Trauma Informed Practices in the Elementary Classroom: Training Modules for Pre Service Teachers

The purpose of this capstone is to explore trauma-informed practices in the elementary classroom, and to develop foundational training modules for pre-service teachers. The need for trauma-informed practices in schools is important as research indicates that children who experience traumatic events are impacted in their academic performance, behavior, and emotional well-being. This capstone reviews the literature on the impact of trauma on children, with an emphasis on how it manifests in the classroom. It highlights the importance of recognizing the symptoms of trauma and how teachers can effectively create a safe and supportive learning environment for all students. The training modules and informational materials were designed to provide pre-service teachers with a foundational knowledge of trauma-informed education, including how to recognize and respond to trauma as well as how to implement social emotional learning and self-regulation practices in the classroom. By equipping pre-service educators with the tools and resources needed to recognize and respond to trauma, we can create a more equitable and supportive learning environment for all students, specifically those who have experienced trauma

Alzheimer’s-Related Amyloid Beta Peptide Aggregates in the Ageing Retina: Implications for Sight Loss and Dementia

Although visual problems are reported by patients with Alzheimer’s disease and dementia, studies into this particular aspect of neuropathology are scarce. The growing awareness of complex pathological processes in the ageing retina and brain, however, enables us to consider this from a new perspective. Here we discuss the latest findings on the wide-ranging visual defects experienced by those suffering from Alzheimer’s disease and dementia. We propose that events leading to chronic degeneration of the retina and the brain in fact share many striking similarities. In particular, we discuss the role of the Alzheimer’s-related amyloid beta (Aβ) group of peptides that has been shown to accumulate in senescent retinas, correlated with increased risk of retinal degeneration. The high photo-oxidative retinal environment creates ideal conditions for Aβ aggregation, evidenced by high Aβ loads reported in aged and donor eyes from patients with age-related macular degeneration. Consequently, longitudinal and non-invasive retinal assessments may provide invaluable information on incipient pathology and disease progression in the retina as well as the senescent brain. Such insights may not only lead to identifying new pathogenic mechanisms in the retina with implications for understanding Alzheimer’s disease but reveal the underlying causes of visual abnormalities reported in patients with dementia

The Alzheimer's-related amyloid beta peptide is internalised by R28 neuroretinal cells and disrupts the microtubule associated protein 2 (MAP-2)

Age-related Macular Degeneration (AMD) is a common, irreversible blinding condition that leads to the loss of central vision. AMD has a complex aetiology with both genetic as well as environmental risks factors, and share many similarities with Alzheimer's disease. Recent findings have contributed significantly to unravelling its genetic architecture that is yet to be matched by molecular insights. Studies are made more challenging by observations that aged and AMD retinas accumulate the highly pathogenic Alzheimer's-related Amyloid beta (A?) group of peptides, for which there appears to be no clear genetic basis. Analyses of human donor and animal eyes have identified retinal A? aggregates in retinal ganglion cells (RGC), the inner nuclear layer, photoreceptors as well as the retinal pigment epithelium. A? is also a major drusen constituent; found correlated with elevated drusen-load and age, with a propensity to aggregate in retinas of advanced AMD. Despite this evidence, how such a potent driver of neurodegeneration might impair the neuroretina remains incompletely understood, and studies into this important aspect of retinopathy remains limited. In order to address this we exploited R28 rat retinal cells which due to its heterogeneous nature, offers diverse neuroretinal cell-types in which to study the molecular pathology of A?. R28 cells are also unaffected by problems associated with the commonly used RGC-5 immortalised cell-line, thus providing a well-established model in which to study dynamic A? effects at single-cell resolution. Our findings show that R28 cells express key neuronal markers calbindin, protein kinase C and the microtubule associated protein-2 (MAP-2) by confocal immunofluorescence which has not been shown before, but also calretinin which has not been reported previously. For the first time, we reveal that retinal neurons rapidly internalised A?1-42, the most cytotoxic and aggregate-prone amongst the A? family. Furthermore, exposure to physiological amounts of A?1-42 for 24 h correlated with impairment to neuronal MAP-2, a cytoskeletal protein which regulates microtubule dynamics in axons and dendrites. Disruption to MAP-2 was transient, and had recovered by 48 h, although internalised A? persisted as discrete puncta for as long as 72 h. To assess whether A? could realistically localise to living retinas to mediate such effects, we subretinally injected nanomolar levels of oligomeric A?1-42 into wildtype mice. Confocal microscopy revealed the presence of focal A? deposits in RGC, the inner nuclear and the outer plexiform layers 8 days later, recapitulating naturally-occurring patterns of A? aggregation in aged retinas. Our novel findings describe how retinal neurons internalise A? to transiently impair MAP-2 in a hitherto unreported manner. MAP-2 dysfunction is reported in AMD retinas, and is thought to be involved in remodelling and plasticity of post-mitotic neurons. Our insights suggest a molecular pathway by which this could occur in the senescent eye leading to complex diseases such as AMD

Factors driving the seasonal and hourly variability of sea-spray aerosol number in the North Atlantic

Four North Atlantic Aerosol and Marine Ecosystems Study (NAAMES) field campaigns from winter 2015 through spring 2018 sampled an extensive set of oceanographic and atmospheric parameters during the annual phytoplankton bloom cycle. This unique dataset provides four seasons of open-ocean observations of wind speed, sea surface temperature (SST), seawater particle attenuation at 660 nm (cp,660, a measure of ocean particulate organic carbon), bacterial production rates, and sea-spray aerosol size distributions and number concentrations (NSSA). The NAAMES measurements show moderate to strong correlations (0.56 \u3c R \u3c 0.70) between NSSA and local wind speeds in the marine boundary layer on hourly timescales, but this relationship weakens in the campaign averages that represent each season, in part because of the reduction in range of wind speed by multiday averaging. NSSA correlates weakly with seawater cp,660 (R = 0.36, P \u3c\u3c 0.01), but the correlation with cp,660, is improved (R = 0.51, P \u3c 0.05) for periods of low wind speeds. In addition, NAAMES measurements provide observational dependence of SSA mode diameter (dm) on SST, with dm increasing to larger sizes at higher SST (R = 0.60, P \u3c\u3c 0.01) on hourly timescales. These results imply that climate models using bimodal SSA parameterizations to wind speed rather than a single SSA mode that varies with SST may overestimate SSA number concentrations (hence cloud condensation nuclei) by a factor of 4 to 7 and may underestimate SSA scattering (hence direct radiative effects) by a factor of 2 to 5, in addition to overpredicting variability in SSA scattering from wind speed by a factor of 5

Colostrum is required for the postnatal ontogeny of small intestine innate lymphoid type 2 cells and successful anti‐helminth defences

No abstract available

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

An investigation of amyloid (Aβ) induced pathology in age-related macular degeneration

Age-related Macular Degeneration (AMD) is the leading cause of irreversible vision loss in the western world, accounting for 8.7% of global blindness. However, current therapeutics are only applicable to 50% of patients and are ineffective in long-term treatment. This is due to an incomplete understanding of the aetiology underpinning Retinal Pigment Epithelium (RPE) and photoreceptor atrophy in AMD. Lysosomal malfunction within the RPE is believed to result in failed photoreceptor outer segment (POS) phagocytosis and the increased accumulation of protein/lipid aggregates in early AMD. Amyloid beta (Aβ), a highly toxic and penetrative peptide associated with Alzheimer’s disease, has also been shown to deposit in the ageing retina and associated with key stages of AMD. The purpose of this work was to elucidate the association of Aβ with AMD pathology and test the hypothesis that Aβ accumulates within RPE lysosomes and perturbs normal organelle function. An in vitro model of the outer retina was successfully established and exploited to investigate the subcellular localisation of Aβ1-42, as well as its effects on lysosomal function. Colocalisation analysis showed that 40.7 ± 8.6% of Aβ resided within RPE lysosomes, whilst live cell imaging and QPCR determined temporal changes in Cathepsin B activity and expression. Elevated Cathepsin B activity was found at 0.5 (p<0.0001) and 3 hours (p=0.0095) post exposure but returned to baseline at 24 and 48 hours, however mRNA expression remained consistent. Increased Aβ colocalisation with lysosomal Cathepsin B continued up to 24 hours despite a decline in activity. A functional assay also assessed Aβ effects on RPE phagocytic function, which showed decreased POS colocalisation with LAMP-1 at 20 hours. Insights into the biological function of Aβ within the retina were gained through ELISA, which demonstrated increased secretion of Aβ from the basal RPE surface (p=0.0004). We also assessed the toxicity of Aβ in vivo using subretinal injections in C57BL6/J mice. Here, ERG and OCT revealed no significant effect on global retinal function or thickness of constituent layers, although Aβ appeared to induce retinal pathology akin to CNV. Finally, a case-control pilot study was initiated to determine the association of vitreous Aβ concentration with AMD. The work presented within this thesis demonstrates the presence of Aβ within RPE lysosomes for the first time, where it potentially modulates the function of RPE clearance mechanisms. Similarly, we associate Aβ with CNV in situ through the novel use of non-invasive imaging techniques. These studies provide mechanistic insights into the cytotoxic effects of Aβ within the retina that could ultimately drive the RPE atrophy and inflammatory processes associated with AMD pathology. In particular, the functional consequences of Aβ on the RPE endolysosomal system may identify Aβ as a novel therapeutic target for early AMD

Securing South Africa\u27s Future Grandmothers Against Poverty and AIDS as a Model for Social Development Change

Focusing on the role of elder women in South Africa as a lens to understand the central connections among HIV/ AIDS, poverty and Human Security provides a distinct approach to analyze women\u27s contributions to community development and social change. Drawing from the theories of Gender and Development and Human Security, this research aims to highlight HIV/ AIDS as a social and political security issue, while underscoring the vitality of the inclusion of women in the processes of peace building, reconciliation, education and social development. Furthermore, the influential role of elder women in South Africa will serve as a model in support of the central connections between gender and human security. From the analysis of original research collected among a group of grandmothers based in Khayelitsha, South Africa, the role of elder women will be situated within the larger structure of poverty and HIV/ AIDS within the larger national context of ongoing socio-economic development processes. Focusing specifically on the grassroots civil society organization Grandmothers Against Poverty and AIDS (GAPA), the social restructuring caused by HIV/AIDS and its impact on elder women will be illuminated as a critical consequence of the global pandemic. While grandmothers take on the dual leading roles of both caretakers and educators, their stories, prevention efforts and contributions to the larger picture of development often go unrecognized. From the original data collected over two field visits to South Africa, this thesis integrates personal narratives of grandmother leaders with an organizational evaluation of the role of GAP A to highlight how elder women, who continually defy race, class and gender stereotypes, overcome both the social and economic obstacles within the context of the dual burden of poverty and HIV/AIDS in this post-apartheid context. Findings from this study demonstrate that elder women provide not only core foundational support systems and community social cohesion within Khayelitsha, but also central human security functions within the larger socio-economic context of South Africa\u27s post-conflict transition. The original data in this study demonstrate how GAPA serves as a replicable model of change and encompasses a larger representation of the power of women\u27s community activism roles in post-conflict social development and peace building

An ex-vivo platform for manipulation and study of Retinal Pigment Epithelial (RPE) cells in long-term culture

Purpose: Impairment of the Retinal Pigment Epithelium (RPE) is strongly correlated with degenerative retinas including Age-related Macular Degeneration (AMD). Studies to elucidate dynamic intracellular processes underlying chronic degeneration of the RPE are limited by poor access of microscopes in the retinal space. Here we combine the use of an ex-vivo platform with live-confocal and ultrastructural imaging to study these events in individual RPE cells of mouse and human origin over long time periods. Our experimental model system provides a powerful tool to recapitulate chronic degenerative mechanisms in early AMD.Methods: Confluent monolayers of RPE cells were grown on a synthetic porous support which mimics the Bruch’s membrane. Cultures were maintained overs several months. We analysed morphology and barrier properties of the RPE monolayer, including expression of junctional complexes, trans-epithelial resistance (TER) as well as directional secretion of key RPE proteins. We used a combination of live-confocal microscopy, immunofluorescence, transmission electron microscopy (TEM), ELISA and biochemical approaches.Results: Ultrastructural studies show formation of a monolayer with features typical of RPE cells, including melanin pigmentation, apical microvilli and basal infoldings. Ultrastructural mapping of lysosomes and mitochondria provided convenient readouts of key organelles linked with RPE dysfunction at nanoscale resolution. A mobile custom-designed chamber allowed longitudinal analysis of live-cellular physiology using organelle-specific probes LysoSensor blue/yellow and MitoTracker in long-term cultures. For the first time we show that primary mouse RPE cells can be cultured for several weeks with an average TER measurement of 55 ±0.69 Ω/cm2. Directionally secreted proteins VEGF (Vascular Endothelial Growth Factor) and Aβ (Amyloid beta) were quantified using ELISA.Conclusions: Our ex-vivo model system which mimics the RPE/Bruch’s complex can be subject to a high degree of experimental manipulation, and is a powerful tool to investigate dynamic intracellular events as well as ultrastructural changes associated with chronic RPE degeneration in the ageing retina. This tool may be utilized to study RPE physiology at single-molecule resolution, providing mechanistic insights into early AMD