| 11. |
- Andersson, Henrik, et al.
(författare)
-
Economic Analysis and Investment Priorities in Sweden's Transport Sector
- 2018
-
Ingår i: Journal of Benefit-Cost Analysis. - : Cambridge University Press. - 2194-5888 .- 2152-2812. ; 9:1, s. 120-146
-
Tidskriftsartikel (refereegranskat)abstract
- Beginning as a planning tool within Sweden's national road administration some 50 years ago, benefit-cost analysis (BCA) has come to be a pillar of the national transport policy because of subsequent strategic choices made by the national parliament. These choices made it necessary to widen the analysis of costs to include also externalities and a foregone conclusion was that efficient investment priorities should be made based on BCA. But no one asked whether the political decision makers or the BCA models were up to that task. This paper reviews the institutional framework and practice of BCA in Sweden for transport infrastructure investment, and considers design issues that have been and still are debated, such as whether the discount rate should include a risk term and how to account for the marginal cost of public funds. A main concern with BCA results is the underestimation of construction costs, making transport sector projects look better than they are. Several ex post analyses have established that a higher NPV ratio increases the probability of being included in the investment program proposal prepared by the agency. The requirement to let projects undergo BCA seems to make planners trim project proposals by trying to reduce investment costs without significantly reducing benefits. This relationship is weaker among profitable projects. Moreover, there is no correlation between rate of return and the probability of being included in the final program, which is established on political grounds.
|
|
| 12. |
|
|
| 13. |
- Andrikopoulos, Petros, et al.
(författare)
-
Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
-
Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
|
|
| 14. |
- Dahl Jensen, Lasse, et al.
(författare)
-
Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish
- 2012
-
Ingår i: Cell Reports. - : Elsevier (Cell Press). - 2211-1247. ; 2:2, s. 231-241
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular mechanisms underlying circadian-regulated physiological processes remain largely unknown. Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation of key genes in zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. Using a promoter-reporter system consisting of various deleted vegf-promoter mutants, we show that Bmal1 directly binds to and activates the vegf promoter via E-boxes. Additionally, we provide evidence that knockdown of Bmal1 leads to impaired Notch-inhibition-induced vascular sprouting. These results shed mechanistic insight on the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis.
|
|
| 15. |
- Dini, Hoda, 1984-, et al.
(författare)
-
Optimization and validation of a dislocation density based constitutive model for as-cast Mg-9%Al-1%Zn
- 2018
-
Ingår i: Materials Science & Engineering. - : Elsevier. - 0921-5093 .- 1873-4936. ; 710, s. 17-26
-
Tidskriftsartikel (refereegranskat)abstract
- A dislocation density-based constitutive model, including effects of microstructure scale and temperature, was calibrated to predict flow stress of an as-cast AZ91D (Mg-9%Al-1%Zn) alloy. Tensile stress-strain data, for strain rates from 10-4 up to 10-1 s-1 and temperatures from room temperature up to 190 °C were used for model calibration. The used model accounts for the interaction of various microstructure features with dislocations and thereby on the plastic properties. It was shown that the Secondary Dendrite Arm Spacing (SDAS) size was appropriate as an initial characteristic microstructural scale input to the model. However, as strain increased the influence of subcells size and total dislocation density dominated the flow stress. The calibrated temperature-dependent parameters were validated through a correlation between microstructure and the physics of the deforming alloy. The model was validated by comparison with dislocation density obtained by using Electron Backscattered Diffraction (EBSD) technique.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Fjälling, M, et al.
(författare)
-
Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.
- 1996
-
Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:9, s. 1519-21
-
Tidskriftsartikel (refereegranskat)abstract
- A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.
|
|
