1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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- Ballan, M., et al.
(author)
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Nuclear physics midterm plan at Legnaro National Laboratories (LNL)
- 2023
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In: European Physical Journal Plus. - 2190-5444. ; 138:8, s. 3-26
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Journal article (peer-reviewed)abstract
- The next years will see the completion of the radioactive ion beam facility SPES (Selective Production of Exotic Species) and the upgrade of the accelerators complex at Istituto Nazionale di Fisica Nucleare – Legnaro National Laboratories (LNL) opening up new possibilities in the fields of nuclear structure, nuclear dynamics, nuclear astrophysics, and applications. The nuclear physics community has organised a workshop to discuss the new physics opportunities that will be possible in the near future by employing state-of-the-art detection systems. A detailed discussion of the outcome from the workshop is presented in this report.
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5. |
- Cornelissen, R., et al.
(author)
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The Cell Envelope Structure of Cable Bacteria
- 2018
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In: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 9
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Journal article (peer-reviewed)abstract
- Cable bacteria are long, multicellular micro-organisms that are capable of transporting electrons from cell to cell along the longitudinal axis of their centimeter-long filaments. The conductive structures that mediate this long-distance electron transport are thought to be located in the cell envelope. Therefore, this study examines in detail the architecture of the cell envelope of cable bacterium filaments by combining different sample preparation methods (chemical fixation, resin-embedding, and cryo-fixation) with a portfolio of imaging techniques (scanning electron microscopy, transmission electron microscopy and tomography, focused ion beam scanning electron microscopy, and atomic force microscopy). We systematically imaged intact filaments with varying diameters. In addition, we investigated the periplasmic fiber sheath that remains after the cytoplasm and membranes were removed by chemical extraction. Based on these investigations, we present a quantitative structural model of a cable bacterium. Cable bacteria build their cell envelope by a parallel concatenation of ridge compartments that have a standard size. Larger diameter filaments simply incorporate more parallel ridge compartments. Each ridge compartment contains a similar to 50 nm diameter fiber in the periplasmic space. These fibers are continuous across cell-to-cell junctions, which display a conspicuous cartwheel structure that is likely made by invaginations of the outer cell membrane around the periplasmic fibers. The continuity of the periplasmic fibers across cells makes them a prime candidate for the sought-after electron conducting structure in cable bacteria.
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6. |
- Plompen, A. J. M., et al.
(author)
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The joint evaluated fission and fusion nuclear data library, JEFF-3.3
- 2020
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In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 56:7
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Research review (peer-reviewed)abstract
- The joint evaluated fission and fusion nuclear data library 3.3 is described. New evaluations for neutron-induced interactions with the major actinides 235U, 238U and 239Pu, on 241Am and 23Na, 59Ni, Cr, Cu, Zr, Cd, Hf, W, Au, Pb and Bi are presented. It includes new fission yields, prompt fission neutron spectra and average number of neutrons per fission. In addition, new data for radioactive decay, thermal neutron scattering, gamma-ray emission, neutron activation, delayed neutrons and displacement damage are presented. JEFF-3.3 was complemented by files from the TENDL project. The libraries for photon, proton, deuteron, triton, helion and alpha-particle induced reactions are from TENDL-2017. The demands for uncertainty quantification in modeling led to many new covariance data for the evaluations. A comparison between results from model calculations using the JEFF-3.3 library and those from benchmark experiments for criticality, delayed neutron yields, shielding and decay heat, reveals that JEFF-3.3 performes very well for a wide range of nuclear technology applications, in particular nuclear energy.
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11. |
- Vriezinga, S. L., et al.
(author)
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Randomized feeding intervention in infants at high risk for celiac disease
- 2014
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In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 371:14, s. 1304-1315
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Journal article (peer-reviewed)abstract
- BACKGROUND A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. RESULTS Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. CONCLUSIONS As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children. (Funded by the European Commission and others; PreventCD Current Controlled Trials number, ISRCTN74582487.)
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12. |
- Costello, David M., et al.
(author)
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Global patterns and controls of nutrient immobilization on decomposing cellulose in riverine ecosystems
- 2022
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In: Global Biogeochemical Cycles. - : John Wiley & Sons. - 0886-6236 .- 1944-9224. ; 36:3
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Journal article (peer-reviewed)abstract
- Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature. Collectively, we demonstrated that exogenous nutrient supply and immobilization are critical control points for decomposition of organic matter.
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13. |
- Shameer, S., et al.
(author)
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TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei
- 2015
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 43:D1, s. D637-D644
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Journal article (peer-reviewed)abstract
- The metabolic network of a cell represents thecatabolic and anabolic reactions that interconvertsmall molecules (metabolites) through the activity ofenzymes, transporters and non-catalyzed chemicalreactions. Our understanding of individual metabolicnetworks is increasing as we learn more aboutthe enzymes that are active in particular cells underparticular conditions and as technologies advanceto allow detailed measurements of the cellularmetabolome. Metabolic network databases areof increasing importance in allowing us to contextualisedata sets emerging from transcriptomic,proteomic and metabolomic experiments. Here wepresent a dynamic database, TrypanoCyc (http://www.metexplore.fr/trypanocyc/), which describesthe generic and condition-specific metabolic networkof Trypanosoma brucei, a parasitic protozoan responsiblefor human and animal African trypanosomiasis.In addition to enabling navigation through the BioCyc-based TrypanoCyc interface, we have alsoimplemented a network-based representation of theinformation through MetExplore, yielding a novel environmentin which to visualise the metabolism ofthis important parasite.
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14. |
- Tiegs, Scott D., et al.
(author)
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Global patterns and drivers of ecosystem functioning in rivers and riparian zones
- 2019
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In: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
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Journal article (peer-reviewed)abstract
- River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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15. |
- Timmers, Elze R, et al.
(author)
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Gut Microbiome Composition in Dystonia Patients
- 2023
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 24:3, s. 1-15
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Journal article (peer-reviewed)abstract
- Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and fatigue, are common. We hypothesise that the gut microbiome might play a role in the pathophysiology of the (non-)motor symptoms in dystonia via the gut-brain axis. This exploratory study investigates the composition of the gut microbiome in dystonia patients compared to healthy controls. Furthermore, the abundance of neuro-active metabolic pathways, which might be implicated in the (non-)motor symptoms, was investigated. We performed both metagenomic and 16S rRNA sequencing on the stool samples of three subtypes of dystonia (27 cervical dystonia, 20 dopa-responsive dystonia and 24 myoclonus-dystonia patients) and 25 controls. While microbiome alpha and beta diversity was not different between dystonia patients and controls, dystonia patients had higher abundances of Ruminococcus torques and Dorea formicigenerans, and a lower abundance of Butyrivibrio crossotus compared to controls. For those with dystonia, non-motor symptoms and the levels of neurotransmitters in plasma explained the variance in the gut microbiome composition. Several neuro-active metabolic pathways, especially tryptophan degradation, were less abundant in the dystonia patients compared to controls. This suggest that the gut-brain axis might be involved in the pathophysiology of dystonia. Further studies are necessary to confirm our preliminary findings.
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18. |
- Miguel-Escalada, Irene, et al.
(author)
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Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes
- 2019
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:7, s. 1137-1148
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Journal article (peer-reviewed)abstract
- Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in three-dimensional (3D) space. Furthermore, their target genes are often unknown. We have created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated enhancers to their target genes, often located hundreds of kilobases away. It also revealed >1,300 groups of islet enhancers, super-enhancers and active promoters that form 3D hubs, some of which show coordinated glucose-dependent activity. We demonstrate that genetic variation in hubs impacts insulin secretion heritability, and show that hub annotations can be used for polygenic scores that predict T2D risk driven by islet regulatory variants. Human islet 3D chromatin architecture, therefore, provides a framework for interpretation of T2D genome-wide association study (GWAS) signals.
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19. |
- Timmers, Elze R., et al.
(author)
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Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients
- 2021
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In: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 91, s. 48-54
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Journal article (peer-reviewed)abstract
- Introduction: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations. Methods: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites. Results: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 μmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (rs = −0.3, p < 0.01), depression (rs = −0.3, p < 0.01) and fatigue (rs = −0.2, p = 0.04). Conclusion: This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.
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20. |
- Timmers, Elze R, et al.
(author)
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Methylation of the serotonin reuptake transporter gene and non-motor symptoms in dystonia patients
- 2022
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In: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 14, s. 1-10
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Journal article (peer-reviewed)abstract
- BACKGROUND: Dystonia is a rare movement disorder, in which patients suffer from involuntary twisting movements or abnormal posturing. Next to these motor symptoms, patients have a high prevalence of psychiatric comorbidity, suggesting a role for serotonin in its pathophysiology. This study investigates the percentage of DNA methylation of the gene encoding for the serotonin reuptake transporter (SLC6A4) in dystonia patients and the associations between methylation levels and presence and severity of psychiatric symptoms.METHODS: Patients with cervical dystonia (n = 49), myoclonus dystonia (n = 41) and dopa-responsive dystonia (DRD) (n = 27) and a group of healthy controls (n = 56) were included. Psychiatric comorbidity was evaluated with validated questionnaires. Methylation levels of 20 CpG sites situated 69 to 213 base pairs upstream of the start codon of SLC6A4 were investigated. Methylation in dystonia patients was compared to healthy controls, correcting for age, and correlated with psychiatric comorbidity.RESULTS: Bootstrapped quantile regression analysis showed that being a dystonia patient compared to a healthy control significantly explains the methylation level at two CpG sites (CpG 24: pseudo-R 2 = 0.05, p = 0.04, CpG 32: pseudo-R 2 = 0.14, p = 0.03). Subgroup analysis revealed that being a DRD patient significantly explained a part of the variance of methylation levels at two CpG sites (CpG 21: pseudo-R 2 = 0.03, p = 0.00, CpG 24: pseudo-R 2 = 0.06, p = 0.03). Regression analysis showed that methylation level at CpG 38 significantly explained a small proportion of the variance of severity score for anxiety (R 2 = 0.07, p = 0.04) and having a diagnosis of depression (Nagelkerke R 2: 0.11, p = 0.00). Genotype of the 5-HTTLPR polymorphism had no additional effect on these associations. CONCLUSIONS: This study showed an association between percentage of methylation at several specific sites of the promoter region of SLCA64 and (dopa-responsive) dystonia patients compared to healthy controls. Furthermore, methylation levels were associated with severity of anxiety and presence of a depressive disorder in the dystonia group. This study suggests alterations in the serotonergic metabolism in dystonia patients, and its relation with the non-motor symptoms.
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22. |
- van Lunteren, M., et al.
(author)
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In Early Axial Spondyloarthritis, Increasing Disease Activity Is Associated with Worsening of Health-related Quality of Life over Time
- 2018
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 45:6, s. 779-784
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Journal article (peer-reviewed)abstract
- Objective. In early axial spondyloarthritis (axSpA), data are lacking about the relationship between disease activity and health-related quality of life (HRQOL). We assessed and quantified the association between change in Ankylosing Spondylitis Disease Activity Score (ASDAS) and HRQOL over time in early axSpA. Methods. Baseline and 1-year data of patients with axSpA fulfilling the Assessment of Spondyloarthritis international Society (ASAS) classification criteria from the SPondyloArthritis Caught Early (SPACE) cohort were analyzed. Associations between change in ASDAS and in physical (PCS) or mental component summary (MCS) of the Medical Outcomes Study Short Form-36 were tested by linear regression models. Age. sex. ASAS criteria arm, and blue- versus white-collar work were tested for effect modification. Subsequently, these factors and medication were tested for confounding. Results. There were 161 patients with axSpA [53% male, mean (+/- SD) age 29.7 (+/- 7.5) yrs, symptom duration 13.6 (+/- 7.2) months, HLA-B27-positive 91%, radiographic sacroiliitis 22%] who had ASDAS of 2.5 (+/- 1.0) and 2.0 (+/- 0.8), PCS of 28.4 (+/- 14.3) and 36.9 (+/- 13.1), and MCS of 48.2 (+/- 13.8) and 493 (+/- 12.0) at baseline and 1 year, respectively. Per unit increase in ASDAS between baseline and 1 year, PCS worsened by 93 points. The same level of disease activity had fewer adverse effects on physical HRQOL in women and white-collar workers. Conclusion. To our knowledge, our data are the first to show that in a broad group of patients with early axSpA, increasing ASDAS is associated with worsening of physical HRQOL, but not mental HRQOL, over time.
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23. |
- von Scheibler, Emma N.M.M., et al.
(author)
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Parkinsonism in Genetic Neurodevelopmental Disorders : A Systematic Review
- 2023
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In: Movement Disorders Clinical Practice. - : Wiley. - 2330-1619. ; 10:1, s. 17-31
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Research review (peer-reviewed)abstract
- Background: With advances in clinical genetic testing, associations between genetic neurodevelopmental disorders and parkinsonism are increasingly recognized. In this review, we aimed to provide a comprehensive overview of reports on parkinsonism in genetic neurodevelopmental disorders and summarize findings related to genetic diagnosis, clinical features and proposed disease mechanisms. Methods: A systematic literature review was conducted in PubMed and Embase on June 15, 2021. Search terms for parkinsonism and genetic neurodevelopmental disorders, using generic terms and the Human Phenotype Ontology, were combined. Study characteristics and descriptive data were extracted from the articles using a modified version of the Cochrane Consumers and Communication Review Group's data extraction template. The protocol was registered in PROSPERO (CRD42020191035). Results: The literature search yielded 208 reports for data-extraction, describing 69 genetic disorders in 422 patients. The five most reported from most to least frequent were: 22q11.2 deletion syndrome, beta-propeller protein-associated neurodegeneration, Down syndrome, cerebrotendinous xanthomatosis, and Rett syndrome. Notable findings were an almost equal male to female ratio, an early median age of motor onset (26 years old) and rigidity being more common than rest tremor. Results of dopaminergic imaging and response to antiparkinsonian medication often supported the neurodegenerative nature of parkinsonism. Moreover, neuropathology results showed neuronal loss in the majority of cases. Proposed disease mechanisms included aberrant mitochondrial function and disruptions in neurotransmitter metabolism, endosomal trafficking, and the autophagic-lysosomal and ubiquitin-proteasome system. Conclusion: Parkinsonism has been reported in many GNDs. Findings from this study may provide clues for further research and improve management of patients with GNDs and/or parkinsonism.
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24. |
- Wall, Helena, et al.
(author)
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Integument, mortality, and skeletal strength in extended production cycles for laying hens - effects of genotype and dietary zinc source
- 2022
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In: British Poultry Science. - : Taylor & Francis Group. - 0007-1668 .- 1466-1799. ; 63:2, s. 115-124
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Journal article (peer-reviewed)abstract
- 1. This study on long-life layers, covering the period 20-100 weeks of age, investigated longitudinal effects on mortality, layer integument, and skeletal properties in Bovans White (BoW) and Lohmann Selected Leghorn Classic (LSL), with or without supplementation with dietary organic zinc (Zn).2. Two experiments, using 1440 layers in furnished small group cages (FC) and 1836 layers in a traditional floor housing system (Floor), were run in parallel. Each replicate consisted of five adjacent cages containing eight hens in each FC, or a pen with 102 layers in the Floor group.3. Mortality was recorded daily. Integument and keel bone condition were scored at 35, 55, 85, and 100 weeks of age on 20% of the layers. Tibial strength was recorded from 933 layers at 100 weeks. Statistical analyses were performed on replicate means, with four to five and nine replicates per combination of hybrid and diet in Floor and FC groups, respectively.4. Cumulative mortality was 9.6% and 16.3% in FC and Floor, respectively, and increased in the latter part of the production cycle, particularly in the Floor group.5. In FC, LSL had inferior feather cover, less keel bone deviation, and shorter claws than BoW. In Floor, LSL had superior feather cover, less severe vent wounds, more bumble foot, and cleaner plumage than BoW. In both production systems, claws grew longer and keel bone deviation became more severe with age.6. In FC, layers fed organic Zn had lower body weight and less keel bone deviation at 100 weeks of age.7. In conclusion, keel bone integrity, claw length, and mortality rate are potential threats to welfare in long-life layers. Feather pecking is a problem that needs addressing at an early stage in the production period. On the whole, organic Zn did not improve welfare conditions in long-life layers.
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25. |
- Alhassan, E., et al.
(author)
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In search of the best nuclear data file for proton induced reactions : Varying both models and their parameters
- 2020
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In: ND 2019. - : EDP Sciences. - 9782759891061
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Conference paper (peer-reviewed)abstract
- A lot of research work has been carried out in fine tuning model parameters to reproduce experimental data for neutron induced reactions. This however is not the case for proton induced reactions where large deviations still exist between model calculations and experiments for some cross sections. In this work, we present a method for searching both the model and model parameter space in order to identify the 'best' nuclear reaction models with their parameter sets that reproduces carefully selected experimental data. Three sets of experimental data from EXFOR are used in this work: (1) cross sections of the target nucleus (2) cross sections of the residual nuclei and (3) angular distributions. Selected models and their parameters were varied simultaneously to produce a large set of random nuclear data files. The goodness of fit between our adjustments and experimental data was achieved by computing a global reduced chi square which took into consideration the above listed experimental data. The method has been applied for the adjustment of proton induced reactions on Co-59 between 1 to 100 MeV. The adjusted files obtained are compared with available experimental data and evaluations from other nuclear data libraries.
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26. |
- Ancelle-Park, R., et al.
(author)
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Summary of the evidence of breast cancer service screening outcomes in Europe and first estimate of the benefit and harm balance sheet
- 2012
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In: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 19, s. 5-13
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Journal article (peer-reviewed)abstract
- Objectives To construct a European 'balance sheet' of key outcomes of population-based mammographic breast cancer screening, to inform policy-makers, stakeholders and invited women. Methods From the studies reviewed, the primary benefit of screening, breast cancer mortality reduction, was compared with the main harms, over-diagnosis and false-positive screening results (FPRs). Results Pooled estimates of breast cancer mortality reduction among invited women were 25% in incidence-based mortality studies and 31% in case-control studies (38% and 48% among women actually screened). Estimates of over-diagnosis ranged from 1% to 10% of the expected incidence in the absence of screening. The combined estimate of over-diagnosis for screened women, from European studies correctly adjusted for lead time and underlying trend, was 6.5%. For women undergoing 10 biennial screening tests, the estimated cumulative risk of a FPR followed by non-invasive assessment was 17%, and 3% having an invasive assessment. For every 1000 women screened biennially from age 50-51 until age 68-69 and followed up to age 79, an estimated seven to nine lives are saved, four cases are over-diagnosed, 170 women have at least one recall followed by non-invasive assessment with a negative result and 30 women have at least one recall followed by invasive procedures yielding a negative result. Conclusions The chance of saving a woman's life by population-based mammographic screening of appropriate quality is greater than that of over-diagnosis. Service screening in Europe achieves a mortality benefit at least as great as the randomized controlled trials. These outcomes should be communicated to women offered service screening in Europe.
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29. |
- Brandsma, Rick, et al.
(author)
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Diagnostic approach to paediatric movement disorders : a clinical practice guide
- 2021
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In: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 63:3, s. 252-258
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Journal article (peer-reviewed)abstract
- Paediatric movement disorders (PMDs) comprise a large group of disorders (tics, myoclonus, tremor, dystonia, chorea, Parkinsonism, ataxia), often with mixed phenotypes. Determination of the underlying aetiology can be difficult given the broad differential diagnosis and the complexity of the genotype–phenotype relationships. This can make the diagnostic process time-consuming and difficult. In this overview, we present a diagnostic approach for PMDs, with emphasis on genetic causes. This approach can serve as a framework to lead the clinician through the diagnostic process in eight consecutive steps, including recognition of the different movement disorders, identification of a clinical syndrome, consideration of acquired causes, genetic testing including next-generation sequencing, post-sequencing phenotyping, and interpretation of test results. The aim of this approach is to increase the recognition and diagnostic yield in PMDs. What this paper adds: An up-to-date description and diagnostic framework for testing of paediatric movement disorders is presented. The framework helps to determine which patients will benefit from next-generation sequencing.
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31. |
- Carlborg, Örjan, et al.
(author)
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Methodological aspects of the genetic dissection of gene expression.
- 2005
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In: Bioinformatics. - 1367-4803 .- 1367-4811. ; 21:10
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Journal article (peer-reviewed)abstract
- MOTIVATION: Dissection of the genetics underlying gene expression utilizes techniques from microarray analyses as well as quantitative trait loci (QTL) mapping. Available QLT mapping methods are not tailored for the highly automated analyses required to deal with the thousand of gene transcripts encountered in the mapping of QTL affecting gene expression (sometimes referred to as eQTL). This report focuses on the adaptation of QTL mapping methodology to perform automated mapping of QTL affecting gene expression.RESULTS: The analyses of expression data on > 12,000 gene transcripts in BXD recombinant inbred mice found, on average, 629 QTL exceeding the genome-wide 5% threshold. Using additional information on trait repeatabilities and QTL location, 168 of these were classified as 'high confidence' QTL. Current sample sizes of genetical genomics studies make it possible to detect a reasonable number of QTL using simple genetic models, but considerably larger studies are needed to evaluate more complex genetic models. After extensive analyses of real data and additional simulated data (altogether > 300,000 genome scans) we make the following recommendations for detection of QTL for gene expression: (1) For populations with an unbalanced number of replicates on each genotype, weighted least squares should be preferred above ordinary least squares. Weights can be based on repeatability of the trait and the number of replicates. (2) A genome scan based on multiple marker information but analysing only at marker locations is a good approximation to a full interval mapping procedure. (3) Significance testing should be based on empirical genome-wide significance thresholds that are derived for each trait separately. (4) The significant QTL can be separated into high and low confidence QTL using a false discovery rate that incorporates prior information such as transcript repeatabilities and co-localization of gene-transcripts and QTL. (5) Including observations on the founder lines in the QTL analysis should be avoided as it inflates the test statistic and increases the Type I error. (6) To increase the computational efficiency of the study, use of parallel computing is advised. These recommendations are summarized in a possible strategy for mapping of QTL in a least squares framework.AVAILABILITY: The software used for this study is available on request from the authors.
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32. |
- Castela Forte, José, et al.
(author)
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Development and Validation of Decision Rules Models to Stratify Coronary Artery Disease, Diabetes, and Hypertension Risk in Preventive Care : Cohort Study of Returning UK Biobank Participants
- 2021
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In: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:12
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Journal article (peer-reviewed)abstract
- Many predictive models exist that predict risk of common cardiometabolic conditions. However, a vast majority of these models do not include genetic risk scores and do not distinguish between clinical risk requiring medical or pharmacological interventions and pre-clinical risk, where lifestyle interventions could be first-choice therapy. In this study, we developed, validated, and compared the performance of three decision rule algorithms including biomarkers, physical measurements, and genetic risk scores for incident coronary artery disease (CAD), diabetes (T2D), and hypertension against commonly used clinical risk scores in 60,782 UK Biobank participants. The rules models were tested for an association with incident CAD, T2D, and hypertension, and hazard ratios (with 95% confidence interval) were calculated from survival models. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), and Net Reclassification Index (NRI). The higher risk group in the decision rules model had a 40-, 40.9-, and 21.6-fold increased risk of CAD, T2D, and hypertension, respectively (p < 0.001 for all). Risk increased significantly between the three strata for all three conditions (p < 0.05). Based on genetic risk alone, we identified not only a high-risk group, but also a group at elevated risk for all health conditions. These decision rule models comprising blood biomarkers, physical measurements, and polygenic risk scores moderately improve commonly used clinical risk scores at identifying individuals likely to benefit from lifestyle intervention for three of the most common lifestyle-related chronic health conditions. Their utility as part of digital data or digital therapeutics platforms to support the implementation of lifestyle interventions in preventive and primary care should be further validated.
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33. |
- Chadwick, MB, et al.
(author)
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Open problems in quantum-mechanical approaches to multistep direct nuclear reactions
- 1999
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In: ACTA PHYSICA SLOVACA. - : SLOVAK ACAD SCIENCES INST PHYSICS. - 0323-0465. ; 49:3, s. 365-379
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Journal article (peer-reviewed)abstract
- Open problems in the theoretical formulation and computational implementation of multistep direct preequilibrium reactions are discussed. Recommendations for future research on both theoretical and experimental aspects of the problem are given.
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34. |
- Dans, Madeline G., et al.
(author)
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Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
- 2024
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
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35. |
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36. |
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37. |
- de koning, jotte Ilbine Jozine Charlotte, et al.
(author)
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GetGreen Vietnam: towards more sustainable behaviour among the urban middle class
- 2016
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In: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 134:part A, s. 178-190
-
Journal article (peer-reviewed)abstract
- In Vietnam, the middle class is expected to grow from 12 million to 33 million people between 2012 and 2020. The growth causes an increase as well as a shift in consumption. Products that were not accessible or affordable before will become increasingly so, such as cars, dishwashers, meat products and air-conditioning. In urban areas the changes are most prominent and so are the side effects: increased amounts of waste, smog, pollution and use of fossil energy or pesticides.The main objective of this study was to identify sustainable behaviour that followed or did not follow from the intervention project GetGreen Vietnam. 604 urban middle class consumers participated in a series of sustainable consumption trainings. Before, during and after the trainings, quantitative and qualitative data was collected on 90 sustainable actions.64% of the participants self-reported to be engaged in a sustainable action before the intervention and this percentage increased to 80% after. The group environment and activity-based meetings of GetGreen Vietnam project (GGVN) were critical for the success of the intervention. Participants reported that before GGVN certain actions were already habitual as a money saving strategy (e.g. sparse electricity use or food leftovers re-use) or due to past scarcity (e.g. sparse water use). Many participants reported the intention to buy sustainable products but fewer participants took action to do so.A powerful strategy toward more sustainable consumption in Vietnam can be to create more group-based activities around the themes of energy and shopping for food. A twofold approach is needed that both installs new sustainable consumption patterns and keeps old habits rooted in daily rituals. Role models should set an example for the young population and consumers and (Vietnamese) producers should be better connected to increase mutual trust and transparency.
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38. |
- De Koning, Tom J., et al.
(author)
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Amino Acid Synthesis Deficiencies
- 2022. - 2
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In: Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, Second Edition. - Cham : Springer International Publishing. - 9783030721848 - 9783030721831 ; , s. 453-467
-
Book chapter (peer-reviewed)abstract
- In recent years the list of disorders affecting amino acid synthesis has grown rapidly. Not only the number of defects has increased, but also the associated clinical phenotypes have expanded spectacular, the latter mainly due to the advances of next-generation sequencing diagnostics. An important reason for the contribution of NGS in the diagnosis of amino acid synthesis disorders is the fact that the biochemical diagnosis of some of these synthesis disorders can be quite challenging, synthesis defects may present with low values of amino acids, or their concentrations can even be completely normal. Defects in the synthesis pathways of serine metabolism, glutamine, glutamate, proline, and asparagine have been reported, and all pose specific challenges to a biochemical diagnosis. An exception to this are the disorders of pyrroline-5-carboxylate (P5C) synthesis where ornithine or proline is strongly elevated and easily detected by plasma amino acid analysis. Finally, Snyder-Robinson, a defect in the synthesis of the polyamine spermine, is discussed here as well, and molecular testing is advised for this disorder as well. Although the amino acid synthesis defects in this chapter are not all in related metabolic pathways, they do share some clinical features. In children the central nervous system is primarily affected, giving rise to (congenital) microcephaly, early-onset seizures, and mental retardation to a variable degree. The brain abnormalities can be accompanied by skin disorders such as cutis laxa in proline defects, collodion-like skin and ichthyosis in serine deficiency, necrolytic erythema in glutamine deficiency, and difficult to classify skin abnormalities in glutaminase hyperactivity. In adults with serine or proline disorders, several forms of polyneuropathy with or without intellectual disability appear to be the major presenting symptom. An exception to this is ornithine aminotransferase deficiency which primarily affects the choroid and retina and Snyder-Robinson syndrome in which mental retardation is accompanied by seizures, dysmorphic features, and severe osteoporosis.
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39. |
- Gudowski, Waclaw, et al.
(author)
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Review of the European project - Impact of Accelerator-Based Technologies on Nuclear Fission Safety (IABAT)
- 2001
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In: Progress in nuclear energy (New series). - 0149-1970 .- 1878-4224. ; 38:1-2, s. 135-151
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Journal article (peer-reviewed)abstract
- The IABAT project - Impact of Accelerator Based Technologies on Nuclear Fission Safety - started in 1996 in the frame of 4(th) Framework Programme of the European Union, R&D specific programme Nuclear fission safety 1994-1998, area A.2 Exploring innovative approaches/Fuel cycle concepts, as one of the first common European activities in ADS. The project was completed October 31, 1999. The overall objective of the IABAT project has been a preliminary assessment of the potential of Accelerator-Driven Systems (ADS) for transmutation of nuclear waste and for nuclear energy production with minimum waste generation. Moreover, more specific topics related to nuclear data and code development for ADS have been studied in more detail. Four ADSs have been studied for different fuel/coolant combinations: liquid metal coolant and solid fuel, liquid metal coolant and dispersed fuel, and fast and thermal molten salt systems. Target studies comprised multiple target solutions and radiation damage problems in a target environment. In a tool development part of the project a methodology of subcriticality monitoring has been developed based on Feynman-alpha and Rossi-alpha methods. Moreover, a new Monte-Carlo burnup code taking full advantage of continuous neutron cross-section data has been developed and benchmarked. Impact on the risk from high-level waste repositories fi om radiotoxicity reduction using ADS has been assessed giving no crystal-clear benefits of ADS for repository radiotoxicity reduction but concluding some important prerequisites for effective transmutation. In proliferation studies important differences between critical reactors and ADS have been underlined and non-proliferation measures have been proposed. In assessment of accelerator technology costing models have been created that allow the circular and linear accelerator options to be compared and the effect of parameter variations examined. The calculations reported show that cyclotron systems would be more economical, due mainly to the advantage of the cost of RF power supplies. However, the accelerator community regards with skepticism the possibility of transporting and extracting more than a 10mA beam current from a 1GeV cyclotron and therefore technical factors may limit the application of cyclotrons. Finally, this review summarizes development of nuclear data in the energy region between 20 Mev and 150 MeV. Neutron and proton transport data files for Fe, Ni, Pb, Th, U-238 and Pu-239 have been created. The high-energy part of the data files consists completely of results from model calculations, which are benchmarked against the available experimental data. Although there is obviously future work left regarding fine-tuning of several parts of the data files, the representation of nuclear reaction information up to 150 MeV is already better than can be attained with intranuclear cascade codes.
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40. |
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41. |
- Hildebrand, Angelica, et al.
(author)
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Elastic Neutron Scattering at 96 MeV
- 2004
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In: Proc. Int. Conf. on Nuclear Data for Science and Technology.
-
Conference paper (other academic/artistic)
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42. |
- Jongs, N, et al.
(author)
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A framework for assessing neuropsychiatric phenotypes by using smartphone-based location data
- 2020
-
In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 211-
-
Journal article (peer-reviewed)abstract
- The use of smartphone-based location data to quantify behavior longitudinally and passively is rapidly gaining traction in neuropsychiatric research. However, a standardized and validated preprocessing framework for deriving behavioral phenotypes from smartphone-based location data is currently lacking. Here, we present a preprocessing framework consisting of methods that are validated in the context of geospatial data. This framework aims to generate context-enriched location data by identifying stationary, non-stationary, and recurrent stationary states in movement patterns. Subsequently, this context-enriched data is used to derive a series of behavioral phenotypes that are related to movement. By using smartphone-based location data collected from 245 subjects, including patients with schizophrenia, we show that the proposed framework is effective and accurate in generating context-enriched location data. This data was subsequently used to derive behavioral readouts that were sensitive in detecting behavioral nuances related to schizophrenia and aging, such as the time spent at home and the number of unique places visited. Overall, our results indicate that the proposed framework reliably preprocesses raw smartphone-based location data in such a manner that relevant behavioral phenotypes of interest can be derived.
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43. |
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44. |
- Koens, Lisette H, et al.
(author)
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A Screening Tool to Quickly Identify Movement Disorders in Patients with Inborn Errors of Metabolism
- 2023
-
In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 38:4, s. 646-653
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Movement disorders are frequent in patients with inborn errors of metabolism (IEMs) but poorly recognized, particularly by nonmovement disorder specialists. We propose an easy-to-use clinical screening tool to help recognize movement disorders.OBJECTIVE: The aim is to develop a user-friendly rapid screening tool for nonmovement disorder specialists to detect moderate and severe movement disorders in patients aged ≥4 years with IEMs.METHODS: Videos of 55 patients with different IEMs were scored by experienced movement disorder specialists (n = 12). Inter-rater agreements were determined on the presence and subtype of the movement disorder. Based on ranking and consensus, items were chosen to be incorporated into the screening tool.RESULTS: A movement disorder was rated as present in 80% of the patients, with a moderate inter-rater agreement (κ =0.420, P < 0.001) on the presence of a movement disorder. When considering only moderate and severe movement disorders, the inter-rater agreement increased to almost perfect (κ = 0.900, P < 0.001). Dystonia was most frequently scored (27.3%) as the dominant phenotype. Treatment was mainly suggested for patients with moderate or severe movement disorders. Walking, observations of the arms, and drawing a spiral were found to be the most informative tasks and were included in the screening tool.CONCLUSIONS: We designed a screening tool to recognize movement disorders in patients with IEMs. We propose that this screening tool can contribute to select patients who should be referred to a movement disorder specialist for further evaluation and, if necessary, treatment of the movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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45. |
- Koning, Nicolas R., et al.
(author)
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A C-H Activation Approach to the Tricyclic Core of Glionitrin A and B
- 2022
-
In: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 7:14, s. 12329-12341
-
Journal article (peer-reviewed)abstract
- Synthesis of diketopiperazines has been of long-standing interest in both natural product synthesis and medicinal chemistry. Here, we present an operationally convenient and efficient approach to the fused indoline-diketopiperazine tricyclic core of glionitrin A/B and related structures using a Pd-catalyzed C-H activation reaction to form the indoline five-membered ring. Exploratory work aimed at elaborating the tricyclic structures into the corresponding natural products is discussed.
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46. |
- Koning, Nicolas R., et al.
(author)
-
Total Synthesis of (−)-Glionitrin A and B Enabled by an Asymmetric Oxidative Sulfenylation of Triketopiperazines
- 2021
-
In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:50, s. 21218-21222
-
Journal article (peer-reviewed)abstract
- Asymmetric construction of dithiodiketopiperazines on otherwise achiral scaffolds remains a pivotal synthetic challenge encountered in many biologically significant natural products. Herein, we report the first total syntheses of (−)-glionitrin A/B and revise the absolute configurations. Emerging from the study is a novel oxidative sulfenylation of triketopiperazines that enables asymmetric formation of dithiodiketopiperazines on sensitive substrates. The concise route paves the way for further studies on the potent antimicrobial and antitumor activities of glionitrin A and the intriguing ability of glionitrin B to inhibit invasive ability of cancer cells.
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47. |
- Koning, Olivier H. J., et al.
(author)
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Fluoroscopic Roentgen stereophotogrammetric analysis (FRSA) to study three-dimensional stent graft dynamics
- 2009
-
In: Journal of Vascular Surgery. - : Elsevier BV. - 1097-6809 .- 0741-5214. ; 50:2, s. 407-412
-
Journal article (peer-reviewed)abstract
- We report the clinical feasibility of fluoroscopic Roentgen stereophotogrammetric analysis (FRSA), a validated method to quantify, real time three-dimensional (3D) dynamic motion of stent grafts and the first clinical results after abdominal and thoracic endovascular repair (EVAR). Stent graft motion was measured at 30 (stereo) frames per second, during the cardiac cycle and in the patient after abdominal EVAR, due to respiratory action. Translational motions of the center of mass, diameter change, and rotational and axial motion could be measured. Quantification of 3D motion was not available until now. FRSA can provide crucial information on the forces exerted oil stent grafts and will, therefore, provide essential information for improvements in stent graft design. (J Vasc Surg 2009;50:407-12.)
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48. |
- Manry, Jérémy, et al.
(author)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
-
Journal article (peer-reviewed)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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49. |
- Nanetti, Lorenzo, et al.
(author)
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Child-to-adult transition : a survey of current practices within the European Reference Network for Rare Neurological Diseases (ERN-RND)
- 2024
-
In: Neurological Sciences. - 1590-1874. ; 45:3, s. 1007-1016
-
Journal article (peer-reviewed)abstract
- Background: Transition from child-centered to adult-centered healthcare is a gradual process that addresses the medical, psychological, and educational needs of young people in the management of their autonomy in making decisions about their health and their future clinical assistance. This transfer is challenging across all chronic diseases but can be particularly arduous in rare neurological conditions. Aim: To describe the current practice on the transition process for young patients in centers participating in the European Reference Network for Rare Neurological Diseases (ERN-RND). Methods: Members of the ERN-RND working group developed a questionnaire considering child-to-adult transition issues and procedures in current clinical practice. The questionnaire included 20 questions and was sent to members of the health care providers (HCPs) participating in the network. Results: Twenty ERN-RND members (75% adult neurologists; 25% pediatricians; 5% nurses or study coordinators) responded to the survey, representing 10 European countries. Transition usually occurs between 16 and 18 years of age, but 55% of pediatric HCPs continue to care for their patients until they reach 40 years of age or older. In 5/20 ERN-RND centers, a standardized procedure managing transition is currently adopted, whereas in the remaining centers, the transition from youth to adult service is usually assisted by pediatricians as part of their clinical practice. Conclusions: This survey demonstrated significant variations in clinical practice between different centers within the ERN-RND network. It provided valuable data on existing transition programs and highlighted key challenges in managing transitions for patients with rare neurological disorders.
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50. |
- Nano, Rita, et al.
(author)
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Heterogeneity of Human Pancreatic Islet Isolation Around Europe : Results of a Survey Study
- 2020
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In: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 104:1, s. 190-196
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Journal article (peer-reviewed)abstract
- Background: Europe is currently the most active region in the field of pancreatic islet transplantation, and many of the leading groups are actually achieving similar good outcomes. Further collaborative advances in the field require the standardization of islet cell product isolation processes, and this work aimed to identify differences in the human pancreatic islet isolation processes within European countries.Methods: A web-based questionnaire about critical steps, including donor selection, pancreas processing, pancreas perfusion and digestion, islet counting and culture, islet quality evaluation, microbiological evaluation, and release criteria of the product, was completed by isolation facilities participating at the Ninth International European Pancreas and Islet Transplant Association (EPITA) Workshop on Islet-Beta Cell Replacement in Milan.Results: Eleven islet isolation facilities completed the questionnaire. The facilities reported 445 and 53 islet isolations per year over the last 3 years from deceased organ donors and pancreatectomized patients, respectively. This activity resulted in 120 and 40 infusions per year in allograft and autograft recipients, respectively. Differences among facilities emerged in donor selection (age, cold ischemia time, intensive care unit length, amylase concentration), pancreas procurement, isolation procedures (brand and concentration of collagenase, additive, maximum acceptable digestion time), quality evaluation, and release criteria for transplantation (glucose-stimulated insulin secretion tests, islet numbers, and purity). Moreover, even when a high concordance about the relevance of one parameter was evident, thresholds for the acceptance were different among facilities.Conclusions: The result highlighted the presence of a heterogeneity in the islet cell product process and product release criteria.
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