| 1. |
- Seyed Khoei, Nazlisadat, et al.
(author)
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Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses
- 2020
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In: BMC Medicine. - : Springer Nature. - 1741-7015. ; 18:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).CONCLUSIONS: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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| 2. |
- Marto, João Pedro, et al.
(author)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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In: Neurology. - 1526-632X. ; 100:7
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Journal article (peer-reviewed)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 3. |
- Shoamanesh, Ashkan, et al.
(author)
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Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke) : an international, randomised, double-blind, placebo-controlled, phase 2b trial
- 2022
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In: The Lancet. - 0140-6736. ; 400:10357, s. 997-1007
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Journal article (peer-reviewed)abstract
- Background: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. Methods: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26–52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose–response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. Findings: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0–4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79–1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93–1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85–1·32]; t statistic –0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91–2·71]). Interpretation: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. Funding: Bayer AG.
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| 4. |
- Wahlund, Björn, et al.
(author)
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EEG data, fractal dimension and multivariate statistics
- 2010
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In: Journal of Computer Science and Engineering. - 2043-9091. ; 3:1, s. 10-16
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Journal article (peer-reviewed)abstract
- The objective of this paper is to discuss the concept of Inverse Problem, i.e. how to obtain information via data about a complex mathematical model. We propose that by merging ideas from applied mathematics with ideas from multivariate statistical inference it is possible to find solutions or good approximation of many complex scientific problems.
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| 5. |
- Janiszewska-Olszowska, Joanna, et al.
(author)
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Effect of orthodontic debonding and residual adhesive removal on 3D enamel microroughness.
- 2016
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In: PeerJ. - : Int Scientific Literature. - 2167-8359. ; 4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Termination of fixed orthodontic treatment is associated with bracket debonding and residual adhesive removal. These procedures increase enamel roughness to a degree that should depend on the tool used. Enamel roughening may be associated with bacterial retention and staining. However, a very limited data exists on the alteration of 3D enamel roughness resulting from the use of different tools for orthodontic clean-up.AIMS: 1. To perform a precise assessment of 3D enamel surface roughness resulting from residual adhesive removal following orthodontic debonding molar tubes. 2. To compare enamel surfaces resulting from the use of tungsten carbide bur, a one-step polisher and finisher and Adhesive Residue Remover.MATERIAL AND METHODS: Buccal surfaces of forty-five extracted human third molars were analysed using a confocal laser microscope at the magnification of 1080× and 3D roughness parameters were calculated. After 20 s etching, molar tubes were bonded, the teeth were stored in 0.9% saline solution for 24 hours and debonded. Residual adhesive was removed using in fifteen specimen each: a twelve-fluted tungsten carbide bur, a one-step finisher and polisher and Adhesive Residue Remover. Then, surface roughness analysis was repeated. Data normality was assessed using Shapiro-Wilk test. Analysis of variance (ANOVA) was used to compare between variables of normal distribution and for the latter-Kruskal-Wallis test.RESULTS: Sa (arithmetical mean height) was significantly different between the groups (p = 0, 01326); the smoothest and most repeatable surfaces were achieved using Adhesive Residue Remover. Similarly, Sq (root mean square height of the scale-limited surface) had the lowest and most homogenous values for Adhesive Residue Remover (p = 0, 01108). Sz (maximum height of the scale-limited surface) was statistically different between the groups (p = 0, 0327), however no statistically significant differences were found concerning Ssk (skewness of the scale-limited surface).DISCUSSION: Confocal laser microscopy allowed 3D surface analysis of enamel surface, avoiding the limitations of contact profilometry. Tungsten carbide burs are the most popular adhesive removing tools, however, the results of the present study indicate, that a one step polisher and finisher as well as Adhesive Residue Remover are less detrimental to the enamel. This is in agreement with a recent study based on direct 3D scanning enamel surface. It proved, that a one-step finisher and polisher as well as Adhesive Residue Remover are characterized by a similar effectiveness in removing residual remnants as tungsten carbide bur, but they remove significantly less enamel.CONCLUSION: Orthodontic debonding and removal of adhesive remnants increases enamel roughness. The smoothest surfaces were achieved using Adhesive Residue Remover, and the roughest using tungsten carbide bur.
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| 6. |
- Selbmann, Alex, et al.
(author)
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Process qualification, additive manufacturing, and postprocessing of a hydrogen peroxide/kerosene 6 kN aerospike breadboard engine
- 2024
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In: Journal of laser applications. - : Laser Institute of America. - 1042-346X .- 1938-1387. ; 36:1
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Journal article (peer-reviewed)abstract
- This contribution addresses the complete process chain of an annular aerospike breadboard engine fabricated by laser powder bed fusion using the nickel-based superalloy Inconel® 718. In order to qualify the material and process for this high-temperature application, an extensive material characterization campaign including density and roughness measurements, as well as tensile tests at room temperature, 700, and 900 °C, was conducted. In addition, various geometric features such as triangles, ellipses, and circular shapes were generated to determine the maximum unsupported overhang angle and geometrical accuracy. The results were taken into account in the design maturation of the manifold and the cooling channels of the aerospike breadboard engine. Postprocessing included heat treatment to increase mechanical properties, milling, turning, and eroding of interfaces to fulfill the geometrical tolerances, thermal barrier coating of thermally stressed surfaces for better protection of thermal loads, and laser welding of spike and shroud for the final assembly as well as quality assurance. This contribution goes beyond small density cubes and tensile samples and offers details on the iterations necessary for the successful printing of large complex shaped functional parts. The scientific question is how to verify the additive manufacturing process through tensile testing, simulation, and design iterations for complex geometries and reduce the number of failed prints.
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