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Herein, we present a new eco-friendly microextraction method based on the magnetite/multi-walled carbon nanotubes reinforced and natural deep eutectic-filled hollow fiber solid/liquid phase microextraction, abbreviated as HF-SLPME, combined with HPLC–DAD analysis. This method has been developed to determine trace levels of phthalate esters, including diethyl phthalate, benzyl butyl phthalate, and di-iso-butyl phthalate in urine, blood plasma, tap water, and groundwater samples. The natural deep eutectic solvents were prepared using terpenoid-derived natural compounds containing menthol and camphor in various ratios. The HF-SLPME device was constructed by reinforcing and immobilizing the synthesized Fe3O4-MWCNTs within the pores of a 2.5 cm segment of hollow fiber microtube through ultrasonication, followed by filling the lumen with the natural deep eutectic solvent with both ends heat sealing. The extraction process was conducted in direct immersion mode. Values of crucial variables for HF-SLPME were optimized through a multivariate methodology based on a central composite design, with 30 extraction tests performed to determine the best conditions. The method exhibited good linearity (correlation coefficients R2> 0.996) over a dynamic range lower than 0.927–103µg L−1. The results show that the limits of detection/quantification for the chosen PEs ranged from 0.19 to 0.27/ 0.65 to 0.92 µg L−1with enrichment factor˃ 37.24. As evidenced by intra- and inter-day precisions, satisfactory reproducibility was achieved with relative standard deviations (RSDs) below 3.7% and 5.1%, respectively. The recoveries of the selected phthalate esters from spiked real samples ranged from 88.4 to 111.1%, with relative standard deviations between 2.3 and 6.5%. This HF-SLPME-HPLC–DAD method offered a new, cost-effective, sensitive microextraction approach for determining and quantifying phthalate esters in aqueous samples with complex matrices.

Purpose: Internet of things (IoT) and big data (BD) could change how the societies function. This paper explores the role of IoT and BD and their impact on customer relationship management (CRM) investments in modern customer service. The purpose of this paper is to develop an analytic hierarchy planning framework to establish criteria weights and to develop a general self-assessment model for determining the most important factors influencing the IoT and BD investment in CRM. The authors found that most studies have focused on conceptualizing the impact of IoT without BD and with limited empirical studies and analytical models. This paper sheds further light on the topic by presenting both IoT and BD aspects of future CRM. Design/methodology/approach: The analytic hierarchy process (AHP) methodology is used to weight and prioritize the factors influencing the IoT and BD investment in modern CRM in the service industry. The AHP framework resulted in a ranking of 21 sustainability sub-factors based on evaluations by experienced information technology and customer service professionals. Findings: The paper provides significant insight on the new frontier of CRM, focusing on the use of IoT and BD and the respective solutions to address them were identified. This study primarily contributes in providing the process of effectively managing and implementing IoT and BD in big businesses by identifying the connecting link between firms and customers. Practical implications: The understanding of new frontier of CRM connective via IoT and BD can solve the dilemmas and challenges linked to the practice of implement IoT and BD in the information systems field. The study provides valuable information and critical analysis of IoT and BD with regard to the integration of CRM. Finally, this study further provides directions for future researchers. Originality/value: IoT and BD are a growing phenomenon, which business decision-makers and information professionals need to consider seriously to properly ascertain the modern CRM dimensions in the digital economies. They also should embrace the proper CRM innovation, which is powered by IoT and BD, and discover how IoT and BD can bring the next level of maturity to CRM “CRM of everything.”

In this paper, we study consensus seeking for a class of linear multi-agent systems (MAS) subject to the inevitable imperfections of packet-based networked communication. These imperfections include unknown non-uniform time-varying transmission delays and limited communication resources. To reduce the utilization of communication resources, we propose a dynamic event-triggered control scheme resulting in aperiodic transmission of information between agents. The proposed framework leads to event-triggered controllers that guarantee the MAS to asymptotically reach consensus, strictly positive lower bounds on the inter-event times and robustness for unknown non-uniform time-varying delays in terms of maximum allowable delays.

Event-triggered control is a control strategy which allows the savings of communication resources in networked control systems. In this paper, we are interested in periodic event-triggering mechanisms in the sense that the triggering condition is only verified at predefined periodic sampling instants, which automatically ensures that Zeno behavior does not occur. We consider the case where both the output measurement and the control input are transmitted asynchronously using two independent triggering conditions. The developed result is dedicated to a class of nonlinear systems, where both the plant model and the feedback law can be described by polynomial functions. The overall problem is modeled and analyzed in the framework of time-delay systems, which allows to derive sum-of-squares (SOS) conditions to guarantee the global asymptotic stability in terms of the sampling period and the parameters of the triggering conditions. The approach is illustrated on a nonlinear numerical example.

Hematopoietic stem cell transplantation (HSCT) can be lifesaving for some of the deadliest hematologic diseases. However, immunosuppression, polypharmacy and risk of infectious complications associated with HSCT can increase morbidity and mortality for recipients. Incidence of acute kidney injury (AKI) after HSCT can be as high as 70%, and concomitant infection can be a therapeutic challenge for oncologists, nephrologists and infectious disease specialists. We illustrate this challenge in the case of a 31-year-old man with acute lymphoblastic leukemia who underwent a double cord HSCT complicated by GvHD, systemic cryptococcal and BK virus infections and AKI. Kidney biopsy showed round to cup-shaped organisms with occasional budding, consistent with Cryptococcusand thrombotic microangiopathy. We discuss our findings and a literature review of disseminated cryptococcal infection with renal involvement after HSCT.

Nephropathy due to BKvirus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKVinfection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause‐specific hazard of kidney function decline, and the Fine–Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BKviruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft‐versus‐host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BKviruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKVinfection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKVinfection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT. In a retrospective review of 2477 patients after allogeneic hematopoietic stem cell transplantation, the authors strongly and independently associate BKV infection with subsequent kidney function decline and worse patient survival.

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline, and the Fine–Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.

Amyloid beta (A) peptides are related to the pathogenesis of Alzheimers disease (AD). The search for therapeutic strategies that lower these peptides has mainly focused on the proteolytic processing of the -amyloid precursor protein (APP), and other post-transcriptional pathways. The transcription factor specificity protein 1 (Sp1) is vital for the regulation of several genes involved in AD including APP and the beta site APP cleaving enzyme 1 (BACE1). We have previously reported that tolfenamic acid promotes the degradation of Sp1 protein (SP1) in pancreatic human cancer cells and mice tumors. This study examines the ability of tolfenamic acid to reduce SP1 levels, and thereby decrease APP transcription and A levels in rodent brains. Tolfenamic acid was administered by oral gavage to C57BL/6 mice at variable dosages and for different time periods. Results have shown that tolfenamic acid was able to downregulate brain protein levels of SP1, APP, and A. These findings demonstrate that interference with upstream transcriptional pathways can lower pathogenic intermediates associated with AD, and thus tolfenamic acid represents a novel approach for the development of a therapeutic intervention for AD.

IntroductionThe recently published Quality Standards for people with coeliac disease (CD) emphasise the importance of annual review 1. This should include review of adherence to gluten-free diet (GFD) and evaluation of symptoms. It is implied that annual review improves dietary adherence and outcomes but there is limited research in this area. We studied whether annual review was associated with improved dietary outcomes in people with CD.MethodA postal questionnaire was sent to 835 patients with CD diagnosed via positive serology and duodenal biopsy, who attended secondary care services at 2 sites (Plymouth hospitals and Royal Cornwall hospital) between 2006 and 2014. Patients were diagnosed at least 24 months earlier. We compared those with and without annual review (AR) and whether they achieved the following desirable dietary status: compliance with GFD being good or excellent; dietary calcium intake of 1000 mg/day; compliance with calcium/vitamin D supplements where appropriate being good or excellent. We assessed adherence to a GFD via a 5-point scale, dietary calcium intake (mg) as determined by a food frequency questionnaire, compliance with calcium/vitamin D supplements (if prescribed) on a 5-point scale. We also compared the number of members of Coeliac UK and those in receipt of gluten-free prescriptions (GFP).ResultsA total of 516 questionnaires (61.8%) were returned. Two-thirds of patients 66% (n338) had AR. Comparing presence of AR against no AR, we found 91% achieved good/excellent adherence to GFD vs 87% (p=NS), good/excellent adherence to prescribed calcium/vitamin D supplements 72% vs 60% (p<0.01). A total of 443 respondents (86%) completed the calcium frequency questionnaire. The mean average estimated dietary calcium intake was 898 mg in those offered an AR vs. 891 mg in those that were not. Those who had AR were more likely to be members of Coeliac UK compared to those with no follow-up (56% vs 44%, p<0.05) and were more likely to have gluten free prescriptions (66% vs. 28%, p<0.05).ConclusionAnnual review for coeliac disease is associated with greater compliance with calcium/vitamin D and a non-significant increase in compliance with gluten free diet. Interestingly most coeliac patients irrespective of AR, achieved nearly 100% recommended daily intake of calcium. AR was associated with provision of prescriptions for gluten free foods which may have implications for people with CD as some clinical commissioning groups have stopped offering gluten free products on prescription.ReferenceCoeliac disease: quality standard (2016) NICE quality standard QS134, statement 5 (annual review).Disclosure of InterestNone Declared

IntroductionAnnual review of coeliac patients to monitor clinical status, dietary adherence and manage further complications is advised by NICE1. We describe adherence to guidelines for patients from adjacent Trusts, one managing patients mainly through a specialist nurse led telephone clinic (NLTC) (Royal Cornwall hospital), the other returning patients to primary care (Plymouth hospitals).MethodPostal questionnaire of 835 patients with coeliac disease (CD), diagnosed via positive serology and duodenal biopsy, who attended secondary care services at one of two hospitals between 2006 and 2014. Patients were diagnosed at least 24 months earlier. Patients reported annual reviews (AR) over the last 3 years, clinical history (weight, height, symptoms, dietary review), investigations (blood tests, vaccinations, DXA referral), prescription of calcium/vitamin D supplements, bisphosphonates and ongoing conditions related to CD i.e. anaemia and osteoporosis.Results516 patients (61.8%) responded. Comparing follow-up between sites, those at Cornwall (84%) were more likely to have AR compared to those at Plymouth (28%) (p<0.0001). In Cornwall, 89% of patients were followed up by NLTC, 2% by GP and 7% by a doctor in outpatients. This is in contrast to Plymouth where all reviews were by GPs. Those under regular review (89% NLTC) had more follow-up tests than those under GPs (Table 1). More patients under GP follow-up had prescriptions for calcium/vitamin D supplements and bisphosphonates. InvestigationsCornwallPlymouthSignificance% (n)% (n)Weight 62 (180) 21 (10) p<0.001 Height 43 (125) 23 (11) p<0.001 Review of symptoms 73 (212) 48 (23) p<0.001 Review of dietary needs 57 (166) 40 (19) p<0.05 Blood tests 78 (225) 71 (34) P=NS Bone scans 66 (191) 48 (23) p<0.05 Vaccinations: pneumococcal pneumonia 38 (110) 31 (15) P=NS Vaccinations: Flu 54 (158) 33 (16) p<0.01 Prescription for calcium/vitamin D 42 (121) 75 (36) p<0.001 Prescription for bisphosphonates 11 (31) 21 (10) p<0.05 Report ongoing symptoms related to CD 35 (122) 48 (82) p<0.005 ConclusionThere is wide variation in local practices of coeliac follow-up and many patients do not get an AR. Only one-third of patients who were discharged back to their GP in Plymouth had an AR compared to 84% in Cornwall where many patients had NLTC review. Patients having AR were more likely to have follow-up tests and investigations in line with NICE guidance and this may result in better outcomes for patients. Future research is required to investigate the optimal way of monitoring patients with CD, the value of self-monitoring and the effect of follow-up on complications associated with CD.ReferenceCoeliac disease: recognition, assessment, and management (2015) NICE guidelines NG20.Disclosure of InterestNone Declared