John Z Liang
, New York City

Infectious Diseases, Clinical Immunology, Pediatrics

PhD
17.61

Publications

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    ABSTRACT: This postlicensure study was conducted to assess immunogenicity and safety of PCV7 catch-up regimens in previously unvaccinated older infants and young children in China. Healthy children 121 days to <72 months were grouped by age and immunized with 1 of 4 PCV7 dosing regimens. Serotype-specific IgG geometric mean concentrations (GMCs) and percentage of subjects with IgG≥0.35μg/mL were assessed before vaccination and 1 and 12 months postvaccination. The incidence of clinically important adverse events (AEs) and serious AEs (SAEs), AEs leading to study withdrawal, and protocol-related AEs were assessed throughout the study. Prevaccination serotype-specific GMCs were generally low in subjects <24 months; the majority of children 24 to <72 months had IgG concentrations ≥0.35μg/mL. One month postvaccination, GMCs were similar across groups for the 7 PCV serotypes, ranging from 3.95 to 13.02μg/mL; the highest antibody levels were observed for serotype 14. Regardless of dosing regimen, >90% of subjects had IgG≥0.35μg/mL for each PCV serotype. At 12-month follow-up, IgG GMCs ranged from 0.65 to 5.19, and all remained above prevaccination IgG GMC; >70% of subjects had IgG≥0.35μg/mL. Older children generally had the most robust immune response both at 1 month postvaccination and during 12-month follow-up. PCV7 was well tolerated. Pyrexia, which was mild to moderate in severity, was the most common AE. Two subjects reported SAEs (n=4), and there was 1 study withdrawal; none of these were considered treatment related. In China, PCV7 catch-up vaccinations given to older infants and young children naive to pneumococcal vaccines resulted in a robust immune response to all serotypes; this response persisted after 1 year. PCV7 was well tolerated in Chinese infants and children. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 06/2015; 82(30). DOI:10.1016/j.vaccine.2015.05.042 · 3.49 Impact Factor
  • John Z Liang · Scott Patterson
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    ABSTRACT: World Health Organization (WHO) guidance was issued in 2009 covering Recommendations to assure the quality, safety and efficacy of pneumococcal conjugate vaccines. From the new WHO guidance (at section C2.2.3, page 27), two primary co-endpoints are recommended: "The endpoints used in the primary analysis should be the percentage of subjects with IgG =0.35 µg/mL AND the serotype-specific IgG GMC (Geometric Mean Concentration) ratios". The purpose of this work is to show simulations to define sample size and power calculation for a study in support of WHO registration requirements accounting for multiplicity across serotypes and across endpoints. A phase 3, parallel-group, randomized, active-controlled, double-blinded trial was to be designed to evaluate immunogenicity of Test Vaccine as compared with Control Vaccine. There were 3 infant series vaccinations and 1 toddler dose vaccination. The IgG data collected after 3 infant series vaccinations are in interest for primary endpoints. Multiplicity across endpoints was controlled by Bonferroni adjustment (i.e. 5% type 1 error was divided equally across endpoints.
    2014 JSM Proceedings; 01/2015
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    ABSTRACT: Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35μg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. Immunogenicity results of MnCCV-CRM197 for PCV13 compared to PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing expanded coverage against pneumococcal disease.
    Vaccine 09/2013; 31(46). DOI:10.1016/j.vaccine.2013.06.049 · 3.49 Impact Factor
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    ABSTRACT: Two randomized trials of 13-valent pneumococcal conjugate vaccine (PCV13) relative to PCV7 evaluated the immune responses of coadministered antigens comprising Infanrix(®) hexa/Infanrix(®)-IPV+Hib (diphtheria, tetanus, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b). After the 3-dose infant series, immunogenic noninferiority was demonstrated for all concomitantly administered antigens between the PCV13 and PCV7 groups. All antigens elicited good booster responses after the toddler dose except pertussis toxoid; however, 99.6% subjects achieved pertussis toxoid protective antibody level ≥5EU/mL in both groups. These results support the concomitant administration of PCV13 and Infanrix hexa/Infanrix-IPV+Hib as part of routine immunization schedules.
    Vaccine 06/2011; 29(35):6042-8. DOI:10.1016/j.vaccine.2011.06.026 · 3.49 Impact Factor
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    ABSTRACT: A 13-valent pneumococcal conjugate vaccine (PCV13) has been developed to improve protection against pneumococcal disease beyond that possible with the licensed 7-valent vaccine (PCV7). This study compared the safety and immunogenicity of PCV13 with those of PCV7 when given as part of the pediatric vaccination schedule recommended in Italy. A total of 606 subjects were randomly assigned to receive either PCV13 or PCV7 at 3, 5, and 11 months of age; all subjects concomitantly received diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type B (DTaP-HBV-IPV/Hib) vaccine. Vaccine reactions were monitored. Antibody responses to DTaP-HBV-IPV/Hib antigens, serotype-specific anticapsular polysaccharide IgG responses, and antipneumococcal opsonophagocytic assay (OPA) activity were measured 1 month after the two-dose primary series and 1 month after the toddler dose. Overall, the safety profile of PCV13 was similar to that of PCV7. The response to DTaP-HBV-IPV/Hib antigens was substantially the same with both PCV13 and PCV7. PCV13 elicited antipneumococcal capsular IgG antibodies to all 13 vaccine serotypes, with notable increases in concentrations seen after the toddler dose. Despite a lower immunogenicity for serotypes 6B and 23F after the primary series of PCV13, responses to the seven common serotypes were comparable between the PCV13 and PCV7 groups when measured after the toddler dose. PCV13 also elicited substantial levels of OPA activity against all 13 serotypes following both the infant series and the toddler dose. In conclusion, PCV13 appeared comparable to PCV7 in safety profile and immunogenicity for common serotypes, demonstrated functional OPA responses for all 13 serotypes, and did not interfere with immune responses to concomitantly administered DTaP-HBV-IPV/Hib vaccine.
    Clinical and vaccine Immunology: CVI 06/2010; 17(6):1017-26. DOI:10.1128/CVI.00062-10 · 2.37 Impact Factor
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    ABSTRACT: Adaptive dose-ranging trials are more efficient than traditional approaches and may be designed to explicitly address the goals and decisions inherent in learn-phase drug development. We report the design, implementation, and outcome of an innovative Bayesian, response-adaptive, dose-ranging trial of an investigational drug in patients with diabetes, incorporating a dose expansion approach to flexibly address both efficacy and safety. The design was developed to assess whether one or more doses of an investigational drug demonstrated superior efficacy to an active control while maintaining an acceptable safety profile. The trial used a two-stage design, in which patients were initially allocated equally to placebo, investigational drug at a low and a medium dose, and an active control. Movement to the second stage was contingent upon evidence of efficacy (measured by change in fasting blood glucose) to add a very low dose of the investigational drug and of safety (measured by weight gain) to add a high dose of the investigational drug. The design incorporated a longitudinal model to maximize use of incomplete data, predictive probabilities to guide the decisions to terminate the trial for futility or move on to Stage 2, and a dose-response model in Stage 2 to borrow information across adjacent doses. Extensive simulations were used to fine tune trial parameters, to define operating characteristics, and to determine the required sample sizes. A data monitoring committee was provided with frequent reports to aid in trial oversight. In Stage 1, as trial data accrued, the predictive probability that either the low or medium dose of the investigational drug was superior to the active control fell to low values. Stage 1 termination was recommended after 199 subjects were randomized, out of a maximum trial size of 500 subjects, and the final sample size was 218. Thus the trial did not progress to Stage 2. Because of the relatively narrow dose range to be assessed, and the inability to utilize the highest dose at the beginning of the trial, a fully responsive-adaptive design incorporating dose-response modeling was not considered a viable option. This limited the efficiency gains possible with a full set of adaptive design elements. The two-stage dose-expansion design functioned as designed, recommending early termination based on a low probability that the tested doses had efficacy greater than the active control.
    Clinical Trials 03/2010; 7(2):121-35. DOI:10.1177/1740774510361541 · 1.94 Impact Factor
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    ABSTRACT: Introduction: Compatibility of coadministration of 13-valent pneumococcal conjugate vaccine (PCV13, serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) with diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b was evaluated in two studies in Germany and Spain. Methods: Infants received Infanrix hexa®, Infanrix hexa-IPV+Hib, and Meningitec® according to national recommendations and were randomly assigned (1:1 ratio) to receive PCV13 or 7-valent pneumococcal conjugate vaccine (Prevenar®, PCV7) at 2, 3, 4, and 11-12 months or at 2, 4, 6 months, and 15 months. Blood draws were taken for serology: one month after dose 2 (Spain only), dose 3, and the toddler dose. The proportion of subjects achieving prespecified antibody levels (responders), and IgG geometric mean concentrations or titers (GMC or GMTs) for each antigen were compared between the PCV13 and PCV7 groups. Results: The evaluable immunogenicity populations in Germany included 564 infants and 547 toddlers; in Spain 579 infants and 545 toddlers. Both responder rates and IgG GMC or GMTs to each antigen were comparable between the two groups, with markedly higher responses after the toddler dose. Noninferiority criteria were met for each antigen with (1) lower limit of 95% CI for the difference in proportions of responders between groups above -0.10; (2) predefined lower limit of 95% CI IgG GMC or GMT ratios above 0.5 (2-fold criterion). Conclusions: PCV13 can be coadministered with DTaP-HBV-IPV-Hib as part of the routine immunization schedule.
    Infectious Diseases Society of America 2009 Annual Meeting; 10/2009
  • John Z Liang
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    ABSTRACT: Studies performed in the United States have shown that upto 1 million needlestick injuries occur every year in USA alone, leading to considerable number of Hepatitis B, C, and HIV infections. Currently no safety needles for use with insulin injection pen systems are available. NovoFine Autocover is a single-use needle designed to minimize the risk of accidental needle-sticks. In an open-label, monocenter trial, 49 subjects (age 19–74, either diabetes nurse educators, diabetes staff nurses or patients with type 1 or 2 diabetes) performed 18 injections (total of 882 safety needle injections) into foam cushions with inert Test Media using the InnoLet insulin delivery system. Participants were briefed in use of both the devices before using them to test the safety needle, comparing it to the BD-Safety Glide Syringe. Seven (7) failures occurred in the activation/locking of the safety needle during the testing, corresponding to a device failure rate of 0.79%. No adverse device effects resulted in an adverse event (needle-stick injury, etc.) during use of the NovoFine Autocover needle. One adverse device effect with a device failure rate of 0.60% was reported when using the InnoLet and 3 adverse device failures of 4.95% were reported when using BD-Safety Glide syringe. Majority (47/49, 96%) of the subjects found no difficulties associated with use of the safety needle. Twenty-nine percent (14/49) subjects would recommend the NovoFine Autocover safety needle and 67% (33/49) subjects said they would recommend both devices. In conclusion, these findings indicate that the safety needle (NovoFine Autocover Needle) could have a significant impact in reducing incidence and risk of needle-stick injuries in diabetes nurse educators, staff nurses and diabetes patients. Preference measures significantly favored the safety needle, indicating a high degree of clinical acceptance of this needle-stick prevention device.
    65th Annual American Diabetes Association (ADA) Meeting, San Diego, California, USA; 06/2005
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    ABSTRACT: Optimal needle length for subcutaneous insulin injection may differ for obese and nonobese patients, which could affect management of diabetes mellitus (DM). The aim of this study was to determine whether 31 gauge (G) x 6 mm (shorter) needles are appropriate alternatives to 29 G x 12.7 mm (longer) needles in obese patients with DM. A multicenter, open-label, randomized, 2-period crossover trial was conducted in insulin-treated patients with type 1 or 2 DM with body mass index >or=30 kg/m(2) and glycosylated hemoglobin A(1c) (HbA(1c)) concentration <or=10%. All patients used the same injection device and were randomized to receive 12 weeks of therapy with 1 injection site (thigh or abdomen) and 1 of the 2 needle lengths. Patients used the same injection site but the alternate needle during the second 12-week period. Sixty-two patients (31 men, 31 women; mean [SD] age, 50.5 [10.6] years; age range, 20-73 years) received treatment. Fifty-six patients completed all 24 weeks of treatment. No differences in glycemic control were found. Double-blind assessments of pain scores and leakage measurements, and results from the World Health Organization Diabetes Treatment Satisfaction Questionnaire and most sections of the Insulin Treatment Satisfaction Questionnaire (ITSQ), indicated no differences. However, patients indicated greater satisfaction with the shorter needle on the ITSQ (P < 0.001). The most common adverse event was injection-site bruising (51% [30/59] for the longer needle vs 34% [21/61] for the shorter needle; P = NS). Eighty-nine percent of patients (49/55) preferred the shorter needle (P < 0.001), and 76% (42/55) had a strong, very strong, or extremely strong preference for it. In obese patients, use of 31 G x 6 mm and 29 G x 12.7 mm needles produced comparable HbA(1c) values, double-blind pain and leakage scores, convenience, and ease of use. However, patients preferred the shorter needle.
    Clinical Therapeutics 10/2004; 26(10):1663-78. DOI:10.1016/j.clinthera.2004.10.007 · 2.59 Impact Factor
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    ABSTRACT: This clinical trial assessed patient preference, satisfaction, and use of an insulin injector/glucose monitor combination device versus syringes and a separate glucose monitor. In a randomized, multicenter, 2-period crossover study, 15 patients with type 1 diabetes were randomized to use either a combined injector/monitor device or syringes, a vial, and a separate glucose monitor, then switched to the alternate treatment. Efficacy, safety, preference, satisfaction, and actual use (via meter download) of the 2 systems were compared. Most of the patients preferred using the combination device to syringes and a separate meter. Results from the Handling of Delivery Systems questionnaire given at the end of the study indicated that 49% of patients felt they tested their blood glucose more often with the combination device than with a separate meter. A higher frequency of daily monitoring was reported with the combination device in patients overall (approximately 1 more reading per week). However, a large subset of patients (32%) showed substantial increases in their frequency of daily glucose monitoring (an average of 1 additional reading per day). Use of the combination device was associated with significant improvements in patient treatment satisfaction.
    The Diabetes Educator 03/2004; 30(2):301-9. DOI:10.1177/014572170403000223 · 1.92 Impact Factor
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    ABSTRACT: InnoLet is a disposable insulin injection device with a large easy-to-read dial, large push button for injection, and audible clicks for each unit injected. This clinical trial assessed patient preference, satisfaction, and utilization of healthcare resources (estimated nursing care) for InnoLet and vial/syringe. Patients with diabetes mellitus (N=79, mean age 68.2+/-8.6 years, duration of diabetes 16.5+/-10.9 years) having visual and/or motor disabilities and having difficulty (or required caregiver assistance) for previous injections by vial/syringe were randomized to use of either InnoLet or vial/syringe for 6 weeks, then switched to the alternate regimen for 6 weeks. At the end of the study, utilization of healthcare resources was assessed in terms of the caregiver time required to assist in preparation, storage, and disposal of each device. For vial/syringe, 60% of patients required assistance in drawing up the appropriate dosage in the syringe, and 36% of patients required assistance when injecting insulin. A major portion of the patients (53%) could independently conduct injections (without nursing/caregiver assistance) during use of InnoLet, versus 20% for vial/syringe. As a result, mean daily nursing costs associated with the injection regimen were US$ 114 for the InnoLet device, and US$ 196 for vial/syringe (P<0.001). A majority of patients (82%) indicated a preference for the InnoLet device (P<0.001).
    Diabetes Research and Clinical Practice 02/2004; 63(1):27-35. DOI:10.1016/j.diabres.2003.08.013 · 2.54 Impact Factor
  • John Z Liang
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    ABSTRACT: Successful therapy of diabetes requires frequent blood glucose monitoring by the patient and frequent countermeasures by the patient in response to glucose meter findings. InDuo® is the first device to combine an insulin injection and BG meter. The safety (adverse events, adverse device effects, and hypoglycemic episodes), efficacy (fasting plasma glucose and fructosamine levels, 7-point blood glucose profiles, and HbA1c); and actual use of a combined meter and injection device (InDuo®) were compared to separate meter and syringe in a multicenter, randomized, crossover study of adult Type 1 diabetes subjects currently on MDI therapy. The enrolled patients (n=125, mean age 42.1 ± 14.3 years, mean HbA1c 7.9 ± 1.2% and frequency of screening BG monitoring 3.9/day) were randomized to use of either InDuo® or a separate meter (Ultra One Touch) and syringe for 6 weeks. Patients were switched to the alternate treatment for 6 weeks. During the study, the overall enrolled population showed a significant mean reduction of 0.54% in the HbA1c values (p < 0.0001). The most common adverse event was upper respiratory tract infection (4% of patients for combination device, 8% of patients for syringe plus monitor). In general, the two device regimens showed no notable differences in incidence of any adverse event. A majority (79%) of the patients preferred treatment with the combination device rather than the syringe and separate monitor. The InDuo® showed small advantages in the frequency of SMBG (1 more reading per week). In conclusion, the use of the InDuo® was associated with significant improvements in patient treatment satisfaction. These improvements were reflected in improved compliance (more injections or blood tests per day) in a substantial portion of the patients tested.
    18th International Diabetes Federation Congress, Paris, France; 08/2003
  • John Z Liang
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    ABSTRACT: Many factors contribute to infrequent BG monitoring by patients, including not having a meter available when dosing. InDuo® is the first combined insulin injector and BG meter. In a randomized, multicenter, two-period crossover study, patients with type 1 diabetes (N=125, mean age 42.1±14.3 years) were randomized to use of either InDuo® or a separate meter (Ultra One Touch) and syringe for 6 weeks. Subjects were then switched to alternate treatment for 6 additional weeks. Preference and satisfaction questionnaires were completed at the end of the study. Overall, the enrolled patients showed significant glycemic improvement in the HbA1c values during the 12-week study (p < 0.001). Patients using InDuo® reported significantly higher overall satisfaction as assessed with the WHO Diabetes Treatment Satisfaction Questionnaire. Use of InDuo® also resulted in significantly higher rating of insulin therapy, lack of interference with lifestyle and ease of injecting when away from home. Overall, 79% of subjects preferred InDuo® to use of separate meter and syringe with convenience, ease of use, and accuracy being major factors (p< 0.001). Other factors in patient preference included specific features like the 5-second BG analysis (60%), small blood sample requirement (55%) and memory functions (91% used BG memory several times a week and 66% used the doser memory several times a week). The Patient Device Handling Questionnaire at the end of the study indicated, 49% of patients felt that they tested BG more often with InDuo® than a separate meter. In conclusion, use of a combined BG meter and insulin doser was associated with treatment satisfaction that was greater than syringe and separate meter, with substantial preference for the combined device leading to implications in treatment compliance.
    18th International Diabetes Federation Congress, Paris, France; 08/2003
  • John Z Liang
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    ABSTRACT: InnoLet® insulin injection device is specifically designed to overcome practical and psychological obstacles which prevent many patients from effectively managing their insulin treatment. InnoLet is a disposable insulin injection device with a large easy-to-read dial, a large button for injection, and audible clicks representing each unit injected. The objective of this study was to evaluate differences in fear of self-injection of insulin (and perception of barriers to compliance with an insulin regimen) for patients using the InnoLet device as compared to the vial/syringe. Diabetes patients (N=79, mean age 68.2 ± 8.6 years, mean HbA1c 7.5 ± 1.4%) with visual and/or motor disabilities were enrolled in this two-period crossover study. Subjects were randomized to use of either vial/syringe or InnoLet for 6 weeks, and then switched to the alternate treatment for 6 weeks. At baseline and end of each period, subjects completed the Diabetes Fear of Self-Injection Questionnaire (D-FISQ, questions about barriers to insulin self-injection, treatment satisfaction and preference). The D-FISQ showed high internal consistency (α=0.94). Overall, InnoLet treatment reduced the number of patients with extreme injection fear (D-FISQ >3) by 53%, while syringe treatment resulted in a 36% increase in extreme injection fear. Changes in fear of self-injection were significantly correlated with changes in treatment satisfaction (r= –0.29, p=0.015) and perceived barriers (r=0.30, p=0.010) but not to socio-demographic and impairment variables. The barrier item feeling awkward with other people around correlated most strongly with D-FISQ changes. In conclusion, InnoLet device offers important psychological benefits to elderly insulin-dependent diabetes patients with visual and or motor disabilities. The clinical significance of these findings is substantial, given the significant health gains that can be obtained with effective insulin therapy.
    American Diabetes Association 63rd Scientific Sessions (461), New Orleans, Louisiana, USA; 06/2003
  • Value in Health 05/2003; 6(3):332-332. DOI:10.1016/S1098-3015(10)64179-4 · 2.89 Impact Factor
  • John Z Liang
    Journal of Harbin Institute of Technology (New Series) 04/1992; 24(Issue 2):1-6.
  • Zhiyuan Liang · Hong Cheng
    Harbin Gongye Daxue Xuebao/Journal of Harbin Institute of Technology 01/1992; 24(2).
  • John Z Liang
    Journal of Harbin Institute of Technology (New Series) 07/1991; Supplementary:166-168.
  • John Z Liang
    Harbin Gongye Daxue Xuebao/Journal of Harbin Institute of Technology 07/1991; Supplementary:p196-198.
  • Zhiyuan Liang · Hong Cheng
    Harbin Gongye Daxue Xuebao/Journal of Harbin Institute of Technology 01/1991; 23(6):Page 15-20.

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