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| 2. |
- Amirkhani, Ardeshir, et al.
(författare)
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Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients
- 2005
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 12:8, s. 625-631
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Tidskriftsartikel (refereegranskat)abstract
- Tryptophan and its metabolites are of great interest in understanding the pathogenesis of multiple sclerosis (MS). The total levels of tryptophan and its metabolites, kynurenine and kynurenic acid were determined in plasma by capillary liquid chromatography electrospray ionisation tandem mass spectrometry. This is the first report of the plasma levels of these analytes in healthy controls and relapsing-remitting MS patients receiving long-term and acute interferon-beta (IFN-beta) treatment. Twenty-four hours post-administration increased kynurenine levels (first IFN MS versus healthy, P = 0.042) and kynurenine/tryptophan ratio (K/T; first IFN MS versus healthy, P =0.027; first IFN MS versus long-term IFN MS, P = 0.036) were found. The long-term IFN MS group had higher K/T ratios at 4 and 12 h post-administration (P = 0.015 and 0.009, respectively). The increase of K/T ratio in the first IFN MS group indicate an induction of the enzyme indolamine-2,3-dioxygenase (IDO), as reported earlier in experimental allergic encephalomyelitis. As IDO is participating in both inflammatory and neurodegenerative processes, further knowledge of its involvement in the pathogenesis of MS is of great importance.
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| 3. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 4. |
- Ahlström, Hanna, et al.
(författare)
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An Earth system law perspective on governing social-hydrological systems in the Anthropocene
- 2021
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Ingår i: Earth System Governance. - : Elsevier BV. - 2589-8116. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The global hydrological cycle is characterized by complex interdependencies and self-regulating feedbacks that keep water in an ever-evolving state of flux at local, regional, and global levels. Increasingly, the scale of human impacts in the Anthropocene is altering the dynamics of this cycle, which presents additional challenges for water governance. Earth system law provides an important approach for addressing gaps in governance that arise from the mismatch between the global hydrological cycle and dispersed regulatory architecture across institutions and geographic regions. In this article, we articulate the potential for Earth system law to account for core hydrological problems that complicate water governance, including delay, redistribution, intertwinements, permanence, and scale. Through merging concepts from Earth system law with existing policy and legal principles, we frame an approach for addressing hydrological problems in the Anthropocene and strengthening institutional fit between established governance systems and the global hydrological cycle. We discuss how such an approach can be applied, and the challenges and implications for governing water as a cycle and complex social-hydrological system, both in research and practice.
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| 5. |
- Falk, Johan, et al.
(författare)
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Exponential Roadmap: Scaling 36 Solutions to Halve Emissions by 2030
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The 2019 Exponential Roadmap focuses on moving from incremental to exponential climate action in the next decade. It presents 36 economically- viable solutions to cut global greenhouse gas emissions 50% by 2030 and the strategies to scale this transformation. The roadmap is consistent with the Paris Agreement’s goal to keep global average temperature “well below 2°C” and aiming for 1.5°C above pre- industrial levels. The 2019 roadmap is the second in the series. Each new roadmap updates solutions that have proven potential to scale and charts progress towards exponential scaling. The roadmap, based on the carbon law (see box) is a collaboration between academia, business and civil society. The roadmap is complemented with a high-ambition narrative, Meeting the 1.5°C Ambition, that presents the case why holding global average temperature increase to just 1.5°C above pre-industrial levels is important. Since the first roadmap, the Intergovernmental Panel on Climate Change (IPCC) published its special report on 1.5°C. The report concluded that the economic and humanitarian risks of a 2°C world are significantly higher than 1.5°C. The remaining emissions budget for 1.5°C is small, and will be exceeded within ten to fifteen years at current emission rates. The window of feasibility is closing rapidly. The global economic benefit of a low-carbon future is estimated at US$26 trillion by 2030 compared with staying on the current high-carbon pathway. The scale of transformation – halving emissions by 2030 – is unprecedented but the speed is not. Some cities and companies can transform significantly faster. Developed nations with significant historic emissions have a responsibility to reduce emissions faster. Greenhouse gas emissions, and the solutions to reduce them, are grouped by six sectors: energy, industry, transport, buildings, food consumption, nature-based solutions (sources and sinks). Meeting the 1.5°C goal means implementing solutions in parallel across all sectors. The solutions must scale exponentially. The roadmap identifies four levers required to scale the transformation as well as necessary actions for each: policy, climate leadership and movements, finance and exponential technology. Implementation must be fair and just or risk deep resistance.
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| 6. |
- Füvesi, Judit, et al.
(författare)
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Proteomics of Cerebrospinal Fluid for Biomarker Discovery in Multiple Sclerosis
- 2013
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Ingår i: Clinical Laboratory International (CLI). - Brussels, Belgium : PanGlobal Media. - 1373-1580. ; 37, s. 29-31
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of reliable biomarkers, which are eligible for the prediction of both disease progression and response to treatment, means a great challenge in the management of multiple sclerosis (MS), a devastating disease of the central nervous system. The results of recent proteomic findings from the cerebrospinal fluid of MS patients hold promise of finding ideal biomarkers in the near future.
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| 7. |
- Persson, Jonas, 1983-, et al.
(författare)
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Phosphodiesterase 10A levels are related to striatal function in schizophrenia : a combined positron emission tomography and functional magnetic resonance imaging study
- 2020
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Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 270:4, s. 451-459
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.
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| 8. |
- Reinisch, Walter, et al.
(författare)
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Clinical Practice of Adalimumab and Infliximab Biosimilar Treatment in Adult Patients With Crohn's Disease
- 2021
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott-Raven Publishers. - 1078-0998 .- 1536-4844. ; 27:1, s. 106-122
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of tumor necrosis factor (TNF) inhibitors has significantly changed the treatment landscape in Crohn's disease (CD). The overall therapeutic achievements with TNF inhibitors such as infliximab, adalimumab, and certolizumab pegol paved the way to push the boundaries of treatment goals beyond symptomatic relief and toward cessation of objective signs of inflammation, including endoscopic remission. Even though these agents are widely used for the treatment of moderate to severe CD, heterogeneity still exists in translating evidence-based guidelines on the use of anti-TNF agents into actual treatment algorithms in CD. This might be due to several reasons including disparities in health expenditure policies; lack of harmonization between countries; and variations in assessment of disease severity, use of disease monitoring tools, or application of treatment targets by physicians. With the advent of biosimilars, patent-free versions of reference biologics are now available to minimize health inequalities in drug availability. In this context, this article aims to provide practical clinical guidance for the use of infliximab and adalimumab biosimilars in patients with moderate to severe CD by outlining different clinical scenarios that patients may encounter during their treatment journey.
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| 9. |
- Rencz, Fanni, et al.
(författare)
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Cost-utility of biological treatment sequences for luminal Crohn's disease in Europe
- 2017
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Ingår i: Expert review of pharmacoeconomics & outcomes research. - : Taylor & Francis. - 1473-7167 .- 1744-8379. ; 17:6, s. 597-606
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study aims to compare the cost-effectiveness of treatment sequences with available biologics, including adalimumab (ADA), biosimilar infliximab (bsIFX), originator infliximab (IFX) and vedolizumab (VEDO) for luminal Crohn's disease in nine European countries.METHODS: A Markov-model was constructed to simulate five-year medical costs and quality-adjusted life years (QALYs). Data on clinical efficacy were obtained from randomised controlled trials. Country-specific unit costs, discount rates and a third-party payer perspective were applied.RESULTS: The bsIFX versus conventional therapy resulted in the most favourable incremental cost-utility ratios (ICURs) ranging from €34,580 (Hungary) to €77,062/QALY (Sweden). Compared to bsIFX, the bsIFX-ADA sequence was more cost-effective than the bsIFX-VEDO sequence with ICURs varying between €70,277 (France) and €162,069/QALY (Germany). The ICURs of the bsIFX-ADA-VEDO sequence versus the bsIFX-ADA strategy were between €206,266 (The Netherlands) and €363,232/QALY (Spain).CONCLUSION: We are the first to compare cost-effectiveness of multiple biological sequences for luminal Crohn's disease. Based on our findings, bsIFX can be recommended as a first-line treatment in patients unresponsive to conventional treatments. While biological sequences only slightly differ in their associated health gains, their costs vary greatly. The bsIFX-ADA-VEDO seems to be the most cost-effective sequence of the available biologics across Europe.
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