THE MANDARIN ORAL MASTERY PROGRAMME AS PERCEIVED BY NON-NATIVE LEARNERS

Background and Purpose: Pinyin is required in learning Mandarin. The challenge of Romanised Pinyin is that learners must decipher the meaning of words based on the change of tone. Communication research is often conducted without accounting for the effects of the change of tone in learning a language. With the aim of avoiding miscommunication while strengthening awareness, Campus Buddies Programme was employed to provide tone practice for learners and consequently explores the effectiveness of the intervention. Methodology: This quantitative classroom-based research gathered information through the administration of a questionnaire. The questionnaire was distributed to 32 Mandarin Level 1 learners identified through purposive sampling. The students studied five topics from the syllabus. A total of 10 native speakers who scored A in Sijil Pelajaran Malaysia (SPM) mentored the learners during the programme. The participants were instructed to answer both pre- and post-tests. Part A consists of demographic details, whereas Part B focuses on the effectiveness of questions and Part C consists of 30 questions of content learned by the respondents. The data were then analysed using SPSS 26 software. Findings: The respondents demonstrated a positive response towards the programme and suggested further improvement ideas such as prolonging the training session and adding more topics and oral activities. The results implicated the programme as a motivator for oral fluency. Many non-native speakers can benefit from conversation with Mandarin native speakers because it is a strong indicator and sound oral mastery strategy. Contributions: This research provides insights into the effectiveness of the current programme in motivating students’ oral learning. The outcome is essential in determining the Mandarin conversation strategy. More studies adopting different variables are proposed to explore correlations from different perspectives in order to improve students’ oral learning. Keywords: Tonal pronunciation, native speakers, non-native speakers, foreign language instruction, Mandarin conversation. Cite as: Chua, N. A., Soon, G. Y., Ibrahim, M. Y., Che Noh, C. H., Mansor, N. R., Embong Eusoff, A. M., Abdul Rashid, R., & Shen, M. (2022). The Mandarin oral mastery programme as perceived by non-native learners. Journal of Nusantara Studies, 7(1), 1-23. http://dx.doi.org/10.24200/jonus.vol7iss1pp1-23

474 Phase 1 study of SEA-TGT, a human, nonfucosylated anti-TIGIT monoclonal antibody with enhanced immune-effector function, in patients with advanced malignancies (SGNTGT-001, trial in progress)

BackgroundT-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory domains (TIGIT), and costimulatory receptor CD226 competitively bind 2 ligands, CD155 and CD112, which are expressed by tumor cells and antigen-presenting cells in the tumor microenvironment.1 2 Dual TIGIT/programmed cell death protein-1 (PD-1) blockade increased tumor antigen-specific CD8+ T-cell expansion and function in vitro and promoted potent antitumor response in vivo.3 4 TIGIT/PD-1 dual blockade using a TIGIT monoclonal antibody (mAb) with intact Fc produced clinical responses in advanced cancer.5 SEA-TGT is an investigational, human, nonfucosylated mAb directed against TIGIT. SEA-TGT binds to TIGIT, blocking inhibitory checkpoint signals directed at T cells. SEA-TGT enhances binding to activating FcγRIIIa and decreases binding to inhibitory FcγRIIb; this depletes immunosuppressive regulatory T cells and amplifies naive and memory T cells, potentially augmenting PD-1 inhibition effects. Preclinically, at suboptimal doses, SEA-TGT plus anti-PD-1 mAbs had superior antitumor activity than either agent alone.6MethodsSafety and antitumor activity of SEA TGT in ~377 adults (≥18 years) will be evaluated in this phase 1, multicenter, open-label, dose-escalation/expansion study. Part A will assess the safety/tolerability of SEA TGT to determine maximum tolerated and recommended doses. Part B will assess the safety and antitumor activity of the recommended dose in disease-specific expansion cohorts. Part C will assess SEA-TGT plus sasanlimab in dose-expansion cohorts after an initial safety run-in. Patients with histologically/cytologically confirmed relapsed/refractory/progressive metastatic solid tumors including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastric/gastroesophageal junction carcinoma, cutaneous melanoma, bladder, cervical, ovarian or triple-negative breast cancer, or selected lymphomas will be eligible for Parts A and B. Part C will enroll patients with histologically confirmed advanced NSCLC (high [tumor proportion score (TPS) ≥50%] and low [TPS=1–49%] PD ligand 1 [PD-L1] expression), cutaneous melanoma, and HNSCC without previous anti–PD-1/PD-L1 therapy exposure. SEA TGT will be administered on Day 1 of 21-day cycles.Laboratory abnormalities, adverse events, dose-limiting toxicities, and dose-level safety and activity are primary endpoints. Secondary endpoints are objective response (OR) and complete response (CR) rates, duration of OR/CR, progression-free survival, overall survival, pharmacokinetics (PK), and antidrug antibodies. Exploratory analysis will include pharmacodynamics (PD), PK/PD relationships, biomarkers, and resistance to SEA-TGT. This trial is recruiting in Europe and North America.Trial RegistrationNCT04254107ReferencesBlake SJ, Dougall WC, Miles JJ, et al. Molecular pathways: Targeting CD96 and TIGIT for cancer immunotherapy. Clin Cancer Res 2016;22(21):5183–5188.Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J ImmunoTher Cancer 2020;8:e000957.Johnston RJ, Comps-Agrar L, Hackney J, et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. Cancer Cell 2014;26(6):923–937.Chauvin JM, Pagliano O, Fourcade J, et al. TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients. J Clin Invest 2015;125(5):2046–2058.Rodriguez-Abreu D, Johnson ML, Hussein MA, et al. Primary analysis of a randomized, double-blind, phase 2 study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE). J Clin Oncol 2020;38(15 suppl):9503.Smith A, Zeng W, Lucas S, et al. Poster 1583. SEA-TGT is an empowered anti-TIGIT antibody that displays superior combinatorial activity with several therapeutic agents. Presented at: American Association for Cancer Research Annual Meeting; April 9–14, 2021; Virtual Meeting.Ethics ApprovalInstitutional review boards or independent ethics committees of participating sites approved the trial, which will be conducted in compliance with the Declaration of Helsinki and International Conference on Harmonisation Guidelines for Good Clinical Practice. All patients will provide written informed consent.

Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial

Purpose In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension. Methods A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety. Results Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration. Conclusion Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure. Trial registration NCT02705755 (first posted March 10, 2016).

Normal Polytopes and Ellipsoids

We show that: (1) unimodular simplices in a lattice 3-polytope cover a neighborhood of the boundary of the polytope if and only if the polytope is very ample, (2) the convex hull of lattice points in every ellipsoid in $\mathbb{R}^3$ has a unimodular cover, and (3) for every $d\geqslant 5$, there are ellipsoids in $\mathbb{R}^d$, such that the convex hulls of the lattice points in these ellipsoids are not even normal. Part (c) answers a question of Bruns, Michałek, and the author.

Marizomib alone or in combination with bevacizumab in patients with recurrent glioblastoma: phase I/II clinical trial data

Background This phase I/II trial in patients with recurrent glioblastoma (GBM) evaluates the safety and preliminary efficacy of marizomib, an irreversible pan-proteasome inhibitor that crosses the blood–brain barrier. Patients and Methods Part A assessed the safety and efficacy of marizomib monotherapy. In Part B, escalating doses of marizomib (0.5–0.8 mg/m2) in combination with bevacizumab were evaluated. Part C explored intra-patient dose escalation of marizomib (0.8–1.0 mg/m2) for the combination. Results In Part A, 30 patients received marizomib monotherapy. The most common AEs were fatigue (66.7%), headache (46.7%), hallucination (43.3%), and insomnia (43.3%). One patient (3.3%) achieved a partial response. In Part B, the recommended phase II dose of marizomib was 0.8 mg/m2 when combined with bevacizumab 10 mg/kg. In Part C, dose escalation to 1.0 mg/m2 was not tolerated. Pooled analysis of 67 patients treated with marizomib ≤0.8 mg/m2 and bevacizumab showed a non-overlapping safety profile consistent with the known safety profile of each agent: the most common grade ≥3 AEs were hypertension (16.4%), confusion (13.4%), headache (10.4%), and fatigue (10.4%). The overall response rate was 34.3%, including 2 patients with complete response. Six-month progression-free survival was 29.8%; median overall survival was 9.1 months. Conclusions The safety profile of marizomib as monotherapy and in combination with bevacizumab was consistent with previous observations that marizomib crosses the blood–brain barrier. Preliminary efficacy did not demonstrate a meaningful benefit of the addition of marizomib to bevacizumab for the treatment of recurrent GBM.

New Intersection Crash Prediction Models for the Second Edition of the Highway Safety Manual

The objective of this research was to develop new intersection crash prediction models for consideration in the second edition of the Highway Safety Manual (HSM), consistent with existing methods in HSM Part C and comprehensive in their ability to address a wide range of intersection configurations and traffic control types in rural and urban areas. The focus of the research was on developing safety performance functions (SPFs) for intersection configurations and traffic control types not currently addressed in HSM Part C. SPFs were developed for the following general intersection configurations and traffic control types: rural and urban all-way stop-controlled intersections; rural three-leg intersections with signal control; intersections on high-speed urban and suburban arterials (i.e., arterials with speed limits greater than or equal to 50 mph); urban five-leg intersections with signal control; three-leg intersections where the through movements make turning maneuvers at the intersections; crossroad ramp terminals at single-point diamond interchanges; and crossroad ramp terminals at tight diamond interchanges. Development of severity distribution functions (SDFs) for use in combination with SPFs to estimate crash severity as a function of geometric design elements and traffic control features was explored; but owing to challenges and inconsistencies in developing and interpreting the SDFs, it was recommended for the second edition of the HSM that crash severity for the new intersection configurations and traffic control types be addressed in a manner consistent with existing methods in Chapters 10, 11, and 12 of the first edition, without use of SDFs.