Cryptorchidism is a common reproductive abnormality, possibly resulting from abnormal hormone production/action by the fetal testis. Insulin-like factor 3 (Insl3) is thought to be involved in gubernaculum development and transabdominal testicular descent, but its importance is unclear, due partly to lack of suitable Insl3 antibodies. We generated (by genetic immunization) and validated a novel antirat Insl3 antibody, which we used to characterize immunoexpression of Insl3 in rat Leydig cells (LCs) from fetal life until adulthood and its relationship to cryptorchidism. Immunoexpression was strong on embryonic day (E) 17.5 and E19.5 and from 35 d of age onward but weak from E21.5 until puberty. Because in utero exposure to di (n-butyl) phthalate (DBP) induces cryptorchidism and suppresses Insl3 gene expression, we investigated Insl3 protein expression in fetal and adult rats exposed to 500 mg/kg.d DBP from E13.5 to E21.5. Expression on E17.5 and E19.5 decreased dramatically after DBP exposure, but there was no consistent correlation between this suppression and abnormal testis position. We also compared expression of Insl3 and P450 side-chain cleavage enzyme in fetal testes from rats exposed in utero to DBP or flutamide (50 mg/kg.d). DBP treatment suppressed expression of both P450 side-chain cleavage enzyme and Insl3 at E19.5, but flutamide exposure had no effect on either protein, demonstrating that Insl3 expression in fetal rat LCs is not androgen regulated. In adult rats, Insl3 expression was suppressed in 80% of cryptorchid and 50% of scrotal testes from rats exposed to DBP, suggesting that prenatal DBP exposure also leads to maldevelopment/malfunction of the adult LC population in some animals.

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Lapatinib plus capecitabine (lap+cap) is approved as treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), who have progressed on prior trastuzumab in the metastatic setting. We previously reported progression-free survival (PFS), overall survival (OS) and safety results from this open-label, multicentre, phase II study (VITAL; NCT01013740) conducted in women with HER2 positive MBC, to evaluate the efficacy and safety of lap plus vinorelbine (lap+vin), an important chemotherapy option for MBC, compared with lap+cap. In total, 112 patients were randomised 2:1 to treatment with lap+vin (N = 75) or lap+cap (N = 37). Results showed that the median PFS (primary endpoint) and OS (secondary endpoint) post-randomisation were comparable between treatment arms, with no new safety signals detected. Here, we assessed the final OS in this study at 40 months post-randomisation. At the time of final analyses, 24 (32%) patients were ongoing in the lap+vin arm, compared with 14 (38%) patients in the lap+cap arm (92% in both arms had discontinued treatment). Median OS in the lap+vin arm was 23.3 months (95% confidence intervals [CI]: 18.5, 31.1), compared with 20.3 months (95% CI: 16.4, 31.8) in the lap+cap arm. The median follow-up in the lap+vin arm was 18.86 months (95% CI: 10.68, 26.02), compared with 19.38 (95% CI: 25.56) months in the lap+cap arm. Similar rates of death (56-57%) were observed in both arms. The final OS was consistent with the previously reported data and suggest that lap+vin offers an effective treatment option for women with HER2-positive MBC.

In June 2005 I carried out a 'cultural mapping' project at the invitation of the Walmajarri Aboriginal owners of Paruku (Lake Gregory) in the south-east Kimberley. The team of white people with their varied expertise who assisted me were geomorphologist Jim Bowler from the Department of Earth Sciences at the University of Melbourne, tourism consultant and trainer Petrine McCrohan from Kimberley TAFE, anthropologist Cathe rine Wohlan from Broome, linguist Eirlys Richards, also from Broome, Mark Ditcham, co-ordinator of the Paruku Indigenous Protected Area, and John Carty, an anthropol ogy doctoral student working for the Palyalatju traditional medicine organisation based at the nearby Balgo community.The project's intention was to bring together scientific and Aboriginal knowledge of the Lake Gregory area, to record traditional stories and oral histories, to make photo graphic and video documentation of campsites, archaeological and geological sites, bush food and bush medicine, and to record place and family names. The central tem plate for this recording process was a large painted canvas map, on which were inscribed dreaming tracks, place names, soakwaters and campsites, the precise areas to which people's ancestors held entitlement, and the locations where large groups of peo ple came together during the period of first encounters between white settlers, missionaries and Aboriginal people. The revisiting of locations and camping out on country provided an opportunity for elders to pool their knowledge of names, places and events now at risk of being forgotten, for the purposes of educating their children in their country and their culture. The inclusion of non-Aboriginal information was an incremental shift towards bridging the gap between knowledge systems, and an attempt to provide a basis for future planning of the management of the lake. In the process of the mapping exercise questions were raised about environmental mainte nance, the protection of artefacts and the increasing impact of tourism. The map and recorded material were later exhibited at the Balgo Culture Centre, allowing the Wal majarri lake people to present their own culturally coherent identity within the large and diverse mix of language groups based in and around Balgo. This paper is a reflective piece with no academic pretensions. It attempts rather to evoke the place and its people, describing the sometimes uneasy interface between white and Aboriginal knowledge systems, and leaving open the constantly evolving possibilities of that encounter. As part of the essay I have included the 'storybook' pro-* * * May 2005Heading west again, towards what feels like home, or the nearest thing to it I have. But always when I arrive there's that small quiver of ambivalence before the fam iliarity takes over, the pleas ure to be back, the daily involvement in the project to hand. This need to keep covering the same ground, straddling the worlds. A nd they are worlds that don't make much space for each other, in spite of the fascination, even obsess...

Desert Lake is a book combining artistic, scientific and Indigenous views of a striking region of north-western Australia. Paruku is the place that white people call Lake Gregory. It is Walmajarri land, and its people live on their Country in the communities of Mulan and Billiluna. This is a story of water. When Sturt Creek flows from the north, it creates a massive inland Lake among the sandy deserts. Not only is Paruku of national significance for waterbirds, but it has also helped uncover the past climatic and human history of Australia. Paruku's cultural and environmental values inspire Indigenous and other artists, they define the place as an enduring home, and have led to its declaration as an Indigenous Protected Area. The Walmajarri people of Paruku understand themselves in relation to Country, a coherent whole linking the environment, the people and the Law that governs their lives. These understandings are encompassed by the Waljirri or Dreaming and expressed through the songs, imagery and narratives of enduring traditions. Desert Lake is embedded in this broader vision of Country and provides a rich visual and cross-cultural portrait of an extraordinary part of Australia.