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5. The impact of the rs8005161 polymorphism on G protein-coupled receptor GPR65 (TDAG8) pH-associated activation in intestinal inflammation

Author

Tcymbarevich I, Eloranta J, Spalinger M, Cosin-Roger J, Lang S, Kullak-Ublick G, Wagner C, Seuwen K, Ruiz P, de Valliere C, Abdelrahman K, Ademi G, Aepli P, Thomas A, Anderegg C, Antonino A, Archanioti E, Arrigoni E, de Jong D, Balsiger B, Basturk P, Bauerfeind P, Becocci A, Belli D, Bengoa J, Biedermann L, Binek J, Blattmann M, Boehm S, Boldanova T, Borovicka J, Braegger C, Brand S, Brugger L, Brunner S, Buhr P, Burnand B, Burk S, Burri E, Buyse S, Cao D, Carstens O, Criblez D, Cunningham S, D'Angelo F, de Saussure P, Degen L, Delarive J, Doerig C, Dora B, Drerup S, Egger M, El-Wafa A, Engelmann M, Ezri J, Felley C, Fliegner M, Fournier N, Fraga M, Franc Y, Frei P, Frei R, Fried M, Froehlich F, Furlano R, Garzoni L, Geyer M, Girard L, Girardin M, Golay D, Good I, Bigler U, Gysi B, Haarer J, Halama M, Haldemann J, Heer P, Heimgartner B, Helbling B, Hengstler P, Herzog D, Hess C, Hessler R, Heyland K, Hinterleitner T, Hirschi C, Hruz P, Juillerat P, Khalid-de Bakker C, Kayser S, Keller C, Knellwolf-Grieger C, Knoblauch C, Kohler H, Koller R, Krieger-Grubel C, Kunzler P, Kusche R, Lehmann F, Macpherson A, Maillard M, Manz M, Marot A, Meier R, Meyenberger C, Meyer P, Michetti P, Misselwitz B, Mosler P, Mottet C, Muller C, Mullhaupt B, Musso L, Neagu M, Nichita C, Niess J, Nydegger A, Obialo N, Ollo D, Oropesa C, Peter U, Peternac D, Petit L, Pittet V, Pohl D, Porzner M, Preissler C, Raschle N, Rentsch R, Restellini A, Restellini S, Richterich J, Ris F, Risti B, Ritz M, Rogler G, Rohrich N, Rossel J, Rueger V, Rusticeanu M, Sagmeister M, Saner G, Sauter B, Sawatzki M, Scharl M, Schelling M, Schibli S, Schlauri H, Schluckebier D, Schmid D, Schmid-Uebelhart S, Schnegg J, Schoepfer A, Seematter V, Seibold F, Seirafi M, Semadeni G, Senning A, Sokollik C, Sommer J, Spalinger J, Spangenberger H, Stadler P, Staub P, Staudenmann D, Stenz V, Steuerwald M, Straumann A, Strebel B, Stulz A, Sulz M, Tatu A, Tempia-Caliera M, Thorens J, Truninger K, Tutuian R, Urfer P, Vavricka S, Viani F, Vogtlin J, Von Kanel R, Vouillamoz D, Vulliamy R, Wiesel P, Wiest R, Wohrle S, Zamora S, Zander S, Wylie T, Zeitz J, Zimmermann D, and Swiss IBD Cohort Study Grp

Subjects
UC, pH-sensing, cAMP, IBD, Acidic pH, RhoA, Inflammatory bowel diseases, CD
Abstract

BackgroundTissue inflammation in inflammatory bowel diseases (IBD) is associated with a decrease in local pH. The gene encoding G-protein-coupled receptor 65 (GPR65) has recently been reported to be a genetic risk factor for IBD. In response to extracellular acidification, proton activation of GPR65 stimulates cAMP and Rho signalling pathways. We aimed to analyse the clinical and functional relevance of the GPR65 associated single nucleotide polymorphism (SNP) rs8005161.Methods1138 individuals from a mixed cohort of IBD patients and healthy volunteers were genotyped for SNPs associated with GPR65 (rs8005161, rs3742704) and galactosylceramidase (rs1805078) by Taqman SNP assays. 2300 patients from the Swiss IBD Cohort Study (SIBDC) were genotyped for rs8005161 by mass spectrometry based SNP genotyping. IBD patients from the SIBDC carrying rs8005161 TT, CT, CC and non-IBD controls (CC) were recruited for functional studies. Human CD14+ cells were isolated from blood samples and subjected to an extracellular acidic pH shift, cAMP accumulation and RhoA activation were measured.ResultsIn our mixed cohort, but not in SIBDC patients, the minor variant rs8005161 was significantly associated with UC. In SIBDC patients, we observed a consistent trend in increased disease severity in patients carrying the rs8005161-TT and rs8005161-CT alleles. No significant differences were observed in the pH associated activation of cAMP production between IBD (TT, CT, WT/CC) and non-IBD (WT/CC) genotype carriers upon an acidic extracellular pH shift. However, we observed significantly impaired RhoA activation after an extracellular acidic pH shift in IBD patients, irrespective of the rs8005161 allele.ConclusionsThe T allele of rs8005161 might confer a more severe disease course in IBD patients. Human monocytes from IBD patients showed impaired pH associated RhoA activation upon an acidic pH shift.

Published
2019

6. Local lighting control in open-plan offices: the influence of office lay-out

Author

de Bakker, C., Aarts, M.P.J., Kort, H.S.M., Meier, Alan, Rosemann, A.L.P., Alexander, Thomas, Bagnara, Sebastiano, Tartaglia, Riccardo, Albolino, Sara, Fujita, Yushi, Health in the Built Environment, Building Lighting, and Building Performance

Subjects
Work performance, Architectural engineering, Computer science, User satisfaction, Control (management), Distraction, Open plan, Office workers, Work environment, Energy efficiency, Occupancy-based lighting control, SDG 7 - Affordable and Clean Energy, SDG 7 – Betaalbare en schone energie
Abstract

Highly granular lighting control involves switching on and off luminaires based on individual occupancy. The resulting high frequency of lighting changes can distract the office workers and negatively impact their work performance. In a cubicle office, this might be less of an issue than in an office without partitions, as users do not have an overview over the space here. We tested this control strategy in both office types and compared the results to determine the influence of office lay-out on the amount and acceptability of distractions that it poses. Our results indicated the opposite: occupants in the cubicle office were more often distracted and rated the distractions as less acceptable than in the bullpen office. As the job function types varied and the bullpen was consequently more dynamic, it seems that the type of work environment is of larger influence on users’ satisfaction with local lighting control. However, more research is required to confirm this finding.

Published
2018

10. Assessing the energy use of occupancy-based lighting control strategies in open-plan offices: a simulation tool

Author

de Bakker, C., van de Voort, Tom, van Duijnhoven, J., Rosemann, A.L.P., Guerrieri, Antonio, Fortino, Giancarlo, Vasilakos, Athanasios V., Zhou, MengChu, Lukszo, Zofia, Palau, Carlos, Liotta, Antonio, Vinci, Andrea, Basile, Francesco, Fanti, Maria Pia, Building Lighting, Built Environment, and Health in the Built Environment

Subjects
Energy consumption, Occupancy patterns, Convergence analysis, SDG 7 - Affordable and Clean Energy, Occupancy spread, Stochastic modelling
Abstract

Occupancy-based lighting control can be applied at several resolution levels. To aid lighting designers in choosing the appropriate solution for a specific open-plan office case, this paper presents a simulation tool which enables calculating the lighting energy use for the different control strategies. By using a stochastic modelling approach and input parameters as users’ function type, the office’s policy and special absences, the model could reflect the actual occupancy behaviour in the office at hand. The results of the model were validated with occupancy data from several studies and found to be similar enough to conclude that the model can be trusted and applied. A convergence analysis showed that 1000 iterations are required to produce these reliable results. This paper discusses the development of the tool, its performance as well as the deviations found between its output and measurements on the average occupancy of the different occupancy types. Further research on occupancy patterns of different job function types would improve the model as well as extend its applicability.

Published
2017

11. The feasibility of highly granular lighting control in open-plan offices: Exploring the comfort and energy saving potential

Author

de Bakker, C., Aarts, M.P.J., Kort, H.S.M., Rosemann, A.L.P., de Bakker, C., Aarts, M.P.J., Kort, H.S.M., and Rosemann, A.L.P.

Abstract

Highly granular lighting control reduces the energy consumption of shared office spaces by automatically controlling lighting at unoccupied desks. Typically, lighting is switched off, but this approach results in non-uniform illuminance distributions. In offices where individual work areas are often not separated by partitions and occupants oversee the entire office space, a dimming approach might be more comfortable. Therefore, this study tests the feasibility of a new concept that involves the use of different dimming levels in the task, surrounding, and background area. We evaluated this concept on both user comfort and the energy use through a user study in a controlled environment (final N = 25). From this work, we concluded that most users (68–84%) are comfortable with different dimming levels throughout a workspace. Initial energy calculations based on assumed activity patterns showed promising results for the four most extreme dimming scenarios (LDP reduction > 26%). We identified two conditions as most promising in achieving both energy savings and comfort, namely when the dimming level was at minimum in the background area of the office space. These findings encourage research to continue investigating individual occupancy-based dimming as it has high practical value in the increasing smart office environment.

Published
2018

12. The energy saving potential of occupancy-based lighting control strategies in open-plan offices: the influence of occupancy patterns

Author

de Bakker, C., van de Voort, Tom, Rosemann, A.L.P., de Bakker, C., van de Voort, Tom, and Rosemann, A.L.P.

Abstract

Occupancy-based lighting control strategies have been proven to be effective in diminishing offices’ energy consumption. These strategies have typically worked by controlling lighting at the room level but, recently, lighting systems have begun to be equipped with sensors on a more fine-grained level, enabling lighting control at the desk level. For some office cases, however, the savings gained using this strategy may not outweigh the costs and design efforts compared to room control. This is because, in some offices, individual occupancy patterns are similar, hence the difference in savings between desk and room control would be minimal. This study examined the influence of occupancy pattern variance within an office space on the relative energy savings of control strategies with different control zone sizes. We applied stochastic modeling to estimate the occupancy patterns, as this method can account for uncertainty. To validate our model, simulation results were compared to earlier studies and real measurements, which demonstrated that our simulations provided realistic occupancy patterns. Next, office cases varying in both job-function type distribution and office policy were investigated on energy savings potential to determine the influence of occupancy pattern variance. The relative energy savings potential of the different control strategies differed minimally for the test cases, suggesting that variations in individual occupancy patterns negligibly influence energy savings. In all cases, lighting control at the desk level showed a significantly higher energy savings potential than strategies with lower control zone granularity, suggesting that it is useful to implement occupancy-based lighting at the desk level in all office cases. This strategy should, thus, receive more attention from both researchers and lighting designers.

Published
2018

13. Geoepidemiology of Primary Biliary Cholangitis: Lessons from Switzerland

Author

Terziroli Beretta-Piccoli, B, Stirnimann, G, Cerny, A, Semela, D, Hessler, R, Helbling, B, Stickel, F, Kalid-de Bakker, C, Bihl, F, Giostra, E, Filipowicz Sinnreich, M, Oneta, C, Baserga, A, Invernizzi, P, Carbone, M, Mertens, J, Terziroli Beretta-Piccoli, B, Stirnimann, G, Cerny, A, Semela, D, Hessler, R, Helbling, B, Stickel, F, Kalid-de Bakker, C, Bihl, F, Giostra, E, Filipowicz Sinnreich, M, Oneta, C, Baserga, A, Invernizzi, P, Carbone, M, and Mertens, J

Abstract

No data on primary biliary cholangitis (PBC) are available in Switzerland. We established a national patient cohort to obtain information on PBC phenotypes and disease course in Switzerland. Local databases in all university hospitals and in two large secondary centers were searched for case finding. In addition, all primary care physicians, gastroenterologists, rheumatologists, and dermatologists were invited to contribute patients from their own medical records. PBC diagnosis was centrally reviewed. Five hundred one PBC patients were identified, 474 were included in data analysis, and 449 of them were enrolled by tertiary centers. The catchment area accounts for approximately one third of the Swiss population or approximately 2.8 million inhabitants. The median age at diagnosis was 53 years, 84% were women, and 86% were anti-mitochondrial antibody positive. The median follow-up was 5.4 years, 12.6% experienced a liver-related endpoint. Splenomegaly was present at diagnosis in one quarter of patients and in half of male patients. Approximately one third were non-responders to ursodeoxycholic acid (UDCA). The median transplant-free survival at 10 years was 85%. The following variables were independently associated with poor outcome: low platelet count at baseline (HR = 0.99, p < 0.0001), elevated alkaline phosphatase at baseline (HR = 1.36, p < 0.0001), elevated bilirubin at baseline (HR = 1.11, p = 0.001), and elevated alanine aminotransaminase (HR = 1.35, p = 0.04) after 12 months of UDCA therapy. The AUROC for the UK-PBC risk score at 5, 10, and 15 years was 0.82. The AUROC for the Globe score at 5, 10, and 15 years was 0.77. Patients included in this study are currently being enrolled in a prospective nationwide registry with biobank, taking advantage of the collaboration network generated by this study. Our study provides the first snapshot of PBC in Switzerland, describing a diagnostic delay with one quarter of patients diagnosed when already in the cirrhotic

Published
2018

15. Localized lighting in open-plan offices

Author

de Bakker, C., Aries, M.B.C., Kort, H.S.M., Rosemann, A.L.P., Building Lighting, Building Performance, and Health in the Built Environment

Subjects
Energy(all), Building and Construction, Psychology(all)
Abstract

Controlling lighting conditions at desk level has proven its energy savings potential. However, in open-plan offices without partitions separating desks this local control might come at expense of users’ comfort. An explorative study in an office building in the Netherlands revealed the influence of local control on users’ satisfaction with the lighting conditions compared to central control. Differences were found to be minimal (from .03 to .58 a 7-point scale), except for users’ satisfaction with the illuminance uniformity throughout the space. This measure was less satisfying with the localized lighting, especially with scenarios where constant background illuminance levels were limited (.81 less). A direct result from this study is the recommendation to use a dimming system when applying local lighting control. More research is however needed to further confirm the findings of this study.

Published
2016

16. Occupants' behaviour: an observation study for energy saving potential on lighting

Author

de Bakker, C., Aries, M.B.C., Kort, H.S.M., Rosemann, A.L.P., Building Lighting, Building Performance, and Health in the Built Environment

Subjects
occupancy sensors, energy consumption, occupancy patterns, lighting control, open office, office employees, SDG 7 - Affordable and Clean Energy
Abstract

Lighting tends to form a large part of the energy consumption in office buildings, which can be influenced by the use of sensors. Several sensor technologies have been developed throughout the years, like for example passive infrared systems. These are however limited in providing an understanding of occupants’ behaviour as they often only measure presence or absence. Chair sensors form one of the latest developments. Although these provide occupancy information on a relatively fine-grained level, it is still unknown to which extent they incorporate all occupants’ behaviour. Therefore, in this study occupants’ behaviour in an open office space was observed as well as measured with chair sensors. The results suggested that chair sensors are only suitable half of the time to control lighting at an individual level. Furthermore, it was found that it is possible to tailor the lighting further to occupants’ behaviour, and thus that even more energy can be saved on lighting use.

Published
2016

17. Praktische relevantie van verlichtingsstrategieën

Author

de Bakker, C., van Duijnhoven, J., Aries, M.B.C., Kort, H.S.M., Rosemann, A.L.P., Building Lighting, Building Performance, and Health in the Built Environment

Abstract

Het afgelopen decennium is ‘het nieuwe werken’ geïntroduceerd. Dit is een nieuwe manier van werken waarbij flexibiliteit centraal staat, zowel in tijden als locatie. Dit nieuwe principe heeft onder meer gezorgd voor een bredere toepassing van kantoortuinen. Een belangrijk kenmerk van dit kantoortype is dat werknemers de werkruimte delen met meerdere collega’s. Voorheen had elk individu een eigen kantoorruimte waar de verlichting gemakkelijk ingesteld kon worden naar zijn of haar eigen wensen. In een kantoortuin dient personeel rekening te houden met de wensen van collega’s.

Published
2016

21. Occupancy-based lighting control in open-plan office spaces: A state-of-the-art review

Author

de Bakker, C., Aries, M.B.C., Kort, H.S.M., Rosemann, A.L.P., de Bakker, C., Aries, M.B.C., Kort, H.S.M., and Rosemann, A.L.P.

Abstract

Lighting accounts for a significant amount of electrical energy consumption in office buildings, up to 45% of the total consumed. This energy consumption can be reduced by as much as 60% through an occupant-dependent lighting control strategy. With particular focus on open-plan offices, where the application of this strategy is more challenging to apply due to differences in individual occupancy patterns, this paper covers (1) to which extent individual occupancy-based lighting control has been tested, (2) developed, and (3) evaluated. Search terms were defined with use of three categories, namely ‘occupancy patterns’, ‘lighting control strategy’, and ‘office’. Relevant articles were selected by a structured search through key online scientific databases and journals. The 24 studies identified as eligible were evaluated on six criteria: (1) study characteristics, (2) office characteristics, (3) lighting system characteristics, (4) lighting control design, (5) post-occupancy evaluation, and (6) conclusions, and this was used to answer the research questions. It was concluded that the strategy has not been tested yet with field studies in open-plan offices, but that it needs further development before it can be applied in these type of offices. Although lighting currently tends to be controlled at workspace level, many aspects of the strategy can be further developed; there is potential to further increase energy savings on lighting within open-plan office spaces. Individual occupancy-based lighting control requires further validation, focussing on the factors influencing its energy savings, on its cost effectiveness, and on its acceptability for users.

Published
2017

23. On the application of wireless sensors and actuators network in existing buildings for occupancy detection and occupancy-driven lighting control

Author

Labeodan, T.M., de Bakker, C., Rosemann, A.L.P., Zeiler, W., Labeodan, T.M., de Bakker, C., Rosemann, A.L.P., and Zeiler, W.

Abstract

Buildings have in recent years been the target of a number of energy efficiency improvement strategies given that they are a major energy end-use sector in most countries. Whilst new buildings due to legislations, increasingly address sustainability and improved energy efficiency considerations, the refurbishment process of older buildings still presents a number of challenges. Advancement in Information and Communication Technology, particularly the application of low-cost Wireless Sensors and Actuators Network does however provide the opportunity to harness yet unrealized energy reduction in existing buildings. This paper presents results from an experimental study evaluating the performance and energy saving potentials of such off-the-shelve, low-cost wireless sensors and actuators network in an existing office building for occupancy detection and occupancy-driven lighting control. The study demonstrates that in addition to improved occupancy information obtainable from Wireless Sensors and Actuators Network, worthwhile savings in the energy consumption of the lighting systems can as well be achieved.

Published
2016

24. Automated blinds with light feedback to increase occupant satisfaction and energy saving

Author

Meerbeek, B.W., de Bakker, C., de Kort, Y.A.W., van Loenen, E.J., Bergman, T., Meerbeek, B.W., de Bakker, C., de Kort, Y.A.W., van Loenen, E.J., and Bergman, T.

Abstract

With the increase of building automation in the work environment, there is a risk that occupants lose their sense of control when decisions on environmental aspects such as temperature, electric lighting, and daylight are made by technology. This paper reports two experiments in which we investigated the effect of the level automation and the type of system expressiveness on users’ satisfaction with an automated blinds system installed on a virtual window. An expressive interface was designed to communicate the status and intentions of the blinds system to the building occupants. The results show that the addition of the expressive interface increased user satisfaction compared to the original system. Moreover, users made less corrections after automatic blind adjustments and adherence to the system suggestions increased. These results demonstrate the potential of expressive interfaces to increase user’s acceptance of automated blinds and thereby realizing the anticipated energy savings.

Published
2016

29. A novel classification of colorectal tumors based on microsatellite instability, the CpG island methylator phenotype and chromosomal instability: implications for prognosis

Author

Simons, C.C.J.M., Simons, C.C.J.M., Hughes, L. A. E., Smits, K. M., Khalid-de Bakker, C. A., de Bruine, A. P., Carvalho, B., Meijer, G. A., Schouten, L. J., van den Brandt, P. A., Weijenberg, M. P., van Engeland, M., Simons, C.C.J.M., Simons, C.C.J.M., Hughes, L. A. E., Smits, K. M., Khalid-de Bakker, C. A., de Bruine, A. P., Carvalho, B., Meijer, G. A., Schouten, L. J., van den Brandt, P. A., Weijenberg, M. P., and van Engeland, M.

Abstract

We studied the overlap between the major (epi)genomic events microsatellite instability (MSI), the CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) in colorectal cancer (CRC), and whether specific (epi)genotypes were associated with CRC-related deaths. Molecular analyses using tumor DNA were successful in 509 CRC cases identified within the Netherlands Cohort Study in the period 1989-1993. Follow-up for the vital status until May 2005 was 100%. MSI (12.6%), CIMP-only (5.3%), CIMP + CIN (13.4%), CIN-only (58.2%) and triple-negative tumors (10.6%) differed significantly regarding tumor localization, differentiation grade, initial adjuvant therapy (AT) use and genetic characteristics (P <0.03). CIMP-only, CIMP + CIN and triple-negative tumors, compared with CIN-only tumors, were significantly associated with a 3.67, 2.44 and 3.78-fold risk of CRC-related deaths after 2-year follow-up (95% confidence intervals, CIs, 1.70-7.91, 1.35-4.41 and 1.97-7.25, respectively), but not after late follow-up. MSI tumors were borderline significantly associated with a 0.40-fold risk of CRC-related deaths after late follow-up (95% CI 0.15-1.03). This is the first study to show that specific (epi)genotypes may hold a differential prognostic value that may vary over time. Although no specific treatment data were available, an explanation for the differential findings over time might be that (epi)genotypes modify therapy response.

Published
2013

35. Geoepidemiology of Primary Biliary Cholangitis: Lessons from Switzerland

Author

Benedetta Terziroli Beretta-Piccoli, Emiliano Giostra, Joachim C. Mertens, Carl Oneta, Felix Stickel, Andreas Cerny, Carolina Kalid-de Bakker, Florian Bihl, Guido Stirnimann, David Semela, Roxane Hessler, Adriana Baserga, Marco Carbone, Beat Helbling, Magdalena Filipowicz Sinnreich, Pietro Invernizzi, University of Zurich, Terziroli Beretta-Piccoli, Benedetta, Terziroli Beretta-Piccoli, B, Stirnimann, G, Cerny, A, Semela, D, Hessler, R, Helbling, B, Stickel, F, Kalid-de Bakker, C, Bihl, F, Giostra, E, Filipowicz Sinnreich, M, Oneta, C, Baserga, A, Invernizzi, P, Carbone, M, and Mertens, J

Subjects
Male, 0301 basic medicine, Delayed Diagnosis, Cholangitis, Cross-sectional study, Drug Resistance, UK-PBC risk score, Cohort Studies, 0302 clinical medicine, Risk Factors, MED/12 - GASTROENTEROLOGIA, Immunology and Allergy, 610 Medicine & health, ddc:616, education.field_of_study, Framingham Risk Score, ddc:617, Liver Cirrhosis, Biliary, Medical record, Ursodeoxycholic Acid, General Medicine, Middle Aged, Treatment Outcome, 10219 Clinic for Gastroenterology and Hepatology, Primary biliary cholangiti, Prospective registry, Cohort, 2723 Immunology and Allergy, Female, 030211 gastroenterology & hepatology, medicine.symptom, Cohort study, Switzerland, medicine.medical_specialty, Population, 03 medical and health sciences, Internal medicine, medicine, Humans, education, Retrospective Studies, business.industry, Globe score, Primary biliary cholangitis, Retrospective cohort study, Survival Analysis, Liver Transplantation, Elevated alkaline phosphatase, Cross-Sectional Studies, 030104 developmental biology, business, Follow-Up Studies
Abstract

No data on primary biliary cholangitis (PBC) are available in Switzerland. We established a national patient cohort to obtain information on PBC phenotypes and disease course in Switzerland. Local databases in all university hospitals and in two large secondary centers were searched for case finding. In addition, all primary care physicians, gastroenterologists, rheumatologists, and dermatologists were invited to contribute patients from their own medical records. PBC diagnosis was centrally reviewed. Five hundred one PBC patients were identified, 474 were included in data analysis, and 449 of them were enrolled by tertiary centers. The catchment area accounts for approximately one third of the Swiss population or approximately 2.8 million inhabitants. The median age at diagnosis was 53 years, 84% were women, and 86% were anti-mitochondrial antibody positive. The median follow-up was 5.4 years, 12.6% experienced a liver-related endpoint. Splenomegaly was present at diagnosis in one quarter of patients and in half of male patients. Approximately one third were non-responders to ursodeoxycholic acid (UDCA). The median transplant-free survival at 10 years was 85%. The following variables were independently associated with poor outcome: low platelet count at baseline (HR = 0.99, p

Published
2018
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36. Longitudinal bone microarchitectural changes are best detected using image registration.

Author

Kemp TD, de Bakker CMJ, Gabel L, Hanley DA, Billington EO, Burt LA, and Boyd SK

Subjects
Aged, Bone and Bones, Female, Humans, Male, Middle Aged, Tibia diagnostic imaging, Tomography, X-Ray Computed, Bone Density, Radius diagnostic imaging
Abstract

Longitudinal studies of bone using high-resolution medical imaging may result in non-physiological measurements of longitudinal changes. In this study, we determined that three-dimensional image processing techniques best capture realistic longitudinal changes in bone density and should therefore be used with high-resolution imaging when studying bone changes over time., Introduction: The purpose of this study was to determine which longitudinal analysis technique (no registration (NR), slice-match (SM) registration, or three-dimensional registration (3DR)) produced the most realistic longitudinal changes in a 3-year study of bone density and structure using high-resolution peripheral quantitative computed tomography (HR-pQCT)., Methods: We assessed HR-pQCT scans of the distal radius and tibia for men and women (N = 40) aged 55-70 years at baseline and 6, 12, 24, and 36 months. To evaluate which longitudinal analysis technique (NR, SM, or 3DR) best captured physiologically reasonable 3-year changes, we calculated the standard deviation of the absolute rate of change in each bone parameter. The data were compared between longitudinal analysis techniques using repeated measures ANOVA and post hoc analysis., Results: As expected, both SM and 3DR better captured physiological longitudinal changes than NR. At the tibia, there were no differences between SM and 3DR; however, at the radius where precision was lower, 3DR produced better results for total bone mineral density., Conclusions: At least SM or 3DR should be implemented in longitudinal studies using HR-pQCT. 3DR is preferable, particularly at the radius, to ensure that physiological changes in bone density are observed.

Published
2020
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37. Safety, tolerability, pharmacokinetics, and immunogenicity of a human monoclonal antibody targeting the G glycoprotein of henipaviruses in healthy adults: a first-in-human, randomised, controlled, phase 1 study.

Author

Playford EG, Munro T, Mahler SM, Elliott S, Gerometta M, Hoger KL, Jones ML, Griffin P, Lynch KD, Carroll H, El Saadi D, Gilmour ME, Hughes B, Hughes K, Huang E, de Bakker C, Klein R, Scher MG, Smith IL, Wang LF, Lambert SB, Dimitrov DS, Gray PP, and Broder CC

Subjects
Adult, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized immunology, Australia, Double-Blind Method, Female, Headache etiology, Humans, Infusions, Intravenous, Male, Antibodies, Monoclonal, Humanized pharmacokinetics, Glycoproteins immunology, Healthy Volunteers, Henipavirus immunology, Immunogenicity, Vaccine, Safety
Abstract

Background: The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults., Methods: In this double-blind, placebo-controlled, single-centre, dose-escalation, phase 1 trial of m102.4, we randomly assigned healthy adults aged 18-50 years with a body-mass index of 18·0-35·0 kg/m 2 to one of five cohorts. A sentinel pair for each cohort was randomly assigned to either m102.4 or placebo. The remaining participants in each cohort were randomly assigned (5:1) to receive m102.4 or placebo. Cohorts 1-4 received a single intravenous infusion of m102.4 at doses of 1 mg/kg (cohort 1), 3 mg/kg (cohort 2), 10 mg/kg (cohort 3), and 20 mg/kg (cohort 4), and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg 72 h apart and were monitored for 123 days. The primary outcomes were safety and tolerability. Secondary outcomes were pharmacokinetics and immunogenicity. Analyses were completed according to protocol. The study was registered on the Australian New Zealand Clinical Trials Registry, ACTRN12615000395538., Findings: Between March 27, 2015, and June 16, 2016, 40 (52%) of 77 healthy screened adults were enrolled in the study. Eight participants were assigned to each cohort (six received m102.4 and two received placebo). 86 treatment-emergent adverse events were reported, with similar rates between placebo and treatment groups. The most common treatment-related event was headache (12 [40%] of 30 participants in the combined m102.4 group, and three [30%] of ten participants in the pooled placebo group). No deaths or severe adverse events leading to study discontinuation occurred. Pharmacokinetics based on those receiving m102.4 (n=30) were linear, with a median half-life of 663·3 h (range 474·3-735·1) for cohort 1, 466·3 h (382·8-522·3) for cohort 2, 397·0 h (333·9-491·8) for cohort 3, and 466·7 h (351·0-889·6) for cohort 4. The elimination kinetics of those receiving repeated dosing (cohort 5) were similar to those of single-dose recipients (median elimination half-time 472·0 [385·6-592·0]). Anti-m102.4 antibodies were not detected at any time-point during the study., Interpretation: Single and repeated dosing of m102.4 were well tolerated and safe, displayed linear pharmacokinetics, and showed no evidence of an immunogenic response. This study will inform future dosing regimens for m102.4 to achieve prolonged exposure for systemic efficacy to prevent and treat henipavirus infections., Funding: Queensland Department of Health, the National Health and Medical Research Council, and the National Hendra Virus Research Program., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Published
2020
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38. A TetR-Family Protein (CAETHG&#95;0459) Activates Transcription From a New Promoter Motif Associated With Essential Genes for Autotrophic Growth in Acetogens.

Author

de Souza Pinto Lemgruber R, Valgepea K, Gonzalez Garcia RA, de Bakker C, Palfreyman RW, Tappel R, Köpke M, Simpson SD, Nielsen LK, and Marcellin E

Abstract

Acetogens can fix carbon (CO or CO 2 ) into acetyl-CoA via the Wood-Ljungdahl pathway (WLP) that also makes them attractive cell factories for the production of fuels and chemicals from waste feedstocks. Although most biochemical details of the WLP are well understood and systems-level characterization of acetogen metabolism has recently improved, key transcriptional features such as promoter motifs and transcriptional regulators are still unknown in acetogens. Here, we use differential RNA-sequencing to identify a previously undescribed promoter motif associated with essential genes for autotrophic growth of the model-acetogen Clostridium autoethanogenum . RNA polymerase was shown to bind to the new promoter motif using a DNA-binding protein assay and proteomics enabled the discovery of four candidates to potentially function directly in control of transcription of the WLP and other key genes of C 1 fixation metabolism. Next, in vivo experiments showed that a TetR-family transcriptional regulator (CAETHG&#95;0459) and the housekeeping sigma factor (σ A ) activate expression of a reporter protein (GFP) in-frame with the new promoter motif from a fusion vector in Escherichia coli . Lastly, a protein-protein interaction assay with the RNA polymerase (RNAP) shows that CAETHG&#95;0459 directly binds to the RNAP. Together, the data presented here advance the fundamental understanding of transcriptional regulation of C 1 fixation in acetogens and provide a strategy for improving the performance of gas-fermenting bacteria by genetic engineering., (Copyright © 2019 de Souza Pinto Lemgruber, Valgepea, Gonzalez Garcia, de Bakker, Palfreyman, Tappel, Köpke, Simpson, Nielsen and Marcellin.)

Published
2019
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39. Cardiopulmonary events during primary colonoscopy screening in an average risk population.

Author

Khalid-de Bakker CA, Jonkers DM, Hameeteman W, de Ridder RJ, Masclee AA, and Stockbrügger RW

Subjects
Aged, Colonoscopy instrumentation, Colonoscopy methods, Confidence Intervals, Conscious Sedation adverse effects, Early Detection of Cancer instrumentation, Early Detection of Cancer methods, Electrocardiography, Female, Humans, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Prospective Studies, Risk Assessment, Risk Factors, Bradycardia etiology, Colonoscopy adverse effects, Colorectal Neoplasms diagnosis, Early Detection of Cancer adverse effects, Hypotension etiology, Hypoxia etiology
Abstract

Background: Large colorectal cancer screening studies using primary colonoscopy have reported a low risk of major complications. Studies on diagnostic and therapeutic colonoscopy have pointed to a frequent occurrence of(minor) cardiopulmonary events, and with the steady increase of colonoscopy screening, it is important to investigate their occurrence in colonoscopy screening., Methods: This study describes the frequency of bradycardia(pulse rate <60 min-1), hypotension (systolic blood pressure(SB P) <90 mmHg), hypoxaemia (blood oxygenation, SaO2<90%) and ECG changes during colonoscopy screening in an average-risk population (hospital personnel, n=214,mean age 54.0±3.8, 39.3% male), without significant comorbidity) and aims at identifying subject-related and/or endoscopic factors associated with their occurrence. All data were collected prospectively. During 214 consecutive primary screening colonoscopies under conscious sedation(midazolam and pethidine), on top of pulse rate and SaO2,blood pressure and a three-channel ECG were recorded every five minutes., Results: No major complications or relevant ECG changes occurred. Hypoxaemia occurred in 119 (55.6%),hypotension in 19 (8.9%) and bradycardia in 12 subjects(5.6%). In multivariate analysis, the sedation level 3 increased the risk of hypoxaemia (OR 4.8, CI 1.7-13.7), and incomplete colonoscopy (OR 5.3, CI 1.6-18.1) was associated with hypotension. Subjects with bradycardia had a longer mean procedure time (38±12 vs. 29±12 min, p<0.05), which did not turn out as a risk factor in a multivariate analysis., Conclusions: Mainly procedure-related and not subject-related factors were found to be associated with the occurrence of cardiopulmonary events in primary colonoscopy screening in this relatively healthy screening population.

Published
2011

40. Opportunistic screening of hospital staff using primary colonoscopy: participation, discomfort and willingness to repeat the procedure.

Author

Khalid-de Bakker CA, Jonkers DM, Hameeteman W, de Ridder RJ, Masclee AA, and Stockbrügger RW

Subjects
Abdominal Pain etiology, Aged, Cathartics adverse effects, Chi-Square Distribution, Colonoscopy adverse effects, Female, Flatulence etiology, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Patient Participation psychology, Sex Factors, Surveys and Questionnaires, Time Factors, Colonoscopy psychology, Colorectal Neoplasms diagnosis, Patient Acceptance of Health Care psychology, Personnel, Hospital psychology
Abstract

Background: Participation in and tolerability of primary colonoscopy screening are presumed to be relatively low. The present study aimed to test its feasibility in a well-informed population of hospital staff using an intensive information campaign, and to identify factors associated with screening colonoscopy rated as uncomfortable., Methods: Data were collected using standardized forms., Results: Out of 1,090 invited employees (50-65 years), 447 (41.0%) participated. Bowel preparation and colonoscopy were rated as 'somewhat to very uncomfortable' by 79.5 and 21.9%, respectively. 96.3% of participants were willing to repeat colonoscopy in the future. Participants rating colonoscopy as uncomfortable were more likely unwilling to repeat the procedure (OR 8.026, CI 2.667-24.154). Multivariate analysis (age- and gender-adjusted) showed an association of colonoscopy rated as uncomfortable with: abdominal pain during colonoscopy (OR 3.185, CI 1.642-6.178), other pain (OR 2.428, CI 1.335-4.416), flatulence (OR 2.175, CI 1.219-3.881), embarrassment (OR 2.843, CI 1.350-5.989), abdominal pain after colonoscopy (OR 1.976, CI 1.041-3.751), and a prolonged procedure time (OR 1.000, CI 1.000-1.001)., Conclusions: Acceptance of primary colonoscopy screening for colorectal neoplasia was high, although participants with symptoms during and after colonoscopy were more likely to rate colonoscopy as uncomfortable. This type of opportunistic screening procedure is suitable for the introduction of screening programs and may be useful in areas that have no access to population-based screening., (Copyright © 2011 S. Karger AG, Basel.)

Published
2011
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41. Comparison of quantification methods of 111In-labelled platelet deposition in peripheral bypass grafts.

Author

Mortelmans L, Verbruggen A, De Bakker C, Vandecruys A, Joosten J, Nevelsteen A, Noyez L, Verstraete M, Vermylen J, and De Roo M

Subjects
Aged, Aorta, Thoracic surgery, Femoral Artery surgery, Humans, Middle Aged, Popliteal Artery surgery, Radionuclide Imaging, Arterial Occlusive Diseases surgery, Blood Platelets, Blood Vessel Prosthesis, Graft Occlusion, Vascular diagnostic imaging, Indium, Radioisotopes
Abstract

The action of antithrombotic drugs can be evaluated by measuring the deposition of 111In-labelled platelets on peripheral bypass grafts several days after injection. This evaluation can be performed qualitatively (visual interpretation on the daily images) or quantitatively. Four different methods which calculate the ratio of platelet uptake with a reference region are compared: two methods use a gamma camera and two a detector. A blood sample or the region under the sternal angle are used as reference. The daily ratio of the counts, recorded by a gamma camera in a region of interest covering the graft, and the blood radioactivity interpolated from a platelet survival curve appears to be the most reliable method. The information of all the ratios can be combined in a single thrombogenicity index which reflects the daily rise of a linear or exponential regression versus time.

Published
1987

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