6 research outputs found
<b>Rapid Whole-Knee Quantification of Cartilage using </b>T<sub>1</sub><b>, </b>T<sup>∗</sup><sub>2</sub><b>, and </b>T<sub>RAFF2</sub><b> mapping with MagneticResonance Fingerprinting</b>
Full text linkObjective: Quantitative Magnetic Resonance Imaging (MRI) holds great promise for the early detection of cartilage deterioration. Here, a Magnetic Resonance Fingerprinting (MRF) framework is proposed for comprehensive and rapid quantification of T 1, T 2 ∗, and T RAFF2 with whole-knee coverage. Methods: A MRF framework was developed to achieve quantification of Relaxation Along a Fictitious Field in the 2nd rotating frame of reference (T RAFF2) along with T 1 and T 2 ∗. The proposed sequence acquires 65 measurements of 25 high-resolution slices, interleaved with 7 inversion pulses and 40 RAFF2 trains, for whole-knee quantification in a total acquisition time of 3:25 min. Comparison with reference T 1, T 2 ∗, and T RAFF2 methods was performed in phantom and in seven healthy subjects at 3 T. Repeatability (test-retest) with and without repositioning was also assessed. Results: Phantom measurements resulted in good agreement between MRF and the reference with mean biases of -54, 2, and 5 ms for T 1, T 2 ∗, and T RAFF2, respectively. Complete characterization of the whole-knee cartilage was achieved for all subjects, and, for the femoral and tibial compartments, a good agreement between MRF and reference measurements was obtained. Across all subjects, the proposed MRF method yielded acceptable repeatability without repositioning (R 2≥ 0.94) and with repositioning (R 2≥ 0.57) for T 1, T 2 ∗, and T RAFF2. Significance: The short scan time combined with the whole-knee coverage makes the proposed MRF framework a promising candidate for the early assessment of cartilage degeneration with quantitative MRI, but further research may be warranted to improve repeatability after repositioning and assess clinical value in patients.</p
An Enhanced Fault Injection Framework for FPGA-Based Soft-Cores
Full text linkContemporary space system architectures necessitate rigorous validation to ensure robust performance post-deployment. Fault injection is a critical methodology that improves confidence in these systems by simulating errors under controlled conditions. Traditional fault injection approaches, such as simulation and emulation, often require costly resources or invasive alterations to the Device Under Test (DUT). The FREtZ tool addresses some of these challenges by facilitating non-invasive bit flip injections into user-bits and Configuration RAM (CRAM) bits via the FPGA's JTAG interface. However, its integration with soft-cores remains limited. This paper introduces a novel fault injection framework that extends the capabilities of the FREtZ tool. Our framework improves both the precision and the efficiency of fault injections in soft-core processors by enabling targeted fault injections at specific clock cycles or program counter locations. Hence, the injection space can be reduced to the DUT, enabling the execution of a thorough injection campaign. The proposed method not only refines the granularity of the fault injections but also streamlines the emulation process, thereby providing a more efficient and less intrusive approach to system testing. This advancement represents a significant step forward in emulation-based fault injection, particularly for complex space system architectures where reliability is paramount
Rotaxane-Functionalized Dyes for Charge-Rectification in p-Type Photoelectrochemical Devices
Full text linkA supramolecular photovoltaic strategy is applied to enhance power conversion efficiencies (PCE) of photoelectrochemical devices by suppressing electron–hole recombination after photoinduced electron transfer (PET). Here, the author exploit supramolecular localization of the redox mediator—in close proximity to the dye—through a rotaxane topology, reducing electron–hole recombination in p-type dye-sensitized solar cells (p-DSSCs). Dye P Rotaxane features 1,5-dioxynaphthalene recognition sites (DNP-arms) with a mechanically-interlocked macrocyclic redox mediator naphthalene diimide macrocycle (3-NDI-ring), stoppering synthetically via click chemistry. The control molecule P Stopper has stoppered DNP-arms, preventing rotaxane formation with the 3-NDI-ring. Transient absorption and time-resolved fluorescence spectroscopy studies show ultrafast (211 ± 7 fs and 2.92 ± 0.05 ps) PET from the dye-moiety of P Rotaxane to its mechanically interlocked 3-NDI-ring-acceptor, slowing down the electron–hole recombination on NiO surfaces compared to the analogue. p-DSSCs employing P Rotaxane (PCE = 0.07%) demonstrate a 30% PCE increase compared to P Stopper (PCE = 0.05%) devices, combining enhancements in both open-circuit voltages (V OC = 0.43 vs 0.36 V) and short-circuit photocurrent density (J SC = −0.39 vs −0.34 mA cm −2). Electrochemical impedance spectroscopy shows that P Rotaxane devices exhibit hole lifetimes (τ h) approaching 1 s, a 16-fold improvement compared to traditional I −/I 3 −-based systems (τ h = 50 ms), demonstrating the benefits obtained upon nanoengineering of interfacial dye-regeneration at the photocathode.</p
Birt-Hogg-Dubé syndrome in apparent primary spontaneous pneumothorax patients; results and recommendations for clinical practice
Full text linkBACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is an inherited disease caused by pathogenic variants in the FLCN gene. One of the characteristics is the increased risk for spontaneous pneumothorax, likely due to the presence of pulmonary cysts mainly distributed under the carina. Due to variable expression and lack of awareness, BHD is likely to be underdiagnosed. We aimed to examine the prevalence of BHD in patients presenting with an apparent primary spontaneous pneumothorax and to evaluate the contribution of chest CT in establishing the diagnosis. METHODS: Patients who presented with apparent primary spontaneous pneumothorax between 2004 and 2017 in a large Dutch teaching hospital were enrolled in this quantitative cross-sectional study. A questionnaire was sent to eligible patients. Patients who completed the questionnaire and consented to further participation were invited to visit the hospital for genetic testing and low dose, volumetric chest CT. RESULTS: Genetic testing was performed in 88 patients with apparent primary spontaneous pneumothorax. Three patients were found to have a pathogenic variant in the FLCN gene (3.4%). No variants of unknown significance were detected. Pulmonary cysts were detected in 14 out of 83 participants with an available chest CT, six had more than one cyst. All three patients with BHD had multiple pulmonary cysts. CONCLUSIONS: Based on previous literature and the present study, we believe that performing a chest CT in every patient presenting with primary spontaneous pneumothorax is justified. Subsequent genetic testing of the FLCN gene should be considered when multiple pulmonary cysts are present. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov with reference NCT02916992. SUMMARY AT A GLANCE: Three out of 88 patients with an apparent primary spontaneous pneumothorax were diagnosed with Birt-Hogg-Dubé syndrome in this study and all three had multiple pulmonary cysts. We believe that performing a chest CT in every patient with an apparent primary spontaneous pneumothorax is justified to identify underlying diseases
Safety, Efficacy and Biomarker Analysis of Crizotinib in MET Mutated Non-Small Cell Lung Cancer - Results from the Drug Rediscovery Protocol
Full text linkPurpose: To provide patients with MET-mutated advanced non-small cell lung cancer (METmut aNSCLC) access to crizotinib, further substantiate evidence of its efficacy and safety in this setting, and find potential biomarkers for nonresponse. Patients and Methods: In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring MET exon 14 skipping or other MET mutations received crizotinib 250 mg BID until disease progression or intolerable toxicity. Primary endpoints were clinical benefit [CB: RECIST v1.1 confirmed partial response, complete response (CR), or stable disease ≥16 weeks] and safety. Patients were enrolled using a Simon-like two-stage design, with eight patients in stage I and if ≥1/8 patients had CB, 24 patients in stage II. Whole-genome sequencing and RNA sequencing were performed on baseline biopsies. Results: Between September 2018 and October 2022, 30 patients started treatment, and 24 were response-evaluable after completing ≥1 full treatment cycle. Two patients (8.3%) achieved CR, 13 (54.2%) partial response, and two (8.3%) stable disease. The CB rate was 70.8% [95% confidence interval (CI), 48.9-87.4], and the objective response rate was 62.5% (95% CI, 40.6-81.2). After 21.2-month median followup, median duration of response, progression-free survival, and overall survival were 9.3 (95% CI, 6.5-not available), 10.2 (95% CI, 6.0-20.1), and 13.0 months (95% CI, 9.0-not available), respectively. Twentythree treatment-related grade ≥ 3 adverse events occurred in 12/30 patients (40%), causing treatment discontinuation in three (10%). One patient (achieving CR) had a tyrosine kinase domain mutation (p.H1094Y), and all other patients had MET exon 14 skipping mutations. Conclusions: Crizotinib is a valuable treatment option in METmut aNSCLC.</p
