| 1. |
- Holmes, Michael V., et al.
(författare)
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Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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| 2. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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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.
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| 3. |
- Schunkert, Heribert, et al.
(författare)
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Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
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Tidskriftsartikel (refereegranskat)abstract
- We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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| 4. |
- Jakobsson Bergstad, Cecilia, 1967, et al.
(författare)
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The influence of socioeconomic factors in the diffusion of car sharing
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In order to put into relationship, the diffusion of car sharing practices and relevant individual sociodemographic and economic factors, the research started analysing the information in some of the national travel surveys administered throughout Europe. From this research, it emerged that in most of the cases information on the use of car sharing for daily mobility at a national level is of poor quality. In particular, the characteristics of car sharing members such as gender, age, car ownership and travel behaviour have been compared with the characteristics of the population living in the same country or city, coming from the national (or city) travel survey. Since there is an urgent demand to reduce the damaging impact of transportation on the environment (air pollution, noise pollution, reduced green areas, traffic accidents, etc.) in urban cities, we aim to answer the following question: What are the main behavioural, psychological and social factors influencing people’s choice to use car sharing? This main question can be operationalized in more specific sub questions: do users and nonusers of car sharing differ, regarding transport choices? Are there differences among ages and genders for specific services and demands? What are the main motives for using car sharing for users and non-users? Are the social, behavioural and psychological aspects influencing people’s intention to use car sharing? If so, to which extent does it occur? In order to answer those questions, this report was structured in 5 main sections: Section 1: In this section multiple sources were exploited in order to give insights about the impact of car sharing on travel behaviours, among different kind of users and different countries/ cities. Section 2: Based on the model of Technology Acceptance Model (TAM) and the Theory of Planned Behaviour (TPB), the latent variables Attitudes, Perceived Behaviour Control (PBC), Perceived Usefulness (PU), Ease of Use (EU), Subjective Norms (SN), Trust, Personal Norms (PN) Environmental Awareness (EA) and Habit were tested in a linear regression model along with sociodemographic variables to predict behaviour intention to use car sharing. The data were collected by STARS partners along EU countries with users and non-users of car sharing. Section 3: In this case study, it is examined how car sharers in Flanders assess the services of different car sharing organisations. Focus was given on membership, car ownership, customer satisfaction, overall characteristics of the service, costs, flexibility and offer of cars with alternative fuels. The influence of socioeconomic factors in the diffusion of car sharing GA n°769513 Page 17 of 243 Section 4: This second case study analysed and compared behavioural data from URBI during two months in Berlin, Milan, Turin and Madrid. Focus was given to patterns and hourly distribution of trips. Section 5: This case study analysed and compared behavioural data for users and non-users of car sharing in Germany. Focus was given to social demographic variables, the use of smartphones, attitudes towards different transport modes, incentives to use car sharing, support to implement car sharing, characterization of users of car sharing and relation to the characteristics of services.
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| 5. |
- Nehrke, Gunnar, et al.
(författare)
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Mobility cultures and mobility styles
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this deliverable is to gather further insight into the underlying social and emotional factors that amplify or mitigate an affinity to car sharing. The present deliverable partly builds on the results of the studies carried out and presented in in D4.1. It is an input for the general account of the underlying sociodemographic and attitudinal factors for car sharing conversion that will be given in D 4.3. Various methods were used in this deliverable. A cluster analysis was employed to identify mobility styles with different mobility habits and different attitudes towards environmental issues in car sharing users and non-users. Qualitative methods such as focus group discussions, a living lab and empathy interviews were used in order to gain more insights into the emotional and attitudinal drivers for private car and car sharing use. The segmentation of current car-sharing users and non-users studied by STARS in D4.1 resulted in five different mobility styles, three styles for car-sharing users and two for non-users. The cluster analysis in D4.2 now shows how these styles differ in respect to travel behaviour, frequency of car use and attitude towards environmental issues. Mobility styles including frequent car use for daily trips are found in two of the three car sharing user groups. Only one mobility style which is centred on public transport shows a more multimodal profile. The fact that the cluster analysis identified a car-focused green mobility style among car sharing users is particularly interesting. This group has the lowest percentage of car free households but also shows a high level of environmental awareness and concern regarding the impact of travels. This discrepancy between actual behaviour and awareness can only be found in car sharing users. This group of car sharing users might be especially open to reducing car use and changing to a more environment friendly mobility behaviour. To better understand attitudes and emotions towards private and shared cars, focus groups were held in Germany and in Flanders, Belgium. Topics discussed in the focus groups included the unbeatable advantage of the private car, the advantages and disadvantages of car sharing and the motivation to use car sharing. The aim was to explore the practical and emotional value both users and non-users see in car sharing and the private car. The participants of the German focus groups where recruited in inner-city urban residential areas with a high density of car sharing offers and excellent access to public transport. Thus these participants have excellent preconditions to adopt a multimodal mobility behaviour. As expected, public transport and bike are the most used options for every day trips among all participants - users as well as non-users of car sharing. Nevertheless, car ownership is still widespread among the German non-users of car sharing. Car use on the other hand is not: two thirds of participants who own a car Mobility cultures and mobility styles GA n°769513 Page 8 of 74 find car traffic nerve wrecking and use their car only on rare and planned occasions. This rare use of the private car also resembles the classic behaviour of roundtrip car sharing customers in Germany. It can be concluded that these non-users would also be targets for a car sharing. However, conversion to car sharing does not happen for two reasons: firstly, the permanent availability of the private car is experienced as a source of emotional security. Secondly, the private car is experienced as the simplest mode of transport since no planning is needed and no bookings need to be done. Present users of car sharing in the German focus groups only rarely discuss poor availability of car sharing cars and the complexity of booking as a problem. It can be concluded, that non-users overestimate the problems they would face with using car sharing. The German focus groups also show that attitude towards environmental issues differ according to the used car sharing variant. Roundtrip car sharing users are much more sustainabilityoriented while free-floating users more often seek convenience. Roundtrip users literally feel proud of doing something good when using car sharing. This same attitude is also very widespread among car sharing users in the Flanders focus groups. In Flanders one focus group with car sharing non-users and four focus groups with car sharing users were held. As in Germany most non-users own a car. They love the flexibility the car provides and are convinced that car sharing has to be cheaper than a private car since planning and booking would add an extra complexity to their mobility. In contrast to the German non-users, non-users in Flanders still have fun when driving a car. In the Flanders car sharing user groups one half of the participants are peer-to-peer users of a special kind: they take part in private car sharing initiatives that share the cars that some of the households own. This makes the Flanders groups a key reference for understanding peer-to-peer car sharing users better. Car sharing users in Flanders have a strong tendency to see cars as a means to an end. The most striking feature is, that more than half of users where introduced to car sharing by relatives and friends. It shows that peer-to-peer marketing is an important factor to trigger conversion to car sharing. In Flanders a living lab was established: households owning a private car were motivated to test-use other modes for very low costs for a month. Almost all participants liked the experiment and one third got motivated to use their private car less afterwards. However, only a few participants incorporated car sharing into their mobility mix during the experiment. This was because households agreed to use the car less during the experiment but still had it available. Thus, when use cases for a car occurred, households reverted to their private car and not to a shared car. This further illustrates an insight from the non-user focus groups in Flanders and Germany: non-users view car sharing as the inferior option compared to the private car. This again raises the question how the value of a car sharing offer can be increased for owners of a private car. Mobility cultures and mobility styles GA n°769513 Page 9 of 74 30 empathy interviews with car sharing customers were carried out in Turin in order to explore the use of free-floating car sharing more deeply. The interviews show that users are on average very satisfied with the car sharing offer. Those living in one-person households are to a great extent carfree. Car sharing for them is a cheaper alternative to buying a car. Larger households and households with kids often substitute a second car they might need with car sharing. Almost all users revert to car sharing as a replacement for public transport rides or as taxi substitute, for example when going to the airport. It is interesting to notice that some suggestions given by the interviewed customers to improve the free-floating service cite features traditionally associated to roundtrip car sharing offers: longer reservation times, better tariff options to leave the town, a higher certainty of car availability near the geographical location of the customer. This again might be a hint that a better integration of services (and their value proposition) is needed to increase customer value. The results of an expert workshop organized by ICLEI showed that in European countries outside Western Europe car sharing is most of the time identified with free-floating car sharing. This is true for the (potential) customers and sometimes also for city authorities. Since the establishment of a free-floating service is a huge investment that is only possible in big cities, the penetration of car sharing throughout these countries is low compared to countries where roundtrip services are more common (like Belgium or Germany).
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| 6. |
- Ng, Bobby G, et al.
(författare)
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ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients.
- 2016
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794.
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Tidskriftsartikel (refereegranskat)abstract
- Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over one hundred genes leading to impaired protein or lipid glycosylation. ALG1 encodes a β1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate (DLO) required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date thirteen mutations in eighteen patients from fourteen families have been described with varying degrees of clinical severity. We identified and characterized thirty-nine previously unreported cases of ALG1-CDG from thirty-two families and add twenty-six new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2 , was seen in all twenty-seven patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder. This article is protected by copyright. All rights reserved.
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