| 1. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 3. |
- George, T. S., et al.
(författare)
-
Organic phosphorus in the terrestrial environment : a perspective on the state of the art and future priorities
- 2018
-
Ingår i: Plant and Soil. - : Springer Netherlands. - 0032-079X .- 1573-5036. ; 427:1-2, s. 191-208
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The dynamics of phosphorus (P) in the environment is important for regulating nutrient cycles in natural and managed ecosystems and an integral part in assessing biological resilience against environmental change. Organic P (P-o) compounds play key roles in biological and ecosystems function in the terrestrial environment being critical to cell function, growth and reproduction.Scope: We asked a group of experts to consider the global issues associated with P-o in the terrestrial environment, methodological strengths and weaknesses, benefits to be gained from understanding the P-o cycle, and to set priorities for P-o research.Conclusions: We identified seven key opportunities for P-o research including: the need for integrated, quality controlled and functionally based methodologies; assessment of stoichiometry with other elements in organic matter; understanding the dynamics of P-o in natural and managed systems; the role of microorganisms in controlling P-o cycles; the implications of nanoparticles in the environment and the need for better modelling and communication of the research. Each priority is discussed and a statement of intent for the P-o research community is made that highlights there are key contributions to be made toward understanding biogeochemical cycles, dynamics and function of natural ecosystems and the management of agricultural systems.
|
|
| 4. |
- Korenblik, R., et al.
(författare)
-
Dragon 1 Protocol Manuscript : Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy
- 2022
-
Ingår i: Cardiovascular and Interventional Radiology. - : Springer. - 0174-1551 .- 1432-086X. ; 45, s. 1391-1398
-
Tidskriftsartikel (refereegranskat)abstract
- Study Purpose The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. Methods The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Results Not applicable. Conclusion DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR.
|
|
| 5. |
- Horwich, A, et al.
(författare)
-
EAU–ESMO consensus statements on the management of advanced and variant bladder cancer - an international collaborative multi-stakeholder effort : under the auspices of the EAU and ESMO Guidelines Committees
- 2019
-
Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:11, s. 1697-1727
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
|
|
| 6. |
- Bilous, A. V., et al.
(författare)
-
Dual-frequency single-pulse study of PSR B0950+08
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
-
Tidskriftsartikel (refereegranskat)abstract
- PSR B0950+08 is a bright nonrecycled pulsar whose single-pulse fluence variability is reportedly large. Based on observations at two widely separated frequencies, 55 MHz (NenuFAR) and 1.4 GHz (Westerbork Synthesis Radio Telescope), we review the properties of these single pulses. We conclude that they are more similar to ordinary pulses of radio emission than to a special kind of short and bright giant pulses, observed from only a handful of pulsars. We argue that a temporal variation of the properties of the interstellar medium along the line of sight to this nearby pulsar, namely the fluctuating size of the decorrelation bandwidth of diffractive scintillation makes an important contribution to the observed single-pulse fluence variability. We further present interesting structures in the low-frequency single-pulse spectra that resemble the "sad trombones"seen in fast radio bursts (FRBs); although for PSR B0950+08 the upward frequency drift is also routinely present. We explain these spectral features with radius-to-frequency mapping, similar to the model developed by Wang et al. (2019, ApJ, 876, L15) for FRBs. Finally, we speculate that μs-scale fluence variability of the general pulsar population remains poorly known, and that its further study may bring important clues about the nature of FRBs.
|
|
| 7. |
- Smits, KM, et al.
(författare)
-
Association of metabolic gene polymorphisms with tobacco consumption in healthy controls
- 2004
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 110:2, s. 266-270
-
Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the association between polymorphisms in several metabolic genes and the consumption of tobacco in a large sample of healthy individuals. The database of the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens was used. All the individuals who were controls from the case-control studies included in the data set with information on smoking habits and on genetic polymorphisms were selected (n = 20,938). Sufficient information was available on the following genes that are involved in the metabolism of tobacco smoke constituents: CYPIAI, GSTMI, GSTTI, NAT2 and GSTPI. None of the tested genes was clearly associated with smoking behavior. Information on smoking dose, available for a subset of subjects, showed no effect of metabolic gene polymorphisms on the amount of smoking. No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected.
|
|
| 8. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
-
Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
-
Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
|
|
| 9. |
- Murray, Alison E., et al.
(författare)
-
Roadmap for naming uncultivated Archaea and Bacteria
- 2020
-
Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
-
Tidskriftsartikel (refereegranskat)abstract
- The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
|
|
| 10. |
- van Cappellen, W., et al.
(författare)
-
Apertif: Phased array feeds for the Westerbork Synthesis Radio Telescope: System overview and performance characteristics
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
-
Tidskriftsartikel (refereegranskat)abstract
- We describe the APERture Tile In Focus (Apertif) system, a phased array feed (PAF) upgrade of the Westerbork Synthesis Radio Telescope that transforms this telescope into a high-sensitivity, wide-field-of-view L-band imaging and transient survey instrument. Using novel PAF technology, up to 40 partially overlapping beams are formed on the sky simultaneously, significantly increasing the survey speed of the telescope. With this upgraded instrument, an imaging survey covering an area of 2300 deg2 is being performed that will deliver both continuum and spectral line datasets, of which the first data have been publicly released. In addition, a time domain transient and pulsar survey covering 15 000 deg2 is in progress. An overview of the Apertif science drivers, hardware, and software of the upgraded telescope is presented, along with its key performance characteristics.
|
|
| 11. |
- Greer, M., et al.
(författare)
-
Lung transplantation after allogeneic stem cell transplantation: a pan-European experience
- 2018
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 51:2
-
Tidskriftsartikel (refereegranskat)abstract
- Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT. SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed. Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p<0.001) the leading risk factor. No SCT-specific risk factors were identified. Recurring malignancy occurred in four patients (4%). Lung transplantation <2 years post-SCT increased all-cause 1-year mortality (HR 7.5, 95% CI 2.3-23.8; p=0.001). Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.
|
|
| 12. |
- Smits, L. P., et al.
(författare)
-
Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome
- 2018
-
Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 7:7
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundIntestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. Methods and ResultsWe performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2weeks thereafter, we determined the ability to produce TMAO from d(6)-choline and d(3)-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. F-18-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as exvivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic F-18-fluorodeoxyglucose uptake, or exvivo cytokine production from peripheral blood mononuclear cells. ConclusionsSingle lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation.
|
|
| 13. |
|
|
| 14. |
- Adams, E. A. K., et al.
(författare)
-
First release of Apertif imaging survey data
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Apertif is a phased-array feed system for the Westerbork Synthesis Radio Telescope, providing forty instantaneous beams over 300 MHz of bandwidth. A dedicated survey program utilizing this upgrade started on 1 July 2019, with the last observations taken on 28 February 2022. The imaging survey component provides radio continuum, polarization, and spectral line data. Aims. Public release of data is critical for maximizing the legacy of a survey. Toward that end, we describe the release of data products from the first year of survey operations, through 30 June 2020. In particular, we focus on defining quality control metrics for the processed data products. Methods. The Apertif imaging pipeline, Apercal, automatically produces non-primary beam corrected continuum images, polarization images and cubes, and uncleaned spectral line and dirty beam cubes for each beam of an Apertif imaging observation. For this release, processed data products are considered on a beam-by-beam basis within an observation. We validate the continuum images by using metrics that identify deviations from Gaussian noise in the residual images. If the continuum image passes validation, we release all processed data products for a given beam. We apply further validation to the polarization and line data products and provide flags indicating the quality of those data products. Results. We release all raw observational data from the first year of survey observations, for a total of 221 observations of 160 independent target fields, covering approximately one thousand square degrees of sky. Images and cubes are released on a per beam basis, and 3374 beams (of 7640 considered) are released. The median noise in the continuum images is 41.4 uJy beam(-1), with a slightly lower median noise of 36.9 uJy beam(-1) in the Stokes V polarization image. The median angular resolution is 11.6 ''/sin delta. The median noise for all line cubes, with a spectral resolution of 36.6 kHz, is 1.6 mJy beam(-1), corresponding to a 3-sigma H i column density sensitivity of 1.8 x 10(20) atoms cm(-2) over 20 km s(-1) (for a median angular resolution of 24 '' x 15 ''). Line cubes at lower frequency have slightly higher noise values, consistent with the global RFI environment and overall Apertif system performance. We also provide primary beam images for each individual Apertif compound beam. The data are made accessible using a Virtual Observatory interface and can be queried using a variety of standard tools.
|
|
| 15. |
- Capodanno, Davide, et al.
(författare)
-
Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease : A Consensus Document from the Academic Research Consortium
- 2023
-
Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 147:25, s. 1933-1944
-
Tidskriftsartikel (refereegranskat)abstract
- Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.
|
|
| 16. |
|
|
| 17. |
- Anguille, Sébastien, et al.
(författare)
-
Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia
- 2017
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:15, s. 1713-1721
-
Tidskriftsartikel (refereegranskat)abstract
- Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P 5 .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age £65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD81 T cells. Long-term OS was correlated with interferon-g1 and tumor necrosis factor-a1 WT1-specific responses in delayed-type hypersensitivity-infiltrating CD81 T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD81 T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224.
|
|
| 18. |
- Boon, Hanneke, 1981-, et al.
(författare)
-
Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients
- 2008
-
Ingår i: Diabetologia. - Heidelberg : Springer Berlin/Heidelberg. - 0012-186X .- 1432-0428. ; 51:10, s. 1893-1900
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The 5'-AMP-activated protein kinase (AMPK) pathway is intact in type 2 diabetic patients and is seen as a target for diabetes treatment. In this study, we aimed to assess the impact of the AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR) on both glucose and fatty acid metabolism in vivo in type 2 diabetic patients. METHODS: Stable isotope methodology and blood and muscle biopsy sampling were applied to assess blood glucose and fatty acid kinetics following continuous i.v. infusion of AICAR (0.75 mg kg(-1) min(-1)) and/or NaCl (0.9%) in ten male type 2 diabetic patients (age 64 +/- 2 years; BMI 28 +/- 1 kg/m(2)). RESULTS: Plasma glucose rate of appearance (R (a)) was reduced following AICAR administration, while plasma glucose rate of disappearance (R (d)) was similar in the AICAR and control test. Consequently, blood glucose disposal (R (d) expressed as a percentage of R (a)) was increased following AICAR infusion (p < 0.001). Accordingly, a greater decline in plasma glucose concentration was observed following AICAR infusion (p < 0.001). Plasma NEFA R (a) and R (d) were both significantly reduced in response to AICAR infusion, and were accompanied by a significant decline in plasma NEFA concentration. Although AMPK phosphorylation in skeletal muscle was not increased, we observed a significant increase in acetyl-CoA carboxylase phosphorylation (p < 0.001). CONCLUSIONS/INTERPRETATION: The i.v. administration of AICAR reduces hepatic glucose output, thereby lowering blood glucose concentrations in vivo in type 2 diabetic patients. Furthermore, AICAR administration stimulates hepatic fatty acid oxidation and/or inhibits whole body lipolysis, thereby reducing plasma NEFA concentration. © 2008 The Author(s).
|
|
| 19. |
- Cochius-den Otter, S, et al.
(författare)
-
The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia
- 2019
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:11, s. e032122-
-
Tidskriftsartikel (refereegranskat)abstract
- Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on ‘trial and error’. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking.Methods and analysisIn an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018–2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided) <0.05 is considered significant in all analyses.Ethics and disseminationEthics approval has been granted by the ethics committee in Rotterdam (MEC-2017-324) and the central Committee on Research Involving Human Subjects (NL60229.078.17) in the Netherlands. The principles of the Declaration of Helsinki, the Medical Research Involving Human Subjects Act and the national rules and regulations on personal data protection will be used. Parental informed consent will be obtained.Trial registration numberNTR6982; Pre-results.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Lakens, Daniel, et al.
(författare)
-
Justify your alpha
- 2018
-
Ingår i: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
-
Tidskriftsartikel (refereegranskat)abstract
- In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
|
|
| 23. |
- Oostrum, L. C., et al.
(författare)
-
Repeating fast radio bursts with WSRT/Apertif
- 2020
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Repeating fast radio bursts (FRBs) present excellent opportunities to identify FRB progenitors and host environments as well as to decipher the underlying emission mechanism. Detailed studies of repeating FRBs might also hold clues as to the origin of FRBs as a population. Aims. We aim to detect bursts from the first two repeating FRBs, FRB 121102 (R1) and FRB 180814.J0422+73 (R2), and to characterise their repeat statistics. We also want to significantly improve the sky localisation of R2 and identify its host galaxy. Methods. We used the Westerbork Synthesis Radio Telescope to conduct extensive follow-up of these two repeating FRBs. The new phased-array feed system, Apertif, allows one to cover the entire sky position uncertainty of R2 with fine spatial resolution in a single pointing. The data were searched for bursts around the known dispersion measures of the two sources. We characterise the energy distribution and the clustering of detected R1 bursts. Results. We detected 30 bursts from R1. The non-Poissonian nature is clearly evident from the burst arrival times, which is consistent with earlier claims. Our measurements indicate a dispersion measure (DM) of 563.5(2) pc cm(-3), suggesting a significant increase in DM over the past few years. Assuming a constant position angle across the burst, we place an upper limit of 8% on the linear polarisation fraction for the brightest burst in our sample. We did not detect any bursts from R2. Conclusions. A single power-law might not fit the R1 burst energy distribution across the full energy range or widely separated detections. Our observations provide improved constraints on the clustering of R1 bursts. Our stringent upper limits on the linear polarisation fraction imply a significant depolarisation, either intrinsic to the emission mechanism or caused by the intervening medium at 1400 MHz, which is not observed at higher frequencies. The non-detection of any bursts from R2, despite nearly 300 h of observations, implies either a highly clustered nature of the bursts, a steep spectral index, or a combination of the two assuming that the source is still active. Another possibility is that R2 has turned off completely, either permanently or for an extended period of time.
|
|
| 24. |
- Smits, P. C., et al.
(författare)
-
Fractional flow reserve-guided multivessel angioplasty in myocardial infarction: three-year follow-up with cost benefit analysis of the Compare-Acute trial
- 2020
-
Ingår i: Eurointervention. - : Europa Digital & Publishing. - 1774-024X. ; 16:3, s. 225-232
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: The Compare-Acute trial showed superiority of fractional flow reserve (FFR)-guided acute complete revascularisation compared to culprit-only treatment in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) at one year. The aim of this study was to investigate the outcome at three years, together with cost analysis of this strategy. Methods and results: After primary percutaneous coronary intervention (PCI), 885 patients with STEMI and MVD were randomised (1:2 ratio) to FFR-guided complete revascularisation (295 patients) or infarct-related artery (IRA)-only treatment (590 patients). After 36 months, the primary endpoint (composite of death, myocardial infarction, revascularisation, stroke) occurred significantly less frequently in the FFR-guided complete revascularisation group: 46/295 patients (15.6%) versus 178/590 patients (30.2%) (HR 0.46, 95% CI: 0.33-0.64; p<0.001). This benefit was driven mainly by the reduction of revascularisations in the follow-up (12.5% vs 25.2%; HR 0.45, 95% CI: 0.31-0.64; p<0.001). Cost analysis shows benefit of the FFR-guided complete revascularisation strategy, which can reduce the cost per patient by up to 21% at one year (8,150(sic) vs 10,319(sic)) and by 22% at three years (8,653(sic) vs 11,100(sic)). Conclusions: In patients with STEMI and MVD, FFR-guided complete revascularisation is more beneficial in terms of outcome and healthcare costs compared to IRA-only revascularisation at 36 months.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Haeck, Joost D. E., et al.
(författare)
-
Percutaneous Coronary Intervention vs Medical Therapy for Coronary Lesions With Positive Fractional Flow Reserve (FFR) but Preserved Pressure-Bounded Coronary Flow Reserve (CFR): A Substudy of the Randomized Compare-Acute Trial
- 2021
-
Ingår i: JOURNAL OF INVASIVE CARDIOLOGY. - 1042-3931 .- 1557-2501. ; 33:7
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives. Performing percutaneous coronary intervention (PCI) for fractional flow reserve (FFR) positive coronary lesions improves clinical outcomes and is recommended by international guidelines. It has been hypothesized that lesions with a positive FFR but a preserved coronary flow reserve (CFR) are less likely to be flow limiting and might best be treated medically. We investigated the association of CFR in FFR-positive lesions with clinical outcomes when treated medically, as well as the treatment effect of PCI vs medical therapy in FFR-positive lesions and a preserved CFR. Methods. We performed a substudy of the randomized, multicenter Compare-Acute trial, in which stabilized ST-segment elevation myocardial infarction (STEMI) patients with non-culprit lesions were randomized to either FFR-guided PCI or medical therapy. Based on baseline and hyperemic pressure gradients, we computed physiologic limits of CFR, the so-called pressure-bounded CFR (pb-CFR), and classified lesions as low (<2) or preserved (>= 2). The primary endpoint was 12-month major adverse cardiac and cerebrovascular event (MACCE) rate, defined as a composite of death from any cause, non-fatal myocardial infarction, revascularization, or cerebrovascular events. Results. A total of 980 lesions from 885 patients were included in this substudy. In lesions with FFR <= 0.80, a total of 249 patients had a pb-CFR<2 and 29 patients had a preserved CFR (pb-CFR >= 2). The rate of MACCE at 1 year was not significantly different between patients with FFR <= 0.80 and pb-CFR <2 vs patients with FFR <= 0.80 and pb-CFR >= 2 (25% vs 17%, respectively; P=.39). Because of randomization, baseline characteristics were well balanced between patients with FFR <= 0.80 and pb-CFR >= 2 treated by either by PCI or medical therapy. Importantly, in patients with FFR <= 0.80 and pb-CFR >= 2, MACCE occurred more frequently in patients treated medically vs patients treated by PCI (44% vs 0%, respectively; P=.01). Conclusions. Preserved or low pb-CFR did not alter clinical outcomes in patients with a positive FFR. Patients with FFR-positive coronary lesions but a preserved CFR had more clinical events when treated medically vs those treated with PCI.
|
|
| 28. |
|
|
| 29. |
- Kootte, R. S., et al.
(författare)
-
Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition
- 2017
-
Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 26:4, s. 611-619
-
Tidskriftsartikel (refereegranskat)abstract
- The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as gamma-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.
|
|
| 30. |
|
|
| 31. |
- Smits, Nicole C., et al.
(författare)
-
The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease
- 2010
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:52, s. 41143-41151
-
Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) is a structurally complex polysaccharide that interacts with a broad spectrum of extracellular effector ligands and thereby is thought to regulate a diverse array of biologic processes. The specificity of HS-ligand interactions is determined by the arrangement of sulfate groups on HS, which creates distinct binding motifs. Biologically important HS motifs are expected to exhibit regulated expression. Yet, there is a profound lack of tools to identify such motifs; consequently, little is known of their structures and functions. We have identified a novel phage display-derived antibody (NS4F5) that recognizes a highly regulated HS motif (HS(NS4F5)), which we have rigorously identified as (GlcNS6S-IdoA2S)(3). HS(NS4F5) exhibits a restricted expression in healthy adult tissues. Blocking HS(NS4F5) on cells in culture resulted in reduced proliferation and enhanced sensitivity to apoptosis. HS(NS4F5) is upregulated in tumor endothelial cells, consistent with a role in endothelial cell activation. Indeed, TNF-α stimulated endothelial expression of HS(NS4F5), which contributed to leukocyte adhesion. In a mouse model of severe systemic AA amyloidosis, HS(NS4F5) was expressed within amyloid deposits, which were successfully detected by microSPECT imaging using NS4F5 as a molecularly targeted probe. Combined, our results demonstrate that NS4F5 is a powerful tool for elucidating the biological function of HS(NS4F5) and can be exploited as a probe to detect novel polysaccharide biomarkers of disease processes.
|
|
| 32. |
- Zaldiva, J, et al.
(författare)
-
Fermentation performance and intracellular metabolite patterns in laboratory and industrial xylose-fermenting Saccharomyces cerevisiae.
- 2002
-
Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 59:4-5, s. 436-442
-
Tidskriftsartikel (refereegranskat)abstract
- Heterologous genes for xylose utilization were introduced into an industrial Saccharomyces cerevisiae, strain A, with the aim of producing fuel ethanol from lignocellulosic feedstocks. Two transformants, A4 and A6, were evaluated by comparing the performance in 4-l anaerobic batch cultivations to both the parent strain and a laboratory xylose-utilizing strain: S. cerevisiae TMB 3001. During growth in a minimal medium containing a mixture of glucose and xylose (50 g/l each), glucose was preferentially consumed. During the first growth phase on glucose, the specific growth rates were 0.26, 0.32, 0.27 and 0.30 h-1 for strains TMB 3001, A (parental strain), A4, and A6, respectively. The specific ethanol productivities were 0.04, 0.13, 0.04 and 0.03 g/g.per hour, for TMB 3001, A, A4 and A6, respectively. The specific xylose consumption rates were 0.06, 0.21 and 0.14 g/g.per hour, respectively for strains TMB 3001, A4 and A6. Xylose consumption resulted mainly in the formation of xylitol, with biomass and ethanol being minor products. The metabolite profile of intermediates in the pentose phosphate pathway and key glycolytic intermediates were determined during growth on glucose and xylose, respectively. The metabolite pattern differed depending on whether glucose or xylose was utilized. The levels of intracellular metabolites were higher in the industrial strains than in the laboratory strain during growth on xylose.
|
|
| 33. |
- Zimmermann, Frederik M., et al.
(författare)
-
Fractional flow reserve-guided percutaneous coronary intervention vs. medical therapy for patients with stable coronary lesions : meta-analysis of individual patient data
- 2019
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 40:2, s. 180-186
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To assess the effect of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) with contemporary drug-eluting stents on the composite of cardiac death or myocardial infarction (MI) vs. medical therapy in patients with stable coronary lesions. Methods and results: We performed a systematic review and meta-analysis of individual patient data (IPD) of the three available randomized trials of contemporary FFR-guided PCI vs. medical therapy for patients with stable coronary lesions: FAME 2 (NCT01132495), DANAMI-3-PRIMULTI (NCT01960933), and Compare-Acute (NCT01399736). FAME 2 enrolled patients with stable coronary artery disease (CAD), while the other two focused on non-culprit lesions in stabilized patients after acute coronary syndrome. A total of 2400 subjects were recruited from 54 sites world-wide with 1056 randomly assigned to FFR-guided PCI and 1344 to medical therapy. The pre-specified primary outcome was a composite of cardiac death or MI. We included data from extended follow-ups for FAME 2 (up to 5.5 years follow-up) and DANAMI-3-PRIMULTI (up to 4.7 years follow-up). After a median follow-up of 35 months (interquartile range 12-60 months), a reduction in the composite of cardiac death or MI was observed with FFR-guided PCI as compared with medical therapy (hazard ratio 0.72, 95% confidence interval 0.54-0.96; P = 0.02). The difference between groups was driven by MI. Conclusion: In this IPD meta-analysis of the three available randomized controlled trials to date, FFR-guided PCI resulted in a reduction of the composite of cardiac death or MI compared with medical therapy, which was driven by a decreased risk of MI.
|
|
