| 1. |
- Duursma, Allard, et al.
(författare)
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UN Peacekeeping at 75: Achievements, Challenges, and Prospects
- 2023
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Ingår i: International Peacekeeping. - : Taylor & Francis. - 1353-3312 .- 1743-906X. ; 30:4, s. 415-476
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Tidskriftsartikel (refereegranskat)abstract
- This year marks the 75th anniversary of what the UN itself understands to be its first peacekeeping operation. It is therefore an appropriate time to reflect on the track record of UN peacekeeping in its efforts to try to maintain and realize peace and security. Moreover, this milestone invites us to ponder what lies ahead in the realm of peacekeeping. For this reason, this forum article brings together both academics and UN officials to assess the achievements and challenges of UN peacekeeping over the past 75 years. Through a dialogue among peacekeeping scholars and practitioners, we hope to identify current trends and developments in UN peacekeeping, as well as explore priorities for the future to improve the effectiveness of peacekeeping operations in terms of achieving their mandate objectives, such as maintaining peace, protecting civilians, promoting human rights, and facilitating reconciliation. This forum article is structured into six thematic sections, each shedding light on various aspects of UN peacekeeping: (1) foundational principles of UN peacekeeping - namely, consent, impartiality, and the (non-)use of force; (2) protection of civilians; (3) the primacy of politics; (4) early warning; (5) cooperation with regional organizations; and (6) the changing geopolitical landscape in which UN peacekeeping operates.
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| 2. |
- Hardy, Timothy, et al.
(författare)
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The European NAFLD Registry : A real-world longitudinal cohort study of nonalcoholic fatty liver disease
- 2020
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Ingår i: Contemporary Clinical Trials. - : Elsevier. - 1551-7144 .- 1559-2030. ; 98
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Tidskriftsartikel (refereegranskat)abstract
- Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS Liver Investigation: Testing Marker Utility in Steatohepatitis consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace.
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| 3. |
- Hohn, Nuri, et al.
(författare)
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Amphiphilic diblock copolymer-mediated structure control in nanoporous germanium-based thin films
- 2019
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Ingår i: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 11:4, s. 2048-2055
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Tidskriftsartikel (refereegranskat)abstract
- Fabrication of porous, foam-like germanium-based (Ge-based) nanostructures is achieved with the use of the amphiphilic diblock copolymer polystyrene-b-polyethylene oxide as structure directing agent. Basic concepts of block copolymer assisted sol-gel synthesis are successfully realized based on the [Ge-9](4-) Zintl clusters as a precursor for Ge-based thin films. Material/elemental composition and crystalline Ge-based phases are investigated via X-ray photoelectron spectroscopy and X-ray diffraction measurements, respectively. Poor-good solvent pair induced phase separation leads to pore sizes in the Ge-based films up to 40 nm, which can be tuned through a change of the molar mixing ratio between polymer template and precursor as proven by grazing incidence small angle X-ray scattering and scanning electron microscopy.
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| 4. |
- Ihne-Schubert, Sandra Michaela, et al.
(författare)
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Cardio-Hepatic Interaction in Cardiac Amyloidosis
- 2024
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Ingår i: Journal of Clinical Medicine. - 2077-0383. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Congestion is associated with poor prognosis in cardiac amyloidosis (CA). The cardio-hepatic interaction and the prognostic impact of secondary liver affection by cardiac congestion in CA are poorly understood and require further characterisation. Methods: Participants of the amyloidosis cohort study AmyKoS at the Interdisciplinary Amyloidosis Centre of Northern Bavaria with proven transthyretin (ATTR-CA) and light chain CA (AL-CA) underwent serial work-up including laboratory tests, echocardiography, and in-depth hepatic assessment by vibration-controlled transient elastography (VCTE) and 13C-methacetin breath test. Results: In total, 74 patients with AL-CA (n = 17), ATTR-CA (n = 26) and the controls (n = 31) were analysed. ATTR-CA patients showed decreased microsomal liver function expressed by maximal percentage of dose rate (PDRpeak) related to hepatic congestion. Reduced PDRpeak in AL-CA could result from altered pharmacokinetics due to changed hepatic blood flow. Liver stiffness as a combined surrogate of chronic liver damage and congestion was identified as a predictor of all-cause mortality. Statistical modelling of the cardio-hepatic interaction revealed septum thickness, NT-proBNP and PDRpeak as predictors of liver stiffness in both CA subtypes; dilatation of liver veins and the fibrosis score FIB-4 were only significant for ATTR-CA. Conclusions: Non-invasive methods allow us to characterise CA-associated hepatic pathophysiology. Liver stiffness might be promising for risk stratification in CA.
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| 5. |
- Ihne-Schubert, Sandra M., et al.
(författare)
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Vector autoregression : Useful in rare diseases?—Predicting organ response patterns in a rare case of secondary AA amyloidosis
- 2023
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Ingår i: PLoS ONE. - 1932-6203. ; 18:8 August
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Tidskriftsartikel (refereegranskat)abstract
- Background Statistical analyses of clinical data are a cornerstone in understanding pathomechanisms of disorders. In rare disorders, cross-sectional datasets of sufficient size are usually not available. Taking AA amyloidosis as an example of a life-threatening rare disorder resulting from of uncontrolled chronic inflammation, we propose techniques from time series analysis to predict organ response to treatment. The advantage of time-series analysis is that it solely relies on temporal variation and therefore allows analyzing organ response to treatment even when the cross-sectional dimension is small. Methods The joint temporal interdependence of inflammatory activity and organ response was modelled multivariately using vector autoregression (VAR) based on a unique 4.5 year spanning data set of routine laboratory, imaging data (e.g., 18F-Florbetaben-PET/CT) and functional investigations of a 68-year-old patient with multi-organ involvement of AA amyloidosis due to ongoing inflammatory activity of a malignant paraganglioma in stable disease for >20 years and excellent response to tocilizumab). Results VAR analysis showed that alterations in inflammatory activity forecasted alkaline phosphatase (AP). AP levels, but not inflammatory activity at the previous measurement time point predicted proteinuria. Conclusion We demonstrate the feasibility and value of time series analysis for obtaining clinically reliable information when the rarity of a disease prevents conventional prognostic modelling approaches. We illustrate the comparative utility of blood, functional and imaging markers to monitor the development and regression of AA amyloidosis.
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| 6. |
- Lee, Jenny, et al.
(författare)
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Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study
- 2023
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Ingår i: Hepatology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0270-9139 .- 1527-3350. ; 78:1, s. 258-271
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F >= 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD. Approach and Results: Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS >= 4;53%), at-risk NASH (NASH with F >= 2;35%), significant (F >= 2;47%), and advanced fibrosis (F >= 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models.Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82). Conclusions: Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.
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| 7. |
- Mcteer, Matthew, et al.
(författare)
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Machine learning approaches to enhance diagnosis and staging of patients with MASLD using routinely available clinical information
- 2024
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 19:2
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Tidskriftsartikel (refereegranskat)abstract
- Aims Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) outcomes such as MASH (metabolic dysfunction associated steatohepatitis), fibrosis and cirrhosis are ordinarily determined by resource-intensive and invasive biopsies. We aim to show that routine clinical tests offer sufficient information to predict these endpoints.Methods Using the LITMUS Metacohort derived from the European NAFLD Registry, the largest MASLD dataset in Europe, we create three combinations of features which vary in degree of procurement including a 19-variable feature set that are attained through a routine clinical appointment or blood test. This data was used to train predictive models using supervised machine learning (ML) algorithm XGBoost, alongside missing imputation technique MICE and class balancing algorithm SMOTE. Shapley Additive exPlanations (SHAP) were added to determine relative importance for each clinical variable.Results Analysing nine biopsy-derived MASLD outcomes of cohort size ranging between 5385 and 6673 subjects, we were able to predict individuals at training set AUCs ranging from 0.719-0.994, including classifying individuals who are At-Risk MASH at an AUC = 0.899. Using two further feature combinations of 26-variables and 35-variables, which included composite scores known to be good indicators for MASLD endpoints and advanced specialist tests, we found predictive performance did not sufficiently improve. We are also able to present local and global explanations for each ML model, offering clinicians interpretability without the expense of worsening predictive performance.Conclusions This study developed a series of ML models of accuracy ranging from 71.9-99.4% using only easily extractable and readily available information in predicting MASLD outcomes which are usually determined through highly invasive means.
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| 8. |
- Mozes, Ferenc E., et al.
(författare)
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Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis
- 2023
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Ingår i: The Lancet Gastroenterology & Hepatology. - : ELSEVIER INC. - 2468-1253. ; 8:8, s. 704-713
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Tidskriftsartikel (refereegranskat)abstract
- Background Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. Methods This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score >= 15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs >= 20 kPa; FIB-4: <1<middle dot>3 vs 1<middle dot>3 to <= 2<middle dot>67 vs >2<middle dot>67; NFS: <-1<middle dot>455 vs -1<middle dot>455 to <= 0<middle dot>676 vs >0<middle dot>676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.Findings Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44<middle dot>7%] were female, median age was 54 years [IQR 44-63), and 1161 [46<middle dot>1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5<middle dot>8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0<middle dot>0001 for all comparisons). The tAUC at 5 years were 0<middle dot>72 (95% CI 0<middle dot>62-0<middle dot>81) for histology, 0<middle dot>76 (0<middle dot>70-0<middle dot>83) for LSM-VCTE, 0<middle dot>74 (0<middle dot>64-0<middle dot>82) for FIB-4, and 0<middle dot>70 (0<middle dot>63-0<middle dot>80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.Interpretation Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.
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| 9. |
- Pavlides, Michael, et al.
(författare)
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Liver investigation: Testing marker utility in steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol
- 2023
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Ingår i: Contemporary Clinical Trials. - : ELSEVIER SCIENCE INC. - 1551-7144 .- 1559-2030. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721
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| 10. |
- Schulze, S., et al.
(författare)
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GRB 120422A/SN 2012bz : Bridging the gap between low- and high-luminosity gamma-ray bursts
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 566
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Tidskriftsartikel (refereegranskat)abstract
- Context. At low redshift, a handful of gamma-ray bursts (GRBs) have been discovered with luminosities that are substantially lower (L-iso less than or similar to 10(48.5) erg s(-1)) than the average of more distant ones (L-iso greater than or similar to 10(49.5) erg s(-1)). It has been suggested that the properties of several low-luminosity (low-L) GRBs are due to shock break-out, as opposed to the emission from ultrarelativistic jets. This has led to much debate about how the populations are connected. Aims. The burst at redshift z = 0.283 from 2012 April 22 is one of the very few examples of intermediate-L GRBs with a gamma-ray luminosity of L-iso similar to 10(49.6-49.9) erg s(-1) that have been detected up to now. With the robust detection of its accompanying supernova SN 2012bz, it has the potential to answer important questions on the origin of low-and high-L GRBs and the GRB-SN connection. Methods. We carried out a spectroscopy campaign using medium-and low-resolution spectrographs with 6-10-m class telescopes, which covered a time span of 37.3 days, and a multi-wavelength imaging campaign, which ranged from radio to X-ray energies over a duration of similar to 270 days. Furthermore, we used a tuneable filter that is centred at H alpha to map star-formation in the host and the surrounding galaxies. We used these data to extract and model the properties of different radiation components and fitted the spectral energy distribution to extract the properties of the host galaxy. Results. Modelling the light curve and spectral energy distribution from the radio to the X-rays revealed that the blast wave expanded with an initial Lorentz factor of Gamma(0) similar to 50, which is a low value in comparison to high-L GRBs, and that the afterglow had an exceptionally low peak luminosity density of less than or similar to 2 x 10(30) erg s(-1) Hz(-1) in the sub-mm. Because of the weak afterglow component, we were able to recover the signature of a shock break-out in an event that was not a genuine low-L GRB for the first time. At 1.4 hr after the burst, the stellar envelope had a blackbody temperature of k(B)T similar to 16 eV and a radius of similar to 7 x 10(13) cm (both in the observer frame). The accompanying SN 2012bz reached a peak luminosity of M-V = -19.7 mag, which is 0.3 mag more luminous than SN 1998bw. The synthesised nickel mass of 0.58 M-circle dot, ejecta mass of 5.87 M-circle dot, and kinetic energy of 4.10x10(52) erg were among the highest for GRB-SNe, which makes it the most luminous spectroscopically confirmed SN to date. Nebular emission lines at the GRB location were visible, which extend from the galaxy nucleus to the explosion site. The host and the explosion site had close-to-solar metallicity. The burst occurred in an isolated star-forming region with an SFR that is 1/10 of that in the galaxy's nucleus. Conclusions. While the prompt gamma-ray emission points to a high-L GRB, the weak afterglow and the low Gamma(0) were very atypical for such a burst. Moreover, the detection of the shock break-out signature is a new quality for high-L GRBs. So far, shock break-outs were exclusively detected for low-L GRBs, while GRB 120422A had an intermediate L-iso of similar to 10(49.6-49.9) erg s(-1). Therefore, we conclude that GRB 120422A was a transition object between low-and high-L GRBs, which supports the failed-jet model that connects low-L GRBs that are driven by shock break-outs and high-L GRBs that are powered by ultra-relativistic jets.
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