Clinical outcomes in patients relapsed/refractory after ≥2 prior lines of therapy for follicular lymphoma: A systematic literature review and meta-analysis

BACKGROUND: Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapy (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT identified through systematic literature review. METHODS: Eligible studies included comparative or non-comparative interventional or observational studies of systemic therapies among adults with FL r/r after ≥2 prior LOT published prior to 31st May 2021. Prior LOT must have included an anti-CD20 monoclonal antibody and an alkylating agent, in combination or separately. Overall response rate (ORR) and complete response (CR) were estimated using inverse-variance weighting with Freeman-Tukey double-arcsine transformations. Kaplan-Meier (KM) curves for progression-free survival (PFS) and overall survival (OS) estimated by reconstructing digitized curves using the Guyot algorithm, and survival analyses were conducted, stratified by ≥2 prior LOT and ≥ 3 prior LOT groups (as defined in the source material). Restricting the analyses to the observational cohorts was investigated as a sensitivity analysis. RESULTS: The analysis-set included 20 studies published between 2014 and 2021. Studies were primarily US and/or European based, with the few exceptions using treatments approved in US/Europe. The estimated ORR was 58.47% (95% confidence interval [CI]: 51.13-65.62) and proportion of patients with CR was 19.63% (95% CI: 15.02-24.68). The median OS among those ≥2 prior LOT was 56.57 months (95% CI: 47.8-68.78) and median PFS was 9.78 months (95% CI: 9.01-10.63). The 24-month OS decreased from 66.50% in the ≥2 prior LOT group to 59.51% in the ≥3 prior LOT group, with a similar trend in PFS at 24-month (28.42% vs 24.13%). CONCLUSIONS: This study found that few r/r FL patients with ≥2 prior LOT achieve CR, and despite some benefit, approximately 1/3 of treated patients die within 24 months. The shorter median PFS with increasing prior LOT suggest treatment durability is suboptimal in later LOT. These findings indicate that patients are underserved by treatments currently available in the US and Europe

Evolution of the fishtail-effect in pure and Ag-doped MG-YBCO

We report on magnetic measurements carried out in a textured YBa$_2$Cu$_3$O$_{7-\delta}$ and YBa$_2$(Cu$_{1-x}$Ag$_x$)$_3$O$_{7-\delta}$ (at $x \approx$ 0.02) crystals. The so-called fishtail-effect (FE) or second magnetization peak has been observed in a wide temperature range 0.4~$<T/T_c<$~0.8 for $\textbf{H}\parallel c$. The origin of the FE arises for the competition between surface barrier and bulk pinning. This is confirmed in a non-monotonically behavior of the relaxation rate $R$. The value $H_{max}$ for Ag-doped crystals is larger than for the pure one due to the presence of additional pinning centers, above all on silver atoms.Comment: 6 pages, 6 figure

Liquid Argon Instrumentation and Monitoring in LEGEND-200

LEGEND is the next-generation experiment searching for the neutrinoless double beta decay in $^{76}$Ge. The first stage, LEGEND-200, takes over the cryogenic infrastructure of GERDA at LNGS: an instrumented water tank surrounding a 64 m$^{3}$ liquid argon cryostat. Around 200 kg of Ge detectors will be deployed in the cryostat, with the liquid argon acting as cooling medium, high-purity passive shielding and secondary detection medium. For the latter purpose, a liquid argon instrumentation is developed, based on the system used in GERDA Phase II. Wavelength shifting fibers coated with TPB are arranged in two concentric barrels. Both ends are read out by SiPM arrays. A wavelength shifting reflector surrounds the array in order to enhance the light collection far from the array. The LLAMA is installed in the cryostat to permanently monitor the optical parameters and to provide in-situ inputs for modeling purposes. The design of all parts of the LEGEND-200 LAr instrumentation is presented. An overview of the geometry, operation principle, and off-line data analysis of the LLAMA is shown

Whole-body vibration training induces hypertrophy of the human patellar tendon

I Brage finner du siste tekst-versjon av artikkelen, og den kan inneholde ubetydelige forskjeller fra forlagets pdf-versjon. Forlagets pdf-versjon finner du på onlinelibrary.wiley.com / In Brage you'll find the final text version of the article, and it may contain insignificant differences from the journal's pdf version. The definitive version is available at onlinelibrary.wiley.comAnimal studies suggest that regular exposure to whole-body vibration (WBV) induces an anabolic response in bone and tendon. However, the effects of this type of intervention on human tendon properties and its influence on the muscle-tendon unit function have never been investigated. The aim of this study was to investigate the effect of WBV training on the patellar tendon mechanical, material and morphological properties, the quadriceps muscle architecture and the knee extension torque–angle relationship. Fifty-five subjects were randomized into either a vibration, an active control, or an inactive control group. The active control subjects performed isometric squats on a vibration platform without vibration. Muscle and tendon properties were measured using ultrasonography and dynamometry. Vibration training induced an increase in proximal (6.3%) and mean (3.8%) tendon cross-sectional area, without any appreciable change in tendon stiffness and modulus or in muscle architectural parameters. Isometric torque at a knee angle of 90° increased in active controls (6.7%) only and the torque–angle relation remained globally unchanged in all groups. The present protocol did not appreciably alter knee extension torque production or the musculo-tendinous parameters underpinning this function. Nonetheless, this study shows for the first time that WBV elicits tendon hypertrophy in humans.Seksjon for fysisk prestasjonsevne / Department of Physical Performanc

A Study of the PDGF Signaling Pathway with PRISM

In this paper, we apply the probabilistic model checker PRISM to the analysis of a biological system -- the Platelet-Derived Growth Factor (PDGF) signaling pathway, demonstrating in detail how this pathway can be analyzed in PRISM. We show that quantitative verification can yield a better understanding of the PDGF signaling pathway.Comment: In Proceedings CompMod 2011, arXiv:1109.104

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports

Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models. Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m2 over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administratio

Characterization of 30 76^{76}Ge enriched Broad Energy Ge detectors for GERDA Phase II

The GERmanium Detector Array (GERDA) is a low background experiment located at the Laboratori Nazionali del Gran Sasso in Italy, which searches for neutrinoless double beta decay of $^{76}$Ge into $^{76}$Se+2e$^-$. GERDA has been conceived in two phases. Phase II, which started in December 2015, features several novelties including 30 new Ge detectors. These were manufactured according to the Broad Energy Germanium (BEGe) detector design that has a better background discrimination capability and energy resolution compared to formerly widely-used types. Prior to their installation, the new BEGe detectors were mounted in vacuum cryostats and characterized in detail in the HADES underground laboratory in Belgium. This paper describes the properties and the overall performance of these detectors during operation in vacuum. The characterization campaign provided not only direct input for GERDA Phase II data collection and analyses, but also allowed to study detector phenomena, detector correlations as well as to test the strength of pulse shape simulation codes.Comment: 29 pages, 18 figure

The first search for bosonic super-WIMPs with masses up to 1 MeV/c2^2 with GERDA

We present the first search for bosonic super-WIMPs as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-beta decay experiment which operates high-purity germanium detectors enriched in $^{76}$Ge in an ultra-low background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c$^2$ to 1 MeV/c$^2$. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c$^2$ have been set. As an example, at a mass of 150 keV/c$^2$ the most stringent direct limits on the dimensionless couplings of axion-like particles and dark photons to electrons of $g_{ae} < 3 \cdot 10^{-12}$ and ${\alpha'}/{\alpha} < 6.5 \cdot 10^{-24}$ at 90% credible interval, respectively, were obtained.Comment: 6 pages, 3 figures, submitted to Physical Review Letters, added list of authors, updated ref. [21