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Larissa Sena Teixeira Mendes,1 Ming-Qing Du,2 Estella Matutes,3 Andrew Wotherspoon11Histopathology Department, Royal Marsden Hospital, London, UK; 2Molecular Malignancy Laboratory and Department of Histopathology, University Hospital NHS Foundation Trust/Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK; 3Hematopathology Unit, Hospital Clinic, Barcelona University, Barcelona, Spain Abstract: Splenic marginal zone lymphoma is a distinct low grade B-cell lymphoma primarily occurring in the spleen and separate from nodal marginal zone lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. It is characterized by a relative indolent course, splenomegaly, moderate lymphocytosis, and an intrasinusoidal pattern of involvement, especially in the bone marrow. It is postulated that the neoplastic clone originates from persistent antigenic stimulation of marginal zone B-cells. Molecular and cytogenetic studies have failed to show specific alterations. There is no standard criterion to initiate treatment, which may include a watch and wait policy, splenectomy, or chemo/immunotherapy. This review highlights the main features of this entity, reassessing the guidelines for diagnosis, prognostic factors, staging, and management published by the SMZL Working Group (2008). Keywords: splenectomy, villous lymphocytes, guidelines

Abstract Background Regulatory applications for cell therapy face more objections compared to conventional small molecule or biological drugs, leading to delays in market approval and clinical adoption. Increased regulatory objections frequently relate to issues regarding preclinical evidence, such as experimental design of animal studies, selection of animal models, endpoints, and determination of mechanism of action. Synthesis and clarification of the preclinical evidence necessary to demonstrate treatment efficacy and advance into early-phase clinical trials is needed to help researchers avoid regulatory objections. Methods We conducted a scoping review in which we searched repositories of the International Council for Harmonisation and all national member organizations (N = 38) for documents related to preclinical studies of cell therapies. Active guidance documents related to cell therapy were included, with no restrictions based on the year or language of publication. Data extraction was conducted in duplicate with conflicts resolved through consensus discussion. Results From 1215 identified documents, a total of 182 were included and analyzed, with 71% originating from ten major regulatory agencies. The most prevalent preclinical item addressed was the mechanism of action (n = 161, 88% of documents), underscoring its importance in bridging preclinical findings to clinical application. Most documents (n = 140, 77%) emphasized the importance of using clinically relevant preclinical models, though specific recommendations on models of disease were less common (n = 81, 45%). Selection of clinically relevant intervention parameters (n = 136, 75%) and outcome measures (n = 121, 66%) were also frequently recommended, but selection of relevant comparator groups appeared less frequently (n = 35, 19%). Furthermore, robust study design elements such as randomization and blinding were less frequently recommended, appearing in 31% of documents (n = 57). Comparison with clinical trial guidance revealed a significant gap in the rigor of study design recommendations for preclinical research. Conclusions Regulatory guidance for preclinical efficacy studies often recommends a strong emphasis on the clinical relevance of animal models, intervention parameters, outcomes, and mechanism of action. Incorporating these recommendations into early preclinical studies should improve the acceptability of preclinical evidence for approval by the relevant national regulators and can be used as a guide to ensure that all evidence that regulators say they expect is efficiently assembled into new clinical trial applications.

Objective: Children diagnosed with cerebral palsy have been reported to be at increased risk of executive function deficits and neurodevelopmental disorders. This population-based cohort study aimed to assess executive function, attention, behaviour, and autism symptomatology in school-aged children with CP, using parent-report measures that can provide insight into everyday functioning in these neurodevelopmental domains. Methods: 74 participants (male n = 51) mean age 9 years 9 months, SD 1 year 1.2 months (range 8 years 0 months to 12 years 11 months), GMFCS I = 45 (60.8%), II = 17 (23%), III = 8 (10.8%), and IV = 4 (5.4%), were assessed on measures of attention and behaviour (Conners-3), executive function (BRIEF), and autism symptomatology (AQ10-Child). Analysis was via one-sample t-tests and MANCOVAs. Results: Participants' scores were elevated in comparison to the general population in all domains, while 29.1% of participants scored above the cut-off level on an autism symptomatology screener. Greatest impairment was reported for working memory (M = 60.7, SD = 10.0, t(72) = 9.2, p < 0.001), peer relations (M = 72.7, SD = 16.2, t(73) = 12.0, p < 0.001), and inattention subscales (M = 66.3, SD = 12.5, t(73) = 11.2, p < 0.001). No statistically significant differences were found for different GMFCS levels on domains of executive functioning. A statistically significant difference was found between GMFCS levels for inattention F(3, 71) = 3.83, p = 0.013, [partial eta-squared] = 0.162, with most elevated scores associated with GMFCS level II (M = 74.1, SD = 14.2). Conclusion: EF, attention and behavioural difficulties, and autism symptomatology are commonly reported in school-aged children with CP. Screening for these comorbidities using ratings scales will assist with early diagnosis and targeted intervention.

Canadian school jurisdictions have taken steps to accommodate objectives to advance cosmopolitan education reflecting principles such as global citizenship, compassion, tolerance, responsibility, and respect within school curricula and educational practice. At the same time, a parallel set of reconciliation-related educational reforms, aligned with the Calls to Action that accompanied the 2015 Truth and Reconciliation Commission final report, have also gained urgency. Elements of reconciliation processes complement visions of cosmopolitanism, including objectives to foster dialogue and understanding between groups and advancements towards more holistic orientations to pedagogy and knowledge. However, conceptually and in practice, several tensions emerge, especially in a context in which educational priorities are contested. In this paper, we explore these connections and tensions with reference to findings from our research examining public perspectives on educational reforms to support reconciliation.

Southern Ocean phytoplankton form the base of the Antarctic food web, influencing higher trophic levels through biomass and community structure. We examined phytoplankton distribution and abundance in the Indian Sector of the Southern Ocean during austral summer as part a multidisciplinary ecosystem survey: Trends in Euphausiids off Mawson, Predators and Oceanography (TEMPO, 2021). Sampling covered six meridional transects from 55-80°E, and from 62°S or 63°S to the ice edge. To determine phytoplankton groups, CHEMTAX analysis was undertaken on pigments measured using HPLC. Diatoms were the dominant component of phytoplankton communities, explaining 56% of variation in chlorophyll a (Chl a), with haptophytes also being a major component. Prior to sampling the sea ice had retreated in a south-westerly direction, leading to shorter ice-free periods in the west (< 44 days, ≤65°E) compared to east (> 44 days, ≥70°E), inducing a strong seasonal effect. The east was nutrient limited, indicated by low-iron forms of haptophytes, and higher silicate:nitrate drawdown ratios (5.1 east vs 4.3 west), pheophytin a (phaeo) concentrations (30.0 vs 18.4 mg m-2) and phaeo:Chl a ratios (1.06 vs 0.53). Biological influences were evident at northern stations between 75-80°E, where krill “super-swarms” and feeding whales were observed. Here, diatoms were depleted from surface waters likely due to krill grazing, as indicated by high phaeo:Chl a ratios (> 0.75), and continued presence of haptophytes, associated with inefficient filtering or selective grazing by krill. Oceanographic influences included deeper mixed layers reducing diatom biomass, and a bloom to the north of the southern Antarctic Circumpolar Current Front in the western survey area thought to be sinking as waters flowed from west to east. Haptophytes were influenced by the Antarctic Slope Front with high-iron forms prevalent to the south only, showing limited iron transfer from coastal waters. Cryptophytes were associated with meltwater, and greens (chlorophytes + prasinophytes) were prevalent below the mixed layer. The interplay of seasonal, biological and oceanographic influences on phytoplankton populations during TEMPO had parallels with processes observed in the BROKE and BROKE-West voyages conducted 25 and 15 years earlier, respectively. Our research consolidates understanding of the krill ecosystem to ensure sustainable management in East Antarctic waters.

Cerebral palsy is a leading cause of physical impairment worldwide. Community support and acceptance influence the opportunities people with cerebral palsy have to participate in all areas of life, but very little is known about the general community's understanding of cerebral palsy. This study investigated knowledge and perceptions of cerebral palsy in the Australian community. A sample of 1,217 adults responded to an open-ended question: 'What is the first thing that comes to mind when you think about cerebral palsy?' Almost half of the sample indicated some awareness that cerebral palsy is a physical disability involving difficulties with muscle control, movement and coordination; however, 20% of the participants had no knowledge or stated incorrect facts. Wheelchairs were the first thing that came to mind for 10% of the sample. Few participants mentioned common comorbidities such as cognitive or communication difficulties. A substantial minority of responses (8%) were characterised by stigma or insensitivity. Although many people in the general community appear to have accurate knowledge about cerebral palsy, misperceptions and stereotypes are likely to impact on quality of life and personal well-being for individuals with cerebral palsy and their families.

Simulation-based learning provides students with unique opportunities to develop key procedural and teamwork skills in close-to-authentic physical learning and training environments. Yet, assessing students' performance in such situations can be challenging and mentally exhausting for teachers. Multimodal learning analytics can support the assessment of simulation-based learning by making salient aspects of students' activities visible for evaluation. Although descriptive analytics have been used to study students' motor behaviours in simulation-based learning, their validity and utility for assessing performance remain unclear. This study aims at addressing this knowledge gap by investigating how indoor positioning analytics can be used to generate meaningful insights about students' tasks and collaboration performance in simulation-based learning. We collected and analysed the positioning data of 304 healthcare students, organised in 76 teams, through correlation, predictive and epistemic network analyses. The primary findings were (1) large correlations between students' spatial-procedural behaviours and their group performances; (2) predictive learning analytics that achieved an acceptable level (0.74 AUC) in distinguishing between low-performing and high-performing teams regarding collaboration performance; and (3) epistemic networks that can be used for assessing the behavioural differences across multiple teams. We also present the teachers' qualitative evaluation of the utility of these analytics and implications for supporting formative assessment in simulation-based learning.

Canadian schools have implemented initiatives in response to the Calls to Action that accompanied the 2015 Truth and Reconciliation Commission final report. This paper aims to address two questions that speak directly to these calls. How have these initiatives been implemented in Canadian classrooms and affected educational practices? How do education stakeholders perceive and experience these initiatives? We present a study conducted in Alberta to explore these questions, drawing on data from interviews and focus groups conducted with 201 Indigenous youth and teachers and parents of Indigenous children. Findings suggest that schools are engaged in innovative activities to introduce knowledge about Indigenous cultures and experiences. Most participants believed, however, that more work is needed to support teachers' ability to include Indigenous content in classrooms and to increase awareness about Indigenous peoples' among non-Indigenous students to prevent discrimination. These tensions can undermine schools' capacities to advance reconciliation.

Notions of "student success" feature prominently in emerging educational discourses and policy orientations. Current policy frameworks focusing on equity, performance, and reconciliation claim to offer validation for perspectives of Indigenous peoples and other racialized communities, but they are simultaneously raising the stakes for individual responsibility and performance. This paper explores these developments by examining how Indigenous students and family members understand and experience educational success in relation to the notions of success advanced by school systems. We present a case study conducted in Alberta, Canada, drawing on data from ten focus groups with 77 Indigenous youth and parents of Indigenous children connected to one school division. Highlighting the ways that social and educational policy frameworks related to employability and performance exacerbate contradictions inherent in settler colonial societies, we reveal how school systems, despite claims to the contrary, continue to adopt practices that undermine the capacity for many Indigenous people to achieve their aspirations.

Australian schools are experiencing an increase in enrolments for students from culturally and linguistically diverse backgrounds. Many of these students, who are frequently from migrant, refugee or asylum-seeker backgrounds, progress academically, but a small number experience learning challenges. In these circumstances, practitioners (school psychologists and guidance counsellors) assess the students to determine underlying factors contributing to limited academic progress, and ways in which the student's learning can be supported and enhanced. However, formal assessment can be challenging due to language and cultural barriers. Considering the gaps in the research and training, the present article proposes an assessment framework and highlights strategies that can be adopted by practitioners at schools to enrich their decision-making and assessment process. Two case studies are used to highlight factors that can impact students' academic difficulties. Further interview protocols and assessment measures that can be used to assist these students and their families are discussed. Ways in which school authorities can guide and support these students in the classroom and in the school are examined.

Abstract The Southern Ocean, its ecosystem, and inhabitants are vulnerable to climate‐mediated shifts in habitat conditions. These changes can affect marine predators in the long term through changes in the distribution, density, and quality of prey. To understand how these changes affect vital rates requires longitudinal studies integrating demography and environmental states. We analyzed 22 years of capture–mark–recapture data to quantify the influence of broad‐scale climate on the survival of male southern elephant seals from Macquarie Island, Tasmania, Australia. Weaning mass was incorporated as a quadratic predictor of survival to account for the known influence of maternal investment. First‐year survival was greatest for weaners weighing 160 kg. Subsequent developmental stages were grouped into juvenile, subordinate, and breeding adult states to reflect the known life history of individuals. We found increased juvenile and subordinate survival with positive values of the previous years' Southern Annular Mode. This is likely due to the northward shift of westerly winds increasing productivity and prey availability in the Sub‐Antarctic region. In contrast to females of this population, the Southern Oscillation Index did not affect male survival. In this highly polygynous mating system, sex‐dependent differences in foraging behavior may be causing the small number of successful breeding adult males to be less susceptible to external influences after reaching the minimum age and body size required to be socially competitive for mating. These extremely large bulls will breed with multiple females and thus make a disproportionate contribution to the gene pool of the next generation. Considering the susceptibility of males to climate influences is therefore highly relevant to assessing the future adaptive capability of the species.