Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients

Purpose This was a phase I/II adoptive T cell trial in 7 locally advanced and metastatic pancreatic cancer patients using 3–8 infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (BATs) to determine safety, the maximum tolerated dose (MTD), immune responses, time to progression (TTP), and overall survival (OS). Study Design: T cells obtained by apheresis were expanded and armed with EGFRBi, cryopreserved for infusions. In a phase I dose escalation, five patients received three weekly infusions of 10–40 × 109 BATs/infusion followed by a booster infusion 3 months later, and 2 patients received 8 infusions twice weekly for 4 weeks in a phase II. The trials were registered at http://www.clinicaltrials.gov, NCT01420874 and NCT02620865. Results: There were no dose-limiting toxicities (DLTs), and the targeted dose of 80 × 109 BATs was met. The median TTP is 7 months, and the median OS is 31 months. Two patients had stable disease for 6.5 and 25+ months, and two patients developed complete responses (CRs) after restarting chemotherapy. Infusions of BATs induced anti-pancreatic cancer cytotoxicity, innate immune responses, cytokine responses (IL-12, IP-10), and shifts in CD4 and CD8 Vβ repertoire with enhanced cytoplasmic IFN-γ staining in the Vβ repertoire of the CD8 subset that suggest specific clonal TCR responses. Conclusions: Infusions of BATs are safe, induce endogenous adaptive anti-tumor responses, and may have a potential to improve overall survival

On the Capital Structure of Real Estate Investment Trusts (REITs)

Much of the literature on capital structure excludes Real Estate Investment Trusts (REITs) due mainly to the unique regulatory environment of these firms. As such, the issue of how REITs choose among different financing options when they raise external capital is largely unexplored. In this paper, we explore two issues on the capital structure of REITs: is there a relationship between market-to-book and leverage ratios, and, is the relationship between market-to-book and leverage ratio temporary or persistent. Our results suggest that REITs with historically high market-to-book ratio tend to have persistently high leverage ratio. In essence, REITs with high growth opportunity and high market valuation raise funds through debt issues. This finding, which is robust to various specifications and econometric tests, is contrary to the financing decisions of non-regulated firms. We attribute it to the special regulatory environment of REITs where, despite no apparent benefits to debt financing, management issues debt. Copyright Springer Science+Business Media, LLC 2007Capital structure, Real Estate Investment Trusts (REITs), External capital, Market-to-book, Leverage ratio,

Modelling and management of a Mediterranean karstic coastal aquifer under the effects of seawater intrusion and climate change

The study and management of the groundwater resources of a large, deep, coastal, karstic aquifer represent a very complex hydrogeological problem. Here, this problem is successfully approached by using an equivalent porous continuous medium (EPCM) to represent a karstic Apulian aquifer (southern Italy). This aquifer, which is located on a peninsula and extends to hundreds of metres depth, is the sole local source of high-quality water resources. These resources are at risk due to overexploitation, climate change and seawater intrusion. The model was based on MODFLOW and SEAWAT codes. Piezometric and salinity variations from 1930 to 2060 were simulated under three past scenarios (up to 1999) and three future scenarios that consider climate change, different types of discharge, and changes in sea level and salinity. The model was validated using surveyed piezometric and salinity data. An evident piezometric drop was confirmed for the past period (until 1999); a similar dramatic drop appears to be likely in the future. The lateral intrusion and upconing effects of seawater intrusion were non-negligible in the past and will be considerable in the future. All phenomena considered here, including sea level and sea salinity, showed non-negligible effects on coastal groundwater.Published115-1285A. Energia e georisorseJCR Journalembargoed_2016050

Experimental analysis of some factors affecting parental expenditure and investment in Gasterosteus aculeatus (Gasterosteidae)

Parental investment is the cost of providing parental care. Parental investment was measured in the paternal stickleback, Gasterosteus aculeatus, by comparing future survival (measured indirectly as energy content of the body) and growth of parental and non-parental males. The time taken by parental males to renest was also measured. Male energy content was unaffected after a single parental cycle and no difference in growth rate was detected. Re-nesting was delayed. The effect of stressing parental males by exposing them to potential predators of their offspring and reducing their ration level, was also investigated. Stressed males had reduced energy contents in comparison with unstressed parental males. The time taken by stressed males to re-nest was unaffected. Males on low rations did not fan significantly less than well-fed males. Males exposed to brood predators did fan significantly less than parental males not exposed to brood predators, but the former did spend nearly 60% of their time attacking the predators when present.</p