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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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- Geneid, A., et al.
(författare)
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Union of the European Phoniatricians position statement on the exit strategy of phoniatric and laryngological services: staying safe and getting back to normal after the peak of coronavirus disease 2019 (issued on 25th May 2020)
- 2020
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Ingår i: Journal of Laryngology and Otology. - : CAMBRIDGE UNIV PRESS. - 0022-2151 .- 1748-5460. ; 134:8, s. 661-664
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Tidskriftsartikel (refereegranskat)abstract
- Background The following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services. Objectives This material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures. Conclusion As evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.
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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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- Hedges, S., et al.
(författare)
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Uroepithelial cells are part of a mucosal cytokine network
- 1994
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Ingår i: Infection and Immunity. - 0019-9567. ; 62:6, s. 2315-2321
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Tidskriftsartikel (refereegranskat)abstract
- This study compared the cytokine production of uroepithelial cell lines in response to gram-negative bacteria and inflammatory cytokines. Human kidney (A498) and bladder (J82) epithelial cell lines were stimulated with either Escherichia coli Hu734, interleukin 1α (IL-1α), or tumor necrosis factor alpha (TNF-α). Supernatant samples were removed, and the RNA was extracted from cells at 0, 2, 6, and 24 h. The secreted cytokine levels were determined by bioassay or immunoassay; mRNA was examined by reverse transcription-PCR. The two cell lines secreted IL-6 and IL-8 constitutively. IL-6 and IL-8 mRNA were constitutively produced in both cell lines; IL-1β mRNA was detected in J82 cells. IL-1α induced significantly higher levels of IL-6 secretion than did E. coli Hu734 or TNF-α. IL-1α and TNF-α induced significantly higher levels of IL-8 secretion than did E. coli Hu734. Secreted IL-1β was not detected; IL-1α and TNF-α were not detected above the levels used for stimulation. IL-1α, IL-1β, IL-6, and IL-8 mRNAs were detected in both cell lines after exposure to the stimulants. TNF-α mRNA was occasionally detected in the J82 cell line after TNF-α stimulation. Cytokine (IL-6 and IL-8) and control (glyceraldehyde 3-phosphate dehydrogenase [G3PDH] and β-actin) mRNA concentrations were quantitated with internal PCR standards. Cytokine mRNA levels relative to β-actin mRNA levels were the highest in E. coli- stimulated cells. In comparison, the cytokine mRNA levels relative to G3PDH mRNA levels were the highest in IL-1α-stimulated cells. β-Actin mRNA levels decreased after bacterial stimulation but not after cytokine stimulation, while G3PDH mRNA levels increased in response to all of the stimulants tested. These results suggested that E. coli Hu734 lowered the β-actin mRNA levels in uroepithelial cells, thus distorting the IL-6 and IL-8 mRNA levels relative to this control. In summary, E. coli IL-1α and TNF-α were found to activate the de novo synthesis and secretion of IL-6 and IL-8 in uroepithelial cells. These results emphasize the role of epithelial cells in cytokine-mediated responses during the early stages of infection.
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- Kostewicz, Edmund S., et al.
(författare)
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PBPK models for the prediction of in vivo performance of oral dosage forms
- 2014
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57:SI, s. 300-321
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Forskningsöversikt (refereegranskat)abstract
- Drug absorption from the gastrointestinal (GI) tract is a highly complex process dependent upon numerous factors including the physicochemical properties of the drug, characteristics of the formulation and interplay with the underlying physiological properties of the GI tract. The ability to accurately predict oral drug absorption during drug product development is becoming more relevant given the current challenges facing the pharmaceutical industry. Physiologically-based pharmacokinetic (PBPK) modeling provides an approach that enables the plasma concentration time profiles to be predicted from preclinical in vitro and in vivo data and can thus provide a valuable resource to support decisions at various stages of the drug development process. Whilst there have been quite a few successes with PBPK models identifying key issues in the development of new drugs in vivo, there are still many aspects that need to be addressed in order to maximize the utility of the PBPK models to predict drug absorption, including improving our understanding of conditions in the lower small intestine and colon, taking the influence of disease on GI physiology into account and further exploring the reasons behind population variability. Importantly, there is also a need to create more appropriate in vitro models for testing dosage form performance and to streamline data input from these into the PBPK models. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the current status of PBPK models available. The current challenges in PBPK set-ups for oral drug absorption including the composition of GI luminal contents, transit and hydrodynamics, permeability and intestinal wall metabolism are discussed in detail. Further, the challenges regarding the appropriate integration of results from in vitro models, such as consideration of appropriate integration! estimation of solubility and the complexity of the in vitro release and precipitation data, are also highlighted as important steps to advancing the application of PBPK models in drug development. It is expected that the "innovative" integration of in vitro data from more appropriate in vitro models and the enhancement of the GI physiology component of PBPK models, arising from the OrBiTo project, will lead to a significant enhancement in the ability of PBPK models to successfully predict oral drug absorption and advance their role in preclinical and clinical development, as well as for regulatory applications.
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- Silvergren, Sanna, et al.
(författare)
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Hygroscopic growth and cloud forming potential of Arctic aerosol based on observed chemical and physical characteristics (a 1 year study 2007-2008)
- 2014
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Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 119:24, s. 14080-14097
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Tidskriftsartikel (refereegranskat)abstract
- Aerosol particle samples were collected, and the particle size distribution was measured during 1 year at the Zeppelin station (474 m asl) on Svalbard. The chemical constituents, hygroscopicity, and cloud forming properties of the aerosol were analyzed. The aerosol contained mostly sulfate and nitrate during the summer, whereas from September to February the main components were sodium and chloride. The highest concentration (20%) of water-soluble organic matter was sampled in December. The hygroscopic growth factors for the water-soluble fraction were 1.56-2.01 at 90% relative humidity, peaking in October, when the measured supersaturations needed for cloud drop formation were also the lowest. Sea-salt components showed a positive correlation with the cloud forming capability, whereas the organic content had no correlation. The hygroscopicity factors, or kappa values, were determined in three ways for each month: (1)kappa(H-TDMA) from measurements of the hygroscopic growth of particles produced from atomization of the filter extracts, (2)kappa(CCNC) from measurements of the critical supersaturation as a function of size for these particles, and (3)kappa(chem) was modeled based on the organic and inorganic composition of the filter samples. Using the measured particle size distributions and the critical activation diameters from the Cloud Condensation Nuclei Counter (CCNC) measurements, it was found that the number of CCN varied more with supersaturation during the summer months. The best agreement between all three kappa values was in December and January. Comparisons with earlier studies do not suggest any trend in the Arctic aerosol seasonal variability over the last decade.
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- Sjogren, H, et al.
(författare)
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Small firm financing in Sweden, 1960-95
- 1996
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Ingår i: BUSINESS HISTORY. - : FRANK CASS CO LTD. ; 38:3
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This article analyses the financial environment facing small firms in Sweden, 1960-95. The Swedish approach to small firms makes no clear distinction between the functions of non-market and market organisations or between private and public lenders. Thei
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- Sjogren, S, et al.
(författare)
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Response on p53
- 1996
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Ingår i: J Natl Cancer Inst. ; 88, s. 1500-
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Tidskriftsartikel (refereegranskat)
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