| 1. |
- Abou, Diane S., et al.
(author)
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Improved 223Ra Therapy with Combination Epithelial Sodium Channel Blockade
- 2021
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 62:12, s. 1751-1758
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Journal article (peer-reviewed)abstract
- [223Ra]RaCl2 is the first approved a-particle-emitting therapy and is indicated for treatment of bonemetastatic castration-resistant prostate cancer. Approximately half the dose is absorbed into the gastrointestinal tract within minutes of administration, limiting disease-site uptake and contributing to toxicity. Here,we investigated the role of enteric ion channels and their modulation for improved therapeutic efficacy and reduced side effects. Methods: Using primary human duodenal organoids (enteroids) asin vitromodelsof the functionalgastrointestinal epithelium, we found that amiloride (epithelial sodium ion channel blocker) and NS-1619 (K+ channel activator) presented significant effects in 223Ramembranal transport.Radioactivedrugdistributionwas evaluated for lead combinations in vivo and in osteosarcoma and prostate cancermodels.Results:Amiloride shifted 223Ra uptake in vivo fromthe gut and nearly doubled the uptake at sites of bone remodeling. Bone tumor growth inhibition with the combination as measured by bioluminescent imaging and radiographywas significantly greater than that with single agents alone, and the combination resulted in noweight loss.Conclusion: This combination of approved agentsmay readily be implemented as a clinical approach to improve the outcomes of bonemetastatic cancer patients with the benefit of ameliorated tolerability. COPYRIGHT
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| 2. |
- Gerdtham, Ulf-Göran, et al.
(author)
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New estimates of the demand for health : Results based on a categorical health measure and Swedish micro data
- 1999
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In: Social science & medicine (1982). - : Elsevier. - 1873-5347 .- 0277-9536. ; 49:10, s. 1325-1332
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Journal article (peer-reviewed)abstract
- In this paper we estimate a 'Grossman' model of demand for health based on Swedish micro data. The data set consists of a random sample of over 5000 individuals taken from the Swedish adult population. Health capital is measured by a categorical measure of overall health status, and an ordered probit model is used to econometrically estimate the demand for health equation. The results are consistent with the theoretical predictions and show that the demand for health increases with income and education and decreases with age, male gender, overweight, living in big cities and being single.
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| 3. |
- McCrae, Cristopher, et al.
(author)
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Lanosterol Synthase Regulates Human Rhinovirus Replication in Human Bronchial Epithelial Cells
- 2018
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In: American Journal of Respiratory Cell and Molecular Biology. - 1044-1549. ; 59:6, s. 713-722
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Journal article (peer-reviewed)abstract
- Human rhinovirus (RV) infections are a significant risk factor for exacerbations of asthma and chronic obstructive pulmonary disease. Thus, approaches to prevent RV infection in such patients would give significant benefit. Through RNA interference library screening, we identified lanosterol synthase (LSS), a component of the cholesterol biosynthetic pathway, as a novel regulator of RV replication in primary normal human bronchial epithelial cells. Selective knock down of LSS mRNA with short interfering RNA inhibited RV2 replication in normal human bronchial epithelial cells. Small molecule inhibitors of LSS mimicked the effect of LSS mRNA knockdown in a concentration-dependent manner. We further demonstrated that the antiviral effect is not dependent on a reduction in total cellular cholesterol but requires a 24-hour preincubation with the LSS inhibitor. The rank order of antiviral potency of the LSS inhibitors used was consistent with LSS inhibition potency; however, all compounds showed remarkably higher potency against RV compared with the LSS enzyme potency. We showed that LSS inhibition led to an induction of 24(S),25 epoxycholesterol, an important regulator of the sterol pathway. We also demonstrated that LSS inhibition led to a profound increase in expression of the innate antiviral defense protein, IFN-beta. We found LSS to be a novel regulator of RV replication and innate antiviral immunity and identified a potential molecular mechanism for this effect, via induction of 24(S),25 epoxycholesterol. Inhibition of LSS could therefore be a novel therapeutic target for prevention of RV-induced exacerbations.
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| 4. |
- Thorburn, Thomas
(author)
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Supply and demand of water transport : studies in cost and revenue structures of ships, ports and transport buyers with respect to their effects on supply and demand of water transport of goods
- 1960
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Doctoral thesis (other academic/artistic)abstract
- In this work the term "water transport of goods" is defined as both the transport of goods by ship and the handling in port, and is assumed to begin the moment the goods to be transported arrive at the port of dispatch by road, rail, smaller vessels or other means of conveyance, and to continue until the goods, loaded on trucks, railway waggons, local boats or by other means of transports leave the port of destination. The object of this study is to analyze some factors (variables) that affect the price making the aim being to clarify the more important relationships in supply and demand of water transport of goods. A feature of all transport is inter-local movement. Every investigation of price making on water transport must therefore deal with the influence of distance. Ships and ports are essential components in transport by water. Different ships and ports have their own particular features. Vessels may be different in size, age and type. Ports are in regions with different types of economic life, distances between them vary, as do their technical equipment, capacity and the like. An investigation should show the relationship of prices and the above-mentioned character of ships and ports. The structure of ships and ports must be taken into consideration. Different types of goods in varying quantities per consignment and with different demands on handling during transport occur in water-borne trade. The demand for transportation is divided unequally between different routes of transport and times of the year. A study should therefor throw light on the relationship between freight making and different ware-owners and types of goods. Prices at a certain moment are affected by factors that require a certain amount of time to make themselves felt. A study should therefore deal with the development in time. The whole of the following study will be connected to the factors mentioned above. Chapter 2-5 will deal with supply of cargo space; in Chapter 6 supply of harbour services will be discussed, and in chapter 7 the demand for water transport. Attempts will be made to analyze theoretically the relationships between the various factors and the main components, as well as certain mutual relationships of the different factors and of the components, in which the discussion will always centre around price making and competition. In chapter 8, finally, a summary will be given of the structure of price making from the aspect of both supply and demand factors as it has emerged in this study.
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| 5. |
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| 6. |
- Timberg, Pontus, et al.
(author)
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Investigation of viewing procedures for interpretation of breast tomosynthesis image volumes: a detection-task study with eye tracking.
- 2013
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In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 23:4, s. 997-1005
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To evaluate the efficiency of different methods of reading breast tomosynthesis (BT) image volumes. METHODS: All viewing procedures consisted of free scroll volume browsing and three were combined with initial cine loops at three different frame rates (9, 14 and 25 fps). The presentation modes consisted of vertically and horizontally orientated BT image volumes. Fifty-five normal BT image volumes in mediolateral oblique view were collected. In these, simulated lesions were inserted, creating four unique image sets, one for each viewing procedure. Four observers interpreted the cases in a free-response task. Time efficiency, visual attention and search were investigated using eye tracking. RESULTS: Horizontally orientated BT image volumes were read faster than vertically when using free scroll browsing only and when combined with fast cine loop. Cine loops at slow frame rates were ruled out as inefficient. CONCLUSIONS: In general, horizontally oriented BT image volumes were read more efficiently. All viewing procedures except for slow frame rates were promising when assuming equivalent detection performance. KEY POINTS : • Breast tomosynthesis is increasingly used for breast cancer detection • There is a benefit in reading breast tomosynthesis image volumes presented horizontally • Align image content to visual field, especially for dynamic 3D images • Reading at slow frame rates was considered inefficient.
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| 7. |
- Abou, Diane S., et al.
(author)
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Preclinical Single Photon Emission Computed Tomography of Alpha Particle-Emitting Radium-223
- 2020
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In: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 35:7, s. 520-529
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Journal article (peer-reviewed)abstract
- Objective: Dose optimization and pharmacokinetic evaluation of α-particle emitting radium-223 dichloride (223RaCl2) by planar γ-camera or single photon emission computed tomography (SPECT) imaging are hampered by the low photon abundance and injected activities. In this study, we demonstrate SPECT of 223Ra using phantoms and small animal in vivo models. Methods: Line phantoms and mice bearing 223Ra were imaged using a dedicated small animal SPECT by detecting the low-energy photon emissions from 223Ra. Localization of the therapeutic agent was verified by whole-body and whole-limb autoradiography and its radiobiological effect confirmed by immunofluorescence. Results: A state-of-the-art commercial small animal SPECT system equipped with a highly sensitive collimator enables collection of sufficient counts for three-dimensional reconstruction at reasonable administered activities and acquisition times. Line sources of 223Ra in both air and in a water scattering phantom gave a line spread function with a full-width-at-half-maximum of 1.45 mm. Early and late-phase imaging of the pharmacokinetics of the radiopharmaceutical were captured. Uptake at sites of active bone remodeling was correlated with DNA damage from the α particle emissions. Conclusions: This work demonstrates the capability to noninvasively define the distribution of 223RaCl2, a recently approved α-particle-emitting radionuclide. This approach allows quantitative assessment of 223Ra distribution and may assist radiation-dose optimization strategies to improve therapeutic response and ultimately to enable personalized treatment planning.
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| 8. |
- Abou, Diane S, et al.
(author)
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Whole-Body and Microenvironmental Localization of Radium-223 in Naïve and Mouse Models of Prostate Cancer Metastasis.
- 2016
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 108:5
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Journal article (peer-reviewed)abstract
- Bone-metastatic, castration-resistant prostate cancer (bmCRPC) represents a lethal stage of the most common noncutaneous cancer in men. The recent introduction of Radium-223 dichloride, a bone-seeking alpha particle (α)-emitting radiopharmaceutical, demonstrates statistically significant survival benefit and palliative effect for bmCRPC patients. Clinical results have established safety and efficacy, yet questions remain regarding pharmacodynamics and dosing for optimized patient benefit.
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| 9. |
- Ben Slimane, Slimane, et al.
(author)
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Tight bounds on the error probability of coded modulation schemes in Rayleigh fading channels
- 1994
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Conference paper (peer-reviewed)abstract
- This paper presents a tight upper bound on the bit error performance of coded modulation schemes in Rayleigh fading channels. Upper and lower bounds on the pairwise error probability are first derived. The upper bound is then expressed in a product form to be used with the transfer function bounding technique. This upper bound has the same simplicity as the union-Chernoff bound while providing closer results to the exact expression. Examples for 4-state and 8-state TCM 8PSK schemes are also given to illustrate the tightness and the application of this upper bound
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| 10. |
- Panican, Alexandru, et al.
(author)
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Säkra kort och öppna dörrar – om normer i gymnasievalsprocessen
- 2014
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In: Den långa vägen till arbetsmarknaden - om unga utanför. - Lund : Studentlitteratur AB. - 9789144093451 ; , s. 161-176
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Book chapter (peer-reviewed)abstract
- Under de senaste decennierna har förutsättningarna för att välja utbildning förändrats drastiskt. Eleverna står inför en lång rad valmöjligheter gällande inriktning, huvudman och skola. Detta ställer nya krav på grundskolan, som förväntas förbereda elever för att göra genomtänkta val. Emellertid tycks inte grundskolans faktiska hantering av dessa frågor ha utvecklats i nämnvärd mening. Tidigare rapporter pekar mot det heterogena studie- och yrkesvägledarlandskapet, vilket innebär otydliga uppdrag och en ojämnhet i hur mycket kommuner och rektorsområden prioriterar studie- och yrkesvägledningen. I detta kapitel fokuseras studie- och yrkesvägledare samt rektorer inom grundskolan, det vill säga aktörer med ansvar för att stödja elever genom gymnasievalet. Hur förhåller sig dessa aktörer till gymnasievalet? Vad säger de om elevernas upplevelser och ageranden i förhållande till gymnasievalet?
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