| 1. |
- Astermark, Jan, et al.
(författare)
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New Inhibitors in the Ageing Population : A Retrospective, Observational, Cohort Study of New Inhibitors in Older People with Hemophilia
- 2022
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 122:6, s. 905-912
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A second peak of inhibitors has been reported in patients with severe hemophilia A (HA) aged >50 years in the United Kingdom. The reason for this suggested breakdown of tolerance in the aging population is unclear, as is the potential impact of regular exposure to the deficient factor by prophylaxis at higher age. No data on hemophilia B (HB) have ever been reported. Aim The ADVANCE Working Group investigated the incidence of late-onset inhibitors and the use of prophylaxis in patients with HA and HB aged ≥40 years. Methods A retrospective, observational, cohort, survey-based study of all patients aged ≥40 years with HA or HB treated at an ADVANCE hemophilia treatment center. Results Information on 3,095 people aged ≥40 years with HA or HB was collected. Of the 2,562 patients with severe HA, the majority (73% across all age groups) received prophylaxis. In patients with severe HA, the inhibitor incidence per 1,000 treatment years was 2.37 (age 40-49), 1.25 (age 50-59), and 1.45 (age 60 +). Overall, the inhibitor incidence was greatest in those with moderate HA (5.77 [age 40-49], 6.59 [age 50-59], and 4.69 [age 60 + ]) and the majority of inhibitor cases were preceded by a potential immune system challenge. No inhibitors in patients with HB were reported. Conclusion Our data do not identify a second peak of inhibitor development in older patients with hemophilia. Prophylaxis may be beneficial in older patients with severe, and possibly moderate HA, to retain a tolerant state at a higher age.
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| 2. |
- Bruel, Laure, et al.
(författare)
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HMI tests in simulator
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The main goal of SASPENCE is to develop and evaluate an innovative system able to perform the Safe Speed and Safe Distance concept, that means to help the driver in avoiding accident situations related to excessive speed or too small headway. So, the system should co-operate seamlessly with the driver, suggesting the proper velocity for the given condition (road structure, traffic situation, etc.) preventing risky and dangerous situations and thus avoiding collision. This support is done through a Human Machine Interface (HMI). It is essential that the HMIs are easily understandable by the driver and that they induce a suitable reaction to the danger, otherwise the system is worthless. The simulator tests are the second step of the HMI design process that counts three of them. After the static tests that have enabled to show up the preferred visual, haptic and acoustic HMI, 8 combinations of HMI have been tested in dynamic conditions in the PSA driving simulator while part of the SASPENCE modules were running and tested. These tests should enable us to understand which HMIs are the best for the driver, that is to say, which HMI makes it possible to give the SASPENCE information in the clearest way to the driver. The main aims of these tests were to evaluate the effects of the SASPENCE system on drivers’ behaviour and to give recommendations for the HMI to be installed in the two test-cars, according to drivers’ preference and the efficiency of the HMI. They were also useful: - to improve the representativeness of the static tests results, - to check the good operation of some modules, that will be implemented in the test cars, and to check the good communication between the driver and the HMI, very early in the project, long before the demonstration cars are ready, - to complete the final road tests by measurements and observations in a more reproducible and observable conditions than the real road test. One interesting result of these tests is that the HMIs that were selected at the end of the static tests appeared to be too complex to be understood when one was driving. Another main result is that the SASPENCE system is efficient, as drivers spend less time in risky situations when driving with the SASPENCE system.
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| 3. |
- Chassagne, Pierre, et al.
(författare)
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Structural Studies of the O-Acetyl-Containing O-Antigen from a Shigella flexneri Serotype 6 Strain and Synthesis of Oligosaccharide Fragments Thereof
- 2013
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; :19, s. 4085-4106
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Tidskriftsartikel (refereegranskat)abstract
- Extensive analysis by NMR spectroscopy of the delipidated lipopolysaccharide of Shigella flexneri serotype 6 strain MDC 2924-71 confirmed the most recently reported structure of the O-antigen repeating unit as {4)--D-GalpA-(13)--D-GalpNAc-(12)--L-Rhap3Ac/4Ac-(12)--L-Rhap-(1}, and revealed the non-stoichiometric acetylation at O-3C/4C. Input from the CASPER program helped to ascertain the fine distribution of the three possible patterns of O-acetylation. The non-O-acetylated repeating unit (ABCD) corresponded to about 2/3 of the population, while 1/4 was acetylated at O-3C (3AcCDAB), and 1/10 at O-4C (4AcCDAB). Di- to tetrasaccharides with a GalpA residue (A) at their reducing end were synthesized as their propyl glycosides following a multistep linear strategy relying on late-stage acetylation at O-3C. Thus, the 3C-O-acetylated and non-O-acetylated targets were synthesized from common protected intermediates. Rhamnosylation was most efficiently achieved by using imidate donors, including at O-4 of a benzyl galacturonate acceptor. In contrast, a thiophenyl 2-deoxy-2-trichloroacetamido-D-galactopyranoside precursor was preferred for chain elongation involving residue B. Final Pd/C-mediated deprotection ensured O-acetyl stability. All of the target molecules represent parts of the O-antigen of S. flexneri 6, a prevalent serotype. Non-O-acetylated oligosaccharides are also fragments of the Escherichia coli O147 O-antigen.
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| 4. |
- Fontana, Carolina, et al.
(författare)
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Structural Studies of Lipopolysaccharide-defective Mutants from Brucella melitensis Identify a Core Oligosaccharide Critical in Virulence
- 2016
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Ingår i: Journal of Biological Chemistry. - : The American Society for Biochemistry and Molecular Biology, Inc.. - 0021-9258 .- 1083-351X. ; 291:14, s. 7727-7741
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Tidskriftsartikel (refereegranskat)abstract
- The structures of the lipooligosaccharides from Brucella melitensis mutants affected in the WbkD and ManB(core) proteins have been fully characterized using NMR spectroscopy. The results revealed that disruption of wbkD gives rise to a rough lipopolysaccharide (R-LPS) with a complete core structure (beta-D-Glcp-(1 -> 4)-alpha-Kdop-(2 -> 4)[beta-D-GlcpN-(1 -> 6)-beta-D-GlcpN-(1 -> 4)[beta-D-GlcpN-(1 -> 6)]-beta-D-GlcpN-(1 -> 3)-alpha-D-Manp-(1 -> 5)]-alpha-Kdop-(2 -> 6)-beta-D-GlcpN3N4P-(1 -> 6)-alpha-D-GlcpN3N1P), in addition to components lacking one of the terminal beta-D-GlcpN and/or the beta-D-Glcp residues (48 and 17%, respectively). These structures were identical to those of the R-LPS from B. melitensis EP, a strain simultaneously expressing both smooth and R-LPS, also studied herein. In contrast, disruption of man-B-core gives rise to a deep-rough pentasaccharide core (beta-D-Glcp-(1 -> 4)-alpha-Kdop-(2 -> 4)-alpha-Kdop-(2 -> 6)-beta-D-GlcpN3N4P-(1 -> 6)-alpha-D-GlcpN3N1P) as the major component (63%), as well as a minor tetrasaccharide component lacking the terminal beta-D-Glcp residue (37%). These results are in agreement with the predicted functions of the WbkD (glycosyltransferase involved in the biosynthesis of the O-antigen) and ManB(core) proteins (phosphomannomutase involved in the biosynthesis of a mannosyl precursor needed for the biosynthesis of the core and O-antigen). We also report that deletion of B. melitensis wadC removes the core oligosaccharide branch not linked to the O-antigen causing an increase in overall negative charge of the remaining LPS inner section. This is in agreement with the mannosyltransferase role predicted for WadC and the lack of GlcpN residues in the defective core oligosaccharide. Despite carrying the O-antigen essential in B. melitensis virulence, the core deficiency in the wadC mutant structure resulted in a more efficient detection by innate immunity and attenuation, proving the role of the beta-D-GlcpN-(1 -> 6)-beta-D-GlcpN-(1 -> 4)[beta-D-GlcpN-(1 -> 6)]-beta-D-GlcpN-(1 -> 3)-alpha-D-Manp-(1 -> 5) structure in virulence.
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| 5. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 6. |
- Klamroth, Robert, et al.
(författare)
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Applicability of the European Society of Cardiology Guidelines on the management of acute coronary syndromes to older people with haemophilia A – A modified Delphi consensus by the ADVANCE Working Group
- 2023
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 29:1, s. 21-32
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Forskningsöversikt (refereegranskat)abstract
- Introduction: As people with haemophilia (PWH) receive better treatment and live longer they are more likely to encounter cardiovascular disease (CVD) and other comorbidities. ESC guidelines for the acute management of patients presenting with acute coronary syndrome (ACS) are based on the non-haemophilia population. Aim: To review the guidelines and propose relevant adaptations for PWHA without inhibitors who are treated with prophylaxis and present with ACS. Methods: As part of the ADVANCE Group, 20 European haemophilia experts used a modified Delphi approach to develop and gain consensus on proposed adaptations of the ESC guidelines for PWHA without inhibitors. Results: Of the 32 Class I recommendations across both guidelines, adaptions were considered necessary and proposed for 15. The adaptions highlight the need to provide sufficient FVIII trough levels at the time of antithrombotic treatment in people with haemophilia A (HA) without inhibitors. Patients receiving emicizumab prophylaxis and requiring oral anticoagulation therapy or combined single antiplatelet plus oral anticoagulation therapy will require additional FVIII replacement therapy. Conclusion: In the absence of high-quality clinical evidence, the combined expert opinion used to develop these adaptions to the current ESC guidelines may help to guide clinicians in their treatment decisions when a PWHA presents with ACS.
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| 7. |
- Parducci, Laura, et al.
(författare)
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Glacial Survival of Boreal Trees in Northern Scandinavia
- 2012
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 335:6072, s. 1083-1086
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Tidskriftsartikel (refereegranskat)abstract
- It is commonly believed that trees were absent in Scandinavia during the last glaciation and first recolonized the Scandinavian Peninsula with the retreat of its ice sheet some 9000 years ago. Here, we show the presence of a rare mitochondrial DNA haplotype of spruce that appears unique to Scandinavia and with its highest frequency to the west-an area believed to sustain ice-free refugia during most of the last ice age. We further show the survival of DNA from this haplotype in lake sediments and pollen of Trondelag in central Norway dating back similar to 10,300 years and chloroplast DNA of pine and spruce in lake sediments adjacent to the ice-free Andoya refugium in northwestern Norway as early as similar to 22,000 and 17,700 years ago, respectively. Our findings imply that conifer trees survived in ice-free refugia of Scandinavia during the last glaciation, challenging current views on survival and spread of trees as a response to climate changes.
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