| 1. |
- Abdo, A. A., et al.
(författare)
-
FERMI/LARGE AREA TELESCOPE DISCOVERY OF GAMMA-RAY EMISSION FROM THE FLAT-SPECTRUM RADIO QUASAR PKS 1454-354
- 2009
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 697:1, s. 934-941
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery by the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope of high-energy gamma-ray (GeV) emission from the flat-spectrum radio quasar PKS 1454-354 (z = 1.424). On 2008 September 4, the source rose to a peak flux of (3.5 +/- 0.7) x 10(-6) ph cm(-2) s(-1) (E > 100 MeV) on a timescale of hours and then slowly dropped over the following 2 days. No significant spectral changes occurred during the flare. Fermi/LAT observations also showed that PKS 1454-354 is the most probable counterpart of the unidentified EGRET source 3EG J1500-3509. Multiwavelength measurements performed during the following days (7 September with Swift; 6-7 September with the ground-based optical telescope Automated Telescope for Optical Monitoring; 13 September with the Australia Telescope Compact Array) resulted in radio, optical, UV, and X-ray fluxes greater than archival data, confirming the activity of PKS 1454-354.
|
|
| 2. |
- Abdo, A. A., et al.
(författare)
-
SUZAKU OBSERVATIONS OF LUMINOUS QUASARS : REVEALING THE NATURE OF HIGH-ENERGY BLAZAR EMISSION IN LOW-LEVEL ACTIVITY STATES
- 2010
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 716:1, s. 835-849
-
Tidskriftsartikel (refereegranskat)abstract
- We present the results from the Suzaku X-ray observations of five flat-spectrum radio quasars (FSRQs), namely PKS 0208-512, Q 0827+243, PKS 1127-145, PKS 1510-089, and 3C 454.3. All these sources were additionally monitored simultaneously or quasi-simultaneously by the Fermi satellite in gamma rays and the Swift UVOT in the UV and optical bands, respectively. We constructed their broadband spectra covering the frequency range from 10(14) Hz up to 10(25) Hz, and those reveal the nature of high-energy emission of luminous blazars in their low-activity states. The analyzed X-ray spectra are well fitted by a power-law model with photoelectric absorption. In the case of PKS 0208-512, PKS 1127-145, and 3C 454.3, the X-ray continuum showed indication of hardening at low energies. Moreover, when compared with the previous X-ray observations, we see a significantly increasing contribution of low-energy photons to the total X-ray fluxes when the sources are getting fainter. The same behavior can be noted in the Suzaku data alone. A likely explanation involves a variable, flat-spectrum component produced via inverse-Compton emission, plus an additional, possibly steady soft X-ray component prominent when the source gets fainter. This soft X-ray excess is represented either by a steep power-law (photon indices Gamma similar to 3-5) or a blackbody-type emission with temperatures kT similar to 0.1-0.2 keV. We model the broadband spectra of the five observed FSRQs using synchrotron self-Compton and/or external-Compton radiation models. Our modeling suggests that the difference between the low-and high-activity states in luminous blazars is due to the different total kinetic power of the jet, most likely related to varying bulk Lorentz factor of the outflow within the blazar emission zone.
|
|
| 3. |
- Bottai, Matteo, et al.
(författare)
-
EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups : a methodology report
- 2017
-
Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 3:2
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups.Methods An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children). The participating clinicians classified each case as IIM or non-IIM. Generally, the classification of any given patient was based on few variables, leaving remaining variables unmeasured. We investigated the strength of the association between all variables and between these and the disease status as determined by the physician. We considered three approaches: (1) a probability-score approach, (2) a sum-of-items approach criteria and (3) a classification-tree approach.Results The approaches yielded several candidate models that were scrutinised with respect to statistical performance and clinical relevance. The probability-score approach showed superior statistical performance and clinical practicability and was therefore preferred over the others. We developed a classification tree for subclassification of patients with IIM. A calculator for electronic devices, such as computers and smartphones, facilitates the use of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.Conclusions The new EULAR/ACR classification criteria provide a patient's probability of having IIM for use in clinical and research settings. The probability is based on a score obtained by summing the weights associated with a set of criteria items.
|
|
| 4. |
- Chester, Mikhail V., et al.
(författare)
-
Sensemaking for entangled urban social, ecological, and technological systems in the Anthropocene
- 2023
-
Ingår i: npj Urban Sustainability. - 2661-8001. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Our urban systems and their underlying sub-systems are designed to deliver only a narrow set of human-centered services, with little or no accounting or understanding of how actions undercut the resilience of social-ecological-technological systems (SETS). Embracing a SETS resilience perspective creates opportunities for novel approaches to adaptation and transformation in complex environments. We: i) frame urban systems through a perspective shift from control to entanglement, ii) position SETS thinking as novel sensemaking to create repertoires of responses commensurate with environmental complexity (i.e., requisite complexity), and iii) describe modes of SETS sensemaking for urban system structures and functions as basic tenets to build requisite complexity. SETS sensemaking is an undertaking to reflexively bring sustained adaptation, anticipatory futures, loose-fit design, and co-governance into organizational decision-making and to help reimagine institutional structures and processes as entangled SETS.
|
|
| 5. |
- Das, Indra J., et al.
(författare)
-
Report of AAPM Task Group 155 : Megavoltage photon beam dosimetry in small fields and non-equilibrium conditions
- 2021
-
Ingår i: Medical physics (Lancaster). - : John Wiley & Sons. - 0094-2405 .- 2473-4209. ; 48:10, s. E886-E921
-
Tidskriftsartikel (refereegranskat)abstract
- Small-field dosimetry used in advance treatment technologies poses challenges due to loss of lateral charged particle equilibrium (LCPE), occlusion of the primary photon source, and the limited choice of suitable radiation detectors. These challenges greatly influence dosimetric accuracy. Many high-profile radiation incidents have demonstrated a poor understanding of appropriate methodology for small-field dosimetry. These incidents are a cause for concern because the use of small fields in various specialized radiation treatment techniques continues to grow rapidly. Reference and relative dosimetry in small and composite fields are the subject of the International Atomic Energy Agency (IAEA) dosimetry code of practice that has been published as TRS-483 and an AAPM summary publication (IAEA TRS 483; Dosimetry of small static fields used in external beam radiotherapy: An IAEA/AAPM International Code of Practice for reference and relative dose determination, Technical Report Series No. 483; Pal-mans et al., Med Phys 45(11):e1123, 2018). The charge of AAPM task group 155 (TG-155) is to summarize current knowledge on small-field dosimetry and to provide recommendations of best practices for relative dose determination in small megavoltage photon beams. An overview of the issue of LCPE and the changes in photon beam perturbations with decreasing field size is provided. Recommendations are included on appropriate detector systems and measurement methodologies. Existing published data on dosimetric parameters in small photon fields (e.g., percentage depth dose, tissue phantom ratio/tissue maximum ratio, off-axis ratios, and field output factors) together with the necessary perturbation corrections for various detectors are reviewed. A discussion on errors and an uncertainty analysis in measurements is provided. The design of beam models in treatment planning systems to simulate small fields necessitates special attention on the influence of the primary beam source and collimating devices in the computation of energy fluence and dose. The general requirements for fluence and dose calculation engines suitable for modeling dose in small fields are reviewed. Implementations in commercial treatment planning systems vary widely, and the aims of this report are to provide insight for the medical physicist and guidance to developers of beams models for radiotherapy treatment planning systems.
|
|
| 6. |
- Adelani, David Ifeoluwa, et al.
(författare)
-
MasakhaNER 2.0: Africa-centric Transfer Learning for Named Entity Recognition
- 2022
-
Ingår i: Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing. - : Association for Computational Linguistics (ACL). ; , s. 4488-4508
-
Konferensbidrag (refereegranskat)abstract
- African languages are spoken by over a billion people, but are underrepresented in NLP research and development. The challenges impeding progress include the limited availability of annotated datasets, as well as a lack of understanding of the settings where current methods are effective. In this paper, we make progress towards solutions for these challenges, focusing on the task of named entity recognition (NER). We create the largest human-annotated NER dataset for 20 African languages, and we study the behavior of state-of-the-art cross-lingual transfer methods in an Africa-centric setting, demonstrating that the choice of source language significantly affects performance. We show that choosing the best transfer language improves zero-shot F1 scores by an average of 14 points across 20 languages compared to using English. Our results highlight the need for benchmark datasets and models that cover typologically-diverse African languages.
|
|
| 7. |
- Chester, Lucy A., et al.
(författare)
-
Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Plasma Endocannabinoid Levels in Healthy Volunteers : A Randomized Double-Blind Four-Arm Crossover Study
- 2024
-
Ingår i: Cannabis and cannabinoid research. - : Mary Ann Liebert. - 2378-8763 .- 2378-8763 .- 2578-5125. ; 9:1, s. 188-198
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The effects of cannabis are thought to be mediated by interactions between its constituents and the endocannabinoid system. Delta-9-tetrahydrocannabinol (THC) binds to central cannabinoid receptors, while cannabidiol (CBD) may influence endocannabinoid function without directly acting on cannabinoid receptors. We examined the effects of THC coadministered with different doses of CBD on plasma levels of endocannabinoids in healthy volunteers.Methods: In a randomized, double-blind, four-arm crossover study, healthy volunteers (n=46) inhaled cannabis vapor containing 10 mg THC plus either 0, 10, 20, or 30 mg CBD, in four experimental sessions. The median time between sessions was 14 days (IQR=20). Blood samples were taken precannabis inhalation and at 0-, 5-, 15-, and 90-min postinhalation. Plasma concentrations of THC, CBD, anandamide, 2-arachidonoylglycerol (2-AG), and related noncannabinoid lipids were measured using liquid chromatography-mass spectrometry.Results: Administration of cannabis induced acute increases in plasma concentrations of anandamide (+18.0%, 0.042 ng/mL [95%CI: 0.023-0.062]), and the noncannabinoid ethanolamides, docosatetraenylethanolamide (DEA; +35.8%, 0.012 ng/mL [95%CI: 0.008-0.016]), oleoylethanolamide (+16.1%, 0.184 ng/mL [95%CI: 0.076-0.293]), and N-arachidonoyl-L-serine (+25.1%, 0.011 ng/mL [95%CI: 0.004-0.017]) (p<0.05). CBD had no significant effect on the plasma concentration of anandamide, 2-AG or related noncannabinoid lipids at any of three doses used. Over the four sessions, there were progressive decreases in the preinhalation concentrations of anandamide and DEA, from 0.254 ng/mL [95%CI: 0.223-0.286] to 0.194 ng/mL [95%CI: 0.163-0.226], and from 0.039 ng/mL [95%CI: 0.032-0.045] to 0.027 ng/mL [95%CI: 0.020-0.034] (p<0.05), respectively.Discussion: THC induced acute increases in plasma levels of anandamide and noncannabinoid ethanolamides, but there was no evidence that these effects were influenced by the coadministration of CBD. It is possible that such effects may be evident with higher doses of CBD or after chronic administration. The progressive reduction in pretreatment anandamide and DEA levels across sessions may be related to repeated exposure to THC or participants becoming less anxious about the testing procedure and requires further investigation. The study was registered on clinicaltrials.gov (NCT05170217).
|
|
| 8. |
- Darwich, Adam S., et al.
(författare)
-
IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 3 : Identifying gaps in system parameters by analysing In Silico performance across different compound classes
- 2017
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 626-642
-
Tidskriftsartikel (refereegranskat)abstract
- Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp (R) Simulator, and GastroPlus (TM)) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom-up" anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (F-oral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foralwas also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on permeation, lack of information on intestinal transporters, or underestimation of solubilisation of weak acids due to less than optimal intestinal model pH settings or underestimation of bile micelle contribution. F-oral was overpredicted for weak bases, suggesting inadequate models for precipitation or lack of in vitro precipitation information to build informed models. Relative bioavailability was underpredicted for both high logP compounds as well as poorly water-soluble compounds, suggesting inadequate models for solubility/dissolution, underperforming bile enhancement models and/or lack of biorelevant solubility measurements. These results indicate areas for improvement in model software, modelling approaches, and generation of applicable input data. However, caution is required when interpreting the impact of drug-specific properties in this exercise, as the availability of input parameters was heterogeneous and highly variable, and the modellers generally used the data "as is" in this blinded bottom-up prediction approach.
|
|
| 9. |
- Mannheimer, C, et al.
(författare)
-
The problem of chronic refractory angina
- 2002
-
Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 23:5, s. 355-370
-
Tidskriftsartikel (refereegranskat)abstract
- It has been recognized that there is a group of patients with severe disabling angina and coronary artery disease who are refractory to conventional forms of treatment. Although this issue has already been debated at the level of the National Societies, we felt that it was appropriate to also tackle it at the European level. This is particularly important in view of the rapid pace of growth of this problem and the lack of a standardized approach. This has encouraged the development of a variety of treatments that vary considerably in terms of cost-effectiveness and safety and require proper validation procedures. The aim of this paper is to draw attention to the problem and start a process that will lead to improvement and harmonization of the care of patients with refractory angina.
|
|
| 10. |
- Margolskee, Alison, et al.
(författare)
-
IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 2 : An introduction to the simulation exercise and overview of results
- 2017
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 610-625
-
Tidskriftsartikel (refereegranskat)abstract
- Orally administered drugs are subject to a number of barriers impacting bioavailability (F-oral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp (R), and GastroPlus (TM)) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters. Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise. Additionally, this prospective simulation exercise may not be representative of prospective modelling in industry, as API information was limited to sparse details. 43 active pharmaceutical ingredients (APIs) from the OrBiTo database were selected for the exercise. Over 4000 simulation output files were generated, representing over 2550 study arm-institution-software combinations and approximately 600 human clinical study arms simulated with overlap. 84% of the simulated study arms represented administration of immediate release formulations, 11% prolonged or delayed release, and 5% intravenous (i.v.). Higher percentages of i.v. predicted area under the curve (AUC) were within two-fold of observed (52.9%) compared to per oral (p.o.) (37.2%), however, F-oral and relative AUC (F-rel) between p.o. formulations and solutions were generally well predicted (64.7% and 75.0%). Predictive performance declined progressing from i.v. to solution and immediate release tablet, indicating the compounding error with each layer of complexity. Overall performance was comparable to previous large-scale evaluations. A general overprediction of AUC was observed with average fold error (AFE) of 1.56 over all simulations. AFE ranged from 0.0361 to 64.0 across the 43 APIs, with 25 showing overpredictions. Discrepancies between software packages were observed for a few APIs, the largest being 606, 171, and 81.7-fold differences in AFE between SimCYP and GI-Sim, however average performance was relatively consistent across the three software platforms.
|
|
