Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure

Febrile neutropenia (FN) is a serious complication of chemotherapy, which can cause significant morbidity and mortality, result in dose delays and reductions and, ultimately, reduce cancer survival. Over the past decade, the availability of biosimilar filgrastim (short-acting granulocyte colony-stimulating factor [G-CSF]) has transformed patient access, with clear evidence of clinical benefit at preventing FN at reduced costs. In 2019, seven biosimilar pegfilgrastims (long-acting G-CSFs) were licensed, creating optimal market conditions and choice for prescribers. FN affects up to 117 per 1000 cancer patients, with mortality rates in the range of 2–21%. By reducing FN incidence and improving chemotherapy relative dose intensity (RDI), G-CSF has been associated with a 3.2% absolute survival benefit. Guidelines recommend primary prophylaxis and that filgrastim be administered for 10–14 days, while pegfilgrastim is administered once per cycle. When taken according to the guidelines, pegfilgrastim and filgrastim are equally effective. However, in routine clinical practice, filgrastim is often under-dosed (< 7 days) and has been shown to be inferior to pegfilgrastim at reducing FN incidence, hospitalisations and maintaining RDI. Once-per-cycle administration with pegfilgrastim might also aid patient adherence. The introduction of biosimilar pegfilgrastim should instigate a rethink of neutropenia management. Biosimilar pegfilgrastim

Dark Matter Search in the Edelweiss Experiment

Preliminary results obtained with 320g bolometers with simultaneous ionization and heat measurements are described. After a few weeks of data taking, data accumulated with one of these detectors are beginning to exclude the upper part of the DAMA region. Prospects for the present run and the second stage of the experiment, EDELWEISS-II, using an innovative reversed cryostat allowing data taking with 100 detectors, are briefly described.Comment: IDM 2000, 3rd International Workshop on the Identification of Dark Matter, York (GB), 18-22/09/2000, v2.0 minor modification

The EDELWEISS Experiment : Status and Outlook

The EDELWEISS Dark Matter search uses low-temperature Ge detectors with heat and ionisation read- out to identify nuclear recoils induced by elastic collisions with WIMPs from the galactic halo. Results from the operation of 70 g and 320 g Ge detectors in the low-background environment of the Modane Underground Laboratory (LSM) are presented.Comment: International Conference on Dark Matter in Astro and Particle Physics (Dark 2000), Heidelberg, Germany, 10-16 Jul 2000, v3 minor revision

Event categories in the EDELWEISS WIMP search experiment

Four categories of events have been identified in the EDELWEISS-I dark matter experiment using germanium cryogenic detectors measuring simultaneously charge and heat signals. These categories of events are interpreted as electron and nuclear interactions occurring in the volume of the detector, and electron and nuclear interactions occurring close to the surface of the detectors(10-20 mu-m of the surface). We discuss the hypothesis that low energy surface nuclear recoils,which seem to have been unnoticed by previous WIMP searches, may provide an interpretation of the anomalous events recorded by the UKDMC and Saclay NaI experiments. The present analysis points to the necessity of taking into account surface nuclear and electron recoil interactions for a reliable estimate of background rejection factors.Comment: 11 pages, submitted to Phys. Lett.

First Results of the EDELWEISS WIMP Search using a 320 g Heat-and-Ionization Ge Detector

The EDELWEISS collaboration has performed a direct search for WIMP dark matter using a 320 g heat-and-ionization cryogenic Ge detector operated in a low-background environment in the Laboratoire Souterrain de Modane. No nuclear recoils are observed in the fiducial volume in the 30-200 keV energy range during an effective exposure of 4.53 kg.days. Limits for the cross-section for the spin-independent interaction of WIMPs and nucleons are set in the framework of the Minimal Supersymmetric Standard Model (MSSM). The central value of the signal reported by the experiment DAMA is excluded at 90% CL.Comment: 14 pages, Latex, 4 figures. Submitted to Phys. Lett.

Background discrimination capabilities of a heat and ionization germanium cryogenic detector

The discrimination capabilities of a 70 g heat and ionization Ge bolometer are studied. This first prototype has been used by the EDELWEISS Dark Matter experiment, installed in the Laboratoire Souterrain de Modane, for direct detection of WIMPs. Gamma and neutron calibrations demonstrate that this type of detector is able to reject more than 99.6% of the background while retaining 95% of the signal, provided that the background events distribution is not biased towards the surface of the Ge crystal. However, the 1.17 kg.day of data taken in a relatively important radioactive environment show an extra population slightly overlapping the signal. This background is likely due to interactions of low energy photons or electrons near the surface of the crystal, and is somewhat reduced by applying a higher charge-collecting inverse bias voltage (-6 V instead of -2 V) to the Ge diode. Despite this contamination, more than 98% of the background can be rejected while retaining 50% of the signal. This yields a conservative upper limit of 0.7 event.day^{-1}.kg^{-1}.keV^{-1}_{recoil} at 90% confidence level in the 15-45 keV recoil energy interval; the present sensitivity appears to be limited by the fast ambient neutrons. Upgrades in progress on the installation are summarized.Comment: Submitted to Astroparticle Physics, 14 page

A large geometric distortion in the first photointermediate of rhodopsin, determined by double-quantum solid-state NMR

Double-quantum magic-angle-spinning NMR experiments were performed on 11,12-C-13(2)-retinylidene-rhodopsin under illumination at low temperature, in order to characterize torsional angle changes at the C11-C12 photoisomerization site. The sample was illuminated in the NMR rotor at low temperature (similar to 120 K) in order to trap the primary photointermediate, bathorhodopsin. The NMR data are consistent with a strong torsional twist of the HCCH moiety at the isomerization site. Although the HCCH torsional twist was determined to be at least 40A degrees, it was not possible to quantify it more closely. The presence of a strong twist is in agreement with previous Raman observations. The energetic implications of this geometric distortion are discussed

Associations between green/blue spaces and mental health across 18 countries

Living near, recreating in, and feeling psychologically connected to, the natural world are all associated with better mental health, but many exposure-related questions remain. Using data from an 18-country survey (n= 16,307) we explored associations between multiple measures of mental health (positive well-being, mental distress, depression/anxiety medication use) and: (a) exposures (residential/recreational visits) to diferent natural settings (green/inland-blue/coastalblue spaces); and (b) nature connectedness, across season and country. People who lived in greener/ coastal neighbourhoods reported higher positive well-being, but this association largely disappeared when recreational visits were controlled for. Frequency of recreational visits to green, inland-blue, and coastal-blue spaces in the last 4 weeks were all positively associated with positive well-being and negatively associated with mental distress. Associations with green space visits were relatively consistent across seasons and countries but associations with blue space visits showed greater heterogeneity. Nature connectedness was also positively associated with positive well-being and negatively associated with mental distress and was, along with green space visits, associated with a lower likelihood of using medication for depression. By contrast inland-blue space visits were associated with a greater likelihood of using anxiety medication. Results highlight the benefts of multi-exposure, multi-response, multi-country studies in exploring complexity in nature-health associations.info:eu-repo/semantics/publishedVersio