| 1. |
- Baumeister, Hannah, et al.
(författare)
-
A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings
-
Ingår i: Brain : a journal of neurology. - 1460-2156. ; 147:7, s. 2400-2413
-
Tidskriftsartikel (refereegranskat)abstract
- Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5), as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD biomarker levels, APOE ε4 carriership, and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of MCI conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, both on the subject and group level, were excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.
|
|
| 2. |
- Thienel, Manuela, et al.
(författare)
-
Immobility-associated thromboprotection is conserved across mammalian species from bear to human
- 2023
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6641, s. 178-187
-
Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.
|
|
| 3. |
|
|
| 4. |
- Bennaceur, A., et al.
(författare)
-
Mechanisms for leveraging models at runtime in self-adaptive software
- 2014
-
Ingår i: Lecture Notes in Computer Science: Dagstuhl Seminar 11481 on Models@run.time; ; 27 November 2011 through 2 December 2011. - Cham : Springer. - 9783319089140
-
Konferensbidrag (refereegranskat)abstract
- Modern software systems are often required to adapt their behavior at runtime in order to maintain or enhance their utility in dynamic environments. Models at runtime research aims to provide suitable abstractions, techniques, and tools to manage the complexity of adapting software systems at runtime. In this chapter, we discuss challenges associated with developing mechanisms that leverage models at runtime to support runtime software adaptation. Specifically, we discuss challenges associated with developing effective mechanisms for supervising running systems, reasoning about and planning adaptations, maintaining consistency among multiple runtime models, and maintaining fidelity of runtime models with respect to the running system and its environment. We discuss related problems and state-of-the-art mechanisms, and identify open research challenges.
|
|
| 5. |
- Brehony, Carina, et al.
(författare)
-
Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development
- 2014
-
Ingår i: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 21:6, s. 847-853
-
Tidskriftsartikel (refereegranskat)abstract
- New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and >= 25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.
|
|
| 6. |
- Brun, Matthias A, et al.
(författare)
-
Semisynthesis of fluorescent metabolite sensors on cell surfaces.
- 2011
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 133:40
-
Tidskriftsartikel (refereegranskat)abstract
- Progress in understanding signal transduction and metabolic pathways is hampered by a shortage of suitable sensors for tracking metabolites, second messengers, and neurotransmitters in living cells. Here we introduce a class of rationally designed semisynthetic fluorescent sensor proteins, called Snifits, for measuring metabolite concentrations on the cell surface of mammalian cells. Functional Snifits are assembled on living cells through two selective chemical labeling reactions of a genetically encoded protein scaffold. Our best Snifit displayed fluorescence intensity ratio changes on living cells significantly higher than any previously reported cell-surface-targeted fluorescent sensor protein. This work establishes a generally applicable and rational strategy for the generation of cell-surface-targeted fluorescent sensor proteins for metabolites of interest.
|
|
| 7. |
- Gernhardt, Benjamin, et al.
(författare)
-
A SEMANTIC REPRESENTATION FOR PROCESS-ORIENTED KNOWLEDGE MANAGEMENT BASED ON FUNCTIONBLOCK DOMAIN MODELS SUPPORTING DISTRIBUTED AND COLLABORATIVE PRODUCTION PLANNING
- 2015
-
Ingår i: PROCEEDINGS OF THE ASME 10TH INTERNATIONAL MANUFACTURING SCIENCE AND ENGINEERING CONFERENCE, 2015, VOL 2. - : AMER SOC MECHANICAL ENGINEERS.
-
Konferensbidrag (refereegranskat)abstract
- Semantic knowledge representation, management, sharing, access, and re-use approaches can support collaborative production planning in a flexible and efficient as well as an effective way. Therefore, semantic-technology based representations of Collaborative Production Process Planning (CAPP) knowledge integrated into a machine readable process formalization is a key enabling factor for sharing such knowledge in cloud-based semantic-enabled knowledge repositories supporting CAPP scenarios as required in the CAPP4SMES project [1]. Beyond that, Small and Medium Enterprises (SMEs) as represented in CAPP4SMES request for a standardized CAPP-oriented product-knowledge- and production-feature representation that can be achieved by applying function-block based knowledge representation models. Semantic Web- and at the same time Cloud-based technologies, tool suites and application solutions which are based on process-oriented semantic knowledge representation methodologies such as Process-oriented Knowledge-based Innovation Management (German: Wissens-basiertes Prozesess-orientiertes Innovationsmanagement, WPIM) [2] can satisfy these needs, supporting the semantic integration, management, access and re-use in a machine readable and integrated representation of distributed CAPP knowledge that is shared within a cloud-based centralized semantic-enabled knowledge repository. Furthermore semantic knowledge representation and querying add value to knowledge-based and computer-aided re-use of such knowledge within CAPP activities and, finally, pave the way towards further automating planning, simulation and optimization support in a semantic web for CAPP.
|
|
| 8. |
- Gernhardt, Benjamin, et al.
(författare)
-
A Semantic Representation for Process-Oriented Knowledge Management to Support Production Planning based on Function Block Domain Models and a Three-level Mediator Architecture
- 2015
-
Konferensbidrag (refereegranskat)abstract
- Semantic knowledge representation, management, sharing, access, and re-use approaches can support collaborative production planning in a flexible and efficient as well as an effective way. Therefore, semantic-technology based representations of Collaborative Production Process Planning (CAPP) knowledge integrated into a machine readable process formalization is a key enabling factor for sharing such knowledge in cloud-based semantic-enabled knowledge repositories supporting CAPP scenarios as required in the CAPP4SMES project [1]. Beyond that, Small and Medium Enterprises (SMEs) as represented in CAPP4SMES request for a standardized CAPP-oriented product-knowledge- and production-feature representation that can be achieved by applying function-block based knowledge representation models. Semantic Web- and at the same time Cloud-based technologies, tool suites and application solutions which are based on process-oriented semantic knowledge representation methodologies such as Process-oriented Knowledge-based Innovation Management (German: Wissens-basiertes Prozesess-orientiertes Innovationsmanagement, WPIM) [2] can satisfy these needs, supporting the semantic integration, management, access and re-use in a machine readable and integrated representation of distributed CAPP knowledge that is shared within a cloud-based centralized semantic-enabled knowledge repository. Furthermore semantic knowledge representation and querying add value to knowledge-based and computer-aided re-use of such knowledge within CAPP activities and, finally, pave the way towards further automating planning, simulation and optimization support in a semantic web for CAPP.
|
|
| 9. |
- Gernhardt, Benjamin, et al.
(författare)
-
IMPLEMENTATION OF A KNOWLEDGE-BASED PRODUCTION PLANNING INCLUDING A DIRECT MANIPULATIVE PROCESS EDITOR AND A MEDIATOR ARCHITECTURE
- 2017
-
Ingår i: PROCEEDINGS OF THE ASME 12TH INTERNATIONAL MANUFACTURING SCIENCE AND ENGINEERING CONFERENCE - 2017, VOL 3. - : AMER SOC MECHANICAL ENGINEERS.
-
Konferensbidrag (refereegranskat)abstract
- Today, in the era of modern Intelligent Production Environments (IPE) and Industry 4.0, the manufacturing of a product takes place in various partial steps and these mostly in different locations, potentially distributed all over the world. The producing companies must assert in the global market and always find new ways to cut costs by saving tax, changing to the best providers, and by using the most efficient and fastest production processes. Furthermore, they must be inevitably based on a cloud-based repository and distributed architectures to make data and information accessible everywhere as well as development processes and knowledge available for a worldwide cooperation. A so called Collaborative Adaptive (Production) Process Planning (CAPP) can be supported by semantic approaches for knowledge representation and management as well as knowledge sharing, access, and re-use in a flexible and efficient way. In this way, to support CAPP scenarios, semantic representations of such knowledge integrated into a machine-readable process formalization is a key enabling factor for sharing in cloud-based knowledge repositories. This is especially required for, e.g., Small and Medium Enterprises (SMEs). When SMEs work together on a production planning for a joint product, they exchange component production and manufacturing change information between different planning subsystems. These exchanges are mostly based on the already well-established Standard for the Exchange of Product model data (STEP), not least to obtain a computer-interpretable representation. Moreover, so-called Function Block (FB) Domain Models could support these planning process. FBs serve as a high-level planning-process knowledge-resource template and to the representation of knowledge. Furthermore, methodologies are required, which based on process-oriented semantic knowledge-representation, such as Process-oriented Knowledge-based Innovation Management (German: Wissens-basiertes Prozess-orientiertes Innovations Management, WPIM). WPIM is already a web and cloud-based tool suites and can represent such planning processes and their knowledge resources and can therefore be used to support the integration and the management of distributed CAPP knowledge in Manufacturing Change Management (MCM), as well as its access and re-use. That is also valid for Assembly-, Logistics- and Layout Planning (ALLP). On the one hand, a collaborative planning in a machine-readable and integrated representation will be possible as well as an optimization for mass production. On the other hand, within a cloud-based semantic knowledge repository, that knowledge can be shared with all partners and contributors. To combine all these functionalities, in 2016 we have already introduced a method, called Knowledge-based Production Planning (KPP). We outlined the theoretical advantages of integrating CAPP with Collaborative Manufacturing Change Management (CMCM) in the last year at MSEC16. In this Paper, we will demonstrate our first implementations of the KPP application with an integrated visual direct manipulative process editor as well as a first prototype of our mediator architecture with a semantic integration including a query library based on the KPP ontology.
|
|
| 10. |
- Gernhardt, Benjamin, et al.
(författare)
-
Knowledge-Based Production Planning Within the Reference Planning Process Supporting Manufacturing Change Management
- 2016
-
Ingår i: Proceedings of the ASME 11TH International Manufacturing Science and Engineering Conference, 2016, VOL 2. - : AMER SOC MECHANICAL ENGINEERS.
-
Konferensbidrag (refereegranskat)abstract
- The manufacturing of a product takes place in several partial steps and these mostly in different locations to save tax or to use the best providers. Therefore, in the era of Internet of Things (IoT) and modem Intelligent Production Environments (IPE) are going to be inevitably based on a cloud-based repository and distributed architecture to make data and information accessible everywhere as well as development processes and knowledge available for worldwide cooperation. Semantic approaches for knowledge representation and management as well as knowledge sharing, access, and re-use can support Collaborative Adaptive Production Process Planning (CAPP) in a flexible, efficient, and effective way. Thus, semantic representations of such CAPP knowledge integrated into a machine readable process formalization is a key enabling factor for sharing such knowledge in cloud-based knowledge repositories supporting CAPP scenarios as required for e.g., Small and Medium Enterprises (SMEs). When such contributors work together on a product component production planning, they exchange component production and manufacturing change information between different planning subsystems which require, e.g., a standardized product-feature and production-machine feature representation. These data exchanges are mostly based on applying the already established Standard for the Exchange of Product model data (STEP) for the computer-interpretable representation and exchange of product manufacturing information. Furthermore, the planning process can be supported by so-called Function Block (FB) based knowledge representation models, serving as a high-level planning-process knowledge-resource template. Web-based and at the same time Cloud-based tool suites, which are based on process-oriented semantic knowledge-representation methodologies, such as Process-oriented Knowledge-based Innovation Management (German: Wissens-basiertes Prozess-orientiertes Innovations Management, WPIM) can satisfy the needs of representing such planning processes and their knowledge resources. In this way, WPIM can be used to support the integration and management of distributed CAPP knowledge, as well as its access and re-use in Manufacturing Change Management (MCM) including Assembly-, Logistics and Layout Planning (ALLP). Therefore, also a collaborative planning and optimization for mass production in a machine readable and integrated representation is possible. On the other hand, that knowledge can be shared within a cloud-based semantic knowledge repository. To integrate all these functionalities, this paper introduces a new method, called Knowledge-based Production Planning (KPP) and outlines the advantages of integrating CAPP with Collaborative Manufacturing Change Management (CMCM). In this way, an enabling basis for achieving ALLP interoperability in Distributed Collaborative Manufacturing and Logistics will be demonstrated.
|
|
| 11. |
- Gernhardt, Benjamin, et al.
(författare)
-
Supporting production planning through semantic mediation of processing functionality
- 2016
-
Konferensbidrag (refereegranskat)abstract
- Semantic approaches for knowledge representation and management as well as knowledge sharing, access and re-use can support Collaborative Adaptive Production Process Planning (CAPP) in a flexible, efficient and effective way. Therefore, semantic representations of such CAPP knowledge integrated into a machine readable process formalization is a key enabling factor for sharing such knowledge in cloud-based knowledge repositories supporting CAPP scenarios as required in the CAPP-4-SMEs project. Beyond that, Small and Medium Enterprises (SMEs) as represented in CAPP-4-SMEs request for a standardized production-feature representation. That can be achieved by applying so-called Function Block (FB) based knowledge representation models. Web-based and at the same time Cloud-based tool suites which are based on process-oriented semantic knowledge-representation methodologies, such as Process-oriented Knowledge-based Innovation Management (German: Wissens-basiertes Prozess-orientiertes Innovations Management, WPIM) can satisfy these needs. In this way, WPIM can be applied to support the integration and management of distributed CAPP knowledge, as well as its access and re-use in a machine readable and integrated representation. On the other hand, that knowledge can be shared within a cloud-based semantic knowledge repository. Furthermore, semantic knowledge representation and querying will add value to the knowledge-based and computer-aided re-use of such machine-readable knowledge resources within CAPP activities. Finally, it will pave the way towards further automating planning, simulation and optimization in a semantic-web for CAPP.
|
|
| 12. |
- Krönke, Anna A., et al.
(författare)
-
Persistent organic pollutants in pregnant women potentially affect child development and thyroid hormone status
- 2022
-
Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447. ; 91:3, s. 690-698
-
Tidskriftsartikel (refereegranskat)abstract
- Background Potentially harmful effects of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) on prenatal development and the endocrine system have been controversially discussed. Methods Working with a German cohort of 324 pregnant women, we assessed POP levels and used robust linear regression models to determine potential associations between maternal POP concentrations and pre- and postnatal development in the children, as well as the thyroid hormone status of the mother and child. Results Maternal p,p '-dichlorodiphenyldichloroethylene (p,p '-DDE) and most measured PCBs positively correlated with postnatal weight gain. We detected no correlation between newborn birth weight and head circumference, respectively, and maternal PCB and p,p '-DDE serum levels, while body length at birth was negatively associated with the maternal serum concentration of PCB 183. Maternal p,p '-DDE and nearly all PCB serum levels showed a negative correlation with maternal free triiodothyronine (FT3). p,p '-DDE and PCB 74 and 118 were negatively associated with maternal thyroid-stimulating hormone levels. In addition, we identified significant associations between maternal POP levels and thyroid hormone parameters of the child. Conclusions These results indicate that POP exposure likely affects different aspects of pre- and postnatal development and impacts the thyroid hormone status of both mother and child. Impact Pregnant women in a German cohort display a substantial accumulation of POPs. Body mass index and age influence maternal serum POP levels. Maternal POP levels show correlations with the child's length at birth and weight gain, and FT3 levels in the mother and child. Our data provide additional evidence for the potentially harmful influence of POPs. Our data indicate that POPs influence pre- and postnatal development.
|
|
| 13. |
- Menkveld, Albert J., et al.
(författare)
-
Nonstandard Errors
- 2024
-
Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
|
|
| 14. |
- Sánchez Van Kammen, Mayte, et al.
(författare)
-
Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia
- 2021
-
Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:11, s. 1314-1323
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.Main Outcomes and Measures: Clinical characteristics and mortality rate.Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination..
|
|
| 15. |
- Schafmayer, Clemens, et al.
(författare)
-
Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms
- 2019
-
Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 68:5, s. 854-865
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. Design Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. Results We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p< 0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3x10-10 and 0.002 (OR allelic = 1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). Conclusion I n silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.
|
|
| 16. |
- Scutelnic, Adrian, et al.
(författare)
-
Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.
- 2022
-
Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
|
|
| 17. |
- Taha, Muhamed-Kheir, et al.
(författare)
-
Interlaboratory Comparison of PCR-Based Identification and Genogrouping of Neisseria meningitidis
- 2005
-
Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 43:1, s. 144-149
-
Tidskriftsartikel (refereegranskat)abstract
- Twenty clinical samples (18 cerebrospinal fluid samples and 2 articular fluid samples) were sent to 11 meningococcus reference centers located in 11 different countries. Ten of these laboratories are participating in the EU-MenNet program (a European Union-funded program) and are members of the European Monitoring Group on Meningococci. The remaining laboratory was located in Burkina Faso. Neisseria meningitidis was sought by detecting several meningococcus-specific genes (crgA, ctrA, 16S rRNA, and porA). The PCR-based nonculture method for the detection of N. meningitidis gave similar results between participants with a mean sensitivity and specificity of 89.7 and 92.7%, respectively. Most of the laboratories also performed genogrouping assays (siaD and mynB/sacC). The performance of genogrouping was more variable between laboratories, with a mean sensitivity of 72.7%. Genogroup B gave the best correlation between participants, as all laboratories routinely perform this PCR. The results for genogroups A and W135 were less similar between the eight participating laboratories that performed these PCRs.
|
|
| 18. |
- Vogel-Heuser, B., et al.
(författare)
-
Selected challenges of software evolution for automated production systems
- 2015
-
Ingår i: 13th International Conference on Industrial Informatics, INDIN 2015, Robinson College, Cambridge, United Kingdom, 22 - 24 July 2015. - : IEEE. - 9781479966493
-
Konferensbidrag (refereegranskat)abstract
- Automated machines and plants are operated for some decades and undergo an everlasting evolution during this time. In this paper, we present three related open evolution challenges focusing on software evolution in the domain of automated production systems, i.e. evolution and co-evolution of (interdisciplinary) engineering models and code, quality assurance as well as variant and version management during evolution.
|
|
| 19. |
- Vogel-Heuser, B., et al.
(författare)
-
Technical debt in Automated Production Systems
- 2015
-
Ingår i: 7th International Workshop on Managing Technical Debt, MTD 2015, Bremen, Germany. - 9781467373784 ; , s. 49-52
-
Konferensbidrag (refereegranskat)abstract
- The term technical debt borrowed from financial debt describes the long-term negative effects of sub-optimal solutions to achieve short-term benefits. It has been widely studied so far in pure software systems. However, there is a lack of studies on technical debt in technical systems, which contain mechanical, electrical and software parts. Automated Production Systems are such technical systems. In this position paper, we introduce technical debt for Automated Production Systems and give examples from the different disciplines. Based on that description, we outline future research directions on technical debt in this field.
|
|
| 20. |
- Wang, Fang, et al.
(författare)
-
Emerging contaminants: A One Health perspective
- 2024
-
Ingår i: Innovation. - 2666-6758. ; 5
-
Forskningsöversikt (refereegranskat)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
|
|
| 21. |
- Wang, Zhaoming, et al.
(författare)
-
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
|
|
| 22. |
- Yi, Chuixiang, et al.
(författare)
-
Climate control of terrestrial carbon exchange across biomes and continents
- 2010
-
Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 5:3
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predict future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks. However, directly observed relationships between climate and terrestrial CO2 exchange with the atmosphere across biomes and continents are lacking. Here we present data describing the relationships between net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 125 unique sites in various ecosystems over six continents with a total of 559 site-years. We find that NEE observed at eddy covariance sites is (1) a strong function of mean annual temperature at mid-and high-latitudes, (2) a strong function of dryness at mid-and low-latitudes, and (3) a function of both temperature and dryness around the mid-latitudinal belt (45 degrees N). The sensitivity of NEE to mean annual temperature breaks down at similar to 16 degrees C (a threshold value of mean annual temperature), above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence.
|
|
