Gendered Violence and International Human Rights: Thinking Non-Discrimination Beyond the Sex Binary

The concept of non-discrimination has been central in the feminist challenge to gendered violence within international human rights law. This article critically explores non-discrimination and the challenge it seeks to pose to gendered violence through the work of Judith Butler. Drawing upon Butler’s critique of heteronormative sex/gender, the article utilises an understanding of gendered violence as effected by the restrictive scripts of sex/gender within heteronormativity to illustrate how the development of non-discrimination within international human rights law renders it ineffective to challenge gendered violence due to its own commitments to binarised and asymmetrical sex/gender. However, the article also seeks to encourage a reworking of non-discrimination beyond the heteronormative sex binary through employing Butler’s concept of cultural translation. Analysis via the lens of cultural translation reveals the fluidity of non-discrimination as a universal concept and offers new possibilities for feminist engagement with universal human rights.

Civilianizing Civil Conflict: Civilian Defense Militias and the Logic of Violence in Intra-State Conflict

This article examines how civilian defense militias shape violence during civil war. We define civilian defense forces as a sedentary and defensive form of pro-government militia that incumbents often use to harness the participation of civilians during a counterinsurgency campaign. We argue that civilian defense forces reduce the problem of insurgent identification. This leads to a reduction in state violence against civilians. However, we also claim that these actors undermine civilian support for insurgents, which leads to an increase in rebel violence against civilians and overall intensification of conflict. A statistical analysis of government and rebel violence against civilians from 1981 to 2005, and a qualitative assessment of a civilian defense force operating in Iraq from 2005 to 2009, offer strong support for our theoretical claims. These findings provide further insight into pro-government militias and their effects on violence. They also have wider ethical implications for the use of civilian collaborators during civil war.

Violence and Commemoration in the New Northern Ireland: Space, Memory and Management

On June 27th 2012, the Deputy First Minister of Northern Ireland and former IRA commander, Martin McGuinness shook hands with Queen Elizabeth II for the first time at an event in Belfast. For many the gesture symbolised the consolidation of Northern Ireland's transition to peace, the meeting of cultures and traditions, and hope for the future. Only a few weeks later however violence spilled onto the streets of north and west Belfast following a series of commemorative parades, marking a summer of hostilities. Those hostilities spread into a winter of protest, riot and discontent around flags and emblems and a year of tensions and commemorative-related violence marked again by a summer of rioting and protest in 2013. Outwardly these examples present two very different pictures of the 'new' Northern Ireland; the former of a society moving forward and putting the past behind it and the latter apparently divided over and wedded to different constructions of the past. Furthermore they revealed two very different 'places', the public handshake in the arena of public space; the rioting and fighting occurring in spaces distanced from the public sphere. This paper has also illustrated the difficulties around the ‘public management’ of conflict and transition as many within public agencies struggle with duties to uphold good relations and promote good governance within an environment of political strife, hostility and continuing violence.

This paper presents the key findings and implications of an exploratory project funded by the Arts and Humanities Research Council, explored the phenomenon of commemorative-related violence in Northern Ireland. We focus on 1) why the performance or celebration of the past can sometimes lead to violence in specific places; 2) map and analyse the levels of commemorative related violence in the past 15 years and 3) look at the public management implications of both conflict and transition at a strategic level within the public sector.

LYRIC/AEG-1 is targeted to different subcellular compartments by ubiquitinylation and intrinsic nuclear localization signals

PURPOSE: LYRIC/AEG-1 has been reported to influence breast cancer survival and metastases, and its altered expression has been found in a number of cancers. The cellular function of LYRIC/AEG-1 has previously been related to its subcellular distribution in cell lines. LYRIC/AEG-1 contains three uncharacterized nuclear localization signals (NLS), which may regulate its distribution and, ultimately, function in cells.

EXPERIMENTAL DESIGN: Immunohistochemistry of a human prostate tissue microarray composed of 179 prostate cancer and 24 benign samples was used to assess LYRIC/AEG-1 distribution. Green fluorescent protein-NLS fusion proteins and deletion constructs were used to show the ability of LYRIC/AEG-1 NLS to target green fluorescent protein from the cytoplasm to the nucleus. Immunoprecipitation and Western blotting were used to show posttranslational modification of LYRIC/AEG-1 NLS regions.

RESULTS: Using a prostate tissue microarray, significant changes in the distribution of LYRIC/AEG-1 were observed in prostate cancer as an increased cytoplasmic distribution in tumors compared with benign tissue. These differences were most marked in high grade and aggressive prostate cancers and were associated with decreased survival. The COOH-terminal extended NLS-3 (amino acids 546-582) is the predominant regulator of nuclear localization, whereas extended NLS-1 (amino acids 78-130) regulates its nucleolar localization. Within the extended NLS-2 region (amino acids 415-486), LYRIC/AEG-1 can be modified by ubiquitin almost exclusively within the cytoplasm.

CONCLUSIONS: Changes in LYRIC/AEG-1 subcellular distribution can predict Gleason grade and survival. Two lysine-rich regions (NLS-1 and NLS-3) can target LYRIC/AEG-1 to subcellular compartments whereas NLS-2 is modified by ubiquitin in the cytoplasm.

Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancer

Chemotherapies that target thymidylate synthase (TS) continue to see considerable clinical expansion in non-small cell lung cancer (NSCLC). One drawback to TS-targeted therapies is drug resistance and subsequent treatment failure. Novel therapeutic and biomarker-driven strategies are urgently needed. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is reported to protect tumor cells from aberrant misincorporation of uracil during TS inhibition. The goal of this study was to investigate the expression and significance of dUTPase in mediating response to TS-targeted agents in NSCLC. The expression of dUTPase in NSCLC cell lines and clinical specimens was measured by quantitative real-time reverse transcriptase PCR and immunohistochemistry. Using a validated RNA interference approach, dUTPase was effectively silenced in a panel of NSCLC cell lines and response to the fluoropyrimidine fluorodeoxyuridine (FUdR) and the antifolate pemetrexed was analyzed using growth inhibition and clonogenic assays. Apoptosis was analyzed by flow cytometry. Significant variation in the quantity and cellular expression of dUTPase was observed, including clear evidence of overexpression in NSCLC cell line models and tumor specimens at the mRNA and protein level. RNA interference-mediated silencing of dUTPase significantly sensitized NSCLC cells to growth inhibition induced by FUdR and pemetrexed. This sensitization was accompanied by a significant expansion of intracellular dUTP pools and significant decreases in NSCLC cell viability evaluated by clonogenicity and apoptotic analyses. Together, these results strongly suggest that uracil misincorporation is a potent determinant of cytotoxicity to TS inhibition in NSCLC and that inhibition of dUTPase is a mechanism-based therapeutic approach to significantly enhance the efficacy of TS-targeted chemotherapeutic agents.

Selecting the best targeted agent in first-line treatment of unresectable liver metastases from colorectal cancer:does the bench have the answers?

For physicians facing patients with organ-limited metastases from colorectal cancer, tumor shrinkage and sterilization of micrometastatic disease is the main goal, giving the opportunity for secondary surgical resection. At the same time, for the majority of patients who will not achieve a sufficient tumor response, disease control remains the predominant objective. Since FOLFOX or FOLFIRI have similar efficacies, the challenge is to define which could be the most effective targeted agent (anti-EGFR or anti-VEGF) to reach these goals. Therefore, a priori molecular identification of patients that could benefit from anti-EGFR or anti-VEGF monoclonal antibodies (i.e. the currently approved targeted therapies for metastatic colorectal cancer) is of critical importance. In this setting, the KRAS mutation status was the first identified predictive marker of response to anti-EGFR therapy. Since it has been demonstrated that tumors with KRAS mutation do not respond to anti-EGFR therapy, KRAS status must be determined prior to treatment. Thus, for KRAS wild-type patients, the choices that remain are either anti-VEGF or anti-EGFR. In this review, we present the most updated data from translational research programs dealing with the identification of biomarkers for response to targeted therapies.

Exposure to Political Violence in Northern Ireland and Outcome of First Episode Psychosis

The impact of political violence on individuals presenting with an episode of first episode psychosis has not been examined. Individuals were assessed for exposure to political violence in Northern Ireland (the “Troubles”) by asking for a response to 2 questions: one asked about the impact of violence “on your area”; the second about the impact of violence “on you or your family’s life.” The participants were separated into 2 groups (high and low impact) for each question. Symptom profiles and rates of substance misuse were compared across the groups at baseline and at 3-year follow up. Of the 178 individuals included in the study 66 (37.1%) reported a high impact of the “Troubles” on their life and 81 (45.5%) a high impact of the “Troubles” on their area. There were no significant differences in symptom profile or rates of substance misuse between high and low groups at presentation. At 3-year follow-up high impact of the “Troubles” on life was associated with higher Positive and Negative Symptom Scale (PANSS) Total (P = .01), PANSS-Positive (P < .05), and PANSS-General (P < .01) scores and lower global assessment of functioning disability (P < .05) scores, after adjusting for confounding factors. Impact of the “Troubles” on area was not associated with differences in symptom outcomes. This finding adds to the evidence that outcomes in psychosis are significantly impacted by environmental factors and suggests that greater attention should be paid to therapeutic strategies designed to address the impact of trauma.

Research Review: The Impact of Domestic Violence on Children

This paper reviews the research on the prevalence and impact of domestic violence on children, and considers how professionals should respond to children’s needs to best provide support and ensure their safety.

‘The Violence of History: Rosa Chacel’s Memorias de Leticia Valle’

Leticia Valle, the eleven-year-old narrator and protagonist of Rosa Chacel’s 1945 novel Memorias de Leticia Valle seduces and destroys her history teacher, Daniel. Here, I argue that Daniel represents traditionalist, right-wing interpretations of Spanish history while also recalling the importance of the colonial wars in Morocco in the build up to the Civil War, and the Nationalists’ use of Moroccan conscripts and recruits within the peninsula. Written at a time when history was being used to justify an armed rebellion, a civil war, and the imposition of a brutal dictatorship, Chacel’s novel depends on ellipses and absence to question historiographical principles. Furthermore, it combines continued reference to Spanish history with the use of violent and militant language. The most devastating conflict of all is between Leticia and Daniel: she silences and dehumanizes him, though she is not able to fully explain what happened. Writing from Switzerland, Chacel’s narrator takes possession of Spanish history at a time when dissent within Spain was being silenced by the Francoist regime.

Violence against women in the Irish War of Independence, 1919-1921

This chapter examines the nature and extent of violence experienced by women in Ireland during the Irish War of Independence (1919-1921) at the hands of both the Crown forces and the Irish Republican Army. It argues that targetted killings of women by either side was rare. The most common forms of such violence can be categorised as physical, gendered (cutting of hair) and psychological (intimidation and the killing of male relatives). It argues that there was a difference between gendered and sexual crime, the latter of which appears to have been very uncommon. A considerable part of the chapter uses theoretical literature on violence against women in conflict zones to explain why sexual violence was uncommon, arguing that neither side had much to gain from its employment, that the Crown forces were aware of the damage it could do to Britain's international reputation and that the terror tactics adopted by the Crown forces were sufficient to achieve their ends without resorting to rape. In regard to the IRA, the absence of any evidence of rape or sexual assault being perpetrated could be attributable to their Catholicism, reliance on support from the community, the efforts of the first Dáil to achieve foreign recognition of the Republic and the role of Cumann na mBan women in the guerrilla conflict. The historiography of women in the Irish revolution is also analysed.

Review of Mark F. Chingono. The State, Violence and Development. The Political Economy of War in Mozambique, 1975–1992.

Book review of: Mark F. Chingono. The State, Violence and Development. The Political Economy of War in Mozambique, 1975–1992. Avebury (Aldershot, Brookfield USA, Hong Kong, Singapore, Sydney), 1996. 291 pp. Foreword by Keith Hart. Tables. Appendix. Selected Bibliography. Index. £42.00. $71.95. Cloth.

Overcoming Resistance to Targeted Therapies in Cancer

The recent discovery of oncogenic drivers and subsequent development of novel targeted strategies has significantly added to the therapeutic armamentarium of anti-cancer therapies. Targeting BCR-ABL in chronic myeloid leukemia (CML) or HER2 in breast cancer has led to practice-changing clinical benefits, while promising therapeutic responses have been achieved by precision medicine approaches in EGFR mutant lung cancer, colorectal cancer and BRAF mutant melanoma. However, although initial therapeutic responses to targeted therapies can be substantial, many patients will develop disease progression within 6-12 months. An increasing application of powerful omics-based approaches and improving preclinical models have enabled the rapid identification of secondary resistance mechanisms. Herein, we discuss how this knowledge has translated into rational, novel treatment strategies for relapsed patients in genomically selected cancer populations.

Development of TMTP-1 targeted designer biopolymers for gene delivery to prostate cancer

Designer biopolymers (DBPs) represent state of the art genetically engineered biomacromolecules designed to condense plasmid DNA, and overcome intra- and extra- cellular barriers to gene delivery. Three DBPs were synthesized, each with the tumor molecular targeting peptide-1 (TMTP-1) motif to specifically target metastases. Each DBP was complexed with a pEGFP-N1 reporter plasmid to permit physiochemical and biological assay analysis. Results indicated that two of the biopolymers (RMHT and RM3GT) effectively condensed pEGFP-N1 into cationic nanoparticles< 100nm and were capable of transfecting PC-3 metastatic prostate cancer cells. Conversely the anionic RMGT DBP nanoparticles could not transfect PC-3 cells. RMHT and RM3GT nanoparticles were stable in the presence of serum and protected the cargo from degradation. Additionally it was concluded that cell viability could recover post-transfection with these DBPs, which were less toxic than the commercially available transfection reagent Lipofectamine® 2000. With both DBPs, a higher transfection efficacy was observed in PC-3 cells than in the moderately metastatic, DU145, and normal, PNT2-C2, cell lines. Blocking of the TMTP-1 receptors inhibited gene transfer indicating internalization via this receptor. In conclusion RMHT and RM3GT are fully functional DBPs that address major obstacles to gene delivery and target metastatic cells expressing the TMTP-1 receptor.