212 research outputs found
First results of a cryogenic optical photon counting imaging spectrometer using a DROID array
Context. In this paper we present the first system test in which we
demonstrate the concept of using an array of Distributed Read Out Imaging
Devices (DROIDs) for optical photon detection. Aims. After the successful S-Cam
3 detector the next step in the development of a cryogenic optical photon
counting imaging spectrometer under the S-Cam project is to increase the field
of view using DROIDs. With this modification the field of view of the camera
has been increased by a factor of 5 in area, while keeping the number of
readout channels the same. Methods. The test has been performed using the
flexible S-Cam 3 system and exchanging the 10x12 Superconducting Tunnel
Junction array for a 3x20 DROID array. The extra data reduction needed with
DROIDs is performed offline. Results. We show that, although the responsivity
(number of tunnelled quasiparticles per unit of absorbed photon energy, e- /eV)
of the current array is too low for direct astronomical applications, the
imaging quality is already good enough for pattern detection, and will improve
further with increasing responsivity. Conclusions. The obtained knowledge can
be used to optimise the system for the use of DROIDs.Comment: 7 pages, 9 figures, accepted for publicaiton in A&
Safety and Efficacy of Extended Interval Dosing for Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer During the COVID-19 Pandemic
INTRODUCTION: Extended interval (EI) dosing for immune checkpoint inhibitor (ICI) mono- or consolidation therapy initiated due to the COVID-19 pandemic led to a significant reduction in ICI-related site visits for patients with stage III and IV non-small cell lung cancer (NSCLC). Here we report the safety and efficacy compared to standard dose (SD) schedules. METHOD: In this retrospective analysis patients who received ICI mono- or consolidation therapy, or adjuvant ICI therapy were assessed. Safety and efficacy of EI dosing with data of SD schedules were compared. RESULTS: One hundred seventeen patients received EI dosing for ICI and 88 patients SD. Patient characteristics were comparable. We observed 237 adverse events in the EI dosing cohort versus 118 in the SD group (p = 0.02). Overall, there was no difference in the occurrence of grade ≥3 adverse events (EI dosing: 21/237 [8.9%]; SD group: 20/118 [17.0%], p = 0.42), except for the pembrolizumab EI dosing cohort. Of all patients who received an EI dosing schedule, however, only 8 (6.8%) were reduced to SD because of toxicity. In 5 (4.3%) patients ICI was permanently stopped because of severe toxicity compared to 11 (12.5%) discontinuations in the SD group. Short-term treatment interruption occurred with similar frequencies in both groups. PFS and OS were comparable in patients receiving pembrolizumab and in those receiving adjuvant durvalumab. Progression-free survival and OS were better in the EI dosing cohort of nivolumab. CONCLUSION: EI dosing for ICI did not lead to an increase of clinically relevant toxicities resulting in dose reduction and/or treatment discontinuation. Efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seems a safe and effective strategy. MICRO ABSTRACT: Aim Retrospective analysis of the safety and efficacy of extended interval dosing (EI) ICI compared to standard dose (SD) schedules. Results 117 patients received EI dosing and 88 SD. In the EI dosing cohort was no increase in toxicity leading to dose reduction and/or discontinuation of treatment. Furthermore, efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seem a safe and effective strategy and should be continued also beyond the COVID-19 pandemic
Interobserver variation in CD30 immunohistochemistry interpretation; consequences for patient selection for targeted treatment
AimsCD30 immunohistochemistry (IHC) in malignant lymphoma is used for selection of patients in clinical trials using brentuximab vedotin, an antibody drug-conjugate targeting the CD30 molecule. For reliable implementation in daily practice and meaningful selection of patients for clinical trials, information on technical variation and interobserver reproducibility of CD30 immunohistochemistry (IHC) staining is required. Methods and resultsWe conducted a three-round reproducibility assessment of CD30 scoring for categorised frequency and intensity, including a technical validation, a live polling' pre- and post-instruction scoring round and a web-based round including individual scoring with additional IHC information to mimic daily diagnostic practice. Agreement in all three scoring rounds was poor to fair ( = 0.12-0.35 for CD30-positive tumour cell percentage and = 0.16-0.41 for staining intensity), even when allowing for one category of freedom in percentage of tumour cell positivity ( = 0.30-0.61). The first round with CD30 staining performed in five independent laboratories showed objective differences in staining intensity. In the second round, approximately half the pathologists changed their opinion on CD30 frequency after a discussion on potential pitfalls, highlighting hesitancy in decision-making. Using fictional cut-off points for percentage of tumour cell positivity, agreement was still suboptimal ( = 0.35-0.60). ConclusionsLack of agreement in cases with heterogeneous expression is shown to influence patient eligibility for treatment with brentuximab vedotin, both in clinical practice and within the context of clinical trials, and limits the potential predictive value of the relative frequency of CD30-positive neoplastic cells for clinical response
The effect of almonds consumption on Blood pressure: A systematic review and dose-response meta-analysis of randomized control trials
The SAFARI Detector System
We give an overview of the baseline detector system for SAFARI, the prime
focal-plane instrument on board the proposed space infrared observatory, SPICA.
SAFARI's detectors are based on superconducting Transition Edge Sensors (TES)
to provide the extreme sensitivity (dark NEP) needed to take advantage of SPICA's cold (<8 K) telescope. In order to
read out the total of ~3500 detectors we use frequency domain multiplexing
(FDM) with baseband feedback. In each multiplexing channel, a two-stage SQUID
preamplifier reads out 160 detectors. We describe the detector system and
discuss some of the considerations that informed its design.Comment: 7 pages, 3 figures, Proc. SPIE 10708, Millimeter, Submillimeter, and
Far-Infrared Detectors and Instrumentation for Astronomy IX, 107080K (9 July
2018); (fixed typo in abstract
Relevance and Effectiveness of Molecular Tumor Board Recommendations for Patients With Non-Small-Cell Lung Cancer With Rare or Complex Mutational Profiles
PURPOSEMolecular tumor boards (MTBs) provide physicians with a treatment recommendation for complex tumor-specific genomic alterations. National and international consensus to reach a recommendation is lacking. In this article, we analyze the effectiveness of an MTB decision-making methodology for patients with non-small-cell lung cancer (NSCLC) with rare or complex mutational profiles as implemented in the University Medical Center Groningen (UMCG).METHODSThe UMCG-MTB comprises (pulmonary) oncologists, pathologists, clinical scientists in molecular pathology, and structural biologists. Recommendations are based on reported actionability of variants and molecular interpretation of pathways affected by the variant and supported by molecular modeling. A retrospective analysis of 110 NSCLC cases (representing 106 patients) with suggested treatment of complex genomic alterations and corresponding treatment outcomes for targeted therapy was performed.RESULTSThe MTB recommended targeted therapy for 59 of 110 NSCLC cases with complex molecular profiles: 24 within a clinical trial, 15 in accordance with guidelines (on label) and 20 off label. All but 16 recommendations involved patients with an EGFR or ALK mutation. Treatment outcome was analyzed for patients with available follow-up (10 on label and 16 off label). Adherence to the MTB recommendation (21 of 26; 81%) resulted in an objective response rate of 67% (14 of 21), with a median progression-free survival of 6.3 months (interquartile range, 3.2-10.6 months) and an overall survival of 10.4 months (interquartile range, 6.3-14.6 months).CONCLUSIONTargeted therapy recommendations resulting from the UMCG-MTB workflow for complex molecular profiles were highly adhered to and resulted in a positive clinical response in the majority of patients with metastatic NSCLC
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