THE EFFECTS OF VIRTUAL PANOPTICISM

As technology further integrates into everyday life, the effects of technological advancement surface. The research contained in this thesis places philosopher Michel Foucault’s ideas of the panoptic, discipline, punishment and a carceral society in a virtual reality thus creating a virtual panopticon. Adapting Foucault’s theories to the present-day technological climate allows researchers to begin understanding the why behind humans’ interactions with various forms of technology (e.g. iPhone usage, Smart TVs, online banking, Alexa/Echo, etc.). Additionally, virtual panopticism sheds light on the corruption of those who manipulate information online to wield power, maintain control and make money. I discuss surveillance capitalism and highlight Foucault’s main influencers such as Karl Marx and Friedrich Nietzsche. By conducting a voluntary survey, participants revealed how they operate within a virtual panopticon specifically in the areas of religion, personal technology usage, literature and film and education. Since thinking directly affects actions, the importance of understanding this information is critical to interpreting modern-day culture. The goal of this research is to reveal the effects of virtual panoptical structures on thinking, while simultaneously emphasizing the need for technological accountability

Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche

Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

The Immunotoxicity of Two Novel Perfluoroether Acids Found in North Carolina’s Cape Fear River

Novel perfluoroether acids (PFEAs) have been identified in surface waters of North Carolina and in the blood of some North Carolina residents. As some per- and polyfluoroalkyl substances (PFAS) are presumed immune hazards to humans, markers of immunotoxicity in young adult female and male C57BL/6 mice were observed following either 30-day oral exposure to perfluoro-2-methoxyacetic acid (PFMOAA), 30-day oral exposure to Nafion by-product 2 (NBP2), or 15-day oral exposure to a mixture of PFMOAA and NBP2. In-life observations were collected and endpoints included: organ weights, immunophenotype of lymphoid organs, natural killer (NK) cell cytotoxicity, liver peroxisomal enzyme activity, and the T-cell dependent antibody response (TDAR). In animals exposed to PFMOAA orally for 30 days the following changes were observed: liver weight statistically increased, in male animals peroxisomal enzyme activity statistically increased, and in male animals the TDAR was statistically suppressed. In animals exposed to NBP2 orally for 30 days the following changes were observed: liver weight statistically increased, spleen and thymus weight statistically decreased, NK cytotoxicity statistically decreased, liver peroxisomal enzyme activity statistically increased, and the TDAR was statistically decreased. In animals exposed to PFMOAA and NBP2 mixtures for 30 days the following changes were observed: one male group had statistically decreased bodyweight, some groups had alterations in organ weights. Our results indicate these novel PFEAs have immunosuppressive and immunomodulatory potential

Alignment of Astrocytes Increases Neuronal Growth in Three-Dimensional Collagen Gels and Is Maintained Following Plastic Compression to Form a Spinal Cord Repair Conduit

After injury to the spinal cord, reactive astrocytes form a glial scar consisting of highly ramified cell processes that constitute a major impediment to repair, partly due to their lack of orientation and guidance for regenerating axons. In some nonmammalian vertebrates, successful central nervous system regeneration is attributed to the alignment of reactive glia, which guide axons across the lesion site. Here, a three-dimensional mammalian cell-seeded collagen gel culture system was used to explore the effect of astrocyte alignment on neuronal growth. Astrocyte alignment was mapped within tethered rectangular gels and was significantly greater at the edge and middle of the gels compared to the control unaligned regions. When neurons were seeded on and within astrocyte gels, neurite length was greatest in the areas of astrocyte alignment. There was no difference in expression of astrocyte reactivity markers between aligned and control areas. Having established the potential utility of astrocyte alignment, the aligned gels were plastic compressed, transforming them into mechanically robust implantable devices. After compression, astrocytes remained viable and aligned and supported neurite outgrowth, yielding a novel method for assembling aligned cellular constructs suitable for tissue engineering and highlighting the importance of astrocyte alignment as a possible future therapeutic intervention for spinal cord repair