| 1. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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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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| 2. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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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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| 3. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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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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| 4. |
- Eliasson, Pernilla T., et al.
(författare)
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The Ruptured Achilles Tendon Elongates for 6 Months After Surgical Repair Regardless of Early or Late Weightbearing in Combination With Ankle Mobilization: A Randomized Clinical Trial
- 2018
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Ingår i: American Journal of Sports Medicine. - : SAGE PUBLICATIONS INC. - 0363-5465 .- 1552-3365. ; 46:10, s. 2492-2502
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment strategies for Achilles tendon rupture vary considerably, and clinical outcome may depend on the magnitude of tendon elongation after surgical repair. The aim of this project was to examine whether tendon elongation, mechanical properties, and functional outcomes during rehabilitation of surgically repaired acute Achilles tendon ruptures were influenced by different rehabilitation regimens during the early postsurgical period. Hypothesis: Restricted early weightbearing that permits only limited motion about the ankle in the early phase of tendon healing limits tendon elongation and improves functional outcome. Study Design:Randomized controlled trial; Level of evidence, 1. Methods: 75 consecutive patients with an acute Achilles tendon rupture were included. They underwent surgical repair, and tantalum beads were placed in the distal and proximal parts of the tendon; thereafter, the patients were randomized into 3 groups. The first group was completely restricted from weightbearing until week 7. The second group was completely restricted from weightbearing until week 7 but performed ankle joint mobilization exercises. The first and second groups were allowed full weightbearing after week 8. The third group was allowed partial weightbearing from day 1 and full weightbearing from week 5. All patients received the same instructions in home exercise guidelines starting from week 9. Results: The rehabilitation regimen in the initial 8 weeks did not significantly influence any of the measured outcomes including tendon elongation. Achilles tendon elongation and tendon compliance continued for up to 6 months after surgery, and muscle strength, muscle endurance, and patient-reported functional scores did not reach normal values at 12 months. Conclusion: Differences in rehabilitation loading pattern in the initial 8 weeks after the repair of an Achilles tendon rupture did not measurably alter the outcome. The time to recover full function after an Achilles tendon rupture is at least 12 months.
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| 5. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 6. |
- Andersson, Sara B. E., et al.
(författare)
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Interlaboratory Validation of Small-Scale Solubility and Dissolution Measurements of Poorly Water-Soluble Drugs
- 2016
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 105:9, s. 2864-2872
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at multiple laboratories using the same experimental protocol. Dissolution was studied in fasted-state simulated intestinal fluid and phosphate buffer (pH 6.5). An additional 6 compounds were used for the development of an IDR measurement guide, which was then validated with 5 compounds. The results clearly showed a need for a standardized protocol including both the experimental assay and the data analysis. Standardization at both these levels decreased the interlaboratory variability. The results also illustrated the difficulties in performing disc IDR on poorly water-soluble drugs because the concentrations reached are typically below the limit of detection. The following guidelines were established: for compounds with Sapp > 1 mg/mL, the disc method is recommended. For compounds with Sapp <100 μg/mL, IDR is recommended to be performed using powder dissolution. Compounds in the interval 100 μg/mL to 1 mg/mL can be analyzed with either of these methods.
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| 7. |
- Bergström, Christel A. S., et al.
(författare)
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Early pharmaceutical profiling to predict oral drug absorption : Current status and unmet needs
- 2014
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57, s. 173-199
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Tidskriftsartikel (refereegranskat)abstract
- Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silica and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. (C) 2013 Elsevier B.V. All rights reserved.
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| 8. |
- Bergström, Christel, 1973-, et al.
(författare)
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Biorelevant intrinsic dissolution profiling in early drug development : Fundamental, methodological, and industrial aspects
- 2019
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 139, s. 101-114
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Forskningsöversikt (refereegranskat)abstract
- Intrinsic dissolution rate (IDR) is the surface specific dissolution rate of a drug. In early drug development, this property (among other parameters) is measured in order to compare different polymorphs and salt forms, guide formulation decisions, and to provide a quality marker of the active pharmaceutical ingredient (API) during production. In this review, an update on different methods and small-scale techniques that have recently evolved for determination of IDR is provided. The importance of biorelevant media and the hydrodynamic conditions of dissolution are also discussed. Different preparation techniques for samples are presented with a focus on disc, particle- and crystal-based methods. A number of small-scale techniques are then described in detail, and their applicability domains are identified. Finally, an updated industrial perspective is provided about IDR's place in the early drug development process.
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| 9. |
- Berthelsen, Ragna, et al.
(författare)
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Combining in vitro and in silico methods for better prediction of surfactant effects on the absorption of poorly water soluble drugs-a fenofibrate case example
- 2014
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 473:1-2, s. 356-365
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to develop a sensitive and discriminative in vitro-in silico model able to simulate the in vivo performance of three fenofibrate immediate release formulations containing different surfactants. In addition, the study was designed to investigate the effect of dissolution volume when predicting the oral bioavailability of the formulations. In vitro dissolution studies were carried out using the USP apparatus 2 or a mini paddle assembly, containing 1000 mL or 100 mL fasted state biorelevant medium, respectively. In silico simulations of small intestinal absorption were performed using the GI-Sim absorption model. All simulation runs were performed twice adopting either a total small intestinal volume of 533 mL or 105 mL, in order to examine the implication of free luminal water volumes for the in silico predictions. For the tested formulations, the use of a small biorelevant dissolution volume was critical for in vitro-in silico prediction of drug absorption. Good predictions, demonstrating rank order in vivo-in vitro-in silico correlations for C-max, were obtained with in silico predictions utilizing a 105 mL estimate for the human intestinal water content combined with solubility and dissolution data performed in a mini paddle apparatus with 100 mL fasted state simulated media.
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| 10. |
- Joyce, Paul, 1989, et al.
(författare)
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Solidification to improve the biopharmaceutical performance of SEDDS: Opportunities and challenges
- 2019
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Ingår i: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 142, s. 102-117
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Forskningsöversikt (refereegranskat)abstract
- Self-emulsifying drug delivery systems (SEDDS) offer potential for overcoming the inherent slow dissolution and poor oral absorption of hydrophobic drugs by retaining them in a solubilised state during gastrointestinal transit. However, the promising biopharmaceutical benefits of liquid lipid formulations has not translated into widespread commercial success, due to their susceptibility to long term storage and in vivo precipitation issues. One strategy that has emerged to overcome such limitations, is to combine the solubilisation and dissolution enhancing properties of lipids with the stabilising effects of solid carrier materials. The development of intelligent hybrid drug formulations has presented new opportunities to harness the potential of emulsified lipids in optimising oral bioavailability for lipophilic therapeutics. Specific emphasis of this review is placed on the impact of solidification approaches and excipients on the biopharmaceutical performance of self-emulsifying lipids, with findings highlighting the key design considerations that should be implemented when developing hybrid lipid-based formulations.
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