Amyloid precursor protein (APP), upon proteolytic degradation, forms aggregates of amyloid β (Aβ) and plaques in the brain, which are pathological hallmarks of Alzheimer’s disease (AD). Cathepsin B is a cysteine protease enzyme that catalyzes the proteolytic degradation of APP in the brain. Thus, cathepsin B inhibition is a crucial therapeutic aspect for the discovery of new anti-Alzheimer’s drugs. In this study, we have employed mixed-feature ligand-based virtual screening (LBVS) by integrating pharmacophore mapping, docking, and molecular dynamics to detect small, potent molecules that act as cathepsin B inhibitors. The LBVS model was generated by using hydrophobic (HY), hydrogen bond acceptor (HBA), and hydrogen bond donor (HBD) features, using a dataset of 24 known cathepsin B inhibitors of both natural and synthetic origins. A validated eight-feature pharmacophore hypothesis (Hypo III) was utilized to screen the Maybridge chemical database. The docking score, MM-PBSA, and MM-GBSA methodology was applied to prioritize the lead compounds as virtual screening hits. These compounds share a common amide scaffold, and showed important interactions with Gln23, Cys29, His110, His111, Glu122, His199, and Trp221. The identified inhibitors were further evaluated for cathepsin-B-inhibitory activity. Our study suggests that pyridine, acetamide, and benzohydrazide compounds could be used as a starting point for the development of novel therapeutics.

The empirical research on dialogue-based pedagogies shows that they improve student outcomes and, thus, teachers should make more use of these methods (Edwards-Groves & Hoare, 2012). However deeper analyses about whether certain modes of dialogue are better than others is under-researched, resulting in little information about which models best help teachers develop effective dialogic learning practices (Howe & Abedin, 2013, p. 325). Some researchers have argued that there is a gap in the literature, as there has been little proper exploration of what constitutes effective classroom dialogue, with practical examples of how to structure discourse for learning lacking in classroom practice (Myhill et al., 2005; Mercer, 2010; Edwards-Groves & Hoare, 2012; Howe & Abedin, 2013). Edwards-Groves and Davidson (2020, p. 126) suggest that "developing a shared language and collective understandings about classroom talk and interaction among teachers, and with and among their students, largely remains taken-for-granted in practice." Howe and Abedin (2013) suggest that this leads to a lack of understanding about models of effective dialogue and allows poorer forms of dialogic pedagogy to persist. Alexander (2004) shares this concern that the most effective kinds of talk in classrooms are not widely practised. Nystrand (1997) also discusses how different modes of classroom discussion engender particular epistemic roles for both teachers and students, which can constrain their thinking and contribute to disadvantage. In sum, "the quality of student learning is closely related to the quality of classroom talk" (p. 29). Therefore, it is vitally important that we are able to demonstrate what kind of talk is most effective in the classroom. This paper identifies different kinds of dialogue-based pedagogies and, through conceptual analysis, articulates the notions of dialogue they assume and the educational implications of these different notions of dialogue. Four types of dialogic pedagogy have been identified in the existing literature. Although they may go by different names to different people, for consistency, this paper will categorise them as Teacher-Directed Dialogue, Mere Conversation, Adversarial Dialogue, and Exploratory Dialogue, each of which will be described in its own subsection.

This chapter argues that there is a gap in current research in Philosophy for/with Children (P4wC) that focusses on teachers' perspectives, and particularly in relation to their beliefs and values. This chapter will look briefly the current status of P4wC in the sphere of education broadly. It will then move on to exploring how teachers' perspectives, through analyses of their beliefs and values, adds significant value in education. This chapter then explores the importance of teachers' beliefs and values specifically in the context of P4wC, identifying the contribution that an analysis of teacher beliefs and values can make. It then concludes by analysing some recent P4wC research which has begun to explore teachers' perspectives, before finishing with future research directions that build on these previous studies which will lay important groundwork for extending the reach of P4wC into education systems.

Introduction: Dystocia is an important contributor to lamb mortality. Most studies that include lamb necropsies report cause of death using proportional mortality (expressed as a proportion of necropsies) rather than mortality incidence (expressed as proportion of lambs born). Understanding dystocia mortality incidence will inform research priorities to address the impact of dystocia.

Research objective: To collate and analyse existing data to determine the incidence of dystocia mortality in lambs and inform future research and extension priorities for improving lamb survival.

Method: Meta-analyses of lamb necropsy data from studies conducted in Australia and New Zealand since 2000. We analysed more than 46,000 lambing records involving 8228 lamb deaths and 6225 lamb necropsies using random effects models with a restricted maximum likelihood estimator to estimate pooled proportional dystocia mortality ratios and weighted summary dystocia mortality incidence (pooled and separately for each birth type).

Results: Dystocia mortality incidence (weighted summary proportion of lamb births) was 10% (95% confidence interval (CI): 8, 12) with very high heterogeneity between farms/studies (I²=98.3%). Dystocia mortality incidence was higher for triplet-born/higher-order-multiples (15%; 95% CI 11, 19) than twin-born (7%; 95% CI 5, 8) and single-born lambs (7%; 95% CI 5, 8). Dystocia proportional mortality (weighted summary proportion of necropsies) was 45% (95% CI 40, 49) with high heterogeneity (I²=92.8%) which was consistent with previous reviews. Multiple-born lambs are at similar or increased risk of dying from dystocia compared to single-born lambs.

Conclusion: Strategies to reduce dystocia impact and improve lamb survival should address risk factors for dystocia in all birth types.