Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A

PolarStar: Expanding the Scalability Horizon of Diameter-3 Networks

In this paper, we present PolarStar, a novel family of diameter-3 network topologies derived from the star product of two low-diameter factor graphs. The proposed PolarStar construction gives the largest known diameter-3 network topologies for almost all radixes. When compared to state-of-the-art diameter-3 networks, PolarStar achieves 31% geometric mean increase in scale over Bundlefly, 91% over Dragonfly, and 690% over 3-D HyperX. PolarStar has many other desirable properties including a modular layout, large bisection, high resilience to link failures and a large number of feasible sizes for every radix. Our evaluation shows that it exhibits comparable or better performance than other diameter-3 networks under various traffic patterns.Comment: 13 pages, 13 figures, 4 table

Children's use of category labels in recall of conceptually related terms

The purpose of this study was to investigate children's failure to use category labels as cues in the recall of conceptually related items. Previous research has shown that despite the fact that the use of these labels as cues increases recall, children do not use them unless constrained to do so by the experimenter. The premise of this investigation was that young children fail to use cues because they are not kept in active memory during the recall process. Therefore, it was predicted that ensuring the presence of category labels in active memory would improve amount of recall. In order to determine the degree of assistance needed by children to keep the category labels in active memory during recall, three recall conditions were constructed which varied in the amount of assistance they gave in the task of remembering

Every Dog Has Its Data:Evaluation of a Technology-Aided Canine Rabies Vaccination Campaign to Implement a Microplanning Approach

Background: Robust dog vaccination coverage is the primary way to eliminate canine rabies. Haiti conducts annual canine mass vaccination campaigns, but still has the most human deaths in the Latin American and Caribbean region. We conducted an evaluation of dog vaccination methods in Haiti to determine if more intensive, data-driven vaccination methods, using smartphones for data reporting and geo-communication, could increase vaccination coverage to a level capable of disrupting rabies virus transmission.Methods: Two cities were designated into “Traditional” and “Technology-aided” vaccination areas. Traditional areas utilized historical methods of vaccination staff management, whereas Technology-aided areas used smartphone-supported spatial coordination and management of vaccination teams. Smartphones enabled real time two-way geo-communication between campaign managers and vaccinators. Campaign managers provided geographic instruction to vaccinators by assigning mapped daily vaccination boundaries displayed on phone handsets, whilst vaccinators uploaded spatial data of dogs vaccinated for review by the campaign manager to inform assignment of subsequent vaccination zones. The methods were evaluated for vaccination effort, coverage, and cost.Results: A total of 11,420 dogs were vaccinated during the 14-day campaign. The technology-aided approach achieved 80% estimated vaccination coverage as compared to 44% in traditional areas. Daily vaccination rate was higher in Traditional areas (41.7 vaccinations per team-day) compared to in technology-aided areas (26.8) but resulted in significantly lower vaccination coverages. The cost per dog vaccinated increased exponentially with the associated vaccination coverage, with a cost of $1.86 to achieve 25$2.51 for 50% coverage, and $3.19 for 70% coverage.Conclusions: Traditional vaccination methods failed to achieve sufficiently high vaccination coverages needed to interrupt sustained rabies virus transmission, whilst the technology-aided approach increased coverage above this critical threshold. Over successive campaigns, this difference is likely to represent the success or failure of the intervention in eliminating the rabies virus. Technology-aided vaccination should be considered in resource limited settings where rabies has not been controlled by Traditional vaccination methods. The use of technology to direct health care workers based on near-real-time spatial data from the field has myriad potential applications in other vaccination and public health initiatives

Factors Affecting the Risk of Free Flap Failure in Microvascular Surgery

Publisher Copyright: © 2016 Jevgeņijs Stepanovs et al.Microvascular free flap surgery, has become an important part of reconstructive surgery during the last decades, as it allows closure of various tissue defects and recovery of organs function. Despite surgical progress resulting in high rates of transferred tissue survival, the risk of pedicle vessels thrombosis still remains a significant problem. A total of 108 articles from Pubmed and Science Direct databases published in 2005-2015 were analysed. This review of the literature assessed the influence of patient-dependent risk factors and different perioperative management strategies on development of microvascular free flap thrombosis. Sufficient evidence for risk associated with hypercoagulation, advanced age and certain comorbidities was identified. Presently, rotational thromboelastometry allows early hypercoagulability detection, significantly changing further patient management. Identification of flap thrombosis promoting surgery-related aspects is also essential in preoperative settings. Choice of anaesthesia and postoperative analgesia, administration of different types and amounts of fluids, blood products and vasoactive agents, temperature control are no less important in perioperative anaesthesiological management. More attention should be focused on timely preoperative evaluation of patient-dependent risk factors, which can influence anaesthesiological and surgical tactics during and after microvascular free flap surgery. Perioperative anaesthesiological management strategy continues to be controversial and therefore it should be performed based on thrombotic risk assessment and patient individual needs, thus improving flap survival rates and surgical outcome.publishersversionPeer reviewe

The Effect of Interleukin-4 and Amphiregulin on the Proliferation of Human Airway Smooth Muscle Cells and Cytokine Release

Airway smooth muscle (ASM) hyperplasia and angiogenesis are important features associated with airway remodeling. We investigated the effect of IL-4 and amphiregulin, an epidermal growth factor family member, on the proliferation of human ASM cells and on the release of vascular endothelial growth factor (VEGF) and monocyte chemotactic protein (MCP)-1 from human ASM cells. Human ASM cells were growth-arrested for 48 hr and incubated with platelet-derived growth factor (PDGF)-BB, interleukin (IL)-4, amphiregulin, and VEGF to evaluate cell proliferation. The cells were treated with PDGF, IL-4 and amphiregulin to evaluate the release of VEGF, MCP-1. IL-4 suppressed unstimulated and PDGF-stimulated ASM cell proliferation. Amphiregulin stimulated ASM cell proliferation in a dose-dependent manner. VEGF did not have any influence on ASM cell proliferation. IL-4 stimulated VEGF secretion by the ASM cells in a dose-dependent manner and showed added stimulatory effects when co-incubated with PDGF. Amphiregulin did not promote VEGF secretion. IL-4 and amphiregulin showed no stimulatory effects on MCP-1 secretion. The results of this study showed that IL-4 had bifunctional effects on airway remodeling, one was the suppression of the proliferation of the ASM cells and the other was the promotion of VEGF release by the ASM cells, and amphiregulin can promote human ASM cell proliferation

Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

© The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.This work was supported by the Leona M. and Harry B. Helmsley Charitable trust (SHARE), the Digestive Diseases Research Core Center C-IID P30 DK42086 at the University of Chicago, the PSC Partners Seeking a Cure Canada and the Sczholtz Family Foundation. K.R.M. is supported by grant no. NS124187. S.C.S. is supported by an American Gastroenterological Association Research Scholar Award, Veterans Affairs Career Development Award (no. ICX002027A01) and the San Diego Digestive Diseases Research Center (no. P30 DK120515). C.Q. is supported by the BBSRC Core Strategic Programme Grant (BB/CSP1720/1, BBS/E/T/000PR9818 and BBS/E/T/000PR9817). I.H.J. is supported by a Rosalind Franklin Fellowship from the University of Groningen and a Netherlands Organization for Scientific Research VIDI grant no. 016.171.047. D.G.S. is supported by grant no. F30DK121470.info:eu-repo/semantics/publishedVersio