Water supply of ancient Egyptian settlements: the role of the state. Overview of a relatively equitable scheme from the Old to New Kingdom (ca. 2543-1077 BC).

This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s12685-015-0150-xThe study of the textual and archaeological evidence shows that the water supply of the settlements of ancient Egypt seems to have worked on a simple and a relatively equitable scheme, at least from the Old Kingdom until the New Kingdom (ca. 2543-1077). The water supply of the inhabitants was completely managed by the state, through the local administration which was charged to bring the water, in general from a rural area, into towns and cities and to redistribute it to the inhabitants. The method of supply is illustrated by several sources of evidence, in particular by the well known case of the "water-carriers" of the village of Deir el-Medina. Thus, drawing together text and archaeology, this paper will demonstrate that over an extended period, even when the city was far from a water source, the state did not set up complex installations such as pipe networks or wells to bring water, but preferred a simpler system using the manpower available

Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. Methodology and Principal Findings: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16. F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B-and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clini

Prognostic value of patient-reported quality of life for survival in oesophagogastric cancer:Analysis from the population-based POCOP study

BACKGROUND: Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. METHODS: Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. RESULTS: In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning. CONCLUSION: In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis.In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo.These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses

Experimental constraints on kinetic and equilibrium silicon isotope fractionation during the formation of non-biogenic chert deposits

Silicon isotopic compositions (δ30Si) of modern and ancient siliceous sedimentary rocks provide valuable information on conditions in depositional environments, but interpretations are hampered by the lack of experimentally validated fractionation factors. Here, we present new constraints on the magnitudes of kinetic and equilibrium isotope effects during chemical precipitation of amorphous silica in batch-reactors at low temperature (10-35°C) and near-neutral pH (7.5-8.5), as analogue for non-biogenic chert formation. Instantaneous fractionation factors, derived from δ30Si-values of the total dissolved (SiTD) silica and mass balance computations with αinst=(δ30Sippt+1000)/(δ30SiTD+1000), decrease with progressive precipitation and reduced reaction rates. This suggests that silica deposition in the batch-reactors is kinetically-dominated at the start of the experiments but approaches a metastable equilibrium after ca. 400hours. Modelled kinetic fractionation factors range from 0.9965 at 10°C, to 0.9976 at 20°C and 0.9993 at 35°C and pH8.5, whereas equilibrium isotope effects are smaller and range from 0.9995 at 10°C, to 1.000 at 20°C and 1.0005 at 35°C. Our results suggest that large isotope effects are only expressed in natural systems where dissolved and precipitated silica are not equilibrated, implying that the kinetic conditions of non-biogenic silica precipitation provide important constraints on silicon isotope ratios of siliceous rocks, with particular relevance for those preserved in the Archean chert recor