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"Luo, Yang Cathy"
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Reading development and difficulties in monolingual and bilingual Chinese children
This volume explores Chinese reading development, focusing on children in Chinese societies and bilingual Chinese-speaking children in Western societies. The book is structured around four themes: psycholinguistic study of reading, reading disability, bilingual and biliteracy development, and Chinese children's literature. It discusses issues that are pertinent to improving language and literacy development, and complex cognitive, linguistic, and socio-cultural factors that underlie language and literacy development. In addition, the book identifies instructional practices that can enhance literacy development and academic achievement. This volume offers an integrative framework of Chinese reading, and deepens our understanding of the intricate processes that underlie Chinese children's literacy development. It promotes research in reading Chinese and celebrates the distinguished and longstanding career of Richard C. Anderson.
Book
The roles of metalinguistic skills in Chinese–English biliteracy development
The study examined the role of phonological awareness and morphological awareness in concurrent and subsequent oral vocabulary among Chinese–English bilingual children who learned Chinese as their heritage language and English as their societal language. Ninety-one Chinese–English bilingual children in kindergarten and Grade 1 who were recruited from Chinese heritage language classes in Canada, participated in the study. They were tested twice, 1 year apart, on a battery of cognitive and literacy measures in Chinese and English. The results indicated that for oral vocabulary, morphological awareness was the only concurrent predictor in both languages. English morphological awareness made a direct contribution to English vocabulary measured a year later. By contrast, the contribution of morphological awareness to vocabulary in Chinese at Time 2 was indirect and mediated by vocabulary at Time 1. Phonological awareness did not make a significant contribution to vocabulary at Times 1 or 2 in either language. Our results highlight the importance of morphological awareness in oral vocabulary for children learning Chinese and English.
Journal Article
The Experiences of Immigrants who Volunteer to Access the Labour Market
National surveys such as the Canadian Survey of Giving, Volunteering and Participating (CSGVP), and the Work and Lifelong Learning (WALL) survey reveal that the volunteering patterns and activities of immigrants and Canadian born volunteers are similar, donating time and energy to their communities (Volunteer Canada, 2007). The growing trend of immigrants doing unpaid work in the public, non-profit and private sectors explicitly to increase their employability, however, raises some interesting conceptual questions about the very definition of volunteer work and issues of power and exploitation in the workplace.
Book Chapter
Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment
Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20–50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers.
BAP1
/−3p21 and
FBXW7
/-chr4 events are always
early
clonal. In contrast,
NF2
/−22q events, leading to Hippo pathway inactivation are predominantly
late
clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of
NF2
/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition.
The impact of intratumour heterogeneity on immune surveillance and clinical outcomes has not been adequately explored in malignant pleural mesothelioma (MPM). Here the authors analyse the influence of evolution on the survival and immune landscape of MPM patients using multi-region sequencing data.
Journal Article
Constitutive inflammation and epithelial-mesenchymal transition dictate sensitivity to nivolumab in CONFIRM: a placebo-controlled, randomised phase III trial
Leveraging adaptive tumour immunity to control mesothelioma via immune checkpoint blockade is now a standard therapeutic approach. However, the determinants of sensitivity remain elusive. Low non-synonymous mutation burden and programmed death-ligand 1 expression, an abundance of immunosuppressive immune cell infiltration, and 9p21 deletion should all mitigate responses to therapy. To address this knowledge gap, we conducted a double blind, placebo-controlled, randomized phase III trial of the PD1 inhibitor, nivolumab (ClinicalTrial.gov registration: NCT03063450). After 37.2 months of follow-up, the primary endpoint of progression free-survival, but not overall survival was met. The nivolumab response rate was 10.3%, and related grade 3 or above adverse events occurred in 20.4% versus 7.2% for placebo. Progression-free and overall survival were longer in nivolumab-treated responders
versus
non-responders. In an exploratory multiomic analysis, blinded whole exome, transcriptome and multiplex immune profiling were used to interrogate R-
versus
NR-subgroups. Non-synonymous and neoantigen mutation burden were no different between groups, however R-mesotheliomas were infiltrated with activated CD8
+
T- and CD19
+
B-lymphocytes, organised into tertiary lymphoid structures. B-cell infiltration correlated with pro-inflammatory chemokines including IL24 and CCL19. Conversely, epithelial-mesenchymal transition and mitosis were associated with resistance to nivolumab. These findings illuminate features which can be leveraged to advance precision immunotherapy in this rare cancer setting.
The sensitivity of mesothelioma to the treatment of immune checkpoint blockade remains elusive. Here this group reports a double blind, placebo-controlled, randomized phase III trial of PD1 inhibitor (Nivolumab) on 332 patients with relapsed mesothelioma, and to uncover determinants of efficacy.
Journal Article
Clinical impact of pharmacogenetic risk variants in a large chinese cohort
Incorporating pharmacogenetics into clinical practice promises to improve therapeutic outcomes by optimizing drug selection and dosage based on genetic factors affecting drug response. A key advantage of PGx-guided therapy is to decrease the likelihood of adverse events. To evaluate the clinical impact of PGx risk variants, we performed a retrospective study using genetic and clinical data from the largest Han Chinese cohort, comprising 486,956 individuals, assembled by the Taiwan Precision Medicine Initiative. We found that nearly all participants carried at least one genetic variant that could affect drug response, with many carrying multiple risk variants. Here we show the detailed analyses of four gene-drug pairs, azathioprine (
NUDT15
/
TPMT
), clopidogrel (
CYP2C19
), statins (
ABCG2
/
CYP2C9
/
SLCO1B1
), and NSAIDs (
CYP2C9
), for which sufficient data exists for statistical power. While the results validate previous findings that PGx risk variants are significantly associated with drug-related adverse events or ineffectiveness, the excess risk of adverse events or lack of efficacy is small compared to that found in those without the PGx risk variants, and most patients with PGx variants do not suffer from adverse events. Our results point to the complexity of implementing PGx in clinical practice and the need for integrative approaches to optimize precision medicine.
Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.
Journal Article
Fine Comparison of the Efficacy and Safety Between GB242 and Infliximab in Patients with Rheumatoid Arthritis: A Phase III Study
IntroductionThis phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy.MethodsPatients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity.ResultsA total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62–68.20%) and 56.89% for the INF group (95% CI 50.90–62.74%). The difference between the two groups was 5.65% with a 95% CI of – 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable.ConclusionsGB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.
Journal Article
Safety and Efficacy of Moroctocog Alfa (AF-CC) in Chinese Patients with Hemophilia A: Results of Two Open-Label Studies
Moroctocog alfa albumin-free cell culture (AF-CC) increases plasma levels of factor VIII (FVIII) activity and, in China, is indicated for the control and prevention of bleeding episodes in patients with hemophilia A. This study aimed to evaluate the efficacy, safety, and recovery data of moroctocog alfa (AF-CC) in patients with hemophilia participating in two open-label studies, both conducted in China.
The authorization study (clinicaltrials.gov identifier NCT00868530) enrolled patients aged ≥6 years, previously treated with ≥1 exposure day of FVIII replacement therapy. The real-world study (clinicaltrials.gov identifier NCT02492984) enrolled patients of any age who were previously untreated or requiring surgical prophylaxis. In both studies, on-demand treatment was administered over 6 months. Key assessments included response to treatment, FVIII inhibitor development, and recovery.
In the authorization study (N = 53; mean age, 23.2 years; severe hemophilia, 23%), response was excellent/good for 90% of infusions at 24 hours. Seven patients developed inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.77 (0.50) and 1.67 (0.45) (IU/dL)/(IU/kg), respectively. In the real-world study (N = 85; mean age, 9.5 years; severe hemophilia, 58%), response was rated as excellent or good for most (87%) on-demand infusions and for all surgical prophylaxis patients (n = 14). Seven patients developed FVIII inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.71 (0.50) and 1.68 (0.31) (IU/dL)/(IU/kg), respectively. No new safety signals were observed in either study.
On-demand treatment and surgical prophylaxis with moroctocog alfa (AF-CC) is safe and effective for both previously treated and previously untreated Chinese patients with hemophilia A.
Journal Article