VR Rates Research Articles

Diagnosis of Forme Fruste Keratoconus Using Corvis ST Sequences with Digital Image Correlation and Machine Learning.

This study aimed to employ the incremental digital image correlation (DIC) method to obtain displacement and strain field data of the cornea from Corvis ST (CVS) sequences and access the performance of embedding these biomechanical data with machine learning models to distinguish forme fruste keratoconus (FFKC) from normal corneas. 100 subjects were categorized into normal (N = 50) and FFKC (N = 50) groups. Image sequences depicting the horizontal cross-section of the human cornea under air puff were captured using the Corvis ST tonometer. The high-speed evolution of full-field corneal displacement, strain, velocity, and strain rate was reconstructed utilizing the incremental DIC approach. Maximum (max-) and average (ave-) values of full-field displacement V, shear strain γxy, velocity VR, and shear strain rate γxyR were determined over time, generating eight evolution curves denoting max-V, max-γxy, max-VR, max-γxyR, ave-V, ave-γxy, ave-VR, and ave-γxyR, respectively. These evolution data were inputted into two machine learning (ML) models, specifically Naïve Bayes (NB) and Random Forest (RF) models, which were subsequently employed to construct a voting classifier. The performance of the models in diagnosing FFKC from normal corneas was compared to existing CVS parameters. The Normal group and the FFKC group each included 50 eyes. The FFKC group did not differ from healthy controls for age (p = 0.26) and gender (p = 0.36) at baseline, but they had significantly lower bIOP (p < 0.001) and thinner central cornea thickness (CCT) (p < 0.001). The results demonstrated that the proposed voting ensemble model yielded the highest performance with an AUC of 1.00, followed by the RF model with an AUC of 0.99. Radius and A2 Time emerged as the best-performing CVS parameters with AUC values of 0.948 and 0.938, respectively. Nonetheless, no existing Corvis ST parameters outperformed the ML models. A progressive enhancement in performance of the ML models was observed with incremental time points during the corneal deformation. This study represents the first instance where displacement and strain data following incremental DIC analysis of Corvis ST images were integrated with machine learning models to effectively differentiate FFKC corneas from normal ones, achieving superior accuracy compared to existing CVS parameters. Considering biomechanical responses of the inner cornea and their temporal pattern changes may significantly improve the early detection of keratoconus.

Increased spine bone density in patients with chronic hepatitis B switched to tenofovir alafenamide: A prospective, multinational study.

Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited. To assess the treatment and renal/bone safety outcomes following the switch to TAF. We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF. We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019). At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable.

Analysis of the application of BIM technology in the combination of interior design and smart home

Abstract This paper aims to explore the application in the combination of interior design and smart homes and constructs an intelligent algorithm of BIM+4D technology by analyzing BIM technology and its application in interior home design. The mathematical relationship of design duration is established on the basis of BIM+4D. Studied the system of BIM+ in interior home design and set up the standard and template of the interior home. The BIM+4D technology intelligent algorithm is used to analyze the survey data and verify the feasibility and development of BIM technology in the combination of interior design and smart homes. The result data shows that the amount of investment in smart home functions is increasing year by year, among which the amount of investment in smart home appliances has been at the forefront. Among the smart home functions, smart home appliances account for the highest percentage, accounting for 80; smart temperature control accounts for 50%, and smart audio accounts for 40%. Home Design VR and AR input amount growth rates of 10%, 20%, 40%, 50%, and 40%, respectively. The research in this paper is beneficial to promote better integration of interior design and smart homes.

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study

It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P= .40) and HCC incidence rates (5.1% vs 4.4%; P= .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P= .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P= .016), but VR and HCC risks were similar. Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE)

Predictors of successful nucleo(s)tide analogue (NA) therapy withdrawal remain elusive. We studied the relationship between end-of-treatment levels of hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg) and outcome after therapy cessation. Patients who discontinued NA therapy in centers in Asia and Europe were enrolled. HBcrAg and HBsAg were measured at treatment cessation, and associations with off-treatment outcomes were explored. The SCALE-B (Surface antigen, Core-related antigen, Age, ALT, and tenofovir for HBV) score was calculated as previously reported. End points included sustained virologic response (VR; hepatitis B virus DNA level <2000 IU/mL), HBsAg loss, and alanine aminotransferase (ALT) flares (>3× upper limit of normal). Re-treated patients were considered nonresponders. We analyzed 572 patients, 457 (80%) were Asian and 95 (17%) were hepatitis B e antigen positive at the start of NA therapy. The median treatment duration was 295 weeks. VR was observed in 267 (47%), HBsAg loss was observed in 24 (4.2%), and ALT flare was observed in 92 (16%). VR (67% vs 42%) and HBsAg loss (15% vs 1.5%) was observed more frequently in non-Asian patients when compared to Asian patients (P < .001). Lower HBcrAg levels were associated with higher rates of VR (odds ratio [OR], 0.701; P < .001) and HBsAg loss (OR, 0.476; P < .001), and lower rates of ALT flares (OR, 1.288; P= .005). Similar results were observed with HBsAg (VR: OR, 0.812; P= .011; HBsAg loss: OR, 0.380; P < .001; and ALT flare: OR, 1.833; P < .001). Lower SCALE-B scores were associated with higher rates of VR, HBsAg loss, and lower rates of ALT flares in both Asian and non-Asian patients (P < .001). In this multicenter study, off-treatment outcomes after NA cessation varied with ethnicity. Lower levels of HBcrAg and HBsAg were associated with favorable outcomes. A risk score comprising both factors can be used for risk stratification.

An easy-to-use baseline scoring system to predict response to peginterferon alfa-2a in patients with chronic hepatitis B in resource-limited settings

Approximately one-third of patients have durable responses after finite (48-week) treatment with peginterferon alfa-2a. The ability to identify patients likely to respond would be particularly useful in resource-limited settings. Data from 1,363 peginterferon alfa-2a recipients (955 hepatitis B 'e' antigen [HBeAg]-positive and 408 -negative) in six studies were analysed. Baseline scoring systems were developed using generalized additive models and multiple logistic regression analysis to predict virological response (VR; HBV DNA <2,000 IU/ml), alone or combined with alanine aminotransferase (ALT) normalization (CR) at 24 weeks post-treatment. Based on the final models, points were assigned for age ≥45 (0) or <45 years (1); male (0) or female (1); hepatitis B surface antigen (HBsAg) >25,000 (0), >7,500-≤25,000 (1), >1,250-≤7,500 (2) or ≤1,250 IU/ml (4); HBV DNA >5 (0) or ≤5 log10 IU/ml (2) and ALT ratio >1-7 (0) or either ≤1 or >7 (1). Higher total scores (range 0-9) indicate higher likelihood of response. VR and CR rates were 28.5% (388/1,363) and 24.4% (332/1,363), respectively, and increased with increasing score: score 0-1 (n=257), VR 14.8%, CR 12.8%; score 2-3 (n=711), VR 23.1%, CR 20.1%; score ≥4 (n=395), VR 47.1%, CR 39.5%. An easy-to-use baseline scoring system for use in settings where HBeAg status and HBV genotypes are unavailable would allow clinicians to identify patients with a low or high chance of achieving a durable post-treatment response to peginterferon alfa-2a. The tool can be used to inform treatment decisions in resource-limited settings.

Efficacy of prolonged entecavir monotherapy in treatment-naïve chronic hepatitis B patients exhibiting a partial virologic response to entecavir.

Background/AimsThe optimal management of patients exhibiting a partial virologic response (PVR) to entecavir (ETV) has not been determined. The aim of this study was to determine the long-term efficacy of prolonged ETV monotherapy in treatment-naïve chronic hepatitis B (CHB) patients exhibiting a PVR to ETV therapy.MethodsThis study included 364 treatment-naïve CHB patients treated with ETV for ≥48 weeks and who received continuous ETV monotherapy for ≥96 weeks. PVR was defined as a decrease in serum hepatitis B virus (HBV) DNA of more than 2 log10 IU/mL from baseline but with detectable HBV DNA by real-time PCR assay at week 48.ResultsFifty-two of the 364 patients (14.3%) showed a PVR. Among them, 41 patients received continuous ETV monotherapy for ≥96 weeks (median duration 144 weeks, range 96-312 weeks), and 40 of these patients (95%) achieved a virologic response (VR, HBV DNA <20 IU/mL) during prolonged ETV monotherapy (median duration 78 weeks, range 60-288 weeks). The cumulative probabilities of a VR at weeks 96, 144, and 192 from treatment initiation were 78.0%, 92.7%, and 95.1%, respectively. The VR rate was 97.2% (35/36) in HBeAg-positive patients and 100% (5/5) in HBeAg-negative patients. In multivariate analysis, HBeAg positivity (odds ratio [OR], 9.231; 95% confidence interval [CI], 1.03-82.91; P=0.047) and a high baseline HBV DNA level (OR, 0.170; 95% CI, 0.08-0.37; P=0.000) were independently associated with a delayed virologic response. No patient developed genotypic resistance to ETV during follow-up.ConclusionsLong-term ETV monotherapy is effective for achieving a VR in treatment-naïve CHB patients exhibiting a PVR to ETV. HBeAg positivity and high baseline HBV DNA level were independently associated with a delayed virologic response.

Management of entecavir-resistant chronic hepatitis B with adefovir-based combination therapies.

To evaluate the long-term efficacy adefovir (ADV)-based combination therapies in entecavir (ETV)-resistant chronic hepatitis B (CHB) patients. Fifty CHB patients with genotypic resistance to ETV at 13 medical centers in South Korea were included for the analysis. All the patients received rescue therapy with the combination of ADV plus ETV (ADV/ETV, n = 23) or ADV plus lamivudine (LMV) (ADV/LMV, n = 27) for more than 12 mo. Patients were monitored at least every 3-4 mo during ADV-based combination therapy by clinical examination as well as biochemical and virological assessments. Hepatitis B virus (HBV) DNA levels were measured by real-time PCR and logarithmically transformed for analysis. Cumulative rates of virologic response (VR; HBV DNA < 20 IU/mL) were calculated using the Kaplan-Meier method, and the difference was determined by a log-rank test. Multivariate logistic regression and Cox proportional hazards models were used to identify independent risk factors significantly associated with short-term and long-term VR, respectively. Baseline median HBV DNA levels were 5.53 (2.81-7.63) log10 IU/mL. The most commonly observed ETV genotypic mutation sites were rt184 and rt202. Patients were treated for a median of 27 (12-45) mo. Overall, cumulative VR rates at 6, 12, 24, and 36 mo were 26%, 36%, 45%, and 68%, respectively. Patients treated with the ADV/ETV combination showed higher cumulative VR rates (35%, 43%, 65%, and 76%, respectively) than those with the ADV/LAM combination (18%, 30%, 30%, and 62%, respectively; P = 0.048). In the multivariate analysis, low baseline HBV DNA levels (< 5.2 log10 IU/mL) and initial virologic response at 3 mo (IVR-3; HBV DNA < 3.3 log10 IU/mL after 3 mo) were independent predictive factors for VR. Patients with favorable predictors achieved cumulative VR rates up to 90% at 36 mo. During the same period, the cumulative incidence of virologic breakthrough was as low as 6% in patients with the both favorable predictors. If tenofovir is not available, ADV/ETV combination could be considered in ETV-resistant patients with low HBV DNA titers, and may be continued if IVR-3 is achieved.

Antiviral effect of entecavir in nucleos(t)ide analogue-naïve and nucleos(t)ide analogue-experienced chronic hepatitis B patients without virological response at week 24 or 48 of therapy.

We investigated the antiviral effect of entecavir in nucleos(t)ide analogue (NA)-naïve and NA-experienced chronic hepatitis B patients without virological response (VR, HBV DNA < 300 copies/mL) at week 24 or 48. A total of 369 NA-naïve and 181 NA-experienced patients treated with entecavir monotherapy were analysed. Of the 369 NA-naïve patients, 34 did not achieve VR at week 48. Of them, patients with HBV DNA ≤ 2000 copies/mL at week 48 achieved a higher VR rate than those with HBV DNA >2000 copies/mL (18/23 vs 3/11, P = 0.004). Two naïve patients with HBV DNA >2000 copies/mL developed entecavir- or lamivudine-resistant mutants. In 98 lamivudine-experienced patients without ever having lamivudine resistance, most patients with VR (72/72) and partial VR (300-10(4) copies/mL; 20/23) at week 24 or VR at week 48 (89/91) could maintain or achieve VR after prolonged therapy. In 75 patients with prior resistance to lamivudine, prolonged entecavir therapy led to low VR rate in those without VR at week 24 (13/45) or 48 (4/34) and high entecavir-resistance rate in those with or without VR at week 24 (6/30 with and 23/45 without) and 48 (8/41 with and 21/34 without). VR at week 48 was an independent predictor (HR 0.14, 95% CI 0.06-0.33) for entecavir-resistant mutant development among the 75 patients with prior lamivudine-resistant mutants. In conclusion, prolonged entecavir treatment resulted in a poor response in naïve patients with HBV DNA >2000 copies/mL at week 48 and patients with prior lamivudine-resistant mutants without VR at week 24 or 48.

Effect of vitamin D supplementation on pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b: a randomized controlled trial

Chronic HCV-infected patients tend to have vitamin D deficiency, suggesting that vitamin D supplementation may enhance the efficacy of treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). We therefore assessed the effects of vitamin D supplementation on viral response to PEG-IFN/RBV. Eighty-four patients with HCV genotype 1b were randomized, 42 to oral vitamin D supplementation (1000IU/day) and 42 to nonsupplementation (control), from week 8 to the end of PEG-IFN/RBV therapy. The primary end point was undetectable HCV RNA at week 24 (viral response [VR]). VR rate at week 24 was significantly higher in the vitamin D than in the control group (78.6% vs 54.8% P=0.037). Adverse events were similar in both groups. When patients were subdivided by IL28B SNP rs8099917 genotype, those with the TT genotype group showed a significantly higher VR rate at week 24 with than without vitamin D supplementation (86.2% vs 63.3% vs P=0.044). Although patients with the TG/GG genotype, who were relatively resistant to PEG-IFN treatment, had similar VR rates at week 24 with and without vitamin D supplementation, the decline in viral load from week 8 to week 24 was significantly greater with than without vitamin D supplementation. Multivariate analysis showed that rs8099917 genotype and vitamin D supplementation contributed significantly to VR at week 24. SVR rates were similar in the vitamin D and control groups [64.3% (27/42) vs 50% (21/42), P=0.19]. Vitamin D supplementation may enhance the effects of PEG-IFN/RBV in HCV genotype 1b-infected patients.

A comparison of 4-year entecavir efficacy in nucleos(t)ide analog-naïve and -experienced adult Taiwanese chronic hepatitis B patients.

To compare the efficacy of entecavir (ETV) monotherapy up to 4years in nucleos(t)ide analog (NA)-experienced and -naïve subjects. One hundred sixty NA-experienced and 282 naïve chronic hepatitis B patients who were treated with ETV were enrolled. Of the 160 NA-experienced patients, 49 had prior lamivudine (LAM)-resistant mutants, 18 had resistant mutants to LAM followed by adefovir (ADV) after switching to ADV sequential therapy (LAM/ADV resistance), and 9 had prior ADV-resistant mutants. NA-resistant mutants were detected by line probe assay. Four years of ETV therapy resulted in virological response (VR, HBV DNA<300 copies/ml), HBeAg seroconversion, and ETV-resistant mutants development in 98.2, 45.2, and <1% of naïve patients, respectively. LAM- and ADV-experienced patients who never developed LAM-resistant mutants had similar VR and ETV-resistant mutant rates to NA-naïve patients. In contrast, prior LAM-resistant mutants were significantly associated with higher ETV-resistant mutants development and reduced VR rates. Patients with prior LAM-resistant mutants but not at baseline had a lower rate of ETV-resistant mutants compared to those with baseline LAM-resistant mutants [hazard ratio (HR): 0.58, 95% confidence interval (CI): 0.35-0.95] and those who had LAM/ADV resistance (HR:0.16, 95% CI:1.0.03-0.76). Early add-on ADV achieved VR in eight of nine patients with ETV-resistant mutants when HBV DNA was <2×10(5) copies/ml. Entecavir was highly efficacious and low resistance in NA-naïve, LAM-, or ADV-experienced patients without LAM-resistant mutants. Patients with prior LAM-resistant mutants but not at baseline had lower ETV-resistant mutant rates compared to those with baseline LAM-resistant mutants or LAM/ADV resistance.

Lamivudine plus adefovir combination therapy for lamivudine resistance in hepatitis-B-related hepatocellular carcinoma patients

Background/AimsLamivudine (LAM) plus adefovir (ADV) combination therapy has been accepted as one of the best treatments for LAM-resistant chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of this combination therapy in hepatocellular carcinoma (HCC) patients.MethodsThe medical records of CHB patients who developed LAM resistance and were treated with LAM plus ADV combination therapy for more than 6 months were reviewed. Their virological response (VR; undetectable HBV DNA) and biochemical response (BR; alanine aminotransferase normalization) were evaluated, and the findings of HCC and non-HCC patients were compared.ResultsThe data from 104 patients (19 with HCC and 85 without HCC) were analyzed. The VR rates did not differ significantly between the HCC and non-HCC groups: 33.3% vs. 55.6% at 12 months (P=0.119), 58.3% vs. 67.2% at 24 months (P=0.742), 50% vs. 69.8% at 36 months (P=0.280), and 66.7% vs. 71.0% at 48 months (P=1.000). The BR rates also did not differ significantly between the groups: 55.6% vs. 84.0% at 12 months (P=0.021), 58.3% vs. 83.8% at 24 months (P=0.057), 70.0% vs. 77.8% at 36 months (P=0.687), and 66.7% vs. 80.6% at 48 months (P=0.591).ConclusionsThe efficacy of LAM plus ADV combination therapy is comparable in HCC and non-HCC patients.

Combined immunogenicity data for a new DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim™) following primary series administration at 2, 4, 6 months of age in Latin America

The immunogenicity of a primary series of a new, fully liquid DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim™), administered at 2, 4, 6 months of age in four clinical studies is reviewed. Immunogenicity data at 1 month after the third vaccination were assessed and pooled from a total of 1270 participants (per-protocol population) in four randomized clinical trials in Argentina, Mexico, and Peru. Hepatitis B vaccine was not administered at birth. All seroprotection (D, T, polio-1, -2, -3, Hep B, PRP-T [Hib]), seroconversion (PT and FHA), and vaccine response (PT and FHA) data were high, and were similar to licensed comparators (pooled SP, SC, and VR rates were 97.1–100%, 96.0–97.0%, and 99.7–99.9%, respectively). These data show the good immunogenicity of this new hexavalent vaccine that can provide the opportunity to increase global compliance to complex pediatric vaccination schedules.

The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine

Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18–55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ≥ 1:32 in initially seronegative; ≥ 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ≥ 98.0% of subjects had rSBA titers ≥ 1:128. Grade 3 solicited AEs were reported in ≤ 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults. This study is registered at clinicaltrials.gov NCT00453986

OL-041 Current distribution of HBV serological markers in chronic HBV patients and its significance in Mongolia

Objectives: At present, there is no consensus of telbivudine (LdT) treatment for chronic hepatitis B (CHB) patients who have poor response to adevofir dipivoxil (ADV) monotherapy. The aim of this study was to assess the therapeutic effectiveness of LdT, administered in combination with ADV in CHB patients with poor response to ADV monotherapy. Methods: Twenty-four adult outpatients aged >18 years with HBVDNA 103 copies/mL and normal alanine aminotransferase (ALT) after at least 48 weeks of ADV initial monotherapy were included and immediately received ADV plus LdT combination treatment in this prospective study. HBVDNA and ALT levels were checked every 3 month. The proportions of patients who achieved virologic response (VR, undetectable HBV-DNA [<103 copies/mL]) were analyzed, and serum creatine kinase (CK) and creatinine (Cr) after combination therapy were observed. Results: At baseline of combination treatment, the mean level of HBVDNA was 4.05 log (10) copies/mL. Compared with baseline, the mean decrease in HBVDNA level at week 12 and 24 were 0.89 log10 and 1.31 log10 copies/mL, respectively, and the decreasing was significant (p < 0.001for week 12, and p < 0.001 for week 24). The VR rate was 41.7% and 66.7% at weeks 12 and 24, respectively, and the difference in VR between week 12 and 24 was significant (p = 0.003). During the initial 24 weeks combination therapy, no elevated ALT, CK, and Cr were detected. Conclusions: Adding LdT may be a good choice for CHB patients with poor response to ADV monotherapy. And further long-term study was necessary to confirm the results.

Tuning the Vibrational Relaxation of CO Bound to Heme and Metalloporphyrin Complexes

Picosecond mid-infrared pump−probe experiments were used to investigate vibrational relaxation (VR, which here denotes loss of excess vibrational energy) of CO bound to synthetic heme and porphyrin complexes with different metal atoms (M = Fe, Ru, Os) and different proximal ligands (imidazoles and pyridines). Isotope effects of 13CO vs 12CO and solvent effects were also studied. A remarkable correlation between the carbonyl vibrational lifetime and the carbonyl vibrational frequency νCO is observed. The vibrational lifetime decreases as νCO decreases. The lifetime−frequency correlation is consistent with a linear relation between carbonyl vibrational relaxation rate and νCO. Hemes and porphyrins show similar lifetime−frequency correlations, but the absolute value of the VR rate in meso-tetraphenylporphyrin complexes is slightly faster than in protoporphyrin IX dimethyl ester heme complexes. The predominant VR process is shown to be intramolecular transfer from CO to heme vibrations, rather than intermolec...

Slowly Propagating Slip Events in a Composite Sample of Granite and Marble.

Slip events with anomalously low rupture velocities are examined through experiments by the use of a rock sample with a pre-existing fault. The rock sample consisted of a block of Akiyoshi marble sandwiched between two blocks of Westerly granite. Sliding along the composite fault is low stress-drop stick-slip motion over the entire fault, though sliding is stable on a pure marble fault and unstable on a pure granite fault under the same experimental conditions. The observed rupture velocity, VR, ranges from 0.1 to 500 m/s, and the observed breakdown stress drop from 0.04 to 0.2 MPa. Combining the data for events in the composite fault with those obtained for stick-slip on faults in pure granite, the breakdown stress drop Δτb can be related to both VR and strain rate byΔτb∝VR0.25 for 0.1 m/s _??_ VR _??_ 3 km/s, Δτb∝e0.25max for 6×10-7/s _??_ e0.25max _??_ 2×10-1/s, where emax stands for the maximum value of observed strain-rate. This clearly indicates that the shear strength between fault surfaces is dependent on strain-rate. We emphasize the possibility of slow earthquakes or episodic creep events in the lower crust and the upper mantle.

The effect of vibrational relaxation on infrared multiphoton excitation

Abstract A model description of vibrational relaxation (redistribution) (VR) in the quasicontinuum (QC) of polyatomic molecules, subject to infrared multiphoton excitation (IR MPE) has been introduced, based on the kinetic equations technique. This model has been applied to the derivation of expressions for the population distributions as well as dissociation quantum yields (QYs) of polyatomic molecules under IR MPE, with special emphasis on the dependence of the obtained QYs on exciting laser pulse intensity and duration as compared to the VR rate constant. Good agreement has been obtained between the theoretically derived dependences of the dissociation QYs in SF 6 on buffer gas pressure and experimental data.