39 research outputs found
Survival Data From a Phase II, Open-Label Study of Pazopanib or Lapatinib Monotherapy in Patients With Advanced and Recurrent Cervical Cancer
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Empowering Ni-Vanuatu women: Amplifying Wantok authority and achieving fair market access
No full textThe Republic of Vanuatu (2004) report on Vanuatu’s implementation of the United Nations Convention on the Elimination of All Forms of Discrimination against Women (CEDAW) notes that many urban disenfranchised Ni-Vanuatu women live in poverty and have little access to paid employment. The women who do gain paid employment in formal jobs rarely gain access to positions of authority. The United Nations (UN) offered two strategies to improve the position of Ni-Vanuatu women in Vanuatu. The first is informed by CEDAW in Article Eleven on Employment. The “Equity Desk of the Vanuatu Department of Strategic Management” and the “Vanuatu Department of Women’s Affairs Gender Planner” (The Republic of Vanuatu, 2004, pp. 12-13) have been charged with the responsibility of implementing Article Eleven and developing Equal Employment Opportunities (EEO) programmes for the public sector. This strategy aims to increase women’s access to paid employment in the formal employment sector and encourage women to achieve positions of authority. The second strategy offered by the UN is the establishment of microfinance projects aimed at providing disenfranchised urban women unable to find employment with a means to own and run microfinance businesses to earn a living. Both these strategies have the overarching aim of improving the well-being of Ni-Vanuatu women.
This study has investigated the extent to which access to formal sector jobs and the implementation of microfinance businesses in the informal sector addresses the well-being of Ni-Vanuatu women. These programmes are being implemented within a complex historical, socio-political cultural and economic environment (Van Trease, 1995). This complexity includes the continuance of Wantok systems of governance in the form of matrilineality (predominant in Vanuatu) and patrilineality (adopted from Christian influences in 1800s and colonial legacy in 1906) (Van Trease, 1987; Facey, 1981; Allen, 1981 & Macdonald-Milne & Thomas, 1981). Matrilineal cultural values bequeath patrimony and legacy of lineage and land inheritance from mothers to daughters. Matrilineal women share power with men in community affairs (Maltali, Sandy & Tamashiro, 2009). In patrilineal communities, patrimony and legacy of lineage and land inheritance is passed from fathers to sons (Van Trease, 1987). Patrilineal mothers and daughters have no lineage, land inheritance, or power-sharing rights (Stege, Maetala, Naupa & Simo 2008). Both Wantok systems are based on communal values practised primarily in the rural sector. Urban centres are organised around a modern-cash and market-economy and a governance framework based on the British Westminster model and the French Head of State model (ILO, 2006). This European generated governance system is underpinned by values informed by liberal competitive individualism and an assumed commitment to meritocracy. It is, however, a system of governance steeped in patriarchal nuances as a direct legacy of the colonial regime now adapted and administered by the Vanuatu’s ruling elite, referred as Vanuatu’s urban patriarchy throughout this thesis.
The theoretical frameworks used in this research draw on both liberal feminist studies and on an adaptation of subaltern scholarship (Thomas & Humphries, 2010 & 2011). The focus is on the legacy of imperialism and colonisation, the politics of power and hegemony, and the expressions of equal rights, emancipation and empowerment as these pertain to the well-being of women in Vanuatu.
Three sets of qualitative empirical observations were collected: i) a focus group discussion with 20 employer and employee representatives; ii) 36 conversations with women employed in the formal employment sector who held positions of authority within their respective organisations; and iii) 39 conversations with women who owned a microfinance business. My field notes were analysed thematically using a point and counterpoint framework crafted from my interest in the work of Huxley (cf Baker & James, 2000a & 2000b & Dawson, 2009). The point is informed by a liberal feminist lens (Gamble, 1999 & Heywood, 2000). A counterpoint to this liberal feminist interpretation is generated from a post-colonial feminist perspective through an adaptation of subaltern studies (Thomas & Humphries 2010 & 2011; Gamble, 1999 & Spivak, 1988). I draw on my Matrilineal Wantok Feminist Voice (MWFV) to form a standpoint in the discussion and to frame insights drawn from the ideas associated with the solidarity economy (Allard, Davidson & Matthaei, 2009; Harvey, 2006 & Harding, 2004).
Point/counterpoint/standpoint for the research as a whole
Point: Liberal feminist strategies for the emancipation of women (and the intended improvement and well-being of their families associated with this perspective) encourage women to pursue better living standards, achieve empowerment in the home, and seek formal jobs or other market-based income opportunities. If in formal jobs, women are encouraged to seek positions of authority. For these women, the major transition in orientation is the move from Wantok-related patterns of responsibilities and opportunities to those made available in the formal Western-generated economy. These Western ways, with emphasis on individualized opportunity, appear to offer financial gain and familial influences, particularly to women born into patrilineal lineage descent groups.
Counterpoint: Viewed through the adaptation of subaltern perspectives that I have applied to the liberal feminist remedies for the enhancement of well-being for the women of Vanuatu, it appears that the women of Vanuatu are involved in multiple and simultaneous complex master/slave relationships (Kohn, 2005 & Honderich, 1995). These relationships are exemplified in salaried/professional occupations held by women, between the women and their employers and work-place cultures, between women and rural and urban patriarchal hegemonies, and between women and the cash and market economy. While EEO activities can be seen to make a difference in the lives of some women, taken together, these interventions are reducing the overall well-being for Ni-Vanuatu women more generally. For the Vanwods microfinance women entrepreneurs, master/slave relationships could be discerned between the Vanwods MFI’s social control of the Mamas, the Vanuatu Government’s imposition of high business licence fees to the Mamas, the Mamas and their greater dependence on the cash and market economy, and the Mamas and their relationship with rural and urban patriarchal hegemonies (Thomas & Humphries, 2010 & 2011). These forms of systemic subservience interpreted from the women’s narratives provide a caution against the uncritical adoption of Western liberal feminist ideals (DeVault, 1990). It is matrilineal women; however, who appear to suffer the most from their move into the urban centres as there they must contend with an urban patriarchal hegemony, an impediment which they had not encountered in their former rural communities governed in accordance with matrilineal Wantok values.
Standpoint: The research findings suggest that all women in this study worked long hours, experiencing discrimination and oppression, received low pay, and experienced increased financial obligations as a result of their engagement in formal and informal jobs. As well as being increasingly dependent on inadequate and unsustainable livelihoods in the urban areas, family and Wantok social relations were challenged and diminished as a consequence of their necessary commitment to their jobs and the demands of urban living. Access to traditional forms of authority and sustenance was undermined.
I conclude that, overall, the implementation of CEDAW-EEO programmes along with the establishment of microfinance projects devised for the emancipation of the disenfranchised women of Vanuatu, while apparently proving beneficial from a liberal feminist interpretation in granting urban women with access to incomes, property and power-sharing, may provide an element of liberation for women of patrilineal descent groups but add new dimensions of patriarchal inhibitors for women of matrilineal descent groups who take up employment under the Westminster rules of governance. The remedies taken as a whole, while promising improved well-being through market-based income generation, remove women from the Wantok kinship social support networks embedded in their indigenous Wantok governance frameworks causing complex problems and hardships for them. Drawing on my Matrilineal Wantok Feminist standpoint position, I suggest that the Solidarity Economy, which combines aspects of market access while still engaging in the traditional systems of social organization, offers an alternative organisational and economic framework for developing and enhancing community well-being in both the rural and urban areas of Vanuatu
Assessment of a cell-line-derived HIF1α gene signature in tumor tissue from a metastatic renal cell carcinoma (RCC) trial of pazopanib.
No full text 408 Background: Microarray and clinical data from a randomized phase II RCC clinical trial were evaluated to examine the HIF1α kidney cancer gene signature developed from cell lines by Shen et al (Cancer Discovery 2011). Methods: Archival FFPE tumor samples were collected from patients (pts) enrolled in a Phase II RCC study of pazopanib (Hutson, JCO 2009). RNA was isolated and microarray analysis was performed at Response Genetics, Inc. (Los Angeles, CA) using the Affymetrix (Affy) U133 plus Array. Affy data were normalized using the MAS5 algorithm. Genes (n=69) identified from experiments in 10 cancer cell lines were mapped to genes on the U133 array. Patterns of expression (exp) among the mapped genes were assessed using multivariate analyses. Putative patterns were assessed for association with HIF1α gene exp levels, and both patterns and HIF1α levels were assessed for association with response rate (RR) (RECIST), and PFS, using nonparametric and Kaplan-Meier analyses. Gene set enrichment analysis (GSEA) was applied to determine if mapped genes were enriched for HIF1α gene exp. Results: RNA was available for 46 of 225 patients; baseline characteristics were similar to the overall study. 41/46 patients had VHL heterozygous mutations; 5/46 patients were VHL wild type. HIF1a gene expression was detected in all 46 patients. 64/69 genes were mapped to the Affy platform. For genes which mapped to multiple probes, the probe closest to the 3` end was used. A potential 4 cluster pattern was identified. These clusters were associated with HIF1α gene exp, but neither clusters nor HIF1α gene exp were associated with clinical response to pazopanib. Conclusions: The observed pattern of gene exp among 46 pts with available data from a Phase II RCC study of pazopanib is consistent with the cell line derived gene set proposed by Shen et al. Patterns are associated with HIF1α exp; neither patterns nor HIF1α exp are associated with clinical response in this small subset of pts. These data support the on-going efforts in bench-to-bedside research. </jats:p
Phase II, Open-Label Study of Pazopanib or Lapatinib Monotherapy Compared With Pazopanib Plus Lapatinib Combination Therapy in Patients With Advanced and Recurrent Cervical Cancer
No full textPurpose Pazopanib and lapatinib are tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit or epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2/neu), respectively. In cervical cancer, EGFR and HER2/neu overexpression and high microvascular density correlate with survival. Patients and Methods Patients with measurable stage IVB persistent/recurrent cervical carcinoma not amenable to curative therapy and at least one prior regimen in the metastatic setting were randomly assigned in a ratio of 1:1:1 to pazopanib at 800 mg once daily, lapatinib at 1,500 mg once daily, or lapatinib plus pazopanib combination therapy (lapatinib at 1,000 mg plus pazopanib at 400 mg once daily or lapatinib at 1,500 mg plus pazopanib at 800 mg once daily). Therapy continued until progression or withdrawal because of adverse events (AEs). Primary end point was progression-free survival (PFS), and secondary end points were overall survival (OS), response rate (RR), and safety. The futility boundary was crossed at the planned interim analysis for combination therapy compared with lapatinib therapy, and the combination was discontinued. Results Of 230 patients enrolled, 152 were randomly assigned to the monotherapy arms: pazopanib (n = 74) or lapatinib (n = 78). Most patients (62%) had recurrent cancer. Pazopanib improved PFS (hazard ratio [HR], 0.66; 90% CI, 0.48 to 0.91; P = .013) and OS (HR, 0.67; 90% CI, 0.46 to 0.99; P = .045). Median OS was 50.7 weeks and 39.1 weeks and RRs were 9% and 5% for pazopanib and lapatinib, respectively. The only grade 3 AE > 10% was diarrhea (11% pazopanib and 13% lapatinib). Grade 4 AEs were 9% (lapatinib) and 12% (pazopanib). Conclusion This study confirms the activity of antiangiogenesis agents in advanced and recurrent cervical cancer and demonstrates the benefit of pazopanib based on the prolonged PFS and favorable toxicity profile. </jats:sec
Translocation of Effector Proteins into Plant Cells by the Flax Rust Pathogen Melampsora lini
No full textDuring infection, rust fungi secrete effector proteins into host plant cells from haustoria to aid in their colonization. How rust effectors are secreted from the haustorium and delivered into the cytoplasm of host cells remains poorly understood. We used an Agrobacterium-mediated transformation procedure to generate stable transgenic flax rust strains expressing the effectors AvrM and AvrP123 fused to yellow fluorescent protein (YFP). We showed that both AvrM-YFP and AvrP123-YFP fusion proteins were secreted by the fungus into a narrow space surrounding the haustorium, likely the extrahaustorial matrix (EHMx); however, only AvrM-YFP was delivered into host cells, triggering a typical resistance phenotype in plants carrying the corresponding resistance (R) gene M. The signal peptide of AvrM was sufficient to direct YFP secretion into the EHMx; however, delivery into the host cell required a larger 105-amino-acid N-terminal fragment of AvrM. These results indicate that translocation of this protein into the host cell from the EHMx is a separate process from secretion into the EHMx and requires a signal present in AvrM between amino acids 34 and 105. This is in contrast to previous observations of AvrM localization after transient expression in plants, highlighting the necessity for analysis in the natural infection system. [Figure: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license
A Chromosome-Scale Genome Assembly of the Flax Rust Fungus Reveals the Two Unusually Large Effector Proteins, AvrM3 and AvrN
No full textRust fungi comprise thousands of species, many of which cause disease on important crop plants. The flax rust fungus Melampsora lini has been a model species for the genetic dissection of plant immunity since the 1940s; however, the highly fragmented and incomplete reference genome has so far hindered progress in effector gene discovery. Here, we generated a fully phased, chromosome-scale assembly of the two nuclear genomes of M. lini strain CH5, resolving an additional 320 Mbp of the sequence. The 482-Mbp dikaryotic genome is at least 79% repetitive, with a large proportion (approximately 40%) of the genome comprising young, highly similar transposable elements. The assembly resolves the known effector gene loci, some of which carry complex duplications that were collapsed in the previous assembly. Using a genetic map followed by manual correction of gene models, we identified the AvrM3 and AvrN genes, which encode unusually large fungal effector proteins and trigger defense responses when co-expressed with the corresponding resistance genes. We located the genes linked to the tetrapolar mating system on chromosomes 4 and 9, but in contrast to the cereal rusts that have one pheromone receptor gene per haplotype, in flax rust, three pheromone receptor genes were found, with two of them closely linked on one haplotype. Taken together, we show that a high-quality assembly is crucial for resolving complex gene loci, and given the increasing number of fungal effectors of large size, the commonly applied criterion for effector candidates of being small proteins needs to be reconsidered. [Figure: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license
Correlation of PD-L1 tumor expression and treatment outcomes in patients with renal cell carcinoma receiving sunitinib or pazopanib : results from COMPARZ, a randomized controlled trial
No full textPurpose: The interaction of programmed death-1 ligand (PDL1) with its receptor (PD-1) on T cells inactivates antitumor immune responses. PD-L1 expression has been associated with poor outcomes in renal cell carcinoma (RCC) but has not been investigated in advanced RCC patients receiving VEGF-targeted therapy. Experimental Design: Formalin-fixed paraffin-embedded specimens were collected at baseline from patients in the COMPARZ trial. Tumor cell PD-L1 expression by IHC was evaluated using Hscore (HS). Dual PD-L1/CD68 staining was used to differentiate PD-L1 tumor expression from tumor-associated macrophages. Intratumor CD8-positive T cells were quantified morphometrically. Associations between biomarkers and survival were investigated using the log-rank test. Results: HS data were available from 453 of 1,110 patients. Sixty-four percent of patients had negative PD-L1 expression (HS = 0). Patients with HS > 55 (n = 59, 13%) had significantly shorter overall survival (OS) than those with HS ≤ 55 in both pazopanib and sunitinib arms (median 15.1 vs. 35.6 and 15.3 vs. 27.8 months, respectively, P = 0.03). In both arms, median OS was shortest in patients with HS > 55 and intratumor CD8- positive T-cell counts > 300 (9.6 and 11.9 months with pazopanib and sunitinib, respectively). Median OS in patients with HS ≤ 55 and CD8-positive T-cell counts ≤ 300 was 36.8 and 28.0 months with pazopanib and sunitinib, respectively. Progression-free survival results were similar to OS results. Conclusions: Increased tumor cell PD-L1, or PD-L1 plus tumor CD8-positive T-cell counts, were associated with shorter survival in patients with metastatic RCC receiving VEGF-targeted agents. These findings may have implications for future design of randomized clinical trials in advanced RCC
Political life writing in the Pacific
No full textThis book aims to reflect on the experiential side of writing political lives in the Pacific region. The collection touches on aspects of the life writing art that are particularly pertinent to political figures: public perception and ideology; identifying important political successes and policy initiatives; grappling with issues like corruption and age-old political science questions about leadership and ‘dirty hands’. These are general themes but they take on a particular significance in the Pacific context and so the contributions explore these themes in relation to patterns of colonisation and the memory of independence; issues elliptically captured by terms like ‘culture’ and ‘tradition’; the nature of ‘self’ presented in Pacific life writing; and the tendency for many of these texts to be written by ‘outsiders’, or at least the increasingly contested nature of what that term means
Association of the hemochromatosis gene with pazopanib-induced transaminase elevation in renal cell carcinoma
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