Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised c

BackgroundRecurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. MethodsA multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ≥6 years; and vaccine safety. DiscussionAs H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis

Affinity maturation of the RLIP76 Ral binding domain to inform the design of stapled peptides targeting the Ral GTPases.

Ral GTPases have been implicated as critical drivers of cell growth and metastasis in numerous Ras-driven cancers. We have previously reported stapled peptides, based on the Ral effector RLIP76, that can disrupt Ral signaling. Stapled peptides are short peptides that are locked into their bioactive form using a synthetic brace. Here, using an affinity maturation of the RLIP76 Ral-binding domain, we identified several sequence substitutions that together improve binding to Ral proteins by more than 20-fold. Hits from the selection were rigorously analyzed to determine the contributions of individual residues and two 1.5 Å cocrystal structures of the tightest-binding mutants in complex with RalB revealed key interactions. Insights gained from this maturation were used to design second-generation stapled peptides based on RLIP76 that exhibited vastly improved selectivity for Ral GTPases when compared with the first-generation lead peptide. The binding of second-generation peptides to Ral proteins was quantified and the binding site of the lead peptide on RalB was determined by NMR. Stapled peptides successfully competed with multiple Ral-effector interactions in cellular lysates. Our findings demonstrate how manipulation of a native binding partner can assist in the rational design of stapled peptide inhibitors targeting a protein-protein interaction

Trait evolution and the coexistence of a species swarm in the tropical forest understory

Part of PhD Dissertation of Brian Sedio. The paper also incorporates J. Wright's long term ecological data on Psychotria from BCI.1. A small number of species rich plant genera make a substantial contribution to the alpha diversity of tropical forests. These ‘species swarms’ (Gentry 1982) challenge a view of community assembly that maintains that niche overlap, and hence, the likelihood of competitive exclusion should increase with phylogenetic affinity. Related species may, however, occupy different microhabitats within a forest stand or, alternatively, differ ecologically in ways that allow them to coexist syntopically. 2. To explore the relationship between phylogenetic history and niche differentiation among sympatric, congeneric species, we performed phylogenetic analyses of microhabitat preferences, photosynthetic and hydraulic traits, and experimental responses to light and water availability for 20 species of Psychotria (Rubiaceae) from Barro Colorado Island (BCI), Panama. 3. The Psychotria present in small (3-m radius), circular plots were more closely related than expected by chance. Photosynthetic and hydraulic traits were both associated with species habitat distributions, but only hydraulic traits were conserved phylogenetically. Experimental responses to water availability were also conserved phylogenetically. Functional trait analyses revealed little or no evidence of niche partitioning within sites. 4. We conclude that Psychotria species’ responses to both light and moisture availability determine their microhabitat distributions on BCI and that evolutionarily conserved hydraulic traits lead to phylogenetic clustering of co-occurring species. 5. Synthesis. The evolutionary conservation of hydraulic traits related to soil moisture tolerance largely explains phylogenetic clustering in the local assembly of the hyperdiverse genus Psychotria. We suggest that close relatives are unlikely to exclude one another from shared habitats because resource availability is determined largely by asymmetric competition with the overstorey, rather than by competition with neighbouring understorey plants. In light of the recent biogeographic admixture in central Panama, the phylogenetic niche conservatism exhibited by Psychotria on BCI raises the possibility of an association between local microhabitats and the ancestral climatic regimes under which major Psychotria lineages evolved before arriving in sympatry.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92470/1/Sedio2012.pd

Lymphoid aggregates that resemble tertiary lymphoid organs define a specific pathological subset in metal-on-metal hip replacements

Aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) has been used to describe the histological lesion associated with metal-on-metal (M-M) bearings. We tested the hypothesis that the lymphoid aggregates, associated with ALVAL lesions resemble tertiary lymphoid organs (TLOs). Histopathological changes were examined in the periprosthetic tissue of 62 M-M hip replacements requiring revision surgery, with particular emphasis on the characteristics and pattern of the lymphocytic infiltrate. Immunofluorescence and immunohistochemistry were used to study the classical features of TLOs in cases where large organized lymphoid follicles were present. Synchrotron X-ray fluorescence (XRF) measurements were undertaken to detect localisation of implant derived ions/particles within the samples. Based on type of lymphocytic infiltrates, three different categories were recognised; diffuse aggregates (51%), T cell aggregates (20%), and organised lymphoid aggregates (29%). Further investigation of tissues with organised lymphoid aggregates showed that these tissues recapitulate many of the features of TLOs with T cells and B cells organised into discrete areas, the presence of follicular dendritic cells, acquisition of high endothelial venule like phenotype by blood vessels, expression of lymphoid chemokines and the presence of plasma cells. Co-localisation of implant-derived metals with lymphoid aggregates was observed. These findings suggest that in addition to the well described general foreign body reaction mediated by macrophages and a T cell mediated type IV hypersensitivity response, an under-recognized immunological reaction to metal wear debris involving B cells and the formation of tertiary lymphoid organs occurs in a distinct subset of patients with M-M implants

The Evolutionary Basis of Naturally Diverse Rice Leaves Anatomy

Rice contains genetically and ecologically diverse wild and cultivated species that show a wide variation in plant and leaf architecture. A systematic characterization of leaf anatomy is essential in understanding the dynamics behind such diversity. Therefore, leaf anatomies of 24 Oryza species spanning 11 genetically diverse rice genomes were studied in both lateral and longitudinal directions and possible evolutionary trends were examined. A significant inter-species variation in mesophyll cells, bundle sheath cells, and vein structure was observed, suggesting precise genetic control over these major rice leaf anatomical traits. Cellular dimensions, measured along three growth axes, were further combined proportionately to construct three-dimensional (3D) leaf anatomy models to compare the relative size and orientation of the major cell types present in a fully expanded leaf. A reconstruction of the ancestral leaf state revealed that the following are the major characteristics of recently evolved rice species: fewer veins, larger and laterally elongated mesophyll cells, with an increase in total mesophyll area and in bundle sheath cell number. A huge diversity in leaf anatomy within wild and domesticated rice species has been portrayed in this study, on an evolutionary context, predicting a two-pronged evolutionary pathway leading to the ‘sativa leaf type’ that we see today in domesticated species

Using Video and Multimodal Classroom Interaction Analysis to Investigate How Information, Misinformation, and Disinformation Influence Pedagogy

Misinformation is accidentally wrong and disinformation is deliberately incorrect (i.e., deception). This article uses the Pedagogy Analysis Framework (paf) to investigate how information, misinformation, and disinformation influence classroom pedagogy. 95 people participated (i.e., one lesson with 7-year-olds, another with 10-year-olds, and three with a class of 13-year-olds). The authors used four video-based methods (lesson video analysis, teacher verbal protocols, pupil group verbal protocols, and teacher interviews). 35 hours of video data (recorded 2013–2020) were analysed using Grounded Theory Methods by the researchers, the class teachers, and groups of pupils (three girls and three boys). The methodology was Straussian Grounded Theory. The authors present how often participants used information, misinformation, and disinformation. They illustrate how the paf helps understand and explain information, misinformation, and disinformation in the classroom by analysing video data transcripts. In addition, the authors discuss participant perceptions of the status of information; overlapping information, misinformation, and disinformation; and information communication difficulties

Multimodal classroom interaction analysis using video-based methods of the pedagogical tactic of (un)grouping

Grouping of people and/or things in school can involve challenging pedagogical problems and is a recurrent issue in research literature. Grouping of pupils sometimes aids learning, but detailed video-based analysis of how teachers (and pupils) group or ungroup (termed ‘(un)grouping’) in classrooms is rare. This multimodal classroom interaction analysis study builds on previous work by exploring how the Pedagogy Analysis Framework can help untangle complicated classroom interactions involving (un)grouping and identifies sixteen types of (un)grouping. The sample size is one class of thirty pupils (10-year-olds), their class teacher, and teaching assistant. Four research methods were used (lesson video analysis, teacher verbal protocols, pupil group verbal protocols, and individual teacher interviews). Six hours of data were video recorded (managed using NVivo). Data were analysed by two educational researchers, the class teacher, and two groups of pupils (three girls and three boys). The methodology is Straussian Grounded Theory. Data were recorded in 2019. We present how often participants (un)grouped during a lesson. We propose and use a grounded theory for (un)grouping which we call the ‘Exclusion, Segregation, Integration, and Inclusion (ESII) model’. Additionally, we discuss how misinformation and disinformation can complicate analysis of (un)grouping and examine different perspectives on (un)grouping

Teachers' perspectives on the relationship between secondary school departments of science and religious education: Independence or mutual enrichment?

There is a gap in the research on the relationship between secondary school subject departments, particularly where, as in the case of science and religious education (RE), there is not the traditional relationship that may be seen in science and maths or across humanities subjects. More awareness of content taught in other departments is important for pupils' coherent experience of curriculum and schooling. This article reports on data from 10 focus groups with 50 participants from six universities, where student teachers of science and RE revealed a complex picture of relationships between the two departments in their placement schools. Furthermore, this article reports findings from a survey where 244 teachers and student teachers of science and RE shared their perspectives on the relationship between the two school departments. The measure was adapted from Barbour's typology, a classification describing the nature of the relationship between science and religion in a range of literature. The terms ‘conflict’, ‘independence’, ‘dialogue’, ‘collaboration’ and ‘integration’ were presented to teachers of both subjects. Little evidence was found of conflict between science and RE departments, but more ‘independence’ than ‘dialogue’ between the two departments was reported. In the light of these findings, the benefits of boundary crossing are explored alongside the role teachers should play in boundary crossing

Science and RE teachers' perspectives on the purpose of RE on the secondary school curriculum in England

Renewed interest in curriculum in English schooling over the past decade has emanated from a particular focus on the place and role of knowledge in the class-room. Significant changes in policy and examination specifications have led to changes in religious educa-tion (RE). However, little is known about teachers' perspectives on the purpose of RE. We asked teach-ers of science and RE what they understood as the purpose of RE on the school curriculum. Data from 10 focus groups and a survey with 276 secondary teachers demonstrated that many secondary teach-ers of science have a different understanding to RE teachers of the purpose of RE on the school curricu-lum. Findings also show a lack of consensus from RE teachers on the purpose of RE, suggesting the impact of the knowledge turn in RE is not as strong as the Ofsted Research Review implies. Findings are signif-icant as little is known about how knowledge works across disciplinary boundaries in schools. If students are to come to a full understanding of how knowledge works, teachers need to have some understanding of how knowledge is being constructed and utilised in other curriculum subjects. Knowledge of the intended purpose of RE is important for respectful co-existence of subjects on the curriculum and essential when RE is declining as a subject in secondary schools