Search

Purpose: The aim of this research is to provide insight into how organizations can co-create value with family members engaged in service journeys of customers experiencing vulnerabilities, thereby paying attention to their organizational practices (i.e. recursive or routinized patterns of organizational actions and behaviors). Design/methodology/approach: To investigate, this research relies upon a multiple case study in a group of nursing homes in Flanders that had the ambition to engage family members in service journeys of their loved ones while measuring their value perceptions as a performance indicator (here, satisfaction with nursing home services). Findings: The case evidence shows that nursing homes co-create value with family members through caring practices that focus on their role as secondary customers (i.e. welcoming, connecting and embedding) and empowering practices that focus on their role as partial employees (i.e. teaming up, informing and listening practices). However, the way in which the different caring and empowering practices are enacted by the nursing home and its staff affects their value co-creation potential. Originality/value: By focusing on the practices with which organizations can co-create value with family members engaged in service journeys of their loved ones, this research bridges the service literature with its attention for value co-creation practices and the literature on customers experiencing vulnerabilities with its focus on extended customer entities.

ObjectivesTo eliminate hepatitis B and C virus (HBV/HCV) as a public health threat by 2030, the WHO focuses on screening key populations, including men who have sex with men (MSM).This study aims to assess HBV and HCV knowledge and awareness and HCV prevalence in MSM in Belgium.MethodsFirst, a questionnaire was designed to assess MSM's knowledge of HBV and HCV infection (disease process, vaccination, treatment and transmission routes). This questionnaire was conducted online, and by means of a tablet-based face-to-face questionnaire at the Antwerp and Belgian Pride. Second, HCV and HIV prevalence data were collected during outreach projects and office screening for sexually transmitted infections (STIs) organised by Sensoa and Exaequo, a Flemish and Walloon sexual health organisation.Results300 MSM completed the questionnaire (median age 36 years; 7.7% HIV+). Mean overall survey scores were low (HBV: 41.1%; HCV: 39.8%). Few participants identified all transmission routes correctly (HBV: 15%; HCV 1%).The degree of education was significantly correlated with HBV knowledge and showed a trend towards correlation with HCV knowledge. HCV knowledge was significantly correlated with high-risk sexual behaviour.The prevalence of HCV and HIV was 0.3% and 1.0%, respectively, in MSM attending commercial gay venues and 0% and 1.9% in MSM attending office STI screening.ConclusionsKnowledge of HBV and HCV infection in MSM is poor. More awareness campaigns are needed, focusing on frequent HCV risk factors (group sex, chemsex, receptive fisting, and sharing of anal toys and anal douching devices), especially targeting low-educated MSM. HBV vaccination of MSM requires continued attention.The prevalence of HCV and HIV was remarkably low in commercial gay venues and may be higher in older MSM or in subcultures where risk factors coexist (eg, chemsex). The cost-effectiveness of internet-based approaches with subsequent at-home testing needs to be evaluated in the future.

Abstract: Task assignment in multi-agent systems is a complex coordination problem, in particular in systems that are subject to dynamic and changing operating conditions. To enable agents to deal with dynamism and change, adaptive task assignment approaches are needed. In this paper, we study two approaches for adaptive task assignment that are characteristic for two classical families of task assignment approaches. FiTA is a field-based approach in which tasks emit fields in the environment that guide idle agents to tasks. DynCNET is a protocol-based approach that extends Standard Contract Net (CNET). In DynCNET, agents use explicit negotiation to assign tasks. We compare both approaches in a simulation of an industrial automated transportation system. Our experiences show that: (1) the performance of DynCNET and FiTA are similar, while both outperform CNET; (2) the complexity to engineer DynCNET is similar to FiTA but much more complex than CNET; (3) whereas task assignment with FiTA is an emergent solution, DynCNET specifies the interaction among agents explicitly allowing engineers to reason on the assignment of tasks, (4) FiTA is inherently robust to message loss while DynCNET requires substantial additional support. The tradeoff between (3) and (4) is an important criteria for the selection of an adaptive task assignment approach in practice.

This article is a contribution to the semantic map of imperatives, prompted by an implicational map proposed earlier in the literature. The tentative semantic map proposed here abstracts away from differences in use that can be attributed to pragmatics, like distinctions between commands, requests, suggestions etc. The functional differentiation resulting from person and number value, which determines a different character of the directive speech act, is adopted as the basis for the characterization of polysemy in imperatives, and taken as the nucleus of the semantic map, which is then expanded by taking into account non-directive meanings, which are also differentiated with regard to the person value from which they develop.

AbstractBackgroundBalloon uncrossable coronary lesions are lesions that cannot be crossed with a conventional balloon. Multiple balloons have been designed to overcome this problem. The Blimp balloon has a very low scoring profile (0.6 mm) with a very high rated burst pressure (30 atmospheres). We aimed to evaluate the efficacy of this balloon compared to customary low-profile balloons.MethodsWe conducted a multicenter, prospective, randomised, controlled trial in which 126 patients with an uncrossable lesion were randomly (1:1 randomization) assigned to treatment first with the Blimp balloon or low-profile balloon. The primary endpoint was the success of crossing the lesion after initial failure with a microcatheter (group A) or with a conventional balloon (group B).ResultsOverall, the first attempt of Blimp was successful in 29 out of 61 cases (48%) while the LP balloon immediately crossed in 30 out 67 cases (45%; p = 0.761). Using a low-profile balloon in the BLIMP group after failure of the Blimp balloon increased the success to 64% (39 out of 61 cases). Using the Blimp balloon in the low-profile first group after failure of the low-profile balloon increased the success to 60% (40 out of 67 cases). After the placement of a guide catheter extension, the overall successful lesion crossing in the BLIMP group was 80% (49 out of 61 cases) compared to 76% (51 out of 67 cases) in the LP Balloon group (p = 0.327).ConclusionsThe Blimp balloon catheter showed no superiority to customary low-profile balloons in uncrossable lesions. It can however be complementary in treating uncrossable lesions.

Background: While numerous studies have explored the patient experience of dialysis or other end-stage kidney disease (ESKD) treatments, few have explored the process of transitioning between dialysis modalities. This study aimed to develop an in-depth understanding of patient and caregiver perceptions and experiences of the transition from peritoneal to haemodialysis (HD) and to identify ways in which transitions can be optimised.Methods: Fifty-four in-depth, semi-structured interviews were undertaken at six study sites across the West Midlands, UK (n= 23), and Queensland, Australia (n= 31). Thirty-nine participants were patients with ESKD; the remainder were family members. An inductive analytical approach was employed, with findings synthesised across sites to identify themes that transcended country differences.Results: Of the 39 patient transitions, only 4 patients reported a wholly negative transition experience. Three cross-cutting themes identified common transition experiences and areas perceived to make a difference to the treatment transition: resistance to change and fear of HD; transition experience shared with family; and bodily adjustment and sense of self.Conclusion: Although each transition is unique to the individual and their circumstances, kidney care services could optimise the process by recognising these patient-led themes and developing strategies that engage with them. Kidney care services should consider ways to keep patients aware of potential future treatment options and present them objectively. There is potential value in integrating expert support before and during treatment transitions to identify and address patient and family concerns.

Purpose: This paper explores the relationship between married women's intrahousehold decision-making participation and marital gender roles, next to factors suggested in the household bargaining literature. Additionally, the authors investigate whether women's employment carries the same importance for decision-making participation as contributions to household incomes. Design/methodology/approach: Using 2011/2012 Nicaraguan Demographic and Health Survey (DHS), the authors estimate multinomial logistic regressions for eight decision-making domains, analyzing three levels of decision-making: wife-dominant or sole decisions, joint decision-making (with the partner) and decision-making by someone else. The authors create an additive index for measuring internalized marital gender roles. Findings: Women's intrahousehold decision-making participation is explained differently depending on the decision-making area and level of participation. Women with a better relative position vis-à-vis partners and not following patriarchal gender roles are more likely to make decisions jointly with their partners, but not alone. Women's age and educational level are the strongest predictors in the analysis. Women's employment reduces their decision-making participation in children's disciplining and daily cooking-related decisions. Research limitations/implications: It focuses on married women only, while marital status might be a determinant of decision-making itself and left out the contribution of unearned incomes. Practical implications: Interventions aimed at increasing women's intrahousehold decision-making participation should not only focus on economic endowments but also comprehend the gendered dynamics governing intrahousehold allocation. Originality/value: The study incorporates quantitative measures of marital gender roles in the study of intrahousehold decision-making. It also contributes to the literature with insights from contexts where women's involvement in employment increased against a background of patriarchal gender roles.

In this article a parallel is drawn between certain functions of irrealis and imperfective in evaluating contexts in Russian and Polish. The functions of irrealis in complementation are twofold: while in propositional complements it reflects irreality, in state-of-affairs complements it reflects temporal and situational unanchoring. This unanchoring function manifests itself also in complements of evaluative (commentative) predicates, where it extracts an event from its situational setting for the purpose of evaluating its intrinsic properties – intrinsic likelihood or desirability. It is argued that the representation of event tokens as event types by means of imperfective verbs in Slavonic performs a similar unanchoring function in evaluative contexts. The data of Slavonic languages, where both unanchoring devices cooccur, enable a coherent explanation of certain hitherto not fully understood phenomena in the domains of mood and aspect and shed a new light on the long-standing problem of the Romance so-called “factive” subjunctive.

Homozygous or compound heterozygous mutations in STRADAcause polyhydramnios, megalencephaly and symptomatic epilepsy syndrome (PMSE), with additional features of distinctive facial traits and severe developmental delay or intellectual disability. This syndrome was first defined in 16 Old Order Mennonite patients, carrying a homozygous STRADAdeletion of exon 9–13. Five additional PMSE patients have been reported since, each of them with loss-of-function variants. We report a female patient with the typical clinical features of PMSE, homozygous for a novel STRADAmissense mutation c.792T>A (p.Ser264Arg) in exon 10. This finding contributes to the further delineation of the phenotype of PMSE.

AbstractThis case report describes an intentional intoxication with 18 g of hydroxychloroquine (HCQ) presenting with unconsciousness, ventricular dysrhythmias, cardiogenic shock and pulmonary oedema. Initial treatment consisted of sodium bicarbonate, lipid emulsion, diazepam and norepinephrine. Because of persistent cardiogenic shock veno-arterial extracorporeal membrane oxygenation (V-A ECMO) was successfully used as a bridge to recovery. This case underscores the possible side effects of HCQ and the importance of considering ECMO in cardiogenic shock caused by HCQ intoxication which may occur also in patients with coronavirus disease 2019 (COVID-19) based on the currently frequent use of such a compound.

Background: Different kidney replacement therapy modalities are available to manage end-stage kidney disease, such as home-based dialysis, in-center hemodialysis, and kidney transplantation. Although transitioning between modalities is common, data on how patients experience these transitions are scarce. This study explores patients’ perspectives of transitioning from a home-based to an in-center modality.Methods: Patients transitioning from peritoneal dialysis to in-center hemodialysis were purposively selected. Semi-structured interviews were performed, digitally recorded, and transcribed verbatim. Data analysis, consistent with Charmaz’ constructivist approach of grounded theory was performed.Results: Fifteen patients (10 males; mean age 62 years) participated. The conditions of the transitioning process impacted the participants’ experiences, resulting in divergent experiences and associated emotions. Some participants experienced a loss of control due to the therapy-related changes. Some felt tied down and having lost independence, whereas others stated they regained control as they felt relieved from responsibility. This paradox of control was related to the patient having or not having (1) experienced a fit of hemodialysis with their personal lifestyle, (2) a frame of reference, (3) higher care requirements, (4) insight into the underlying reasons for transitioning, and (5) trust in the healthcare providers.Conclusions: Care teams need to offer opportunities to elicit patients’ knowledge and fears, dispel myths, forge connections with other patients, and visit the dialysis unit before transition to alleviate anxiety. Interventions that facilitate a sense of control should be grounded in the meaning that the disorder has for the person and how it impacts their sense of self.

BackgroundAcute chest syndromes (ACS) may be associated with upper respiratory tract infections, but the epidemiology of viral and intracellular respiratory pathogens in children with sickle cell disease (SCD) is not precisely known. The aim of this study was to describe the epidemiology of viral and intracellular respiratory pathogens in children with SCD presenting with fever and/or ACS.Materials and methodsAn observational, prospective, single-centre cohort study with nested case–control analysis was conducted on children with SCD admitted from October 2016 to October 2017 for fever and/or ACS to the paediatric department of Robert Debré university hospital, Paris, France. They were screened for 20 respiratory pathogens by a multiplex PCR in the nasopharynx (FilmArray).ResultsWe included 101 children. M/F sex ratio of 0.45. The median age was 3.2 years (IQR: 1.4–8.2). At least one pathogen was isolated in 67 patients (67%). The most frequent viruses were as follows: rhinovirus (n=33), adenovirus (n=14), respiratory syncytial virus (n=13) and parainfluenza viruses (n=11). Mycoplasma pneumoniaewas detected in one case. Twenty-three (23%) presented with or developed ACS. A nested case–control analysis was performed, after pairing ACS with non-ACS children for age and inclusion period. There was no statistical association between any viral detection or multiple viral infection, and ACS (p=0.51) even though parainfluenza viruses were twice as common in ACS.ConclusionsViral detection in febrile children with SCD is frequent, but its association with ACS was not demonstrated. In this study, M. pneumoniaewas rare in young children with SCD experiencing ACS.

Budesonide has been proven to be an effective treatment for microscopic colitis (MC). However, the two current commercially available preparations are released in the ileum. Beclomethasone dipropionate (Clipper®) is a synthetic corticosteroid with topical colonic release. This study aimed to explore whether an open-label treatment with beclomethasone dipropionate is an effective treatment for MC. Prospectively collected data of 30 patients from six centres were retrospectively analysed. All patients had a confirmed diagnosis of idiopathic MC (lymphocytic and collagenous colitis) and were symptomatic (i.e.?=?21 loose stools over a seven-day period). Treatment consisted of 10?mg beclomethasone daily for four weeks, followed by 5?mg daily for another four weeks. The primary end point was the proportion of patients in remission (i.e. a mean of?

Background Budesonide has been proven to be an effective treatment for microscopic colitis (MC). However, the two current commercially available preparations are released in the ileum. Beclomethasone dipropionate (Clipper®) is a synthetic corticosteroid with topical colonic release.Objective This study aimed to explore whether an open-label treatment with beclomethasone dipropionate is an effective treatment for MC.Methods Prospectively collected data of 30 patients from six centres were retrospectively analysed. All patients had a confirmed diagnosis of idiopathic MC (lymphocytic and collagenous colitis) and were symptomatic (i.e. ≥ 21 loose stools over a seven-day period). Treatment consisted of 10 mg beclomethasone daily for four weeks, followed by 5 mg daily for another four weeks. The primary end point was the proportion of patients in remission (i.e. a mean of < 3 stools/day and a mean of <1 watery stool per day) after an eight-week treatment period. Secondary end points were the proportion of patients responding to therapy at weeks 4 and 8, remission at weeks 4 and 12 and relapse at week 12. Reported adverse events were collected.Results Overall, at week 8, remission was achieved in 70%, and 77% of patients were responding to treatment. After four weeks of treatment, 80% were responding, and 67% were in remission. Four weeks after stopping treatment, 60% were still in remission.Conclusion This open-label study suggests that an eight-week course of beclomethasone could be a promising and relatively safe treatment for MC. A randomised controlled study is warranted.

Data on the efficacy and safety of the long-acting somatostatin analogue lanreotide (LAN) for postoperative dumping syndrome are lacking. We performed a double-blind, randomised and placebo-controlled crossover study of LAN Autogel® 90?mg in postoperative dumping. Adults with a positive prolonged oral glucose tolerance test or spontaneous hypoglycaemia and total dumping score (DS)?=?10 despite dietary measures were treated with three monthly injections of LAN or placebo in a randomised crossover fashion with an eight-week wash-out period. Primary outcome was the effect of LAN on total DS versus placebo. Secondary outcomes were the effect on early and late DS, treatment assessment, quality of life and safety. Of 24 included patients (66.7% female; age 49.1?±?2.1 years), 12 were randomised to LAN first. Pooled DS after three injections were lower compared to baseline after LAN (median=14 (interquartile range (IQR) 11.5–23) vs. median?=?22 (IQR 16–27); p?=?0.03) but not placebo (median?=?20 (IQR 15–27) vs. median?=?23 (IQR 13–29); p?=?0.15). Improvement of early (median?=?7.5 (IQR 4.5–13) vs. median?=?12 (IQR 9–16); p?=?0.03) but not late (median?=?7 (IQR 6–10.3) vs. median?=?9 (IQR 6–13); p?=?0.26) DS was seen. Overall treatment assessment correlated with change in DS (r?=?–0.69, p?=?0.004). Symptom improvement was not associated with changes in quality of life. Of the 81 reported adverse events, 44 occurred on LAN compared to 37 on placebo (p?>?0.05), with seven serious adverse events on LAN. LAN is effective for treating early postoperative dumping symptoms, although side effects are common and quality of life is not significantly affected.

Background Data on the efficacy and safety of the long-acting somatostatin analogue lanreotide (LAN) for postoperative dumping syndrome are lacking.Objective We performed a double-blind, randomised and placebo-controlled crossover study of LAN Autogel® 90 mg in postoperative dumping.Methods Adults with a positive prolonged oral glucose tolerance test or spontaneous hypoglycaemia and total dumping score (DS) ≥ 10 despite dietary measures were treated with three monthly injections of LAN or placebo in a randomised crossover fashion with an eight-week wash-out period. Primary outcome was the effect of LAN on total DS versus placebo. Secondary outcomes were the effect on early and late DS, treatment assessment, quality of life and safety.Results Of 24 included patients (66.7% female; age 49.1 ± 2.1 years), 12 were randomised to LAN first. Pooled DS after three injections were lower compared to baseline after LAN (median=14 (interquartile range (IQR) 11.5–23) vs. median = 22 (IQR 16–27); p= 0.03) but not placebo (median = 20 (IQR 15–27) vs. median = 23 (IQR 13–29); p= 0.15). Improvement of early (median = 7.5 (IQR 4.5–13) vs. median = 12 (IQR 9–16); p= 0.03) but not late (median = 7 (IQR 6–10.3) vs. median = 9 (IQR 6–13); p= 0.26) DS was seen. Overall treatment assessment correlated with change in DS (r= –0.69, p= 0.004). Symptom improvement was not associated with changes in quality of life. Of the 81 reported adverse events, 44 occurred on LAN compared to 37 on placebo (p> 0.05), with seven serious adverse events on LAN.Conclusions LAN is effective for treating early postoperative dumping symptoms, although side effects are common and quality of life is not significantly affected.

The article deals with the notions of deaccusative and antipassive reflexives. The term ‘deaccusative’ is used in the literature to refer to what appears to be a derivation reflexivizing a transitive verb and replacing its direct object with an oblique object. The term suggests a unitary operation, and its function has been identified, in recent work, as antipassive. The aim of this paper is to show that, though some ‘deaccusatives’ are antipassive, the group of verbs sometimes referred to as deaccusatives is, in fact, a heterogeneous conglomerate comprising a few minor constructions but also pairings of reflexive and non-reflexive verbs that are due to alternations in argument marking with specific lexical classes or simply to diachronic accident.

The article deals with the notion of so-called converse reflexives, illustrated from Slavic and Baltic. It is argued that, though the notion of reflexive converses, i. e. pairs of converses formally differentiated by the reflexive marker, is uncontroversial, that of converse reflexives as a subtype of reflexives (middles) and a distinct gram-type in voice typology, is mistaken, as the converse effect is the result not only of the reflexive derivation but also of several other factors, viz. argument conflation and complement-modifier indeterminacy. Basically, the so-called converse reflexives are just anticausatives.

Vedolizumab is a recently available monoclonal antibody targeting a4ß7 integrin for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD). The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April–September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician’s global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

Background Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD).Objective The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life.Methods A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April–September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician’s global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores.Results Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported.Conclusion Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

AbstractProsthetic valve endocarditis (PVE) is a serious infection with potentially fatal consequences. Early detection is crucial for successful management and outcome. The diagnosis of PVE is challenging and is based on the Duke criteria (DC) in which echocardiography plays a crucial role. However, transthoracic and transoesophageal echocardiography have less diagnostic value in PVE compared to native valve endocarditis. Combined computed tomography and fluorodeoxyglucose positron emission is a new technique providing improved diagnostic accuracy in PVE. This paper presents a case and reviews on the role of positron emission tomography/computed tomography in PVE.

Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive–compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4’s function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.

ObjectiveAlthough several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials.DesignMEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA).ResultsOf 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy.ConclusionsCurrent best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development.

Bile acids regulate the expression of intestinal bile acid transporters and are natural ligands for nuclear receptors controlling inflammation. Accumulating evidence suggests that signaling through these receptors is impaired in inflammatory bowel disease. We investigated whether tauroursodeoxycholic acid (TUDCA), a secondary bile acid with cytoprotective properties, regulates ileal nuclear receptor and bile acid transporter expression and assessed its therapeutic potential in an experimental model of Crohn’s disease (CD). Gene expression of the nuclear receptors farnesoid X receptor, pregnane X receptor and vitamin D receptor and the bile acid transporters apical sodium-dependent bile acid transporter and organic solute transporter α and β was analyzed in Caco-2 cell monolayers exposed to tumor necrosis factor (TNF)α, in ileal tissue of TNFΔARE/WTmice and in inflamed ileal biopsies from CD patients by quantitative real-time polymerase chain reaction. TNFΔARE/WTmice and wild-type littermates were treated with TUDCA or placebo for 11 weeks and ileal histopathology and expression of the aforementioned genes were determined. Exposing Caco-2 cell monolayers to TNFα impaired the mRNA expression of nuclear receptors and bile acid transporters, whereas co-incubation with TUDCA antagonized their downregulation. TNFΔARE/WTmice displayed altered ileal bile acid homeostasis that mimicked the situation in human CD ileitis. Administration of TUDCA attenuated ileitis and alleviated the downregulation of nuclear receptors and bile acid transporters in these mice. These results show that TUDCA protects bile acid homeostasis under inflammatory conditions and suppresses CD-like ileitis. Together with previous observations showing similar efficacy in experimental colitis, we conclude that TUDCA could be a promising therapeutic agent for inflammatory bowel disease, warranting a clinical trial.

Bile acids regulate the expression of intestinal bile acid transporters and are natural ligands for nuclear receptors controlling inflammation. Accumulating evidence suggests that signaling through these receptors is impaired in inflammatory bowel disease. We investigated whether tauroursodeoxycholic acid (TUDCA), a secondary bile acid with cytoprotective properties, regulates ileal nuclear receptor and bile acid transporter expression and assessed its therapeutic potential in an experimental model of Crohn's disease (CD). Gene expression of the nuclear receptors farnesoid X receptor, pregnane X receptor and vitamin D receptor and the bile acid transporters apical sodium-dependent bile acid transporter and organic solute transporter α and β was analyzed in Caco-2 cell monolayers exposed to tumor necrosis factor (TNF)α, in ileal tissue of TNFΔARE/WTmice and in inflamed ileal biopsies from CD patients by quantitative real-time polymerase chain reaction. TNFΔARE/WTmice and wild-type littermates were treated with TUDCA or placebo for 11 weeks and ileal histopathology and expression of the aforementioned genes were determined. Exposing Caco-2 cell monolayers to TNFα impaired the mRNA expression of nuclear receptors and bile acid transporters, whereas co-incubation with TUDCA antagonized their downregulation. TNFΔARE/WTmice displayed altered ileal bile acid homeostasis that mimicked the situation in human CD ileitis. Administration of TUDCA attenuated ileitis and alleviated the downregulation of nuclear receptors and bile acid transporters in these mice. These results show that TUDCA protects bile acid homeostasis under inflammatory conditions and suppresses CD-like ileitis. Together with previous observations showing similar efficacy in experimental colitis, we conclude that TUDCA could be a promising therapeutic agent for inflammatory bowel disease, warranting a clinical trial.

With only 5.1% of the population fully vaccinated against COVID-19, Tanzania has one of the lowest vaccination rates in the world and after two years of changing policies regarding the disease, the country struggles to get its vaccination campaign on the rails. In this study, we identify the determinants of COVID-19 vaccination willingness in two villages of the Mvomero district in Eastern Tanzania. Based on survey data, we performed univariate analyses to assess differences in vaccination intention for various social groups, and built a four-dimensional multivariate ordered logistic regression model that comprises respondents' personal and socioeconomic characteristics, the channels through which they get their information, their attitudes and perceptions towards COVID-19, and their social network embeddedness. Only 37.0% of the respondents indicated that they would be willing to get vaccinated against COVID-19. Vaccination willingness differed significantly according to gender, age, educational attainment and religion; with men, the elderly, people with post-secondary education and Catholics and Muslims more likely to accept a vaccine. Predictors of vaccination willingness were gender, age, social media and informal contacts as information sources, perceived effectiveness of the vaccine and of alternative medicine, fear of side effects, a general dislike of vaccines, and the proportion of vaccinated people and the highest value of trust in international organisations in one’s network. Although people’s attitudes and perceptions have the largest share of the explanatory value, our model shows that all four of our model’s building blocks were imperative in explaining vaccination willingness. Therefore, our paper presents a compelling case for the inclusion of respondents' social embeddedness as a common dimension for exploratory models of vaccination willingness.

Peroxisome proliferator-activated receptors (PPAR) play an important role in the regulation of lipid and glucose metabolism, inflammatory, and vascular responses. We show the effect of treatment with two PPAR agonists, fenofibrate (FF) and rosiglitazone (RSG), on ob/oband LDLR-double deficient mice, by combined gene-expression and metabolomic analyses. Male mice were daily treated for 12 weeks with RSG (10 mg·kg1–·day–1per os (p.o.), n= 8) and FF (50 mg·kg1–·day–1p.o., n= 8). Twelve untreated ob/oband LDLR-double deficient mice were used as controls. To integrate the transcriptomic and metabolomic results, we designed a hierarchical algorithm, based on the average linkage method in clustering. Data were also interpreted with the Ingenuity Pathway Analysis program. FF and RSG treatments significantly increased the hepatic triglyceride content in the liver when compared with the control group, and the treatments induced an increase in the number and size of hepatic lipid droplets. Both drugs simultaneously activate pro-steatotic and antisteatotic metabolic pathways with a well-ordered result of aggravation of the hepatic lipid accumulation. The present study is a cautionary note not only to researchers on the basic mechanism of the action of PPAR activators but also to the use of these compounds in clinical practice.

Hematogenous osteoarticular infections of the hand and the wrist in children with sickle cell anemia are rare and no specific studies for this location have been published.

The increasing prevalence of obesity has significant implications for healthcare, more particularly since it is a major risk factor for type 2 diabetes and cardiovascular diseases. However, not every obese patient is at the same risk of developing future metabolic and cardiovascular complications. Therefore, there is an urgent need for novel biomarkers for early identification of obese patients at high risk. Possible candidate biomarkers are microRNAs, which are highly conserved non-coding RNA molecules of approximately 22 nucleotides that exert post-transcriptional effects on gene expression. They are expressed in a tissue- and cell-type specific manner, play essential roles in many biological and pathological processes and are released in human peripheral blood in a disease-specific manner where they remain stable due to association with lipoprotein and phospholipids. All these characteristics suggest that they are putative diagnostic biomarkers. This review summarizes microRNAs with a functional role in the pathogenesis of atherosclerosis, myocardial infarction, ischemia/reperfusion injury and cardiac remodeling. It emphasizes those which have already been deregulated in association with obesity-related risk factors clustered in the metabolic syndrome. It demonstrates that several microRNAs which have been claimed to be biomarkers for cardiovascular diseases have already been deregulated in association with metabolic disorders prior to cardiovascular diseases. Finally, it summarizes which of these functionally validated microRNAs are deregulated in the circulation making them easily accessible for detection and thus into candidate biomarkers for early diagnosis of obesity-induced cardiovascular events.

Advanced traffic information systems can assist drivers in reducing their travel times by making better use of available road capacity. In assessing their practical applicability, however, it is important to assess the overhead that various advanced traffic information systems bring. This paper evaluates the communication overhead for a decentralized, delegate multi-agent system based advanced traffic information system and for a centralized system. We document the relationship between the communication overhead and travel time reduction for both systems. This analysis can help in weighing both factors when designing a practical traffic information system in a real-world scenario.Advanced traffic information systems can assist drivers in reducing their travel times by making better use of available road capacity. In assessing their practical applicability, however, it is important to assess the overhead that various advanced traffic information systems bring. This paper evaluates the communication overhead for a decentralized, delegate multi-agent system based advanced traffic information system and for a centralized system. We document the relationship between the communication overhead and travel time reduction for both systems. This analysis can help in weighing both factors when designing a practical traffic information system in a real-world scenario.

AbstractThe notion of interpretive deontics, based on that of interpretive use as defined by Sperber and Wilson (1986), was introduced in Holvoet and Konickaja (2011). The present article builds further on the results presented there. Starting out from the interpretive deontic uses of the Polish modal verb miećand establishing their connection with other uses of this verb, the author attempts to give a more complete picture of conceptual relations in the domain of deontic modality than was available until now. The investigation is based on the semantic map method.

This study provided insight into the degree of microbial contamination in the processing chain of prepacked (bagged) lettuce in two Belgian fresh-cut produce processing companies. The pathogens Salmonellaand Listeria monocytogeneswere not detected. Total psychrotrophic aerobic bacterial counts (TPACs) in water samples, fresh produce, and environmental samples suggested that the TPAC is not a good indicator of overall quality and best manufacturing practices during production and processing. Because of the high TPACs in the harvested lettuce crops, the process water becomes quickly contaminated, and subsequent TPACs do not change much throughout the production process of a batch. The hygiene indicator Escherichia coliwas used to assess the water management practices in these two companies in relation to food safety. Practices such as insufficient cleaning and disinfection of washing baths, irregular refilling of the produce wash baths with water of good microbial quality, and the use of high product/water ratios resulted in a rapid increase in E. coliin the processing water, with potential transfer to the end product (fresh-cut lettuce). The washing step in the production of fresh-cut lettuce was identified as a potential pathway for dispersion of microorganisms and introduction of E. colito the end product via cross-contamination. An intervention step to reduce microbial contamination is needed, particularly when no sanitizers are used as is the case in some European Union countries. Thus, from a food safety point of view proper water management (and its validation) is a critical point in the fresh-cut produce processing industry.

The mechanism for the obesity-asthma association is unknown. This study evaluated the hypothesis that systemic oxidant stress explains this association.

Plasma levels of lipoprotein-associated phospholipase A2(Lp-PLA2) and oxidized low density lipoprotein (oxLDL) have been identified as risk factors for cardiovascular disease. Lp-PLA2is the sole enzyme responsible for the hydrolysis of oxidized phospholipids on LDL particles in atherosclerotic plaques. We have studied the relationship between Lp-PLA2and oxLDL in carotid endarterectomy (CEA) tissues and in matched plasmas. In extracts from CEA anatomical segments, the levels of oxLDL were significantly associated with the levels of Lp-PLA2protein (r= 0.497) and activity (r= 0.615). OxLDL and Lp-PLA2mass/activity were most abundant in the carotid bifurcation and internal segments where plaque was most abundant. In extracts from CEA atheroma, the levels of oxLDL and Lp-PLA2were significantly correlated (r= 0.634). In matched plasma and atheroma extracts, the levels of Lp-PLA2were negatively correlated (r= − 0.578). The ratio of Lp-PLA2to oxLDL was higher in atheromatous tissue (277:1) than in normal tissue (135:1) and plasma (13:1). Immunohistochemical experiments indicated that in plaques, oxLDL and Lp-PLA2existed in overlapping but distinctly different distribution. Fluorescence microscopy showed both oxLDL and Lp-PLA2epitopes on the same LDL particle in plasma but not in plaque. These results suggest that the relationship between Lp-PLA2and oxLDL in the atherosclerotic plaque is different from that in the plasma compartment.

Plasma levels of lipoprotein-associated phospholipase A2(Lp-PLA2) and oxidized low density lipoprotein (oxLDL) have been identified as risk factors for cardiovascular disease. Lp-PLA2is the sole enzyme responsible for the hydrolysis of oxidized phospholipids on LDL particles in atherosclerotic plaques. We have studied the relationship between Lp-PLA2and oxLDL in carotid endarterectomy (CEA) tissues and in matched plasmas. In extracts from CEA anatomical segments, the levels of oxLDL were significantly associated with the levels of Lp-PLA2protein (r = 0.497) and activity (r = 0.615). OxLDL and Lp-PLA2mass/activity were most abundant in the carotid bifurcation and internal segments where plaque was most abundant. In extracts from CEA atheroma, the levels of oxLDL and Lp-PLA2were significantly correlated (r = 0.634). In matched plasma and atheroma extracts, the levels of Lp-PLA2were negatively correlated (r = – 0.578). The ratio of Lp-PLA2to oxLDL was higher in atheromatous tissue (277:1) than in normal tissue (135:1) and plasma (13:1). Immunohistochemical experiments indicated that in plaques, oxLDL and Lp-PLA2existed in overlapping but distinctly different distribution. Fluorescence microscopy showed both oxLDL and Lp-PLA2epitopes on the same LDL particle in plasma but not in plaque. These results suggest that the relationship between Lp-PLA2and oxLDL in the atherosclerotic plaque is different from that in the plasma compartment.

It is not well known which exercise intensity is needed to obtain blood pressure reductions in response to endurance training. We therefore compared the effect of training at lower and higher intensity on blood pressure, and, in addition on other cardiovascular risk factors, in at least 55-year-old sedentary men and women.

With many researchers in the Multi-Agent System (MAS) community, we share the opinion that too much of the quality and relevant research in the area of MAS is underrepresented in the development of complex distributed systems in practice today. In our experience, a Babylonic mismatch is a crucial factor in this fact – research on MAS profiles itself as an isolated community and, as such, may create artificial thresholds to convince mainstream software developers of its merits. We argue that integrating the concepts and techniques from agent-based software engineering within mainstream software engineering provides opportunities to amplify the industrial adoption of MAS. To ground this position, we discuss MAS engineering from the perspective of the software engineering area that we are most familiar with: software architecture.

•Co-education and learning are an essential principle of the ICA’s statement on Cooperative Identity.•Social embeddedness and social capital play a crucial role in promoting knowledge sharing and learning behaviour among cooperative members.•Knowledge-based and position-based hierarchies play prominent roles in information sharing and advice sharing.•Just being the leader in the collective does not earn members’ trust. Members seek help or collaborate with leaders who have the required knowledge and skills to solve their issues.

Pesticides are useful for agriculture because of their ability to protect crops against pests. At the same time, excessive loading of pesticides in water bodies can produce toxic conditions that harm sensitive aquatic species, and render the water unfit for human consumption. Therefore, measures need to be designed, evaluated and undertaken in order to reduce pesticide pollution. In this study we focus on the Nil catchment, a small basin situated in the centre of Belgium. The necessary database and a watershed model (Soil and Water Assessment Tool—SWAT) were available to simulate different agricultural management scenarios. In order to make the model accurately predict pesticide loading to the river and instream transport, it was necessary to make several modifications to the source code. Special attention was given to implement an estimator for point losses (e.g. cleaning of spray equipment) and droplet drift, and improve the representation of physical processes in filter strips. The closing of mass balances is also described. Once the model was modified and calibrated, it could be used to simulate the pesticide mitigation strategies and evaluate their effectiveness. The simulation results revealed that strip-cropping seems to be more efficient than the sowing of cover crops, contour farming, the construction of filter strips, a 40% reduction of point losses and finally conservation agriculture. Several recommendations are given for further improvement of SWAT for management use.

Automatic Guided Vehicles (AGVs) are fully automated vehicles that are able to transport goods in an industrial environment. To cope with new and future system requirements such as flexibility and openness, we have applied a situated Multiagent System (MAS) to develop a decentralised control architecture for AGV transportation systems. In this paper, we give an overview of the software architecture of the system and we zoom in on two specific concerns: transport assignment and collision avoidance. We discuss the evaluation of the software architecture and the test results obtained from realistic simulations and a demonstrator system that we have developed. The architectural design and development of this real-world application teaches us that the primary use of a situated MAS comes from the way in which it structures the software. In particular, the set of adaptive agents that coordinate through the environment allows us to shape the software architecture of the transport application to provide the required functionalities of the system and achieve the important quality goals of flexibility and openness.

Experience with a multiagent architecture for an industrial Automatic Guided Vehicle Transportation System (AGVTS) reveals a lack of support for relating and composing multiple views in architectural descriptions. This prevents separating concerns while maintaining a good overview of the architecture as a whole, hampering changeability. We argue for explicit support for relating and composing views. Concretely, we propose three types of relations that allow specifying and composing structural views. As validation, we extend xADL with concepts of relations and compositions. The usability and consequences of this extension are assessed in the context of the multiagent architecture for the AGVTS. We learn that the approach improves changeability by offering explicit support for (1) separating concerns in separate views and (2) composing the overall architecture. There is an additional cost of documenting relations. Nevertheless, documenting view relations gives rise to architectural descriptions that are more expressive and less ambiguous.

Background: Elevated oxidized low‐density lipoprotein (oxLDL) is associated with atherosclerosis and high cardiovascular risk. Previously, we identified 18 genes in coronary plaque macrophages of hypercholesterolemic pigs that correlated with plaque oxLDL. Objective: To determine which of these genes were differentially expressed in blood monocytes and correlated with blood and plaque oxLDL and with plaque complexity. Methods: RNA expression in monocytes of 27 hypercholesterolemic and 12 control pigs was analyzed with quantitative real‐time polymerase chain reaction. Results: Five of 12 genes with detectable expression in monocytes were overexpressed (at P<0.01 level) in blood monocytes of hypercholesterolemic pigs: ABCA1, SCD, IRF1, SDC2, and TLR2. ABCA1RNA expression in blood monocytes correlated with blood oxLDL, and its RNA and protein expression was increased prior to atherosclerotic plaque formation. Higher expression of ABCA1in monocytes was associated with higher plaque complexity and higher plaque oxLDL. Immunostaining of coronary plaques showed the association of ABCA1 with macrophages, lipids, and oxLDL; ABCA1 protein correlated with plaque oxLDL (R2 = 0.66; P<0.0001). In THP‐1 monocytes, oxLDL induced ABCA1expression. OxLDL‐induced foam cell generation in THP‐1 and human monocyte‐derived macrophages was associated with a further increase of ABCA1expression. Conclusions: The increase of ABCA1 in monocytes in association with blood oxLDL prior to atherosclerotic lesion formation and the association of higher ABCA1 with higher plaque complexity suggests that ABCA1 is an early biomarker of atherosclerosis. Studies in humans are warranted.

‘Takotsubo’ cardiomyopathy, more recently called transient left ventricular apical ballooning syndrome, is a recently described acute cardiac syndrome.This increasingly reported syndrome consists of an acute onset of transient extensive akinesia of the apical and mid-portions of the left ventricle, producing ballooning of the apex in systole in the absence of significant coronary artery disease.The syndrome is accompanied by angina-like chest pain, electrocardiographic changes and minimal release of cardiac enzymes and biomarker levels, mimicking an acute myocardial infarction and is often preceded by an episode of emotional or physical stress, which may play a key role in the pathogenesis of the disorder. However, the exact mechanism still remains unknown.We describe the history of an 83-year-old man presenting to the emergency department with clinical findings of acute myocardial infarction with ST-segment elevation in the precordial leads, but emergency coronarography showed no significant obstruction. Left ventricular angiography demonstrated the typical apical ballooning. ST-segment elevation in the precordial leads on the admission ECG resolved the day after, but new anginal chest pain was accompanied by transient ST-segment elevation in the inferior leads, suggesting multivessel coronary spasm. Awareness of the existence of the syndrome is important and should be considered in the differential diagnosis of patients presenting with an acute coronary syndrome.

Rubinstein–Taybi syndrome is a well‐characterized genetic syndrome caused by haploinsufficiency of CBP in a majority of individuals. In 10% of cases a microdeletion in 16p13.3 affecting CBP is detected. We report on a patient with a de novo 345–480 kb micro‐duplication the region, encompassing only CBP and TRAP1. This boy presented with various minor physical anomalies, moderate mental retardation, and an atrial septal defect, but none of the other typical characteristics of the Rubinstein–Taybi syndrome, such as the broad thumbs and first toes or facial characteristics. This finding implicates CBP as one of the causative genes for the trisomy 16p13 syndrome, and indicates this is a contiguous gene syndrome. © 2007 Wiley‐Liss, Inc.