| 201. |
- Capobianco, Ivan, et al.
(författare)
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Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment (CAPRA) score : is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS)?
- 2022
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Ingår i: Hepatobiliary surgery and nutrition. - Hong Kong : AME Publishing Company. - 2304-3881 .- 2304-389X. ; 11:1, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preoperative patient selection in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is not always reliable with currently available scores, particularly in patients with primary liver tumor. This study aims to (I) to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and (II) to create a score predicting 90-day mortality preoperatively. Methods: Thirteen high-volume centers participated in this retrospective multicentric study. A risk analysis based on patient characteristics, underlying disease and procedure type was performed to identify risk factors and model the CAPRA score. A nonparametric receiver operating characteristic analysis was performed to estimate the predictive ability of our score against the Charlson Comorbidity Index (CCI), the age-adjusted CCI (aCCI), the ALPPS risk score before Stage 1 (ALPPS-RS I) and Stage 2 (ALPPS-RS2). The model was internally validated applying bootstrapping. Results: A total of 451 patients were included. Mortality was 14.4%. The CAPRA score is calculated based on the following formula: (0.1*age) - (2*BSA) +1 (in the presence of primary liver tumor) +1 (in the presence of severe cardiovascular disease) +2 (in the presence of moderate or severe diabetes) +2 (in the presence of renal disease) +2 (if classic ALPPS is planned). The predictive ability was 0.837 for the CAPRA score, 0.443 for CCI, 0.519 for aCCI, 0.693 for ALPPS-RS I and 0.807 for ALPPS-RS2. After 1,000 cycles of bootstrapping the C statistic was 0.793. The accuracy plot revealed a cut-off for optimal prediction of postoperative mortality of 4.70. Conclusions: Comorbidities play an important role in ALPPS and should be carefully considered when planning the procedure. By assessing the patients preoperative condition in relation to ALPPS, the CAPRA score has a very good ability to predict postoperative mortality.
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| 202. |
- Chapman, Henry N., et al.
(författare)
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Femtosecond diffractive imaging with a soft-X-ray free-electron laser
- 2006
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Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2473 .- 1745-2481. ; 2:12, s. 839-843
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Tidskriftsartikel (refereegranskat)abstract
- Theory predicts(1-4) that, with an ultrashort and extremely bright coherent X-ray pulse, a single diffraction pattern may be recorded from a large macromolecule, a virus or a cell before the sample explodes and turns into a plasma. Here we report the first experimental demonstration of this principle using the FLASH soft-X-ray free-electron laser. An intense 25 fs, 4 x 10(13) W cm(-2) pulse, containing 10(12) photons at 32 nm wavelength, produced a coherent diffraction pattern from a nanostructured non-periodic object, before destroying it at 60,000 K. A novel X-ray camera assured single-photon detection sensitivity by filtering out parasitic scattering and plasma radiation. The reconstructed image, obtained directly from the coherent pattern by phase retrieval through oversampling(5-9), shows no measurable damage, and is reconstructed at the diffraction-limited resolution. A three-dimensional data set may be assembled from such images when copies of a reproducible sample are exposed to the beam one by one(10).
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| 203. |
- Chapman, Henry N, et al.
(författare)
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Femtosecond time-delay X-ray holography
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 448:7154, s. 676-679
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Tidskriftsartikel (refereegranskat)abstract
- Extremely intense and ultrafast X-ray pulses from free-electron lasers offer unique opportunities to study fundamental aspects of complex transient phenomena in materials. Ultrafast time-resolved methods usually require highly synchronized pulses to initiate a transition and then probe it after a precisely defined time delay. In the X-ray regime, these methods are challenging because they require complex optical systems and diagnostics. Here we propose and apply a simple holographic measurement scheme, inspired by Newton's 'dusty mirror' experiment1, to monitor the X-ray-induced explosion of microscopic objects. The sample is placed near an X-ray mirror; after the pulse traverses the sample, triggering the reaction, it is reflected back onto the sample by the mirror to probe this reaction. The delay is encoded in the resulting diffraction pattern to an accuracy of one femtosecond, and the structural change is holographically recorded with high resolution. We apply the technique to monitor the dynamics of polystyrene spheres in intense free-electron-laser pulses, and observe an explosion occurring well after the initial pulse. Our results support the notion that X-ray flash imaging2, 3 can be used to achieve high resolution, beyond radiation damage limits for biological samples4. With upcoming ultrafast X-ray sources we will be able to explore the three-dimensional dynamics of materials at the timescale of atomic motion.
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| 204. |
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| 205. |
- Cortese, Samuele, et al.
(författare)
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Psychopharmacology in children and adolescents: unmet needs and opportunities
- 2024
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Ingår i: The Lancet Psychiatry. - 2215-0366 .- 2215-0374. ; 11:2, s. 143 - 154
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Forskningsöversikt (refereegranskat)abstract
- Psychopharmacological treatment is an important component of the multimodal intervention approach to treating mental health conditions in children and adolescents. Currently, there are many unmet needs but also opportunities, alongside possible risks to consider, regarding the pharmacological treatment of mental health conditions in children and adolescents. In this Position Paper, we highlight and address these unmet needs and opportunities, including the perspectives of clinicians and researchers from the European College of Neuropsychopharmacology–Child and Adolescent Network, alongside those of experts by lived experience from national and international associations, via a survey involving 644 participants from 13 countries, and of regulators, through representation from the European Medicines Agency. We present and discuss the evidence base for medications currently used for mental disorders in children and adolescents, medications in the pipeline, opportunities in the development of novel medications, crucial priorities for the conduct of future clinical studies, challenges and opportunities in terms of the regulatory and legislative framework, and innovations in the way research is conducted, reported, and promoted.
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| 206. |
- Cox, Zachary L, et al.
(författare)
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Guideline-Directed Medical Therapy Tolerability in Patients With Heart Failure and Mitral Regurgitation: The COAPT Trial.
- 2023
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Ingår i: JACC. Heart failure. - 2213-1787. ; 11:7, s. 791-805
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Tidskriftsartikel (refereegranskat)abstract
- In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, a central committee of heart failure (HF) specialists optimized guideline-directed medical therapies (GDMT) and documented medication and goal dose intolerances before patient enrollment.The authors sought to assess the rates, reasons, and predictors of GDMT intolerance in the COAPT trial.Baseline use, dose, and intolerances of angiotensin-converting enzyme inhibitors (ACEIs) angiotensin II receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were analyzed in patients with left ventricular ejection fraction (LVEF) ≤40%, in whom maximally tolerated doses of these agents as assessed by an independent HF specialist were required before enrollment.A total of 464 patients had LVEF ≤40% and complete medication information. At baseline, 38.8%, 39.4%, and 19.8% of patients tolerated 3, 2, and 1 GDMT classes, respectively (any dose); only 1.9% could not tolerate any GDMT. Beta-blockers were the most frequently tolerated GDMT (93.1%), followed by ACEIs/ARBs/ARNIs (68.5%), and then MRAs (55.0%). Intolerances differed by GDMT class, but hypotension and kidney dysfunction were most common. Goal doses were uncommonly achieved for beta-blockers (32.3%) and ACEIs/ARBs/ARNIs (10.2%) due to intolerances limiting titration. Only 2.2% of patients tolerated goal doses of all 3 GDMT classes.In a contemporary trial population with HF, severe mitral regurgitation, and systematic HF specialist-directed GDMT optimization, most patients had medical intolerances prohibiting 1 or more GDMT classes and achieving goal doses. The specific intolerances noted and methods used for GDMT optimization provide important lessons for the implementation of GDMT optimization in future clinical trials. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).
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| 207. |
- Cruz, Paulo J. S., et al.
(författare)
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Crack sensor with embedded optical fibre : Sustainable Bridges. Background document 5.3
- 2007
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Rapport (refereegranskat)abstract
- This document reports the development of a distributed optical fibre crack sensor. This sensor can be employed for detection of cracks and measurement of crack widths in concrete structures. The basic principle of operation for the crack sensor is based on intensity variation of the optical power within the optical fibre due to the initiation and opening of cracks.The present report summarizes the improvements introduced in the sensor to make it appropriate for crack monitoring in bridges, performed by researchers of the University of Minho, in Portugal. The primary objectives of the work were:1) To select the proper polymeric material for making the plate;2) To optimize the manufacture process;3) To assure the bonding between the plate sensor and concrete members;4) To determine the corresponding calibration curves of intensity losses versus the crack aperture;5) The application of the plate sensor to the monitoring of single crack RC beams and masonry slabs and the monitoring of multiple cracks on RC beams;6) The field implementation of the plate sensor.The field implementation of the plate sensor in the destructive test carried out in the ÖvikBridge, in the north of Sweden, is also included. The main purpose of this test was to demonstratethe capability of the sensor plate to detect cracks and measure the crack opening in concrete railway bridges. This report provides the description of the bridge and gives an overview of the procedures for wiring and installing the sensor plate.
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| 208. |
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| 209. |
- Devoy, Anny, et al.
(författare)
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Generation and analysis of innovative genomically humanized knockin SOD1, TARDBP (TDP-43), and FUS mouse models
- 2021
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Ingår i: iScience. - : Elsevier. - 2589-0042. ; 24:12
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a fatal neurodegenerative disorder, and continued innovation is needed for improved understanding and for developing therapeutics. We have created next-generation genomically humanized knockin mouse models, by replacing the mouse genomic region of Sod1, Tardbp (TDP-43), and Fus, with their human orthologs, preserving human protein biochemistry and splicing with exons and introns intact. We establish a new standard of large knockin allele quality control, demonstrating the utility of indirect capture for enrichment of a genomic region of interest followed by Oxford Nanopore sequencing. Extensive analysis shows that homozygous humanized animals only express human protein at endogenous levels. Characterization of humanized FUS animals showed that they are phenotypically normal throughout their lifespan. These humanized strains are vital for preclinical assessment of interventions and serve as templates for the addition of coding or non-coding human ALS/FTD mutations to dissect disease pathomechanisms, in a physiological context.
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| 210. |
- Dewan, Pooja, et al.
(författare)
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Heart failure with reduced ejection fraction: comparison of patient characteristics and clinical outcomes within Asia and between Asia, Europe and the Americas.
- 2019
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 21:5, s. 577-587
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Tidskriftsartikel (refereegranskat)abstract
- Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world.We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0-63.9 years) than in Western Europe (67.9 years) and North America (66.6 years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100 patient-years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan.Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences.
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