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1. Sixty years later: A replication study of McGuire's first inoculation experiment

Author

Fransen, M.L., Mollen, S., Das, E., Vermeulen, I., Rains, S.A., Fransen, M.L., Mollen, S., Das, E., Vermeulen, I., and Rains, S.A.

Abstract

Item does not contain fulltext, Inoculation theory was introduced 60 years ago, after McGuire and Papageorgis (1961) published their first study on how resistance to persuasion can be induced. They demonstrated that people who are pre-exposed to weakened arguments against an attitude or position they currently hold (i.e., inoculated) are less affected by a subsequent strong counter-attitudinal message than people who are pre-exposed to arguments consistent with their attitude (i.e., supportive defense treatment) or to no arguments. Although these results significantly impacted both science and practice on a general level, rigid tests of the key theoretical propositions are lacking. We conducted a highly powered replication study (N = 679) and found that an inoculation treatment is more effective in increasing resistance toward persuasion compared to a supportive defense treatment and a no-treatment control condition. Our results were mostly consistent with McGuire and Papageorgis’s original work., 13 september 2023, 10 p.

Published
2023

2. Correction to Fransen et al. (2023)

Author

Fransen, M.L., Mollen, S., Das, E., Vermeulen, I., Rains, S.A., Fransen, M.L., Mollen, S., Das, E., Vermeulen, I., and Rains, S.A.

Abstract

Item does not contain fulltext, 1 p.

Published
2023

3. Effect of source type and protective message on the critical evaluation of news messages on Facebook: Randomized controlled trial in the Netherlands

Author

Folkvord, F., Snelting, F., Anschutz, D.J., Hartmann, T., Theben, A., Gunderson, L., Vermeulen, I., Lupiáñez-Villanueva, F., Folkvord, F., Snelting, F., Anschutz, D.J., Hartmann, T., Theben, A., Gunderson, L., Vermeulen, I., and Lupiáñez-Villanueva, F.

Abstract

Item does not contain fulltext, Background: Disinformation has become an increasing societal concern, especially due to the speed that news is shared in the digital era. In particular, disinformation in the health care sector can lead to serious casualties, as the current COVID-19 crisis clearly shows. Objective: The main aim of this study was to experimentally examine the effects of information about the source and a protective warning message on users’ critical evaluation of news items, as well as the perception of accuracy of the news item. Methods: A 3 (unreliable vs reliable vs no identified source) × 2 (with protective message vs without) between-subject design was conducted among 307 participants (mean age 29 (SD 10.9] years). Results: The results showed a significant effect of source information on critical evaluation. In addition, including a protective message did not significantly affect critical evaluation. The results showed no interaction between type of source and protective message on critical evaluation. Conclusions: Based on these results, it is questionable whether including protective messages to improve critical evaluation is a way to move forward and improve critical evaluation of health-related news items, although effective methodologies to tackle the spread of disinformation are highly needed. Trial Registration: ClinicalTrials.gov NCT05030883; https://clinicaltrials.gov/ct2/show/NCT05030883

Published
2022

7. Predictive power of screening for antibodies against insulinoma-associated protein 2 beta (IA-2β) and zinc transporter-8 to select first-degree relatives of type 1 diabetic patients with risk of rapid progression to clinical onset of the disease: implications for prevention trials

Author

De Grijse, J., Asanghanwa, M., Nouthe, B., Albrecher, N., Goubert, P., Vermeulen, I., Van Der Meeren, S., Decochez, K., Weets, I., Keymeulen, B., Lampasona, V., Wenzlau, J., Hutton, J. C., Pipeleers, D., Gorus, F. K., and the Belgian Diabetes Registry

Published
2010
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10. I Express and Therefore I Am: Lynn Hershman Leeson's (In)Visible and (Dis-)Embodied Constructed Identities

Author

Vermeulen, I., Trakilovic, M. (Thesis Advisor), Vermeulen, I., and Trakilovic, M. (Thesis Advisor)

Abstract

In this thesis I evaluate the role of the body, visuality and visibility in constituting identities by analysing The Dante Hotel and The Novalis Hotel, two art installations made by Lynn Hershman Leeson. The differences between the art installations characterize the shift from materiality and surveillance to digitality and dataveillance. Surveillance tactics rely on visibility and read the surveyed objects' bodies through their outward performed bodily inscriptions. In contemporary society, dataveillance processes have emerged. These mechanisms do not rely on visible bodies anymore but have the power to deduce identities from metadata. I investigate how this shift is emphasized in the art installations in which material and digital artefacts are deliberately arranged by Hershman Leeson in order to represent the identities of the former inhabitants. By anticipating processes of signification with regards to the inanimate objects, Hershman Leeson implies identities for the audience to infer. By departing from a poststructuralist methodological framework and using semiotics as research method, I deconstruct the socially constructed and naturalised relation between signs and its connotations upon which both surveillance and dataveillance mechanisms rely in order to construct their objects' identities. By using the concept of performativity, a concept specifically helpful in understanding how identity is founded on socially constructed conventions, and the concept of the simulacrum or hyperreal, a concept that is useful for understanding how socially constructed conventions are perpetuated, I show how contemporary dataveillance mechanisms reinforce the arbitrary relation between signs and meanings and create false notions of 'realities' and agency.

Published
2019

11. Assessment of an optimistic bias in social media messages

Author

Suzana Bašić, Spijkers, Benthe S., Ouwerkerk, J. W., Vermeulen, I. E., Guido van Koningsbruggen, Antske Fokkens, and Vermeulen, Ivar

Subjects
SDG 10 - Reduced Inequalities
Abstract

Consistent with psychological theory and research, in the present study we demonstrate that people display a generic optimistic bias by showing more positive sentiment in social media messages about the future rather than the past. In addition, we outline a method for evaluating the validity of the commercial monitoring tool used for the automated sentiment analysis, thereby assessing the usefulness of such a tool in web-based research into human behavior.

Published
2018

12. Simulation of Future Electric Vehicle Charging behavior: effects of transition from PHEV to FEV

Author

Vermeulen, I, Helmus, JR, Lees, M, van den Hoed, R, Kenniscentrum Techniek, Lectoraat Energie en Innovatie, and Urban Technology

Abstract

The Netherlands is a frontrunner in the field of public charging infrastructure, having a high number of public charging stations per electric vehicle (EV) in the world. During the early years of adoption (2012-2015) a large percentage of the EV fleet were Plugin Hybrid Electric Vehicles (PHEV)due to the subsidy scheme at that time. With an increasing number of Full Electric Vehicles (FEVs) on the market and a current subsidy scheme for FEV only, a transition of the EV fleet from PHEV to FEV is expected. This is hypothesized to have effect on charging behavior of the complete fleet, reason to understand better how PHEVs and FEVs differ in charging behavior and how this impacts charging infrastructure usage. In this paper, the effects of the transition of PHEV to FEV is simulated by extending an existing Agent Based Model. Results show important effects of this transition on charging infrastructure performance.

Published
2018

13. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with e coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance.

Author

Pollard J., Arabi Y., Athan E., Lorenc P., Baker P., Roberts L., Beatson S.A., Peleg A.Y., Harris-Brown T., Paterson D.L., McNamara J., Sieler R., Garlick J., Costa J., Roney J., Pratt N., Tabaja H., Kmeid J., Tayyar R., El Zein S., Jones S., Cowan R., Lin B., Rad B., MacMorran E., Dinleyici R., Istanbullu A., Ceylan B., Mert A., Hashhoush M., Dalwi T., Korman T., Azzam R., Birrell M., Hughes C., Khan S., Lau J., Lee L., Lim K., Lin Y.D., Lister D., New D., Rafiei N., Stewart J., Tai A., Trad M.A., Aye Yeung V., McBride S., Holland D., Hopkins C., Luey C., Taylor S., Morpeth S., Finney M., Martin M., Holland U., Ali J., Jureen R., Underwood N., Henderson A., Runnegar N., Slavin M., Robinson O., Rishu A., Shawkat S., Fish J., Chin Liew K., Newton P., Merelli M., Carnelutti A., Ussai S., Pecori D., Izharuddin E., Young B., Ding Y., Ram R., Kelly J., Joshi N., Richards G., Smith O., Alli A., Vermeulen I., Wright B., Grey C., Stewart A., Reddy D., Wasserman S., Richi H., Sultana K., Alanazi N., Bin Awad E., Franzetti F., Stolz A., De Kock E., Magongoa T., Dutoit M., Russo A., Dentone C., Eisen D., Heyer L., Harris P.N.A., Tambyah P.A., Lye D.C., Mo Y., Lee T.H., Yilmaz M., Alenazi T.H., Falcone M., Bassetti M., Righi E., Rogers B.A., Kanj S., Bhally H., Iredell J., Mendelson M., Boyles T.H., Looke D., Miyakis S., Walls G., Al Khamis M., Zikri A., Crowe A., Ingram P., Daneman N., Griffin P., Pollard J., Arabi Y., Athan E., Lorenc P., Baker P., Roberts L., Beatson S.A., Peleg A.Y., Harris-Brown T., Paterson D.L., McNamara J., Sieler R., Garlick J., Costa J., Roney J., Pratt N., Tabaja H., Kmeid J., Tayyar R., El Zein S., Jones S., Cowan R., Lin B., Rad B., MacMorran E., Dinleyici R., Istanbullu A., Ceylan B., Mert A., Hashhoush M., Dalwi T., Korman T., Azzam R., Birrell M., Hughes C., Khan S., Lau J., Lee L., Lim K., Lin Y.D., Lister D., New D., Rafiei N., Stewart J., Tai A., Trad M.A., Aye Yeung V., McBride S., Holland D., Hopkins C., Luey C., Taylor S., Morpeth S., Finney M., Martin M., Holland U., Ali J., Jureen R., Underwood N., Henderson A., Runnegar N., Slavin M., Robinson O., Rishu A., Shawkat S., Fish J., Chin Liew K., Newton P., Merelli M., Carnelutti A., Ussai S., Pecori D., Izharuddin E., Young B., Ding Y., Ram R., Kelly J., Joshi N., Richards G., Smith O., Alli A., Vermeulen I., Wright B., Grey C., Stewart A., Reddy D., Wasserman S., Richi H., Sultana K., Alanazi N., Bin Awad E., Franzetti F., Stolz A., De Kock E., Magongoa T., Dutoit M., Russo A., Dentone C., Eisen D., Heyer L., Harris P.N.A., Tambyah P.A., Lye D.C., Mo Y., Lee T.H., Yilmaz M., Alenazi T.H., Falcone M., Bassetti M., Righi E., Rogers B.A., Kanj S., Bhally H., Iredell J., Mendelson M., Boyles T.H., Looke D., Miyakis S., Walls G., Al Khamis M., Zikri A., Crowe A., Ingram P., Daneman N., and Griffin P.

Abstract

IMPORTANCE Extended-spectrum beta-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum beta-lactamase producers. OBJECTIVES To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae. DESIGN, SETTING, AND PARTICIPANTS Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. INTERVENTIONS Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. MAIN OUTCOMES AND MEASURES The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. RESULTS Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6

Published
2018

15. Predictive power of screening for antibodies against insulinoma-associated protein 2 beta (IA-2β) and zinc transporter-8 to select first-degree relatives of type 1 diabetic patients with risk of rapid progression to clinical onset of the disease: implications for prevention trials

Author

De Grijse, J, Asanghanwa, M, Nouthe, B, Albrecher, N, Goubert, P, Vermeulen, I, Vander Meeren, Sam, Decochez, K, Weets, I, Keymeulen, B, Lampasona, V, Wenzlau, J, Hutton, J C, Pipeleers, D, Gorus, F K, Belgian Diabetes Registry, Faculty of Medicine and Pharmacy, Pathology/molecular and cellular medicine, Faculty of Sciences and Bioengineering Sciences, Pathologic Biochemistry and Physiology, Internal Medicine Specializations, and Clinical sciences

Subjects
Adult, Male, Adolescent, autoantibodies, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Predictive Value of Tests, HLA-DQ Antigens, HLA-DQ, Internal Medicine, medicine, Humans, Insulin, Receptor-Like Protein Tyrosine Phosphatases, Class 8, Risk factor, First-degree relatives, Child, Cation Transport Proteins, Insulinoma, Family Health, Type 1 diabetes, business.industry, zinc, Autoantibody, medicine.disease, Diabetes Mellitus, Type 1, Zinc Transporter 8, Immunology, Female, business
Abstract

AIMS/HYPOTHESIS: We investigated whether screening for insulinoma-associated protein (IA-2) beta (IA-2beta) autoantibodies (IA-2betaA) and zinc transporter-8 (ZnT8) autoantibodies (ZnT8A) improves identification of first-degree relatives of type 1 diabetic patients with a high 5-year disease risk, which to date has been based on assays for insulin autoantibodies (IAA), GAD autoantibodies (GADA) and IA-2 autoantibodies (IA-2A). METHODS: IA-2betaA and ZnT8A (using a ZnT8 carboxy-terminal hybrid construct, CW-CR, carrying 325Arg and 325Trp) were determined by radiobinding assay in 409 IAA(+), GADA(+) and/or IA-2A(+) siblings or offspring (

Published
2009
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18. The logic of organizational markets: thinking through resource partitioning theory

Author

Vermeulen, I., Bruggeman, J., ILLC (FNWI/FGw), and ASSR (FMG)

Abstract

Resource partitioning theory claims that Increasing concentration enhances the life chances of specialist organizations. We systemati- cally think through this theory,specify implicit background assump- tions,sharpen concepts,and rigorously check the theory s logic.As a result,we increase the theory s explanatory power,and claim contrary to received opinion that under certain eneral conditions, resource partitioning and the proliferation of specialists can take place independently of organizational mass and relative size effects, size localized competition,diversifying consumer tastes, increasing number of dimensions of the resource space,and changing niche widths. Our analysis makes furthermore clear that specialist and generalist strategies are asymmetric, and shows that not concentration enhances the life chances of specialists but economies of scale instead.Under the conditions explicated,we argue that if scale economies come to dominate,the number of organizations in the population increases, regardless of the incumbents sizes.

Published
2001

19. Bildung bij McDowell: kritische reflectie in de Space of Reasons

Author

Vermeulen, I., Anderson, J. (Thesis Advisor), Lievers, M., Vermeulen, I., Anderson, J. (Thesis Advisor), and Lievers, M.

Abstract

Een oude vraag in de meta-ethiek is de vraag of ethische eigenschappen zich in de werkelijkheid bevinden, of een projectie zijn van onze geest op die werkelijkheid. John McDowell stelt een alternatief voor, volgens hem leren we in onze opvoeding om ethische eigenschappen waar te nemen in de werkelijkheid. Dit is een onderdeel van een fatsoenlijke opvoeding, waarbij we conceptuele vermogens aanleren, dit duidt hij aan met de term Bildung. In deze scriptie heb ik onderzocht wat een fatsoenlijke Bildung kan inhouden en wat een goede kritische dimensie kan zijn van waaruit we onze eigen ethische kijk op de werkelijkheid kunnen beoordelen.

Published
2012

20. The logic of organizational markets: thinking through resource partitioning theory

Author

Vermeulen, I., Bruggeman, J., and SOM Research Institute

Subjects
Niches (economie), Concurrentie, Markt, Logica, Organisatiesociologie, 85.08
Abstract

Resource partitioning theory claims that Increasing concentration enhances the life chances of specialist organizations. We systemati- cally think through this theory,specify implicit background assump- tions,sharpen concepts,and rigorously check the theory s logic.As a result,we increase the theory s explanatory power,and claim contrary to received opinion that under certain eneral conditions, resource partitioning and the proliferation of specialists can take place independently of organizational mass and relative size effects, size localized competition,diversifying consumer tastes, increasing number of dimensions of the resource space,and changing niche widths. Our analysis makes furthermore clear that specialist and generalist strategies are asymmetric, and shows that not concentration enhances the life chances of specialists but economies of scale instead.Under the conditions explicated,we argue that if scale economies come to dominate,the number of organizations in the population increases, regardless of the incumbents sizes.

Published
2000

21. Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pédiatrie, Vandemeulebroucke, E, Keymeulen, B, Decochez, K, Weets, I, De Block, C, Féry, F, Van de Velde, U, Vermeulen, I, De Pauw, P, Mathieu, C, Pipeleers, D G, Gorus, F K, Belgian Diabetes Registry, Beckers, Dominique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pédiatrie, Vandemeulebroucke, E, Keymeulen, B, Decochez, K, Weets, I, De Block, C, Féry, F, Van de Velde, U, Vermeulen, I, De Pauw, P, Mathieu, C, Pipeleers, D G, Gorus, F K, Belgian Diabetes Registry, and Beckers, Dominique

Abstract

The aim of the study was to investigate the use of hyperglycaemic clamp tests to identify individuals who will develop diabetes among insulinoma-associated protein-2 antibody (IA-2A)-positive first-degree relatives (IA-2A(+) FDRs) of type 1 diabetic patients. Hyperglycaemic clamps were performed in 17 non-diabetic IA-2A(+) FDRs aged 14 to 33 years and in 21 matched healthy volunteers (HVs). Insulin and C-peptide responses were measured during the first (5-10 min) and second (120-150 min) release phase, and after glucagon injection (150-160 min). Clamp-induced C-peptide release was compared with C-peptide release during OGTT. Seven (41%) FDRs developed diabetes 3-63 months after their initial clamp test. In all phases they had lower C-peptide responses than non-progressors (p < 0.05) and HVs (p < 0.002). All five FDRs with low first-phase release also had low second-phase release and developed diabetes 3-21 months later. Two of seven FDRs with normal first-phase but low second-phase release developed diabetes after 34 and 63 months, respectively. None of the five FDRs with normal C-peptide responses in all test phases has developed diabetes so far (follow-up 56 to 99 months). OGTT-induced C-peptide release also tended to be lower in progressors than in non-progressors or HVs, but there was less overlap in results between progressors and the other groups using the clamp. Clamp-derived functional variables stratify risk of diabetes in IA-2A(+) FDRs and may more consistently identify progressors than OGTT-derived variables. A low first-phase C-peptide response specifically predicts impending diabetes while a low second-phase response may reflect an earlier disease stage. ClinicalTrials.gov NCT00654121 The insulin trial was financially supported by Novo Nordisk Pharma nv.

Published
2010

23. The consequents of organizer ecologies: A logical formalization

Author

Kuilman, J., Vermeulen, I., Li, Jiatao, Kuilman, J., Vermeulen, I., and Li, Jiatao

Abstract

Density delay theory, which predicts that higher levels of competition at founding will lead organizations to have persistently higher failure rates throughout their existence, has traditionally been among the least contested theories in organizational ecology. A growing number of empirical studies, however, have failed to support the theory's predictions, suggesting that density delay in its current form apparently does not apply to all populations in all conditions. Rather than discarding the theory altogether, we apply insights from the burgeoning literature on pre-entry ecologies to make sense of this empirical anomaly and use logical formalization to synthesize arguments of both theory fragments in a single, logically sound framework. Our results suggest that the nature of the density delay effect depends to a large extent on the chosen observation window, and, possibly, a confounding with the number of organizers concurrently present in the pre-entry stages. In addition, we derive a number of testable hypotheses that should strengthen research on both density delay and pre-entry ecologies.

Published
2008

24. Natuurvriendelijke oevers met een natte strook: Een 1- of 2- dimensionale stromingsberekening voor de wateruitwisseling

Author

Vermeulen, I. (author) and Vermeulen, I. (author)

Abstract

Het onderzoek waarvan in dit rapport verslag is gedaan, had als doel 'het bepalen voor welke afmetingen van een natte strook van een natuurvriendelijke oever een 1- of 2-dimensionale stromingsberekening moet worden gemaakt'. Bij het aanleggen van een natuurvriendelijke oever met vooroeverconstructie worden berekeningen gemaakt om de wateruitwisseling van het kanaal met de natte strook te voorspellen. Momenteel worden deze berekeningen gemaakt met een speciaal, door de Dienst Weg- en Waterbouwkunde (DWW) ontwikkeld, programma PLONS. PLONS staat voor: Positionering en Lengteverdeling van de Openingen in de Natte Strook-verdediging. PLONS is gebaseerd op de 1-dimensionale lange golf vergelijkingen. PLONS is ontwikkeld voor de berekening van de waterbeweging in een natte strook. De toepassingsmogelijkheden zijn beperkt tot smalle stroken. Momenteel zijn natte stroken in de praktijk kort en smal, de golfbeweging kan in deze situatie als 1-dimensionaal geschematiseerd worden. Op grond van metingen mag aangenomen worden dat PLONS hiervoor voldoet. Echter de huidige ontwikkelingen leiden tot bredere stroken waardoor de verhouding lengte/breedte van de natte stroken kleiner wordt. Hier kan niet a priori aangenomen worden dat de golfbeweging een 1-dimensionale beweging is. Daarom is middels dit onderzoek nagegaan in hoeverre PLONS voor dergelijke stroken voldoet. Hiervoor is een vergelijking gemaakt tussen PLONS en een 2-dimensionaal programma, WAQUA. WAQUA is gebaseerd op de lange golf vergelijkingen in twee richtingen en geïntegreerd over de diepte. Om WAQUA te testen zijn bestaande natte stroken geschematiseerd in WAQUA. De berekeningen van WAQUA voor de waterstanden en de stroomsnelheden in de natte strook zijn vergeleken met metingen in het Noordhollands kanaal en Kanaal Wessem-Nederweert. Uit deze vergelijkingen blijkt dat voor vooroeverconstructies in de vorm van een damwand, een dichte dam met buizen of een doorlatende dam de berekeningsresultaten nagenoeg gelijk zijn, Hydraulic Engineering, Civil Engineering and Geosciences

Published
1996

25. Predictive power of screening for antibodies against insulinoma-associated protein 2 beta (IA-2β) and zinc transporter-8 to select first-degree relatives of type 1 diabetic patients with risk of rapid progression to clinical onset of the disease: implications for prevention trials

Author

Grijse, J., Asanghanwa, M., Nouthe, B., Albrecher, N., Goubert, P., Vermeulen, I., Meeren, S., Decochez, K., Weets, I., Keymeulen, B., Lampasona, V., Wenzlau, J., Hutton, J., Pipeleers, D., and Gorus, F.

Abstract

We investigated whether screening for insulinoma-associated protein (IA-2) beta (IA-2β) autoantibodies (IA-2βA) and zinc transporter-8 (ZnT8) autoantibodies (ZnT8A) improves identification of first-degree relatives of type 1 diabetic patients with a high 5-year disease risk, which to date has been based on assays for insulin autoantibodies (IAA), GAD autoantibodies (GADA) and IA-2 autoantibodies (IA-2A). IA-2βA and ZnT8A (using a ZnT8 carboxy-terminal hybrid construct, CW-CR, carrying 325Arg and 325Trp) were determined by radiobinding assay in 409 IAA+, GADA+ and/or IA-2A+ siblings or offspring (<40 years) of type 1 diabetic patients consecutively recruited by the Belgian Diabetes Registry. The median (interquartile range) age of the first-degree relatives was 12 (6–19) years. Of the first-degree relatives, 24% were IA-2A+ ( n = 97), 14% ( n = 59) IA-2βA+ and 20% ( n = 80) ZnT8A+. IA-2βA and ZnT8A were significantly ( p < 0.001) associated with IA-2A and prediabetes ( n = 86); in IA-2A− first-degree relatives ( n = 312) the presence of IA-2βA and ZnT8A was associated with an increased progression rate to diabetes ( p < 0.001). Positivity for IA-2A and/or ZnT8A emerged as the most sensitive combination of two markers to identify first-degree relatives with a 5-year progression rate to diabetes of 45% (survival analysis) and as strongest predictor of diabetes (Cox regression analysis). Omission of first-degree relatives protected by HLA-DQ genotypes or maternal diabetes reduced the group to be followed from n = 409 to n = 246 (40%) with minor loss in the number of prediabetic IA-2A+ or ZnT8A+ first-degree relatives identified ( n = 3). IA-2A+ and/or ZnT8A+ first-degree relatives may be the participants of choice in future secondary prevention trials with immunointervention in relatives of type 1 diabetic patients. [ABSTRACT FROM AUTHOR]

Published
2010
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26. Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients

Author

Vandemeulebroucke, E, Keymeulen, B, Decochez, K, Weets, I, De Block, C, Féry, F, Van de Velde, U, Vermeulen, I, De Pauw, P, Mathieu, C, Pipeleers, D G, Gorus, F K, Belgian Diabetes Registry, Beckers, Dominique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pédiatrie, Internal Medicine Specializations, Pathologic Biochemistry and Physiology, Public Health Sciences, Diabetes Pathology & Therapy, Diabetes Clinic, Faculty of Medicine and Pharmacy, Medical Biochemistry, and Pathology/molecular and cellular medicine

Subjects
Adult, medicine.medical_specialty, Diabetes risk, Adolescent, type 1 diabetes, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Risk Assessment, Diabetes mellitus genetics, chemistry.chemical_compound, Young Adult, clamp test, Reference Values, Internal medicine, Diabetes mellitus, HLA-DQ Antigens, Internal Medicine, medicine, Diabetes Mellitus, Humans, Insulin, Family, Risk factor, Medical History Taking, Autoantibodies, Type 1 diabetes, C-Peptide, business.industry, C-peptide, IA-2 antibody, Glucose clamp technique, medicine.disease, Diabetes Mellitus, Type 1, chemistry, Hyperglycemia, Immunology, Glucose Clamp Technique, Human medicine, business
Abstract

AIMS/HYPOTHESIS: The aim of the study was to investigate the use of hyperglycaemic clamp tests to identify individuals who will develop diabetes among insulinoma-associated protein-2 antibody (IA-2A)-positive first-degree relatives (IA-2A(+) FDRs) of type 1 diabetic patients. METHODS: Hyperglycaemic clamps were performed in 17 non-diabetic IA-2A(+) FDRs aged 14 to 33 years and in 21 matched healthy volunteers (HVs). Insulin and C-peptide responses were measured during the first (5-10 min) and second (120-150 min) release phase, and after glucagon injection (150-160 min). Clamp-induced C-peptide release was compared with C-peptide release during OGTT. RESULTS: Seven (41%) FDRs developed diabetes 3-63 months after their initial clamp test. In all phases they had lower C-peptide responses than non-progressors (p

27. Inhibition of intracellular versus extracellular cathepsin D differentially alters the liver lipidome of mice with metabolic dysfunction-associated steatohepatitis.

Author

Vermeulen I, Li M, van Mourik H, Yadati T, Eijkel G, Balluff B, Godschalk R, Temmerman L, Biessen EAL, Kulkarni A, Theys J, Houben T, Cillero-Pastor B, and Shiri-Sverdlov R

Abstract

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) progressing to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatic inflammation, has significantly increased in recent years due to unhealthy dietary practices and sedentary lifestyles. Cathepsin D (CTSD), a lysosomal protease involved in lipid homeostasis, is linked to abnormal lipid metabolism and inflammation in MASH. Although primarily intracellular, CTSD can be secreted extracellularly. Our previous proteomics research has shown that inhibition of extracellular CTSD results in more anti-inflammatory effects and fewer potential side effects compared to intracellular CTSD inhibition. However, the correlation between reduced side effects and alterations in the hepatic lipid composition remains unknown. This study aims to investigate the correlation between intra- and extracellular CTSD inhibition and potential alterations in the hepatic lipid composition in MASH. Low-density lipoprotein receptor knockout (Ldlr -/- ) mice were fed a high-fat diet for 10 weeks and received subcutaneous injections every 2 days of vehicle, intracellular CTSD inhibitor (GA-12), or extracellular CTSD inhibitor (CTD-002). Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize and compare the lipid composition in liver tissues. Hepatic phosphatidylcholine remodeling was observed with both inhibitors, suggesting their therapeutic potential in treating MASH. Treatment with an intracellular CTSD inhibitor resulted in elevated levels of cardiolipin, reactive oxygen species, phosphatidylinositol, phosphatidylethanolamine, and lipids that are linked to mitochondrial dysfunction and inflammation, and induced more oxidative stress. The observed modifications in lipid composition demonstrate the clinical advantages of extracellular CTSD inhibition as a potentially beneficial therapeutic approach for MASH., (© 2024 The Author(s). The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Published
2024
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28. Spatial omics reveals molecular changes in focal cortical dysplasia type II.

Author

Vermeulen I, Rodriguez-Alvarez N, François L, Viot D, Poosti F, Aronica E, Dedeurwaerdere S, Barton P, Cillero-Pastor B, and Heeren RMA

Subjects
Animals, Humans, Mice, Male, TOR Serine-Threonine Kinases metabolism, TOR Serine-Threonine Kinases genetics, Female, Disease Models, Animal, Brain metabolism, Brain pathology, Proteome metabolism, Focal Cortical Dysplasia, Malformations of Cortical Development, Group I genetics, Malformations of Cortical Development, Group I metabolism, Malformations of Cortical Development, Group I pathology, Proteomics, Epilepsy
Abstract

Focal cortical dysplasia (FCD) represents a group of diverse localized cortical lesions that are highly epileptogenic and occur due to abnormal brain development caused by genetic mutations, involving the mammalian target of rapamycin (mTOR). These somatic mutations lead to mosaicism in the affected brain, posing challenges to unravel the direct and indirect functional consequences of these mutations. To comprehensively characterize the impact of mTOR mutations on the brain, we employed here a multimodal approach in a preclinical mouse model of FCD type II (Rheb), focusing on spatial omics techniques to define the proteomic and lipidomic changes. Mass Spectrometry Imaging (MSI) combined with fluorescence imaging and label free proteomics, revealed insight into the brain's lipidome and proteome within the FCD type II affected region in the mouse model. MSI visualized disrupted neuronal migration and differential lipid distribution including a reduction in sulfatides in the FCD type II-affected region, which play a role in brain myelination. MSI-guided laser capture microdissection (LMD) was conducted on FCD type II and control regions, followed by label free proteomics, revealing changes in myelination pathways by oligodendrocytes. Surgical resections of FCD type IIb and postmortem human cortex were analyzed by bulk transcriptomics to unravel the interplay between genetic mutations and molecular changes in FCD type II. Our comparative analysis of protein pathways and enriched Gene Ontology pathways related to myelination in the FCD type II-affected mouse model and human FCD type IIb transcriptomics highlights the animal model's translational value. This dual approach, including mouse model proteomics and human transcriptomics strengthens our understanding of the functional consequences arising from somatic mutations in FCD type II, as well as the identification of pathways that may be used as therapeutic strategies in the future., Competing Interests: Declaration of competing interest Natalia Rodriguez-Alvarez, Liesbeth Francois, Delphine Viot, Stefanie Dedeurwaerdere and Patrick Barton were employed at UCB pharma at the time of the study, and some may have access to share/stock options. The remaining authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
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29. Effect of Source Type and Protective Message on the Critical Evaluation of News Messages on Facebook: Randomized Controlled Trial in the Netherlands.

Author

Folkvord F, Snelting F, Anschutz D, Hartmann T, Theben A, Gunderson L, Vermeulen I, and Lupiáñez-Villanueva F

Subjects
Adult, Humans, Netherlands, COVID-19 prevention & control, Social Media
Abstract

Background: Disinformation has become an increasing societal concern, especially due to the speed that news is shared in the digital era. In particular, disinformation in the health care sector can lead to serious casualties, as the current COVID-19 crisis clearly shows., Objective: The main aim of this study was to experimentally examine the effects of information about the source and a protective warning message on users' critical evaluation of news items, as well as the perception of accuracy of the news item., Methods: A 3 (unreliable vs reliable vs no identified source) × 2 (with protective message vs without) between-subject design was conducted among 307 participants (mean age 29 (SD 10.9] years)., Results: The results showed a significant effect of source information on critical evaluation. In addition, including a protective message did not significantly affect critical evaluation. The results showed no interaction between type of source and protective message on critical evaluation., Conclusions: Based on these results, it is questionable whether including protective messages to improve critical evaluation is a way to move forward and improve critical evaluation of health-related news items, although effective methodologies to tackle the spread of disinformation are highly needed., Trial Registration: ClinicalTrials.gov NCT05030883; https://clinicaltrials.gov/ct2/show/NCT05030883., (©Frans Folkvord, Freek Snelting, Doeschka Anschutz, Tilo Hartmann, Alexandra Theben, Laura Gunderson, Ivar Vermeulen, Francisco Lupiáñez-Villanueva. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 31.03.2022.)

Published
2022
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31. Mycolates of Mycobacterium tuberculosis modulate the flow of cholesterol for bacillary proliferation in murine macrophages.

Author

Vermeulen I, Baird M, Al-Dulayymi J, Smet M, Verschoor J, and Grooten J

Subjects
Animals, Cell Differentiation drug effects, Foam Cells drug effects, Foam Cells metabolism, Granuloma metabolism, Granuloma pathology, Humans, Lipid Droplets drug effects, Lipid Droplets metabolism, Lung metabolism, Lung pathology, Macrophages drug effects, Mice, Mycobacterium tuberculosis chemistry, Mycobacterium tuberculosis pathogenicity, Mycolic Acids chemical synthesis, Tuberculosis metabolism, Tuberculosis microbiology, Tuberculosis pathology, Cholesterol metabolism, Granuloma drug therapy, Macrophages metabolism, Mycolic Acids administration & dosage, Tuberculosis drug therapy
Abstract

The differentiation of macrophages into lipid-filled foam cells is a hallmark of the lung granuloma that forms in patients with active tuberculosis (TB). Mycolic acids (MAs), the abundant lipid virulence factors in the cell wall of Mycobacterium tuberculosis (Mtb), can induce this foam phenotype possibly as a way to perturb host cell lipid homeostasis to support the infection. It is not exactly clear how MAs allow differentiation of foam cells during Mtb infection. Here we investigated how chemically synthetic MAs, each with a defined stereochemistry similar to natural Mtb-associated mycolates, influence cell foamy phenotype and mycobacterial proliferation in murine host macrophages. Using light and laser-scanning-confocal microscopy, we assessed the influence of MA structure first on the induction of granuloma cell types, second on intracellular cholesterol accumulation, and finally on mycobacterial growth. While methoxy-MAs (mMAs) effected multi-vacuolar giant cell formation, keto-MAs (kMAs) induced abundant intracellular lipid droplets that were packed with esterified cholesterol. Macrophages from mice treated with kMA were permissive to mycobacterial growth, whereas cells from mMA treatment were not. This suggests a separate yet key involvement of oxygenated MAs in manipulating host cell lipid homeostasis to establish the state of TB., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

Published
2017
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32. Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.

Author

Van Dalem A, Demeester S, Balti EV, Keymeulen B, Gillard P, Lapauw B, De Block C, Abrams P, Weber E, Vermeulen I, De Pauw P, Pipeleers D, Weets I, and Gorus FK

Subjects
Adolescent, Adult, Autoantibodies blood, Child, Child, Preschool, Diabetes Mellitus, Type 1 pathology, Fasting, Female, Glucose Tolerance Test, Glycated Hemoglobin metabolism, Humans, Hyperglycemia pathology, Insulin blood, Insulin Resistance genetics, Insulin-Secreting Cells metabolism, Insulin-Secreting Cells pathology, Male, Prognosis, Regression Analysis, C-Peptide blood, Diabetes Mellitus, Type 1 blood, Hyperglycemia blood, Proinsulin blood
Abstract

Background: The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release., Methods: Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (AutoDelfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche). High-risk multiple autoantibody-positive first-degree relatives (n = 49; age 5-39) were tested for fasting PI:C, HOMA2-IR and hyperglycemic clamp and followed for 20-57 months (interquartile range)., Results: TT-TRFIA values for proinsulin, C-peptide and PI:C correlated significantly (r2 = 0.96-0.99; P<0.001) with results obtained with separate methods. TT-TRFIA achieved better between-day %CV for PI:C at three different levels (4.5-7.1 vs 6.7-9.5 for separate methods). In high-risk relatives fasting PI:C was significantly and inversely correlated (rs = -0.596; P<0.001) with first-phase C-peptide release during clamp (also with second phase release, only available for age 12-39 years; n = 31), but only after normalization for HOMA2-IR. In ROC- and Cox regression analysis, HOMA2-IR-corrected PI:C predicted 2-year progression to diabetes equally well as clamp-derived C-peptide release., Conclusions: The reproducibility of PI:C benefits from the automated simultaneous determination of both hormones. HOMA2-IR-corrected PI:C may serve as a minimally invasive alternative to the more tedious hyperglycemic clamp test., Competing Interests: The authors have declared that no competing interests exist.

Published
2016
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33. HLA-A*24 is an independent predictor of 5-year progression to diabetes in autoantibody-positive first-degree relatives of type 1 diabetic patients.

Author

Mbunwe E, Van der Auwera BJ, Vermeulen I, Demeester S, Van Dalem A, Balti EV, Van Aken S, Derdelinckx L, Dorchy H, De Schepper J, van Schravendijk C, Wenzlau JM, Hutton JC, Pipeleers D, Weets I, and Gorus FK

Subjects
Adolescent, Child, Diabetes Mellitus, Type 1 immunology, Female, HLA-A24 Antigen genetics, HLA-A24 Antigen metabolism, Humans, Male, Risk Factors, Young Adult, Autoantibodies blood, Diabetes Mellitus, Type 1 genetics, Genetic Predisposition to Disease, HLA-A24 Antigen blood
Abstract

We investigated whether HLA-A*24 typing complements screening for HLA-DQ and for antibodies (Abs) against insulin, GAD, IA-2 (IA-2A), and zinc transporter-8 (ZnT8A) for prediction of rapid progression to type 1 diabetes (T1D). Persistently Ab(+) siblings/offspring (n = 288; aged 0-39 years) of T1D patients were genotyped for HLA-DQA1-DQB1 and HLA-A*24 and monitored for development of diabetes within 5 years of first Ab(+). HLA-A*24 (P = 0.009), HLA-DQ2/DQ8 (P = 0.001), and positivity for IA-2A ± ZnT8A (P < 0.001) were associated with development of T1D in multivariate analysis. The 5-year risk increased with the number of the above three markers present (n = 0: 6%; n = 1: 18%; n = 2: 46%; n = 3: 100%). Positivity for one or more markers identified a subgroup of 171 (59%) containing 88% of rapid progressors. The combined presence of HLA-A*24 and IA-2A(+) ± ZnT8A(+) defined a subgroup of 18 (6%) with an 82% diabetes risk. Among IA-2A(+) ± ZnT8A(+) relatives, identification of HLA-A*24 carriers in addition to HLA-DQ2/DQ8 carriers increased screening sensitivity for relatives at high Ab- and HLA-inferred risk (64% progression; P = 0.002). In conclusion, HLA-A*24 independently predicts rapid progression to T1D in Ab(+) relatives and complements IA-2A, ZnT8A, and HLA-DQ2/DQ8 for identifying participants in immunointervention trials.

Published
2013
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34. Simultaneous measurement of plasma concentrations of proinsulin and C-peptide and their ratio with a trefoil-type time-resolved fluorescence immunoassay.

Author

De Pauw PE, Vermeulen I, Ubani OC, Truyen I, Vekens EM, van Genderen FT, De Grijse JW, Pipeleers DG, Van Schravendijk C, and Gorus FK

Subjects
Antibodies, Monoclonal, Autoantibodies blood, C-Peptide immunology, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 immunology, Fluorescent Antibody Technique, Humans, Proinsulin immunology, C-Peptide blood, Proinsulin blood
Abstract

Background: When the concentrations of 2 or more substances are measured separately, their molar ratios are subject to the additive imprecisions of the different assays. We hypothesized that the cumulative error for concentration ratios of peptides containing a common sequence might be minimized by measuring the peptides simultaneously with a "trefoil-type" immunoassay., Methods: As a model of this approach, we developed a dual-label time-resolved fluorescence immunoassay (TRFIA) to simultaneously measure proinsulin, C-peptide, and the proinsulin-C-peptide ratio (PI/C). A monoclonal antibody captures all C-peptide-containing molecules, and 2 differently labeled antibodies distinguish between proinsulin-like molecules and true C-peptide., Results: The trefoil-type TRFIA was capable of measuring plasma C-peptide and proinsulin simultaneously without mutual interference at limits of quantification of 48 and 8125 pmol/L, and 2.1 and 197 pmol/L, respectively. Within-laboratory imprecision values for the trefoil-type TRFIA ranged between 8.4% and 12% for the hormone concentrations. Unlike the hormone results obtained with separate assays, imprecision did not increase when PI/C was calculated from trefoil assay results (P < 0.05). Peptide concentrations were highly correlated with results obtained in individual comparison assays (r(2) > or = 0.965; P < 0.0001). The total error for PI/C obtained with the trefoil-type TRFIA remained < or = 25% over a broader C-peptide range than with separate hormone assays (79-7200 pmol/L vs 590-4300 pmol/L C-peptide). Preliminary data indicate little or no interference by heterophile antibodies., Conclusions: The developed trefoil-type TRFIA is a reliable method for simultaneous measurement of proinsulin, C-peptide, and PI/C and provides proof of principle for the development of other trefoil-type multiple-label immunoassays.

Published
2008
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