and their quantum efficiencies, and the mirror reflectivity and Winston cone response to incoming radiation. This document summarizes different methods to determine how the camera gains and mirror reflectivity have evolved over time and how we can calibrate this changing throughput in reconstruction pipelines for imaging atmospheric Cherenkov telescopes. The implementation is validated against seven years of observations with the VERITAS telescopes of the Crab Nebula, which is a reference object in very-high-energy astronomy.
Results.
Regular optical throughput monitoring and the corresponding signal calibrations are found to be critical for the reconstruction of extensive air shower images. The proposed implementation is applied as a correction to the signals of the photomultiplier tubes in the telescope simulation to produce fine-tuned instrument response functions. This method is shown to be effective for calibrating the acquired
γ
-ray data and for recovering the correct energy of the events and photon fluxes. At the same time, it keeps the computational effort of generating Monte Carlo simulations for instrument response functions affordably low.
Although globus pallidus internus deep brain stimulation is a widely accepted treatment for Parkinson disease, there is persistent variability in outcomes that is not yet fully understood. In this ...pilot study, we aimed to investigate the potential role of globus pallidus internus segmentation using probabilistic tractography as a supplement to traditional targeting methods.
Eleven patients undergoing globus pallidus internus deep brain stimulation were included in this retrospective analysis. Using multidirection diffusion-weighted MR imaging, we performed probabilistic tractography at all individual globus pallidus internus voxels. Each globus pallidus internus voxel was then assigned to the 1 ROI with the greatest number of propagated paths. On the basis of deep brain stimulation programming settings, the volume of tissue activated was generated for each patient using a finite element method solution. For each patient, the volume of tissue activated within each of the 10 segmented globus pallidus internus regions was calculated and examined for association with a change in the Unified Parkinson Disease Rating Scale, Part III score before and after treatment.
Increasing volume of tissue activated was most strongly correlated with a change in the Unified Parkinson Disease Rating Scale, Part III score for the primary motor region (Spearman
= 0.74,
= .010), followed by the supplementary motor area/premotor cortex (Spearman
= 0.47,
= .15).
In this pilot study, we assessed a novel method of segmentation of the globus pallidus internus based on probabilistic tractography as a supplement to traditional targeting methods. Our results suggest that our method may be an independent predictor of deep brain stimulation outcome, and evaluation of a larger cohort or prospective study is warranted to validate these findings.
Abstract
Flat-spectrum radio quasars (FSRQs) are the most luminous blazars at GeV energies but only rarely emit detectable fluxes of TeV gamma rays, typically during bright GeV flares. We explore the ...gamma-ray variability and spectral characteristics of three FSRQs that have been observed at GeV and TeV energies by Fermi-LAT and VERITAS, making use of almost 100 hr of VERITAS observations spread over 10 yr: 3C 279, PKS 1222+216, and Ton 599. We explain the GeV flux distributions of the sources in terms of a model derived from a stochastic differential equation describing fluctuations in the magnetic field in the accretion disk and estimate the timescales of magnetic flux accumulation and stochastic instabilities in their accretion disks. We identify distinct flares using a procedure based on Bayesian blocks and analyze their daily and subdaily variability and gamma-ray energy spectra. Using observations from VERITAS, as well as Fermi, Swift, and the Steward Observatory, we model the broadband spectral energy distributions of PKS 1222+216 and Ton 599 during very high energy (VHE)–detected flares in 2014 and 2017, respectively, strongly constraining the jet Doppler factors and gamma-ray emission region locations during these events. Finally, we place theoretical constraints on the potential production of PeV-scale neutrinos during these VHE flares.
Abstract
We report on the search for very-high-energy gamma-ray emission from the regions around three nearby supersonic pulsars (PSR B0355+54, PSR J0357+3205, and PSR J1740+1000) that exhibit long ...X-ray tails. To date there is no clear detection of TeV emission from any pulsar tail that is prominent in X-ray or radio. We provide upper limits on the TeV flux, and luminosity, and also compare these limits with other pulsar wind nebulae detected in X-rays and the tail emission model predictions. We find that at least one of the three tails is likely to be detected in observations that are a factor of 2–3 more sensitive. The analysis presented here also has implications for deriving the properties of pulsar tails, for those pulsars whose tails could be detected in TeV.
Abstract
The Breakthrough Listen Initiative is conducting a program using multiple telescopes around the world to search for “technosignatures”: artificial transmitters of extraterrestrial origin ...from beyond our solar system. The Very Energetic Radiation Imaging Telescope Array System (VERITAS) Collaboration joined this program in 2018 and provides the capability to search for one particular technosignature: optical pulses of a few nanoseconds in duration detectable over interstellar distances. We report here on the analysis and results of dedicated VERITAS observations of Breakthrough Listen targets conducted in 2019 and 2020 and of archival VERITAS data collected since 2012. Thirty hours of dedicated observations of 136 targets and 249 archival observations of 140 targets were analyzed and did not reveal any signals consistent with a technosignature. The results are used to place limits on the fraction of stars hosting transmitting civilizations. We also discuss the minimum pulse sensitivity of our observations and present VERITAS observations of CALIOP: a space-based pulsed laser on board the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations. The detection of these pulses with VERITAS, using the analysis techniques developed for our technosignature search, allows a test of our analysis efficiency and serves as an important proof of principle.
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