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IntroductionCytisinicline (known as cytisine), a nicotinic acetylcholine receptor partial agonist, is a smoking cessation aid currently marketed in Central and Eastern Europe using a 1.5-mg/tablet 25-day downward titration schedule. No prior studies have evaluated other doses or administration schedules. This study evaluated the effects of a higher dosage and simplified dosing schedule on drug efficacy and tolerability.MethodsORCA-1 was a double-blind, randomized, placebo-controlled clinical trial that provided cytisinicline or placebo tablets plus behavioral support for 25 days. Adult smokers (>10 cigarettes daily) committed to quitting smoking were randomized to compare 2 cytisinicline doses (1.5 mg and 3 mg) versus placebo, and 2 administration schedules [downward titration versus 3 times daily (TID)]. Primary outcome was a reduction in expected cigarettes smoked at end of treatment; secondary outcomes were biochemically confirmed 7-day abstinence at Week 4 and continuous abstinence from Weeks 5 to 8.ResultsAmong 254 participants, those in cytisinicline arms (regardless of dose or schedule) had greater reductions in cigarettes smoked versus placebo, with differences observed in 3 cytisinicline arms statistically significant versus placebo. All cytisinicline arms had statistically significantly higher abstinence rates at Week 4 versus placebo. Both cytisinicline arms using TID schedules had statistically significantly higher continuous abstinence rates from Weeks 5 to 8 compared with placebo. Participants in the cytisinicline 3-mg TID arm had the highest abstinence rate. There were no safety concerns with either 1.5-mg or 3-mg cytisinicline.ConclusionBased on simpler dose scheduling, excellent tolerability, and best-continued abstinence rate, cytisinicline 3-mg TID was selected for future Phase 3 studies.ImplicationsAlthough the 1.5-mg 25-day titration schedule has been marketed in Central and Eastern Europe for decades, this study explored using a higher dosage and a simplified dosing schedule for impact on cytisinicline efficacy and tolerability. Based on these results, a Phase 3 program was initiated using cytisinicline 3-mg tablets on a TID schedule for potential market approval in the United States.

The serine-rich repeat (SRR) glycoproteins of gram-positive bacteria are a family of adhesins that bind to a wide range of host ligands, and expression of SRR glycoproteins is linked with enhanced bacterial virulence. The biogenesis of these surface glycoproteins involves their intracellular glycosylation and export via the accessory Sec system. Although all accessory Sec components are required for SRR glycoprotein export, Asp2 of Streptococcus gordonii also functions as an O-acetyltransferase that modifies GlcNAc residues on the SRR adhesin gordonii surface protein B (GspB). Because these GlcNAc residues can also be modified by the glycosyltransferases Nss and Gly, it has been unclear whether the post-translational modification of GspB is coordinated. We now report that acetylation modulates the glycosylation of exported GspB. Loss of O-acetylation due to aps2 mutagenesis led to the export of GspB glycoforms with increased glucosylation of the GlcNAc moieties. Linkage analysis of the GspB glycan revealed that both O-acetylation and glucosylation occurred at the same C6 position on GlcNAc residues and that O-acetylation prevented Glc deposition. Whereas streptococci expressing nonacetylated GspB with increased glucosylation were significantly reduced in their ability to bind human platelets in vitro, deletion of the glycosyltransferases nss and gly in the asp2 mutant restored platelet binding to WT levels. These findings demonstrate that GlcNAc O-acetylation controls GspB glycosylation, such that binding via this adhesin is optimized. Moreover, because O-acetylation has comparable effects on the glycosylation of other SRR adhesins, acetylation may represent a conserved regulatory mechanism for the post-translational modification of the SRR glycoprotein family.

The purpose of this case study was to investigate the perception and experience of ten new faculty member participants in paired teaching. Along with providing evidence for paired teaching as an avenue for professional development in higher education, the study provides experiential narratives of paired teaching relationships as an illustration of the process. Key outcomes of the study include: the value of peer-to-peer engagement for prompting reflection on practice and facilitation of instructor use of active learning approaches within the classroom.

Teacher education programmes are embedded in both higher and K-12 education contexts. This study explores how collective teacher agency is developed and manifested within two online teacher education courses in a Canadian university and a Chinese university, respectively, under the Covid-19 pandemic context. Employing a digital ethnographic approach, this study reveals that: (1) the structural changes caused by the pandemic create common goals for collective teacher agency to develop; (2) collective teacher agency is motivated by caring for student well-being and honing of teaching skills; and (3) the asynchronous course structure hindered Chinese student teachers' collective efforts to improve teaching but afforded the Canadian group greater collective agency in connecting with their schools. Importantly, this study highlights the role of emotions in facilitating collective agency and argues that emotions are an integral but often overlooked part of teacher agency.

This study describes the practicum-mentors' identity in a teacher education context based on Dialogical Self Theory (DST) and the related 'position' and 'I-position' concepts. Participants were 48 Spanish and Canadian primary and secondary teachers who participated via an online written survey. The data were analysed using qualitative and quantitative procedures. Findings show a comprehensive description of nine types of positions and twenty types of I-positions. Based on these categories, three clusters of practicum-mentors, which represent three different ways of being a mentor, were identified: (1) a collaborative partner focused on student-teacher (ST) professional development, including the design, and teaching of ST skills acquisition; (2) a collaborative partner focused on design, teaching, and assessment of ST skills acquisition, and (3) a coaching partner focused on teaching and individualised ST learning. The findings can promote closer collaboration between universities and schools concerning the design of more relevant professional development for mentors based on the three identified ways of being a mentor.

The serine-rich repeat (SRR) glycoproteins are a family of adhesins found in many Gram-positive bacteria. Expression of the SRR adhesins has been linked to virulence for a variety of infections, including streptococcal endocarditis. The SRR preproteins undergo intracellular glycosylation, followed by export via the accessory Sec (aSec) system. This specialized transporter is comprised of SecA2, SecY2 and three to five accessory Sec proteins (Asps) that are required for export. Although the post-translational modification and transport of the SRR adhesins have been viewed as distinct processes, we found that Asp2 of Streptococcus gordonii also has an important role in modifying the SRR adhesin GspB. Biochemical analysis and mass spectrometry indicate that Asp2 is an acetyltransferase that modifies N-acetylglucosamine (GlcNAc) moieties on the SRR domains of GspB. Targeted mutations of the predicted Asp2 catalytic domain had no effect on transport, but abolished acetylation. Acetylated forms of GspB were only detected when the protein was exported via the aSec system, but not when transport was abolished by secA2 deletion. In addition, GspB variants rerouted to export via the canonical Sec pathway also lacked O-acetylation, demonstrating that this modification is specific to export via the aSec system. Streptococci expressing GspB lacking O-acetylated GlcNAc were significantly reduced in their ability bind to human platelets in vitro, an interaction that has been strongly linked to virulence in the setting of endocarditis. These results demonstrate that Asp2 is a bifunctional protein involved in both the post-translational modification and transport of SRR glycoproteins. In addition, these findings indicate that these processes are coordinated during the biogenesis of SRR glycoproteins, such that the adhesin is optimally modified for binding. This requirement for the coupling of modification and export may explain the co-evolution of the SRR glycoproteins with their specialized glycan modifying and export systems.

Agency and structure postulate a dialectic relationship: agents' actions shape and are shaped by social structure in a spiral and dynamic manner. Empirical studies in pre-collegiate science education contexts, however, tend to focus on individual's positionality instead of the engagement between agency and structure. This paper first charts the theoretical and methodological terrains of agency and structure from sociological, critical/post-structural, and psychological perspectives. It then reviews empirical studies on the agency-structure dialectic in pre-collegiate science education with a focus on their theoretical frameworks (agency), research contexts (structure), and related methods and methodologies. The reviewed studies are divided into four categories: teacher agency, teacher-and-student agency, student agency, and administrator agency. The results reveal how the agency-structure dialectic is taken up and studied in science education and how the notions of culture and language provide the possibility for hybrid perspectives of agency. We argue that the notion of emergence, based on the engagement within and among individual and collective agencies and structures, is the key to move beyond the current agency-structure dialectic in science education.

This study examines a group of teachers' moral agency in the context of China's curriculum reform. While the reform possesses neo-liberal features such as decentralisation and education for global competitiveness, it also attempts to undermine the long-standing influence of exam-oriented education in China. Employing ethnographic approaches, the results indicate that teachers' moral agency within this context has three specific foci: (1) directing students to become moral people; (2) dedication to teaching; and (3) developing knowledge for and about teaching. Although the study acknowledges that external accountabilities do constrain teachers' autonomy, teachers' moral agency is shaped and enabled by engagement with students and teachers still have a say in what is educationally desirable.

This study explores how physics teachers in a high school negotiate the relationships between individual and collective agencies in the context of the on-going curriculum reform in China. Drawing on Bandura's social cognitive theory, the study employs ethnographical methods including observation, interviewing, and the researcher's and teachers' reflective journaling through the researcher's involvement with various school activities. The findings indicate that collective teacher agency creates a platform for individual teachers' professional development, a conducive culture for teacher collaboration, and provides concrete examples that individual teachers can constantly refer to, reflect upon, and learn from for reform implementation. The results offer an understanding of the influences underlying physics teachers' agency deployment as they engage with curriculum reform processes, especially the negotiation between individual and collective agencies. The findings justify a case for preparing physics teachers on how to deploy both individual and collective agencies in the face of the complicated social structures and ultimately shed light on the desired curriculum decentralization in the Chinese school system.

This study examines how a cohort of 32 Chinese student teachers experience a 3-week Intensive Study Abroad Programme in Canada, which focused on facilitating understanding of teaching and learning from an international perspective. Research findings underscore the effectiveness of a context responsive approach to cross-cultural teaching and learning that places emphasis upon modelling and deliberate explication of teaching practice, experiential learning and dialogic reflection.

Scientific argumentation skills are important for students for expressing their opinions, making decisions and solving problems in daily life. Previous studies have focused on students' scientific argumentation skills, but few studies have proposed an instructional model for specifically developing these skills by creating a supportive classroom atmosphere that considers factors that may influenced on students' ability to successfully enact argumentation practices. In this study, researchers have adapted the Argument-Driven Inquiry (ADI) model, which is a model that meets several important criteria for fostering argumentation in the classroom and we have revised the model to satisfy practical constraints faced by teachers and students in Thai classroom contexts. In this study, we describe our revised Argument-Driven Inquiry (rADI) model and provide examples of how this model was used to increase students' scientific argumentation skills when learning about socio-scientific issues. We additionally examine factors, such as gender, reasoning ability, prior experience with scientific argumentation, and content knowledge to determine what influence they may have on students' post-instruction scientific argumentation skills. Specifically, we examined the effect the rADI model had on students' abilities after controlling for covariates. We surveyed 155 Grade 10 students to assess their scientific argumentation skills using a set of situational open-ended questions. The data were analyzed using descriptive statistics, correlation, and ANCOVA. Findings indicated that 1) most students could develop or improve scientific argumentation skills after the instruction in most components, although the supportive argument element tended to be weaker; 2) pretest scientific argumentation skills was correlated with posttest scientific argumentation skills, but gender, content knowledge, and reasoning ability were not correlated with posttest scientific argumentation skills; 3) and after controlling for pretest scientific argumentation skills, students in the experimental group produced higher posttest scores of scientific argumentation skills than those taught by the conventional approach (p < 0.05). Outcomes from our study using the rADI model may be beneficial to teachers who seek to improve students' scientific argumentation skills in science classrooms in the Thai context. Implications for local and international use of rADI are discussed.

This exploratory study examines the evolving nature of Chinese pre-service teachers' identity in relation to their experiences of school-based learning to teach during an 8-week internship. The results suggest that the identities of the four Chinese pre-service teachers in this study are anchored by two dimensions: their commitment to teaching and their perception of the teacher's role. After the internship, the four pre-service teachers' identities all shifted with respect to these two dimensions. The findings address an issue of potential conceptual confusion about the relationship between identity and learning to teach, which is neither linear nor unidirectional, but reciprocal. Further, the outcomes of this study suggest that there is a need to be more sensitive and responsive to identity shifts as students negotiate the transition from being a pre-service teacher to practicing professional. Lastly, this study conducted in a non-Western professional context, that is, a Chinese Teacher Education and Chinese School context, offers a valuable but missing perspective on teacher identity in the Western literature.

Taking on an agentic perspective, this study employed a digital ethnographic approach to examine a science teacher's emotional experiences in an online graduate science education course during the COVID‐19 pandemic. Veronika, the teacher, revealed her feelings of grievance and loss to the graduate course cohort at the advent of large‐scale school closures. Her emotions, shared through the online course, connected the members of the cohort to overcome emotional and pedagogical difficulties caused by the pandemic. She received both emotional and professional support from the cohort and designed an environmental related learning activity that centered on fun and connection in science learning. The activity stimulated students' positive emotions and simultaneously served to reset Veronika's emotions. This study underlined that emotions connect teachers during a social crisis in ways that address obstacles encountered in teaching and learning. Lessons for teacher education include providing space for and acknowledging emotions in teaching, especially in times of stress and the importance of fostering agentic actions, collegiality, and collaboration by explicitly connecting an individual's emotions and beliefs to their professional practice. [ABSTRACT FROM AUTHOR]

This case study sought to determine the professional development circumstances in which a preservice teacher learned rules of practice (Wittgenstein, 1996) on practicum while interacting with a cooperating teacher and university supervisor. Borrowing from a theoretical conceptualization of teacher professional development based on the postulates of a general theory of learning (Berducci, 2004; Nelson, 2008) and collective action (Wittgenstein, 1996), this study showed that teaching rules of practice is (i) effective when it makes use of contexts and exemplars anchored in the preservice teacher's experience and, (ii) before the preservice teacher is able to follow the rules in the classroom, he needs to be monitored by the cooperating teacher and university supervisor within a community of practice. These share with the preservice teacher the cognitive background and associated intentions that they bring to the setting and that he does not (yet) have and that he will construct through discourse and actual teaching. (Contains 1 figure and 2 tables.)

This research paper explores pre-service science teachers' understandings of classroom research, problems in conducting classroom research and the supports that pre-service science teachers need from their cooperating teachers to help them conduct a classroom research project during the internship period. The participants in this study are 19 pre-service science teachers in a teacher education institution situated in Western Thailand. The research instruments included a questionnaire about the understanding of classroom research and interviews with the pre-service science teachers regarding the problems in conducting a classroom research project and the supports that they need from their cooperating teachers in conducting the classroom research project. The data were analysed using descriptive statistics and content analysis. The results indicate that most of the pre-service science teachers understood the principles of classroom research. The problems the pre-service science teachers encountered in conducting classroom research were the limitation of time, generating suitable research question and selecting the innovation to solve the problem. Pre-service science teachers would like recommendations from their cooperating teachers more frequently for promoting the pre-service science teachers' confidence and efficiency in their chosen classroom research projects. This study has direct implications for the ways in which we introduce and engage pre-service science teachers into inquiry-oriented practice in their chosen profession. A questionnaire and an interview protocol are appended. [This research was funded by the Kasetsart University Graduate School.]

The scholarship of teaching and learning (SoTL) is a distinctive form of research that is shaped by multidisciplinary contexts and focuses on practice-driven institutional/curricula/classroom inquiries with an explicit transformational agenda. This essay provides critical insight to the importance of communities of SoTL practitioners, diverse investigations and methodological approaches within and across disciplines. For example, through an integrated and iterative process, a community of SoTL researchers plays a critical role to enhance and sustain on-going SoTL research. Equal to all forms of research endeavour, interpretations of SoTL research require a healthy scepticism, analysis of methodological rigour, and an openness to alternative perspectives and analysis.

This study investigated a professional learning community of cooperating teachers and university-based teacher educators. To examine our roles and perspectives as colleagues in teacher education, we drew on frameworks in teacher learning and complexity science. Monthly group meetings of this inquiry community were held over two school years in a suburban school district in British Columbia. Participants' current and prior experiences in the role of cooperating teacher provided rich topics for conversation. Our analysis illustrates how aspects of complexity thinking both enable and promote teacher learning, in this instance, the professional development of cooperating teachers. The study highlights (a) key tensions that allow for deeper exploration of issues, (b) the need for flexibility that is open to contingency, (c) the importance of reducing hierarchical structures to enable networks to develop, and (d) improvisation as a key ingredient for teacher learning. (Contains 2 tables, 2 figures, and 2 footnotes.) ["The Teacher Education Conversation: A Network of Cooperating Teachers" was written with Dianne Coulter, Tina Grigoriadis, Stephanie Hardman, Lee Hunter, Jane Kinegal, Bianca Li, Jeff Mah, Karen Mastin, David Partridge, Kathleen Salbuvik, Mitch Ward, Frederick Weil, Janet White, Kang Changyun, and Gaalen Erickson.]

The intent of this paper is to make sense of and share with a broader community of teachers and teacher educators a professional development phenomenon that is peculiar to the Chinese elementary and secondary school context. This practice, known as the Open Class, has at least three forms: intra-school, inter-school, and competitive. These forms are defined and delineated at the outset of the paper with particular attention to the distinguishing characteristics of each. This conceptual groundwork paves the way for a detailed historical accounting of this phenomenon over the past 65 years. What we learn is that the Open Class, as a professional development strategy, has waxed and waned based on the political and educational emphases of the day but nonetheless is alive and well in modern-day China. Indeed, it is so commonplace that it has become a norm in Chinese schools. While there remains much to be learned about the Open Class, four lessons learned as a result of the exposition offered in this paper provide a strong basis and valuable springboard for further exploration.