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Simply extending lifespan is not enough. We need treatments that boost resilience to multiple age-related diseases, argue Ilaria Bellantuono and 12 co-signatories. Simply extending lifespan is not enough. We need treatments that boost resilience to multiple age-related diseases, argue Ilaria Bellantuono and 12 co-signatories.

Human life expectancy has increased dramatically in the last century and as a result also the prevalence of a variety of age-related diseases and syndromes. One such syndrome is frailty, which is defined as a combination of organ dysfunctions leading to increased vulnerability to adverse health outcomes. In humans, frailty is associated with various biomarkers of ageing and predicts relevant outcomes such as responses to therapies and progression of health status and mortality. Moreover, it is relatively easy to assess. To foster translation of mechanistic understanding of the ageing process and, importantly, of interventions that may extend healthy lifespan, frailty scales have been reverse translated into mice in recent years. We will review these approaches with a view to identify what is known and what is not known at present about their validity, reproducibility and reliability with a focus on the potential for further improvement. (C) 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license.

A locoregional recurrence after definitive chemoradiation (dCRT) for patients with inoperable or unresectable esophageal cancer occurs in about 50% of the patients and is a major cause of failure with a poor prognosis. The aim of this study was to determine the pattern of locoregional recurrence and its prognostic factors after dCRT in order to search for improvements in radiation treatment. We retrospectively reviewed 184 patients treated with external beam radiotherapy (50.4 Gray/28 fractions), combined with weekly concurrent paclitaxel and carboplatin. Locoregional recurrences were defined by clinical signs of recurrent or progressive disease, combined with progression on computed tomography/positron emission tomography-computed tomography scan, or suspicious endoscopic findings and/or histological proof of recurrence. The site of locoregional recurrence was analyzed with respect to the borders of the radiation fields. After a mean follow up of 22.8 months, 76 patients (41%) had evidence of locoregional recurrence. The 3-years locoregional recurrence-free rate was 45%. The majority of locoregional recurrences occurred within 12 months, nearly all within 24 months. The majority of these patients failed at the site of the primary tumor (86%). Infield locoregional recurrences at the site of the lymph nodes only occurred in 1% compared with 57% at the site of the primary tumor only. Outfield locoregional lymph node recurrences occurred in 22%, without infield recurrence occurred in only 4% of all patients. The 1-, 3-, and 5-year overall survival was 65%, 28%, and 21%, respectively. The current analysis demonstrates that a locoregional recurrence after dCRT occurs in 41% of the patients, the majority at the site of the primary tumor. These data suggest a benefit of dose intensification of the primary tumor, but not at the site of the lymph nodes. Higher radiation doses should be assessed with prospective trials.

This paper introduces the PFTijah system, a text search system that is integrated with an XML/XQuery database management system. We present examples of its use, we explain some of the system internals, and discuss plans for future work. PFTijah is part of the open source release of MonetDB/XQuery.

Numerous assays exist that measure the function of stem cells. In this article, we review in detail the history and future of existing stem cell assays. Hematopoietic stem cells (HSCs) are historically the most well studied, but new developments in stem cell research, including the claim of stem cell plasticity, have caused controversies related to technical issues, as well as to semantics. Stem cell research requires proper definitions, and utilization of stem cell assays, especially since research on non-HSCs that lack solid stem cell assays, is rapidly evolving. These emerging fields may benefit from what has been learned from HSC assays: most important, that the true potential of stem cells can only be assessed retrospectively. This also relates to new developments in HSC research, when limiting numbers of in vitro–manipulated stem cells are transplanted. The most conflicting results arise when cells express stem cell characteristics in one assay but not in another. Should we adjust our definition of a stem cell? If so, when do we decide a claim of stem cell activity to be justified? We therefore recommend using multiple stem cell assays, preferably at least one in vivo assay. These assays should measure functionality of the putative stem cell population.

The omental lymphoid organ (OLO) is a part of the greater omentum composed of vascularized milky spots situated between fat cells and containing lymphocytes, plasma cells and macrophages. We analysed the disappearance of intraperitoneally injected tumor cells from the peritoneal cavity and their infiltration into and disappearance from the OLO and the parathymic lymph nodes (PTLN) that drain the peritoneal cavity. After intraperitoneal inoculation of irradiated syngeneic tumor cells, they were visible in the OLO within 24 h. After 3 days, no tumor cells were seen anymore, but there were many macrophages that had phagocytosed tumor cells. After intraperitoneal inoculation of nonirradiated syngeneic tumor cells, a solid growing tumor mass developed in the OLO. The PTLN were also invaded by these nonirradiated tumor cells within 24 h as transfer of cell suspensions of these lymph nodes into naive mice leads to the death of the recipient mice due to tumor growth. However, from day 6 onwards, after tumor inoculation, these lymph nodes contained no tumor cells, despite progressive tumor growth intraperitoneally and in the liver and lungs. In allogeneic mice, tumor cells were rejected in the OLO after 7-10 days. Simultaneously, the number of lymphocytes and macrophages increased and a plasma cell reaction developed. The PTLN did not have tumor-inducing potency at any stage after intraperitoneal tumor injection. This study suggests, that the PTLN are more effective in the (local) eradication of tumor cells than the OLO. Still, considering its immunological potential, the OLO might be important as 'inducer' of immunological reactions in the peritoneal cavity.