Education, Exploration and the Elephant in the Room: A Narrative Inquiry of Sexuality and Sex Education among Adolescents with Physical Disabilities

Guided by a constructivist paradigm, this qualitative research study used a multidimensional form of narrative inquiry in order to understand the experiences of learning about sexuality among adolescents with physical disabilities, and in turn, how these experiences influence the way they view themselves as sexual beings. For the purposes of this research, in-depth narrative interviews were conducted with adolescents who have physical disabilities and parents of youth with physical disabilities, as well as a focus group with health professionals. The findings from this study demonstrate that these adolescents often face challenges in accessing disability- specific sex information due to a lack of appropriate resources, discomfort with the topic among educators, health professionals and parents, as well as the pervasive social myth that views people with disabilities as asexual. The data from this study contributes to the literature about sexuality among adolescents with physical disabilities by drawing attention to this important but often overlooked issue, as well as offering recommendations for future resource development that could help empower these youth with the knowledge and skills needed to engage in safe, healthy and fulfilling relationships

Cripping sex education: lessons learned from a programme aimed at young people with mobility impairments

This paper analyses sexuality and relationship education (SRE) in a Swedish college programme aimed at young people with mobility impairments. Interviews and focus groups were conducted to explore students’ experiences of the structure, content and usefulness of SRE, and college personnel’s SRE practices. Results show that, although many of the issues covered are pertinent for all youth, being disabled raises additional concerns: for example how to handle de-sexualising attitudes, possible sexual practices, and how reliance on assistance impacts upon privacy. Crip theory is used as an analytical framework to identify, challenge and politicise sexual norms and practices. Students’ experiences of living in a disablist, heteronormative society can be used as resources to develop cripistemologies, which challenge the private/public binary that often de-legitimises learners’ experiences and separates them from teachers’ ‘proper’ knowledge production. Crip SRE would likely hold bene ts for non-disabled pupils as well, through its use of more inclusive pedagogy and in work to expand sexual possibilities. Crip SRE has the potential to disrupt taken-for-granted​ dis/ability and sexuality divides as well as to politicise issues that many young people presently experience as ‘personal shortcomings’

Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by mutations in the Krebs cycle enzyme fumarate hydratase (FH). It has been proposed that "pseudohypoxic" stabilization of hypoxia-inducible factor-α (HIF-α) by fumarate accumulation contributes to tumorigenesis in HLRCC. We hypothesized that an additional direct consequence of FH deficiency is the establishment of a biosynthetic milieu. To investigate this hypothesis, we isolated primary mouse embryonic fibroblast (MEF) lines from Fh1-deficient mice. As predicted, these MEFs upregulated Hif-1α and HIF target genes directly as a result of FH deficiency. In addition, detailed metabolic assessment of these MEFs confirmed their dependence on glycolysis, and an elevated rate of lactate efflux, associated with the upregulation of glycolytic enzymes known to be associated with tumorigenesis. Correspondingly, Fh1-deficient benign murine renal cysts and an advanced human HLRCC-related renal cell carcinoma manifested a prominent and progressive increase in the expression of HIF-α target genes and in genes known to be relevant to tumorigenesis and metastasis. In accord with our hypothesis, in a variety of different FH-deficient tissues, including a novel murine model of Fh1-deficient smooth muscle, we show a striking and progressive upregulation of a tumorigenic metabolic profile, as manifested by increased PKM2 and LDHA protein. Based on the models assessed herein, we infer that that FH deficiency compels cells to adopt an early, reversible, and progressive protumorigenic metabolic milieu that is reminiscent of that driving the Warburg effect. Targets identified in these novel and diverse FH-deficient models represent excellent potential candidates for further mechanistic investigation and therapeutic metabolic manipulation in tumors

Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.Peer reviewe

The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling

Homozygosity for the G allele of rs6983267 at 8q24 increases colorectal cancer (CRC) risk approximately 1.5 fold. We report here that the risk allele G shows copy number increase during CRC development. Our computer algorithm, Enhancer Element Locator (EEL), identified an enhancer element that contains rs6983267. The element drove expression of a reporter gene in a pattern that is consistent with regulation by the key CRC pathway Wnt. rs6983267 affects a binding site for the Wnt-regulated transcription factor TCF4, with the risk allele G showing stronger binding in vitro and in vivo. Genome-wide ChIP assay revealed the element as the strongest TCF4 binding site within 1 Mb of MYC. An unambiguous correlation between rs6983267 genotype and MYC expression was not detected, and additional work is required to scrutinize all possible targets of the enhancer. Our work provides evidence that the common CRC predisposition associated with 8q24 arises from enhanced responsiveness to Wnt signaling