The mid-infrared (mid-IR) continuum generation based on broadband second harmonic generation (SHG) (or difference frequency generation) is of great interest in a wide range of applications such as ...free space communications, environmental monitoring, thermal imaging, high-sensitivity metrology, gas sensing, and molecular fingerprint spectroscopy. The second-order nonlinear optic (NLO) crystals have been spotlighted as a material platform for converting the wavelengths of existing lasers into the mid-IR spectral region or for realizing tunable lasers. In particular, the spectral coverage could be extended to ~19 µm with non-oxide NLO crystals. In this paper, we theoretically and numerically investigated the broadband SHG properties of non-oxide mid-IR crystals in three categories: chalcopyrite semiconductors, defect chalcopyrite, and orthorhombic ternary chalcogenides. The technique is based on group velocity matching between interacting waves in addition to birefringent phase matching. We will describe broadband SHG characteristics in terms of beam propagation directions, spectral positions of resonance, effective nonlinearities, spatial walk-offs between interacting beams, and spectral bandwidths. The results will show that the spectral bandwidths of the fundamental wave allowed for broadband SHG to reach several hundreds of nm. The corresponding SH spectral range spans from 1758.58 to 4737.18 nm in the non-oxide crystals considered in this study. Such broadband SHG using short pulse trains can potentially be applied to frequency up-conversion imaging in the mid-IR region, in information transmission, and in nonlinear optical signal processing.
Background & Aims
Regorafenib demonstrated a clinical benefit for patients with unresectable hepatocellular carcinoma (uHCC) in the phase III RESORCE trial. Considering the heterogeneity of uHCC and ...discrepancies in its characteristics between prospective trials and daily practice, real‐life evidence is necessary.
Methods
This multicentre, retrospective analysis was performed by the Korean Cancer Study Group. In total, 440 patients who received regorafenib between January 2017 and November 2019 were identified in nine tertiary referral hospitals in Korea.
Results
All patients received prior sorafenib, and the median time‐to‐progression (TTP) on sorafenib was 3.9 months (range, 0.2‐71.6). Regorafenib was used as the second, third and fourth to seventh lines of therapy in 305 (69.3%), 115 (26.1%) and 20 (4.5%) patients respectively. According to the RECIST v1.1, the overall response rate was 7.7% (n = 34), and the median progression‐free survival (PFS) and overall survival (OS) were 3.2 (95% CI, 2.8‐3.5) and 12.1 (95% CI, 9.7‐14.5) months respectively. Immune checkpoint inhibitors (ICIs) were given in 115 patients (26.1%) prior to regorafenib. There were no differences in PFS and OS with regorafenib according to the prior use of ICIs (PFS, P = .61; OS, P = .63). The occurrence of hand‐foot skin reaction (HFSR) was associated with a better OS (P < .001).
Conclusions
The real‐life clinical outcomes of regorafenib for patients who progressed on prior systemic therapy including ICIs were consistent with the phase III trial results. HFSR was significantly associated with better OS with regorafenib.
The generation and detection of nonclassical light of about 2 μm has good potential in an emerging field of high-sensitivity metrology, especially gravitational wave detection, as well as free-space ...quantum communication. A pair of photons is generated through a spontaneous parametric down-conversion (SPDC) process in a nonlinear optic crystal, which can be properly entangled in a spatial region where two beams with each polarization overlap or in a Sagnac-loop interferometer configuration. We investigated theoretically and numerically Type II SPDC in a potassium niobate (KNbO3, KN) crystal, which is useful as a material platform for generating photon pairs of high spectral purity in the 2-μm range. The technique is based on the frequency degenerate SPDC under Type II extended phase matching (EPM). We described the EPM characteristics of KN and showed that it is practically feasible for a 1064-nm pumped SPDC under moderate temperature conditions. The effective nonlinear optic coefficient of KN is at least four-times larger than those of other crystals using the Type II EPM approach, which implies a significant improvement in SPDC efficiency. The joint spectral analysis showed that a pair of photons can be generated with a high purity of 0.995 through proper pump filtering.
Recent advances of high-quality lithium niobate (LN) on insulator technology have revitalized the progress of novel chip-integrated LN-based photonic devices and accelerated application research. One ...of the promising technologies of interest is the generation of entangled photon pairs based on spontaneous parametric down-conversion (SPDC) in LNs. In this paper, we investigated, theoretically and numerically, Type II SPDC in two kinds of LNs—undoped and 5-mol% MgO doped LNs. In each case, both non-poled and periodically poled crystals were considered. The technique is based on the SPDC under Type II extended phase matching, where the phase matching and the group velocity matching are simultaneously achieved between interacting photons. The proposed approach has not yet been reported for LNs. We discussed all factors required to generate photon pairs in LNs, in terms of the beam propagation direction, the spectral position of photons, and the corresponding effective nonlinearities and walk-offs. We showed that the spectral positions of the generated photon pairs fall into the mid-infrared region with high potential for free-space quantum communication, spectroscopy, and high-sensitivity metrology. The joint spectral analyses showed that photon pairs can be generated with high purities of 0.995–0.999 with proper pump filtering.
We investigated the high-purity entangled photon-pair generation in five kinds of “non-poled” potassium titanyl phosphate (KTP) isomorphs (i.e., KTiOPO4, RbTiOPO4, KTiOAsO4, RbTiOAsO4, and ...CsTiOAsO4). The technique is based on the spontaneous parametric down-conversion (SPDC) under Type II extended phase matching (EPM), where the phase matching and the group velocity matching are simultaneously achieved between the interacting photons in non-poled crystals rather than periodically poled (PP) KTPs that are widely used for quantum experiments. We discussed both theoretically and numerically all aspects required to generate photon pairs in non-poled KTP isomorphs, in terms of the range of the beam propagation direction (or the spectral range of photons) and the corresponding effective nonlinearities and beam walk-offs. We showed that the SPDC efficiency can be increased in non-poled KTP isomorphs by 29% to 77% compared to PPKTP cases. The joint spectral analyses showed that photon pairs can be generated with high purities of 0.995–0.997 with proper pump filtering. In contrast to the PPKTP case, where the EPM is achieved only at one specific wavelength, the spectral position of photon pairs in the non-poled KTP isomorphs can be chosen over the wide range of 1883.8–2068.1 nm.
High theoretical capacity and low-cost copper sulfide (Cu
S)-based anodes have gained great attention for advanced sodium-ion batteries (SIBs). However, their practical application may be hindered ...due to their unstable cycling performance and problems with the dissolution of sodium sulfides (Na
S) into electrolyte. Here, we employed metal organic framework (MOF-199) as a sacrificial template to fabricate nanoporous Cu
S with a large surface area embedded in the MOF-derived carbon network (Cu
S-C) through a two-step process of sulfurization and carbonization via H
S gas-assisted plasma-enhanced chemical vapor deposition (PECVD) processing. Subsequently, we uniformly coated a nanocarbon layer on the Cu
S-C through hydrothermal and subsequent annealing processes. The physico-chemical properties of the nanocarbon layer were revealed by the analytical techniques of high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDS), and scanning electron microscopy (SEM). We acquired a higher SIB performance (capacity retention (~93%) with a specific capacity of 372 mAh/g over 110 cycles) of the nanoporous Cu
S-C/C core/shell anode materials than that of pure Cu
S-C. This encouraging SIB performance is attributed to the key roles of a nanocarbon layer coated on the Cu
S-C to accommodate the volume variation of the Cu
S-C anode structure during cycling, enhance electrical conductivity and prevent the dissolution of Na
S into the electrolyte. With these physico-chemical and electrochemical properties, we ensure that the Cu
S-C/C structure will be a promising anode material for large-scale and advanced SIBs.
We investigate the high-purity entangled photon pair generation in a recently developed borate crystal, Ba3Mg3(BO3)3F3. The technique is based on the spontaneous parametric down-conversion under the ...extended phase matching (EPM), where the phase matching and the group velocity matching between the interacting photons are satisfied simultaneously in bulk crystals with point symmetry of orthorhombic mm2 (thus showing biaxial birefringence). We will discuss all the theoretical aspects required for the generation of photon pairs in mm2 biaxial crystals, which are much more complex than the cases of uniaxial crystals (e.g., β-BaB2O4 and LiNbO3) and periodically poled crystals that are widely used in the field. Our study includes theoretical and numerical investigations of two types of EPM and their corresponding effective nonlinearities and spatial walk-offs. The results show that two types of EPM are satisfied over the specific range in the direction of pump wave vector, corresponding to its spectral ranges of 876.15–1052.77 nm for Type I and 883.92–914.33 nm for Type II. The joint spectral analyses show that photon-pairs can be generated with high purities of 0.997 with a proper pump filtering (for Type II), and 0.833 even without pump filtering (for Type I).
Background:
Atezolizumab plus bevacizumab (Ate/Bev) demonstrated promising efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III IMbrave150 trial. However, ...patients with Child–Pugh B HCC were excluded in the abovementioned prospective trial. Therefore, we aimed to investigate the efficacy and safety of Ate/Bev in patients with Child–Pugh B HCC.
Methods:
This multicenter retrospective study included 36 patients with Child–Pugh B advanced HCC who received Ate/Bev at four cancer referral centers between May 2020 and August 2021. Comparative analyses were performed with an independent cohort of patients with Child–Pugh A HCC from the same registry (n = 133).
Results:
All patients received Ate/Bev as first-line systemic treatment for advanced HCC. The objective response and disease control rates of patients in the Child–Pugh groups B and A were 11.1% and 58.3% and 34.6% and 76.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.0 months 95% confidence interval (CI), 1.7–4.3) and 7.7 months (95% CI, 4.8–10.6) in the Child–Pugh B group, whereas the median PFS and OS were 9.6 months (95% CI, 5.1–14.2) and not reached (95% CI, not available) in the Child–Pugh A group, respectively. Compared to the Child–Pugh A group, grade 3–4 adverse events (AEs) were more common in the Child–Pugh B group (44.4% versus 15.8, p < 0.001), with the most frequent grade 3–4 AEs being gastrointestinal bleeding (n = 6, 16.7%), neutropenia (n = 5, 13.9%), and thrombocytopenia (n = 4, 11.1%).
Conclusions:
In the Child–Pugh B subgroup of patients with advanced HCC, Ate/Bev treatment showed modest clinical activity. However, due to the increased frequency of serious AEs, careful evaluation of treatment response and AE management is required in this subgroup of patients.
Here, we fabricate poly(vinylidene fluoride-
-hexafluoropropene) (PVDF-
-HFP) by electrospinning for a gel polymer electrolyte (GPE) for use in flexible Li-ion batteries (LIBs). As a solvent, we use
...-methyl-2-pyrrolidone (NMP), which helps produce the cross-linked morphology of PVDF-
-HFP separator, owing to its low volatility. The cross-linked PVDF-
-HFP separator shows an uptake rate higher than that of a commercialized polypropylene (PP) separator. Moreover, the PVDF-
-HFP separator shows an ionic conductivity of 2.3 × 10
S/cm at room temperature, comparable with previously reported values. An LIB full-cell assembled with the PVDF-
-HFP-based GPE shows capacities higher than its counterpart with the commercialized PP separator, confirming that the cross-linked PVDF-
-HFP separator provides highly efficient ionic conducting pathways. In addition, we integrate a flexible LIB cell using the PVDF-
-HFP GPE with a flexible organic light emitting diode (OLED), demonstrating a fully flexible unit of LIB and OLED.
We elucidated the clinical and immunologic implications of serum IL-6 levels in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Ate/Bev).
We ...prospectively enrolled 165 patients with unresectable HCC (discovery cohort: 84 patients from three centres; validation cohort: 81 patients from one centre). Baseline blood samples were analysed using a flow cytometric bead array. The tumour immune microenvironment was analysed using RNA sequencing.
In the discovery cohort, clinical benefit 6 months (CB6m) was defined as complete or partial response, or stable disease for ≥6 months. Among various blood-based biomarkers, serum IL-6 levels were significantly higher in participants without CB6m than in those with CB6m (mean 11.56 vs. 5.05 pg/ml, p = 0.02). Using maximally selected rank statistics, the optimal cut-off value for high IL-6 was determined as 18.49 pg/ml, and 15.2% of participants were found to have high IL-6 levels at baseline. In both the discovery and validation cohorts, participants with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev treatment compared with those with low baseline IL-6 levels. In multivariable Cox regression analysis, the clinical implications of high IL-6 levels persisted, even after adjusting for various confounding factors. Participants with high IL-6 levels showed reduced interferon-γ and tumour necrosis factor-α secretion from CD8+ T cells. Moreover, excess IL-6 suppressed cytokine production and proliferation of CD8+ T cells. Finally, participants with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumour microenvironment.
High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment.
Although patients with hepatocellular carcinoma who respond to treatment with atezolizumab and bevacizumab exhibit favourable clinical outcomes, a fraction of these still experience primary resistance. We found that high baseline serum levels of IL-6 correlate with poor clinical outcomes and impaired T-cell response in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab.
Display omitted
•Patients with high baseline IL-6 had worse survival outcomes following Ate/Bev.•Excess IL-6 impaired cytokine production and proliferation of CD8+ T cells.•High serum IL-6 levels were associated with non-T-cell-inflamed tumours.
PDF
