| 1. |
- Gron, Kurt J., et al.
(författare)
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Archaeological cereals as an isotope record of long-term soil health and anthropogenic amendment in southern Scandinavia
- 2021
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 253
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Tidskriftsartikel (refereegranskat)abstract
- Maintaining soil health is integral to agricultural production, and the archaeological record contains multiple lines of palaeoclimatic and palaeoenvironmental proxy evidence that can contribute to the understanding and analysis of long-term trajectories of change that are key for contextualizing 21st century global environmental challenges. Soil is a capital resource and its nutrient balance is modified by agricultural activities, making it necessary to ensure soil productivity is maintained and managed through human choices and actions. Since prehistory this has always been the case; soil is a non-renewable resource within a human lifetime. Here, we present and interpret carbon and nitrogen isotope analysis of charred cereals from southern Scandinavia. Anthropogenic effects on soils are evident from the initiation of farming 6000 years ago, as is amendment to counteract its effects. The earliest cereals were planted on pristine soils, and by the late Neolithic, agriculture extensified. By the Iron Age it was necessary to significantly amend depleted soils to maintain crop yields. We propose that these data provide a record of soil water retention, net precipitation and amendment. From the start of the Neolithic there is a concurrent decrease in both Δ13C and δ15N, mitigated only by the replacement of soil organic content in the form of manure in the Iron Age. The cereal isotopes provide a record of trajectories of agricultural sustainability and anthropogenic adaptation for nearly the entire history of farming in the region.
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| 2. |
- Svensson, Emma, et al.
(författare)
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The Effect of Botulinum Toxin Type A Injections on Stricture Formation, Leakage Rates, Esophageal Elongation, and Anastomotic Healing Following Primary Anastomosis in a Long- and Short-Gap Esophageal Atresia Model : A Protocol for a Randomized, Controlled, Blinded Trial in Pigs
- 2021
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Ingår i: International Journal of Surgery Protocols. - : IJS Press. - 2468-3574. ; 25:1, s. 171-177
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Tidskriftsartikel (refereegranskat)abstract
- Background:Esophageal atresia (EA) is a congenital malformation affecting 1:3000-4500 newborns. Approximately 15% have a long-gap EA (LGEA), in which case a primary anastomosis is often impossible to achieve. To create continuity of the esophagus patients instead have to undergo lengthening procedures or organ interpositions; methods associated with high morbidity and poor functional outcomes. Esophageal injections of Botulinum Toxin Type A (BTX-A) could enable primary anastomosis and mitigate stricture formation through decreased tissue tension.Methods and Analysis:In this randomized controlled blinded animal trial, 24 pigs are divided into a long- or short-gap EA group (LGEA and SGEA, respectively) and randomized to receive BTX-A or isotonic saline injections. In the LGEA group, injections are given endoscopically in the esophageal musculature. After seven days, a 3 cm esophageal resection and primary anastomosis is performed. In the SGEA group, a 1 cm esophageal resection and primary anastomosis is performed, followed by intraoperative injections of BTX-A or isotonic saline. After 14 days, stricture formation, presence of leakage, and esophageal compliance is assessed using endoscopic and manometric techniques, and in vivo and ex vivo contrast radiography. Tissue elongation is evaluated in a stretch-tension test, and the esophagus is assessed histologically to evaluate anastomotic healing.Ethics and Dissemination:The study complies with the ARRIVE guidelines for animal studies and has been approved by the Danish Animal Experimentation Council. Results will be published in peer-reviewed journals and presented at national and international conferences.
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| 3. |
- Anthon, Carl Thomas, et al.
(författare)
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Platelet transfusions in adult ICU patients with thrombocytopenia : A sub-study of the PLOT-ICU inception cohort study
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown.STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 10 9/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 10 11 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 10 11 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 10 9/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.
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| 4. |
- Baquero, María-Rosario, et al.
(författare)
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Polymorphic mutation frequencies in Escherichia coli : emergence of weak mutators in clinical isolates
- 2004
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Ingår i: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 186:16, s. 5538-5542
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in the rifampin resistance mutation frequency (f) were studied in 696 Escherichia coli strains from Spain, Sweden, and Denmark. Of the 696 strains, 23% were weakly hypermutable (4 x 10(-8) < or = f < 4 x 10(-7)), and 0.7% were strongly hypermutable (f > or = 4 x 10(-7)). Weak mutators were apparently more frequent in southern Europe and in blood isolates (38%) than in urinary tract isolates (25%) and feces of healthy volunteers (11%).
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| 5. |
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| 6. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 7. |
- Biasin, Elisa, et al.
(författare)
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Anisotropy enhanced X-ray scattering from solvated transition metal complexes
- 2018
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 25:2, s. 306-315
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Tidskriftsartikel (refereegranskat)abstract
- Time-resolved X-ray scattering patterns from photoexcited molecules in solution are in many cases anisotropic at the ultrafast time scales accessible at X-ray free-electron lasers (XFELs). This anisotropy arises from the interaction of a linearly polarized UV-Vis pump laser pulse with the sample, which induces anisotropic structural changes that can be captured by femtosecond X-ray pulses. In this work, a method for quantitative analysis of the anisotropic scattering signal arising from an ensemble of molecules is described, and it is demonstrated how its use can enhance the structural sensitivity of the time-resolved X-ray scattering experiment. This method is applied on time-resolved X-ray scattering patterns measured upon photoexcitation of a solvated di-platinum complex at an XFEL, and the key parameters involved are explored. It is shown that a combined analysis of the anisotropic and isotropic difference scattering signals in this experiment allows a more precise determination of the main photoinduced structural change in the solute, i.e. the change in Pt - Pt bond length, and yields more information on the excitation channels than the analysis of the isotropic scattering only. Finally, it is discussed how the anisotropic transient response of the solvent can enable the determination of key experimental parameters such as the instrument response function.The analysis of time-resolved X-ray scattering patterns collected at an XFEL upon photoexcitation of a di-platinum complex in solution is described. The analysis quantitatively considers the anisotropy of the signal.
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| 8. |
- Cabrera Molero, Inés, et al.
(författare)
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Cross-layer adaptation for TCP-based applications in WCDMA systems
- 2005
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Konferensbidrag (refereegranskat)abstract
- In this paper, we consider TCP-based applications over a high bandwidth wireless channel, such as the High-Speed Downlink Packet Access (HSDPA) channel in aWCDMAsystem, in two setups: a nominal one that employs end-to-end TCPReno and a new one that employs Cross-Layer Adaptation (CLA) in the form of Radio Network Feedback (RNF). For theCLAsetup, the Radio Resource Management unit in the Radio Network Controller (RNC) provides a proxy with reports on the radio link bandwidth and the queue level. The proxy transport layer takes appropriate actions on these reports. By doing so, it utilizes the air-interface spectrum more efficiently and keeps the layer-2 queue in the RNCclose a predetermined level. These new control mechanisms are evaluated through ns-2 simulations. In a number of realistic use cases it is shown that the new CLAsetup reduces the time to serve users, and substantially increases the radio link utilization and decreases the required buffer size in the RNC.
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| 9. |
- Claussen, Anetta, et al.
(författare)
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Impact of demographics and disease progression on the relationship between glucose and HbA1c
- 2017
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Ingår i: European Journal of Pharmaceutical Sciences. - : ELSEVIER SCIENCE BV. - 0928-0987 .- 1879-0720. ; 104, s. 417-423
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Tidskriftsartikel (refereegranskat)abstract
- Context: Several studies have shown that the relationship between mean plasma glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations. Especially race has previously been referred to shift the regression line that links MPG to HbA1c at steady-state (Herman & Cohen, 2012).Objective: To assess the influence of demographic and disease progression-related covariates on the intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model.Data: Longitudinal patient-level data from 16 late-phase trials in type 2 diabetes with a total of 8927 subjects was used to study covariates for the relationship between MPG and HbA1c. The analysed covariates included age group, HMI, gender, race, diabetes duration, and pre-trial treatment. Differences between trials were taken into account by estimating a trial-to-trial variability component.Participants: Participants included 47% females and 20% above 65 years. 77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were analysed together as other races.Analysis: Estimates of the change in the intercept of the MPG-HbA1c relationship due to the mentioned covariates were determined using a longitudinal model.Results: The analysis showed that pre-trial treatment with insulin had the most pronounced impact associated with a 0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group also had an impact on the MPG-HbA1c relationship.Conclusion: Our analysis shows that the relationship between MPG and HbA1c is relatively insensitive to covariates, but shows small variations across populations, which may be relevant to take into account when predicting HbA1c response based on MPG measurements in clinical trials.
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| 10. |
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| 11. |
- Felix, Janine F, et al.
(författare)
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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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| 12. |
- Fiorenzi, Marco, et al.
(författare)
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Enhancing TCP over HSDPA by cross-layer signalling
- 2007
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Ingår i: GLOBECOM 2007: 2007 IEEE GLOBAL TELECOMMUNICATIONS CONFERENCE. - 9781424410422 ; , s. 5362-5366
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Konferensbidrag (refereegranskat)abstract
- A comprehensive performance evaluation of a cross-layer solution to increase users' downlink data rates over HSDPA is provided. The solution consists of a proxy entity between a server and the Radio Network Controller, and cross-layer signalling from the base station to the proxy. The performance of the solution is evaluated though a detailed ns-2 simulator environment, which includes all HSDPA features, as well as some existing TCP enhancing protocols widely adopted for internet traffic over wireless links. Numerical results show that the proxy significantly increases the users' throughput, while also improving the utilization of the radio resources.
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| 13. |
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| 14. |
- Frimodt-Møller, Niels, et al.
(författare)
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Apramycin efficacy against carbapenem- and aminoglycoside-resistant Escherichia coli and Klebsiella pneumoniae in murine bloodstream infection models
- 2024
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier. - 0924-8579 .- 1872-7913. ; 64:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe aminoglycoside apramycin has been proposed as a drug candidate for the treatment of critical Gram-negative systemic infections. However, the potential of apramycin in the treatment of drug-resistant bloodstream infections (BSIs) has not yet been assessed.MethodsThe resistance gene annotations of 40 888 blood-culture isolates were analysed. In vitro profiling of apramycin comprised cell-free translation assays, broth microdilution, and frequency of resistance determination. The efficacy of apramycin was studied in a mouse peritonitis model for a total of nine Escherichia coli and Klebsiella pneumoniae isolates.ResultsGenotypic aminoglycoside resistance was identified in 87.8% of all 6973 carbapenem-resistant Enterobacterales blood-culture isolates, colistin resistance was shown in 46.4% and apramycin in 2.1%. Apramycin activity against methylated ribosomes was > 100-fold higher than that for other aminoglycosides. Frequencies of resistance were < 10-9 at 8 × minimum inhibitory concentration (MIC). Tentative epidemiological cut-offs (TECOFFs) were determined as 8 µg/mL for E. coli and 4 µg/mL for K. pneumoniae. A single dose of 5 to 13 mg/kg resulted in a 1-log colony-forming unit (CFU) reduction in the blood and peritoneum. Two doses of 80 mg/kg resulted in an exposure that resembles the AUC observed for a single 30 mg/kg dose in humans and led to complete eradication of carbapenem- and aminoglycoside-resistant bacteraemia.ConclusionEncouraging coverage and potent in vivo efficacy against a selection of highly drug-resistant Enterobacterales isolates in the mouse peritonitis model warrants the conduct of clinical studies to validate apramycin as a drug candidate for the prophylaxis and treatment of BSI.
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| 15. |
- Gustafsson, Ingegerd
(författare)
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Biological and Pharmacological Factor that Influence the Selection of Antibiotic Resistance
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic treatment causes an ecological disturbance on the human microflora. Four commensal bacteria: E. coli, enterococci, a-streptococci and coagulase-negative staphylococci, from patients with extensive, high antibiotic usage were investigated with regard to resistance pattern and mutation frequency. Among 193 investigated strains it was found that high antibiotic usage selected for resistant bacteria and enriched for bacteria with a small but significantly increased mutation frequency.The relative biological fitness cost of resistance in Staphylococcus epidermidis was assessed in a human in vivo model where the indigenous flora was present. In vitro data of the bacterial growth rate correlated well to in vivo fitness assayed in the competition experiments on skin.An in vitro kinetic model was shown to be a useful tool to establish the pharmacokinetic and pharmacodynamic (PK/PD) indices for efficacy of antibiotics. It was confirmed that the time, when the concentration exceeds the minimal inhibitory concentration (MIC), correlates with efficacy for b-lactam antibiotics. To achieve maximal killing for penicillin-resistant pneumococci, with an MIC of 2 mg/L, the peak concentration was also of importance.Suboptimal dosing regimen facilitates selection of resistance. Penicillin-resistant pneumococci were easily selected in a mixed population with penicillin-sensitive, -intermediate and -resistant pneumococci in an in vitro kinetic model. The selection of the resistant strain was prevented when the benzylpenicillin concentration exceeded the MIC for approximately 50% of 24 h.
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| 16. |
- Haldrup, Kristoffer, et al.
(författare)
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Ultrafast X-Ray Scattering Measurements of Coherent Structural Dynamics on the Ground-State Potential Energy Surface of a Diplatinum Molecule
- 2019
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Ingår i: Physical Review Letters. - 0031-9007. ; 122:6
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Tidskriftsartikel (refereegranskat)abstract
- We report x-ray free electron laser experiments addressing ground-state structural dynamics of the diplatinum anion Pt2POP4 following photoexcitation. The structural dynamics are tracked with <100 fs time resolution by x-ray scattering, utilizing the anisotropic component to suppress contributions from the bulk solvent. The x-ray data exhibit a strong oscillatory component with period 0.28 ps and decay time 2.2 ps, and structural analysis of the difference signal directly shows this as arising from ground-state dynamics along the PtPt coordinate. These results are compared with multiscale Born-Oppenheimer molecular dynamics simulations and demonstrate how off-resonance excitation can be used to prepare a vibrationally cold excited-state population complemented by a structure-dependent depletion of the ground-state population which subsequently evolves in time, allowing direct tracking of ground-state structural dynamics.
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| 17. |
- Have Beck, Iben, et al.
(författare)
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Association Between Prenatal and Early Postnatal Exposure to Perfluoroalkyl Substances and IQ Score in 7-Year-Old Children From the Odense Child Cohort
- 2023
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Ingår i: American Journal of Epidemiology. - 0002-9262. ; 192:9, s. 1522-1535
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFAS) are persistent chemicals capable of crossing the placenta and passing into breast milk. Evidence suggests that PFAS exposure may affect brain development. We investigated whether prenatal or early postnatal PFAS exposure was associated with intelligence quotient (IQ) scores in schoolchildren from the Odense Child Cohort (Denmark, 2010–2020). We assessed concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) in maternal serum collected during the first trimester of pregnancy and in child serum at age 18 months. At 7 years of age, children completed an abbreviated version of the Wechsler Intelligence Scale for Children, Fifth Edition, from which Full Scale Intelligence Quotient (FSIQ) and Verbal Comprehension Index scores were estimated. In multiple linear regression analyses conducted among 967 mother-child pairs, a doubling in maternal PFOS and PFNA concentrations was associated with a lower FSIQ score, while no significant associations were observed for PFOA, PFHxS, or PFDA. PFAS concentrations at age 18 months and duration of breastfeeding were strongly correlated, and even in structural equation models it was not possible to differentiate between the opposite effects of PFAS exposure and duration of breastfeeding on FSIQ. PFAS exposure is ubiquitous; therefore, an association with even a small reduction in IQ is of public health concern.
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| 18. |
- Hellman, Jarl, et al.
(författare)
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Associations of bolus insulin injection frequency and smart pen engagement with glycaemic control in people living with type 1 diabetes
- 2023
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Ingår i: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326.
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Tidskriftsartikel (refereegranskat)abstract
- AimTo evaluate whether both bolus insulin injection frequency and smart pen engagement were associated with changes in glycaemic control, using real-world data from adults with type 1 diabetes (T1D).Materials and MethodsAdults using a smart pen (NovoPen 6) to administer bolus insulin (fast-acting insulin aspart or insulin aspart) alongside continuous glucose monitoring were eligible for inclusion. Smart pen engagement was characterized by number of days with pen data uploads over the previous 14 days. Glycaemic control was evaluated by analysing glucose metrics.ResultsOverall, data from 1194 individuals were analysed. The number of daily bolus injections was significantly associated with time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]; P < 0.0001). Individuals administering, on average, three daily bolus insulin injections had an estimated 11% chance of achieving >70% TIR. The probability of achieving >70% TIR increased with the mean number of daily bolus injections. However, the percentage of TIR was lower on days when individuals administered higher-than-average numbers of injections. The observed mean number of daily bolus injections administered across the study population was lower than the optimal number required to reach glycaemic targets (4.8 injections vs. 6-8 injections). Smart pen engagement was significantly associated with improved TIR.ConclusionsGlycaemic control was associated with daily bolus insulin injection frequency and smart pen engagement. A treatment regimen combining an optimal bolus injection strategy, and effective smart pen engagement, may improve glycaemic control among adults with T1D.
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| 19. |
- Jacobsson, Krister, et al.
(författare)
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ACK-clock dynamics in network congestion control - An inner feedback loop with implications on inelastic flow impact
- 2006
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Ingår i: PROCEEDINGS OF THE 45TH IEEE CONFERENCE ON DECISION AND CONTROL. - 9781424401710 ; , s. 1882-1887
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Konferensbidrag (refereegranskat)abstract
- The focus of this paper is the window mechanism in network congestion control, whereby packet acknowledgments control when new packets are being sent This constitutes an inner control loop that so far has received little attention. We provide a novel model of this loop that bridges between the standard integrator link model and the more recent static link model. The model is in validation experiments shown to be accurate. It is also shown that as the amount of inelastic cross-traffic increases the dynamics of this inner loop becomes slower. This may influence overall performance and stability in scenarios with heavy inelastic flows.
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| 20. |
- Jacobsson, Krister, et al.
(författare)
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Estimation of RTT and bandwidth for congestion Control Applications in Communication Networks
- 2004
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Konferensbidrag (refereegranskat)abstract
- Heterogeneous communication networks with their variety of application demands, uncertain time-varying traffic load, and mixture of wired and wireless links pose several challenging problem in modeling and control. In this paper we focus on the round-trip time (RTT), which is a particularly important variable for efficient end-to-end congestion control, and on bandwidth estimation. Based on a simple aggregated model of the network, an algorithm combining a Kalman filter and a change detection algorithm is proposed for RTT estimation. It is illustrated on real data that this algorithm provides estimates of significantly better accuracy as compared to the RTT estimator currently used in TCP, especially in scenarios where new cross-trafficflows cause bottle-neck queues to rapidly build up which in turn induces rapid changes of the RTT. Standard techniques for bandwidth estimation is based on measurements of inter-arrival times of packets as the bandwidth is proportional to the inverse of the inter-arrival time. Two main classes of bandwidth estimators are analyzed wrt how variations in the inter-arrival times affect the estimates. It is shown that linear time-invariant filtering of instantaneous bandwidth estimates does not change the bias. In contrast to this, smoothing the inter-arrival-time samples, does give a bias reduction which depends on the smoothing filter. Hence, with such approach, noise attenuation can be traded against tracking ability wrt changes in the actual bandwidth.
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| 21. |
- Jacobsson, Krister, et al.
(författare)
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Round trip time estimation in communication networks using adaptive Kalman filtering
- 2004
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Konferensbidrag (refereegranskat)abstract
- Heterogeneous communication networks with their variety of application demands, uncertain time-varying traffic load, and mixture of wired and wireless links pose several challenging problem in modeling and control. In this paper we focus on the roundtrip time (RTT), which is a particularly important variable for efficient end-to-end congestion control. Based on a simple aggregated model of the network, an algorithm combining a Kalmanfilter and a change detection algorithm is proposed for RTT estimation. It is illustrated on real data that this algorithm provides estimates of significantly better accuracy as compared to the RTT estimator currently used in TCP, especially in scenarios where new cross-trafficflows cause a bottle-neck link to rapidly build up a queue, which in turn induces rapid changes of the RTT.
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| 22. |
- Jacobsson, Krister, et al.
(författare)
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Some modeling and estimation issues in control of heterogeneous networks
- 2004
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Konferensbidrag (refereegranskat)abstract
- Heterogeneous communication networks with their variety of application demands, uncertain time-varying trafc load, and mixture of wired and wireless links pose several challenging problem in modeling and control. In this paper we focus on the round-trip time (RTT), which is a particularly important variable for efficient end-to-end congestion control. Based on a simple aggregated model of the network, an algorithm combining a Kalman lter and a change detection algorithm is proposed for RTT estimation. It is illustrated on real data that this algorithm provides estimates of significantly better accuracy as compared to the RTT estimator currently used in TCP.We also analyze how wireless links affect the RTT distribution. Link re-transmissions induce delays which do not conform to the assumptions on which the transport protocol is based. This causes undesired TCP control actions which reduce throughput. A link layer solution based on adding carefully selected delays to certain packets is proposed to counteract this problem.
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| 23. |
- Jakobsson, Martin, et al.
(författare)
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Arctic Ocean glacial history
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 92, s. 40-67
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Forskningsöversikt (refereegranskat)abstract
- While there are numerous hypotheses concerning glacial interglacial environmental and climatic regime shifts in the Arctic Ocean, a holistic view on the Northern Hemisphere's late Quaternary ice-sheet extent and their impact on ocean and sea-ice dynamics remains to be established. Here we aim to provide a step in this direction by presenting an overview of Arctic Ocean glacial history, based on the present state-of-the-art knowledge gained from field work and chronological studies, and with a specific focus on ice-sheet extent and environmental conditions during the Last Glacial Maximum (LGM). The maximum Quaternary extension of ice sheets is discussed and compared to LGM. We bring together recent results from the circum-Arctic continental margins and the deep central basin; extent of ice sheets and ice streams bordering the Arctic Ocean as well as evidence for ice shelves extending into the central deep basin. Discrepancies between new results and published LGM ice-sheet reconstructions in the high Arctic are highlighted and outstanding questions are identified. Finally, we address the ability to simulate the Arctic Ocean ice sheet complexes and their dynamics, including ice streams and ice shelves, using presently available ice-sheet models. Our review shows that while we are able to firmly reject some of the earlier hypotheses formulated to describe Arctic Ocean glacial conditions, we still lack information from key areas to compile the holistic Arctic Ocean glacial history.
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| 24. |
- Jansåker, Filip, et al.
(författare)
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Novel risk factors associated with common vaginal infections : a nationwide primary health care cohort study: Novel risk factors for vaginal infections
- 2022
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Ingår i: International Journal of Infectious Diseases. - : Elsevier BV. - 1201-9712. ; 116, s. 380-386
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to estimate the association between potential risk factors and common vaginal infections using nationwide primary health care and other national registers. Methods: An open cohort study consisting of 2,357,711 women aged 15 years to 50 years (2001 to 2018) was conducted in Sweden. The outcomes were first event of vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV) in relation to sociodemographic factors. Cox regression models were used. Sensitivity analyses including diabetes mellitus, contraceptive use, and cervical cancer were conducted. Results: The incidence rates per 1,000 person-years for VVC and BV were 3.3 (95% confidence interval [CI] 3.2-3.3) and 3.4 (95% CI 3.4-3.4), respectively. In the fully adjusted model, sociodemographic factors were significantly associated with both outcomes. Compared with Swedish-born women, women from Middle East/North Africa had the highest risk of VVC (hazard ratio [HR] 2.77, 95% CI, 2.72-2.83), followed by Africa (excluding North Africa) (HR 2.53, 95% CI, 2.45-2.61), and Latin America and the Caribbean (HR 2.18, 95% CI, 2.09-2.27). For BV, women from Latin America and the Caribbean had the highest risk (HR 1.83, 95% CI, 1.75-1.92). Conclusion: This study presents novel risk factors associated with medically attended vaginal infections. Women from non-Western countries seem to develop these conditions disproportionately.
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| 25. |
- Jansåker, Filip, et al.
(författare)
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The association between common urogenital infections and cervical neoplasia – A nationwide cohort study of over four million women (2002–2018)
- 2022
-
Ingår i: The Lancet Regional Health - Europe. - : Elsevier BV. - 2666-7762. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cervical cancer is a major cause of mortality and morbidity in women worldwide. This study aimed to estimate the association between common urogenital infections and cervical neoplasia. Methods: A multi-register national cohort study of 4,120,557 women aged ≥15 years (2002–2018) was conducted. The outcomes were cervical cancer and carcinoma in situ (Swedish Cancer Register). The main predictors were urogenital infections—(urinary) cystitis, (bacterial) vaginosis, (candida) vulvovaginitis. Incidence rates per 10,000 person-years were calculated (using the European Standard Population). Cox regression was used to estimate hazard ratios (HR) while adjusting for possible confounders—other genital infections (e.g., cervicitis, salpingitis, urogenital herpes), parity, and sociodemographic factors. Findings: In 39·0 million person-years of follow-up, the incidence rate for cervical cancer was 1·2 (95% CI 1·1–1·2) per 10,000 person-years and the figure for cervical carcinoma in situ was more than tenfold higher. The fully adjusted HRs for cervical cancer were 1·31 (95% CI 1·15 and 1·48) and 1·22 (95% CI 1·16 and 1·29) for vaginosis and cystitis, respectively. Vaginosis showed a gradient association to carcinoma in situ. Vulvovaginitis was inversely associated with cervical cancer, but not significantly related with carcinoma in situ in the fully adjusted model. A temporal association with cervical cancer was observed for vaginosis and vulvovaginitis (inversely) but not for cystitis. Interpretation: In this large nationwide cohort of women, medically attended common urogenital infections were independently associated with cervical neoplasia, but cystitis was not temporally associated with cervical neoplasia. These findings could be used to increase focus on preventive measures, HPV-vaccination programmes, HPV-analyses- and cervical cancer screening, especially in women suffering from vaginosis. Future studies on the causal mechanism are warranted before generalized public health recommendations can be made. Funding: Region Skåne, Tore Nilsons Stiftelse, and Swedish Society of Medicine.
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| 26. |
- Jansåker, Filip, et al.
(författare)
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The Risk of Pyelonephritis Following Uncomplicated Cystitis : A Nationwide Primary Healthcare Study
- 2022
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Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The risk of pyelonephritis following uncomplicated lower urinary tract infection (cystitis) in women has not been studied in well-powered samples. This is likely due to the previous lack of nationwide primary healthcare data. We aimed to examine the risks of pyelonephritis following cystitis in women and explore if antibiotic treatment, cervical cancer, parity, and sociodemographic factors are related to these risks. Methods: This was a nationwide cohort study (2006–2018) of 752,289 women diagnosed with uncomplicated cystitis in primary healthcare settings. Of these, 404 696 did not redeem an antibiotic prescription within five days from cystitis. Logistic regression models were used to calculate odds ratios for pyelonephritis within 30 days and 90 days following the cystitis event. Results: Around one percent (7454) of all women with cystitis were diagnosed with pyelonephritis within 30 days, of which 78.2% had not redeemed an antibiotic for their cystitis. Antibiotic treatment was inversely associated with both outpatient registration and hospitalization due to pyelonephritis, with odds ratios of 0.85 (95% CI 0.80 to 0.91) and 0.65 (95% CI 0.55 to 0.77), respectively. Sociodemographic factors, parity, and cervical cancer were, with few exceptions (e.g., age and region of residency), not associated with pyelonephritis. Conclusions: Antibiotic treatment was inversely associated with pyelonephritis, but the absolute risk reduction was low. Non-antibiotic treatment for cystitis might be a safe option for most women. Future studies identifying the women at the highest risks will help clinicians in their decision making when treating cystitis, while keeping the ecological costs of antibiotics in mind.
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| 27. |
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| 28. |
- Knudsen, Jenny Dahl, et al.
(författare)
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Selection of Resistant Streptococcus pneumoniae during Penicillin Treatment In Vitro and in Three Animal Models.
- 2003
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Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 47:8, s. 2499-2506
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacokinetic (PK) and pharmacodynamic (PD) properties for the selection of resistant pneumococci were studied by using three strains of the same serotype (6B) for mixed-culture infection in time-kill experiments in vitro and in three different animal models, the mouse peritonitis, the mouse thigh, and the rabbit tissue cage models. Treatment regimens with penicillin were designed to give a wide range of T>MICs, the amounts of time for which the drug concentrations in serum were above the MIC. The mixed culture of the three pneumococcal strains, 107 CFU of strain A (MIC of penicillin, 0.016 µg/ml; erythromycin resistant)/ml, 106 CFU of strain B (MIC of penicillin, 0.25 µg/ml)/ml, and 105 CFU of strain C (MIC of penicillin, 4 µg/ml)/ml, was used in the two mouse models, and a mixture of 105 CFU of strain A/ml, 104 CFU of strain B/ml, and 103 CFU of strain C/ml was used in the rabbit tissue cage model. During the different treatment regimens, the differences in numbers of CFU between treated and control animals were calculated to measure the efficacies of the regimens. Selective media with erythromycin or different penicillin concentrations were used to quantify the strains separately. The efficacies of penicillin in vitro were similar when individual strains or mixed cultures were studied. The eradication of the bacteria, independent of the susceptibility of the strain or strains or the presence of the strains in a mixture or on their own, followed the well-known PK and PD rules for treatment with ß-lactams: a maximum efficacy was seen when the T>MIC was >40 to 50% of the observation time and the ratio of the maximum concentration of the drug in serum to the MIC was >10. It was possible in all three models to select for the less-susceptible strains by using insufficient treatments. In the rabbit tissue cage model, a regrowth of pneumococci was observed; in the mouse thigh model, the ratio between the different strains changed in favor of the less-susceptible strains; and in the mouse peritonitis model, the susceptible strain disappeared and was overgrown by the less-susceptible strains. These findings with the experimental infection models confirm the importance of eradicating all the bacteria taking part in the infectious process in order to avoid selection of resistant clones.
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| 29. |
- Komp Lindgren, Patricia, et al.
(författare)
-
Biological cost of single and multiple norfloxacin resistance mutations in Escherichia coli implicated in urinary tract infections
- 2005
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 49:6, s. 2343-2351
-
Tidskriftsartikel (refereegranskat)abstract
- Resistance to fluoroquinolones in urinary tract infection (UTIs)caused by Escherichia coli is associated with multiple mutations,typically those that alter DNA gyrase and DNA topoisomeraseIV and those that regulate AcrAB-TolC-mediated efflux. We askedwhether a fitness cost is associated with the accumulation ofthese multiple mutations. Mutants of the susceptible E. coliUTI isolate Nu14 were selected through three to five successivesteps with norfloxacin. Each selection was performed with theMIC of the selected strain. After each selection the MIC wasmeasured; and the regions of gyrA, gyrB, parC, and parE, previouslyassociated with resistance mutations, and all of marOR and acrRwere sequenced. The first selection step yielded mutations ingyrA, gyrB, and marOR. Subsequent selection steps yielded mutationsin gyrA, parE, and marOR but not in gyrB, parC, or acrR. Resistance-associatedmutations were identified in almost all isolates after selectionsteps 1 and 2 but in less than 50% of isolates after subsequentselection steps. Selected strains were competed in vitro, inurine, and in a mouse UTI infection model against the startingstrain, Nu14. First-step mutations were not associated withsignificant fitness costs. However, the accumulation of threeor more resistance-associated mutations was usually associatedwith a large reduction in biological fitness, both in vitroand in vivo. Interestingly, in some lineages a partial restorationof fitness was associated with the accumulation of additionalmutations in late selection steps. We suggest that the relativebiological costs of multiple mutations may influence the evolutionof E. coli strains that develop resistance to fluoroquinolones.
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| 30. |
- Marcusson, Linda L, et al.
(författare)
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Interplay in the Selection of Fluoroquinolone Resistance and Bacterial Fitness
- 2009
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 5:8, s. e1000541-
-
Tidskriftsartikel (refereegranskat)abstract
- Fluoroquinolones are antibacterial drugs that inhibit DNA Gyrase and Topoisomerase IV. These essential enzymes facilitate chromosome replication and RNA transcription by regulating chromosome supercoiling. High-level resistance to fluoroquinolones in E. coli requires the accumulation of multiple mutations, including those that alter target genes and genes regulating drug efflux. Previous studies have shown some drug-resistance mutations reduce bacterial fitness, leading to the selection of fitness-compensatory mutations. The impact of fluoroquinolone-resistance on bacterial fitness was analyzed in constructed isogenic strains carrying up to 5 resistance mutations. Some mutations significantly decreased bacterial fitness both in vitro and in vivo. We identified low-fitness triple-mutants where the acquisition of a fourth resistance mutation significantly increased fitness in vitro and in vivo while at the same time dramatically decreasing drug susceptibility. The largest effect occurred with the addition of a parC mutation (Topoisomerase IV) to a low-fitness strain carrying resistance mutations in gyrA (DNA Gyrase) and marR (drug efflux regulation). Increased fitness was accompanied by a significant change in the level of gyrA promoter activity as measured in an assay of DNA supercoiling. In selection and competition experiments made in the absence of drug, parC mutants that improved fitness and reduced susceptibility were selected. These data suggest that natural selection for improved growth in bacteria with low-level resistance to fluoroquinolones could in some cases select for further reductions in drug susceptibility. Thus, increased resistance to fluoroquinolones could be selected even in the absence of further exposure to the drug.
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| 31. |
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| 32. |
- Möller, Niels
(författare)
-
Automatic control in TCP over wireless
- 2005
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Over the last decade, both the Internet and mobile telephony has become parts of daily life, changing the ways we communicate and search for information. These two distinct tools are now slowly merging. The topic of this thesis is TCP over wireless, and the automatic control that is used both within the system, from the link-layer power control to the end-to-end congestion control. It consists of three main contributions. The first contribution is a proposed split-connection scheme for downloads to a mobile terminal. A wireless mobile terminal requests a file or a web page from a proxy, which in turn requests the data from a server on the Internet. During the file transfer, the radio network controller (RNC) sends radio network feedback (RNF) messages to the proxy. These messages include information about bandwidth changes over the radio channel, and the current RNC queue length. A novel control mechanism in the proxy uses this information to adjust the sending rate. The stability and convergence speed of the proxy controller is analyzed theoretically. The performance of the proposed controller is compared to end-to-end TCP Reno, using ns-2 simulations of realistic use cases. It is shown that the proxy control is able to reduce the response time experienced by users, and increase the utilization of the radio channel. The changes are loalized to the RNC and the proxy; no changes are required to the TCP implementation in terminal or server. The second contribution is the analysis of an uplink channel using power control and link-layer retransmissions. To be able to design the link-layer mechanisms in a systematic way, good models for the link-layer processes, and their interaction with TCP, are essential.The use of link-layer retransmissions transforms a link with constant delay and random losses into a link with random delay and almost no losses. As seen from the TCP end points, the difference between such a link and a wired one is no longer the loss rate, but the packet delay distribution. Models for the power control and link-layer retransmissions on the link are used to derive packet delay distribution, and its impact on TCP performance is investigated. The final contribution considers ways to optimize the link-layer processes. The main result is that TCP performance, over a wireless link with random retransmission delays, can be improved by adding carefully chosen artificial delays to certain packets. The artificial delays are optimized off-line and applied on-line. The additional delay that is applied to a packet depends only on the retransmission delay experienced by that same packet, and this information is available locally at the link.
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| 33. |
- Möller, Niels, et al.
(författare)
-
Congestion control for small queues : analysis and evaluation of a new protocol
- 2008
-
Ingår i: Proceedings of the 47th IEEE Conference on Decision and Control Cancun, Mexico, Dec. 9-11, 2008. - : IEEE conference proceedings. - 9781424431236 ; , s. 1416-1421
-
Konferensbidrag (refereegranskat)abstract
- A new congestion control protocol is presented, analyzed and experimentally evaluated. It consists of the standard inner-loop ACK-clock and a novel outer-loop adjusting the window size based on congestion signaling from the network. The aim of the new protocol is to maintain the efficiency and fairness properties of TCP, but with significantly smaller bottleneck queues and thereby it takes the sharing with real-time traffic into account. Stability properties of the protocol is proved using a recent fluid-flow traffic model. Experimental comparisons with New Reno and Vegas illustrate the advantages of the new protocol with respect to throughput, delay, utilization, and fairness.
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| 34. |
- Möller, Niels, et al.
(författare)
-
Influence of power control and link-level retransmissions on wireless TCP
- 2003
-
Ingår i: QUALITY FOR ALL. - Berlin, Heidelberg : Springer Berlin Heidelberg. ; , s. 193-202
-
Konferensbidrag (refereegranskat)abstract
- A fundamental assumption of the TCP protocol is that packet losses indicate congestion on the network. This is a problem when using TCP over wireless links, because a noisy radio transmission may erroneously indicate congestion and thereby reduce the TCP sending rate. Two partial solutions, that improve the quality of the radio link, are power control and link-level retransmissions. By modeling these two lower layers of control loops, we derive an analytical modei of the delay distribution for IP packets traversing a link. We investigate the effect on TCP, in particular the performance degradation due to spurious timeouts and spurious fast retransmits caused by delays and reorder on the link. It is shown that the models allow us to quantify the throughput degradation. The results indicate that link-level control and TCP interact, and that tuning one or the other is needed in order to improve performance.
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| 35. |
- Möller, Niels, et al.
(författare)
-
Inter-protocol fairness between TCP New Reno and TCP Westwood
- 2007
-
Ingår i: 2007 Next Generation Internet Networks. - 9781424408566 ; , s. 127-134
-
Konferensbidrag (refereegranskat)abstract
- In this paper we investigate the effect of introducing TCP Westwood+ on regular TCP New Reno. By means of analytical modeling and ns-2 simulations, we demonstrate that the two protocols get different shares of the available bandwidth in the network. Our main result is that the bandwidth sharing between the two protocols depends on one crucial parameter: the ratio between the bottleneck router buffer size and the bandwidth delay product. If the ratio is smaller than one, TCP Westwood+ takes more bandwidth. On the contrary, if the ratio is greater than one, it is TCP New Reno which gets the larger part. Inspired by our results, we propose a simple modification to the window decrease algorithm in TCP Westwood+ that solves the unfairness problem for large buffer sizes. For small buffers, the unfairness problem is still open.
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| 36. |
- Möller, Niels, et al.
(författare)
-
Making retransmission delays in wireless links friendlier to TCP
- 2004
-
Konferensbidrag (refereegranskat)abstract
- Heterogeneous communication networks with their variety of application demands, uncertain time-varying traffic load, and mixture of wired and wireless links pose several challenging problem in modeling and control. In this paper we focus on the packet delay, which is an important variable for efficient end-to-end congestion control. In particular, we study the delay effects of radio links which use power control and link-layer retransmissions. Link-layer retransmissions induce delays which do not conform to the assumptions on which the transport protocol is based. This causes undesired TCP control actions which reduce throughput. A link-layer solution based on adding carefully selected delays to certain packets is proposed to counteract this problem. All information needed for this is available locally at the link.
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| 37. |
- Möller, Niels, et al.
(författare)
-
Modeling and control of IP transport in cellular radio links
- 2005
-
Konferensbidrag (refereegranskat)abstract
- A fundamental assumption of the TCP protocol is that packet losses indicate congestion on the network. This is a problem when using TCP over wireless links, because a noisy radio transmission may erroneously indicate congestion and thereby reduce the TCP sending rate. Two partial solutions, which improve the quality of the radio link, are power control and link-layer retransmissions. We consider a radio channel with multiple users and traffic classes, and investigate how parameters in the radio model influences TCP-related quality measures, such as the average delay and the probability of spurious timeout. The results indicate that the outer loop power control is robust to uncertainties in the radio model. This robustness property supports separation between the radio layer design and the IP and TCP layers.
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| 38. |
- Möller, Niels
(författare)
-
On Schonhage's algorithm and subquadratic integer GCD computation
- 2008
-
Ingår i: Mathematics of Computation. - 0025-5718 .- 1088-6842. ; 77:261, s. 589-607
-
Tidskriftsartikel (refereegranskat)abstract
- We describe a new subquadratic left-to-right GCD algorithm, inspired by Schonhage's algorithm for reduction of binary quadratic forms, and compare it to the first subquadratic GCD algorithm discovered by Knuth and Schonhage, and to the binary recursive GCD algorithm of Stehle and Zimmer-mann. The new GCD algorithm runs slightly faster than earlier algorithms, and it is much simpler to implement. The key idea is to use a stop condition for HGCD that is based not on the size of the remainders, but on the size of the next difference. This subtle change is sufficient to eliminate the back-up steps that are necessary in all previous subquadratic left-to-right GCD algorithms. The subquadratic GCD algorithms all have the same asymptotic running time, O(n(log n)(2) log log n).
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| 39. |
- Möller, Niels
(författare)
-
Robust HGCD with no backup steps
- 2006
-
Ingår i: Mathematical Software-ICMS 2006, Proceedings. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 3540380841 ; , s. 194-204
-
Konferensbidrag (refereegranskat)abstract
- Subquadratic divide-and-conquer algorithms for computing the greatest common divisor have been studied for a couple of decades. The integer case has been notoriously difficult, with the need for "backup steps" in various forms. This paper explains why backup steps are necessary for algorithms based directly on the quotient sequence, and proposes a robustness criterion that can be used to construct a "half-gcd" algorithm without any backup steps.
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| 40. |
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| 41. |
- Möller, Niels, et al.
(författare)
-
Supporting end-to-end applications over HSDPA by cross-layer signalling
- 2007
-
Ingår i: IEEE WIRELESS COMMUNICATIONS & NETWORKING CONFERENCE, VOLS 1-9. - NEW YORK : IEEE. - 9781424406586 ; , s. 3858-3863
-
Konferensbidrag (refereegranskat)abstract
- A new control structure is proposed to improve user experience of wireless Internet. Information on radio bandwidth and queue length available in the radio network, close to the base station, is used in a proxy that resides between the Internet and the cellular system. The control algorithm in the proxy sets the window size according to event-triggered information on radio bandwidth changes and time-triggered information on the queue length at the wireless link. The mechanism is compared to TCP Reno in two simulation scenarios. The first scenario models a dedicated channel with stepwise changes in the bandwidth, while the second scenario models the High-speed Downlink Shared Channel recently introduced by 3GPP. The proposed mechanism significantly reduces the amount of buffer space needed in the radio network, and it also gives modest improvements to user response time and link utilization. Reduced buffering is particularly beneficial for third-party end-to-end real-time services such as voice, video, and online gaming.
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| 42. |
- Möller, Niels, et al.
(författare)
-
Using radio network feedback to improve TCP performance over cellular networks
- 2005
-
Ingår i: Proceedings of the 44th IEEE Conference on Decision and Control, and the European Control Conference 2005. - : IEEE. - 0780395689 ; , s. 7434-7439
-
Konferensbidrag (refereegranskat)abstract
- A new control structure is proposed to improve user experience of wireless Internet. Information on radio bandwidth and queue length available in the radio network controller (RNC), close to the base station, is used in a proxy that resides between the Internet and the cellular system. The control algorithm in the proxy sets the window size according to event-triggered information on radio bandwidth changes and time-triggered information on the queue length of the RNC. A stability analysis of the hybrid control system is performed. In a number of realistic use cases evaluated in ns-2, the new control structure is compared to a nominal one that employs end-to-end TCP Reno. It is shown that the proposed solution reduces the time to serve users, increases the radio link utilization, and decreases the required buffer size in the RNC.
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| 43. |
- Möller, Niels, 1971-
(författare)
-
Window-based congestion control : Modeling, analysis and design
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents a model for the ACK-clock inner loop, common to virtually all Internet congestion control protocols, and analyzes the stability properties of this inner loop, as well as the stability and fairness properties of several window update mechanisms built on top of the ACK-clock. Aided by the model for the inner-loop, two new congestion control mechanisms are constructed, for wired and wireless networks. Internet traffic can be divided into two main types: TCP traffic and real-time traffic. Sending rates for TCP traffic, e.g., file-sharing, uses window-based congestion control, and adjust continuously to the network load. The sending rates for real-time traffic, e.g., voice over IP, are mostly independent of the network load. The current version of the Transmission Control Protocol (TCP) results in large queueing delays at bottlenecks, and poor quality for real-time applications that share a bottleneck link with TCP. The first contribution is a new model for the dynamic relationship between window sizes, sending rates, and queue sizes. This system, with window sizes as inputs, and queue sizes as outputs, is the inner loop at the core of window-based congestion control. The new model unifies two models that have been widely used in the literature. The dynamics of this system, including the static gain and the time constant, depend on the amount of cross traffic which is not subject to congestion control. The model is validated using ns-2 simulations, and it is shown that the system is stable. For moderate cross traffic, the system convergence time is a couple of roundtrip times. When introducing a new congestion control protocol, one important question is how flows using different protocols share resources. The second contribution is an analysis of the fairness when a flow using TCP Westwood+ is introduced in a network that is also used by a TCP New Reno flow. It is shown that the sharing of capacity depends on the buffer size at the bottleneck link. With a buffer size matching the bandwidth-delay product, both flows get equal shares. If the buffer size is smaller, Westwood+ gets a larger share. In the limit of zero buffering, it gets all the capacity. If the buffer size is larger, New Reno gets a larger share. In the limit of very large buffers, it gets 3/4 of the capacity. The third contribution is a new congestion control mechanism, maintaining small queues. The overall control structure is similar to the combination of TCP with Active Queue Management (AQM) and explicit congestion notification, where routers mark some packets according to a probability which depends on the queue size. The key ideas are to take advantage of the stability of the inner loop, and to use control laws for setting and reacting to packet marks that result in more frequent feedback than with AQM. Stability analysis for the single flow, single bottleneck topology gives a simple stability condition, which can be used to guide tuning. Simulations, both of the fluid-flow differential equations, and in the ns-2 packet simulator, show that the protocol maintains small queues. The simulations also indicate that tuning, using a single control parameter per link, is fairly easy. The final contribution is a split-connection scheme for downloads to a mobile terminal. A wireless mobile terminal requests a file from a web server, via a proxy. During the file transfer, the Radio Network Controller (RNC) informs the proxy about bandwidth changes over the radio channel, and the current RNC queue length. A novel control mechanism in the proxy uses this information to adjust the window size. In simulation studies, including one based on detailed radio-layer simulations, both the user response time and the link utilization are improved, compared TCP New Reno, Eifel and Snoop, both for a dedicated channel, and for the shared channel in High-Speed Downlink Packet Access.
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| 44. |
- Nahi, Hareth, et al.
(författare)
-
Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in multiple myeloma but not gain 1q21.
- 2016
-
Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 96:1, s. 46-54
-
Tidskriftsartikel (refereegranskat)abstract
- Chromosomal aberrations have significant prognostic importance in multiple myeloma (MM). However, proteasome inhibitors (PI) and IMiDs may partly overcome the poor prognostic impact of some of them. In this study, we investigated a population-based consecutive cohort newly diagnosed patients with MM admitted during a defined time period to hospitals in Denmark, Norway, and Sweden. The impact of treatment modality on the prognostic importance of specific chromosomal aberration was investigated, with special reference to gain 1q21. The median follow-up of patients still alive at analysis was 40months for the high-dose (HDT)-treated ones and 29months for the whole population. Three hundred forty-seven patients with a known 1q21 status were included in this study. The 347 patients were divided into three groups, that is, 119 patients with the 1q21 gain, 105 patients with other aberrations (OA), that is, del(13q), del(17p), t(4,14), and/or (14;16), and 123 patients with no aberrations (NA). The groups were compared in terms of overall survival (OS), time to progression (TTP), and response. The 3-yr OS for patients with gain 1q21 was 60% compared to patients with OA 74% and NO 82% (gain 1q21 vs. NO P<0.001; gain 1q21 vs. OA P=0.095). If treated with PI or IMiDs, the 3-yr OS was 58% for patients with gain 1q21 compared to patients with OA 78% and NO 78%, respectively (P=0.041, P=0.140). In HDT patients, the 3-yr OS was 69% for patients with gain 1q21 compared to patients with OA 84% and NO 88%, respectively (P<0.008, P=0.600). Thus, neither HDT nor using PI or IMiDs could overcome the poor prognostic impact of gain 1q21, while these drugs and HDT seemed to improve OS in patients with OA, approaching the survival in NO. Further, gain 1q21 appears to be one of the most important poor prognostic chromosomal aberrations in multiple myeloma with current treatments. Trials using new drugs or allogeneic transplantation are warranted.
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| 45. |
- Nielsen, Karen Leth, et al.
(författare)
-
Escherichia coli causing recurrent urinary tract infections: Comparison to non-recurrent isolates and genomic adaptation in recurrent infections
- 2021
-
Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 9:7
-
Tidskriftsartikel (refereegranskat)abstract
- Recurrent urinary tract infection (rUTI) remains a major problem for many women and therefore the pursuit for genomic and phenotypic traits which could define rUTI has been ongoing. The present study applied a genomic approach to investigate recurrent urinary tract infections by comparative analyses of recurrent and non-recurrent Escherichia coli isolates from general practice. From whole-genome sequencing data, phylogenetic clustering and genomic traits were studied on a collection of isolates which caused recurrent infection compared to non-recurrent isolates. In addition, genomic variation between the 1st and following infection was studied on a subset of the isolates. Evidence of limited adaptation between the recurrent infections based on single nucleotide polymorphism analyses with a range of 0–13 non-synonymous single nucleotide polymorphisms (SNPs) between the paired isolates. This included an overrepresentation of SNPs in metabolism genes. We identified several genes which were more common in rUTI isolates, including nine fimbrial genes, however, not significantly after false-discovery rate. Finally, the results show that recurrent isolates of the present dataset are not distinctive by variation in the core genome, and thus, did not cluster distinct from non-rUTI isolates in a SNP phylogeny.
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| 46. |
- Nielsen, Roni, et al.
(författare)
-
Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients
- 2019
-
Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 139:18, s. 2129-2141
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased circulating plasma-3-OHB levels in these patients are unknown. Consequently, the authors' aim was to modulate circulating 3-OHB levels in HFrEF patients and evaluate: (1) changes in cardiac output (CO); (2) a potential doseresponse relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO 2); and (4) whether the cardiovascular response differed between HFrEF patients and age-matched volunteers.METHODS: Study 1: 16 chronic HFrEF patients (left ventricular ejection fraction: 37 +/- 3%) were randomized in a crossover design to 3-hour of 3-OHB or placebo infusion. Patients were monitored invasively with a Swan-Ganz catheter and with echocardiography. Study 2: In a doseresponse study, 8 HFrEF patients were examined at increasing 3-OHB infusion rates. Study 3 to 4: 10 HFrEF patients and 10 age-matched volunteers were randomized in a crossover design to 3-hour 3-OHB or placebo infusion. MEE and MVO 2 were evaluated using 11C-acetate positron emission tomography.RESULTS: 3-OHB infusion increased circulating levels of plasma 3-OHB from 0.4 +/- 0.3 to 3.3 +/- 0.4 mM (P< 0.001). CO rose by 2.0 +/- 0.2 L/min (P< 0.001) because of an increase in stroke volume of 20 +/- 2 mL (P< 0.001) and heart rate of 7 +/- 2 beats per minute (bpm) (P< 0.001). Left ventricular ejection fraction increased 8 +/- 1% (P< 0.001) numerically. There was a dose-response relationship with a significant CO increase of 0.3 L/min already at plasma-3-OHB levels of 0.7 mM (P< 0.001). 3-OHB increased MVO 2 without altering MEE. The response to 3-OHB infusion in terms of MEE and CO did not differ between HFrEF patents and age-matched volunteers.CONCLUSIONS: 3-OHB has beneficial hemodynamic effects in HFrEF patients without impairing MEE. These beneficial effects are detectable in the physiological concentration range of circulating 3-OHB levels. The hemodynamic effects of 3-OHB were observed in both HFrEF patients and age-matched volunteers. 3-OHB may potentially constitute a novel treatment principle in HFrEF patients.
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| 47. |
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| 48. |
- Pičmanová, Martina, et al.
(författare)
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A recycling pathway for cyanogenic glycosides evidenced by the comparative metabolic profiling in three cyanogenic plant species
- 2015
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Ingår i: Biochemical Journal. - : Portland Press. - 0264-6021 .- 1470-8728. ; 469:3, s. 375-389
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Tidskriftsartikel (refereegranskat)abstract
- Cyanogenic glycosides are phytoanticipins involved in plant defence against herbivores by virtue of their ability to release toxic hydrogen cyanide (HCN) upon tissue disruption. In addition, endogenous turnover of cyanogenic glycosides without the liberation of HCN may offer plants an important source of reduced nitrogen at specific developmental stages. To investigate the presence of putative turnover products of cyanogenic glycosides, comparative metabolic profiling using LC–MS/MS and high resolution MS (HR–MS) complemented by ion-mobility MS was carried out in three cyanogenic plant species: cassava, almond and sorghum. In total, the endogenous formation of 36 different chemical structures related to the cyanogenic glucosides linamarin, lotaustralin, prunasin, amygdalin and dhurrin was discovered, including di- and tri-glycosides derived from these compounds. The relative abundance of the compounds was assessed in different tissues and developmental stages. Based on results common to the three phylogenetically unrelated species, a potential recycling endogenous turnover pathway for cyanogenic glycosides is described in which reduced nitrogen and carbon are recovered for primary metabolism without the liberation of free HCN. Glycosides of amides, carboxylic acids and ‘anitriles’ derived from cyanogenic glycosides appear as common intermediates in this pathway and may also have individual functions in the plant. The recycling of cyanogenic glycosides and the biological significance of the presence of the turnover products in cyanogenic plants open entirely new insights into the multiplicity of biological roles cyanogenic glycosides may play in plants.
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| 49. |
- Sandberg, Anne, et al.
(författare)
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Intra- and Extracellular Activities of Dicloxacillin and Linezolid against a Clinical Staphylococcus aureus Strain with a Small-Colony-Variant Phenotype in an In Vitro Model of THP-1 Macrophages and an In Vivo Mouse Peritonitis Model
- 2011
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 55:4, s. 1443-1452
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Tidskriftsartikel (refereegranskat)abstract
- The small colony variant (SCV) phenotype of Staphylococcus aureus has been associated with difficult-to-treat infections, reduced antimicrobial susceptibility and intracellular persistence. This study represents a detailed intra- and extracellular investigation of a clinical wild type (WT) S. aureus strain and its counterpart SCV phenotype both in vitro and in vivo, using the THP-1 cell line model and mouse peritonitis model respectively. Both phenotypes infected the mouse peritoneum intra- and extracellularly. The SCV phenotype was less virulent, showed distinct bacterial clearance, reduced multiplication capacity and reduced internalization ability. Some of the SCV infected mice were, however, still culture positive up to 96 h post infection and the phenotype could spread to the mouse kidney and furthermore revert to the more virulent WT phenotype in both the mouse- peritoneum and kidney. The SCV phenotype is therefore, despite reduced virulence, an important player in the S. aureus pathogenesis. In the THP-1 cell line model, both dicloxacillin (DCX) and linezolid (LZD) reduced the intracellular inoculum of both phenotypes by approximately 1-1.5 log10 in vitro, while DCX was considerably more effective against extracellular bacteria. In the mouse peritonitis model, DCX and LZD were also able to control both the intra- and extracellular infection caused by either phenotype. Treatment with a single dose of DCX and LZD was, however, insufficient to clear the SCVs in the kidneys and the risk of recurrent infection remained. This stresses the importance of optimal dosing of the antibiotic when SCVs are present.
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| 50. |
- Trobos, Margarita, 1980, et al.
(författare)
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Natural transfer of sulphonamide and ampicillin resistance between Escherichia coli residing in the human intestine.
- 2009
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Ingår i: The Journal of antimicrobial chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 63:1, s. 80-6
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether the sulphonamide resistance gene sul2 could be transferred between Escherichia coli in the human gut.Nine volunteers ingested a 10(9) cfu suspension of sulphonamide-susceptible, rifampicin-resistant E. coli recipients of human origin. Three hours later, they ingested a 10(7) cfu suspension of a sulphonamide-resistant (MIC>1024 mg/L) E. coli donor of pig origin. Stool samples were collected 24 h prior to ingestion, daily for 7 days and at days 14 and 35. Samples were plated on selective plates and monitored for the acquisition of sulphonamide-resistance by the recipient from the indigenous or administrated donor E. coli. Possible transconjugants were typed by PFGE and tested for the presence of plasmids containing the sul2 gene, which was also sequenced.Concentrations of the human and animal E. coli reached a maximum of 7.5x10(6) cfu/g faeces and colonized for more than 7 days, and 2x10(8) cfu/g for more than 14 days, respectively. On day 2, a transconjugant was detected in one volunteer. This volunteer was colonized with sulphonamide-resistant E. coli at day 0. The transconjugant was sul2-positive, had an MIC>1024 mg/L for sulfamethoxazole and the same PFGE profile as the recipient. The resident E. coli transferred a plasmid (>63 kb), containing the sul2 gene, to the recipient. The sul2 sequence of the transconjugant was identical to that of the volunteer's own E. coli from day 0, but differed from the animal strain. Co-transfer of ampicillin resistance was also demonstrated.Transfer of sul2 was observed between E. coli bacteria in the human intestine. The transconjugant's sul2 gene came from the volunteer's own flora. The origin of the E. coli donor is unknown.
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