Clinical validation of an immunochromatographic SARS-Cov-2 IgM/IgG antibody assay with Japanese cohort.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a major health threat. To overcome COVID-19, appropriate diagnosis methods are urgently needed. The aim of this study was to clinically evaluate the colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG antibody (Ab). METHODS: Patients confirmed COVID-19 (n = 51) were recruited prospectively from the Musashino Red Cross hospital and Tokyo Medical and Dental University Medical Hospital, between March and May 2020. And the analytical specificity was assessed with serum samples of patients without COVID-19 (n = 100) collected between August to September 2019 before SARS-CoV-2 was first reported in China. RESULTS: Among COVID-19 patients, a total of 87 serum samples were tested for SARS-Cov-2 IgM/IgG Ab assay. IgM was detected 71.0 %, 86.9 %, and 83.3 % at day8-14, 15-28, >29 after symptom onset and IgG was detected in 81.6 %, 87.0 %, and 94.4 %, respectively. The sensitivity of IgM and IgG Ab after day8 assay was significantly higher than before day7, respectively (p=0.0016, 0.0003). There were no positive results in 100 serum samples from patients without COVID-19. CONCLUSION: The SARS-Cov-2 IgM/IgG Ab assay had 79.7% / 86.1% sensitivity (the 8 days after from onset) and 100% specificity in this population.

Generation of vector polarization in a Nd:YAG laser.

We demonstrated the generation of an azimuthally and radially polarized laser beam in a Nd:YAG laser in which a birefringent yttrium vanadate (c-cut YVO4) crystal was used as the intra-cavity polarization discriminator. AP and RP with respective output 2.4W (o-o efficiency of 35.4%, M2 = 2.3) and 2.52W (o-o efficiency of 37.2%, M2 = 2.4) were generated at absorbed pump power 6.78W. We discuss a simple method for converting between azimuthal and radial polarizations by only regulating input pump power and mechanism of mode selection in the laser. This vector laser will facilitate many applications.

Thin-rod Yb:YAG amplifiers for high average and peak power lasers.

The concept of a high-power thin-rod Yb:YAG laser amplifier with high-brightness diode pumping was proposed. The principle of the amplifier parameter variation aimed at achieving an efficient signal gain at different power levels was developed. Three versions of thin-rod gain modules were implemented, where small and strong signal gains were studied experimentally. The ultrafast laser system with high average power (28 W) and high pulse energy (2.5 mJ) was created on the basis of the unique thin-rod gain modules.

Interstate Migration and Employer-to-Employer Transitions in the United States: New Evidence From Administrative Records Data.

Declines in migration across labor markets have prompted concerns that the U.S. economy is becoming less dynamic. In this study, we examine the relationship between residential migration and employer-to-employer transitions in the United States, using both survey and administrative records data. We first note strong disagreement between the Current Population Survey (CPS) and other migration statistics on the timing and severity of any decline in U.S. interstate migration. Despite these divergent patterns for overall residential migration, we find consistent evidence of a substantial decline in economic migration between 2000 and 2010. We find that composition and the returns to migration have limited ability to explain recent changes in interstate migration.

Yb3+-doped CaF2-LaF3 ceramics laser.

Highly transparent ceramic is an attractive gain medium for high-power lasers due to its high fracture toughness, homogeneity, and size scalability. Here we report the first Yb3+-doped CaF2-LaF3 ceramics laser. Codoping of La3+ ion can reduce the formation of Yb2+ ions and enhance the laser efficiency. In the laser experiment, the maximum output power of 4.36 W and the maximum slope efficiency of 69.5% were obtained with a 3% La, 2% Yb sample and a 2% La, 1% Yb sample, respectively. Due to the combined properties of Yb:CaF2 and a ceramic laser gain medium, Yb:CaF2-LaF3 ceramic is a promising gain medium for a high-power ultrashort pulse laser and amplifier.

Thin-tapered-rod Yb:YAG laser amplifier.

The concept of the thin-tapered-rod Yb:YAG amplifier with waveguide pumping is proposed and implemented. It is shown that such an amplifier demonstrates considerably higher small signal gain and is less affected by thermal effects than the thin-rod ("single-crystal fiber") amplifier. In the developed amplifier, a small signal gain as high as 23 per pass is achieved.

Multi-wavelength Yb:YAG/Nd3+:YVO4 continuous-wave microchip Raman laser.

Multi-wavelength continuous-wave (CW) Raman lasers in a laser diode pumped Yb:YAG/Nd3+:YVO4 microchip Raman laser have been demonstrated for the first time to our best knowledge. The multi-wavelength laser of the first Stokes radiation around 1.08 µm has been achieved with a Raman shift of 261 cm-1 for a-cut Nd:YVO4 crystal corresponding to the fundamental wavelength at 1.05 µm. Multi-wavelength laser operation simultaneously around 1.05 and 1.08 µm has been achieved under the incident pump power between 1.5 and 1.7 W. Multi-wavelength Raman laser with frequency separation of 1 THz around 1.08 µm has been obtained when the incident pump power is higher than 1.7 W. The maximum Raman laser output power of 260 mW at 1.08 µm is obtained and the corresponding optical-to-optical conversion efficiency is 4.2%. Elliptically polarized fundamental laser and linearly polarized Raman laser were observed in an Yb:YAG/Nd:YVO4 CW microchip Raman laser. The experimental results of linearly polarized, multi-wavelength Yb:YAG/Nd:YVO4 CW microchip Raman laser with adjustable frequency separation provide a novel approach for developing potential compact laser sources for Terahertz generation.

Submillisievert CT using model-based iterative reconstruction with lung-specific setting: An initial phantom study.

OBJECTIVE: To assess image quality of filtered back-projection (FBP) and model-based iterative reconstruction (MBIR) with a conventional setting and a new lung-specific setting on submillisievert CT. METHODS: A lung phantom with artificial nodules was scanned with 10 mA at 120 kVp and 80 kVp (0.14 mSv and 0.05 mSv, respectively); images were reconstructed using FBP and MBIR with conventional setting (MBIRStnd) and lung-specific settings (MBIRRP20/Tx and MBIRRP20). Three observers subjectively scored overall image quality and image findings on a 5-point scale (1 = worst, 5 = best) compared with reference standard images (50 mA-FBP at 120, 100, 80 kVp). Image noise was measured objectively. RESULTS: MBIRRP20/Tx performed significantly better than MBIRStnd for overall image quality in 80-kVp images (p < 0.01), blurring of the border between lung and chest wall in 120p-kVp images (p < 0.05) and the ventral area of 80-kVp images (p < 0.001), and clarity of small vessels in the ventral area of 80-kVp images (p = 0.037). At 120 kVp, 10 mA-MBIRRP20 and 10 mA-MBIRRP20/Tx showed similar performance to 50 mA-FBP. MBIRStnd was better for noise reduction. Except for blurring in 120 kVp-MBIRStnd, MBIRs performed better than FBP. CONCLUSION: Although a conventional setting was advantageous in noise reduction, a lung-specific setting can provide more appropriate image quality, even on submillisievert CT. KEY POINTS: • Lung-specific submillisievert 10 mA-MBIR CT setting has similar performance to 50 mA-FBP • The new lung-specific settings improve vessel clarity and blurring of borders • The new settings may provide more appropriate images than conventional settings.

Thermal effects in Yb:YAG single-crystal thin-rod amplifier.

This work presents a new design for the laser gain module based on a ytterbium-doped yttrium aluminum garnet (Yb:YAG) single-crystal thin rod. Thermal effects (temperature, phase, and polarization distortion of laser radiation) and small signal gain are investigated both experimentally and theoretically. We then analyzed the influence of thermal effects and amplified spontaneous emission on the power scaling of the laser based on the gain module. A small signal gain as high as 3.3 per pass was experimentally achieved.

Changes in plasma vascular endothelial growth factor at 8 weeks after sorafenib administration as predictors of survival for advanced hepatocellular carcinoma.

BACKGROUND: A new predictive biomarker for determining prognosis in patients with hepatocellular carcinoma (HCC) who receive sorafenib is required, because achieving a reduction in tumor size with sorafenib is rare, even in patients who have a favorable prognosis. Vascular endothelial growth factor (VEGF) receptor is a sorafenib target. In the current study, the authors examined changes in plasma VEGF concentrations during sorafenib treatment and determined the clinical significance of VEGF as a prognostic indicator in patients with HCC. METHODS: Plasma VEGF concentrations were serially measured in 63 patients with advanced HCC before and during sorafenib treatment. A plasma VEGF concentration that decreased >5% from the pretreatment level at 8 weeks was defined as a "VEGF decrease." An objective tumor response was determined using modified Response Evaluation Criteria in Solid Tumors 1 month after the initiation of therapy and every 3 months thereafter. RESULTS: Patients who had a VEGF decrease at week 8 (n=14) had a longer median survival than those who did not have a VEGF decrease (n=49; 30.9 months vs 14.4 months; P=.038). All patients who had a VEGF decrease survived for >6 months, and the patients who had both a VEGF decrease and an α-fetoprotein response (n=6) survived during the observation period (median, 19.7 months; range, 6.5-31.0 months). In univariate analyses, a VEGF decrease, radiologic findings classified as progressive disease, and major vascular invasion were associated significantly with 1-year survival; and, in multivariate analysis, a VEGF decrease was identified as an independent factor associated significantly with survival. CONCLUSIONS: A plasma VEGF concentration decrease at 8 weeks after starting sorafenib treatment may predict favorable overall survival in patients with advanced HCC.

Prognostic importance of volumetric measurements in stage I lung adenocarcinoma.

PURPOSE: To perform volumetric analysis of stage I lung adenocarcinomas by using an automated computer program and to determine value of volumetric computed tomographic (CT) measurements associated with prognostic factors and outcome. MATERIALS AND METHODS: Consecutive patients (n = 145) with stage I lung adenocarcinoma who underwent surgery after preoperative chest CT were enrolled. By using volumetric automated computer-assisted analytic program, nodules were classified into three subgroups: pure ground glass, part solid, or solid. Total tumor volume, solid tumor volume, and percentage of solid volume of each cancer were calculated after eliminating vessel components. One radiologist measured the longest diameter of the solid tumor component and of total tumor with their ratio, which was defined as solid proportion. The value of these quantitative data by examining associations with pathologic prognostic factors and outcome measures (disease-free survival and overall survival) were analyzed with logistic regression and Cox proportional hazards regression models, respectively. Significant parameters identified at univariate analysis were included in the multiple analyses. RESULTS: All 22 recurrences occurred in patients with nodules classified as part solid or solid. Multiple logistic regression analysis revealed that percentage of solid volume of 63% or greater was an independent indicator associated with pleural invasion (P = .01). Multiple Cox proportional hazards regression analysis revealed that percentage of solid volume of 63% or greater was a significant indicator of lower disease-free survival (hazard ratio, 18.45 [95% confidence interval: 4.34, 78.49]; P < .001). Both solid tumor volume of 1.5 cm(3) or greater and percentage of solid volume of 63% or greater were significant indicators of decreased overall survival (hazard ratio, 5.92 and 9.60, respectively [95% confidence interval: 1.17, 30.33 and 1.17, 78.91, respectively]; P = .034 and .036, respectively). CONCLUSION: Two volumetric measurements (solid volume, ≥1.5 cm(3); percentage of solid volume, ≥63%) were found to be independent indicators associated with increased likelihood of recurrence and/or death in patients with stage I adenocarcinoma.

Risk factors for exceeding the Milan criteria after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma.

Radiofrequency ablation (RFA) is an effective and safe noninvasive treatment for hepatocellular carcinoma (HCC) and may be useful as a bridging therapy in liver transplantation. The prognosis after liver transplantation for patients within the Milan criteria is excellent. This study was aimed at identifying risk factors associated with exceeding the Milan criteria after initial locally curative RFA therapy. Among 554 primary HCC patients, 323 with early-stage HCC after RFA were analyzed (mean age = 66 years). Two hundred forty-eight patients had hepatitis C virus, 33 patients had hepatitis B virus, and 41 patients had neither hepatitis B nor hepatitis C; 256, 67, and 0 patients were classified as Child-Pugh A, B, and C, respectively. The rates of cumulative overall survival and recurrence exceeding the Milan criteria were analyzed with Kaplan-Meier analysis, and factors associated with overall survival were determined with Cox proportional hazards analysis. The cumulative overall survival rates at 1, 3, 5, and 10 years were 96.2%, 84.4%, 69.9%, and 40.6% respectively, without liver transplantation. The cumulative rates of recurrence exceeding the Milan criteria at 1, 3, and 5 years were 15.1%, 46.0%, and 61.1% respectively. An alpha-fetoprotein (AFP) level > 100 ng/mL and recurrence within 1 year after initial ablation were independently associated with earlier recurrence exceeding the Milan criteria and overall survival. The 3- and 5-year survival rates for patients with both risk factors were 33.5% and 22.6%, respectively, despite an early stage at initial ablation. In conclusion, a higher AFP level and HCC recurrence within 1 year of RFA are risk factors for exceeding the Milan criteria and for overall survival. Early liver transplantation or adjuvant therapy should be considered for patients with both risk factors.

α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C.

UNLABELLED: The effects of interferon (IFN) treatment and the post-IFN treatment α-fetoprotein (AFP) levels on risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) are unknown. To determine the relationship between AFP and alanine transaminase (ALT) levels and HCC risk, a cohort consisting of 1,818 patients histologically proven to have CHC treated with IFN were studied. Cumulative incidence and HCC risk were analyzed over a mean follow-up period of 6.1 years using the Kaplan-Meier method and Cox proportional hazard analysis. HCC developed in 179 study subjects. According to multivariate analysis, older age, male gender, advanced fibrosis, severe steatosis, lower serum albumin levels, non sustained virological response (non-SVR), and higher post-IFN treatment ALT or AFP levels were identified as independent factors significantly associated with HCC development. Cutoff values for ALT and AFP for prediction of future HCC were determined as 40 IU/L and 6.0 ng/mL, respectively, and negative predictive values of these cutoffs were high at 0.960 in each value. The cumulative incidence of HCC was significantly lower in patients whose post-IFN treatment ALT and AFP levels were suppressed to less than the cutoff values even in non-SVR patients. This suppressive effect was also found in patients whose post-IFN treatment ALT and AFP levels were reduced to less than the cutoff values despite abnormal pretreatment levels. CONCLUSION: Post-IFN treatment ALT and AFP levels are significantly associated with hepatocarcinogenesis. Measurement of these values is useful for predicting future HCC risk after IFN treatment. Suppression of these values after IFN therapy reduces HCC risk even in patients without HCV eradication.

1 W single-frequency Tm-doped ZBLAN fiber MOPA around 810 nm.

We demonstrate a tunable narrow-linewidth fiber MOPA system around 810 nm for the light source of the Sr optical lattice clock. The coherent cw light source with a wavelength of 813.42 nm was generated by a combination of a narrow linewidth external-cavity laser diode and a Tm-doped ZBLAN fiber amplifier, which was upconversion-pumped by an Yb-doped fiber laser at 1064 nm. The maximum output power of 1.1 W was obtained with the launched power of 17 W, which is the highest power obtained from a Tm-doped fiber amplifier ever reported.

Demonstration of a Yb3+-doped Lu3Al5O12 ceramic thin-disk laser.

Yb:LuAG ceramic is very promising for thin-disk laser and amplifier architectures since it exhibits a higher thermal conductivity at high doping concentrations and a larger emission cross section than Yb:YAG. In this Letter, we present what we believe to be the first demonstration of a thin-disk laser based on Yb:LuAG ceramic. A maximum output power of 101 W with an optical efficiency of 56% and a slope efficiency of 64% was obtained with a multimode laser resonator. Fundamental-mode laser operation with near diffraction limited beam quality (M2≈1.22) was also achieved. The fundamental-mode laser resonator showed the output power of 49 W, an optical efficiency of 31%, and a slope efficiency of 44%. A linearly polarized output beam was demonstrated in multimode operation using an intracavity Brewster window. The depolarization loss was measured to be as low as 0.15% per round trip.

Reduced organic anion transporter expression is a risk factor for hepatocellular carcinoma in chronic hepatitis C patients: a propensity score matching study.

OBJECTIVES: Recent reports indicated that reduced SLC22A7 (a gene-encoding organic anion transporter 2) expression in noncancerous liver tissue predicts hepatocellular carcinoma (HCC) recurrence after curative resection. Our study aimed to elucidate the association between SLC22A7 expression and HCC development in chronic hepatitis C patients. METHODS: HCC recurrence after local ablation therapy and SLC22A7 expression in noncancerous liver tissue were analyzed in 20 patients. Subsequently, the association between de novo HCC development and SLC22A7 expression was examined at baseline in 38 hepatitis C patients without HCC who subsequently developed HCC as well as in 76 hepatitis C patients who did not develop HCC and were matched for age, gender and stage of fibrosis. RESULTS: In the patients whose HCC had been cured, reduced SLC22A7 expression in noncancerous liver tissue was significantly associated with a high incidence of multifocal HCC recurrence. In patients without HCC at baseline, cumulative incidence of de novo HCC development was significantly higher with a reduced SLC22A7 expression than with a normal expression (p = 0.01). This difference remained significant among patients without known risk factors for HCC like age and advanced fibrosis. CONCLUSION: Reduced SLC22A7 expression in the liver indicates a significant risk for HCC development in chronic hepatitis C, independently of other risk factors.

Prospective comparison of real-time tissue elastography and serum fibrosis markers for the estimation of liver fibrosis in chronic hepatitis C patients.

AIM: Real-time tissue elastography (RTE) is a non-invasive method for the measurement of tissue elasticity using ultrasonography. Liver fibrosis (LF) index is a quantitative method for evaluation of liver fibrosis calculated by RTE image features. This study aimed to investigate the significance of LF index for predicting liver fibrosis in chronic hepatitis C patients. METHODS: In this prospective study, 115 patients with chronic hepatitis C who underwent liver biopsy were included, and the diagnostic accuracy of LF index and serum fibrosis markers was evaluated. RESULTS: RTE imaging was successfully performed on all patients. Median LF index in patients with F0-1, F2, F3 and F4 were 2.61, 3.07, 3.54 and 4.25, respectively, demonstrating a stepwise increase with liver fibrosis progression (P < 0.001). LF index (odds ratio [OR] = 5.3, 95% confidence interval [CI] = 2.2-13.0) and platelet count (OR = 0.78, 95% CI = 0.68-0.89) were independently associated with the presence of advanced fibrosis (F3-4). Further, LF index was independently associated with the presence of minimal fibrosis (F0-1) (OR = 0.25, 95% CI = 0.11-0.55). The area under the receiver-operator curve (AUROC) of LF index for predicting advanced fibrosis (0.84) was superior to platelets (0.82), FIB-4 index (0.80) and aspartate aminotransferase/platelet ratio index (APRI) (0.76). AUROC of LF index (0.81) was superior to platelets (0.73), FIB-4 index (0.79) and APRI (0.78) in predicting minimal fibrosis. CONCLUSION: LF index calculated by RTE is useful for predicting liver fibrosis, and diagnostic accuracy of LF index is superior to serum fibrosis markers.

Impaired brain activity in cirrhotic patients with minimal hepatic encephalopathy: Evaluation by near-infrared spectroscopy.

AIM: Near-infrared spectroscopy (NIRS) is a tool that could non-invasively measure the regional cerebral oxygenated hemoglobin (oxy-Hb) concentration with high time resolution. The aim of the present study is to reveal the time-dependent regional cerebral oxy-Hb concentration change coupled with brain activity during task performance in patients with minimal hepatic encephalopathy (MHE). METHODS: Cerebral oxy-Hb concentration was measured by using NIRS in 29 cirrhotic patients without overt hepatic encephalopathy (HE). Of those, 16 patients who had abnormal electroencephalography findings were defined as having MHE. Responsive increase in oxy-Hb during a word-fluency task was compared between MHE and non-MHE patients. RESULTS: There was no difference in the maximum value of oxy-Hb increase between patients with and without MHE (0.26 ± 0.12 vs 0.32 ± 0.22 mM·mm, P = 0.37). However, the pattern of the time course changes of oxy-Hb was different between the two groups. The MHE group was characterized by a gradual increase of oxy-Hb throughout the task compared to steep and repetitive increase in the non-MHE group. Increase in oxy-Hb concentration at 5 s after starting the task was significantly small in the MHE group compared to the non-MHE (0.03 ± 0.05 vs 0.11 ± 0.09 mM·mm, P = 0.006). CONCLUSION: The cerebral oxygen concentration is poorly reactive in response to tasks among cirrhotic patients without overt HE but having abnormal electroencephalography findings. These impaired responses in regional cerebral oxy-Hb concentration may be related to the latent impairment of brain activity seen in MHE.

Association of gene expression involving innate immunity and genetic variation in interleukin 28B with antiviral response.

UNLABELLED: Innate immunity plays an important role in host antiviral response to hepatitis C viral (HCV) infection. Recently, single nucleotide polymorphisms (SNPs) of IL28B and host response to peginterferon α (PEG-IFNα) and ribavirin (RBV) were shown to be strongly associated. We aimed to determine the gene expression involving innate immunity in IL28B genotypes and elucidate its relation to response to antiviral treatment. We genotyped IL28B SNPs (rs8099917 and rs12979860) in 88 chronic hepatitis C patients treated with PEG-IFNα-2b/RBV and quantified expressions of viral sensors (RIG-I, MDA5, and LGP2), adaptor molecule (IPS-1), related ubiquitin E3-ligase (RNF125), modulators (ISG15 and USP18), and IL28 (IFNλ). Both IL28B SNPs were 100% identical; 54 patients possessed rs8099917 TT/rs12979860 CC (IL28B major patients) and 34 possessed rs8099917 TG/rs12979860 CT (IL28B minor patients). Hepatic expressions of viral sensors and modulators in IL28B minor patients were significantly up-regulated compared with that in IL28B major patients (≈ 3.3-fold, P < 0.001). However, expression of IPS-1 was significantly lower in IL28B minor patients (1.2-fold, P = 0.028). Expressions of viral sensors and modulators were significantly higher in nonvirological responders (NVR) than that in others despite stratification by IL28B genotype (≈ 2.6-fold, P < 0.001). Multivariate and ROC analyses indicated that higher RIG-I and ISG15 expressions and RIG-I/IPS-1 expression ratio were independent factors for NVR. IPS-1 down-regulation in IL28B minor patients was confirmed by western blotting, and the extent of IPS-1 protein cleavage was associated with the variable treatment response. CONCLUSION: Gene expression involving innate immunity is strongly associated with IL28B genotype and response to PEG-IFNα/RBV. Both IL28B minor allele and higher RIG-I and ISG15 expressions and RIG-I/IPS-1 ratio are independent factors for NVR.

Study of the thermo-optical constants of Yb doped Y2O3, Lu2O3 and Sc2O3 ceramic materials.

Thermally induced depolarization and thermal lens of three Konoshima Chemical Co. laser-ceramics samples Yb(3+):Lu(2)O(3)(C(Yb) ≈ 1.8 at.%), Yb(3+):Y(2)O(3)(C(Yb) ≈ 1.8 at.%), and Yb(3+):Sc(2)O(3) (C(Yb) ≈ 2.5 at.%) were measured in experiment at different pump power. The results allowed us to estimate the thermal conductivity of the investigated ceramic samples and compare their thermo-optical properties. The thermo-optical constants P and Q and its sign measured for these materials at the first time.