83 research outputs found
Effective Approaches With Young Adults: A Guide for Probation Services
The aim of this guide is to give probation practitioners, whether in the National Probation Service or Community Rehabilitation Companies, the tools to deliver a more effective approach to young adults. It provides practical suggestions for effective ways to engage young adults and support their desistance from crime. It also includes suggestions for managers on what they can do to enable practitioners to improve outcomes within probation services
Discontinuation of BRAF/MEK-Directed Targeted Therapy after Complete Remission of Metastatic Melanoma—A Retrospective Multicenter ADOReg Study
The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progressionfree (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma.
Long-term survivors have been identified particularly among patients with a complete response
(CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who
achieved a CR maintain a durable response and whether treatment cessation might be a safe option
in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical
course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with
BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi
therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg.
Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP)
and response to second-line treatments were collected and analyzed. Of 461 patients who received
BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%)
mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT
(n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP
compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients
who received TT for more than 16 months and who discontinued TT for other reasons than TP or
toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates
to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint
inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable
number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary realworld cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to
ongoing TT but was also found in patients who discontinued TT
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy
We measure the energy emitted by extensive air showers in the form of radio
emission in the frequency range from 30 to 80 MHz. Exploiting the accurate
energy scale of the Pierre Auger Observatory, we obtain a radiation energy of
15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV
arriving perpendicularly to a geomagnetic field of 0.24 G, scaling
quadratically with the cosmic-ray energy. A comparison with predictions from
state-of-the-art first-principle calculations shows agreement with our
measurement. The radiation energy provides direct access to the calorimetric
energy in the electromagnetic cascade of extensive air showers. Comparison with
our result thus allows the direct calibration of any cosmic-ray radio detector
against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI.
Supplemental material in the ancillary file
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