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\"Tracing the formation of the modern concept of literature in 20th century China, this book examines the emergence of the Chinese socialist realist novel in relation to the literary and philosophical currents globalized in the wake of capitalist modernity\"--Provided by publisher.

D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II–IIIB gastric cancer. The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II–IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m2 twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m2 on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229). 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4–41·7) in the chemotherapy and surgery group and 34·3 months (25·6–41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69–79) in the chemotherapy and surgery group and 59% (53–64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44–0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. F Hoffmann-La Roche and Sanofi-Aventis.

ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment. This Phase 2 open label study assessed the safety, efficacy and pharmacokinetic profile of ATL1102 administered as 25 mg weekly by subcutaneous injection for 24 weeks in 9 non-ambulatory boys with DMD aged 10-18 years. The main objective was to assess safety and tolerability of ATL1102. Secondary objectives included the effect of ATL1102 on lymphocyte numbers in the blood, functional changes in upper limb function as assessed by Performance of Upper Limb test (PUL 2.0) and upper limb strength using MyoGrip and MyoPinch compared to baseline. Eight out of nine participants were on a stable dose of corticosteroids. ATL1102 was generally safe and well tolerated. No serious adverse events were reported. There were no participant withdrawals from the study. The most commonly reported adverse events were injection site erythema and skin discoloration. There was no statistically significant change in lymphocyte count from baseline to week 8, 12 or 24 of dosing however, the CD3+CD49d+ T lymphocytes were statistically significantly higher at week 28 compared to week 24, four weeks past the last dose (mean change 0.40x109/L 95%CI 0.05, 0.74; p = 0.030). Functional muscle strength, as measured by the PUL2.0, EK2 and Myoset grip and pinch measures, and MRI fat fraction of the forearm muscles were stable throughout the trial period. ATL1102, a novel antisense drug being developed for the treatment of inflammation that exacerbates muscle fibre damage in DMD, appears to be safe and well tolerated in non-ambulant boys with DMD. The apparent stabilisation observed on multiple muscle disease progression parameters assessed over the study duration support the continued development of ATL1102 for the treatment of DMD. Clinical Trial Registration. Australian New Zealand Clinical Trials Registry Number: ACTRN12618000970246.

Astodrimer sodium is a dendrimer molecule with antiviral and virucidal activity against SARS-CoV-2 and other respiratory viruses in vitro, and has previously been shown to be safe and well tolerated, and not systemically absorbed, when applied to the vaginal mucosa. To investigate its potential utility as a topical antiviral, astodrimer sodium has been reformulated for application to the nasal mucosa to help reduce viral load before or after exposure to respiratory infection. The current investigation assessed the safety, tolerability and absorption of astodrimer sodium 1% antiviral nasal spray. This was a single-centre, double-blinded, randomized, placebo-controlled, exploratory clinical investigation. Forty healthy volunteers aged 18 to 65 years with no clinically significant nasal cavity examination findings were randomized 3:1 to astodrimer sodium nasal spray (N = 30) or placebo (N = 10) at an Australian clinical trials facility. An initial cohort of participants (N = 12 astodrimer, N = 4 placebo) received a single application (one spray per nostril) to assess any acute effects, followed by a washout period, before self-administering the spray four times daily for 14 days to represent an intensive application schedule. Extent of absorption of astodrimer sodium via the nasal mucosa was also assessed in this cohort. A second cohort of participants (N = 18 astodrimer, N = 6 placebo) self-administered the spray four times daily for 14 days. The primary endpoint was safety, measured by frequency and severity of treatment emergent adverse events (TEAEs), including clinically significant nasal cavity examination findings, in the safety population (all participants randomized who administered any spray). Participants were randomized between 6 January 2021 and 29 March 2021. TEAEs occurred in 8/10 (80%) participants in the placebo arm and 19/30 (63.3%) participants in the astodrimer sodium arm; all were of mild intensity. TEAEs considered potentially related to study product occurred in 5/10 (50%) participants receiving placebo and 10/30 (33.3%) of participants receiving astodrimer sodium. No participants experienced serious AEs, or TEAEs leading to withdrawal from the study. No systemic absorption of astodrimer sodium via the nasal mucosa was detected. Astodrimer sodium nasal spray was well tolerated and is a promising innovation warranting further investigation for nasal administration to potentially reduce infection and spread of community acquired respiratory virus infections. Trial Registration: ACTRN12620001371987, first registered 22-12-2020 (Australia New Zealand Clinical Trials Registry, https://anzctr.org.au/ ).

In August 2006, the Australian government approved subsidized trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, and it was mandated that HER2 testing should be performed using in situ hybridization (ISH) rather than immunohistochemistry (IHC). Here we review results of the first regulated, nationwide program to provide HER2 ISH testing for all newly diagnosed breast cancer patients, with a particular emphasis on cases where IHC and ISH results were discordant. Data from all laboratories participating in the program were collated. Cases with an equivocal ISH test result [by chromogenic ISH (CISH) or silver ISH (SISH)] were tested centrally by fluorescence ISH. Most laboratories also performed HER2 IHC, and 200 cases with discordant IHC and ISH results were selected for further analysis in a central laboratory. A total of 26 laboratories were involved and 53,402 tests were reported. Over a 4-year period the HER2 positivity rate decreased for primary cancers from 23.8 to 14.6 %, but remained relatively constant for samples from metastases. Average ISH reporting times were <5 days for all yearly reporting periods. Test-repeat rates decreased for CISH (8.9–3.6 %) and SISH (13.7–8.4 %). Only 12 of 196 cases remained discordant after retesting in a central laboratory. These findings demonstrate the successful implementation of a regulated, national program that continues to collect data on HER2 status. The results also highlight the differences in IHC interpretation between local laboratories and a central, more experienced, laboratory. This model could be used to establish future biomarker-testing programs in other countries.

IntroductionThe objective of this study was to observe the patterns of usage, efficacy, and safety of tocilizumab (TCZ) in clinical practice in patients with rheumatoid arthritis.MethodsData on the real-world usage, efficacy, and safety of TCZ were collected from patients during routine follow-up visits conducted over a 6-month period. Patients were grouped by previous exposure to biologic therapies (biologic exposed vs. biologic naive).ResultsOf 1912 patients enrolled from 16 countries, 639 (33.4%) received TCZ monotherapy and 1273 (66.6%) received TCZ combination therapy. At baseline, 1073 patients (56.1%) were biologic naive and 839 (43.9%) were biologic exposed. At 6 months, 1504 patients (78.7%) continued to receive TCZ treatment, with no descriptive differences in retention rates between biologic-exposed and biologic-naive patients and between patients receiving TCZ monotherapy or combination therapy. Dose and use of methotrexate and prednisone were reduced at 6 months. Efficacy at 6 months, including patient-reported outcomes, was demonstrated in both biologic-naive and biologic-exposed groups. Adverse events (AEs) occurred in 817 patients [42.7%; incidence rate: 179 events per 100 patient-years (PY)], and serious AEs (SAEs) occurred in 118 patients (6.2%; 17 events per 100 PY), with comparable rates of AEs and SAEs between subgroups.ConclusionIn routine clinical practice, TCZ discontinuation rates were low and unaffected by prior use of biologics. Effectiveness was similar between groups, and no new safety signals were identified.FundingF. Hoffmann-La Roche.

Tracing the formation of the modern concept of literature in 20th century China, this book examines the emergence of the Chinese socialist realist novel in relation to the literary and philosophical currents globalized in the wake of capitalist modernity.

Among patients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B, the rates of suppression of hepatitis B virus DNA to below 20,000 copies per milliliter were 43 percent with peginterferon alfa-2a alone, 44 percent with peginterferon alfa-2a plus lamivudine, and 29 percent with lamivudine alone after 48 weeks of treatment and 24 weeks of follow-up; the rates of suppression to below 400 copies per milliliter were 19 percent, 20 percent, and 7 percent, respectively. Peginterferon alfa-2a was more effective than lamivudine for HBeAg-negative chronic hepatitis B. Chronic infection with hepatitis B virus (HBV) is a major global health problem, affecting more than 400 million people worldwide. 1 Chronic hepatitis B is associated with serious complications, including liver failure, cirrhosis, and hepatocellular carcinoma. Hepatitis B e antigen (HBeAg)–negative chronic hepatitis B represents a late phase of the infection that is characterized by progressive liver damage 2 , 3 and viral variants with changes in the precore or core promoter region, 4 , 5 which abolish or suppress the expression of HBeAg. Spontaneous, sustained remissions are rare in HBeAg-negative chronic hepatitis B, 6 which has a poor prognosis. HBeAg-negative chronic hepatitis B occurs throughout . . .

Purpose The 2 reported trials investigated the effectiveness of treatment with peginterferon alfa-2a in Asian patients with chronic hepatitis B (CHB). Methods Patients with HBeAg-positive ( n  = 708) or HBeAg-negative ( n  = 332) CHB were enrolled in 2 randomized, double blind, placebo-controlled studies. Patients received peginterferon alfa-2a 180 μg once weekly, peginterferon plus lamivudine 100 mg per day, or lamivudine alone for 48 weeks. Patients were followed up at 6 and 12 months posttreatment. Results Peginterferon alfa-2a provided significantly higher rates of HBeAg seroconversion (31%) in HBeAg-positive patients than did lamivudine (19%, P  = 0.005) 6 months posttreatment, irrespective of genotype. Of these, 83% achieving seroconversion during treatment or early posttreatment sustained their response at 12 months posttreatment. In patients who seroconverted, 69% maintained HBV DNA suppression at <10,000 copies/ml and alanine aminotrasferase (ALT) normalization. In HBeAg-negative patients, peginterferon produced a significantly higher combined response of HBV DNA at <20,000 copies/ml and ALT normalization (45%) than lamivudine (31%, P  = 0.032), irrespective of genotype. Almost 80% of these patients sustained their response at 12 months posttreatment. Conclusions In conclusion, a finite course of peginterferon alfa-2a provides significant and sustained treatment benefit in Asian CHB patients, who have traditionally been regarded as difficult to treat.

Studies of Chinese dialectical materialism have long neglected the important philosophical dimension of Hegelian thought and its influence on Chinese Marxism. This essay examines the work of Zhang Shiying of Beijing University, whose studies of Hegel's works on dialectical logic in the 1950s sought to clarify the nature of Hegel's speculative dialectic and its relation to dialectical materialism. Like Lenin before him, Zhang believed that Hegel's works on logic offered a more profound reflection on materialism than had previously been recognized by Marxist critics of German idealism. Zhang's sensitive reading of both Hegel's Science of Logic and the Encyclopedia Logic highlights the problem of the speculative dialectic and negativity. Examined here is Zhang's analysis of the Hegelian dialectic in light of contemporary accounts of the role of Hegelian negativity in poststructuralist thought.