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| 2. |
- Bitsch, Bertram, et al.
(författare)
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The structure of protoplanetary discs around evolving young stars
- 2015
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 575
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Tidskriftsartikel (refereegranskat)abstract
- The formation of planets with gaseous envelopes takes place in protoplanetary accretion discs on time scales of several million years. Small dust particles stick to each other to form pebbles, pebbles concentrate in the turbulent flow to form planetesimals and planetary embryos and grow to planets, which undergo substantial radial migration. All these processes are influenced by the underlying structure of the protoplanetary disc, specifically the profiles of temperature, gas scale height, and density. The commonly used disc structure of the minimum mass solar nebula (MMSN) is a simple power law in all these quantities. However, protoplanetary disc models with both viscous and stellar heating show several bumps and dips in temperature, scale height, and density caused by transitions in opacity, which are missing in the MMSN model. These play an important role in the formation of planets, since they can act as sweet spots for forming planetesimals via the streaming instability and affect the direction and magnitude of type-I migration. We present 2D simulations of accretion discs that feature radiative cooling and viscous and stellar heating, and they are linked to the observed evolutionary stages of protoplanetary discs and their host stars. These models allow us to identify preferred planetesimal and planet formation regions in the protoplanetary disc as a function of the disc's metallicity, accretion rate, and lifetime. We derive simple fitting formulae that feature all structural characteristics of protoplanetary discs during the evolution of several Myr. These fits are straightforward for applying to modelling any growth stage of planets where detailed knowledge of the underlying disc structure is required.
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| 3. |
- Goodall, G., et al.
(författare)
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Biphasic insulin aspart 70/30 vs. insulin glargine in insulin naïve type 2 diabetes patients : modelling the long-term health economic implications in a Swedish setting
- 2008
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Ingår i: International journal of clinical practice (Esher). - : Wiley-Blackwell Publishing Inc.. - 1368-5031 .- 1742-1241. ; 62:6, s. 869-876
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the long-term clinical and economic outcomes of biphasic insulin aspart 70/30 (BIAsp 70/30) treatment vs. insulin glargine in insulin naïve, type 2 diabetes patients failing oral antidiabetic drugs in a Swedish setting.METHODS: A published and validated computer simulation model (the CORE Diabetes Model) was used to project life expectancy, quality-adjusted life expectancy (QALE) and costs over patient lifetimes. Cohort characteristics [54.5% male, mean age 52.4 years, 9 years mean diabetes duration, mean glycosylated haemoglobin (HbA1c) 9.77%] and treatment effects were based on results from the Initiate Insulin by Aggressive Titration and Education (INITIATE) clinical trial. Direct medical costs were accounted in 2006 Swedish Kronor (SEK) and economic and clinical benefits were discounted at 3% per annum.RESULTS: Biphasic insulin aspart 70/30 treatment when compared with insulin glargine treatment was associated with improvements in discounted life expectancy of 0.21 years (13.10 vs. 12.89 years) and QALE of 0.21 quality-adjusted life years (QALYs) (9.16 vs. 8.96 QALYs). Reductions in the incidence of diabetes-related complications in the BIAsp 70/30 treatment arm led to reduced total costs of SEK 10,367 when compared with insulin glargine (SEK 396,475 vs. SEK 406,842) over patient lifetimes. BIAsp 70/30 treatment was projected to be dominant (cost and lifesaving) when compared with insulin glargine in the base case analysis.CONCLUSIONS: Biphasic insulin aspart 70/30 treatment was associated with improved clinical outcomes and reduced costs compared with insulin glargine treatment over patient lifetimes. These results were driven by improved HbA1c levels associated with BIAsp 70/30 compared with insulin glargine and the accompanying reduction in diabetes-related complications despite increases in body mass index.
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| 5. |
- Rodriguez-Sanchez, J. L., et al.
(författare)
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Fission dynamics at high excitation energies investigated in complete kinematics measurements
- 2017
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 863:1, s. Article no 012047-
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Konferensbidrag (refereegranskat)abstract
- Light-charged particles emitted in proton-induced fission reactions on 208 Pb have been measured at different kinetic energies: 370A, 500A, and 650A MeV. The experiment was performed by the SOFIA collaboration at the GSI facilities in Darmstadt (Germany). The inverse kinematics technique was combined with a setup especially designed to measure light-charged particles in coincidence with fission fragments. The data were compared with different model calculations to assess the ground-to-saddle dynamics. The results confirm that transient and dissipative effects are required for an accurate description of the fission observables.
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| 6. |
- Schwabl, P, et al.
(författare)
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Colonization and genetic diversification processes of Leishmania infantum in the Americas
- 2021
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 139-
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Tidskriftsartikel (refereegranskat)abstract
- Leishmania infantum causes visceral leishmaniasis, a deadly vector-borne disease introduced to the Americas during the colonial era. This non-native trypanosomatid parasite has since established widespread transmission cycles using alternative vectors, and human infection has become a significant concern to public health, especially in Brazil. A multi-kilobase deletion was recently detected in Brazilian L. infantum genomes and is suggested to reduce susceptibility to the anti-leishmanial drug miltefosine. We show that deletion-carrying strains occur in at least 15 Brazilian states and describe diversity patterns suggesting that these derive from common ancestral mutants rather than from recurrent independent mutation events. We also show that the deleted locus and associated enzymatic activity is restored by hybridization with non-deletion type strains. Genetic exchange appears common in areas of secondary contact but also among closely related parasites. We examine demographic and ecological scenarios underlying this complex L. infantum population structure and discuss implications for disease control.
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| 8. |
- Szabo, Eva, 1973-
(författare)
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Molecular and clinical genetic studies of a novel variant of familial hypercalcemia
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Familial primary hyperparathyroidism (HPT) is a rare disorder that is treated surgically and mostly occurs in association with tumor-susceptibility syndromes, like multiple endocrine neoplasia and the hyperparathyroidism-jaw tumor syndrome. Familial hypercalciuric hypercalcemia (FHH) is another cause of hereditary hypercalcemia that generally is considered to require no treatment and is genetically and pathophysiologically distinct from HPT. Inactivating mutations in the calcium receptor gene cause FHH, whereas the down-regulated expression of the CaR in HPT never has been coupled to CaR gene mutations.Family screening revealed a hitherto unknown familial condition with characteristics of both FHH and HPT. The hypercalcemia was mapped to a point mutation in the intracellular domain of the CaR gene that was coupled to relative calcium resistance of the PTH release by transient expression in HEK 294 cells. Unusually radical excision of parathyroid glands was required to normalise the hypercalcemia. The mildly enlarged parathyroid glands displayed hyperplasia with nodular components. Frequent allelic loss on especially 12q was found and contrasts to findings in HPT. Allelic loss was also seen in loci typical for primary HPT like 1p, 6q and 15q, but not 11q13. Quantitative mRNA analysis showed that the glands had mild increase in a proliferation index (PCNA/GAPDH mRNA ratio) and mild reduction in genes important to parathyroid cell function, like CaR, PTH, VDR and LRP2.A previously unrecognized variant of hypercalcemia is explored that could be one explanation for persistent hypercalcemia after apparently typical routine operations for HPT. It also raises the issue of possibilities to treat FHH with parathyroidectomy provided it is radical enough.
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| 9. |
- Riddle, Matthew C., et al.
(författare)
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Monogenic diabetes : From genetic insights to population-based precision in care. reflections from a diabetes care editors’ expert forum
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:12, s. 3117-3128
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Tidskriftsartikel (refereegranskat)abstract
- Individualization of therapy based on a person’s specific type of diabetes is one key element of a “precision medicine” approach to diabetes care. However, applying such an approach remains difficult because of barriers such as disease heterogeneity, difficulties in accurately diagnosing different types of diabetes, multiple genetic influences, incomplete understanding of pathophysiology, limitations of current therapies, and environmental, social, and psychological factors. Monogenic diabetes, for which single gene mutations are causal, is the category most suited to a precision approach. The pathophysiological mechanisms of monogenic diabetes are understood better than those of any other form of diabetes. Thus, this category offers the advantage of accurate diagnosis of nonoverlapping etiological subgroups for which specific interventions can be applied. Although representing a small proportion of all diabetes cases, monogenic forms present an opportunity to demonstrate the feasibility of precision medicine strategies. In June 2019, the editors of Diabetes Care convened a panel of experts to discuss this opportunity. This article summarizes the major themes that arose at that forum. It presents an overview of the common causes of monogenic diabetes, describes some challenges in identifying and treating these disorders, and reports experience with various approaches to screening, diagnosis, and management. This article complements a larger American Diabetes Association effort supporting implementation of precision medicine for monogenic diabetes, which could serve as a platform for a broader initiative to apply more precise tactics to treating the more common forms of diabetes.
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| 10. |
- Pedersen, Marie, et al.
(författare)
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Meniscus or Cartilage Injury at the Time of Anterior Cruciate Ligament Tear Is Associated With Worse Prognosis for Patient-Reported Outcome 2 to 10 Years After Anterior Cruciate Ligament Injury : A Systematic Review
- 2020
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Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - : Journal of Orthopaedic & Sports Physical Therapy (JOSPT). - 0190-6011 .- 1938-1344. ; 50:9, s. 490-502
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: (1) To assess prognostic factors for patient-reported outcome measures (PROMs) and physical activity 2 to 10 years after anterior cruciate ligament reconstruction (ACLR) or anterior cruciate ligament (ACL) injury, and (2) to assess differences in prognostic factors between patients treated with ACLR and with rehabilitation alone.DESIGN: Prognosis systematic review.LITERATURE SEARCH: Systematic searches were performed in PubMed, Web of Science, and SPORTDiscus.STUDY SELECTION CRITERIA: We selected prospective cohort studies and randomized clinical trials that included adults or adolescents undergoing either ACLR or rehabilitation alone after ACL rupture. Studies had to assess the statistical association between potential prognostic factors (factors related to patient characteristics, injury, or knee symptoms/function measured at baseline or within 1 year) and outcomes (PROMs and physical activity).DATA SYNTHESIS: Our search yielded 997 references. Twenty studies met the inclusion criteria. Seven studies with low or moderate risk of bias remained for data synthesis.RESULTS: Moderate-certainty evidence indicated that concomitant meniscus and cartilage injuries were prognostic factors for worse PROMs 2 to 10 years after ACLR. Very low-certainty evidence suggested that body mass index, smoking, and baseline PROMs were prognostic factors for worse outcome. Very low-certainty evidence suggested that female sex and a worse baseline Marx Activity Rating Scale score were prognostic factors for a worse Marx Activity Rating Scale score 2 to 10 years after ACLR. There was a lack of studies on prognostic factors after rehabilitation alone.CONCLUSION: Concomitant meniscus and cartilage injuries were prognostic factors for worse long-term PROMs after ACLR. The certainty was very low for other prognostic factors. J Orthop Sports Phys Ther 2020;50(9):490-502. Epub 1 Aug 2020. doi:10.2519/jospt.2020.9451.
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