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The article presents the discussion on roles, expectations, and responsibilities of teachers. Topics include providing pre-service teachers with abilities to be adaptive experts making decisions based on varying contexts, choose practices aligning with the beliefs and core values; and promoting self-authorship in pre-service teachers in preparation for the demands of being a first year teacher.

This article reflects on Stellenbosch University Writing Lab’s pedagogical approach to multilingualism and inclusivity within the complex and political nature of multilingual language policies at a South African university. The Writing Lab has always been promoted as a facility for all students, not just those in need of ‘remedial’ support. This was a departure from earlier academic literacies models that tended to view students from nondominant language groups in terms of deficits. Academic literacies research has pointed to the shortcomings of these earlier approaches and to the value conflicts that arise from them. We, in contrast, argue that Carter’s (2009) writing centre paradox provides a dynamic rhetorical space in which to explore issues around South African multilingualism and inclusivity in higher education, and for this reason we do not wish to resolve the paradox. Instead, we use it to critically appraise our type of equitable multilingualism and maintain and honour multivocality. We also argue that South African writing centres enjoy a somewhat different trajectory from that of many other academic literacies spaces by virtue of the one-to-one pedagogy and mutualistic approach we follow at these writing centres. This has allowed us simultaneously more agency and less agency and we need to use this paradoxical position strategically in our institutions. Using the Writing Lab as a case study, we reflect on the ways in which the Writing Lab gives life to its ethos of being a multilingual and inclusive space for academic transformation within the institution’s language policy. To support our reflections, we draw on descriptions of the organisational structure of the Lab, feedback received from strategic role players and observations of interactions performed in the various Lab spaces. We also consider the Writing Lab in terms of South African writing centre scholarship to see how the Lab’s philosophy and ethos compare with the ideals.

In post-apartheid South Africa, writing centres exist in almost every university to address the academic writing needs of students. At Stellenbosch University Writing Lab, writing consultants use collaborative learning and peer feedback in their work with writers in one-to-one consultations. As part of a larger research project about how students in a Health Professions Education Master’s degree responded to different types of feedback, our study focuses on whether the feedback received in a writing consultation compares to, or differs from, the feedback from the class group members. Our findings suggest that in general the students were open to interventions such as writing consultations. Furthermore, peer feedback from both a class group member as well as a writing consultant was experienced as useful. The study further shows that the consultants’ approach to giving feedback was in line with the pedagogy practised in writing centres. The article concludes with measures that were implemented to address uncertainties identified in the study. We recommend that the purpose of consultations be clarified to lecturers, that consultations be integrated in the writing process before the assignment is marked and, to minimise role confusion, that consultants describe to students the way consultations work at the beginning of the consultation.

he study on the relationship of identity, language and teaching and learning was conducted by a team of eight members at a higher education institution in the Western Cape. The aims of the research were to investigate the relationship between language, identity and learning, to show how this investigation can benefit dialogue about transformation, and to facilitate the research development of the team. The research design made use of narrative and educational biography in semi-structured interviews with 64 staff members and 100 students. The study supports views of identity as constructed and non-unitary. It shows how language, both as proficiency in the dominant medium of communication and as discourse, is a key component of identity in a higher education institution. The interviews demonstrated how, according to lecturers and students, language and discourse function as primary influences on individuals’ acculturation and integration into the academic community. According to the interviewees, language as a marker of identity is interwoven with other aspects of identity. It is both a resource and a source of identification and affiliation. The research demonstrated that dialogue and self reflection can be facilitated via research into identity, teaching and learning, and that this can be beneficial for both the interviewees and the research team.

The botulinum neurotoxins (BoNTs) are di-chain bacterial proteins responsible for the paralytic disease botulism. Following binding to the plasma membrane of cholinergic motor nerve terminals, BoNTs are internalized into an endocytic compartment. Although several endocytic pathways have been characterized in neurons, the molecular mechanism underpinning the uptake of BoNTs at the presynaptic nerve terminal is still unclear. Here, a recombinant BoNT/A heavy chain binding domain (Hc) was used to unravel the internalization pathway by fluorescence and electron microscopy. BoNT/A-Hc initially enters cultured hippocampal neurons in an activity-dependent manner into synaptic vesicles and clathrin-coated vesicles before also entering endosomal structures and multivesicular bodies. We found that inhibiting dynamin with the novel potent Dynasore analog, Dyngo-4a™, was sufficient to abolish BoNT/A-Hc internalization and BoNT/A-induced SNAP25 cleavage in hippocampal neurons. Dyngo-4a also interfered with BoNT/A-Hc internalization into motor nerve terminals. Furthermore, Dyngo-4a afforded protection against BoNT/A-induced paralysis at the rat hemidiaphragm. A significant delay of >30% in the onset of botulism was observed in mice injected with Dyngo-4a. Dynamin inhibition therefore provides a therapeutic avenue for the treatment of botulism and other diseases caused by pathogens sharing dynamin-dependent uptake mechanisms. [ABSTRACT FROM AUTHOR]

Patients with relapsed/refractory (R/R) transformed diffuse large B-cell lymphoma (DLBCL) from indolent B-cell lymphomas, including Richter transformation (RT), have a poor prognosis. PD-1/PD-L1 antibodies produce modest objective and complete response rates (ORR and CRR) in B-NHL as monotherapy but may synergize with immunogenic chemotherapies like gemcitabine and oxaliplatin (GemOx). Thus, we evaluated the safety and efficacy of atezolizumab plus rituximab and GemOx (R-GemOx+Atezo) in R/R transformed DLBCL, including RT. We conducted a phase I trial including patients with transformed DLBCL after ≥1 prior therapy. Patients received up to 4 cycles of R-GemOx-+Atezo. Patients in CR could then proceed to Ratezo maintenance until progression. A safety lead-in with dose-limiting toxicity (DLT) evaluation was enrolled to confirm the recommended phase 2 dose (RP2D), followed by 2 expansion cohorts: one for transformed follicular lymphoma (FL) and another for non-FL transformed DLBCL, including RT. Twenty-seven patients were enrolled. One of the 6 safety lead-in patients had a DLT attributed to atezolizumab, a grade 4 Stevens-Johnson syndrome (SJS). The most common grade ≥3 events were neutropenia (18.5%), lymphopenia (18.5%), and thrombocytopenia (14.8%). The overall and complete response rates (ORR and CRR) were 59% and 33%, respectively. The ORR and CRR in transformed FL were 79% and 43%, and 38% and 23% in transformed non-FL, respectively. The median PFS and OS of the total population were 4.2 and 7.7 months, respectively. R-GemOx+Atezo was well tolerated and demonstrated promising preliminary efficacy in patients with R/R transformed DLBCL.

Outcomes after programmed death-1 (PD-1) blockade in B-cell lymphomas are disappointing with few durable responses. Histone deacetylase inhibitors exhibit favorable immunomodulatory effects and demonstrate synergistic anti-tumor immune responses with anti-PD-1 therapy in preclinical models. We, therefore, developed a phase I study to evaluate the safety and preliminary efficacy of pembrolizumab with vorinostat in relapsed/refractory B-cell lymphomas. Patients were treated in a dose-escalation cohort using a Rolling 6 design followed by an expansion cohort at the recommended phase II dose (R2PD). Fifty-two patients were enrolled (32 Hodgkin and 20 non-Hodgkin lymphoma [NHL]). Here, we report safety data from the dose escalation cohort, and the toxicity and efficacy within NHL patients. Vorinostat was administered twice daily on days 1-5 and 8-12 (dose-level [DL]1: 100 mg; DL2: 200 mg) and pembrolizumab (200 mg) was administered on day 1 of each 3-week cycle. Of six patients treated at DL1, one had a dose-limiting toxicity (DLT) (Stevens-Johnson syndrome [SJS]), and one of six had a DLT at DL2 (thromboembolism); therefore, DL2 was the RP2D. The patient developing SJS was treated with corticosteroids, infliximab, and cyclosporine but ultimately died of invasive fungal infection from the extensive immunosuppression used to treat the SJS. The most common adverse events were hypertension, diarrhea, and cytopenias. Of 20 NHL patients, nine had follicular lymphoma (FL) and 11 had diffuse large B-cell lymphoma (DLBCL). Five DLBCL patients had primary mediastinal B-cell lymphoma (PMBL). The complete and overall response rates (CR and ORR) were 11% and 22% for FL and 45% and 55% for all DLBCL. Amongst DLBCL, the CR and ORR was 80% and 80% for PMBL and 17% and 33% for non-PMBL. In conclusion, pembrolizumab with vorinostat was tolerable and produced responses in relapsed/refractory B-cell NHL, with particularly notable efficacy in PMBL (clinicaltrials gov. Identifier: NCT03150329).

The botulinum neurotoxins (BoNTs) are di-chain bacterial proteins responsible for the paralytic disease botulism. Following binding to the plasma membrane of cholinergic motor nerve terminals, BoNTs are internalized into an endocytic compartment. Although several endocytic pathways have been characterized in neurons, the molecular mechanism underpinning the uptake of BoNTs at the presynaptic nerve terminal is still unclear. Here, a recombinant BoNT/A heavy chain binding domain (Hc) was used to unravel the internalization pathway by fluorescence and electron microscopy. BoNT/A-Hc initially enters cultured hippocampal neurons in an activity-dependent manner into synaptic vesicles and clathrin-coated vesicles before also entering endosomal structures and multivesicular bodies. We found that inhibiting dynamin with the novel potent Dynasore analog, Dyngo-4a(TM), was sufficient to abolish BoNT/A-Hc internalization and BoNT/A-induced SNAP25 cleavage in hippocampal neurons. Dyngo-4a also interfered with BoNT/A-Hc internalization into motor nerve terminals. Furthermore, Dyngo-4a afforded protection against BoNT/A-induced paralysis at the rat hemidiaphragm. A significant delay of >30% in the onset of botulism was observed in mice injected with Dyngo-4a. Dynamin inhibition therefore provides a therapeutic avenue for the treatment of botulism and other diseases caused by pathogens sharing dynamin-dependent uptake mechanisms.