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1.
  • Abelev, Betty, et al. (författare)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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2.
  • Abelev, Betty, et al. (författare)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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3.
  • Abelev, Betty, et al. (författare)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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4.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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6.
  • Settele, Josef, et al. (författare)
  • Rice ecosystem services in South-east Asia
  • 2018
  • Ingår i: Paddy and Water Environment. - : Springer. - 1611-2490 .- 1611-2504. ; 16:2, s. 211-224
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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7.
  • Alexander, Stephen P. H., et al. (författare)
  • The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
  • 2023
  • Ingår i: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
  • Tidskriftsartikel (refereegranskat)abstract
    • The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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8.
  • Fisher, Michael J., et al. (författare)
  • Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1)
  • 2021
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 141:4, s. 605-617
  • Tidskriftsartikel (refereegranskat)abstract
    • Low-grade gliomas (LGGs) are the most common childhood brain tumor in the general population and in individuals with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Surgical biopsy is rarely performed prior to treatment in the setting of NF1, resulting in a paucity of tumor genomic information. To define the molecular landscape of NF1-associated LGGs (NF1-LGG), we integrated clinical data, histological diagnoses, and multi-level genetic/genomic analyses on 70 individuals from 25 centers worldwide. Whereas, most tumors harbored bi-allelic NF1 inactivation as the only genetic abnormality, 11% had additional mutations. Moreover, tumors classified as non-pilocytic astrocytoma based on DNA methylation analysis were significantly more likely to harbor these additional mutations. The most common secondary alteration was FGFR1 mutation, which conferred an additional growth advantage in multiple complementary experimental murine Nf1 models. Taken together, this comprehensive characterization has important implications for the management of children with NF1-LGG, distinct from their sporadic counterparts.
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10.
  • Nieuwenhuijse, David F., et al. (författare)
  • Setting a baseline for global urban virome surveillance in sewage
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2020, The Author(s). The rapid development of megacities, and their growing connectedness across the world is becoming a distinct driver for emerging disease outbreaks. Early detection of unusual disease emergence and spread should therefore include such cities as part of risk-based surveillance. A catch-all metagenomic sequencing approach of urban sewage could potentially provide an unbiased insight into the dynamics of viral pathogens circulating in a community irrespective of access to care, a potential which already has been proven for the surveillance of poliovirus. Here, we present a detailed characterization of sewage viromes from a snapshot of 81 high density urban areas across the globe, including in-depth assessment of potential biases, as a proof of concept for catch-all viral pathogen surveillance. We show the ability to detect a wide range of viruses and geographical and seasonal differences for specific viral groups. Our findings offer a cross-sectional baseline for further research in viral surveillance from urban sewage samples and place previous studies in a global perspective.
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11.
  • Yildiz, Yildiz, et al. (författare)
  • Functional and genetic characterization of the non-lysosomal glucosylceramidase 2 as a modifier for Gaucher disease
  • 2013
  • Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gaucher disease (GD) is the most common inherited lysosomal storage disorder in humans, caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA1). GD is clinically heterogeneous and although the type of GBA1 mutation plays a role in determining the type of GD, it does not explain the clinical variability seen among patients. Cumulative evidence from recent studies suggests that GBA2 could play a role in the pathogenesis of GD and potentially interacts with GBA1. Methods: We used a framework of functional and genetic approaches in order to further characterize a potential role of GBA2 in GD. Glucosylceramide (GlcCer) levels in spleen, liver and brain of GBA2-deficient mice and mRNA and protein expression of GBA2 in GBA1-deficient murine fibroblasts were analyzed. Furthermore we crossed GBA2-deficient mice with conditional Gba1 knockout mice in order to quantify the interaction between GBA1 and GBA2. Finally, a genetic approach was used to test whether genetic variation in GBA2 is associated with GD and/or acts as a modifier in Gaucher patients. We tested 22 SNPs in the GBA2 and GBA1 genes in 98 type 1 and 60 type 2/3 Gaucher patients for single-and multi-marker association with GD. Results: We found a significant accumulation of GlcCer compared to wild-type controls in all three organs studied. In addition, a significant increase of Gba2-protein and Gba2-mRNA levels in GBA1-deficient murine fibroblasts was observed. GlcCer levels in the spleen from Gba1/Gba2 knockout mice were much higher than the sum of the single knockouts, indicating a cross-talk between the two glucosylceramidases and suggesting a partially compensation of the loss of one enzyme by the other. In the genetic approach, no significant association with severity of GD was found for SNPs at the GBA2 locus. However, in the multi-marker analyses a significant result was detected for p.L444P (GBA1) and rs4878628 (GBA2), using a model that does not take marginal effects into account. Conclusions: All together our observations make GBA2 a likely candidate to be involved in GD etiology. Furthermore, they point to GBA2 as a plausible modifier for GBA1 in patients with GD.
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15.
  • Beck, Florian, et al. (författare)
  • Devitalization of adjacent teeth following maxillary sinus floor augmentation : A retrospective radiographic study
  • 2018
  • Ingår i: Clinical Implant Dentistry and Related Research. - : John Wiley & Sons. - 1523-0899 .- 1708-8208. ; 20:5, s. 763-769
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Elevation of the schneiderian membrane, during maxillary sinus floor augmentation (MSFA) may theoretically result in devitalization of adjacent teeth, which are in a close spatial relationship to the sinus floor. Purpose: To assess retrospectively the probability of devitalization of teeth adjacent to the osteotomy site after MSFA in a relatively large number of patients. Materials and Methods: All MSFA procedures, performed at a university oral surgery clinic within a time period of 10 years, were assessed on the following eligibility criteria: (1) presence of vital teeth (ie, not root canal treated and no periapical radiolucency on a panoramic radio- graph taken just after MSFA), (2) presence of a 3 to 12 months postoperative radiograph of the teeth adjacent to the osteotomy site displaying the root apices, and (3) complete medical records up to at least 12 months postoperatively. The radiographs of the different time points were compared and any changes in the radiographic status of the adjacent teeth (eg, develop- ment of a periapical lesion, root canal treatment, etc.) were recorded and the spatial relationship of the adjacent teeth to the maxillary sinus classified. Results: Out of 684 MSFAs, 257 fulfilled the inclusion criteria and involved 357 adjacent teeth, of which 221 presented close to and/or intimate relationship to the sinus. In only a single case, tooth vitality might have been lost due to the procedure. Thus, the probability for tooth devitali- zation for teeth with close to and/or intimate spatial relationship to the sinus floor ranged from 0.45% to 0.7%. Conclusions: Even for teeth with apices very close to and/or intimately related to the sinus tooth devitalization after MSFA is an extremely rare complication; that is, the probability of tooth devitalization after MSFA is ≤0.7%.
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16.
  • Beck, Florian, et al. (författare)
  • Is MRI a viable alternative to CT/CBCT to identify the course of the inferior alveolar nerve in relation to the roots of the third molars?
  • 2021
  • Ingår i: Clinical Oral Investigations. - : Springer. - 1432-6981 .- 1436-3771. ; 25, s. 3861-3871
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo assess the reliability of judging the spatial relation between the inferior alveolar nerve (IAN) and mandibular third molar (MTM) based on MRI or CT/CBCT images.MethodsAltogether, CT/CBCT and MRI images of 87 MTMs were examined twice by 3 examiners with different degrees of experience. The course of the IAN in relation to the MTM, the presence/absence of a direct contact between IAN and MTM, and the presence of accessory IAN were determined.ResultsThe IAN was in > 40% of the cases judged as inferior, while an interradicular position was diagnosed in < 5% of the cases. The overall agreement was good (κ = 0.72) and any disagreement between the imaging modalities was primarily among the adjacent regions, i.e., buccal/lingual/interradicular vs. inferior. CT/CBCT judgements presented a very good agreement for the inter- and intrarater comparison (κ > 0.80), while MRI judgements showed a slightly lower, but good agreement (κ = 0.74). A direct contact between IAN and MTM was diagnosed in about 65%, but in almost 20% a disagreement between the judgements based on MRI and CT/CBCT was present resulting in a moderate overall agreement (κ = 0.60). The agreement between the judgements based on MRI and CT/CBCT appeared independent of the examiner’s experience and accessory IAN were described in 10 cases in MRI compared to 3 cases in CT/CBCT images.ConclusionsA good inter- and intrarater agreement has been observed for the assessment of the spatial relation between the IAN and MTM based on MRI images. Further, MRI images might provide advantages in the detection of accessory IAN compared to CT/CBCT.Clinical relevanceMRI appears as viable alternative to CT/CBCT for preoperative assessment of the IAN in relation to the MTM.
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17.
  • Björkman, Anne, 1981, et al. (författare)
  • Plant functional trait change across a warming tundra biome
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
  • Tidskriftsartikel (refereegranskat)abstract
    • The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
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18.
  • Brommesson, Peter, et al. (författare)
  • Assessing intrastate shipments from interstate data and expert opinion
  • 2021
  • Ingår i: Royal Society Open Science. - : Royal Society of Open Science. - 2054-5703. ; 8:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Live animal shipments are a potential route for transmitting animal diseases between holdings and are crucial when modelling spread of infectious diseases. Yet, complete contact networks are not available in all countries, including the USA. Here, we considered a 10% sample of Interstate Certificate of Veterinary Inspections from 1 year (2009). We focused on distance dependence in contacts and investigated how different functional forms affect estimates of unobserved intrastate shipments. To further enhance our predictions, we included responses from an expert elicitation survey about the proportion of shipments moving intrastate. We used hierarchical Bayesian modelling to estimate parameters describing the kernel and effects of expert data. We considered three functional forms of spatial kernels and the inclusion or exclusion of expert data. The resulting six models were ranked by widely applicable information criterion (WAIC) and deviance information criterion (DIC) and evaluated through within- and out-of-sample validation. We showed that predictions of intrastate shipments were mildly influenced by the functional form of the spatial kernel but kernel shapes that permitted a fat tail at large distances while maintaining a plateau-shaped behaviour at short distances better were preferred. Furthermore, our study showed that expert data may not guarantee enhanced predictions when expert estimates are disparate.
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19.
  • Darmoise, Alexandre, et al. (författare)
  • Lysosomal alpha-galactosidase controls the generation of self lipid antigens for natural killer T cells.
  • 2010
  • Ingår i: Immunity. - : Elsevier BV. - 1097-4180 .- 1074-7613. ; 33:2, s. 216-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Natural Killer T (NKT) cells are lipid-reactive, CD1d-restricted T lymphocytes important in infection, cancer, and autoimmunity. In addition to foreign antigens, NKT cells react with endogenous self lipids. However, in the face of stimulating self antigen, it remains unclear how overstimulation of NKT cells is avoided. We hypothesized that constantly degraded endogenous antigen only accumulates upon inhibition of alpha-galactosidase A (alpha-Gal-A) in lysosomes. Here, we show that alpha-Gal-A deficiency caused vigorous activation of NKT cells. Moreover, microbes induced inhibition of alpha-Gal-A activity in antigen-presenting cells. This temporary enzyme block depended on Toll-like receptor (TLR) signaling and ultimately triggered lysosomal lipid accumulation. Thus, we present TLR-dependent negative regulation of alpha-Gal-A as a mechanistic link between pathogen recognition and self lipid antigen induction for NKT cells.
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20.
  • Farnocchia, Davide, et al. (författare)
  • The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
  • 2023
  • Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
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21.
  • Fullen, Brona, et al. (författare)
  • Management of Chronic Low Back Pain and the Impact on Patients' Personal and Professional Lives : Results From an International Patient Survey
  • 2022
  • Ingår i: Pain Practice. - : Wiley-Blackwell Publishing Inc.. - 1530-7085 .- 1533-2500. ; 22:4, s. 463-477
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The objective of this study was to investigate the impact of chronic low back pain (CLBP) on patients' personal and professional lives, and management strategies applied to treat CLBP.METHODS: A 60-question survey was developed and respondents from 16 countries with a self-reported physician's diagnosis of CLBP were recruited via an online market research survey panel. Respondents were stratified as having mild, moderate, or severe pain. Target sample sizes per country and for pain severity were set. Data were weighted according to the known population and prevalence of CLBP in each country, and the number of respondents from that country.RESULTS: Results from 9,642 CLBP patients indicated that almost a quarter of patients with severe CLBP report a psychological comorbidity. Prescription pain medications were more commonly used by patients with severe CLBP (56%) than those with mild (20%) or moderate (34%) CLBP. Among those with severe CLBP who had been prescribed pain medication, 58% were prescribed opioids, with 1 in 4 patients using opioids for more than 5 years. Patients were primarily managed by general practitioners/primary care physicians, physiotherapists, neurologists, or orthopedic surgeons. CLBP negatively impacted patients' daily activities, social lives, and work productivity.CONCLUSION: CLBP has pronounced effects on patients' personal relationships, ability to work, and daily living. Almost 1 in 4 patients with severe CLBP reported a psychological comorbidity. Adherence to guidelines appears inconsistent, which is noteworthy as a substantial subgroup of patients with severe CLBP had been prescribed opioid medication for more than 5 years. Improved education is required to support healthcare professionals (HCPs) in identifying and understanding the complex biopsychosocial needs of CLBP patients to optimize pain management, and to encourage referral of CLBP patients to physiotherapists and psychologists.
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22.
  • Gao, Hong, et al. (författare)
  • The landscape of tolerated genetic variation in humans and primates
  • 2023
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
  • Tidskriftsartikel (refereegranskat)abstract
    • Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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23.
  • Gilbertson, Kendra, et al. (författare)
  • The Importance of Livestock Demography and Infrastructure in Driving Foot and Mouth Disease Dynamics
  • 2022
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 12:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Transboundary animal diseases, such as foot and mouth disease (FMD) pose a significant and ongoing threat to global food security. Such diseases can produce large, spatially complex outbreaks. Mathematical models are often used to understand the spatio-temporal dynamics and create response plans for possible disease introductions. Model assumptions regarding transmission behavior of premises and movement patterns of livestock directly impact our understanding of the ecological drivers of outbreaks and how to best control them. Here, we investigate the impact that these assumptions have on model predictions of FMD outbreaks in the U.S. using models of livestock shipment networks and disease spread. We explore the impact of changing assumptions about premises transmission behavior, both by including within-herd dynamics, and by accounting for premises type and increasing the accuracy of shipment predictions. We find that the impact these assumptions have on outbreak predictions is less than the impact of the underlying livestock demography, but that they are important for investigating some response objectives, such as the impact on trade. These results suggest that demography is a key ecological driver of outbreaks and is critical for making robust predictions but that understanding management objectives is also important when making choices about model assumptions.
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24.
  • Goetsch, L., et al. (författare)
  • Influence of administration dose and route on the immunogenicity and protective efficacy of BBG2Na, a recombinant respiratory syncytial virus subunit vaccine candidate
  • 2000
  • Ingår i: Vaccine. - 0264-410X .- 1873-2518. ; 18:24, s. 2735-2742
  • Tidskriftsartikel (refereegranskat)abstract
    • The immunogenicity and protective efficacy of BBG2Na, a novel recombinant respiratory syncytial virus subunit vaccine candidate, was assessed in BALB/c mice under various conditions of dose, administration route and number of immunisations. A single intra-peritoneal (i.p.) dose of 2 mu g, or two doses of 0.2 mu g, were sufficient to induce elevated RSV-A serum antibodies and sterilising lung protective immunity. Serum antibody titres were significantly boosted following second immunisations, but not a third. Of three routes of immunisation, i.p. induced the highest RSV-A antibody titres, followed in efficacy by the intramuscular (i.m.) and subcutaneous (s.c.) routes. Nonetheless, all three routes induced comparable and sterilising lung protection. In contrast, upper respiratory tract protection was observed only after i.p. vaccination, although significant viral titre reductions were evident following i.m. or s.c. immunisations. Interestingly, Pepscan analyses indicated that antibody epitope usage was highest in i.p. and lowest in i.m. immunised mice, respectively. Nonetheless, all routes resulted in antibody responses to known lung protective epitopes (protectopes). Thus, the prevention of serious lower respiratory tract disease, the principle goal of a RSV vaccine, but not URT infection, is dose dependent but unlikely to be influenced by the route of BBG2Na administration.
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25.
  • Hjorth, Lars, et al. (författare)
  • Survivorship after childhood cancer: PanCare: A European Network to promote optimal long-term care.
  • 2015
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 51:10, s. 1203-1211
  • Tidskriftsartikel (refereegranskat)abstract
    • Survival after childhood cancer has improved substantially over recent decades. Although cancer in childhood is rare increasingly effective treatments have led to a growing number of long-term survivors. It is estimated that there are between 300,000 and 500,000 childhood cancer survivors in Europe. Such good survival prospects raise important questions relating to late effects of treatment for cancer. Research has shown that the majority will suffer adverse health outcomes and premature mortality compared with the general population. While chronic health conditions are common among childhood cancer survivors, each specific type of late effect is very rare. Long-term effects must be considered particularly when addressing complex multimodality treatments, and taking into account the interaction between aspects of treatment and genotype. The PanCare Network was set up across Europe in order to effectively answer many of these questions and thereby improve the care and quality of life of survivors. The need for a structured long-term follow-up system after childhood cancer has been recognised for some time and strategies for implementation have been developed, first nationally and then trans-nationally, across Europe. Since its first meeting in Lund in 2008, the goal of the PanCare Network has been to coordinate and implement these strategies to ensure that every European survivor of childhood and adolescent cancer receives optimal long-term care. This paper will outline the structure and work of the PanCare Network, including the results of several European surveys, the start of two EU-funded projects and interactions with relevant stakeholders and related projects.
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26.
  • Hudson, Thomas J., et al. (författare)
  • International network of cancer genome projects
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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27.
  • Hulme, Mike, et al. (författare)
  • Letter: Science-Policy Interface: Beyond Assessments
  • 2011
  • Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 333:6043, s. 697-698
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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28.
  • Keck, Michaela Kristina, et al. (författare)
  • Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
  • 2023
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
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29.
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30.
  • Kuderna, Lukas F. K., et al. (författare)
  • A global catalog of whole-genome diversity from 233 primate species
  • 2023
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648, s. 906-913
  • Tidskriftsartikel (refereegranskat)abstract
    • The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage wholegenome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.
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31.
  • Kuderna, Lukas F. K., et al. (författare)
  • Identification of constrained sequence elements across 239 primate genomes
  • 2024
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
  • Tidskriftsartikel (refereegranskat)abstract
    • Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
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32.
  • Kälsch, Hagen, et al. (författare)
  • Are air pollution and traffic noise independently associated with atherosclerosis : the Heinz Nixdorf Recall Study
  • 2014
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:13, s. 853-60
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Living close to high traffic has been linked to subclinical atherosclerosis, however it is not clear, whether fine particulate matter (PM) air pollution or noise, two important traffic-related exposures, are responsible for the association. We investigate the independent associations of long-term exposure to fine PM and road traffic noise with thoracic aortic calcification (TAC), a reliable measure of subclinical atherosclerosis.METHODS AND RESULTS: We used baseline data (2000-2003) from the German Heinz Nixdorf Recall Study, a population-based cohort of 4814 randomly selected participants. We assessed residential long-term exposure to PM with a chemistry transport model, and to road traffic noise using façade levels from noise models as weighted 24 h mean noise (Lden) and night-time noise (Lnight). Thoracic aortic calcification was quantified from non-contrast enhanced electron beam computed tomography. We used multiple linear regression to estimate associations of environmental exposures with ln(TAC+1), adjusting for each other, individual, and neighbourhood characteristics. In 4238 participants (mean age 60 years, 49.9% male), PM2.5 (aerodynamic diameter ≤2.5 µm) and Lnight are both associated with an increasing TAC-burden of 18.1% (95% CI: 6.6; 30.9%) per 2.4 µg/m(3) PM2.5 and 3.9% (95% CI 0.0; 8.0%) per 5dB(A) Lnight, respectively, in the full model and after mutual adjustment. We did not observe effect measure modification of the PM2.5 association by Lnight or vice versa.CONCLUSION: Long-term exposure to fine PM and night-time traffic noise are both independently associated with subclinical atherosclerosis and may both contribute to the association of traffic proximity with atherosclerosis.
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33.
  • Lauber, Chris, et al. (författare)
  • Deciphering the Origin and Evolution of Hepatitis B Viruses by Means of a Family of Non-enveloped Fish Viruses
  • 2017
  • Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 22:3, s. 387-399,e1-e6
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatitis B viruses (HBVs), which are enveloped viruses with reverse-transcribed DNA genomes, constitute the family Hepadnaviridae. An outstanding feature of HBVs is their streamlined genome organization with extensive gene overlap. Remarkably, the similar to 1,100 bp open reading frame (ORF) encoding the envelope proteins is fully nested within the ORF of the viral replicase P. Here, we report the discovery of a diversified family of fish viruses, designated nackednaviruses, which lack the envelope protein gene, but otherwise exhibit key characteristics of HBVs including genome replication via proteinprimed reverse-transcription and utilization of structurally related capsids. Phylogenetic reconstruction indicates that these two virus families separated more than 400 million years ago before the rise of tetrapods. We show that HBVs are of ancient origin, descending from non-enveloped progenitors in fishes. Their envelope protein gene emerged de novo, leading to a major transition in viral lifestyle, followed by co-evolution with their hosts over geologic eras.
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34.
  • Lurati Buse, Giovanna A., et al. (författare)
  • Risk assessment for major adverse cardiovascular events after noncardiac surgery using self-reported functional capacity : international prospective cohort study
  • 2023
  • Ingår i: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 130:6, s. 655-665
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Guidelines endorse self-reported functional capacity for preoperative cardiovascular assessment, although evidence for its predictive value is inconsistent. We hypothesised that self-reported effort tolerance improves prediction of major adverse cardiovascular events (MACEs) after noncardiac surgery.METHODS: This is an international prospective cohort study (June 2017 to April 2020) in patients undergoing elective noncardiac surgery at elevated cardiovascular risk. Exposures were (i) questionnaire-estimated effort tolerance in metabolic equivalents (METs), (ii) number of floors climbed without resting, (iii) self-perceived cardiopulmonary fitness compared with peers, and (iv) level of regularly performed physical activity. The primary endpoint was in-hospital MACE consisting of cardiovascular mortality, non-fatal cardiac arrest, acute myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care or resulting in a prolongation of stay on ICU/intermediate care (≥24 h). Mixed-effects logistic regression models were calculated.RESULTS: In this study, 274 (1.8%) of 15 406 patients experienced MACE. Loss of follow-up was 2%. All self-reported functional capacity measures were independently associated with MACE but did not improve discrimination (area under the curve of receiver operating characteristic [ROC AUC]) over an internal clinical risk model (ROC AUCbaseline 0.74 [0.71-0.77], ROC AUCbaseline+4METs 0.74 [0.71-0.77], ROC AUCbaseline+floors climbed 0.75 [0.71-0.78], AUCbaseline+fitnessvspeers 0.74 [0.71-0.77], and AUCbaseline+physical activity 0.75 [0.72-0.78]).CONCLUSIONS: Assessment of self-reported functional capacity expressed in METs or using the other measures assessed here did not improve prognostic accuracy compared with clinical risk factors. Caution is needed in the use of self-reported functional capacity to guide clinical decisions resulting from risk assessment in patients undergoing noncardiac surgery.CLINICAL TRIAL REGISTRATION: NCT03016936.
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35.
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36.
  • Petelenz-Kurdziel, Elzbieta, et al. (författare)
  • Quantification of cell volume changes upon hyperosmotic stress in Saccharomyces cerevisiae.
  • 2011
  • Ingår i: Integrative biology : quantitative biosciences from nano to macro. - : Oxford University Press (OUP). - 1757-9708 .- 1757-9694. ; 3:11, s. 1120-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell volume is a biophysical property, which is of great importance for quantitative characterisations of biological processes, such as osmotic adaptation. It also is a crucial parameter in the most common type of mathematical description of cellular behaviour-ordinary differential equation (ODE) models, e.g. the integrative model of the osmotic stress response in baker's yeast (E. Klipp, B. Nordlander, R. Kruger, P. Gennemark and S. Hohmann, Nat. Biotechnol., 2005, 23, 975-982). Until recently only rough estimates of this value were available. In this study we measured the mean volume of more than 300 individual yeast cells (Saccharomyces cerevisiae). We quantitatively characterised the dependence between the relative cell volume and the concentration of osmoticum in the cell surrounding. We also followed the recovery of the cellular volume over time, as well as the influence of increased external osmolarity on the nuclear volume. We found that cell shrinkage caused by shifts in the external osmolarity is proportional to the stress intensity only up to 1000 mM NaCl. At this concentration the yeast cells shrink to approximately 55% of their unstressed volume and this volume is maintained even in the case of further osmolarity increase. We observed that returning to the initial, unstressed volume takes more than 45 minutes for stress concentrations exceeding 100 mM NaCl and that only cells treated with the latter concentration are able to fully regain their initial size within the course of the experiment. We postulate that the cytoplasm plays a protective role for the nucleus by buffering the changes in volume caused by external osmolarity shifts. In conclusion, we quantitatively characterised the dynamics of cell volume changes caused by hyperosmotic stress, providing an accurate description of a biophysical cell property, which is crucial for precise mathematical simulations of cellular processes.
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37.
  • Schuette, Moritz, et al. (författare)
  • Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling 44,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
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38.
  • Sellman, Stefan, et al. (författare)
  • Modeling nation-wide US swine movement networks at the resolution of the individual premises
  • 2022
  • Ingår i: Epidemics. - : Elsevier. - 1755-4365 .- 1878-0067. ; 41
  • Tidskriftsartikel (refereegranskat)abstract
    • The spread of infectious livestock diseases is a major cause for concern in modern agricultural systems. In the dynamics of the transmission of such diseases, movements of livestock between herds play an important role. When constructing mathematical models used for activities such as forecasting epidemic development, evaluating mitigation strategies, or determining important targets for disease surveillance, including between -premises shipments is often a necessity. In the United States (U.S.), livestock shipment data is not routinely collected, and when it is, it is not readily available and mostly concerned with between-state shipments. To bridge this gap in knowledge and provide insight into the complete livestock shipment network structure, we have developed the U.S. Animal Movement Model (USAMM). Previously, USAMM has only existed for cattle shipments, but here we present a version for domestic swine. This new version of USAMM consists of a Bayesian model fit to premises demography, county-level livestock industry variables, and two limited data sets of between-state swine movements. The model scales up the data to simulate nation-wide networks of both within-and between-state shipments at the level of individual premises. Here we describe this shipment model in detail and subsequently explore its usefulness with a rudimentary predictive model of the prevalence of porcine epidemic diarrhea virus (PEDv) across the U.S. Additionally, in order to promote further research on livestock disease and other topics involving the movements of swine in the U.S., we also make 250 synthetic premises-level swine shipment networks with complete coverage of the entire conterminous U.S. freely available to the research community as a useful surrogate for the absent shipment data.
  •  
39.
  • Sellman, Stefan, et al. (författare)
  • Modeling US cattle movements until the cows come home: Who ships to whom and how many?
  • 2022
  • Ingår i: Computers and Electronics in Agriculture. - : ELSEVIER SCI LTD. - 0168-1699 .- 1872-7107. ; 203
  • Tidskriftsartikel (refereegranskat)abstract
    • Livestock movements between agricultural premises is an important pathway for the spread of infectious disease. Data providing details about the origin and destination of shipments, as well as information about the shipment size is an important component of computer models used to formulate mitigation strategies and design surveillance programs. The United States (U.S.) currently lacks a comprehensive database of farm animal shipments, which hinders such efforts. With the U.S. Animal Movement Model (USAMM), earlier work has successfully scaled up from limited data based on interstate certificates of veterinary inspection (CVI) to comprehensive county-level shipment networks at the national scale. In this work, we present three major improvements to earlier versions of USAMM: (1) increased resolution of the model and simulated networks to the level of individual premises; (2) predictions of shipment sizes; (3) taking into account the types and herd sizes of the premises. We fitted parameters in a Bayesian framework to two sets of CVI data consisting of sub-samples of one years between-state beef and dairy shipments. Through posterior predictive simulation, we then created 1,000 synthetic beef and dairy networks, which we make publicly available to support livestock disease modeling. The simulated networks were validated against summary statistics of the training data as well as out-of-sample CVI data from subsequent years. This new development opens up the possibility of using USAMM in a broader spectrum of applications where information about shipment size and premises identity is necessary and gives novel insights into the U.S. cattle shipment network.
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40.
  • Tonetti, Maurizio S, et al. (författare)
  • Periodontitis and atherosclerotic cardiovascular disease : consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases
  • 2013
  • Ingår i: Journal of periodontology. - 1943-3670. ; 84:4 Suppl, s. S24-S29
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: This consensus report is concerned with the association between periodontitis and atherosclerotic cardiovascular disease (ACVD). Periodontitis is a chronic multifactorial inflammatory disease caused by microorganisms and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss; as such, it is a major public health issue.AIMS: This report examined biological plausibility, epidemiology and early results from intervention trials. PLAUSIBILITY: Periodontitis leads to entry of bacteria in the blood stream. The bacteria activate the host inflammatory response by multiple mechanisms. The host immune response favors atheroma formation, maturation and exacerbation. Epidemiology: In longitudinal studies assessing incident cardiovascular events, statistically significant excess risk for ACVD was reported in individuals with periodontitis. This was independent of established cardiovascular risk factors. The amount of the adjusted excess risk varies by type of cardiovascular outcome and across populations by age and gender. Given the high prevalence of periodontitis, even low to moderate excess risk is important from a public health perspective. Intervention: There is moderate evidence that periodontal treatment: (i) reduces systemic inflammation as evidenced by reduction in C-reactive protein (CRP) and improvement of both clinical and surrogate measures of endothelial function; but (ii) there is no effect on lipid profiles--supporting specificity. Limited evidence shows improvements in coagulation, biomarkers of endothelial cell activation, arterial blood pressure and subclinical atherosclerosis after periodontal therapy. The available evidence is consistent and speaks for a contributory role of periodontitis to ACVD. There are no periodontal intervention studies on primary ACVD prevention and there is only one feasibility study on secondary ACVD prevention.CONCLUSIONS: It was concluded that: (i) there is consistent and strong epidemiologic evidence that periodontitis imparts increased risk for future cardiovascular disease; and (ii) while in vitro, animal and clinical studies do support the interaction and biological mechanism, intervention trials to date are not adequate to draw further conclusions. Well-designed intervention trials on the impact of periodontal treatment on prevention of ACVD hard clinical outcomes are needed.
  •  
41.
  • Tonetti, Maurizio S, et al. (författare)
  • Periodontitis and atherosclerotic cardiovascular disease : consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases
  • 2013
  • Ingår i: Journal of Periodontology. - : John Wiley & Sons Inc.. - 1943-3670 .- 0022-3492. ; 84:4 Suppl, s. S24-S29
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: This consensus report is concerned with the association between periodontitis and atherosclerotic cardiovascular disease (ACVD). Periodontitis is a chronic multifactorial inflammatory disease caused by microorganisms and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss; as such, it is a major public health issue. AIMS: This report examined biological plausibility, epidemiology and early results from intervention trials. PLAUSIBILITY: Periodontitis leads to entry of bacteria in the blood stream. The bacteria activate the host inflammatory response by multiple mechanisms. The host immune response favors atheroma formation, maturation and exacerbation. Epidemiology: In longitudinal studies assessing incident cardiovascular events, statistically significant excess risk for ACVD was reported in individuals with periodontitis. This was independent of established cardiovascular risk factors. The amount of the adjusted excess risk varies by type of cardiovascular outcome and across populations by age and gender. Given the high prevalence of periodontitis, even low to moderate excess risk is important from a public health perspective. Intervention: There is moderate evidence that periodontal treatment: (i) reduces systemic inflammation as evidenced by reduction in C-reactive protein (CRP) and improvement of both clinical and surrogate measures of endothelial function; but (ii) there is no effect on lipid profiles--supporting specificity. Limited evidence shows improvements in coagulation, biomarkers of endothelial cell activation, arterial blood pressure and subclinical atherosclerosis after periodontal therapy. The available evidence is consistent and speaks for a contributory role of periodontitis to ACVD. There are no periodontal intervention studies on primary ACVD prevention and there is only one feasibility study on secondary ACVD prevention. CONCLUSIONS: It was concluded that: (i) there is consistent and strong epidemiologic evidence that periodontitis imparts increased risk for future cardiovascular disease; and (ii) while in vitro, animal and clinical studies do support the interaction and biological mechanism, intervention trials to date are not adequate to draw further conclusions. Well-designed intervention trials on the impact of periodontal treatment on prevention of ACVD hard clinical outcomes are needed.
  •  
42.
  • Tsao, K., et al. (författare)
  • Effects of regional differences and demography in modelling foot-and-mouth disease in cattle at the national scale
  • 2020
  • Ingår i: Interface Focus. - : Royal Society Publishing. - 2042-8898 .- 2042-8901. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Foot-and-mouth disease (FMD) is a fast-spreading viral infection that can produce large and costly outbreaks in livestock populations. Transmission occurs at multiple spatial scales, as can the actions used to control outbreaks. The US cattle industry is spatially expansive, with heterogeneous distributions of animals and infrastructure. We have developed a model that incorporates the effects of scale for both disease transmission and control actions, applied here in simulating FMD outbreaks in US cattle. We simulated infection initiating in each of the 3049 counties in the contiguous US, 100 times per county. When initial infection was located in specific regions, large outbreaks were more likely to occur, driven by infrastructure and other demographic attributes such as premises clustering and number of cattle on premises. Sensitivity analyses suggest these attributes had more impact on outbreak metrics than the ranges of estimated disease parameter values. Additionally, although shipping accounted for a small percentage of overall transmission, areas receiving the most animal shipments tended to have other attributes that increase the probability of large outbreaks. The importance of including spatial and demographic heterogeneity in modelling outbreak trajectories and control actions is illustrated by specific regions consistently producing larger outbreaks than others. © 2019 The Author(s) Published by the Royal Society. All rights reserved.
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