English

This paper serves as a foundational piece, aiming to investigate the potential of critical disability theory (CDT) and disability critical race theory (DisCrit) in shedding light on students' perceptions of their own exceptionalities and how this can impact their educational achievement in subjects like math, physical education, and English. While there is a substantial body of research focusing on CDT, teacher attitudes, and non-identified student attitudes towards disabilities, there is a lack of research exploring the connections between CDT, DisCrit, and students' attitudes towards their own exceptionalities. It is crucial to acknowledge how students perceive their own exceptionalities, as internalizing ableist prejudice and discrimination can lead to students viewing their exceptionalities as hindrances or barriers, which can detrimentally affect their academic development. However, by embracing the activist work of CDT and DisCrit scholars and shifting ableist perspectives towards a strengths-based approach that highlights individuals' resilience and fortitude. This shift in mindset has the potential to enhance students' overall academic success

The Migration of Indians to Eastern Africa: A Case Study of the Ismaili Community, 1866-1966

Much of the Ismaili settlement in Eastern Africa, together with several other immigrant communities of Indian origin, took place in the late nineteenth century and early twentieth centuries. This thesis argues that the primary mover of the migration were the edicts, or Farmans, of the Ismaili spiritual leader. They were instrumental in motivating Ismailis to go to East Africa. Although there were other Indian groups from the general geographical area of Western Indian and Gujarat who also migrated to East Africa, the crucial factor in the migration of Ismailis were the edicts or Farmans of the Imams. My thesis argues that the Farmans or edicts played a very important role in persuading Ismailis to move to East Africa. Though other groups from Gujarat and Western India also moved to East Africa, the Ismailis followed the edicts or Farmans of the Imam and this was the major factor for the Ismailis to move. Ismaili history is replete with migratory movements, whether due to persecution or economic reasons. The religious leader of the Ismailis, the Imam or the Imam of the Time as he is known as by the Ismailis, including all the Aga Khans to date, sought to bring the Ismailis out of their poverty and famine-stricken land and settle into more favored economic areas under British jurisdiction. This thesis will demonstrate that Aga Khan III actively promoted the movement of the Ismailis to East Africa. His edicts shaped the migration of Ismailis and they provided uneducated people the reason as well as the motivation to go together with a sense of reassurance. I will use personal oral histories which add to the historiography to make my case for both Ismailis and the Ithnasheris, the largest Shia Muslim community. Since Ismailis are generally a closed community and actively practiced Taqia (secret practice), I will use whatever written material I have been able to find to make my case. The Ithnasheris were also Khojas who had split from the main Khoja Ismaili community in India because of their objection to the control being exercised by the Imam, Aga Khan I, who had arrived in Sind Province in 1843 from Persia. Though they were part of the Shia sect, the Ismailis who converted to the Ithnasheri sect, became Shias but maintained the Khoja name. To support my argument, I draw on oral histories of both Ismailis and Ithnasheris as there is no written record of any pronouncements by the leaders of the Ismailis and it is entirely oral history by word of mouth. This thesis adds substantially to the historiography of the subject matter. Since written accounts are not available, my oral history recollections accomplish this

Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial†

We examined the effect of MSI status in a trial-based cohort of 1254 stage II and III colon cancer (CC) patients treated with 5-FU/LV or FOLFIRI. We confirm that for stage II CC MSI is strongly prognostic for RFS and OS. No significant differences were found between treatment arms. Adding irinotecan to 5-FU did not benefit MSI-H tumors. RFS was better for MSI-H CC both in the right and left colo

Medical Sciences 4300: London-Middlesex Suicide Prevention Council

Suicide is an issue that affects people of all backgrounds, and takes the lives of many individuals every year. The London-Middlesex Suicide Prevention Council (LMSPC), an organization established in 1990, seeks to provide suicide prevention training to members of the community. They seek to engage community members in prevention and intervention by recognizing warning signs that may exist among the London-Middlesex region. The three main programs that strive to deliver these skills are ASIST, ASK, and safeTALK, each with a slightly different focus. LMSPC’s current goal is to increase access to these services through external grants and potential partnerships. Our Community Engaged Learning (CEL) project aimed at creating a repository of grants to allow LMSPC to improve the targeting of their grant applications. Through these grants, the organization will be able to host more classes, and provide training at subsidized prices to increase community access. Additionally, this project worked to produce a series of infographics, which will hopefully increase education on myths regarding suicide, and the available training programs via LMSPC’s social media platforms. Online advocacy provides a point of first contact to potential participants of LMSPC’s three programs, and educates the community on the difficult truths of suicide. Although a lot of progress has been made over the past several months, the fight against suicide is far from over. Going forward, LMSPC will continue to strengthen partnerships, and grow their organization through external grants. Ultimately, this organization’s impacts are incredibly significant and far-reaching as they work to save lives, and make the London-Middlesex region a safer environment

Cross-species analysis of genetically engineered mouse models of MAPK-driven colorectal cancer identifies hallmarks of the human disease

Effective treatment options for advanced colorectal cancer (CRC) are limited, survival rates are poor and this disease continues to be a leading cause of cancer-related deaths worldwide. Despite being a highly heterogeneous disease, a large subset of individuals with sporadic CRC typically harbor relatively few established ‘driver’ lesions. Here, we describe a collection of genetically engineered mouse models (GEMMs) of sporadic CRC that combine lesions frequently altered in human patients, including well-characterized tumor suppressors and activators of MAPK signaling. Primary tumors from these models were profiled, and individual GEMM tumors segregated into groups based on their genotypes. Unique allelic and genotypic expression signatures were generated from these GEMMs and applied to clinically annotated human CRC patient samples. We provide evidence that a Kras signature derived from these GEMMs is capable of distinguishing human tumors harboring KRAS mutation, and tracks with poor prognosis in two independent human patient cohorts. Furthermore, the analysis of a panel of human CRC cell lines suggests that high expression of the GEMM Kras signature correlates with sensitivity to targeted pathway inhibitors. Together, these findings implicate GEMMs as powerful preclinical tools with the capacity to recapitulate relevant human disease biology, and support the use of genetic signatures generated in these models to facilitate future drug discovery and validation efforts

ZIC1 gene expression is controlled by DNA and histone methylation in mesenchymal proliferations

AbstractRNA and protein analysis revealed the consistent upregulation of the neural transcription factors ZIC1 and ZIC4 in desmoid tumors and other fibroproliferative disorders. The 5′ flanking region of the ZIC1 promoter was unmethylated in desmoid tumor fibroblasts, while a hypermethylated ZIC1 promoter was found in human and mouse cell lines not expressing the gene. In addition, expressing cells showed a H3K4me2 at the ZIC1 promoter, whereas non-expressing cells showed higher levels of H3K9me2 in the same region. To our knowledge, this is the first report describing ZIC1 expression in mesenchymal proliferations and a role for DNA methylation in the control of ZIC1 expression

DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.

PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR