Frequency comb generation via synchronous pumped χ(3) resonator on thin-film lithium niobate.

Resonator-based optical frequency comb generation is an enabling technology for a myriad of applications ranging from communications to precision spectroscopy. These frequency combs can be generated in nonlinear resonators driven using either continuous-wave (CW) light, which requires alignment of the pump frequency with the cavity resonance, or pulsed light, which also mandates that the pulse repetition rate and cavity free spectral range (FSR) are carefully matched. Advancements in nanophotonics have ignited interest in chip-scale optical frequency combs. However, realizing pulse-driven on-chip Kerr combs remains challenging, as microresonator cavities have limited tuning range in their FSR and resonance frequency. Here, we take steps to overcome this limitation and demonstrate broadband frequency comb generation using a χ(3) resonator synchronously pumped by a tunable femtosecond pulse generator with on-chip amplitude and phase modulators. Notably, employing pulsed pumping overcomes limitations in Kerr comb generation typically seen in crystalline resonators from stimulated Raman scattering.

Betel-nut chewing does not influence PD-L1 expression rates in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC): A prospective biomarker prevalence study.

This study explored the relationship between betel-nut chewing and programmed death-ligand 1 (PD-L1) expression in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients in Taiwan. A total 280 R/M HNSCC patients, predominantly male, were evaluated; 75.4 % of whom chewed betel-nut. The prevalence of PD-L1 expression (combined positive score ≥1) was 94.3 % with similar PD-L1 expression rates between betel-nut-exposed and non-exposed groups. PD-L1 prevalence did not differ in those who received prior first-or second-line systemic therapy. In summary, betel-nut exposure did not notably affect PD-L1 expression rates in R/M HNSCC patients in Taiwan.

Relaxation of the electro-optic response in thin-film lithium niobate modulators.

Thin-film lithium niobate (TFLN) is a promising electro-optic (EO) photonics platform with high modulation bandwidth, low drive voltage, and low optical loss. However, EO modulation in TFLN is known to relax on long timescales. Instead, thermo-optic heaters are often used for stable biasing, but heaters incur challenges with cross-talk, high power, and low bandwidth. Here, we characterize the low-frequency (1 mHz to 1 MHz) EO response of TFLN modulators, investigate the root cause of EO relaxation and demonstrate methods to improve bias stability. We show that relaxation-related effects can enhance EO modulation across a frequency band spanning 1kHz to 20kHz in our devices - a counter-intuitive result that can confound measurement of half-wave voltage (V π) in TFLN modulators. We also show that EO relaxation can be slowed by more than 104-fold through control of the LN-metal interface and annealing, offering progress toward lifetime-stable EO biasing. Such robust EO biasing would enable applications for TFLN devices where cross-talk, power, and bias bandwidth are critical, such as quantum devices, high-density integrated photonics, and communications.

Contextual factors influencing the association between the Affordable Care Act's Medicaid expansion and Veteran VA-Medicaid dual enrollment.

OBJECTIVE: To evaluate changes in dual enrollment after Affordable Care Act Medicaid expansion by VA priority group, (e.g., service connection), sex, and type of state expansion. STUDY SETTING: Our cohort was all Veterans ages 18-64 enrolled in VA and eligible for benefits due to military service-connection or low income from 2011 to 2016; the unit of analysis was person-year. STUDY DESIGN: Difference-in-difference and event-study analysis. The outcome was dual VA-Medicaid enrollment for at least 1 month annually. Medicaid expansion, VA priority status, whether a state expanded by a Section 1115 waiver, and sex were independent variables. We controlled for race, ethnicity, age, disease burden, distance to VA facilities, state, and year. DATA EXTRACTION METHODS: We used data from the VA Corporate Data Warehouse (CDW) regarding age and VA Priority Group to select our cohort of VA-enrolled individuals. We then took the cohort and crossed checked it with Medicaid Analytic Extract (MAX) and T-MSIS Analytic Files (TAF) to determine Medicaid enrollment status. PRINCIPAL FINDINGS: Service-connected Veterans experienced lower dual-enrollment increases across all sex and state-waiver groups (3.44 percentage points (95% CI: 1.83, 5.05 pp) for women, 3.93 pp (2.98, 4.98) for men, 4.06 pp (2.85, 5.27) for non-waiver states, and 3.00 pp (1.58 to 4.41) for waiver states) than Veterans who enrolled in the VA due to low income (8.19 pp (5.43, 10.95) for women, 9.80 pp (7.06, 12.54) for men, 10.21 pp (7.17, 13.25) for non-waiver states, and 7.39 pp (5.28, 9.50) for waiver states). CONCLUSIONS: Medicaid expansion is associated with dual enrollment. Dual-enrollment changes are greatest in those enrolled in the VA due to low income, but do not differ by sex or expansion type. Results can help VA identify groups disproportionately likely to have potential care-coordination issues due to usage of multiple health care systems.

Foodborne pathogen inactivation in fruit juices utilizing commercial scale high-pressure processing: Effects of acidulants and pH.

The effects of juice pH, type of acidulant, and post-treatment refrigeration on the high-pressure processing (HPP) inactivation of Escherichia coli O157:H7, Salmonella enterica, and Listeria monocytogenes in acid beverages were evaluated. Inoculated apple, orange, and grape juices (at their original pH and adjusted to pH 4.00, 4.50, and 5.00) were treated at 550 MPa for 1 min at 5 °C. In addition, inoculated model solutions acidified to a pH of 5.00 with acetic, citric, malic, and tartaric acids were treated at 400 MPa for 1 min at 5 °C. The effect of refrigerated storage for 24 h after treatment on pathogen inactivation in both experiments was also assessed. A greater than 5-log reduction of the three pathogens inoculated was achieved in all juices immediately after HPP at the juices' original pH, and of L. monocytogenes under all experimental conditions. Refrigerated storage for 24 h after HPP treatment improved the inactivation of E. coli O157:H7, to >5-log reduction, at pH 4.00 in apple juice and of Salmonella in the three juices at pH 4.00. The type of acidulant did not significantly (p > 0.01) affect E. coli or Salmonella inactivation in acidified model solutions but a greater than 5-log reduction after HPP was only achieved for L. monocytogenes when acetic acid was used. The effectiveness of HPP for pathogen inactivation depended largely on product pH and the target pathogen of concern.

Treatment Patterns and Health Resource Utilization in Patients With HR+/ HER2- Locally Advanced or Metastatic Breast Cancer in a Real-World Setting in Taiwan.

OBJECTIVES: This study aimed to understand current treatment patterns and healthcare resource utilization (HRU) of women with locally advanced or metastatic breast cancer (advanced breast cancer [ABC]) in Taiwan overall and within the subgroup of patients who were postmenopausal women with no previous systemic therapy in the ABC setting. METHODS: A chart review of anonymized data on patient characteristics, treatment patterns, and HRU was conducted via an online physician survey including 118 patient charts from women ≥ 18 years old with hormone receptor positive/human epidermal growth receptor negative ABC, diagnosed between 2015 and 2017. RESULTS: The mean age of all patients was 56.6 years (range 29-83). Among the 118 patients, the most common first-line systemic therapy group after diagnosis of ABC was endocrine-based therapy (39.0%) or endocrine therapy (ET) plus chemotherapy (ChT) combinations (38.1%). In the postmenopausal subgroup (n = 56), ET-based therapy was the most common (44.6%). Oncologist visits, at annual rate of 9.20 (95% confidence interval 8.81-9.60), and hospitalizations, at annual rate of 1.08 (95% confidence interval 0.96-1.22), were key drivers of HRU. Of the 118 patients, the 72 with at least one ChT agent in their first-line regimen had an annual hospitalization rate of 1.4 versus 0.45 admissions compared with the 46 patients on first-line ET-based therapy. CONCLUSIONS: Current treatment patterns suggest an unmet need for new medications that lead to reduction in high rate of ChT use. Results can inform future evaluations of new ABC treatments that estimate the health economic impact of their adoption in Taiwan.

Integrated femtosecond pulse generator on thin-film lithium niobate.

Integrated femtosecond pulse and frequency comb sources are critical components for a wide range of applications, including optical atomic clocks1, microwave photonics2, spectroscopy3, optical wave synthesis4, frequency conversion5, communications6, lidar7, optical computing8 and astronomy9. The leading approaches for on-chip pulse generation rely on mode-locking inside microresonators with either third-order nonlinearity10 or with semiconductor gain11,12. These approaches, however, are limited in noise performance, wavelength and repetition rate tunability 10,13. Alternatively, subpicosecond pulses can be synthesized without mode-locking, by modulating a continuous-wave single-frequency laser using electro-optic modulators1,14-17. Here we demonstrate a chip-scale femtosecond pulse source implemented on an integrated lithium niobate photonic platform18, using cascaded low-loss electro-optic amplitude and phase modulators and chirped Bragg grating, forming a time-lens system19. The device is driven by a continuous-wave distributed feedback laser chip and controlled by a single continuous-wave microwave source without the need for any stabilization or locking. We measure femtosecond pulse trains (520-femtosecond duration) with a 30-gigahertz repetition rate, flat-top optical spectra with a 10-decibel optical bandwidth of 12.6 nanometres, individual comb-line powers above 0.1 milliwatts, and pulse energies of 0.54 picojoules. Our results represent a tunable, robust and low-cost integrated pulsed light source with continuous-wave-to-pulse conversion efficiencies an order of magnitude higher than those achieved with previous integrated sources. Our pulse generator may find applications in fields such as ultrafast optical measurement19,20 or networks of distributed quantum computers21,22.

Mirror-induced reflection in the frequency domain.

Mirrors are ubiquitous in optics and are used to control the propagation of optical signals in space. Here we propose and demonstrate frequency domain mirrors that provide reflections of the optical energy in a frequency synthetic dimension, using electro-optic modulation. First, we theoretically explore the concept of frequency mirrors with the investigation of propagation loss, and reflectivity in the frequency domain. Next, we explore the mirror formed through polarization mode-splitting in a thin-film lithium niobate micro-resonator. By exciting the Bloch waves of the synthetic frequency crystal with different wave vectors, we show various states formed by the interference between forward propagating and reflected waves. Finally, we expand on this idea, and generate tunable frequency mirrors as well as demonstrate trapped states formed by these mirrors using coupled lithium niobate micro-resonators. The ability to control the flow of light in the frequency domain could enable a wide range of applications, including the study of random walks, boson sampling, frequency comb sources, optical computation, and topological photonics. Furthermore, demonstration of optical elements such as cavities, lasers, and photonic crystals in the frequency domain, may be possible.

Second-line treatment of advanced hepatocellular carcinoma: Time for more individualized treatment options?

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease. It is an aggressive disease that often progresses rapidly when it fails to respond to treatment. As such, patients have limited opportunities to try different subsequent-line treatment regimens. In the last 5 years, the number of agents and/or regimens available for the treatment of advanced HCC has significantly increased, which has made treatment choices for this patient population increasingly complex. In the second-line setting, several phase III trials of regorafenib (RESORCE), ramucirumab (REACH/REACH-2), and cabozantinib (CELESTIAL) have demonstrated clinically meaningful survival benefits in patients with the disease. However, the median overall survival of patients with advanced HCC remains unchanged at approximately 12 mo from the start of systemic second-line therapy, with a limited duration of response. Evidence from the REACH/REACH-2 trials demonstrated for the first time that baseline alpha-fetoprotein (AFP) levels can be used as an identification factor to select those who are likely to benefit the most from ramucirumab treatment. Ramucirumab is both well tolerated and efficacious and has a clinically acceptable safety profile. Therefore, it should be considered an option for patients with AFP levels ≥ 400 ng/mL.

Treatment Patterns and Health Resource Utilization in Patients With Hepatocellular Carcinoma After Failure of Sorafenib in Real-World Setting in Taiwan.

OBJECTIVES: This study aimed to characterize current treatment patterns and healthcare resource utilization (HRU) observed among patients with hepatocellular carcinoma (HCC) after the failure of sorafenib in real-world setting in Taiwan. METHODS: A chart review was conducted in 130 patients; the inclusion criteria were patients with HCC who were aged 20 years or older and had received systemic therapy or best supportive care after failure of first-line systemic treatment with sorafenib between 2016 and 2018. Anonymized data on patient characteristics, treatment pathways, and survival were abstracted. RESULTS: The mean age of patients was 61.7 years (range 27-84); of these 130 patients, 103 (79%) were male, 81 (62%) had high alpha-fetoprotein (AFP) levels (≥400 ng/mL), and 96 (78.0%) were deceased at the time of data abstraction. After sorafenib therapy, 60 patients (46%) received systemic therapy, including nivolumab monotherapy (42%) and chemotherapy (25%). Oncologist visits at a semiannual per-patient rate of 3.7 (95% confidence interval [CI] 3.4-4.0) and hospitalizations at rate of 1.1 (95% CI 1.0-1.3) were the key contributors to HRU. Semiannual per-patient hospitalization rate was 1.3 (95% CI 1.1-1.5) in the high-AFP group. Median survival from discontinuation of sorafenib was 6.9 months (95% CI 5.9-9.0). CONCLUSIONS: This real-world evidence research on treatment patterns reflected substantial HRU consistent with the severity of HCC, particularly in the high-AFP group. Findings highlighted continuing high mortality in HCC, underlying a need for new treatments that can lengthen survival. Results can inform future evaluations of new HCC treatments that estimate the health economic impact of their adoption in Taiwan.

Patient Perspectives on Health-Related Quality of Life in Diffuse Large B-Cell Lymphoma Treated with Car T-Cell Therapy: A Qualitative Study.

INTRODUCTION: Chimeric antigen receptor T-cell (CAR T) therapy offers a potentially curative option for patients with relapsed and refractory hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL). Patient-reported experiences with CAR T therapy are limited and have not been well characterized. The purpose of this qualitative study was to explore patient descriptions of key domains of health-related quality of life (HRQoL) in DLBCL patients treated with CAR T therapy. METHODS: A targeted literature review was initially conducted to inform the development of the interview guide comprising predetermined open-ended questions. Two focus groups were conducted with a total of 18 patients with DLBCL identified from patient advisory boards. Focus group sessions were recorded and transcribed verbatim. MAXQDA 18.2.0 qualitative data analysis software was utilized to facilitate a constant-comparative coding process to identify key concepts. RESULTS: Eight domain impairments (social functioning, emotional functioning, fatigue, physical functioning, cognitive functioning, role functioning, sleep, and pain/discomfort) were identified from the qualitative analysis and endorsed by DLBCL patients treated with CAR T. Compared with before CAR T therapy, patients reported increased impairment in every domain during or immediately after CAR T therapy. This impairment improved for each domain 6 months after CAR T therapy except for pain/discomfort. Compared with before CAR T therapy, improvement in impairment for each domain was observed 6 months after CAR T therapy except for fatigue, sleep, and pain/discomfort. CONCLUSION: This study provides meaningful information regarding the impact of CAR T therapy on HRQoL in patients with DLBCL throughout their treatment journey. Health care professionals and investigators can utilize these data in examining existing patient-reported outcome (PRO) measures that are used in DLBCL clinical trials and to better understand the needs of DLBCL survivors.

An Overview of the Treatment Efficacy and Side Effect Profile of Pharmacological Therapies in Asian Patients with Breast Cancer.

Breast cancer (BC) among Asians accounts for ~ 40% of the global BC burden. Differences in BC risk, presentation, tumor biology, and response to treatment exist between Asian and non-Asian patients; however, Asian patients are often under-represented in clinical trials. This narrative review summarizes the efficacy and safety of pharmacological therapies for BC in Asian populations, with a focus on outcomes in Asian versus non-Asian patients treated with chemotherapy, hormone therapy, anti-human epidermal growth factor receptor-2 targeted therapies, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, mammalian target of rapamycin inhibitors, bone-targeted therapies, poly-ADP ribose polymerase, phosphoinositide 3-kinase, and checkpoint inhibitors. While most therapies have demonstrated comparable efficacy and safety in Asian and non-Asian patients with BC, differences that are largely attributed to pharmacogenetic variations between populations exist. Pharmacogenetic differences may contribute to a reduced clinical benefit of tamoxifen, whereas improved clinical outcomes have been reported with tyrosine kinase inhibitors and CDK4/6 inhibitors in Asian versus non-Asian patients with BC. In particular, Asian patients have an increased incidence of hematological toxicities, including neutropenia, although adverse events can be effectively managed using dose adjustments. Recent trials with CDK4/6 inhibitors have increased efforts to include Asians within study subsets. Future clinical trials enrolling higher numbers of Asian patients, and an increased understanding of differences in patient and tumor genetics between Asians and non-Asians, have the potential to incrementally improve the management of BC in Asian patients.

How May Ramucirumab Help Improve Treatment Outcome for Patients with Gastrointestinal Cancers?

GI cancers are characterized by high recurrence rates and a dismal prognosis and there is an urgent need for new therapeutic approaches. This is a narrative review designed to provide a summary of the efficacy as measured by overall survival, progression free survival, and safety data from phase 3 randomized controlled GI clinical trials of ramucirumab including those from important pre-specified patient subgroups and evidence from real clinical practice worldwide. Quality of life (QOL) is discussed where data are available. Our aim was to summarize the efficacy and safety of ramucirumab in the treatment of GI cancers using these existing published data with a view to demonstrating how ramucirumab may help improve treatment outcome for patients with GI cancers. The data indicate that ramucirumab is efficacious, safe, and tolerable across the intent-to-treat patient populations as a whole and across several pre-specified subgroups, even those whose disease is traditionally more difficult to treat. Furthermore, survival outcomes observed in real-world clinical practice demonstrate similar data from phase 3 clinical trials even in patients with complications, suggesting that the benefits of ramucirumab translate in actual clinical practice.

Efficacy and Safety of Ramucirumab in Asian and Non-Asian Patients with Advanced Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Individual Data Analysis of Two Randomized Studies.

OBJECTIVE: REACH-2 and REACH were randomized, placebo-controlled, double-blind, multicenter phase 3 trials which showed survival benefits of ramucirumab treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP). We evaluated the efficacy and safety of ramucirumab in Asian and non-Asian patients with AFP ≥400 ng/mL from REACH-2 and REACH. METHODS: We pooled Asian and non-Asian patients from the REACH-2 and REACH trials and performed an individual patient data meta-analysis. Overall survival (OS) and progression-free survival were evaluated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated with a stratified Cox regression model. RESULTS: In the pooled REACH-2 and REACH patient population, 291 Asian patients were randomly assigned to receive ramucirumab (n = 168) or placebo (n = 123), and 251 non-Asian patients received ramucirumab (n = 148) or placebo (n = 103). The median OS was significantly longer in the ramucirumab arm in comparison to the placebo arm for Asian patients (8.08 vs. 4.76 months, stratified HR 0.73 [95% CI 0.56-0.95], p = 0.0189) and non-Asian patients (7.98 vs. 5.22 months, stratified HR 0.65 [95% CI 0.49-0.86], p = 0.0028). The overall response rate (ORR) and disease control rate (DCR) were significantly higher in the ramucirumab arm compared to the placebo arm for Asian patients (ORR: 4.2 vs. 0.8%; DCR: 53.6 vs. 33.3%) and non-Asian patients (ORR: 6.8 vs. 1.0%; DCR: 59.5 vs. 41.7%). The most common grade ≥3 treatment-emergent adverse events reported in the ramucirumab arm were hypertension (7.7%), decreased appetite (1.2%), and ascites (1.2%) for Asian patients and hypertension (16.9%), ascites (8.8%), asthenia (4.7%), and fatigue (5.4%) for non-Asian patients. DISCUSSION AND CONCLUSION: This pooled analysis of the REACH-2/REACH trials demonstrates significant benefits, with a manageable safety profile, of ramucirumab treatment in Asian and non-Asian patients with advanced HCC and baseline AFP ≥400 ng/mL.

Safety and Preliminary Efficacy of Ramucirumab in Combination with FOLFOX4 in Patients with Advanced Hepatocellular Carcinoma: A Nonrandomized, Open-Label, Phase Ib Study.

LESSONS LEARNED: The combination of ramucirumab (8 mg/kg intravenous, day 1 every 2 weeks) and FOLFOX4 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC) was not sufficiently tolerated. Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with HCC. Dose modification and patient selection should be considered for the future development of ramucirumab plus FOLFOX chemotherapy for advanced HCC. BACKGROUND: The objective of this study was to investigate the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of ramucirumab plus FOLFOX4 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients received ramucirumab (8 mg/kg) intravenously (IV) on day 1, followed by FOLFOX4 (oxaliplatin 85 mg/m2 IV on day 1, folinic acid 200 mg/m2 IV, bolus fluorouracil [5-FU] 400 mg/m2 , and a continuous infusion of 5-FU 600 mg/m2 over 22 hours, on days 1 and 2) every 2 weeks. The primary endpoint was to assess the safety and tolerability of the combination therapy. RESULTS: Eight patients (6 men, 2 women) were treated; all eight patients experienced at least one treatment-emergent adverse event (TEAE) of grade ≥3. Dose-limiting toxicities occurred in three patients (37.5%): hepatic hemorrhage (grade 4), blood bilirubin increased (grade 3), and febrile neutropenia (grade 3). Two patients discontinued study because of hepatic hemorrhage (grade 4) and blood bilirubin increase (grade 3). Six deaths occurred due to progressive disease, and no deaths due to TEAEs. CONCLUSION: There were no unexpected safety findings with ramucirumab plus FOLFOX4 based on the known safety and toxicity of this regimen. The combination was not sufficiently tolerated in patients with advanced HCC at the specified dose and schedule.

Does Pemetrexed Work in Targetable, Nonsquamous Non-Small-Cell Lung Cancer? A Narrative Review.

Pemetrexed is currently mainly considered for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) negative for gene mutations/rearrangements (wild-type disease (WTD)). This narrative review aimed to highlight the role of pemetrexed in the treatment of onco-driven nonsquamous advanced NSCLC by reviewing published clinical studies. For epidermal growth factor receptor (EGFR) mutations, patient survival following first-line pemetrexed-platinum was longer than for WTD. Later-line pemetrexed-based treatment after tyrosine kinase inhibitor (TKI) failure provided greater benefits than non-pemetrexed regimens. First- and later-line pemetrexed-based therapy also provided survival benefits in patients with anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearrangements. In patients with rearranged during transfection (RET) proto-oncogene rearrangements, survival with pemetrexed was similar to that in ALK- and ROS1-positive patients and longer than that in patients with Kirsten rat sarcoma (KRAS) virus proto-oncogene mutations or WTD, although the available studies were limited. For Erb-b2 receptor tyrosine kinase 2 (ERRB2) mutations, first-line pemetrexed showed outcomes similar to those for EGFR and KRAS alterations. Data on pemetrexed in patients with KRAS mutations or MNNG HOS-transforming (MET) expression were limited. Pemetrexed could be an option for first- and second-line treatment for TKI failure in nonsquamous advanced NSCLC with select targetable driver mutations.

Raman lasing and soliton mode-locking in lithium niobate microresonators.

The recent advancement in lithium-niobite-on-insulator (LNOI) technology is opening up new opportunities in optoelectronics, as devices with better performance, lower power consumption and a smaller footprint can be realised due to the high optical confinement in the structures. The LNOI platform offers both large χ (2) and χ (3) nonlinearities along with the power of dispersion engineering, enabling brand new nonlinear photonic devices and applications for the next generation of integrated photonic circuits. However, Raman scattering and its interaction with other nonlinear processes have not been extensively studied in dispersion-engineered LNOI nanodevices. In this work, we characterise the Raman radiation spectra in a monolithic lithium niobate (LN) microresonator via selective excitation of Raman-active phonon modes. The dominant mode for the Raman oscillation is observed in the backward direction for a continuous-wave pump threshold power of 20 mW with a high differential quantum efficiency of 46%. We explore the effects of Raman scattering on Kerr optical frequency comb generation. We achieve mode-locked states in an X-cut LNOI chip through sufficient suppression of the Raman effect via cavity geometry control. Our analysis of the Raman effect provides guidance for the development of future chip-based photonic devices on the LNOI platform.

Ramucirumab in the second-line treatment of metastatic colorectal cancer: a narrative review of literature from clinical trials.

The development of new anti-angiogenic agents targeting the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor pathways has greatly expanded the therapeutic options for patients with metastatic colorectal cancer (mCRC). Although these new agents have considerably improved survival outcomes compared with conventional chemotherapeutic regimens, the optimal integration of these drugs into the management of patients with mCRC continues to develop. One particular challenge is the identification of patient subgroups that will benefit from treatment with a specific targeted agent. In RAISE, a phase III randomized, placebo-controlled clinical trial, the VEGF receptor 2 antagonist ramucirumab in combination with fluorouracil plus leucovorin and irinotecan demonstrated efficacy as a second-line treatment for patients with mCRC. Ramucirumab is approved for the treatment of patients with mCRC in Taiwan but, due to lack of reimbursement, is often reserved for use as a third-line or later treatment. This narrative review of prespecified and post-hoc analyses of the RAISE study data, and data from other ramucirumab trials and real-world studies, summarizes the efficacy and tolerability of ramucirumab in the second-line treatment of different subpopulations of patients with mCRC. The aim was to identify patients most likely to benefit from treatment with second-line ramucirumab, with a view to illustrating the potential benefit of integrating this regimen into Taiwanese or Asian treatment practice.

The combined effect of high pressure processing and dimethyl dicarbonate to inactivate foodborne pathogens in apple juice.

Novel processing technologies can be used to improve both the microbiological safety and quality of food products. The application of high pressure processing (HPP) in combination with dimethyl dicarbonate (DMDC) represents a promising alternative to classical thermal technologies. This research work was undertaken to investigate the combined effect of HPP and DMDC, which was aimed at reaching over 5-log reduction in the reference pathogens Escherichia coli O157:H7, Salmonella enterica, and Listeria monocytogenes inoculated in apple juice. Different strains of each species were tested. The pressure (ranging from 100 to 600 MPa), dwell time (from 26 to 194 s), and DMDC (from 116 to 250 mg/L) were tested based on a central composite rotatable design. The dwell time, in the studied range, did not have a significant effect (p > 0.1) on the pathogens´ reduction. All treatments achieved a greater than 5-log reduction for E. coli O157:H7 and L. monocytogenes. The reductions for S. enterica were also greater than 5-log for almost all tested combinations. The results for S. enterica suggested that it is more resistant to HPP and DMDC compared with E. coli O157:H7 and L. monocytogenes. The findings of this study showed that DMDC at low concentrations can be added to apple juice to reduce the parameters conventionally applied in HPP. The combined use of HPP and DMDC was highly effective under the conditions of this study.

Is ramucirumab and paclitaxel therapy beneficial for second-line treatment of metastatic gastric or junctional adenocarcinoma for patients with ascites? Analysis of RAINBOW phase 3 trial data.

PURPOSE: Second-line treatment with ramucirumab-paclitaxel has demonstrated statistically significant and clinically meaningful survival outcomes compared to paclitaxel-alone in patients with advanced gastric cancer (HR=0.807, 95% CI 0.678-0.962; P=0.017). Post hoc, exploratory analyses of RAINBOW patient data were performed to examine whether ascites impacted the efficacy and safety of ramucirumab-paclitaxel. PATIENTS AND METHODS: Patients were placed in with- or without-ascites subgroups based on baseline information collected on case report forms. The Kaplan-Meier method was used to estimate median progression-free survival (PFS) and overall survival (OS) of the ascites subgroups. HR and 95% CI were calculated using the Cox proportional hazards model. Survival distributions within the two arms in each ascites subgroup were compared using the log-rank test. RESULTS: There were 36% of RAINBOW trial patients (237/665) that had ascites at baseline (with-ascites subgroup); 64% of patients (428/665) had no baseline ascites (without-ascites subgroup). Most baseline characteristics were balanced. The with-ascites subgroup had a higher percentage of patients with peritoneal metastases (91% vs 23%) as expected. Overall survival for the with-ascites subgroup was worse than for the without-ascites subgroup (median OS for placebo-treated patients: 5.2 vs 8.5 months, respectively). However, OS treatment effects did not seem to differ significantly among patients with ascites (OS stratified HR=0.864, 95% CI=0.644-1.161; P=0.3362) vs those without ascites (OS stratified HR=0.745, 95% CI=0.593-0.936; P=0.0115). Similar results were observed for PFS. Ramucirumab treatment was associated with a greater incidence of all-grade vomiting for the with-ascites subgroup vs the without-ascites subgroup (ramucirumab arm: 39.2% vs 18.8%; placebo arm: 23.3% vs 19.5%, respectively). The incidence of adverse events of special interest was not elevated among the ramucirumab-treated ascites subgroup over the without-ascites subgroup. CONCLUSION: The benefit/risk profile of ramucirumab-paclitaxel remains favorable in patients with ascites and is consistent with the findings of the RAINBOW trial.