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SUMMARY Objective Fertility preservation (FP) is a widespread practice in paediatric oncology when gonadotoxic medications such as cyclophosphamide (CPO) are used. FP practice outside of oncology has not been studied, although nephrologists regularly use CPO. This is the first study to explore FP practice by paediatric nephrologists when CPO is used. Design Survey study. Descriptive statistics and chi-squared analyses were employed to analyse the data. Participants US paediatric nephrologists were sent a survey via email. The survey queried participants about FP practice behaviours, FP attitudes and barriers to practice. Main Outcome Measures Of 579 nephrologists invited, 32% responded to the survey. Results CPO was dosed in mg/kg by 23% of physicians, g/m2 by 40% and both by 37%. About 80% agreed that pubertal females should be offered a fertility referral, while 58% report that they actually refer. Factors negatively associated with referral include lack of training, lack of referral network and adherence to gonadotoxic dose limits. Results were similar for male patients. Conclusion The survey showed that FP practice in the United States is widespread among nephrologists. Lack of referral networks is a notable barrier for nephrologists. Perceived adherence to dose limits may be problematic given the variable dosing regimens utilised. This is due to the risk of unintended overdose in large adolescents dosed in mg/kg whose cumulative dose exceeds gonadotoxic limits in g/m2. This paper has implications for nephrology care providers and other specialists who utilise CPO, generalists who care for these patients and oncologists with extant FP referral networks.

Two species of European commensal murids, the Norway rat norvegicus and the ship rat Rattus rattus, have colonized two island archipelagos of comparable size and temperate climate but in opposite hemispheres and with opposite outcomes. Ship rats were common commensals in Britain until replaced by Norway rats; Norway rats were hugely abundant in native forests throughout New Zealand until widely replaced by ship rats. Interference explains the first case, as ship rats are smaller than Norway rats and are always vulnerable to aggressive competition from them, but some other explanation is needed for the second case. We used the marginal value theorem to investigate exploitation competition between these two species in arboreal habitats. We observed the climbing behaviour and ‘giving-up time’ of captive rats of both species searching for food at different heights above the ground. Our data confirmed that the smaller size and greater agility of R. rattus give it a competitive advantage in foraging for scattered small food items above ground. We propose that (1) the outcomes of the interactions between the two rat species in any given place depend on the distribution of food resources in structurally complex habitat, moderated by winter temperatures; (2) the different outcomes of invasions by the two species can be explained in Britain by interference competition, and in New Zealand by exploitation competition and by the absence of specialist arboreal rodents (squirrels).

Bcl-xL functions as a dominant regulator of apoptotic cell death and is implicated in chemotherapeutic resistance of malignant pleural mesothelioma (MPM). Mesothelioma cell lines demonstrate increasing levels of Bcl-xL as resistant clones are selected invitro. Moreover, upon introduction of antisense oligonucleotides specific to Bcl-xL mRNA, MPM cells are sensitized to chemotherapeutic agents. Here we describe the therapeutic effects of a novel combination therapy, Bcl-xL antisense oligonucleotide (ASO 15999) and cisplatin, on mesothelioma cell lines in vitro and invivo; in addition, efficacy of ASO 15999 in decreasing tumor load as well as its effect on survival in an animal model. Finally, we initiated preliminary toxicity studies involved with intraperitoneal (IP) injections of ASO 15999 into mice. This novel combination, with doses of cisplatin four times below established IC50 levels, significantly decreased viability of MPM cell lines after 48 hr. The growth of established mouse flank human tumor xenografts was reduced with intra-tumor administration of ASO 15999. Local spread and development of IP xenografts was reduced with treatments of ASO alone, and survival of mice afflicted with these xenografts was prolonged after administration of ASO alone and ASO 15999 + cisplatin combination therapy. These findings suggest that ASO 15999 sensitizes MPM cell lines to the toxic effects of cisplatin. ASO 15999 induced reduction of Bcl-xL is effective in slowing the progression of human mesothelioma cell lines both in vitro and in vivo. More notably, the combination of Bcl-xL ASO and cisplatin extends survival in an orthotopic tumor xenograft model. © 2008 Wiley-Liss, Inc.