Klebsiella pneumoniae (CR-KP) infections in solid organ transplant recipients are associated with high morbidity and mortality. We report a case of a fatal donor-derived CR-KP infection in a combined kidney-pancreas transplant. Given the short interval of time between donor hospitalization and organ procurement, information concerning the donor CR-KP positivity arrived only 72 hours after transplant. Based on this experience, we believe that knowledge of the donor's CR-KP status should be mandatory before procurement and, if positive, pancreas donation should be contraindicated. Carbapenem-resistant First described in 2001 concerning an isolate collected in a North Carolina Hospital in 1996, CR-KP infections have spread rapidly worldwide, becoming a serious healthcare problem associated with increased cost and length of stay as well as worse patient outcomes , 4.Moreover, given their stay in intensive care units under mechanical ventilation and their severe illness requiring vasopressor support, deceased multiorgan donors are also another high-risk category for CR-KP transmission, leading potentially to donor-derived infection of recipients .Unfortunately, definitive information concerning the donor's cultures may be still unknown during the times of procurement and implantation, resulting in an indefinite risk for donor-derived CR-KP transmission.We report the case of a 37-year-old diabetic female, who underwent a combined kidney-pancreas transplant in our centre in April 2014.Donor was a 26-year-old male who remained in ICU for only 18 hours before procurement and was considered a “standard” risk for infections.Simultaneous pancreas and left kidney transplant was performed by first placing the pancreatic graft in the right lower intraperitoneal cavity, with vascularization on the recipient's right common iliac axis and a duodenoenterostomy for the exocrine drainage. Then a standard kidney transplant was performed placing the graft in the left iliac fossa.Intravenous (IV) amoxicillin doses were continued for 48 hours as perioperative antibiotic prophylaxis. Klebsiella pneumoniae (CR-KP), susceptible only to colistin (MIC = 2 mg/L); the donor's blood cultures were negative. Combined IV preemptive antibiotic therapy with colistin , meropenem (dose: 2 gr./BID), and tigecycline  was started.On POD 3, the donor's sputum, bronchoalveolar lavage cultures, and the rectal swab were positive for carbapenem-resistantFour days later, the recipient's blood cultures revealed a CR-KP infection and a picture of peritonitis required an urgent relaparotomy which showed an enteric leak from duodenoileal anastomosis with surrounding necrotic tissue, which imposed the removal of the pancreatic graft.Evidence of CR-KP was confirmed in the intraoperative swabs collected from the duodenal graft. XbaI  and subjected to PFGE with the CHEF DRII device . All isolates exhibited the same PFGE macrorestriction profile, confirming the donor-derived infections.Comparison of all the donor's isolates to the recipient's blood isolate by pulsed-field gel electrophoresis  revealedAntibiotic was continued for six weeks, until cultures tested negative; on POD 70, the patient was discharged with normal kidney function, remaining colonized for CR-KP by positive rectal swab.One month later, the patient was readmitted for a pseudoaneurysm of the right common iliac artery with surrounding liquid collection, found to be CR-KP positive and colistin resistant . Patient underwent right iliac replacement with heterologous homograft which was then infected by CR-KP requiring a subsequent silver graft substitution. Triple IV antibiotic therapy with ertapenem (500 mg/daily), meropenem (2 g/BID), and tigecycline  was reintroduced but the iliac wound cultures remained CR-KP positive, subsequently developing a picture of sepsis. In the following weeks, the patient's condition progressively worsened and, unfortunately, she died as a result of multiorgan failure 195 days after transplant.There is very little data on this argument and, to the best of our knowledge, this is the first case reporting a donor-derived CR-KP infection in a kidney-pancreas transplant recipient. In the 15 published cases of donor-derived CR-KP infection in solid organ transplant , 13 had an uneventful outcome while 2 recipients died (one after receiving a lung from an asymptomatic carrier of CR-KP in the respiratory tract and one after receiving a kidney from a donor with CR-KP urine infection) , 8. ThesHowever, our experience revealed peculiar aspects of pancreas donation. In a colonized subject, the CR-KP bacteria remain silent and mainly at the level of the gastrointestinal tract; in this setting, in the event of a pancreas transplant in which the graft necessarily includes a duodenal tract, there could be a high potential risk of direct bacterial transmission from the duodenal graft to the recipient.In our case, the intraoperative swab collected proved the presence of CR-KP bacteria in the explanted duodenal graft. However, we cannot state that the CR-KP infection was directly responsible for the duodenal-ileal anastomotic leak but it was certainly one of the main causes of the sequence of unfavourable events which led to the patient's death. As a result of this experience, we believe that pancreas donation should also be contraindicated in the event of colonized CR-KP donors.Given the short time interval between donor hospitalization and organ procurement (<24 hours), we learnt of the positivity of the rectal swab only three days after transplant. We believe it would be crucial to receive this information before harvesting, to optimize the organ allocation process. These reasons highlight the importance of prompt interinstitutional information sharing among the donor's hospital doctors, local organ coordination centre, and transplant teams. Moreover, we believe that in selected cases, such as ours, the use of faster diagnostic assays such as real-time PCR , 10 shou


Postpartum hemorrhage is the leading cause of maternal mortality in low- and middle-income countries. While evidence on uterine balloon tamponade efficacy for severe hemorrhage is encouraging, little is known about safety of this intervention. The objective of this study was to evaluate the safety of an ultra-low-cost uterine balloon tamponade package (named ESM-UBT) for facility-based management of uncontrolled postpartum hemorrhage (PPH) in Kenya and Sierra Leone.Data were collected on complications/adverse events in all women who had an ESM-UBT device placed among 92 facilities in Sierra Leone and Kenya, between September 2012 and December 2015, as part of a multi-country study. Three expert maternal health investigator physicians analyzed each complication/adverse event and developed consensus on whether there was a potential causal relationship associated with use of the ESM-UBT device. Adverse events/complications specifically investigated included death, hysterectomy, uterine rupture, perineal or cervical injury, serious or minor infection, and latex allergy/anaphylaxis.Of the 201 women treated with an ESM-UBT device in Kenya and Sierra Leone, 189 (94.0%) survived. Six-week or longer follow-up was recorded in 156 of the 189 (82.5%). A causal relationship between use of an ESM-UBT device and one death, three perineal injuries and one case of mild endometritis could not be completely excluded. Three experts found a potential association between these injuries and an ESM-UBT device highly unlikely.The ESM-UBT device appears safe for use in women with uncontrolled PPH.Trial registration was not completed as data was collected as a quality assurance measure for the ESM-UBT kit. Postpartum hemorrhage (PPH) is the leading cause of maternal mortality in low- and middle-income countries. Although reduction of maternal mortality has been a worldwide focus since 1990, a recent World Health Organization report on progress from 1990 to 2015 described that PPH-associated mortality remains unacceptably high, with 54,000 deaths in sub-Saharan Africa in 2015 alone .First-line treatment for PPH includes administration of uterotonic agents. When hemorrhage persists, if available, alternative methods may be employed, including uterine balloon tamponade (UBT), non-pneumatic anti-shock trousers, and surgical interventions such as uterine artery embolization, B-Lynch compression sutures, and ultimately hysterectomy. In low-resource settings, access to surgical services is limited or non-existent, thus women with uncontrolled hemorrhage often die. Until recently, UBT devices were unavailable in these regions –4.Over the past 7 years our team has designed, developed, implemented, and refined a PPH evidence-based package utilizing an ultra-low-cost condom-based uterine balloon called Every Second Matters for Mothers and Babies–UBT (ESM-UBT) –8. When While the data to date support a high degree of efficacy of the ESM-UBT package in arresting uncontrolled PPH, with 98% survival overall, a critical and incomplete part of the equation defining overall impact is understanding the safety profile of the ESM-UBT device . To dateIn this study, our goal was to better understand the safety profile of the ESM-UBT device by following all women who presented to our Kenya and Sierra Leone ESM-UBT facilities in whom an ESM-UBT device was placed for uncontrolled PPH.All women were enrolled who had an ESM-UBT device placed between September 2012 and December 2015, among the 92 facilities active with the ESM-UBT package in Kenya and Sierra Leone. Facilities were defined as active when 85% or more of their skilled birth attendants trained in ESM-UBT, ESM-UBT wall charts were mounted in each delivery area, and ESM-UBT manuals and devices were readily available. Data on improvised UBT kits placed by providers not trained on the ESM-UBT protocol were not included in this analysis  . The UBTData on adverse events/complications were collected via a multi-pronged approach to include telephone and in-person interviews with patients, village chiefs and community health workers; review of health facility records; and examination of data cards included in each of the ESM-UBT device kits. After a provider placed a UBT, the UBT provider filled out a data card and contacted the study coordinator. The study coordinators then visited the UBT facility to verify the data, formally interviewed the UBT provider and compared the data card with the patient’s chart. The data collection cards documented the kit tracking number, facility name, delivery date and time, interventions performed prior to UBT placement, mental status and vital signs at the time of UBT placement, effectiveness of hemorrhage control, steps taken after UBT placement, need for maternal resuscitation or transfusion, and adverse events. Adverse events/complications specifically sought included death, hysterectomy, uterine rupture, perineal or cervical injury, serious or minor infection, and latex allergy/anaphylaxis. Data were collected prospectively for the time interval between delivery and facility discharge throughout the entire study time period. Adverse events/complications data collection was extended to include follow-up at two and 6 weeks following facility discharge, beginning in October 2014. The field data collection team conducted formal follow-up interviews of UBT providers and mothers who had undergone UBT placement. Six-week or longer follow-up data were collected retrospectively for women who had an ESM-UBT device placed prior to October 2014. Three expert maternal health investigator physicians  analyzed each complication/adverse event and deliberated on whether there was a potential causal relationship associated with use of the ESM-UBT device. The three experts were instructed to err on the side of attributing possible causality if there was doubt in certainty. In cases of disagreement the three were asked to discuss and arrive at consensus on categorization.Descriptive data analysis was performed utilizing Microsoft Excel 2015  and STATA 13.1 . This study was approved by the institutional review board of Partners HealthCare , the ethical review committee of Maseno University School of Medicine  and the Office of the Sierra Leone Ethics and Scientific Review Committee . Verbal informed consent was obtained in each case.Among the 92 ESM-UBT active facilities, 201 women were treated with an ESM-UBT device for uncontrolled PPH in Kenya  and Sierra Leone  between September 2012 and December 2015. One-hundred and eighty-nine (94.0%) of the 201 women survived. All 201 women had their ESM-UBT devices placed at a health facility and 146 (76.0%) of 192 by a midlevel provider . One hundred and fifty-six (77.6%) of the 201 received a single dose of prophylactic antibiotics. The mean ages were 27.1 years in Kenya and 25.8 years in Sierra Leone. The median number of prior pregnancies was 2.0 in both countries. Thirty-nine (25.0%) of the hemorrhaging women in Kenya and 22 (46.8%) in Sierra Leone met criteria for advanced shock. Six (3.0%) of the 201 deliveries were via cesarean section , by each of the facilities’ internal processes and by our own research team (Table One hundred and eighty-four (97.5%) of the 189 women who survived uncontrolled PPH had data recorded on adverse events/complications for the time interval between delivery and facility discharge Table . Three (One (0.5%) of the 184 underwent hysterectomy (unclear reasoning since hemorrhage reportedly had been arrested) and none experienced uterine rupture, serious or minor infection, or latex allergy/anaphylaxis in the time interval between ESM-UBT device placement and facility discharge.Expert review of the adverse events and complications in the interval between delivery and facility discharge agreed that although unlikely, one of the twelve deaths (pulmonary embolism) and the three perineal injuries could have been related to use of the ESM-UBT device. No other adverse events potentially caused by an ESM-UBT device were thought to have occurred during this time interval.One hundred and fifty-six (82.5%) of the 189 women who survived uncontrolled PPH subsequent to ESM-UBT device placement were followed for at least 6 weeks post-discharge Table . Thirty-Review of the adverse events and complications in the interval between facility discharge and 6 weeks post-delivery agreed that the one case of endometritis could have been associated with use of the ESM-UBT device. No other adverse events potentially caused by an ESM-UBT device were reported during this time interval.While efficacy of the ESM-UBT package has previously been reported, this investigation aimed to examine the safety of the ESM-UBT device –8. Of thNine (75.0%) of the 12 women who died were in advanced hemorrhagic shock at the time of ESM-UBT device placement and two were septic  prior to delivery  in our study underwent non-emergency hysterectomy subsequent to ESM-UBT placement, however, neither appeared related to ESM-UBT device use. In fact, the hysterectomy rate in this population of 201 women with uncontrolled PPH was low compared to expected rates of 3.8–35.0% , 18–21. During the six-week follow-up period, two women (1.3%) were noted to have minor infections despite having been administered a single dose of prophylactic antibiotics. One was diagnosed with mild endometritis and one an infection of her episiotomy site. It was unlikely that the ESM-UBT device contributed to the episiotomy wound infection, but, quite possible, despite her prolonged labor and cesarean section, that use of the ESM-UBT device contributed to the one case of suspected endometritis. At baseline, endometritis is diagnosed after 1–3% of vaginal deliveries and is ten times more common following cesarean section . In our This study is the largest case series to date examining the safety of a condom UBT device. A lack of absolute certainty of the diagnoses was one of the primary limitations. A second limitation was that the authors examined the data and attributed causation, thus inviting potential reporting bias. To mitigate this bias, the investigators were intentionally inclusive in assigning potential association and/or causation. Another limitation was the incomplete follow-up out to 6 weeks post-delivery despite the multi-pronged approach to data collection. Almost all women lost to follow-up were from the nomadic tribes along the border with Somalia, primarily in Garissa County, Kenya. However, given that the multi-pronged data collection included direct communication with, and interviews of, rural community health workers and local health providers in all the settings where ESM-UBT devices were placed, it was unlikely any deaths were missed. Another limitation was the potential for recall bias when women were asked to recount their experience months subsequent to placement of an ESM-UBT device. However, we expected that most women would recall such injuries, infections or other complications even after the passage of time. Additionally, although it is difficult to draw causal inferences about adverse events in a case series study design, the authors believe that a randomized controlled trial would have been unethical.Although it is impossible to assign causation between ESM-UBT device placement and the adverse events with complete certainty, it appears that, at worst, the ESM-UBT device was associated with one death, three perineal injuries, and one case of mild endometritis among the women in this study. Since the adverse events and complication rates were not above expected baseline in women among the general population of deliveries, and since most of the potential associations between these adverse events and the ESM-UBT device were not likely, it appears that the risk of ESM-UBT device-associated harm is low when used in women with uncontrolled PPH. In this case series, the ESM-UBT device appears safe for use in women with uncontrolled PPH.In this case series, the ESM-UBT device appears safe for use in women with uncontrolled PPH. Future studies on UBT should seek to further define harm versus benefit and optimal use characteristics, clarify the role of antibiotics, develop models for sustainability and scale, and identify additional opportunities for ending maternal death and disability from PPH.


The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus. The manifestation of PML requires the presence of an active, genetically rearranged form of the JC virus within CNS glial cells, coupled with the loss of appropriate JC virus-specific immune responses. The reliability of metrics used to predict risk for PML could be improved if all three components, i.e., viral genetic strain, localization, and host immune function, were taken into account. Advances in our understanding of the critical lymphocyte subpopulation changes induced by these MS therapies and ability to detect viral mutation and reactivation will facilitate efforts to develop these metrics. Progressive multifocal leukoencephalopathy (PML) is a rare polyomavirus-associated disease involving progressive damage to brain white matter that often results in permanent disability or death. PML was first characterized in the 1950s in immunocompromised patients with lymphoproliferative disorders . ImmunosThe AIDS epidemic of the 1980s led to a dramatic increase in new cases of PML, which helped fuel research toward the mechanism, risk factors, diagnostic markers, and possible therapeutic interventions for this devastating disease . UnfortuThe immunomodulatory drugs natalizumab, fingolimod, and dimethyl fumarate (DMF) have greater efficacy in reducing relapses for many relapsing-remitting MS (RRMS) patients than older treatments, such as interferon-β and glatiramer acetate, but have also led some patients to develop PML . NatalizThe most commonly used clinical metric for identifying patients at risk for developing PML is absolute lymphocyte count. Unfortunately, this metric has not been a reliable predictor. Indeed due to its mechanism of action, fingolimod generally lowers lymphocyte counts to a greater extent than natalizumab or DMF –12, but Three factors identified to help stratify the pool of natalizumab-treated MS patients at greatest risk for developing PML include the presence of JCV antibodies in patient’s serum, previous use of immunosuppressive drugs, and use of natalizumab exceeding 24 months . A patieSince PML has occurred in the context of several MS disease-modifying therapies, a better understanding of how PML develops under each of these conditions could lead to the identification of universal predictive risk factors, as well as those factors that are unique. Recent work suggests that efforts toward the combined monitoring of specific lymphocyte subsets, JCV reactivation, and viral genomic rearrangements within the central nervous system (CNS) may offer better insight toward predicting risk  is associated with T-cell exhaustion, and blockade of PD-1 can help restore immune responsiveness . Relativpeptides . The resy stages . Howevery stages , 40. FurNotably, in the context of murine polyomavirus, both susceptible and resistant mouse strains produce a similar antibody response, but differ in the strength of their antigen-specific cytotoxic T-lymphocyte (CTL) responses . In the + B-cells  cells in the absence of the VLA-4/VCAM-1 interaction  that has been approved for the treatment of RRMS and Crohn’s disease . Natalizeraction , 61. Sin the CNS .Migration into the CNS is a two-step process, in which immune cells first migrate into CSF-drained perivascular, leptomeningeal, and ventricular spaces for the purpose of immunosurveillance. Interaction with antigen-presenting cells within these compartments then allows for the α6β1 integrin-mediated migration of activated lymphocytes across the glial limitans barrier into the CNS parenchyma in a cytokine-dependent manner . This tw+ T-cells and initiating a T-lymphocyte response in the CNS . Consequently, the results of these studies are affected by the selection of cytokines assayed, and the + T-cells in two of the PML patients produced IL-10 in response to JCV, and increased levels of IL-10 were detected in the CSF from 50% of early stage PML patients. The increased CSF IL-10 may be related to the loss of CD49d+CD4+ T-cells within the CNS.One pilot study found that peripheral JCV viremia was associated with decreased IFN-γ responsiveness to a JCV VP1 peptide library over the course of natalizumab treatment . Another+ T-cell deficiency led to the development of a population of IL-10-producing PD-1+ CD8+ Treg cells during viral reactivation  receptor. The loss of S1P receptors prevents lymphocytes from traversing the endothelial barriers of lymphatic compartments, effectively trapping them . This lefunction  and thate to JCV . The inie to JCV . In recee to JCV .+ B-lymphocyte and CD4+ T-lymphocyte populations, which have been reported to reach a steady state by 3 months of treatment  within the CSF was found not to change, despite decreases in the blood  has been found to be significantly increased after 12 months of treatment with DMF , which serves as the attachment receptor for the virus  protein , 133, an protein . However protein . Similareceptors . The epieceptors . Furthereceptors . InteresBased on the NCCR sequence structure, four classes of JCV variants have been characterized. While particular variants are preferentially found in certain tissues, they have all been detected to some extent within both the CNS and the periphery . CorrespMany viruses have been shown to modify the contents of host cellular secretions to promote their own spread and survival . Exosomein vivo  and T-antigen are antagonistic to each other. SRSF1 inhibits the splicing of JCV pre-mRNA transcripts, which is necessary for the production of the individual viral proteins . Further B-cells  and CD8+ T-cells  followin T-cells .The disparity of PML incidence may also be related to direct treatment-specific changes within the astrocytes themselves. While the secretion of pro-inflammatory cytokines by immune cells may be beneficial to the containment of JCV, the expression of pro-inflammatory-associated factors by astrocytes could actually contribute to JCV reactivation. A microarray analysis comparing glial cells lines resistant to JCV with those that are susceptible to JCV infection revealed that resistant cells expressed lower levels of pro-inflammatory cytokine and chemokine gene transcripts . This diTherefore, decreases in pro-inflammatory signaling within astrocytes by some immunomodulatory therapies, including fingolimod and DMF, could potentially lower the risk of JCV reactivation with the CNS. Fingolimod treatment suppresses TNFα-induced pro-inflammatory genes, primarily cytokines, in human astrocytes, which confers neuroprotection . CriticaReactivation of latent JCV within astrocytes is a potential gateway to PML. Astrocytes are actively involved in oligodendrocyte survival, differentiation, and myelination through extensive cross-talk between the two glial subtypes . Viral cC terminus of the JCV VP1 gene, which are believed to enhance replication in cerebellar granule cells and provide for the evasion of immune detection  variants that confer risk toward MS and other autoimmune diseases are involved in the function of the immune system , 201. CoVariation in IL-10 signaling could also contribute to PML risk. Polymorphisms in the IL-10 promoter, which mitigate the severity of MS , may alsCase reports of supposedly immunocompetent individuals who developed PML offer some insight into which genes may be most relevant. The ability of IFN-γ to inhibit T-antigen in a Jak/Stat-dependent manner , suggest+ T-cell lymphocytopenia coupled with increases in IL-10-producing regulatory subsets specifically within the CNS may be most relevant. It is also unclear whether having latent JCV within the brain prior to immunosuppression confers greater risk than having it in the periphery, as well as how the mutant form of the virus develops. New biomarkers of reactivation and assays to monitor viral genomic sequences may help address these questions and provide for better monitoring strategies to reduce the future incidence of PML in MS patients.Ultimately, more studies are needed to determine why some patients develop PML. There appears to be a general scheme of immunosuppression leading to JCV reactivation and mutation toward a form that infects glia. Continued immunosuppression then inhibits effective viral clearance and culminates in PML. However, there are still many open questions regarding the details. Not all types of immunosuppression induce PML, and clearly not all immunosuppressed patients develop PML. Current studies suggest that CD4EM and YM-D contributed to the concept, design, and writing of this review.EM has no conflict of interest. No commercial funding was received to support this work. YM-D has served as a consultant and/or received grant support from Acorda, Bayer Pharmaceutical, Biogen Idec, EMD Serono, Genzyme, Novartis, Questor, Chugai, and Teva Neuroscience.


A systematic study on the bending state and performance of the battery is presented. The battery withstands bending radii of at least 14 mm achieving 70% of the theoretical capacity. Here, we reveal that convex bending has a positive effect on battery capacity showing an average increase of 5.5%, whereas concave bending decreases the capacity by 4% in contrast with recent studies. We show that the change in capacity upon bending may well be associated to the Li-ion diffusion kinetic change through the electrode when different external forces are applied. Finally, an encapsulation scheme is presented allowing sufficient bending of the device and operation for at least 500 cycles in air. The results are meant to improve the understanding of the phenomena present in thin-film batteries while undergoing bending rather than showing improvements in battery performance and lifetime.The growing demand of flexible electronic devices is increasing the requirements of their power sources. The effect of bending in thin-film batteries is still not well understood. Here, we successfully developed a high active area flexible all-solid-state battery as a model system that consists of thin-film layers of Li  A shift from fossil to renewable energies, development of practical electrical vehicles, mobile electronics, and Internet of Things devices lead to a strong demand of high-energy, high-power, high-rate capability, long lifetime, high-output voltage, safe, low-cost, environment-friendly, and rechargeable batteries. Lithium (Li) and Li-ion batteries (LIBs) are outperforming most alternative battery chemistries. Li chemistry provides much higher power and energy densities in both gravimetric and volumetric terms which are the most important parameters for applications in portable electronics such as smart phones, digital cameras, and laptops . Convent.6 million in 2015 to $958.4 million by 2022 .https://doi.org/10.1080/14686996.2018.1468199.Supplemental data for this article can be accessed


This work explicitly focuses on key challenges linked to multi-level context modeling, reasoning and fusioning based on the mlCAF open-source ontology. More specifically, it addresses the interpretation of contexts from three different domains, their fusioning conforming to richer contextual information. This paper contributes in terms of ontology evolution with additional domains, context definitions, rules and inclusion of semantic queries. For the framework evaluation, multi-level cross-domain contexts collected from 20 users were used to ascertain abstract contexts, which served as basis for behavior modeling and lifestyle identification. The experimental results indicate a context recognition average accuracy of around 92.65% for the collected cross-domain contexts.The emerging research on automatic identification of user’s contexts from the cross-domain environment in ubiquitous and pervasive computing systems has proved to be successful. Monitoring the diversified user’s contexts and behaviors can help in controlling lifestyle associated to chronic diseases using context-aware applications. However, availability of cross-domain heterogeneous contexts provides a challenging opportunity for their fusion to obtain abstract information for further analysis. This work demonstrates extension of our previous work from a single domain  to multiple domains  for context-awareness. We propose  In the last two decades, significant work has been performed by developing CA prototypes, middleware, and applications [contexts. However, it is challenging in context-aware infrastructure to exploit, integrate, and culture to enrich the fused information in the changing environment. It is pertinent to mention that most existing context-aware solutions cater contextual information in various discrete domains [Context-awareness (CA) is considered to be an essential element in the ubiquitous and pervasive computing systems  and is wications . CA prov domains ,7 and arContext fusioning (CF) is considered as an integral part of any context-aware system . For cohKeeping in mind the above-mentioned facts, our motivation was to design and develop an efficient framework to fuse the multi-levels cross-domain contexts for providing a richer contextual information. To achieve this goal, this study was undertaken with the following objectives: (1) extend the state-of-the-art context-awareness approaches from a single domain  to cross-domains  see , (2) infWeb Ontology Language (OWL) reasoning paradigm comprising of constraint-based rules  and Semantic Query-Enhanced Web Rule Language (SQWRL) based queries (offline) for recognizing contexts and behavioral patterns; (3) proof of concept for ontology modeling, framework implementation, and evaluation in health and wellness domains.The key contributions of this research are: (1) enhanced physical activity domain ontology  with incmulti-level Context-Awareness Framework (mlCAF) is proposed, which fuses the multi-levels cross-domain contexts efficiently to provide a richer context-awareness information to its users. This study is the extension of our previous work [In this study, an open source efficient framework ous work ,13, whichttp://uclab.khu.ac.kr/) project named Mining Minds (http://www.miningminds.re.kr/)  states physical inactivity and unhealthy dietary practices are the key risk factors for this chronic disease. However, these key risk factors are modifiable through environmental, behavioral and lifestyle changes but they require raising people’s self-awareness.For the realization of mlCAF, this study has considered diabetes scenario, as it has a strong relationship between physical activity, and dietary habits . UsuallyDiabetes  by WorldMining Minds platform, the evolved ontology illustrated with examples and the extended architecture. Vertical Fusioning and Horizontal Fusioning techniques. The rest of the paper is organized as follows: Context-aware (CA) systems from an Internet of Things (IoT) perspective were also surveyed [Nowadays, the most dominant context information consumers are mobile applications, which engage different capabilities of sensors in the shape of context . Sensor-surveyed  as for hsurveyed  introducFeel@Home environment [The heterogeneous domains handle dynamic contexts in a smart environment, to represent daily life activities correctly and assist people well-being with technologies . The croironment  addresseironment , in whicironment  developeContext act as a key binding element for integrating information at different levels  in multiService-oriented Context-Aware Middleware that works on server-based architecture style with underlying ontology. This provides context-aware services in smart home and vehicle environment. It supports information sensing, semantic representation, and reasoning of context using SOCAM ontology by modeling person, activities along with locations leaving out nutrition contextual aspects. At the same time, CoBrA [Amongst different context modeling approaches such as: (1) key-value pairs; (2) model-oriented; (3) logic-based; (4) ontologies , we are e, CoBrA  is also e, CoBrA  recognizWeb Ontology Language (OWL) and Semantic Web Rule Language (SWRL) can be integrated to execute knowledge-base system. OWL can be used for problem-solving modeling in terms of ontological development and SWRL may be applied for effective knowledge inference. Using these technologies, Chi et al. [Decision Support Systems based on the fusion of context-based information. OWL knowledge-based systems and SWRL can infer new knowledge regarding habit associations of users in a smart home environment [In order to increase the ontological expressiveness and query answering, i et al.  construci et al.  provide i et al.  proposesironment .Multi-level Context-aware Framework (mlCAF). In order to obtain real-time abstract and richer context in cross-domains, fusioning can be incorporated to infer the abstract contexts in health and wellness domains. Moreover, our proposed framework enables CA platforms to provide better context to adopt behavior and life style.We have adopted context fusioning techniques in context-awareness with the support of the proposed framework called Mining Minds, an innovative platform based on concepts of the digital health and wellness paradigm, provides personalized healthcare and wellness support. It is mainly the collection of innovative services, tools, and techniques applied collectively to monitor human’s daily life data, generated from heterogeneous sources. To provide innovative services and utilize different tools, the Mining Minds platform architecture [Data Curation Layer, Information Curation Layer (ICL), Knowledge Curation Layer, Service Curation Layer and Supporting Layer [Data Curation Layer is in charge of acquisition, processing and persisting the asynchronous, real time, multimodal sensory data obtained through heterogeneous sources like SNS, smart phone, Kinect, wearable biomedical devices etc. This processed sensory data is used by ICL [Low-level Context (LLC), and infer High-level Context (HLC). Health and wellness knowledge is maintained through domain experts or knowledge engineers in Knowledge Curation Layer, which contains rules used to determine personal contexts and behavior. Service Curation Layer caters users with personalized situation aware recommendations based on determined context and knowledge from Knowledge Curation Layer. Finally supporting layer is responsible for advanced analytics, feedback, privacy and security for the Mining Minds platform.itecture  is dividng Layer . In a nud by ICL  to modelMining Minds supports automatic behavior identification through inferring multimodal human context using heterogeneous sensory data. These contexts are identified at two granular layers namely Low-level Context Awareness (LLCA) and High-level Context Awareness (HLCA). LLCA comprises of physical activities, emotions, and location, which are obtained through machine learning classification techniques. These are applied over sensory data obtained through several devices, such as smart watches, smart phones or Kinect video devices [Mining Minds platform. devices . Also, fMining Minds seamlessly supports people’s lifestyles by intelligently fusing human’s daily physical activities and nutrition information along with emotion and location. Behavioral patterns can be derived using diverse HLCs, modeled through inferring over LLCA. ICL layer utilizes the Mining Minds Context Ontology (MMCO), which is considered as conceptual backbone for modeling, representing, and inferring HLCs from LLCs. Existing framework [ramework  lack capThere is a strong relationship between physical activity, dietary habits, and diabetes for people suffering from some chronic disease. Usually, exercises are recommended to all those people who suffer from diabetes as a part of a glycemic control and overall health . In dailMining Minds Context Ontology (MMCO) [In the context modeling world, ontologies outweigh non-semantic models in terms of knowledge sharing, flexibility, reusability, abstraction and validation . Ontology (MMCO)  models dy (MMCO)  used aroMining Minds, human context is understood as any information characterizing the physical, nutritional, emotional, health and social situation of a person leading towards the better identification of human behavior. In the development of OWL2 ontologies, Classes act as a source of an abstraction mechanism for organizing resources with similar characteristics. Furthermore, individuals, also called instances, are members of the OWL Classes and can be related to others using properties. In Mining Minds, the subClassOf constraint is used for designing, assigning classes and individuals for LLC, and HLC. These HLCs are further categorized as Physical Activity High-level Contexts (PA-HLCs), Nutrition High-level Contexts (N-HLCs) and Clinical High-level Contexts (C-HLCs) classes. The main concept of MMCO ontology is the HighLevelContext class, which has three subclasses as PhysicalActivityContext, NutritionContext and ClinicalContext defining the different high-level contexts in the domains of physical activity, nutrition and clinical. The Location, Emotion, Activity, Food, BloodPressure, BloodGlucose, and WaterIntake classes have been described to model the different Low-level Contexts (LLCs). These classes are related to the class HighLevelContext, with the help of object properties hasLocation, hasEmotion, hasActivity [hasFood, hasBloodPressure and hasBloodGlucose.In Activity , hasFoodActivity, Location, and Emotion. PA-HLC includes contexts for sedentary and active physical activities such as OfficeWork, HouseWork, Amusement, Gardening, Commuting, Sleeping, Exercising, and Inactivity discussed in detail by Villalonga et al. [Food which is described in a 57 food-item list and further categorized into 10 broader groups. This categorization and major nutrient identifications are performed in accordance with guidance and suggestions provided by United States Department of Agriculture  on daily food consumptions. Specifically, the different recognized Foods are categorized using 10 disjoint subclasses of the Food class, namely Grain, Meat, SeaFood, Eggs, MilkAndDairyProducts, Legumes, Nuts, Fruits, Vegetable, and Snacks. The identified 57 food items are members of these classes, as can be visualized in MMCO [Food. The C-HLCs are modeled based on LLCs comprising of 6 LLCs categories for BloodGlucose, 5 LLCs for BloodPressure and 3 LLCs for WaterIntake. BloodGlucose values obtained through smart glucose meter, BloodPressure values captured through smart blood pressure monitor, and accumulated water intake values obtained through smart cup. Finally C-HLC reflects four major health states for diabetic patients, such as normal, moderate, high risk and very high risk health state.The scalable MMCO comprehensively models contexts at different abstraction levels. PA-HLC are modeled based on the LLCs belonging to the categories a et al. . The N-H in MMCO . N-HLC mPhysicalActivityContext comprises of eight disjoint subclasses as discussed in our previous work [NutritionContext and ClinicalContext classes are further divided into disjoint subclasses. The NutritionContext class, which represent N-HLCs has three disjoint subclasses decided based on major nutrient in food items, they are named as Carbohydrates, Protein, and Fats. The ClinicalContext class, which represents C-HLC class, is further subdivided as NormalHealthState, ModerateHealthState, HighRiskHealthState, and VeryHighRiskHealthState also shown in NutritionContext and ClinicalContext subclasses are defined through complement classes, existential and universal axioms. These axioms constitute the necessary conditions required for equivalent anonymous class definitions. The equivalent anonymous classes for these NutritionContext and ClinicalContext subclasses have been described in Protégé and are shown in The ous work . HoweverFats class, NutritionContext and (hasActivity some Eating) and (hasLocation some (Home or Office or Restaurant)) and (hasActivity only (eating) and (hasLocation only (Home or Officeor Restaurant)) and ) and (hasFood only (Beef or Chicken Snack or Fried Food or Ham or HamBurger or IceCream or Mackerel or Milk or Peanut or Pork)). This assures that to become instance of the defined class Fats, an individual of the NutritionContext class must have an object property of type hasActivity, which has to be associated with an instance of the Eating class, and this object property must take as only value an instance of the Eating class. Moreover, the instance of the NutritionContext class must also meet the condition for having a property of type hasLocation relating to an instance of the Home or Office or Restaurant class and only to an instance of the Home or Office or Restaurant class. The instance referring the NutritionContext class has an object property of type hasEmotion, this property must also relate to an instance of the Happiness class, the Disgust class, the Boredom class, the Anger class, or the Neutral class. Finally, the property of type hasFood, must relate to an instance of the Beef class, the ChickenSnack class, the FriedFood class, the Ham class, the HamBurger class, the IceCream class, the Mackerel class, the Milk class, the Peanut class, or the Pork class. In the definition and for inferring of Fats class the hasFood object property and hasActivity some Eating axioms are mandatory due to existential and universal restrictions on the involved object properties in addition to hasLocation and hasEmotion object properties. Similar class concept equivalence definitions are formulated for other N-HLCs, Carbohydrates and Protein classes and C-HLC subclasses i.e., NormalHealthState, ModerateHealthState, HighRiskHealthState, and VeryHighRiskHealthState.In order to explain equivalent Class concepts, the N-HLC is modeled via the Mining Minds, the core technologies devised for the inference and modeling of the user’s context constitutes the Information Curation Layer, which is further subdivided to Low-level Context Awareness (LLCA) and High-Level Context Awareness (HLCA) as mentioned in Low-level Context (LLC) using machine learning approaches and it also becomes the basis for inferring in order to obtain High-Level Contexts (HLC) of three types i.e., Physical Activity High-Level Context (PA-HLC), Nutrition High-Level Context (N-HLC) and Clinical High-Level Context (C-HLC). The components drawn in by bold lines are the architectural perspective contributions to the existing work in order to improve context recognition and better behavioral modeling using nutritional and clinical information. LLCs contain seven main context categories Activities, Locations, Emotions, Food, BloodSugar, BloodPressure, and WaterIntake, which are recognized through respective recognizers. Activity LLC is identified from the body actions and mobility, positioning systems helps in identifying Location LLC, Emotion LLC is obtained from the user sentiments detected through voice recognizing systems [Food LLC is obtained using labels of food items sent by users by capturing pictures of meals by using smart-phone. BloodSugar values are taken using a smart glucose meter, which communicates with the Mining Minds platform using API, BloodPressure is measured using the smart blood pressure monitor, and WaterIntake notifier gets input from the smart cup.In  systems . Food LLHigh-Level Context Builder, High-Level Context Reasoner, High-Level Context Notifier, and Context Ontology Manager. The HLC Builder receives the low-level information activities, emotions, locations, food, BloodSugar, BloodPressure and WaterIntake levels identified by LLCA and maps into ontological concepts named as unclassified context. The Physical Activity Context Synchronizer searches for concurrent LLC information related to activities, emotions, and locations whereas the Nutrition Context Synchronizer takes Food LLC into account additionally. Similarly, Clinical Context Synchronizer collects BloodGlucose and BloodSugar LLCs and synchronize them. The Physical Activity, Nutrition and Clinical Context Instantiator create a new instance of an unclassified HLC which links to the corresponding LLCs w.r.t. time. The unclassified PA-HLC, N-HLC and C-HLC are communicated to the HLC Reasoner for its validity and classification. The Context Verifier examines the syntactic and semantic consistency of the unclassified context. The Context Classifier administers ontological inference and classifies the unclassified context into one of the different PA-HLC, N-HLC or C-HLC. The PA-HLC, N-HLC and C-HLC Notifier notifies the newly identified PA-HLC, N-HLC and C-HLC to other Mining Minds layers for the creation of personalized health, wellness services [Context Ontology Manager is responsible for the persistence of MMCO, storage of LLC, PA-HLC, N-HLC, C-HLC and supports SPARQL/SQWRL queries for retrieval of LLCs, HLCs and behavioral contexts.HLCA as shown in services  and neceThe main purpose of context reasoning is to check the consistency of contexts as well as deducing high-level implicit context information from low-level explicit contexts. In this study, ontology-based reasoning is performed with additional assistance for user-defined SWRL rules and SPARQL/SQWRL queries.transitive property, subClassOf, subPropertyOf, disjointWith and inverseOf properties. However, inclusion of complex rules increases the expressibility of ontological model, which enhances the ability of handling the multi-level context assertions.In Ontology-based reasoning, inferring is done based on ontological constraint-based rules exploiting Semantic Query-Enhanced Web Rule Language (SQWRL) on top of SWRL provides SQL-like operators for querying and extracting semantic information. SQWRL uses SQWRL Query API (https://github.com/protegeproject/swrlapi/wiki/SQWRLQueryAPI) interface for executing the queries and accessing the results in a two-dimensional table.SWRL rules, an extension to OWL-DL is one of semantic rule representation for representing knowledge. These rules are designed to obtain the desired outcome based on already stored facts meeting several conditions and adds more power to OWL capabilities for deductive reasoning. Integration of SWRL to ontological based inferring systems have shown their importance for context-aware applications . OntologMining Minds, we ideally focused on a solution catering contexts from multiple domains, as a proof of concept, we considered PA-HLC, N-HLC and C-HLC such that these are handled separately on one-level, fused together on another level and finally more concrete and abstract multi-level cross-domain contexts are obtained suggesting human behavior and lifestyle. This has helped in increasing the ability to apply our proposed solution to multi-domains, which initially was only composed of physical activity domain.In the https://github.com/protegeproject/swrlapi) which works on top of OWL-based SWRL and SQWRL [In nd SQWRL  query laPhysicalActivityContext class, i.e., an unclassified PA-HLC, can be determined to be associated with one of the eight PhysicalActivityContext subclasses as mentioned in [NutritionContext class can be determined to be a member of one of the three NutritionContext subclasses: Fats, Carbohydrates, and Protein. Similarly, an instance of the ClinicalContext class, can be determined to be a member of one of the four ClinicalContext subclasses: NormalHealthState, ModerateHealthState, HighRiskHealthState, and VeryHighRiskHealthState. The instances of the Food class are asserted through the hasFood property, whereas instances of the BloodGlucose and BloodPressure classes are asserted using hasBloodGlucose and BloodPressure properties respectively. Reasoning in OWL is based on the Open World Assumption (OWA), which means that an assumption cannot be made for something if it does not exist until its nonexistence is declared explicitly. Following is an example discussed in order to illustrate the modeling principles and the inference logic through MMCO in the Protégé tool as shown in NutritionContext class for which the object property hasActivity has been asserted to take the value act_eating, hasEmotion object property has been asserted to take the value emo_happiness, hasFood property has been asserted to take the value food_fried_food, hasLocation property has been asserted to take the value loc_restaurant and hasUser property has been asserted to take the value Bob; where act_eating is an instance of the Eating class, emo_happiness is an instance of the Happiness class food_fried_food is an instance of the Fried_Food class and loc_restaurant is an instance of the Restaurant class. Due to the OWA, the instance of the NutritionContext class has been asserted the type (hasActivity only act_eating) and the type (hasEmotion only emo_happiness) and (hasFood only food_fried_food) and the type (hasLocation only loc_restaurant) and the type (hasUser only Bob). The reasoner is used to automatically classify this instance of the NutritionContext class. The instance complies with the Fats class definition; therefore, it is classified as being a member of the Fats class. The Context Reasoner infers Fats using vertical fusioning as LLC belongs to nutrition domain i.e., Food name and Activity Eating comes from physical activity domain as shown in Carbohydrates and Protein. These contexts are concurrent, due to their overlapping temporal properties, we considered them as they are handled through vertical fusioning inferring. This process is scalable as we can fuse as many concurrent contexts depending on ontological modeling and service requirements.The MMCO is utilized to infer PA-HLC, N-HLC and C-HLC in a vertical fusioning manner utilizing ontological reasoning (Level-II). Using Pellet reasoner, an instance of the ioned in . An instAn example scenario is plotted in The SWRL rules have been designed over and above with MMCO constraint-based rules, by keeping temporal characteristics of concurrent low-level contexts, inferred PA-HLC and N-HLC in view. SWRL combines these atomic dynamic contexts to provide a complete picture of highly interrelated atomic low-level contexts, PA-HLC and N-HLC. The general form of SWRL rule looks like as mentioned below.The contexts obtained using vertical fusioning do not provide enough evidence to establish human behavior as long as they belong to user’s context at the point of time as shown in the example scenario, Using SWRL rules, retrieval through SQWRL, horizontal fusioning of cross-domain contexts from different levels is accomplished.Semantic Web APIs. Furthermore the evaluation for results and introduction of advanced queries along with detailed description are presented.The following sections discuss in detail about the implementation test environment, which was constructed using Microsoft Windows 7 on the top of AMD A10-5800K APU with 12 GB of RAM. Java engine was executed with Eclipse IDE Luna that ran using JRE 1.8.0_45-b15 64-bit version.All experiments were performed on a single machine under 64bit Enterprise edition of https://maven.apache.org/) based project management with Java along with available open source library, Apache Jena v2.11.2 (https://jena.apache.org/). The component High-Level Context Builder receives unstructured low-level information, namely locations, activities, emotions, food, BloodGlucose, and BloodPressure. The Context Mapper maps received low-level information in the form of the label for Activity, Location, Emotions, Food, BloodGlucose, and BloodPressure along with meta-data comprising of Start-time, user-info, etc., using semantic web framework including RDFS [http://owlapi.sourceforge.net/).The implementation  of HLCA ing RDFS , OWL2 [4ing RDFS , and OWLPhysical Activity Context Synchronizer takes concurrent low-Level contexts like Activity, Location and Emotion valid at the same moment in time. Similarly, Nutrition Context Synchronizer processes whenever food low-level context has arrived. Nutrition context synchronizer takes the “Eating” activity low-level context along with Food low-level context in addition to emotion and location. The synchronized LLCs are obtained by SPARQL queries [Union operators capable of combining two or more SELECT statements as mentioned in Block 1 and Block 2. Block 1 retrieves results pertaining to underlying cross-domain LLCs whereas Block 2 structure is designed to retrieve nutrition LLCs. The obtained synchronized LLCs are remodeled to unclassified HLCs depending on the concurrent LLCs. These different synchronized LLCs can be visualized in High-Level Context Reasoner receives either three types of unclassified HLCs, i.e., PA-HLC, N-HLC or C-HLC for their verification and classification. Firstly, the Context Verifier checks the semantic and syntactic consistency of the unclassified HLCs and then the Context Classifier performs the ontological inference and identifies the membership of the unclassified HLCs with the help of Pellet (https://www.w3.org/2001/sw/wiki/Pellet), an open source OWL-DL reasoner. All the contexts are stored in Jena TDB (https://jena.apache.org/documentation/tdb/). The Physical Activity Context Notifier or Nutrition Context Notifier makes the newly inferred HLCs Mining Minds or any third party entity for behavior analysis and recommendation generation.It transforms this information into ontological triple format. The  queries  using UnLow-Level Contexts and 36,276 recognized High-Level Contexts belonging to 20 different adult volunteers in real environment using MM platform involving mlCAF framework. In example scenario, we considered user’s LLC, PA-HLC and N-HLC spanning over-a-week as a case study to explain and provide enough evidence for vertical fusioning and horizontal fusioning, so that we can validate sedentary and active behaviors. The graphical representation mentioned in The evaluation has consisted in the collection of around 141,872 Precision: Number of HLC correctly inferred by mlCAF divided by the total number of HLC defined in MMCO.Recall: Number of HLC correctly answered by the mlCAF divided by the total number of mlCAF in the dataset.Heatmap confusion matrix representation shown in Unidentified PA-HLC and N-HLC, it was realized that Unclassified HLCs are inferred to Unidentified PA-HLC and N-HLC with some missing or wrongly identified low-level contexts as shown in Uncertainty exists in ontological reasoning which leads to ambiguous results. By carefully analyzing In order to check disk space utilization, resources were examined by persisting RDF dataset pertaining to 20 different users. meal frequency is also determined and queried. In this study, we presented SQWRL related to query constructions for behavior context based on user sedentary behaviors and also considered identification of meal frequency.In context-awareness for user personalization, SWRL/SQWRL queries were designed to aid horizontal fusioning to obtain human behavior. As mentioned in Rule 1. Sedentary Behavior(i)If the user “u” has location “Loc_Gym”.(ii)The user “u” has PA-HLC as “Exercising” and it has some start time and end time.(iii)The duration is less than two hours.(iv)The difference in a number of days is less than seven days i.e., in a week.(v)User “u” has “Sedentary Behavior” if “Exercising” PA-HLC is less than two hours in a week.The meaning of the rule is as follows:Rule 2. Lightly Active(i)subClassOf of PA-HLC.If the user “u” has a low intensity activity such as walking “Act_Walking” which is (ii)The user “u” has PA-HLC as “Exercising” with start-time and end-time.(iii)If the duration is between one hour and three hours.(iv)If the difference in the number of days is less than seven days i.e., in a week.(v)Activity as Act_Walking in a week.This SQWRL query selects the users “u” a “Lightly Active” if “Exercising” PA-HLC is between one hour and three hours but with LLC Rule 3. Moderately Active(i)subClassOf of PA-HLC.If the user “u” has a moderately intensive activity such as Running with instance “Act_Running”, which is (ii)The user “u” has PA-HLC as “Exercising” with start-time and end-time.(iii)If the duration is between three hour and five hours.(iv)If the difference in the number of days is less than seven days i.e., in a week.(v)Activity as Act_Running in a week.This SQWRL query selects the users “u” a “Moderately Active” if “Exercising” PA-HLC is between three hours and five hours but with LLC Rule 4. Very Active(i)If the user “u” has high intensive “Exercising” with start-time and end-time as PA-HLC.(ii)The duration of “Exercising” is between one hour and three hours.(iii)The intensive “Exercising” is being performed daily.(iv)Very Active behavioral context as they are regularly engaged in performing physical activities.This designed SQWRL query will retrieve a list of all users who perform high intensive “Exercising” and they are termed as having Rule 5. Extremely Active(i)If the user “u” has vigorous-intensive “Exercising” with start-time and end-time as PA-HLC.(ii)The duration of “Exercising” is between one hour and three hours.(iii)The vigorous-intensive “Exercising” is being performed twice a day.(iv)Extremely Active behavior, who perform intensive workouts twice a day having an overall duration of two hours or more.This SQWRL query will retrieve a list of all users who perform vigorous-intensive “Exercising” and the resultant users are considered to be of Rule 6. Meal Frequency(i)If the user “u” has some activity “Eating”.(ii)The user “u” has N-HLC as “Eating” and it has some start time and end time.(iii)Count the activity “Eating” per day.(iv)The presented SQWRL query calculates the frequency of an activity “Eating” in a day for the users and returns all users with given conjunctive conditions.These captured human behaviors using VF and HF are transmitted to other Mining Minds platform layers for further support to user’s health and wellbeing by monitoring physical activity, nutrition, and health-related states.multi-level Context-aware Framework mlCAF, methods for transforming Low-Level Contexts (LLCs) into Physical Activity High-Level Context (PA-HLC), Nutrition High-Level Context (N-HLC) and Clinical High-Level Context (C-HLC). These PA-HLC, N-HLC and C-HLC are transformed using ontological based inference resulting in the vertical fusioning for cross-domain low-level contexts. In this work, the Mining Minds Context Ontology (MMCO) was extended to cater cross-domain contexts from physical activity, nutrition and clinical domains in order to identify major nutritional patterns and behaviors for users. It is pertinent to mention that a broader picture of human behavior modeling and lifestyle determination is obtained by using SWRL/SQWRL additionally as a horizontal fusioning, which keeps on creating associations amongst PA-HLC, N-HLC, C-HLC, and even LLCs at different levels. The main motivation behind this work lies in correctly identifying user’s daily life contexts, behavior identification, as lifestyle, which lead to better community care and wellness. So the key direction that underpins our ongoing research in the Mining Minds involves real-time human behavior modeling and lifestyle prediction using cross-domain contexts. In this regard, experimental results indicate a context recognition average accuracy of around 92.65% for the inferred cross-domain contexts at different fusioning levels. Moreover, investigations are still underway for the identification for more efficient context fusioning mechanism through semantic technologies. it is confirmed that there is still a need for relevant data within in the referred time, which is to be used in the Mining Minds with MMCO for more accurate PA-HLC, N-HLC and C-HLC contexts situation analysis. In addition, creation and execution of more SWRL/SQWRL rules will have a significant impact on the overall platform in terms of better behavioral modeling and lifestyle identification. In future, we are planning to extend SWRL/SQWRL for lifestyle modeling and perform prediction analysis using inductive reasoning by applying data-driven approaches on gathered dataset i.e., A-Box assertions in the Jena Triple-store Database. This paper has presented the ontology-based modeling and cross-domain context fusioning, associated implementation using


No such association was found in boys. In conclusion, our data show that girls with a poorer quality diet show higher hs-CRP levels already at a pre-pubertal age.The influence of diet on inflammation in children remains unclear. We aimed to analyze the influence of diet on high-sensitivity C-reactive protein (hs-CRP) levels in a pre-pubertal population free of other influences that may affect hs-CRP levels. We determined hs-CRP levels in 571 six- to eight-year-old children using an hs-CRP ELISA kit. Information on food and nutrient intake was obtained through a food-frequency questionnaire. Overall dietary quality was assessed using the Healthy Eating Index (HEI). We found that girls in the highest tertile of hs-CRP levels had a higher intake of saturated fatty acid, and lower intakes of fiber and vitamin E and a lower HEI score when compared to those in tertiles 1 and 2. We also observed a significant decrease in fruit and vegetable intakes by hs-CRP tertile. Factor analysis showed that a dietary pattern that was loaded most strongly with vegetable, fruit, fiber and vitamin A and E intakes correlated negatively (−0.132,  Obesity is associated with dysregulation of adipocytokine release, resulting in an increase in the secretion of a number of inflammatory factors that have been associated with an increased cardiovascular risk profile, even in early life . C-reactIt is accepted that pathological processes related to the development of arteriosclerosis, which leads to an increased cardiovascular risk, begin in early life ,4 and arDiet composition is related to inflammatory status . SeveralVegetables and fruit also have high fiber content, and therefore multiple studies have analyzed the potential influence of fiber on plasma CRP levels in adults . Even thThe relationship between hs-CRP and dietary patterns has also been investigated ,18. DietIn our study we aimed to investigate whether dietary factors are associated with hs-CRP levels in a large, well-defined, population-based sample of pre-pubertal children. We have analyzed the hypothesis that a healthy dietary pattern could be associated with lower hs-CRP levels in children.Our study included a population-based sample of 571 six- to eight-year-old children (301 girls and 270 boys). Subjects were participants in a cross-sectional study designed to analyze cardiovascular risk factors in Spanish schoolchildren, the Four Provinces Study. Data was gathered cross-sectionally from representative samples of children  in the four cities participating in the study. Children were selected through random cluster-sampling of schools, stratified by sex and socio-economic level . Dietary information was gathered on a total of 1,112 children, comprising 557 (50.1%) boys and 555 (49.9%) girls. The overall response rate was 85%, with a similar rate in all four cities . In thisParents were required to sign a written consent form allowing t heir children to participate. All children reported by their parents to be suffering from metabolic, endocrine, liver or kidney disorders were excluded from the study. Ten children with hs-CRP levels equal or above 10 mg/L were excluded to avoid the influence of acute infection. The study protocol was approved by the Ethics Committee of Clinical Investigation of the Fundación Jiménez Díaz . The investigation fulfils the principles contained in the Declaration of Helsinki and subsequent reviews, as well as the prevailing Spanish legislation on clinical research in human subjects.The same team consisting of one physician and several nurses was in charge of blood extractions and physical measurements (weight and height).2) was calculated from these parameters.Measurements (weight and height) were taken with fasting children barefoot and wearing light clothing. Height was measured to the last millimetre using a portable stadiometer, and weight was measured to the last 0.1 kg using a standardized electronic digital scale. Body mass index (BMI) . The sensitivity of the assay was 0.15 mg/L. The intra-assay and inter-assay precision were between 4%–6% and 8%–12%, respectively.The relationship between hs-CRP levels and diet was evaluated by analyzing the association between hs-CRP with nutrients, food items, HEI and whole dietary patterns determined by factor analysis. Information on food and nutrient intake was obtained through a food-frequency questionnaire (FFQ) initially developed for use on adults and previously validated in Spain by Martín-Moreno and cols . For theThe final version of the questionnaire included a total of 77 food codes grouped into 11 categories by nutrient composition. For each food, the standard serving size was defined  and the mean frequency of consumption of such servings over the previous year was ascertained. The questionnaire provided the option of answering, in an open-ended way, in terms of the frequency per day, week, month or year. Using Spanish food-composition tables, a food frequency conversion program was designed, which furnished a database with the annual food consumption and daily nutrient intake frequencies for each individual surveyed.Overall dietary quality was assessed using the HEI . This int-test or Mann-Whitney test to compare nutrient intake by sex. ANOVA or Kruskal-Wallis test and the corresponding Post Hoc test were used to compare the means of nutrient and food intake depending on hs-CRP levels tertile. To identify major dietary patterns experimental factor analysis was conducted. The identified factors were rotated using a Varimax rotation to ensure that standardized, non-correlated dietary patterns were identified. The Kaiser–Meyer–Olkin (KMO) test was used to evaluate data adequacy for factor analysis. Eigen values higher than one and the Screen plot determined whether the factor should be retained. Regression factor scores were used for partial correlation analyses investigating the association between dietary patterns and hs-CRP.Statistical analysis was performed using the SPSS software package, version 21.0 . As the sensitivity of the assay was 0.15 mg/L, observations of hs-CRP within the interval of concentrations from 0 to 0.15 mg/L (33% of the children) were set to 0.15 mg/L. Children with hs-CRP levels equal or above 10 mg/L were excluded of the analysis. As a sex-dependent association between diet and hs-CRP has been previously described [The sample group was made up of 571 children (301 girls and 270 boys), with an average age of 6.7 years. Hs-CRP levels were higher in girls than in boys . The eneWe analyzed the nutrient intake by tertile of hs-CRP levels after adjusting for BMI . In girlThese differences were not apparent in boys.p < 0.05). Girls in the highest hs-CRP tertile had a significantly lower intake of fruit (173.2 g/day) compared to those in tertile 2 (194 g/day) or tertile 1 (210 g/day) (p < 0.05). Again, no differences were found in boys.In accordance with the decrease in fiber by hs-CRP tertile described above, we observed a decrease in fruit and vegetable intakes by hs-CRP tertiles in girls . Girls ip < 0.05).When analyzing specific foods, we observed that marmalade intake was significantly related to hs-CRP levels, with the highest intake associated with the lowest hs-CRP tertile when compared to the higher tertiles  with hs-CRP in girls after adjusting by BMI. No associations were found between hs-CRP levels and the high fat diet. No correlations for either of the patterns were found in boys.To identify dietary patterns that could be related to hs-CRP levels, principle component factor analysis was performed. Examination of the subsequent Kaiser–Meyer–Olkin (KMO) measure of sampling adequacy showed that the sample was factorable (KMO = 0.662). By examining the Screen plot and Eigen values, four factors were selected in our population. Two main factors explained most of the variance in food intake. Factor 1 explained 26% of the variance in food intake. It loaded most strongly on fiber, fruit, fruit and vegetable, and vitamin A and E intakes . This faWe measured hs-CRP levels in a large, population-based sample of pre-pubertal children in Spain, and identified a number of dietary factors associated with hs-CRP levels in girls. Our results show that a high intake of saturated fat and a low intake of fiber and vitamins are related to the highest hs-CRP levels in girls. Furthermore, our findings emphasize that a low HEI score is associated with the highest hs-CRP levels. We also identified a “high vegetable intake dietary pattern” that is associated with lower hs-CRP levels. Our study adds to the literature that has investigated this association in children, finding an association of hs-CRP levels with a characteristic high fiber, high vegetable intake pattern in a well-defined cohort of pre-pubertal girls. The association of fat intake with hs-CRP levels has been extensively studied in adults ,8,25, anThe association between a higher intake of fruit and vegetables and lower hs-CRP levels appears to be consistent in both adults ,11 and cThe reason behind the different association depending on sex in our children is unclear. Children in our study showed no significant difference in mean BMI or in the intake of fiber, vitamins or vegetables, and are all pre-pubertal and therefore lacking potential hormonal influences that could affect this association. It is possible that the differences could be attributed to the influence of hormones such as leptin on energy homeostasis. Leptin levels are significantly higher in girls than in boys  and haveThe high fiber content and high antioxidant levels related to vegetables and fruit may contribute to explaining the association between vegetable and fruit intake and hs-CRP levels. In our population we confirmed a significantly high fiber intake in girls with lower hs-CRP levels. The association of fiber with CRP levels has been reported in some studies ,32, althFurthermore, an inverse association of hs-CRP with vitamin A and vitamin E has been reported in our study, supporting the fact that antioxidant nutrients may be responsible for lowering hs-CRP levels. In support of this theory, some studies in adults have reported inverse associations between hs-CRP and other antioxidants, such as vitamin C, vitamin A and β-carotene ,11,13, aInterestingly, specific foods such as marmalade were significantly associated with hs-CRP levels in our girls. Unfortunately, in our study we lack information regarding the type of marmalade children are consuming. However, similar to our results, a significant inverse association between honey/jam intake and CRP levels was described in the IDEFICS Study in European children .In our study, the overall dietary quality was measured using the HEI . We founConsistent with the results discussed previously, we found that a high vegetable intake pattern had a significant negative association with hs-CRP levels in girls. Our pattern was defined by a high fiber intake, a high intake of fruit and vegetables, and a high intake of vitamins A and E. In studies in adults, similar patterns have been negatively associated with hs-CRP levels ,32; howeThe main limitation of our study was the method of collecting dietary information. FFQs introduce the potential for recall bias, which is of particular importance in children. We countered this issue by obtaining dietary information from the primary carer of each child, trying to minimize recall bias. Particularly debatable is the definition of the terms “simple and complex carbohydrates”. In addition to fiber, complex carbohydrates in our study included several forms of carbohydrates, including starches. This may contribute to the lack of a significant association between hs-CRP levels and complex carbohydrates, despite our finding of an association between hs-CRP and fiber.In conclusion, we showed that specific dietary factors—namely saturated fat, fruit and vegetable and fiber intake, and vitamins A and E—were associated with variations in hs-CRP levels in girls, independent of BMI. We identified a high vegetable intake pattern that negatively correlated with hs-CRP. These findings suggest that diet seems to be related to hs-CRP levels already at the pre-pubertal age, emphasizing the need for dietary guidelines in preventing high hs-CRP levels from childhood.


Plant lectins are proteins that reversibly bind carbohydrates and are assumed to play an important role in plant development and resistance. Through the binding of carbohydrate ligands, lectins are involved in the perception of environmental signals and their translation into phenotypical responses. These processes require down-stream signaling cascades, often mediated by interacting proteins. Fusing the respective genes of two interacting proteins can be a way to increase the efficiency of this process. Most recently, proteins containing jacalin-related lectin (JRL) domains became a subject of plant resistance responses research. A meta-data analysis of fusion proteins containing JRL domains across different kingdoms revealed diverse partner domains ranging from kinases to toxins. Among them, proteins containing a JRL domain and a dirigent domain occur exclusively within monocotyledonous plants and show an unexpected high range of family member expansion compared to other JRL-fusion proteins. Rice, wheat, and barley plants overexpressing OsJAC1, a member of this family, are resistant against important fungal pathogens. We discuss the possibility that JRL domains also function as a decoy in fusion proteins and help to alert plants of the presence of attacking pathogens. Arabidopsis thaliana. A prominent example is the brassinosteroid receptor BRI1 (brassinosteroid insensitive 1) that contains an extracellular leucine-rich repeat (LRR) domain .In this review, we will summarize recent advances in our understanding of the role of chimeric lectin-containing proteins in plant defense, with special emphasis on those chimeric proteins containing a JRL domain.The majority of eukaryotic proteins consist of more than one domain, i.e., are chimeric . These mIn general, lectins are sugar-binding proteins with at least one non-catalytic domain enabling them to selectively recognize and reversibly bind to particular carbohydrates . These gGalanthus nivaili agglutinin-related), and C-  types [The majority of known plant lectins consist of one or more lectin domains coupled to another, unrelated domain . The most) types . Beside t) types .Amaranthus was reported to enhance resistance to aphids when ectopically expressed in transgenic tobacco and cotton by affecting the growth and development of the invading pest [Nicotiana tabacum agglutinin, originally discovered in tobacco leaves after jasmonate treatment [O-GlcNAc moieties of core histone proteins. It is hypothesized that the binding of Nictaba to chromatin results in enhanced transcription of defense-related genes [Sambucus (elderberry) a variety of ricin B domain-containing proteins was identified, including SNA-I and SNA-V, and the constitutive expression of the corresponding two genes in transgenic tobacco was shown to enhance resistance to tobacco mosaic virus [Artocarpus integrifolia L.) [Contrary to most lectins, the amaranthin domain itself has no sugar binding site(s); however, a specific head-to-tail arrangement of two amaranthin subunits establishes a T-antigen disaccharide binding site . The nucing pest . Calretiing pest . The faming pest . Nictabareatment . Expressed genes . The riced genes . Unlike ed genes . Within ic virus ,23. Seveic virus . jacalinolia L.) . JRLs arolia L.) . Althougolia L.) .Arabidopsis thaliana [Fusarium graminearum and Blumeria graminis [Many JRLs have been shown to be associated with disease resistance, abiotic stress signaling, wounding, and insect damage . For exathaliana . Moreovegraminis . OsJAC1,graminis .Most recently, Krattinger et al.  identifiProteins containing JRL domains are not exclusive to plants, but rather are present in various species of different taxonomic groups. We identified 3000 JRL domain-containing proteins in a Uniprot data base search using the Pfam domain PF01419 as query . Out of Phytophthora protein 1 (NPP1) domain, are specific for Oomycetes and 4.7% of JRL proteins in Oomycetes comprise an NPP1 domain (In bacteria the majority of JRL proteins (69.6%) are fusion proteins with one or more exonuclease-endonuclease-phosphatase (EEP) domain . The lar1 domain . ProteinDrosophila kelch open reading frame (ORF) 1 protein [In plants, single-domain JRL proteins and multi-JRL domain proteins account for the majority of proteins with a JRL domain; however, a variety of chimeric JRL proteins containing unrelated domains can be found . In eudi protein ,40. The  protein . The F-b protein .Members of the Liliopsida show the highest diversification of chimeric JRL proteins compared to plants of other classes . FrequenProteins containing a dirigent, Pkc, or RX-CC domain are discussed regarding their involvement in pathogen resistance. Proteins of the RX-CC domain superfamily are similar to the potato resistance protein Rx. Rx has a modular structure consisting of a coiled-coil (CC) domain, a nucleotide-binding (NB), and a leucine-rich repeat (LRR) domain, and mediates resistance to potato virus X . The P-lSo far, we have focused on the question of which unrelated domain superfamilies occur as partners in JRL fusion proteins and how frequently they are found in different taxonomic groups. Next, we were interested in the question of whether there are specific domain compositions within the plethora of different chimeric JRL-proteins that appear noticeably more often than others, or are specific for different taxonomic groups. In Fusarium head blight [By correlating these data, we show that while single- and multi-domain JRL proteins with up to three JRL domains are found in prokaryota and eukaryota, proteins with more than three JRL domains are only present in eukaryota . It is pd blight .Domains of plant-specific chimeric JRLs include kelch, RX-CC, ricin, PKc, or dirigent domains. Interestingly, JRL proteins with three carboxy-terminal kelch domains or an amino-terminal F-box domain are specific for eudicotyledonous plants and, to our knowledge, cannot be found in the group of monocotyledons (Liliopsida) . In contDirigent proteins are generally assumed to play an important role in the biosynthesis of lignins and lignans . In bothPoaceae-specific monocot chimeric jacalins [Magnaporthe oryzae, Rhizoctonia solanii, or Xanthomonas oryzae [Recently, we reported our novel findings regarding the dirigent domain-containing chimeric JRL protein OsJAC1 of rice . OsJAC1 jacalins . When ovs oryzae . Overexps oryzae . The arts oryzae .The Rosetta stone theory hypothesizes that fusion proteins are an indication for the cooperative activity of proteins with the respective single domains . In thisBoth aspects—the identification of interacting pairs of dirigent and JRL proteins in dicots, as well as the characterization of the still poorly-described mode of action of monocot chimeric jacalins—will be important steps in advancing our understanding of plant resistance.


To compare rates of all-cause, liver-related, and AIDS-related mortality among individuals who are HIV-monoinfected with those coinfected with HIV and hepatitis B (HBV) and/or hepatitis C (HCV) viruses.An ongoing observational cohort study collating routinely collected clinical data on HIV-positive individuals attending for care at HIV treatment centres throughout the United Kingdom.Individuals were included if they had been seen for care from 2004 onwards and had tested for HBV and HCV. Crude mortality rates  were calculated among HIV-monoinfected individuals and those coinfected with HIV, HBV, and/or HCV. Poisson regression was used to adjust for confounding factors, identify independent predictors of mortality, and estimate the impact of hepatitis coinfection on mortality in this cohort.Among 25 486 HIV-positive individuals, with a median follow-up 4.5 years, HBV coinfection was significantly associated with increased all-cause and liver-related mortality in multivariable analyses: adjusted rate ratios (ARR) [95% confidence intervals (95% CI)] were 1.60 (1.28–2.00) and 10.42 (5.78–18.80), respectively. HCV coinfection was significantly associated with increased all-cause  and liver-related mortality . Neither HBV nor HCV coinfection were associated with increased AIDS-related mortality: ARRs (95% CI) 1.07 (0.63–1.83) and 0.40 (0.20–0.81), respectively.The increased rate of all-cause and liver-related mortality among hepatitis-coinfected individuals in this HIV-positive cohort highlights the need for primary prevention and access to effective hepatitis treatment for HIV-positive individuals. Since the introduction of combination antiretroviral therapy (cART) for the treatment of HIV infection, rates of AIDS-related morbidity and mortality have fallen. HIV-positive individuals who are diagnosed promptly and have good access to cART are now expected to live a near normal lifespan. When HIV-positive individuals do die, they are less likely to die from AIDS-related causes than in the pre or early cART era. However, the proportion of people who die from liver-related causes has increased, with these deaths largely being related to coinfection with either hepatitis B virus (HBV) and/or hepatitis C virus (HCV) –5.HIV-positive individuals coinfected with HBV and/or HCV have higher rates of progression to chronic hepatitis infection –8 and fa+ cell count)  or HCV (a positive HCV antibody or positive HCV RNA test result). This involved detailed review of the clinical HIV notes of coinfected individuals seen for care from 2004 onwards. This process aimed to verify the hepatitis-coinfected individuals as well as collect detailed information on the treatment and outcomes of hepatitis infection among these individuals. As part of this process, additional information on the cause of death was collected for those individuals who were known to have died.Individuals were included in this analysis if they had attended any one of the 11 centres where additional hepatitis data collection were conducted from 2004 onwards and had ever been tested for HBsAg and antibody to HCV (anti-HCV) or HCV RNA. Individuals were defined as being HBV infected from the date of their first positive HBsAg test and being HCV infected from the date of their first positive anti-HCV or HCV RNA test.In addition to information on deaths received from clinics, for deaths prior to 2011, the UK CHIC dataset has been linked to data from the Office for National Statistics (ONS) using soundex codes, initials, date of birth, and sex. From 2011 onwards, the UK CHIC dataset was linked to mortality data from Public Health England (PHE). Where these linkages provided additional information on date and cause of death, the UK CHIC dataset was updated.Causes of death were coded as liver related, AIDS related, or neither. Deaths were coded as liver related where there was clear evidence that disease in the liver had contributed to death. This included, for example, decompensated liver disease, hepatocellular carcinoma and liver failure, and cancers with liver metastases. Where a nonliver-related cause of death was recorded but there was additional mention of viral hepatitis, this was not coded as a liver-related death. Deaths were coded as AIDS related either where AIDS was stated as a cause of death or where the cause of death included conditions included on the Centres for Disease Control and Prevention list of AIDS-defining conditions . Coding Individuals were followed from the latest of their first HBV or HCV test, entry into UK CHIC, or 1 January 2004. In some cases, individual deaths may be reported to a clinic a long time after the individual last attended the clinic. To prevent extended follow-up among these individuals, an additional 6 months of follow-up was added to all individuals. Subsequently, all deaths which occurred within 6 months of the last date that an individual was seen for care in UK CHIC were included in the analysis. Where the recorded date of death was more than 6 months after the last date which they were seen , follow-up was censored at 6 months after their last date of follow-up to prevent extended follow-up among those individuals who die. In addition, since different centres report data with varying cutoff dates, all data were censored at 31 December 2011.Individuals were categorized at baseline as HIV monoinfected, HIV/HBV coinfected, HIV/HCV coinfected, or HIV/HBV/HCV triple infected. Individuals moved in one direction from HIV monoinfected to a coinfection or triple infection category if there was evidence of a positive test result during follow-up. The total number of person-years of follow-up was calculated for each coinfection category using the date at which an individual entered that coinfected category and their last date of follow-up within that category. Mortality rates were calculated as the total number of deaths divided by the total person-years of follow-up within each category.+ cell count, HIV viral load, cART, and calendar year were updated every 3 months in the analysis. Hepatitis coinfection status was updated whenever a change occurred. Given the close relationship between HIV viral load and cART, these two variables were combined to form a composite covariate which focussed on whether or not viral load was detectable and whether or not an individual was receiving any cART: on cART and viral load less than 50 copies/ml; on cART and viral load 50–10 000 copies/ml; on cART and viral load more than 10 000 copies/ml; off cART and viral load less than 50 copies/ml; and off cART and viral load at least 50 copies/ml.Poisson regression was used to identify predictors of all-cause, liver-related, and AIDS-related mortality. Fixed covariates were ethnicity and HIV exposure group as reported by the clinics. Age, CD4+ cell count, HIV viral load and treatment, and year of follow-up. Although ethnicity was associated with mortality in univariable analysis, inclusion of ethnicity in the final models did not alter the effect of coinfection on mortality and therefore this was not included in the final models. Models of all-cause, liver-related, and AIDS-related mortality were adjusted for the same confounders to allow for comparison.Final models were created using a backwards selection process to identify those factors that cofounded the effect of coinfection on mortality and to achieve a parsimonious model. Final models were adjusted for age, HIV exposure group, CD4HIV-positive IDU have higher mortality rates than HIV-positive individuals who acquired their HIV infection through other routes –26. In tA total of 25 486 individuals contributed 121 814 person-years of follow-up to the analysis. Median follow-up time was 4.6 years  per person. Overall, 1065 individuals (4.2%) died during follow-up. Baseline characteristics of included individuals are shown in Table All categories of hepatitis coinfection were significantly associated with an increased risk of all-cause mortality both in univariable and multivariable analysis Table . In multThe effect of hepatitis coinfection on the risk of liver-related mortality was greater than its effect on all-cause mortality Table . After aHepatitis coinfection was not associated with an increased risk of AIDS-related mortality after adjusting for confounding factors Table . Compare+ cell counts, and having a high HIV viral load while being on cART were associated with increased mortality (data not shown).Some other associations were also observed. In all models, having acquired HIV infection through IDU was a strong predictor of mortality. In addition, increasing age, lower CD4When individuals who acquired their HIV through IDU were excluded from the models of all-cause mortality and liver-related mortality, there were no changes to the direction of the associations between hepatitis coinfection and increased mortality. The effect sizes also remained similar (data not shown). When IDU were excluded from the model of AIDS-related mortality, the association between HIV/HCV coinfection and decreased risk of liver-related mortality became nonsignificant ; however, the direction of the effect remained the same.In the UK CHIC study, among patients under follow-up in an era of effective treatment for HIV infection, coinfection with HBV or HCV was significantly associated with increased all-cause mortality even after adjusting for other known predictors of mortality. The association between liver-related mortality and coinfection was even more striking. In contrast, HIV/HBV coinfection and HIV/HBV/HCV triple infection was not associated with AIDS-related mortality.There was some evidence of a protective effect of HCV on the risk of AIDS-related mortality. IDU usually acquire HCV very soon after they start injecting drugs and, therefore, are likely to have been infected with HCV for longer than individuals who have acquired their infections through other routes. IDU also have higher rates of other causes of mortality than individuals who do not inject drugs. Therefore, the protective effect of HCV infection with regard to AIDS-related mortality when IDU are included in the model may be because of long-standing HCV infection, or other mortality specifically associated with injecting behaviours, acting as competing risks for AIDS-related mortality. After excluding IDU from the analysis the effect became nonsignificant; however, the effect size remained the same. It is possible that this is an effect of the recent outbreaks of acute HCV among MSM. These men are likely to be well engaged with HIV care and are therefore less likely to experience AIDS events.The association of HIV/HBV coinfection with increased all-cause mortality and the even larger effect of HBV infection on the risk of liver-related mortality has been seen in other cohorts ,20,27–29The association between increased mortality and HIV/HCV coinfection has also been shown in other cohorts –39. In t+ cell count were all significantly associated with increased all-cause, liver-related, and AIDS-related mortality. The observed association between all-cause, liver-related, and AIDS-related mortality and cART/viral load is less intuitive. Being on cART and having a high HIV viral load may be a sign of treatment failure. Alternatively, these could be individuals who have become very unwell from liver disease and have, therefore, opted to stop taking cART. In each of these cases, individuals could be expected to very unwell compared with individuals in the other HIV treatment/viral load categories which might explain the increased risk of mortality.In assessing the association of hepatitis coinfection with mortality, some other associations were also observed. As expected, IDU and older age and lower CD4The study has some limitations. First, although the linkages of the UK CHIC dataset and data from ONS and PHE have resulted in very reliable data on the number of individuals who have died, accurately establishing cause of death is difficult. Therefore, it is possible that the number of AIDS-related and liver-related deaths are underestimated as cause of death data remains incomplete. In addition, data within UK CHIC are obtained from HIV clinics which may be more likely to have a record of a death related directly to HIV (including AIDS-related death) than death from other causes (including liver-related death). However, it is hoped that the use of three sources of death data  have limited introduction of any bias because of differential reporting of deaths within HIV clinics.Conversely, it is also possible that the number of liver-related deaths is overestimated in coinfected individuals as a known hepatitis diagnosis may influence how a death is reported. In this analysis, the impact of this was minimized by not coding a death as liver related purely on the basis of a mention of viral hepatitis infection and by coding the deaths without knowledge of the individual's hepatitis status.Efforts to improve the reporting of deaths in UK CHIC have intensified in more recent years. In particular, linkage to PHE data were first conducted using a dataset that contained data up to the end of 2010. Therefore, it is likely that from 2010 onwards a higher proportion of individuals who had died would have information recorded in UK CHIC. This may have introduced some bias with increased deaths having been reported in more recent years.Although every effort has been made in the analyses presented to adjust for potential confounding factors, there may be some residual confounding. Information on drug use was only available if IDU was the individual's probable route of HIV exposure. Drug use (including non-IDU) is associated with hepatitis coinfection ,42 and mHepatitis D virus (HDV) is associated with an increased risk of mortality among HIV/HBV-coinfected individuals . The HDVDespite these limitations, the analyses presented utilized a large cohort of HIV-positive individuals and, as such, provide estimates of mortality among HIV and hepatitis-coinfected individuals in the United Kingdom. Directly acting agents for treatment of HCV infection are now available which have high rates of cure. If patients are able to access these treatments the increased risk of mortality from HCV infection may be mitigated. The findings of this study highlight the need for primary prevention strategies and the importance of ensuring prompt diagnosis of hepatitis coinfection among HIV-positive individuals and effective linking of coinfected individuals to treatment and monitoring to limit the progression of liver disease.UK CHIC Steering Committee: Jonathan Ainsworth, Sris Allan, Jane Anderson, Abdel Babiker, David Chadwick, Valerie Delpech, David Dunn, Martin Fisher, Brian Gazzard, Richard Gilson, Mark Gompels, Phillip Hay, Teresa Hill, Margaret Johnson, Sophie Jose, Stephen Kegg, Clifford Leen, Fabiola Martin, Mark Nelson, Chloe Orkin, Adrian Palfreeman, Andrew Phillips, Deenan Pillay, Frank Post, Jillian Pritchard, Caroline Sabin, Achim Schwenk, Anjum Tariq, Roy Trevelion, John Walsh.UK CHIC Central Co-ordination: University College London ; Medical Research Council Clinical Trials Unit at UCL (MRC CTU at UCL), London .UK CHIC Participating Centres: Brighton and Sussex University Hospitals NHS Trust ; Chelsea and Westminster Hospital NHS Foundation Trust, London ; King's College Hospital NHS Foundation Trust, London ; Mortimer Market Centre, University College London ; Royal Free NHS Foundation Trust/University College London ; Imperial College Healthcare NHS Trust, London ; North Middlesex University Hospital NHS Trust, London ; The Lothian University Hospitals NHS Trust, Edinburgh ; North Bristol NHS Trust ; Middlesbrough, South Tees Hospitals NHS Foundation Trust ; Woolwich, Lewisham and Greenwich NHS Trust ; Public Health England, London (V. Delpech); UK Community Advisory Board (R. Trevelion).UK CHIC is funded by the Medical Research Council Grant Numbers G000019, G0600337 G0900274. Additional funding was received from Bristol Myers Squibb, Abbott, Boehringer Ingelheim, Gilead Sciences, and Merck Sharp & Dohme for collection of data regarding coinfected individuals.Contributions: Study design: A.T., C.A.S.; data analysis: A.T.; first draft of the manuscript: A.T. C.A.S. All authors contributed to the data interpretation, final version of the manuscript and approved the submission.There are no conflicts of interest.