46 research outputs found
Overcoming process-related barriers in modular high-rise building projects
Modular projects can be of higher quality, a safer, faster and more predictable construction process, and less environmental nuisance compared to a traditional on-site project. High-rise projects seem to be particularly suitable for modular building methods, however there are still some process-related barriers. Research so far has not focused on collaboration forms for modular high-rise projects. This paper examines which collaboration form fits best for a modular high-rise project by conducting an international case study research. From the case studies it is debatable whether the current PDMs meet the need for modular concepts; modular buildings will benefit more from a long-term collaboration with fixed partnerships. This requires a complete different approach to the construction industry. Until then, the best match should be sought by matching the customer profile to the PDM characteristics. The most suitable PDM is dependent on the client profile that can be determined by 17 selection criteria
The FOAM study : Is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial
This is an investigator initiated trial, VU medical center Amsterdam is the sponsor, contact information: prof. CJM de Groot, Department of Obstetrics and Gynaecology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands, Tel: +ā31-204444444. This study is funded by ZonMw, a Dutch organization for Health Research and Development, project number 837001504. ZonMW gives financial support for the whole project. IQ Medical Ventures provides the ExEm FOAMĀ® kits. The funding bodies have no role in the design of the study; collection, analysis, and interpretation of data; and in writing the manuscript.Peer reviewedPublisher PD
Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial
Funding Information: The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foamVR kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.Peer reviewedPublisher PD
B-cell targeting with anti-CD38 daratumumab:implications for differentiation and memory responses
B cellātargeted therapies, such as CD20-targeting mAbs, deplete B cells but do not target the autoantibody-producing plasma cells (PCs). PC-targeting therapies such as daratumumab (anti-CD38) form an attractive approach to treat PC-mediated diseases. CD38 possesses enzymatic and receptor capabilities, which may impact a range of cellular processes including proliferation and differentiation. However, very little is known whether and how CD38 targeting affects B-cell differentiation, in particular for humans beyond cancer settings. Using in-depth in vitro B-cell differentiation assays and signaling pathway analysis, we show that CD38 targeting with daratumumab demonstrated a significant decrease in proliferation, differentiation, and IgG production upon T cellādependent B-cell stimulation. We found no effect on T-cell activation or proliferation. Furthermore, we demonstrate that daratumumab attenuated the activation of NF-ĪŗB in B cells and the transcription of NF-ĪŗBātargeted genes. When culturing sorted B-cell subsets with daratumumab, the switched memory B-cell subset was primarily affected. Overall, these in vitro data elucidate novel non-depleting mechanisms by which daratumumab can disturb humoral immune responses. Affecting memory B cells, daratumumab may be used as a therapeutic approach in B cellāmediated diseases other than the currently targeted malignancies.</p
B-cell targeting with anti-CD38 daratumumab:implications for differentiation and memory responses
B cellātargeted therapies, such as CD20-targeting mAbs, deplete B cells but do not target the autoantibody-producing plasma cells (PCs). PC-targeting therapies such as daratumumab (anti-CD38) form an attractive approach to treat PC-mediated diseases. CD38 possesses enzymatic and receptor capabilities, which may impact a range of cellular processes including proliferation and differentiation. However, very little is known whether and how CD38 targeting affects B-cell differentiation, in particular for humans beyond cancer settings. Using in-depth in vitro B-cell differentiation assays and signaling pathway analysis, we show that CD38 targeting with daratumumab demonstrated a significant decrease in proliferation, differentiation, and IgG production upon T cellādependent B-cell stimulation. We found no effect on T-cell activation or proliferation. Furthermore, we demonstrate that daratumumab attenuated the activation of NF-?B in B cells and the transcription of NF-?Bātargeted genes. When culturing sorted B-cell subsets with daratumumab, the switched memory B-cell subset was primarily affected. Overall, these in vitro data elucidate novel non-depleting mechanisms by which daratumumab can disturb humoral immune responses. Affecting memory B cells, daratumumab may be used as a therapeutic approach in B cellāmediated diseases other than the currently targeted malignancies
Hysterosalpingo-foam sonography versus hysterosalpingography during fertility work-up: an economic evaluation alongside a randomized controlled trial
STUDY QUESTION: What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER: During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference ā1.2%, 95% CI: ā3.4% to 1.5%; PĀ¼ 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1160 infertile women (18ā41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategiesāmanagement based on HyfoSy results versus HSG resultsāthe estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference ā1.2%; 95% CI: ā3.4% to 1.5%). For the procedures itself, HyFoSy cost e136 and HSG e280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were e3307 for the HyFoSy strategy and e3427 for the HSG strategy (mean difference eā119; 95% CI: eā125 to eā114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was e10 042, meaning that by using HyFoSy instead of HSG we would save e10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION: When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS: Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S): FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEmĀ®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consultingāand travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746
An experimental study on the temperature dependence of CO2 explosive evaporation
The need for transportation and storage of CO2 in bulk quantities is likely to increase in the near future. The handling of CO2 on such scale gives rise to a number of technological challenges and safety aspects. The accidental rupture of a vessel containing liquefied CO2 may lead to a Boiling Liquid Expanding Vapour Explosion (BLEVE). Whether explosive evaporation of liquefied CO2 is also possible at storage temperatures below the homogeneous nucleation temperature 271 K (ā2 Ā°C) is unclear. This article describes the results of 12 experiments with 40 L CO2 cylinders at various temperatures to investigate the temperature dependence of explosive evaporation. The cylinders were opened with linear shaped charges to simulate a near instantaneous rupture, and blast was measured at various locations. The observed blast could be clearly attributed to explosive evaporation. The results show that below the homogeneous nucleation temperature, BLEVE blast does not disappear abruptly, but instead follows a gradual decay. Predictions with a numerical BLEVE blast model overestimate the observed blast peak overpressure and impulse, but qualitatively show a similar behaviour. The energy lost by the acceleration of the cylinder parts is a possible reason for overestimations of the model. The consequence of the test results is that for accident scenarios with CO2 at low temperatures a BLEVE should not be neglected in hazard assessments. Future large scale bulk storage will take place at a 105 times larger volume than the cylinders applied in the current small scale experiments. We expect that the blast-reducing effects of a tank shell will disappear at such scale. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007ā2013) under grant agreement nĀ° 241381
Two-year outcomes after conventional or endovascular repair of abdominal aortic aneurysms.
Contains fulltext :
49240.pdf (publisher's version ) (Open Access)BACKGROUND: Two randomized trials have shown better outcomes with elective endovascular repair of abdominal aortic aneurysms than with conventional open repair in the first month after the procedure. We investigated whether this advantage is sustained beyond the perioperative period. METHODS: We conducted a multicenter, randomized trial comparing open repair with endovascular repair in 351 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable candidates for both techniques. Survival after randomization was calculated with the use of Kaplan-Meier analysis and compared with the use of the log-rank test on an intention-to-treat-basis. RESULTS: Two years after randomization, the cumulative survival rates were 89.6 percent for open repair and 89.7 percent for endovascular repair (difference, -0.1 percentage point; 95 percent confidence interval, -6.8 to 6.7 percentage points). The cumulative rates of aneurysm-related death were 5.7 percent for open repair and 2.1 percent for endovascular repair (difference, 3.7 percentage points; 95 percent confidence interval, -0.5 to 7.9 percentage points). This advantage of endovascular repair over open repair was entirely accounted for by events occurring in the perioperative period, with no significant difference in subsequent aneurysm-related mortality. The rate of survival free of moderate or severe complications was also similar in the two groups at two years (at 65.9 percent for open repair and 65.6 percent for endovascular repair; difference, 0.3 percentage point; 95 percent confidence interval, -10.0 to 10.6 percentage points). CONCLUSIONS: The perioperative survival advantage with endovascular repair as compared with open repair is not sustained after the first postoperative year
Process Designs for Converting Propylene Glycol to Acrylic Acid via Lactic Acid and Allyl Alcohol
The chemical industry is currently facing the challenge of developing biobased production processes suitable for a more sustainable chemical industry. Acrylic acid produced from monopropylene glycol is a good candidate to become a cost-competitive and sustainable platform chemical. The propylene glycol price is expected to drop due to the expected abundance of propylene glycol as a sugar hydrogenolysis byproduct, which is required to make the conversion to acrylic acid cost-competitive. Two different processes for the conversion of propylene glycol to acrylic acid are evaluated in this work, either by (1) low temperature oxidation of propylene glycol to lactic acid and high temperature dehydration to acrylic acid or by (2) high temperature dehydration of propylene glycol to allyl alcohol and further high temperature oxidation to acrylic acid. Liquid-liquid extraction was found to be a key operation in both production processes. At similar overall yields, the allyl alcohol route appears inherently favored, as a result of the opportunity to integrate the reaction heat available at high temperature. To conclude, the price of propylene glycol has to drop by 45-55% to make the biobased production of acrylic acid from propylene glycol economically feasible