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- Olalde, I., et al.
(författare)
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The Beaker phenomenon and the genomic transformation of northwest Europe
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
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Tidskriftsartikel (refereegranskat)abstract
- From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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- Albert, F, et al.
(författare)
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Laser produced X-ray source in the 10-60 keV range at 1 kHz. Modified irradiation schemes in order to reach medical imaging quality
- 2001
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Ingår i: Journal de Physique IV. - : EDP Sciences. - 1155-4339. ; 11:PR2, s. 429-432
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Tidskriftsartikel (refereegranskat)abstract
- By tightly focusing ultra-short pulses from a Ti:sapphire terawatt laser onto a high-Z metallic target, hard x-ray pulses of short duration are produced. In most of our previous work concerning x-rays, a 150 mJ laser pulse with a 110 A duration has been used. Using mostly tin and tantalum targets, hard x-rays in the 10-60 keV range have been produced and used in differential absorption imaging around the K-alpha absorption edge of a contrast agent and also in imaging employing gated viewing for suppression of scattered radiation. In order to increase the x-ray yield (shortening the acquisition time) an increase in the laser repetition rate is desirable while still staying in the K-alpha energy regime. We have used a I kHz repetition-rate laser delivering 35 fs pulses in order to work towards these goals. We have clear evidence of hard x-ray generation above 30 keV, even for low laser pulse energies. We also studied the effect of a fs prepulse. The medical imaging capability of the source was explored. The use of a prepulse has been optimized in order to improve the image quality as well as the overall x-ray generation yield.
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- Brändén, Gisela, 1975, et al.
(författare)
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Structure-based ligand design to overcome CYP inhibition in drug discovery projects
- 2014
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446. ; 19:7, s. 905-911
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Forskningsöversikt (refereegranskat)abstract
- Cytochrome P450 (CYP) enzymes are key players in xenobiotic metabolism, and inhibition of CYPs can therefore result in unwanted drug-drug interactions. Within drug discovery, CYP inhibition can cause delays in the progression of candidate drugs, or even premature closure of projects. During the past decade, a massive effort in the pharmaceutical industry and academic research has produced a wealth of structural information in the CYP field. In this short review, we will describe how structure-based approaches can be used in the pharmaceutical industry to work away from CYP inhibition, with a focus on the opportunities and challenges. We will show two examples from our own work where structural information on CYP2C9 and CYP3A4 inhibitor complexes have been successfully exploited in ongoing drug discovery projects.
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- Hayden, JA, et al.
(författare)
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Exercise treatment effect modifiers in persistent low back pain: an individual participant data meta-analysis of 3514 participants from 27 randomised controlled trials
- 2020
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Ingår i: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 54:21, s. 1277-
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain is one of the leading causes of disability worldwide. Exercise therapy is widely recommended to treat persistent non-specific low back pain. While evidence suggests exercise is, on average, moderately effective, there remains uncertainty about which individuals might benefit the most from exercise.MethodsIn parallel with a Cochrane review update, we requested individual participant data (IPD) from high-quality randomised clinical trials of adults with our two primary outcomes of interest, pain and functional limitations, and calculated global recovery. We compiled a master data set including baseline participant characteristics, exercise and comparison characteristics, and outcomes at short-term, moderate-term and long-term follow-up. We conducted descriptive analyses and one-stage IPD meta-analysis using multilevel mixed-effects regression of the overall treatment effect and prespecified potential treatment effect modifiers.ResultsWe received IPD for 27 trials (3514 participants). For studies included in this analysis, compared with no treatment/usual care, exercise therapy on average reduced pain (mean effect/100 (95% CI) −10.7 (−14.1 to –7.4)), a result compatible with a clinically important 20% smallest worthwhile effect. Exercise therapy reduced functional limitations with a clinically important 23% improvement (mean effect/100 (95% CI) −10.2 (−13.2 to –7.3)) at short-term follow-up. Not having heavy physical demands at work and medication use for low back pain were potential treatment effect modifiers—these were associated with superior exercise outcomes relative to non-exercise comparisons. Lower body mass index was also associated with better outcomes in exercise compared with no treatment/usual care. This study was limited by inconsistent availability and measurement of participant characteristics.ConclusionsThis study provides potentially useful information to help treat patients and design future studies of exercise interventions that are better matched to specific subgroups.Protocol publicationhttps://doi.org/10.1186/2046-4053-1-64
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