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Women with disabilities until now have remained on the periphery of social justice movements due to the invisibility of women with disabilities issues, the limitations of current contextual and situational analysis to reflect the intersectionality of gender and disability and the minimal resources that organizations representing women with disabilities receive to do their work. While this is slowly changing, much more needs to be urgently done so that women with disabilities can participate in and benefit from development.

MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy-related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune-related functions, was strongly correlated with imputed intratumoral immune infiltrates of T cells, natural killer cells, cytotoxic lymphocytes, and macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publicly available The Cancer Genome Atlas data set. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival.

Background: Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early. Methods: Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass. Results: Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P

Background: Black women with triple negative breast cancer have 46% lower survival rates; this may be due to differences in tumor biology. We analyzed presurgical plasma microRNA of white (W) and black (B) women with TNBC enrolled in the breast ovarian tissue bank to detect if differences in the pre-surgical plasma microRNA could be detected in B patients relative to W patients relative to healthy controls. Aims: MicroRNA in pre-surgical plasma of TNBC W or B was compared to plasma from controls race and age matched controls to assess if differences in plasma and tumor microRNA may explain the survival disparity observed in B. We addressed 2 questions 1) are the patterns in the pre-surgical miRNA profiles different between W and B patients, differences that could explain outcomes discrepancy? 2) What are the miRs changes in patients W or B relative to healthy controls? Methods: Between 2004 and 2011 plasma miRNAs was measured before, after surgery, during and after chemotherapy in 73 surgical breast cancer patients and 11 age and race matched controls. We also analized miRs in the tumor and benign adjacent breast in 5 specimes. Samples were analyzed using qRT-PCR in the ABI's TaqMan OpenArray Panel for 750 miRs. Samples were spiked with ath-miR-159a and hsa-miR-320 most strongly correlated in its expression to ath-miR-159a through the Pearson correlation coefficient. 2-sample t-test was used for comparisons between means and ANOVA followed by post-hoc test to compare the mean response between subject factors of interest. All tests were 2-tailed; statistical significance was set at p < 0.05. Results: 44 W and 23 B, mean age at surgery 48 years (range 35–78) and 11 controls – mean age 44 years (range 35–67). Black TNBC patients did not express over 70 % of pre-surgical plasma miRs present in the W pre-surgical plasma. B over-expressed high levels of miR-1244, -190 and -638, which were not detected in any of the W patients (p < 0.005). W patients and controls expressed miRs10a, -190, -502-3p, -548, and -9* not detected in B TNBC patients. White patients over-expressed over 80% of plasma miRs present in controls, while black patients over-expressed only 30% of miRs present in controls (P < 0.005). Conclusions: Patterns of pre-surgical miR expression are different in B versus W patients with TNBC. In B the presence of TNBC leads to silence in circulating plasma miRs in comparison to W and controls. In W the presence of the tumor increases the miR “chatter”. Black patients have a different “communication” style between host-TNBC when analyzed by the response of plasma microRNA. This difference may call for different treatment protocols for patients. Specific treatment interventions, such as administration of chemotherapy before surgery, in an attempt to increase the microRNA levels in plasma may improve the outcomes of black patients with TNBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-13.

e17070Background: MicroRNAs (miRNA) have been established as key regulators of tumor gene expression as well as prime biomarker candidates for clinical phenotypes. We analyzed the regulatory structure of miRNAs and their colocalized gene targets in EOC tissue to construct a regulatory signature for clinical prognosis. Methods: FFPE blocks of primary EOC tumor tissue with > 80% tumor cells were selected for 20 patients (stage ≥ IIc) for whom follow up data was available. Expression levels of mRNA and miRNA were assayed separately. An integrated analysis was performed to identify miRNA/mRNA regulatory clusters. Gene set enrichment analysis (GSEA) was carried out on the coexpression of putative miRNA target genes, from the miRTarBase database, with their respective miRNAs, to identify enriched categories for each miRNA. MiRNAs with at least one significantly enriched category from the MSigDB C2 dataset at a false discovery rate of 0.05 were chosen. For each enriched category of each miRNA, a regulon was defi...

The purpose of this review is to canvas policies and, to the extent possible, practices of major multilateral and bilateral development agencies, aimed at including disability in development. Development that includes disability, as referenced in this review, is understood as development in which persons with disabilities participate as both actors and beneficiaries. It can be achieved by disability specific initiatives, by adding disability-specific components to development programs, by fully inclusive programming, designed to include disability concerns into all development processes, or by a combination of these approaches. While this review does not claim to be exhaustive, it does attempt to provide as comprehensive as possible an overview of policies and practices on disability and development (D&D), both within and among the United Nations (UN) system, and among major bilateral development agencies. It should be noted that this is a dynamic issue and thus many development agencies are either in the process of crafting new disability policies or strategies or are currently reviewing their existing approaches with a view to modifying or amending them. Section two of this report reviews the international legal and policy framework pertinent to the consideration of D&D with particular attention to the Convention on the Rights of Persons with Disabilities (CRPD) and Millennium Development Goals (MDGs). Section three reviews multilateral agencies and structures, particularly those within the UN system, and reviews their existing policies and/or practices related to D&D. Section four includes coverage of regional structures supporting the inclusion of disability in development. Section five identifies bilateral development agencies that, either as matter of written policy or as evidenced through practice, have taken steps to design and implement programs and practices that are inclusive of disability. Section six provides conclusions.

This paper will explore the application of Fineman's vulnerability thesis in the context of the barriers to participation experienced by disabled people. It will address three central issues: 1. The role of the State in promoting the substantive equality of disabled citizens 2. The potential of the vulnerability thesis in bridging the gap between positive and negative rights 3. A holistic approach to disability discrimination based on vulnerability theory In particular, this paper will focus on the multi-faceted nature of discrimination and analyse Fineman's guidance on how the State might redress this through investigating the systemic reasons for disadvantage and exclusion. It will also consider the effectiveness of providing legal remedies based on the vulnerabilities of individuals (assessed through environmental, social and cultural factors) rather than based on membership of a particular minority group.

e12561 Background: Specific tissue miRNAs play an important role in tissue identity, differentiation and function. MiR-17-92 cluster is deleted in 20% of ovarian cancers. This is essential in embry...

e16557 Background: It is estimated that over 20,000 new cases of ovarian cancer are diagnosed annually. The workup of ovarian mass and diagnosis of cancer present a significant challenge on both pa...

e12560 Background: Outcomes of breast cancer patients depend on a number of phenotypic and molecular markers present in the malignancy. MicroRNAs dysregulation, often inhibiting gene expression, ar...

It is proposed that the pruritus of cholestasis is, in part, centrally mediated by endogenous opioid peptides. The expression of these peptides and their receptors on neurons displays a circadian rhythm, as does the scratching activity in patients with cholestasis and pruritus. Because light has regulatory effects on circadian rhythms via retinothalamic pathways, we hypothesized that bright-light therapy (BLT) reflected toward the eyes might alter the pruritus of cholestasis. To test this hypothesis, we studied the effect of BLT on this form of pruritus.Eight patients with chronic liver disease of different etiologies and pruritus were studied in an open-label, pilot study of 8-wk duration. BLT (10,000 lux) was administered for up to 60 min twice a day. Pruritus was assessed subjectively by a visual analog scale from which a visual analog score (VAS) was derived, and objectively, by a scratching activity monitoring system that recorded hourly scratching activity (HSA).In seven of the eight patients studied, the mean HSA was lower during BLT. BLT was associated with a mean decrease in HSA of 32.2% (p = 0.123). The mean VAS for pruritus was lower in six patients during BLT; the mean VAS score derived from the eight patients studied decreased by 42% (p = 0.05) during treatment.The results of this short-term study suggest that the pruritus of cholestasis is responsive to bright light reflected toward the eyes and that in some patients, BLT may ameliorate this form of pruritus.

1046 Background: Breast cancer is by far more common in W than in B women. Black women have more aggressive disease that occurs almost a decade earlier, it is usually triple negative and has a lower survival. Objectives to determine 1) if plasma miRNA expression differs between B and W women, and 2) if variation in miRs may explain the observed survival difference in TNBC in W compared to B women. Methods: We determined miRNA profiles in plasma collected before removal of breast tumors in three groups of W and B women: 1) normal controls (N), 2) TN and 2) ER/PR positive BC. Expression miRNA profiling of 754 miRNAs on the ABI Open Array detected 101miRNAs in plasma. We compared miRNA expression in cancer patients and race-matched controls. A moderated t-statistic through the R/Bioconductor 'limma' was used to compare the mean response between subject factors of interest. Results with a p

Background: Epithelial ovarian cancer accounts for 90% of all cases of malignant tumors of the ovaries, the majority of patients are diagnosed at stage III disease with 70% of them succumbing to their disease within 5 years. Objectives: We addressed 3 questions 1) are there patterns in the pre-surgical miRNA profiles between survivors of stage III ovarian cancer and patients who do not survive the disease “surviving pattern” (SP) 2) are there changes in the miRNA profiles that occur during or after chemotherapy that convert patients into SP. 3) Do patients with benign ovarian masses have the SP? Methods: Between 2004 and 2011 we investigated in patterns of circulating miRNAs collected before, after surgery, during and after chemotherapy in patients presenting for surgery for ovarian masses. We also collected blood at ovarian cancer relapse and tumor and benign ovary (if available) for miRNA analysis. Raw Ct values obtained from Taqman and software Data Assist. Data were processed via programming language R. Raw data were normalized using the least variable miRNA from dataset. Differential expression was studied using the R/Bioconductor package “limma” using moderated t-statistic allowing both 2 sample comparison and multiple sample comparison. Only results with a p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4150. doi:1538-7445.AM2012-4150

Objective: To compare the therapeutic effectiveness of daily exposure to narrowband (NB) UV-B vs broadband (BB) UV-B with and without tar. Design: Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study. Narrowband UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet. Narrowband UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar (Goeckerman treatment) below the waist. Setting: General clinical research center of a university hospital inpatient unit. Patients: Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study. Main Outcome Measures: Clinical efficacy was measured weekly using psoriasis severity scoring. Therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression). Results: Clinical resolution of psoriasis was achieved on 86% of paired sites treated with NB UV-B vs 73% treated with BB UV-B. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88% of lesions treated with NB UV-B vs 59% treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment. Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment. Conclusions: Narrowband UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis, with faster clearing and more complete disease resolution. The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0— minimum erythema dose exposure. Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases. Arch Dermatol. 1997;133:1514-1522