| 1. |
- Edger, Patrick P., et al.
(författare)
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The butterfly plant arms-race escalated by gene and genome duplications
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:27, s. 8362-8366
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Tidskriftsartikel (refereegranskat)abstract
- Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.
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| 2. |
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| 3. |
- Arpaia, Riccardo, 1985, et al.
(författare)
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Engineering underdoped CuO2 nanoribbons in nm-thick a -axis YBa2Cu3 O7-δ films
- 2024
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Ingår i: Physical Review Materials. - : American Physical Society. - 2475-9953. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- In underdoped cuprate high-Tc superconductors, various local orders and symmetry-breaking states, in addition to superconductivity, reside in the CuO2 planes. The confinement of the CuO2 planes can therefore play a fundamental role in modifying the hierarchy between the various orders and their intertwining with superconductivity. Here we present the growth of a-axis oriented YBa2Cu3O7-δ films, spanning the whole underdoped side of the phase diagram. In these samples, the CuO2 planes are confined by the film thickness, effectively forming unit-cell-thick nanoribbons. The unidirectional confinement at the nanoscale enhances the in-plane anisotropy of the films. By x-ray diffraction and resistance vs temperature measurements, we have discovered the suppression of the orthorhombic-to-tetragonal transition at low dopings, and a very high anisotropy of the normal state resistance in the b-c plane, the latter being connected to a weak coupling between adjacent CuO2 nanoribbons. These findings show that the samples we have grown represent a novel system, different from the bulk, where future experiments can possibly shed light on the rich and mysterious physics occurring within the CuO2 planes.
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| 4. |
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| 5. |
- Bergqvist, Davis, et al.
(författare)
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Benartärsjukdom – inget nytt sedan SBU-rapporten
- 2011
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Ingår i: Läkartidningen. - : Läkartidningen Förlag. - 0023-7205 .- 1652-7518. ; 108:8, s. 403-405
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Huvudresultaten i SBU:s benischemirapport sammanfattas.Inga nya studier av öppna eller endovaskulära behandlingsmetoder har nämnvärt förändrat behandlingsstragegin vid benartärsjukdom.Ett läkemedel – cilostazol – har godkänts för symtomatisk behandling vid claudicatio intermittens.Kontrollerade studier pågår för att lokalt stimulera kärlnybildning i ischemisk muskulatur.
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| 6. |
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| 7. |
- Cao, Ziquan, et al.
(författare)
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Hypoxia-induced retinopathy model in adult zebrafish
- 2010
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Ingår i: Nature Protocols. - : Nature Publishing Group. - 1754-2189 .- 1750-2799. ; 5:12, s. 1903-1910
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia-induced vascular responses, including angiogenesis, vascular remodeling and vascular leakage, significantly contribute to the onset, development and progression of retinopathy. However, until recently there were no appropriate animal disease models recapitulating adult retinopathy available. In this article, we describe protocols that create hypoxia-induced retinopathy in adult zebrafish. Adult fli1: EGFP zebrafish are placed in hypoxic water for 3-10 d and retinal neovascularization is analyzed using confocal microscopy. It usually takes 11 d to obtain conclusive results using the hypoxia-induced retinopathy model in adult zebrafish. This model provides a unique opportunity to study kinetically the development of retinopathy in adult animals using noninvasive protocols and to assess therapeutic efficacy of orally active antiangiogenic drugs.
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| 8. |
- Cao, Ziquan, 1982-
(författare)
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VEGF-mediated vascular functions in health and disease
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Angiogenesis is essential for physiological processes including embryonic development, tissue regeneration, and reproduction. Under various pathological conditions the same angiogenic process contribute to the onset, development, and progression of many human diseases including cancer, diabetic complications, ocular disease, chronic inflammation and cardiovascular disease. Vascular endothelial growth factor (VEGF) is a key angiogenic factor for physiological and pathological angiogenesis. In addition to its strong angiogenic activity, VEGF also potently induces vascular permeability, often causing tissue edema in various pathological tissues. VEGF transduces its vascular signal through two tyrosine kinase receptors-VEGFR1 and VEGFR2, the latter being a functional receptor that mediates both angiogenic and vascular permeability effects. To study physiological and pathological functions of VEGF, we developed novel zebrafish disease models that permit us to study hypoxia-induced retinopathy and cancer metastasis processes. We have also administered anti-VEGF and anti-VEGFR specific antibodies to healthy mice to study the homeostatic role of VEGF in the maintenance of vascular integrity and its functions in various tissues and organs.Finally, using a zebrafish model, we evaluated if VEGF expression is regulated by circadian clock genes. In paper I, we developed protocols that create hypoxia-induced retinopathy in adult zebrafish. Adult fli1:EGFP zebrafish were placed in hypoxic water for 3-10 days with retinal neovascularization being analyzed using confocal microscopy. This model provides a unique opportunity to kinetically study the development of retinopathy in adult animals using non-invasive protocols and to assess the therapeutic efficacy of orally administered anti-angiogenic drugs. In paper II, we developed a zebrafish metastasis model to dissect the complex events of hypoxia-induced tumor cell invasion and metastasis in association with angiogenesis at the single-cell level. In this model, fluorescent DiI-labeled human or mouse tumor cells were implanted into the perivitelline cavity of 48-hour-old zebrafish embryos, which were subsequently placed in hypoxic water for 3 days. Tumor cell invasion, metastasis and pathological angiogenesis were analyzed using fluorescent microscopy in the living fish. The average experimental time for this model is 7 days. Our protocol offers an opportunity to study molecular mechanisms of hypoxia-induced cancer metastasis. In paper III, we show that systemic delivery of an anti-VEGF or an anti-VEGF receptor (VEGFR)-2 neutralizing antibody cause global vascular regression in mice. Among all examined tissues, the vasculature in endocrine glands, intestinal villi, and the uterus are most affected in response to VEGF or VEGFR-2 blockades. Pro-longed anti-VEGF treatment resulted in a significant decrease in the circulating levels of the predominant thyroid hormone, free thyroxine, but not the minimal isoform of triiodothyronine, suggesting that chronic anti-VEGF treatment impairs thyroid function. These findings provide structural and functional bases of anti-VEGF-specific druginduced side effects in relation to vascular changes in healthy tissues. In paper IV, we show that disruption of the circadian clock by constant exposure to light coupled with genetic manipulation of key genes in the 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. These results offer mechanistic insights into 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. Overall, the results in this thesis provide further insight to angiogenic mechanistic properties in tissues and suggest possible novel therapeutic targets for the treatment of various angiogenesis-dependent diseases.
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| 9. |
- Dahl Jensen, Lasse, et al.
(författare)
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Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish
- 2012
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Ingår i: Cell Reports. - : Elsevier (Cell Press). - 2211-1247. ; 2:2, s. 231-241
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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.
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| 10. |
- Dahl Jensen, Lasse, et al.
(författare)
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Zebrafish Models to Study Hypoxia-Induced Pathological Angiogenesis in Malignant and Nonmalignant Diseases
- 2011
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Ingår i: Birth Defects Research. Part C: Embryo Today Reviews. - : John Wiley and Sons.Ltd. - 1542-975X .- 1542-9768. ; 93:2, s. 182-193
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Forskningsöversikt (refereegranskat)abstract
- Most in vivo preclinical disease models are based on mouse and other mammalian systems. However, these rodent-based model systems have considerable limitations to recapitulate clinical situations in human patients. Zebrafish have been widely used to study embryonic development, behavior, tissue regeneration, and genetic defects. Additionally, zebrafish also provides an opportunity to screen chemical compounds that target a specific cell population for drug development. Owing to the availability of various genetically manipulated strains of zebrafish, immune privilege during early embryonic development, transparency of the embryos, and easy and precise setup of hypoxia equipment, we have developed several disease models in both embryonic and adult zebrafish, focusing on studying the role of angiogenesis in pathological settings. These zebrafish disease models are complementary to the existing mouse models, allowing us to study clinically relevant processes in cancer and nonmalignant diseases, which otherwise would be difficult to study in mice. For example, dissemination and invasion of single human or mouse tumor cells from the primary site in association with tumor angiogenesis can be studied under normoxia or hypoxia in zebrafish embryos. Hypoxia-induced retinopathy in the adult zebrafish recapitulates the clinical situation of retinopathy development in diabetic patients or age-related macular degeneration. These zebrafish disease models offer exciting opportunities to understand the mechanisms of disease development, progression, and development of more effective drugs for therapeutic intervention.
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| 11. |
- Dong, Mei, et al.
(författare)
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Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis
- 2013
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Ingår i: Cell Metabolism. - : Elsevier (Cell Press). - 1550-4131 .- 1932-7420. ; 18:1, s. 118-129
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E-/- [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.
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| 12. |
- Ferreira, Daniel, et al.
(författare)
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Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor
- 2015
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 43, s. 1059-1072
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Tidskriftsartikel (refereegranskat)abstract
- © 2015-IOS Press and the authors. New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age-and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.
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| 13. |
- Fröjse, Rolf, 1958-
(författare)
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Exploring Intestinal Ischemia : An experimental study
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Unrecognized intestinal mucosal ischemia in severely ill patients may trigger development of multiple organ failure. Such ischemia can be evaluated by intraluminal tonometry reflecting mucosal PCO2 and intramucosal pH (pHi). The aims were to develop an apparatus for continuous saline tonometry (CST), to analyse circulatory control mechanisms during intestinal hypoperfusion and to evaluate the effect of dopexamine on intestinal circulation. Methods: A modified standard tonometry catheter was integrated in a closed system with circulating saline. By measuring saline PCO2 in a measurement unit pHi could be calculated. This novel system was tested in vitro and in vivo. In a porcine study, CST was evaluated against standard saline tonometry, tissue oxygenation (PO2 TISSUE), jejunal mucosal perfusion (laser doppler flowmetry; LDF) and mesenteric net lactate flux during graded reductions of superior mesenteric arterial pressure (PSMA). Local control mechanisms for maintenance of intestinal oxygenation were analysed. Effects of dopexamine on the intestinal vascular bed were explored. Mucosal lactate production was assessed by microdialysis.Results: CST measured accurate PCO2 values and changes in pHi during restricted intestinal circulation and at reperfusion. Local control mechanisms were insufficient at a PSMA of 30 mmHg, pHi was reduced to 7.10 and intestinal net lactate production was demonstrated. Absence of anaerobic intestinal metabolism was verified at PSMA ≥ 50 mmHg, pHi ≥ 7.22 and a PCO2 gap ≤ 15.8 mmHg. Dopexamine induced negative regional metabolic effects at the lowest PSMA, as expressed by decreased PO2 TISSUE and pHi, increased PCO2 gap and intestinal net lactate production. Conclusions: CST reflected changes in pHi, induced by intestinal hypoperfusion and at reperfusion. Levels of PSMA, pHi and PCO2 gap as indicators of aerobic conditions were defined. Dopexamine induced a decrease of PO2 TISSUE and pHi as well as an increase in lactate flux at the lowest PSMA level.
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| 14. |
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| 15. |
- Gottsäter, Anders, et al.
(författare)
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Viktigt behandla riskfaktorer vid kritisk extremitetsischemi
- 2007
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Ingår i: Läkartidningen. - 0023-7205. ; 104:11, s. 4-860
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic critical limb ischaemia (CLI) have a one-year mortality of around 20%, and a ten-year survival of around 25%, mainly due to concomitant cardio- and cerebrovascular atherosclerotic disease. Risk factors for the development of peripheral atherosclerosis and CLI are the same as for cardio- and cerebrovascular atherosclerosis; diabetes mellitus, hyperlipidaemia, arterial hypertension, and smoking are common in CLI patients. As risk factor studies in CLI and peripheral arterial occlusive disease (PAOD) are few, treatment recommendations are often based on studies in patients with cardio- or cerebrovascular atherosclerosis and it can therefore not be definitely established that the recommendations are adequate for CLI patients. While waiting for specific studies, CLI patients should be treated according to current guidelines for other atherosclerotic patients. Medical risk factor treatment in CLI is often suboptimal in relation to recommendations, however, and both better treatment and more studies of medical risk factors in CLI patients are therefore needed.
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| 16. |
- Jönsson, Björn, 1951-
(författare)
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On leg ischaemia : aspects of epidemiology and diagnostics
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first part of this thesis consists of a population-based epidemiological study on symptomatic leg arterial disease in a Swedish community, based on a postal questionnaire and systolic ankle pressure measurements, with calculation of the ankle-brachial pressure index (ABPI; usually ≥ 1.0 in healthy subjects). The second part investigates alternative methods for ankle systolic pressure measurements, with the potential of automation.(Papers I-III) A postal questionnaire on leg symptoms and concomitant diseases was distributed to all the inhabitants of Vadstena 50-89 years old (n=7,524). The response rate was 92% and of those reporting any leg pain, 80% (353/441) attended an examination with ABPI determination. Symptomatic leg ischaemia (SLI) was defined as leg pain on walking + ABPI ≤ 0.8. The prevalence was 4.1 %, increasing with age, with no major difference between men and women. Other manifestations of arteriosclerotic disease (previous angina pectoris, myocardial infarction or cerebrovascular incident), hypertension and diabetes mellitus were more prevalent among SLI cases than in healthy subjects. At a four-year follow-up, the age and sex adjusted mortality ratio was almost doubled in SLI subjects. Their relative risk of a myocardial infarction, cardiac death and death due to any cardiovascular event was 2.7, 2.0 and 1.9, respectively, compared to an age and sex matched control group. In SLI subjects without a previous history of ischaemic heart disease, the relative risk of a myocardial infarction was 3.1. Cardiovascular disease alone was mainly responsible for the increased risk of death. At a ten-year follow-up, a baseline ABPI up to 0.8 was inversely correlated with mortality. In a Cox regression model, a low ABPI was significantly and independently associated with an increased risk of death. An ABPI of 0.81-0.99 was not associated with an increased mortality risk. Over ten years, 1/7 of the SLI cases had a leg vascular reconstructive procedure, the majority within the first two years, and 1/14 underwent a major amputation. In conclusion, in spite of the good prognosis of the local disease, SLI can be looked upon as a marker for generalised arteriosclerotic disease and as a risk predictor for severe arteriosclerotic events and premature death.(Papers IV-VI) Oscillometric technique, commonly used for automatic arm blood pressure measurements, was validated against the CW Doppler in systolic ankle pressure determination in healthy subjects and in patients with leg arterial disease. While performing adequately in healthy subjects, it was found to be invalid in leg arterial disease. The oscillometric technique was deemed as not suitable for use as an automatic ankle pressure recorder in the diagnosis ofleg arteriosclerotic disease.A new technique, based on a two-channel photoplethysmographic (PPG) probe (880nm) placed underneath the pneumatic cuff, together with electronics, was developed and compared with both CW Doppler and intra-arterial recordings in subjects without vascular disease, and with the CW Doppler in leg arterial disease. On visual analysis of the PPG curves, the agreement was good. An automatic algorithm for analysis of PPG-data gave comparable results. The PPG method is a promising technique for future automation of systolic ankle pressure measurements, and for inclusion in a complete ABPI recorder.
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| 17. |
- Karami, Azadeh, et al.
(författare)
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Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:11, s. 1316-1328
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase. Method: Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed. Results: Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-beta, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. Discussion: A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.
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| 18. |
- Koraen, L., et al.
(författare)
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Claudicatio intermittens
- 2010
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Ingår i: Läkartidningen. - : Lakartidningen. - 0023-7205 .- 1652-7518. ; 107:29-31, s. 1774-1779
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Tidskriftsartikel (refereegranskat)
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| 19. |
- Letterstål, Anna, et al.
(författare)
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Risk attitudes to treatment among patients with severe intermittent claudication
- 2008
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Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 47:5, s. 988-994
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo determine claudication patients' risk attitude to invasive treatment and whether this treatment is cost effective.MethodsQuality of life and health state utility status of 50 consecutive patients with severe intermittent claudication was assessed and compared with ankle-brachial pressure index values (ABPI) and results from treadmill tests before and after endovascular or open revascularization. Health utility scores were then calculated and used in a cost-utility analysis.ResultsBefore surgery, patients were assigned a utility score of 0.51 (EQ-5D index) for their disease, and the standard gamble (SG) and time trade-off (TTO) median scores were 0.88 and 0.70, respectively. Before treatment, a weak correlation (r = 0.43, P < .001) between having a high risk perception of treatment and patients' walking distance were observed, where patients able to walk short distances accepted a higher risk. After treatment, ABI (P = .003) and walking distance (P = .002) improved significantly as well the physical components of the quality of life instruments (P < .001). The surgical treatment generated an improvement in quality of life expressed in QALYs equivalent to 0.17. With an estimated survival of 5 years, it adds up to a value of 0.85, corresponding to a sum of 51,000 US$ gained.ConclusionsPatients with severe intermittent claudication are risk-seeking when it comes to surgical treatment and their risk attitude is correlated to their walking ability and quality of life. The incremental QALYs gained by treatment are achieved at a reasonable cost and revascularization appears to be cost effective.
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| 20. |
- Malmstedt, J, et al.
(författare)
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Influence of perioperative blood glucose levels on outcome after infrainguinal bypass surgery in patients with diabetes
- 2006
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Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 93:11, s. 1360-1367
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High glucose levels are associated with increased morbidity and mortality after coronary surgery and in intensive care. The influence of perioperative hyperglycaemia on the outcome after infrainguinal bypass surgery among diabetic patients is largely unknown. The aim was to determine whether high perioperative glucose levels were associated with increased morbidity after infrainguinal bypass surgery.METHODS: Ninety-one consecutive diabetic patients undergoing primary infrainguinal bypass surgery were identified from a prospective vascular registry. Risk factors, indication for surgery, operative details and outcome data were extracted from the medical records. Exposure to perioperative hyperglycaemia was measured using the area under the curve (AUC) method; the AUC was calculated using all blood glucose readings during the first 48 h after surgery.RESULTS: Multivariable analysis showed that the AUC for glucose (odds ratio (OR) 13.35, first versus fourth quartile), renal insufficiency (OR 4.77) and infected foot ulcer (OR 3.38) was significantly associated with poor outcome (death, major amputation or graft occlusion at 90 days). Similarly, the AUC for glucose (OR 14.45, first versus fourth quartile), female sex (OR 3.49) and tissue loss as indication (OR 3.30) was associated with surgical wound complications at 30 days.CONCLUSION: Poor perioperative glycaemic control was associated with an unfavourable outcome after infrainguinal bypass surgery in diabetic patients.
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| 21. |
- Malmstedt, Jonas, et al.
(författare)
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Outcome after leg bypass surgery for critical limb ischemia is poor in patients with diabetes
- 2008
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Ingår i: Diabetes Care. - Alexandria, VA, United States : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 31:5, s. 887-892
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—Our aim was to assess the risk of major amputation or death after leg bypass surgery for critical limb ischemia in patients with diabetes versus those without.RESEARCH DESIGN AND METHODS—We did a population-based cohort study by linking nationwide databases in Sweden. We identified 1,840 patients in the Swedish Vascular Registry who had their first leg bypass procedure for critical lower-limb ischemia between 1 January 2001 and 31 December 2003—742 with and 1,098 without diabetes. Our primary end point was first major amputation of the limb on which bypass was done or death. Individuals were followed up until 31 December 2005 through the National Hospital Patient Registry and the Cause-of-Death Registry.RESULTS—Incidence of ipsilateral amputation or death was higher in patients with diabetes than in patients without (30.2 vs. 22 events/100 person-years; crude hazard ratio [HR] 1.32 [95% CI 1.17–1.50]). Similarly, individuals with diabetes had a shorter amputation-free survival period than individuals without (2.3 years, range 1.9–2.8 vs. 3.4 years, range 3.1–3.7). Adjustment for demographic characteristics, comorbidities, and risk factors for amputation or death did not substantially affect the risk (HR 1.46 [95% CI 1.26–1.69]). The effect was more pronounced in male (1.75 [1.47–2.08]) than in female (1.35 [1.11–1.64]) patients after adjustment for age.CONCLUSIONS—Diabetes is associated with lower amputation–free survival after leg bypass for critical limb ischemia. Patients with diabetes and limb ischemia need intensified treatment of diabetes-related risk factors to improve outcome.
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| 22. |
- Manca, Nicola, et al.
(författare)
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Integration of High-Tc Superconductors with High-Q-Factor Oxide Mechanical Resonators
- 2024
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Ingår i: Advanced Functional Materials. - : John Wiley and Sons Inc. - 1616-3028 .- 1616-301X. ; In Press
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Tidskriftsartikel (refereegranskat)abstract
- Micro-mechanical resonators are building blocks of a variety of applications in basic science and consumer electronics. This device technology is mainly based on well-established and reproducible silicon-based fabrication processes with outstanding performances in term of mechanical Q-factor and sensitivity to external perturbations. Broadening the functionalities of micro-electro-mechanical systems (MEMS) by the integration of functional materials is a key step for both applied and fundamental science. However, combining functional materials with silicon-based devices is challenging. An alternative approach is directly fabricating MEMS based on compounds inherently showing non-trivial functional properties, such as transition metal oxides. Here, a full-oxide approach is reported, where a high- (Formula presented.) superconductor YBa2Cu3O7 (YBCO) is integrated with high Q-factor micro-bridge resonators made of single-crystal LaAlO3 (LAO) thin films. LAO resonators are tensile strained, with a stress of about 350 MPa, show a Q-factor above 200k, and have low roughness. YBCO overlayers are grown ex situ by pulsed laser deposition and YBCO/LAO bridges show zero resistance below 78 K and mechanical properties similar to those of bare LAO resonators. These results open new possibilities toward the development of advanced transducers, such as bolometers or magnetic field detectors, as well as experiments in solid state physics, material science, and quantum opto-mechanics.
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| 23. |
- Mattila, Robert
(författare)
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Hidden Markov models : Identification, control and inverse filtering
- 2018
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The hidden Markov model (HMM) is one of the workhorse tools in, for example, statistical signal processing and machine learning. It has found applications in a vast number of fields, ranging all the way from bioscience to speech recognition to modeling of user interactions in social networks. In an HMM, a latent state transitions according to Markovian dynamics. The state is only observed indirectly via a noisy sensor – that is, it is hidden. This type of model is at the center of this thesis, which in turn touches upon three main themes.Firstly, we consider how the parameters of an HMM can be estimated from data. In particular, we explore how recently proposed methods of moments can be combined with more standard maximum likelihood (ML) estimation procedures. The motivation for this is that, albeit the ML estimate possesses many attractive statistical properties, many ML schemes have to rely on local-search procedures in practice, which are only guaranteed to converge to local stationary points in the likelihood surface – potentially inhibiting them from reaching the ML estimate. By combining the two types of algorithms, the goal is to obtain the benefits of both approaches: the consistency and low computational complexity of the former, and the high statistical efficiency of the latter.The filtering problem – estimating the hidden state of the system from observations – is of fundamental importance in many applications. As a second theme, we consider inverse filtering problems for HMMs. In these problems, the setup is reversed; what information about an HMM-filtering system is exposed by its state estimates? We show that it is possible to reconstruct the specifications of the sensor, as well as the observations that were made, from the filtering system’s posterior distributions of the latent state. This can be seen as a way of reverse engineering such a system, or as using an alternative data source to build a model.Thirdly, we consider Markov decision processes (MDPs) – systems with Markovian dynamics where the parameters can be influenced by the choice of a control input. In particular, we show how it is possible to incorporate prior information regarding monotonic structure of the optimal decision policy so as to accelerate its computation. Subsequently, we consider a real-world application by investigating how these models can be used to model the treatment of abdominal aortic aneurysms (AAAs). Our findings are that the structural properties of the optimal treatment policy are different than those used in clinical practice – in particular, that younger patients could benefit from earlier surgery. This indicates an opportunity for improved care of patients with AAAs.
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| 24. |
- Mirarchi, Giovanni, et al.
(författare)
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Tuning the ground state of cuprate superconducting thin films by nanofaceted substrates
- 2024
-
Ingår i: Communications Materials. - : Springer Nature. - 2662-4443. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Anisotropic transport properties have been assessed in a number of cuprate superconductors, providing evidence for a nematic state. We have recently shown that in ultra-thin YBa2Cu3O7−δ films, where nematicity is induced via strain engineering, there is a suppression of charge density wave scattering along the orthorhombic a-axis and a concomitant enhancement of strange metal behavior along the b-axis. Here we develop a microscopic model, that is based on the strong interaction between the substrate facets and the thin film, to account for the unconventional phenomenology. Based on the atomic force microscopy imaging of the substrates’ surface, the model is able to predict the absence (presence) of nematicity and the resulting transport properties in films grown on SrTiO3 (MgO) substrates. Our result paves the way to new tuning capabilities of the ground state of high-temperature superconductors by substrate engineering.
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| 25. |
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| 26. |
- Palmer-Kazen, U, et al.
(författare)
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Exercise in patients with intermittent claudication elicits signs of inflammation and angiogenesis.
- 2009
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 38, s. 689-696
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Previous studies have demonstrated elevation of systemic levels of inflammatory cytokines after treadmill exercise in patients with intermittent claudication (IC), but it is unknown if growth factor expression also is stimulated. The aim of this study was to assess whether physical exercise-induced ischemia elicits an inflammatory response and increase in local and systemic vascular growth factor expression in patients with IC. Methods Nineteen patients with IC had plasma concentrations of inflammatory markers (IL-6, TNF-alpha, hs-CRP) and vascular growth factors (VEGF and FGF-2) measured before and at four time points after a treadmill exercise test. In 10 patients a gastrocnemius muscle biopsy was obtained to measure VEGF and FGF-2 mRNA. Plasma concentrations of vWF were also measured. Five patients who underwent the treadmill test without experiencing calf pain were enrolled as controls. Results Plasma concentrations of IL-6 increased after exercise (p = 0.004), while TNF-alpha and hs-CRP were unchanged (p = 0.191 and p = 0.709, respectively). Plasma concentrations of VEGF were similar (p = 0.151) at the different time points after exercise but FGF-2 levels decreased (p = 0.013). In biopsies after treadmill testing VEGF-A mRNA was increased (p = 0.043), but no change was observed for FGF-2 (p = 0.456). Conclusion Exercise in IC triggers an inflammatory response as exemplified by elevated concentrations of IL-6. After exercise-induced pain, VEGF mRNA in calf muscle is increased. Therefore, it is plausible that angiogenesis is stimulated by exercise in IC.
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| 27. |
- Pellegrino, Luca, et al.
(författare)
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A Hybrid Superconductor/Nanomechanical Magnetic Field Detector for Biomagnetism
- 2023
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Ingår i: 2023 IEEE Nanotechnology Materials and Devices Conference, NMDC 2023. ; , s. 770-771
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Konferensbidrag (refereegranskat)abstract
- We report the results of the OXiNEMS project (www.oxinems.eu) concerning the realization of a high-sensitivity magnetometer made by a magnetic nanomechanical resonator coupled to a nanopatterned superconducting thin film structure integrated with a superconducting loop. We discuss the basic working principle of the device, its first characterizations and the instrumentation we developed to measure the device performances in view of its application in the field of biomagnetism.
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| 28. |
- Pereira Filho, Antonio J. G., et al.
(författare)
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Impact of Ankle Brachial Index Calculations on Peripheral Arterial Disease Prevalence and as a Predictor of Cardiovascular Risk
- 2022
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 64:2-3, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to estimate the prevalence and predictive accuracy for cardiovascular (CV) morbidity by using different ankle brachial index (ABI) calculation methods in the general population.Methods: ABI measurements and questionnaire data were collected from 5 080 randomly selected citizens aged 60 - 90 years. A 10 year follow up with data from Swedish national health registries was carried out. ABI was calculated using as numerator the highest (ABI-HI) or the lowest (ABI-LO) ankle BP obtained in each leg. Subjects were defined as references or having peripheral arterial disease (PAD) based on ABI-LO (Group 1) or ABI-HI (Group 2). Prevalence, mortality, CV events and risk were then analysed for these three groups, and their predictive power by using the area under the curve (AUC).Results: A total of 4 909 inhabitants were included in the cohort (References: 83.8%, Group 1: 6.7% and Group 2: 9.6%). The prevalence of PAD was 16% using ABI-LO, and 9.6% using ABI-HI. The 10 year all cause mortality for references and Groups 1 and 2 was 27.6%, 48.8%, and 67.2%, respectively. The overall age adjusted hazard ratio (95% confidence interval) for the composite outcome of CV mortality and a non-fatal CV event was 1.25 (1.06 - 1.49) for Group 1 and 2.11 (1.85 - 2.39) for Group 2. The prediction accuracy for ABI < 0.9 in predicting CV event measured with AUC was 0.60 for ABI-HI and 0.62 for ABI-LO.Conclusion: An ABI < 0.9 should be considered a strong risk marker for future CV morbidity. Applying the traditional ABI calculation method of using the highest measured ankle BP, a group of subjects with high CV risk may be overlooked for intervention, and this why the lowest ankle BP should be the preferred for risk stratification. However, as a single predictive tool an ABI < 0.9 cannot adequately discriminate which individual will have a future CV event regardless of calculation method used.
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| 29. |
- Persson, Johannes, et al.
(författare)
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Science and proven experience : a Swedish variety of evidence-based medicine?
- 2016
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Konferensbidrag (refereegranskat)abstract
- A key question for evidence-based medicine (EBM) is how best to model the way in which EBM should “[integrate] individual clinical expertise and the best external evidence” (Sackett et al. 1996). We argue that the formulations and models available in the literature today are modest variations on a common theme and face very similar problems. For example, both the early and updated models of evidence-based clinical decisions presented in Haynes, Devereaux and Guyatt (2002) assume (with Sackett, et. al., 1996) that EBM consists of, among other things, evidence from clinical research and clinical expertise. On this A-view, EBM describes all that goes on in a specific justifiable medical decision. There is, however, an alternative interpretation of EBM, the B-view, in which EBM describes just one component of the decision situation (a component usually based on evidence from clinical research) and in which, together with other types of evidence, EBM leads to a justifiable clincial decision but does not describe the decision itself. This B-view is inspired by a 100-years older version of EBM, a Swedish standard requiring medical decision-making and practice to be in accordance with ‘science and proven experience’. In the paper we outline how the Swedish concept leads to an improved understanding of the way in which scientific evidence and clinical experience can and cannot be integrated in light of EBM. In addition the paper sketches the as yet unexplored historical background to EBM.
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| 30. |
- Persson, Johannes, et al.
(författare)
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Science and proven experience : a Swedish variety of evidence based medicine and a way to better risk analysis?
- 2019
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Ingår i: Journal of Risk Research. - : Informa UK Limited. - 1366-9877 .- 1466-4461. ; 22:7, s. 833-843
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Tidskriftsartikel (refereegranskat)abstract
- A key question for evidence-based medicine (EBM) is how best to model the way in which EBM should‘[integrate] individual clinical expertise and the best external evidence’. We argue that the formulations and models available in the literature today are modest variations on a common theme and face very similar problems when it comes to risk analysis, which is here understood as a decision procedure comprising a factual assessment of risk, the risk assessment, and the decision what to do based on this assessment, the risk management. Both the early and updated models of evidence-based clinical decisions presented in the writings of Haynes, Devereaux and Guyatt assume that EBM consists of, among other things, evidence from clinical research together with information about patients’ values and clinical expertise. On this A-view, EBM describes all that goes on in a specific justifiable medical decision. There is, however, an alternative interpretation of EBM, the B-view, in which EBM describes just one component of the decision situation (a component usually based on evidence from clinical research) and in which, together with other types of evidence, EBM leads to a justifiable clincial decision but does not describe the decision itself. This B-view is inspired by a 100-years older version of EBM, a Swedish standard requiring medical decision-making, professional risk-taking and practice to be in accordance with‘science and proven experience’(VBE). In the paper, we outline how the Swedish concept leads to an improved understanding of the way in which scientific evidence and clinical experience can and cannot be integrated in light of EBM. How scientific evidence and clinical experience is integrated influences both the way we do risk assessment and risk management. In addition, the paper sketches the as yet unexplored historical background to VBE and EBM.
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| 31. |
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| 32. |
- Påhlsson, Hans-Ivar, et al.
(författare)
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The optimal cuff width for measuring toe blood pressure
- 2007
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Ingår i: Angiology. - : Sage Publications. - 0003-3197 .- 1940-1574. ; 58:4, s. 472-476
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Tidskriftsartikel (refereegranskat)abstract
- To determine the optimal cuff width for measuring toe blood pressure in patients with lower limb ischemia, this experimental prospective study examined 20 patients with symptoms of peripheral arterial disease referred for vascular examination or vascular surgery. Toe blood pressure was measured hydrostatically by the pole test using cuffs of different widths. Pole test reflects the true physiological blood pressure value and was the reference method. Blood pressures obtained using the cuffs were related to this value and to patients' toe circumference. With the 2.5-cm cuff, the patients had a mean pole test toe blood pressure of 28 mm Hg (range, 6-55 mm Hg). Compared with pole test results, the toe blood pressure was 15.6 mm Hg (95% confidence interval [CI], 8-23 mm Hg) higher when measured using the 2.0-cm cuff (P < .001) and 4.5 mm Hg (95% CI, 0-9 mm Hg) higher when measured using the 2.5-cm cuff (P = .07). Using the 1.5-cm and 3.0-cm cuffs, the differences were 27.0 mm Hg (95% CI, 13-43 mm Hg) and -2.0 mm Hg (95% CI, -11 to 8 mm Hg), respectively. The cuff width greatly affects the obtained toe blood pressure value, and larger cuffs correspond better to the hydrostatic pressure. For clinical use and as a reporting standard, we propose that toe blood pressure measurements should be made using a 2.5-cm-wide cuff.
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| 33. |
- Rouhi, Pegah, et al.
(författare)
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Hypoxia-induced metastasis model in embryonic zebrafish
- 2010
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Ingår i: Nature Protocols. - : Nature Publishing Group. - 1754-2189 .- 1750-2799. ; 5:12, s. 1911-1918
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia facilitates tumor invasion and metastasis by promoting neovascularization and co-option of tumor cells in the peritumoral vasculature, leading to dissemination of tumor cells into the circulation. However, until recently, animal models and imaging technology did not enable monitoring of the early events of tumor cell invasion and dissemination in living animals. We recently developed a zebrafish metastasis model to dissect the detailed events of hypoxia-induced tumor cell invasion and metastasis in association with angiogenesis at the single-cell level. In this model, fluorescent DiI-labeled human or mouse tumor cells are implanted into the perivitelline cavity of 48-h-old zebrafish embryos, which are subsequently placed in hypoxic water for 3 d. Tumor cell invasion, metastasis and pathological angiogenesis are detected under fluorescent microscopy in the living fish. The average experimental time for this model is 7 d. Our protocol offers a remarkable opportunity to study molecular mechanisms of hypoxia-induced cancer metastasis.
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| 34. |
- Sahli, David, 1976-
(författare)
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Early arterial disease of the lower extremities in diabetes : diagnostic evaluation and risk markers
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the present thesis was to assess the occurrence of early lower extremity arterial disease (LEAD) in patients with diabetes and to assess novel potential risk markers for development or worsening of LEAD in the same patients. In parallel different measures of impaired peripheral circulation were evaluated.The measurement of ankle-to- brachial blood pressure index (ABI) to screen for asymptomatic LEAD in diabetic subjects is unreliable since a large proportion of patients have stiff ankle arteries (mediasclerosis) and thus may display a too high ABI. We studied type 1-, type 2 diabetic and non-diabetic subjects without a previous history of LEAD and a composite variable of ankle – plus toe blood pressures and indices was compared to ABI alone in detecting LEAD. Significantly more subjects with reduced peripheral circulation were detected using the composite variable compared to ABI alone. This was particularly true in diabetic subjects, about 30% of whom had signs of impaired peripheral circulation. Thus, it was found that toe blood pressure measurements, alone or in combination with ankle blood pressure measurements, increase the sensitivity for finding early asymptomatic LEAD in diabetic subjects. No significant difference in reproducibility between measurements of absolute ankle- and toe blood pressure and indices was found, but a correlation between systemic (brachial) and toe blood pressure variations over time may suggest that indices are more correct in assessing peripheral arterial circulation.Furthermore, toe blood pressure measurements can be performed using either the great toe or dig II and a strong concordance is found between these measurements. In addition, since the pole-test, another non-invasive method to measure peripheral blood pressure which is less sensitive to the presence of mediasclerosis compared to ABI, correlated significantly with toe blood pressure measurements this method may be used as an alternative screening method in subjects with previously known LEAD.Age, hypertension and glycemic control are well known risk factors and, in addition, high tissue plasminogen activator (tPA) activity turned out to be a novel early marker for asymptomatic LEAD in diabetic subjects, particularly in patients with type 2 diabetes. Age and hyperglycemia are the most important risk factors for development and progression of subclinical lower extremity arterial disease in type 2 diabetic subjects. No independent associations between markers of inflammation, such as CRP, interleukin-6 and TNF-α and early asymptomatic LEAD were seen among non-diabetic or diabetic subjects.In conclusion, impaired arterial circulation in the lower extremities is common in diabetic subjects even in the absence of symptoms. Including toe blood pressure measurement when screening for asymptomatic LEAD in diabetic subjects improves the ability to detect reduced peripheral circulation and this method avoids falsely elevated blood pressures readings due to mediasclerosis in the ankle arteries. Moreover, an altered fibrinolytic activity should be further evaluated as an early marker of atherosclerosis and LEAD.
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| 35. |
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| 36. |
- Sahlin, Nils-Eric, et al.
(författare)
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Så uppfattar tandläkare beprövad erfarenhet : några resultat från en enkätstudie
- 2020
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Ingår i: Tandläkartidningen. - 0039-6982. ; 2020:7, s. 50-54
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Tidskriftsartikel (refereegranskat)abstract
- Inom tandvården gäller patientsäkerhetslagen, som säger att tandläkare ska ”utföra sitt arbete i överensstämmelse med vetenskap och beprövad erfarenhet”. Forskningsprogrammet Vetenskap och Beprövad Erfarenhet, VBE, har undersökt hur man inom tandvården samt hälso- och sjukvården ser på beprövad erfarenhet. Resultatet visar bland annat att tandläkare och tandhygienister graderar personlig erfarenhet, beprövad erfarenhet och vetenskaplig evidens högre än de som jobbar ihälso- och sjukvården.
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| 37. |
- Sahlin, Nils-Eric, et al.
(författare)
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The Ontology of Decision-Making
- 2019
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Ingår i: Maurinian Truths : Essays in Honour of Anna-Sofia Maurin on her 50th Birthday - Essays in Honour of Anna-Sofia Maurin on her 50th Birthday. - 9789188899538 - 9789188899545 ; , s. 107-114
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 38. |
- Sahlin, Nils-Eric, et al.
(författare)
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Varför uppfattar tandläkare beprövad erfarenhet som de gör? : uppföljning av resultatet från enkätstudien
- 2020
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Ingår i: Tandläkartidningen. - 0039-6982. ; 112:9, s. 58-61
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Tidskriftsartikel (refereegranskat)abstract
- Tandläkare och tandhygienister graderar beprövad och personlig erfarenhet som bas för sunt beslutsfattande högre än de som jobbar inom hälso- och sjukvården. Varför det är så är inte enkelt att besvara, men det är rimligt att anta att tandläkarnas syn på beprövad och personlig erfarenhet påverkas av rådande kunskapsläge, den organisation inom vilken de verkar samt gällande lagar och förordningar.
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| 39. |
- Sartipy, Fredrik, et al.
(författare)
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Cardiovascular long-term outcome and prophylactic treatment patterns in peripheral arterial disease in a population-based cohort
- 2019
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : OXFORD UNIV PRESS. - 2058-5225 .- 2058-1742. ; 5:4, s. 310-320
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study evaluates 10-year follow-up data on associated comorbidity, mortality, and pharmacological treatment patterns for men and women with different stages of peripheral arterial disease (PAD) in a population-based setting.Methods and results: This was a prospective observational population-based cohort study, based on physical examinations and questionnaires at baseline supplemented with national register data between 2005 and 2015. Subjects were placed in subgroups defined by ankle-brachial index levels and reported symptoms; asymptomatic PAD (APAD), intermittent claudication (IC), severe limb ischaemia (SLI), or references (Ref). Cox proportional hazards regression models were used for analysis with adjustments for sex and baseline age and comorbidity. The cohort consisted of 5080 subjects (45% males). At baseline, APAD, IC, and SLI were prevalent in 559 (11%), 320 (6.3%), and 78 (1.5%) subjects, respectively. A significant increased risk for cardiovascular (CV) death, even when adjusted for age and baseline morbidity, were noted in all PAD stages as compared with reference group with a small difference between APAD and IC, an adjusted hazard ratio 1.80 (confidence interval 1.45-2.22) and 1.95 (1.50-2.53), respectively. Only about 60% of PAD subjects received medical prophylactic treatment as recommended in guidelines.Conclusion: Peripheral arterial disease subjects had significantly increased CV morbidity and mortality risks, especially males. Asymptomatic PAD subjects confer similar risk for CV events as symptomatic patients. Our findings motivate enhanced preventive efforts of all PAD stages, including in asymptomatic disease.
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| 40. |
- Sartipy, Fredrik, et al.
(författare)
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Presence of asymptomatic Peripheral Arterial Disease in combination with common risk factors elevates the cardiovascular risk Substantially
- 2022
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Ingår i: INTERNATIONAL JOURNAL OF CARDIOLOGY CARDIOVASCULAR RISK AND PREVENTION. - Philadelphia, PA, United States : Elsevier. - 2772-4875. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: This study evaluates the risks for adverse cardiovascular (CV) events in Asymptomatic Peripheral Arterial Disease (APAD) combined with different traditional CV risk factors. Methods: A population-based observational study of 8000 subjects, identified 559 subjects as having APAD through ankle-brachial index (ABI) measurements and questionnaires regarding limb symptoms. This cohort and subgroups classified by presence of different traditional CV risk factors at baseline were assessed for 10 years on CV outcome. The recorded endpoints were all-cause mortality, CV mortality and non-fatal CV events. Results: Before subdividing the APAD subjects, the CV mortality incidence was 28.5 deaths per 1000 person-years as compared to 8.7 deaths for references without APAD. For subjects with hypertension at baseline the CV mortality incidence was 35.4 when combined with APAD and 11.7 without. In women with hypertension but without other risk factors, presence of APAD increased the age-adjusted Hazard Ratio (HR) for fatal and non-fatal CV events by 1.86 [CI 1.54,2.24, p < 0.001]. Conclusions: ABI measurements should be considered an important indication for aggressive multifactorial risk factor reduction in populations with any other prevalent CV risk factor. In hypertension, diabetes mellitus and a smoking history, coexisting APAD contributes significantly to the increased age-adjusted CV risk.
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| 41. |
- Sartipy, Fredrik, et al.
(författare)
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Ten Year Mortality in Different Peripheral Arterial Disease Stages : A Population Based Observational Study on Outcome
- 2018
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 55:4, s. 529-536
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to determine long-term mortality rates and the underlying cause of death for subjects with different peripheral arterial disease (PAD) stages in a population based setting. Methods: A randomly selected population sample of 5080 subjects was enrolled in the study in 2004-2005. Participants completed health state questionnaires and underwent ankle brachial index (ABI) measurements for classification into PAD severity stages and reference subjects. A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death, which was then compared with PAD stage determined at baseline in 2005. Results: The 10 year all cause mortality was 27% for reference cases, 56% for asymptomatic PAD (APAD), 63% for intermittent claudication (IC), and 75% for severe limb ischaemia (SLI). Among all PAD subjects, cardiovascular (CV) causes were the most common main cause of death (45%) and a CV event was present as either the main or one of the three most common contributing causes of death in 64% of the cases. The age adjusted hazard ratios for a main cause of death by a CV event were 1.9 (95% CI 1.5-2.3) for APAD, 2.6 (95% CI 2.1-3.4) for IC, and 3.5 (95% CI 2.3-5.2) for SLI. Conclusion: PAD subjects, including the APAD subjects, are still at high risk of CV death. The mortality risks are more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage. Awareness and improved risk reduction management of PAD are still warranted.
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| 42. |
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| 43. |
- Sigvant, B, et al.
(författare)
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Asymptomatic peripheral arterial disease: is pharmacological prevention of cardiovascular risk cost-effective?
- 2011
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Ingår i: EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION and REHABILITATION. - : Lippincott Williams and Wilkins. - 1741-8267. ; 18:2, s. 254-261
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral arterial disease (PAD) is associated with an increased risk of early death in cardiovascular (CV) disease. The majority of PAD subjects are asymptomatic with a prevalence of 11 per cent among the elderly. Long-term drug prevention aiming to minimize disease progression and CV events in these subjects is probably beneficial, but expensive. The purpose of this analysis was to evaluate the cost-effectiveness of pharmacological risk reduction in subclinical PAD. Long-term costs and quality-adjusted life years (QALYs) were estimated by employing a decision-analytic model for ACE-inhibitor, statin, aspirin and non-aspirin anti-platelet therapy. Rates of CV events without treatment were derived from epidemiological studies and event rate reduction were retrieved from clinical trials. Costs and health-related quality of life estimates were obtained from published sources. All four drugs reduced CV events. Using ACE-inhibition resulted in a heart rate (HR) of 0.67 (95% CI: 0.55-0.79), statins 0.74 (0.70-0.79), and clopidogrel 0.72 (0.43-1.00). Aspirin had a HR of 0.87 and the 95% CI passed included one (0.72-1.03). ACE-inhibition was associated with the largest reduction in events leading to the highest gain in QALYs (7.95). Furthermore, ACE-inhibitors were associated with the lowest mean cost (sic)40.556. In conclusion, while all drugs reduced CV events, ACE-inhibition was the most cost-effective. These results suggest that we should consider efforts to identify patients with asymptomatic PAD and, when identified, offer ACE-inhibition.
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| 44. |
- Sigvant, Birgitta, et al.
(författare)
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Differences in presentation of symptoms between women and men with intermittent claudication
- 2011
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Ingår i: BMC Cardiovascular Disorders. - : BioMed Central. - 1471-2261 .- 1471-2261. ; 11:39
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Tidskriftsartikel (refereegranskat)abstract
- Background: More women than men have PAD with exception for the stage intermittent claudication (IC). The purpose of this study was to evaluate differences in disease characteristics between men and women when using current diagnostic criteria for making the diagnosis IC, defined as ABI less than 0.9 and walking problems. Study Design: Cohort study Methods: 5040 elderly (median age 71) subjects participated in a point-prevalence study 2004. They had their ABI measured and filled out questionnaires covering medical history, current medication, PAD symptoms and walking ability. The prevalence of IC was 6.5% for women and 7.2% for men (P = 0.09). A subset of subjects with IC (N = 56) was followed up four years later with the same procedures. They also performed additional tests aiming to determine all factors influencing walking ability. Results: Men with IC had more concomitant cardiovascular disease and a more profound smoking history than women. Women, on the other hand, reported a lower walking speed (P less than 0.01) and more joint problems (P = 0.018). In the follow up cohort ABI, walking ability and amount of atherosclerosis were similar among the sexes, but women more often reported atypical IC symptoms. Conclusion: Sex differences in the description of IC symptoms may influence diagnosis even if objective features of PAD are similar. This may influence accuracy of prevalence estimates and selection to treatment.
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| 45. |
- Sigvant, Birgitta, et al.
(författare)
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Risk factor profile and use of cardiovascular drugprevention in women and men with peripheral artery disease
- 2009
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8267 .- 1741-8275. ; 16:1, s. 39-46
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine cardiovascular comorbidities and use of cardiovascular disease preventive drugs in patients with peripheral arterial disease (PAD), with special attention to sex differences. Design A cross-sectional point-prevalence study. Patients A population sample of patients that are 60-90 years old. Setting Primary care areas in four Swedish regions. Main outcome measures Prevalence of PAD stages, comorbidities and medication use. Results The prevalence of any type of PAD was 18.0% (range 16-20), of asymptomatic peripheral arterial disease (APAD) was 11.1% (range 9-13), intermittent claudication was 6.8% (range 6.5-7.1), and of critical limb ischemia (CLI) was 1.2% (range 1.0-1.5). APAD and CLI were more common in women. Statins were used by 17.5% (range 16.9-18.2), 29.4% (range 29.0-30.1), and 30.3% (range 29.9-30.8) of the patients with APAD, intermittent claudication, and CLI, respectively, and antiplatelet therapy was reported by 34.1% (range 33.7-34.3), 47.6% (range 47.3-47.9), and 60.2% (range 59.1-60.7). The odds ratio for having APAD was 1.7 (range 1.2-2.4) for women with a smoking history of 10 years in relation to nonsmokers. This association was observed only in men who had smoked for at least 30 years or more. Preventive drug use was more common in men with PAD. Compared with women they had an odds ratio of 1.3 (range 1.1-1.5) for lipid-lowering therapy, 1.3 (range 1.0-1.7) for β-blockers or angiotensin-converting enzyme inhibitors, and 1.5 (range 1.2-1.9) for antiplatelet therapy. Conclusion The patients' risk factor profiles differed among the PAD stages. Smoking duration already seemed to be a risk factor for women with PAD after 10 years of smoking, as compared with 30 years for men, and fewer women reported use of preventive medication. These observations may partly explain the sex differences in prevalence that were observed.
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| 46. |
- Sigvant, B., et al.
(författare)
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The Risk of Disease Progression in Peripheral Arterial Disease is Higher than Expected: A Meta-Analysis of Mortality and Disease Progression in Peripheral Arterial Disease
- 2016
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 51:3, s. 395-403
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Forskningsöversikt (refereegranskat)abstract
- Objective: Peripheral arterial, disease (PAD) afflicts up to 20% of older people and is associated with a high risk of cardiovascular (CV) morbidity, but a rather low risk of progression of leg symptoms. These risk estimations are largely taken from cohort studies performed 20 years ago. To test the validity of this, available data were systematically reviewed and attempts were made to perform meta-analyses of CV risk and disease progression. Methods: A database literature search was conducted of the period 1990-2015 using related subject headings. Inclusion criteria were cohort studies for PAD, sample size >100 subjects, follow up time >= 1 year, and studies presenting endpoints covering mortality and/or CV events. Analyses were performed for a reference population, as well as groups with asymptomatic PAD (APAD), symptomatic PAD, and subjects with ankle brachial index <0.9. Results: Of 354 identified articles, 35 were eligible for systematic review. Sample size varied between 109 and 16,440 subjects. Mean age in the cohorts ranged from 56 to 81 years (SD 10.8) and mean follow up was 6.3 years (range 1-13). Most included patients with symptomatic PAD had IC (91%). Symptomatic PAD subjects had higher 5 year cumulative CV mortality than the reference population, 13% versus 5%. During follow up, approximately 7% of APAD patients progressed to IC, and 21% of IC patients were diagnosed as having critical limb ischemia, with 4-27% undergoing amputations. Conclusion: The risk to the limb is underestimated in PAD patients, whereas the CV related morbidity is more moderate than stated in the guidelines. The latter observation is especially valid for IC patients. These findings should be considered when evaluating patients for treatment. (C) 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
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| 47. |
- Trabaldo, Edoardo, 1990, et al.
(författare)
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Mapping the Phase Diagram of a YBa2Cu3 O7-δ Nanowire Through Electromigration
- 2022
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Ingår i: Physical Review Applied. - 2331-7019. ; 17:2
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Tidskriftsartikel (refereegranskat)abstract
- We use electromigration (EM) to tune the oxygen content of YBa2Cu3O7-δ (YBCO) nanowires. During EM, the dopant oxygen atoms in the nanowire are moved under the combined effect of electrostatic force and Joule heating. The EM current can be tuned to either deplete or replenish nanowires with oxygen, allowing fine tuning of its hole-doping level. Electrical transport measurements and Kelvin probe microscopy corroborate good homogeneity of the doping level along the electromigrated nanowires. Thus, EM provides an effective method to study transport properties of YBCO in a wide doping range at the nanoscale in one and the same device.
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| 48. |
- Tritsaris, Katerina, et al.
(författare)
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IL-20 is an arteriogenic cytokine that remodels collateral networks and improves functions of ischemic hind limbs
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:39, s. 15364-15369
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Tidskriftsartikel (refereegranskat)abstract
- Successful therapeutic angiogenesis for the treatment of ischemic disorders relies on selection of optimal proangiogenic or arteriogenic agents that are able to promote establishment of functional collateral networks. Here, we show that IL-20, a pleiotropic inflammatory cytokine, displays an imperative effect on vascular remodeling. Stimulation of both large and microvascular endothelial cells with IL-20 leads to activation of receptor-dependent multiple intracellular signaling components, including increased phosphorylation levels of JAK2/STAT5, Erk1/2, and Akt; activation of small GTP-binding proteins Rac and Rho; and intracellular release of calcium. Surprisingly, IL-20 significantly promotes endothelial cell tube formation without affecting their proliferation and motility. These findings suggest that the vascular function of IL-20 involves endothelial cell organization, vessel maturation, and remodeling. Consistent with this notion, delivery of IL-20 to the ischemic muscle tissue significantly improves arteriogenesis and blood perfusion in a rat hind-limb model. Our findings provide mechanistic insights on vascular functions of IL-20 and define therapeutic implication of this cytokine for the treatment of ischemic disorders.
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| 49. |
- Trotter, Dinko E. Gonzalez, et al.
(författare)
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In Vivo Imaging of the Programmed Death Ligand 1 by F-18 PET
- 2017
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 58:11, s. 1852-1857
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Tidskriftsartikel (refereegranskat)abstract
- Programmed death ligand 1 (PD-L1) is an immune regulatory ligand that binds to the T-cell immune check point programmed death 1. Tumor expression of PD-L1 is correlated with immune suppression and poor prognosis. It is also correlated with therapeutic efficacy of programmed death 1 and PD-L1 inhibitors. In vivo imaging may enable real-time follow-up of changing PD-L1 expression and heterogeneity evaluation of PD-L1 expression across tumors in the same subject. We have radiolabeled the PD-L1-binding Affibody molecule NOTA-Z(PD-L1_1) with F-18 and evaluated its in vitro and in vivo binding affinity, targeting, and specificity. Methods: The affinity of the PD-L1-binding Affibody ligand Z(PD-L1_1) was evaluated by surface plasmon resonance. Labeling was accomplished by maleimide coupling of NOTA to a unique cysteine residue and chelation of F-18-AlF. In vivo studies were performed in PD-L1-positive, PD-L1-negative, and mixed tumor-bearing severe combined immunodeficiency mice. Tracer was injected via the tail vein, and dynamic PET scans were acquired for 90 min, followed by gamma-counting biodistribution. Immunohistochemical staining with an antibody specific for anti-PD-L1 (22C3) was used to evaluate the tumor distribution of PD-L1. Immunohistochemistry results were then compared with ex vivo autoradiographic images obtained from adjacent tissue sections. Results: NOTA-Z(PD-L1_1) was labeled, with a radiochemical yield of 15.1% +/- 5.6%, radiochemical purity of 96.7% +/- 2.0%, and specific activity of 14.6 +/- 6.5 GBq/mu mol. Surface plasmon resonance showed a NOTA-conjugated ligand binding affinity of 1 nM. PET imaging demonstrated rapid uptake of tracer in the PD-L1-positive tumor, whereas the PD-L1-negative control tumor showed little tracer retention. Tracer clearance from most organs and blood was quick, with biodistribution showing prominent kidney retention, low liver uptake, and a significant difference between PD-L1-positive (percentage injected dose per gram [%ID/g] = 2.56 +/- 0.33) and -negative (% ID/g = 0.32 +/- 0.05) tumors (P = 0.0006). Ex vivo autoradiography showed excellent spatial correlation with immunohistochemistry in mixed tumors. Conclusion: Our results show that Affibody ligands can be effective at targeting tumor PD-L1 in vivo, with good specificity and rapid clearance. Future studies will explore methods to reduce kidney activity retention and further increase tumor uptake.
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| 50. |
- Wahlberg, Eric, et al.
(författare)
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Development of Graphene Quantum Hall Effect AC Metrology at RISE
- 2024
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Konferensbidrag (refereegranskat)abstract
- We present the first steps taken towards a graphene quantum Hall effect ac resistance standard at RISE. A new measurement setup has been developed including a graphene quantum Hall effect device suitable for the kilohertz range and a coaxial cryoprobe to be used together with a coaxial impedance bridge based on inductive voltage dividers. 1:1 ratio resistance measurements of the graphene device against a 12.9 kΩ ac resistance standard resulted in a linear frequency dependent (≈ 0.2(μΩ/Ω)/kHz) deviation from the quantized dc value.
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