The development of a glucose prediction model in critically ill patients

Purpose: The aim of the current study is to develop a prediction model for glucose levels applicable for all patients admitted to the ICU with an expected ICU stay of at least 24 h. This model will be incorporated in a closed-loop glucose system to continuously and automatically control glucose values. Methods: Data from a previous single-center randomized controlled study was used. All patients received a FreeStyle Navigator II subcutaneous CGM system from Abbott during their ICU stay. The total dataset was randomly divided into a training set and a validation set. A glucose prediction model was developed based on historical glucose data. Accuracy of the prediction model was determined using the Mean Squared Difference (MSD), the Mean Absolute Difference (MAD) and a Clarke Error Grid (CEG). Results: The dataset included 94 ICU patients with a total of 134,673 glucose measurements points that were used for modelling. MSD was 0.410 +/- 0.495 for the model, the MAD was 5.19 +/- 2.63 and in the CEG 99.8% of the data points were in the clinically acceptable regions. Conclusion: In this study a glucose prediction model for ICU patients is developed. This study shows that it is possible to accurately predict a patient's glucose 30 min ahead based on historical glucose data. This is the first step in the development of a closed-loop glucose system. (C) 2021 Elsevier B.V. All rights reserved

A Southern Hemisphere record of global trace-metal drawdown and orbital modulation of organic-matter burial across the Cenomanian–Turonian boundary (Ocean Drilling Program Site 1138, Kerguelen Plateau)

Despite its assumed global nature, there are very few detailed stratigraphic records of the late Cenomanian to the early Turonian Oceanic Anoxic Event 2 from the Southern Hemisphere. A highly resolved record of environmental changes across the Cenomanian\u2013Turonian boundary interval is presented from Ocean Drilling Program Site 1138 on the central Kerguelen Plateau (southern Indian Ocean). The new data lead to three key observations. Firstly, detailed biostratigraphy and chemostratigraphy indicate that the record of Oceanic Anoxic Event 2 is not complete, with a hiatus spanning the onset of the event. A decrease in glauconite and highly weathered clays after the onset of Oceanic Anoxic Event 2 marks the end of the hiatus interval, which can be explained by a relative sea-level rise that increased sediment accommodation space on the Kerguelen Plateau margin. This change in depositional environment controlled the timing of the delayed peak in organic-matter burial during Oceanic Anoxic Event 2 at Site 1138 compared with other Oceanic Anoxic Event 2 locations worldwide. A second key observation is the presence of cyclic fluctuations in the quantity and composition of organic matter being buried on the central Kerguelen Plateau throughout the latter stages of Oceanic Anoxic Event 2 and the early Turonian. A close correspondence between organic matter, sedimentary elemental compositions and sediments recording sea-floor oxygenation suggests that the cycles were mainly productivity-driven phenomena. Available age-control points constrain the periodicity of the coupled changes in sedimentary parameters to ca 20 to 70 ka, suggesting a link between carbon burial and astronomically forced climatic variations (precession or obliquity) in the Southern Hemisphere mid-latitudes both during, and after, Oceanic Anoxic Event 2: fluctuations that were superimposed on the impact of global-scale processes. Finally, trace-metal data from the black-shale unit at Site 1138 provide the first evidence from outside of the proto-North Atlantic region for a global drawdown of seawater trace-metal (Mo) inventories during Oceanic Anoxic Event 2

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

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.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

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

Monobenzone-induced depigmentation: from enzymatic blockade to autoimmunity

Autoimmune side-effects such as vitiligo regularly occur during melanoma immunotherapy. As vitiligo development is associated with a superior prognosis, the active induction of vitiligo in melanoma patients can be a useful tactic. The potent skin-depigmenting agent monobenzone can be used successfully for this purpose. However, until recently, the mechanism of action behind monobenzone-induced skin depigmentation was unclear. Lately, the mechanistic basis for the augmented immunogenicity of monobenzone-exposed pigmented cells has been unveiled, and their active role in the induction of autoimmune T-cell-mediated vitiligo has become apparent. Here, we provide an immunological framework in which we condense this knowledge to an integrated theory of the generation of monobenzone-induced vitilig