MACROPHAGES FROM CROHN'S DISEASE PATIENTS EXHIBIT DEFICIENT REPAIR FUNCTIONS

AbstractBackground: Mucosal healing is becoming a major goal in the treatment of Crohn's disease. It has been previously reported that myeloid cells induce mucosal healing in a mouse model of acute colitis. The aim in this study is to investigate the pro-repair function of myeloid cells in healthy donors (HD) and Crohn's disease patients (CD).Methods: Peripheral blood mononuclear cells (PBMC) from HD and CD patients were isolated from blood samples and tested either directly or after differentiation ex-vivo into macrophages (Μφ). Intestinal macrophages (IMACs) were isolated from the bowel mucosa of patients undergoing intestinal surgical resections. Through an in vitro wound healing assay the repairing ability of these various human myeloid cells and the mechanisms responsible of wound healing were evaluated.Results: PBMC and myeloid CD14+ cells from HD and CD were not able to repair at any tested cell concentration. Μφ from HD and ulcerative colitis (UC) patients were able to induce wound healing and this capacity was partially mediated by Hepatocyte Growth Factor (HGF). Remarkably, CD Μφ were unable to promote wound healing and produced lower levels of HGF as compared to Μφ from HD or UC patients. In particular, Μφ from CD in active phase (ACD) exhibited the weakest repair function, but this defect was rescued if rh- GM-CSF was added during the differentiation of PBMCs. Interestingly, IMACs from HD promoted wound healing and produced HGF.Conclusion: We demonstrated that CD Μφ, unlike HD or UC Μφ, were defective in promoting wound healing, in particular if coming from an ACD. This deficient pro-repair function was related to a lower production of HGF. IMACs from HD colonic mucosa induced wound healing, confirming the results obtained with Μφ. Our results are in keeping with the current theory of CD as an innate immunodeficiency. In this context, Μφ may be responsible for the mucosal repair defects observed in CD patients and for the subsequent chronic activation of the adaptive immune response

Particle acceleration and radiation friction effects in the filamentation instability of pair plasmas

The evolution of the filamentation instability produced by two counter-streaming pair plasmas is studied with particle-in-cell (PIC) simulations in both one (1D) and two (2D) spatial dimensions. Radiation friction effects on particles are taken into account. After an exponential growth of both the magnetic field and the current density, a nonlinear quasi-stationary phase sets up characterized by filaments of opposite currents. During the nonlinear stage, a strong broadening of the particle energy spectrum occurs accompanied by the formation of a peak at twice their initial energy. A simple theory of the peak formation is presented. The presence of radiative losses does not change the dynamics of the instability but affects the structure of the particle spectra.Comment: 8 pages, 8 figures, submitted to MNRA

Intestinal perforation after surgical treatment for incisional hernia. iatrogenic or idiopathic?

Intestinal perforation (IP) is a life-threatening gastroenterological condition requiring urgent surgical care, which may present itself as an uncommon complication following incisional hernia repair surgery, most often because of iatrogenic traumatism occurring during the procedure. However, we report a case where a spontaneous onset can be hypothesised. A 60-years-old patient underwent repair of an abdominal laparocele, through rectus abdominis muscle plasty, 5 years after development of an incisional hernia due to exploratory laparotomy for the treatment of acute appendicitis. Xipho-pubic scar was excised and umbilicus and supra-umbilical hernia sac dissected, a linear median incision was performed along the sub-umbilical linea alba, reaching preperitoneal plane to assess any intestinal loop adherence to the abdominal wall. After limited viscerolysis, abdominal wall defect was corrected by 'rectus abdominis muscle plasty' and umbilicus reconstruction by Santanelli technique. Postoperative course was uneventful until Day 29, with sudden onset of epigastric pain, fever and bulge. Sixty cubic centimeter pus was drained percutaneously and cavity was rinsed with a 50% H2O2 and H2O V-V solution until draining clear fluid. Symptoms recurred two days later, while during rinsing presented dyspnoea. X-Ray and CT scan diagnosed IP, and she underwent under emergency an exploratory laparotomy, leading to right hemicolectomy extended to last ileal loops and middle third of the transverse, right monolateral salpingo-ovariectomy and a temporary ileostomy by general surgeon. Twenty-three days later an ileostomy reversal surgery was performed and 8 days after she was discharged. At latest follow-up patient showed fair conditions, complaining abdominal pain and diarrhoea, attributable to the extensive intestinal resection. IP following incisional hernia repair, is reported as uncommon and early postoperative complication. In our case, the previous regular postoperative course with late onset lead us to hypothesise a possible idiopathic etiopathogenesis, because of a strangulation followed by gangrene and abscess formation, which might begin before the incisional hernia repair and unnoticed at the time surgery was performed

Follow-up after curative resection for gastric cancer. Is it time to tailor it?

There is still no consensus on the follow-up frequency and regimen after curative resection for gastric cancer. Moreover, controversy exists regarding the utility of follow-up in improving survival, and the recommendations of experts and societies vary considerably. The main reason to establish surveillance programs is to diagnose tumor recurrence or metachronous cancers early and to thereby provide prompt treatment and prolong survival. In the setting of gastric malignancies, other reasons have been put forth: (1) the detection of adverse effects of a previous surgery, such as malnutrition or digestive sequelae; (2) the collection of data; and (3) the identification of psychological and/or social problems and provision of appropriate support to the patients. No randomized controlled trials on the role of follow-up after curative resection of gastric carcinoma have been published. Herein, the primary retrospective series and systematic reviews on this subject are analyzed and discussed. Furthermore, the guidelines from international and national scientific societies are discussed. Follow-up is recommended by the majority of institutions; however, there is no real evidence that follow-up can improve long-term survival rates. Several studies have demonstrated that it is possible to stratify patients submitted to curative gastrectomy into different classes according to the risk of recurrence. Furthermore, promising studies have identified several molecular markers that are related to the risk of relapse and to prognosis. Based on these premises, a promising strategy will be to tailor follow-up in relation to the patient and tumor characteristics, molecular marker status, and individual risk of recurrence

X-ray and UV correlation in the quiescent emission of Cen X-4, evidence of accretion and reprocessing

We conducted the first long-term (60 days), multiwavelength (optical, ultraviolet, and X-ray) simultaneous monitoring of Cen X-4 with daily Swift observations, with the goal of understanding variability in the low mass X-ray binary Cen X-4 during quiescence. We found Cen X-4 to be highly variable in all energy bands on timescales from days to months, with the strongest quiescent variability a factor of 22 drop in the X-ray count rate in only 4 days. The X-ray, UV and optical (V band) emission are correlated on timescales down to less than 110 s. The shape of the correlation is a power law with index gamma about 0.2-0.6. The X-ray spectrum is well fitted by a hydrogen NS atmosphere (kT=59-80 eV) and a power law (with spectral index Gamma=1.4-2.0), with the spectral shape remaining constant as the flux varies. Both components vary in tandem, with each responsible for about 50% of the total X-ray flux, implying that they are physically linked. We conclude that the X-rays are likely generated by matter accreting down to the NS surface. Moreover, based on the short timescale of the correlation, we also unambiguously demonstrate that the UV emission can not be due to either thermal emission from the stream impact point, or a standard optically thick, geometrically thin disc. The spectral energy distribution shows a small UV emitting region, too hot to arise from the accretion disk, that we identified as a hot spot on the companion star. Therefore, the UV emission is most likely produced by reprocessing from the companion star, indeed the vertical size of the disc is small and can only reprocess a marginal fraction of the X-ray emission. We also found the accretion disc in quiescence to likely be UV faint, with a minimal contribution to the whole UV flux.Comment: 5 pages, 4 figures, submitted to Proc. Int. Conf. Physics at the Magnetospheric Boundary, Geneva, Switzerland (25-28 June, 2013

Daily, multiwavelength Swift monitoring of the neutron star low-mass X-ray binary Cen X-4: evidence for accretion and reprocessing during quiescence

We conducted the first long-term (60 days), multiwavelength (optical, ultraviolet, and X-ray) simultaneous monitoring of Cen X-4 with daily Swift observations from June to August 2012, with the goal of understanding variability in the low mass X-ray binary Cen X-4 during quiescence. We found Cen X-4 to be highly variable in all energy bands on timescales from days to months, with the strongest quiescent variability a factor of 22 drop in the X-ray count rate in only 4 days. The X-ray, UV and optical (V band) emission are correlated on timescales down to less than 110 s. The shape of the correlation is a power law with index gamma about 0.2-0.6. The X-ray spectrum is well fitted by a hydrogen NS atmosphere (kT=59-80 eV) and a power law (with spectral index Gamma=1.4-2.0), with the spectral shape remaining constant as the flux varies. Both components vary in tandem, with each responsible for about 50% of the total X-ray flux, implying that they are physically linked. We conclude that the X-rays are likely generated by matter accreting down to the NS surface. Moreover, based on the short timescale of the correlation, we also unambiguously demonstrate that the UV emission can not be due to either thermal emission from the stream impact point, or a standard optically thick, geometrically thin disc. The spectral energy distribution shows a small UV emitting region, too hot to arise from the accretion disk, that we identified as a hot spot on the companion star. Therefore, the UV emission is most likely produced by reprocessing from the companion star, indeed the vertical size of the disc is small and can only reprocess a marginal fraction of the X-ray emission. We also found the accretion disc in quiescence to likely be UV faint, with a minimal contribution to the whole UV flux.Comment: 19 pages, 6 figures, 4 table

A federated approach to Android malware classification through Perm-Maps

In the last decades, mobile-based apps have been increasingly used in several application fields for many purposes involving a high number of human activities. Unfortunately, in addition to this, the number of cyber-attacks related to mobile platforms is increasing day-by-day. However, although advances in Artificial Intelligence science have allowed addressing many aspects of the problem, malware classification tasks are still challenging. For this reason, the following paper aims to propose new special features, called permission maps (Perm-Maps), which combine information related to the Android permissions and their corresponding severity levels. Such features have proven to be very effective in classifying different malware families through the usage of a convolutional neural network. Also, the advantages introduced by the Perm-Maps have been enhanced by a training process based on a federated logic. Experimental results show that the proposed approach achieves up to a 3% improvement in average accuracy with respect to J48 trees and Naive Bayes classifier, and up to 16% compared to multi-layer perceptron classifier. Furthermore, the combined use of Perm-Maps and federated logic allows dealing with unbalanced training datasets with low computational efforts

Walking the tightrope: Circular economy breadth and firm economic performance

The circular economy (CE) can bring benefits but also pitfalls to the production processes, affecting a firm's economic performance. Using data from European SMEs, we empirically investigate, from the perspective of self-determination theory, the extent to which the breadth of CE activities, that is, the number of CE activities undertaken by a firm, affects a firm's economic performance. Our study theorizes and shows that there is an inverted U-shaped effect brought about by the number of CE activities on economic performance. This research advances our scientific understanding of the CE and provides managers with suggestions on how to maximize the benefits generated by the CE in terms of economic performance by implementing the right amount of CE activities

Artificial neural networks for resources optimization in energetic environment

Resource Planning Optimization (RPO) is a common task that many companies need to face to get several benefits, like budget improvements and run-time analyses. However, even if it is often solved by using several software products and tools, the great success and validity of the Artificial Intelligence-based approaches, in many research fields, represent a huge opportunity to explore alternative solutions for solving optimization problems. To this purpose, the following paper aims to investigate the use of multiple Artificial Neural Networks (ANNs) for solving a RPO problem related to the scheduling of different Combined Heat & Power (CHP) generators. The experimental results, carried out by using data extracted by considering a real Microgrid system, have confirmed the effectiveness of the proposed approach

LTV stochastic systems stabilization with large and variable input delay

In this paper we propose a solution to the state-feedback and output-feedback stabilization problem for linear time-varying stochastic systems affected by arbitrarily large and variable input delay. It is proved that under the proposed controller the underlying stochastic process is exponentially centered and mean square bounded. The solution is given through a set of delay differential equations with cardinality proportional to the delay bound. The predictor is based on the semigroup generated by the closed-loop system in absence of delay, and its computation is described by a numerically reliable and robust method. In the deterministic case this method generates the same optimal trajectories as in the delay-less case