| 1. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 2. |
- Arkell, Karolina, et al.
(författare)
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Mechanistic Modeling of Reversed-Phase Chromatography of Insulins with Potassium Chloride and Ethanol as Mobile-Phase Modulators
- 2017
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 2, s. 136-146
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the adsorption mechanism in reversed-phase chromatography (RPC) of proteins and to develop a model for the effect of dual mobile phase modulators—a salt and an organic solvent—on this process. Two different adsorption mechanisms were considered: (1) pure association of a protein molecule and one or more ligands and (2) displacement of the organic modulator, with which the adsorbent is saturated, by the protein upon association with one or more ligands. One model was then derived from each of the two considered mechanisms, combining thermodynamic theories on salting-in, RPC, and the solubility of proteins. The model was then applied to chromatographic data from an earlier report as well as supplementary data for solubility and vapor–liquid equilibria, and case-specific simplifications were made. We found that an adaptation of Kirkwood’s electrostatic theories to hydrophobic interaction chromatography describes the observed effect of KCl well. Combining chromatographic and solubility data for one of the insulins, we concluded that the variation in the activity coefficient of the insulin with respect to the concentration of ethanol alone cannot describe its effect on retention. Consequently, one or more other phenomena must affect the adsorption process. Our second model fits the retention data well, supporting the hypothesis that ethanol is directly involved in the adsorption mechanism in this case. Using additional experiments at a high-protein load, we extended the linear-range equilibrium model into a dynamic model for preparative conditions. This model shows good agreement with the high-load data for one of the insulin variants, without any additional effects of the modulator concentrations on the adsorption capacity.
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| 3. |
- de Waard, Anne-Karien M., et al.
(författare)
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Barriers and facilitators to participation in a health check for cardiometabolic diseases in primary care : A systematic review
- 2018
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Ingår i: European Journal of Preventive Cardiology. - : SAGE PUBLICATIONS LTD. - 2047-4873 .- 2047-4881. ; 25:12, s. 1326-1340
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Forskningsöversikt (refereegranskat)abstract
- Background: Health checks for cardiometabolic diseases could play a role in the identification of persons at high risk for disease. To improve the uptake of these health checks in primary care, we need to know what barriers and facilitators determine participation.Methods: We used an iterative search strategy consisting of three steps: (a) identification of key-articles; (b) systematic literature search in PubMed, Medline and Embase based on keywords; (c) screening of titles and abstracts and subsequently full-text screening. We summarised the results into four categories: characteristics, attitudes, practical reasons and healthcare provider-related factors.Results: Thirty-nine studies were included. Attitudes such as wanting to know of cardiometabolic disease risk, feeling responsible for, and concerns about one's own health were facilitators for participation. Younger age, smoking, low education and attitudes such as not wanting to be, or being, worried about the outcome, low perceived severity or susceptibility, and negative attitude towards health checks or prevention in general were barriers. Furthermore, practical issues such as information and the ease of access to appointments could influence participation.Conclusion: Barriers and facilitators to participation in health checks for cardiometabolic diseases were heterogeneous. Hence, it is not possible to develop a one size fits all' approach to maximise the uptake. For optimal implementation we suggest a multifactorial approach adapted to the national context with special attention to people who might be more difficult to reach. Increasing the uptake of health checks could contribute to identifying the people at risk to be able to start preventive interventions.
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| 4. |
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| 5. |
- Dudley, Bernard J., et al.
(författare)
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Measurements of uncertainty in macrophyte metrics used to assess European lake water quality
- 2013
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Ingår i: Hydrobiologia. - : Springer Science and Business Media LLC. - 0018-8158 .- 1573-5117. ; 704:1, s. 179-191
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Tidskriftsartikel (refereegranskat)abstract
- Uncertainty is an important factor in ecological assessment, and has important implications for the ecological classification and management of lakes. However, our knowledge of the effects of uncertainty in the assessment of different ecological indicators is limited. Here, we used data from a standardized campaign of aquatic plant surveys, in 28 lakes from 10 European countries, to assess variation in macrophyte metrics across a set of nested spatial scales: countries, lakes, sampling stations, replicate transects, and replicate samples at two depth-zones. Metrics investigated in each transect included taxa richness, maximum depth of colonisation and two indicators of trophic status: Ellenberg’s N and a metric based on phosphorus trophic status. Metrics were found to have a slightly stronger relationship to pressures when they were calculated on abundance data compared to presence/absence data. Eutrophication metrics based on helophytes were found not to be useful in assessing the effects of nutrient pressure. These metrics were also found to vary with the depth of sampling, with shallower taxa representing higher trophic status. This study demonstrates the complex spatial variability in macrophyte communities, the effect of this variability on the metrics, and theimplications to water managers, especially in relation to survey design.
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| 6. |
- Hilt, Sabine, et al.
(författare)
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Response of submerged macrophyte communities to external and internal restoration measures in north temperate shallow lakes
- 2018
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Submerged macrophytes play a key role in north temperate shallow lakes by stabilizing clear-water conditions. Eutrophication has resulted in macrophyte loss and shifts to turbid conditions in many lakes. Considerable efforts have been devoted to shallow lake restoration in many countries, but long-term success depends on a stable recovery of submerged macrophytes. However, recovery patterns vary widely and remain to be fully understood. We hypothesize that reduced external nutrient loading leads to an intermediate recovery state with clear spring and turbid summer conditions similar to the pattern described for eutrophication. In contrast, lake internal restoration measures can result in transient clear-water conditions both in spring and summer and reversals to turbid conditions. Furthermore, we hypothesize that these contrasting restoration measures result in different macrophyte species composition, with added implications for seasonal dynamics due to differences in plant traits. To test these hypotheses, we analyzed data on water quality and submerged macrophytes from 49 north temperate shallow lakes that were in a turbid state and subjected to restoration measures. To study the dynamics of macrophytes during nutrient load reduction, we adapted the ecosystem model PCLake. Our survey and model simulations revealed the existence of an intermediate recovery state upon reduced external nutrient loading, characterized by spring clear-water phases and turbid summers, whereas internal lake restoration measures often resulted in clear-water conditions in spring and summer with returns to turbid conditions after some years. External and internal lake restoration measures resulted in different macrophyte communities. The intermediate recovery state following reduced nutrient loading is characterized by a few macrophyte species (mainly pondweeds) that can resist wave action allowing survival in shallowareas, germinate early in spring, have energy-rich vegetative propagules facilitating rapid initial growth and that can complete their life cycle by early summer. Later in the growing season these plants are, according to our simulations, outcompeted by periphyton, leading to late-summer phytoplankton blooms. Internal lake restoration measures often coincide with a rapid but transient colonization by hornworts, waterweeds or charophytes. Stable clear-water conditions and a diverse macrophyte flora only occurred decades after external nutrient load reduction or when measures were combined.
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| 7. |
- Hughes, Carmel M, et al.
(författare)
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Provision of pharmaceutical care by community pharmacists : a comparison across Europe
- 2010
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Ingår i: Pharmacy World & Science. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 32:4, s. 472-487
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the provision of pharmaceutical care by community pharmacists across Europe and to examine the various factors that could affect its implementation. Methods A questionnaire-based survey of community pharmacies was conducted within 13 European countries. The questionnaire consisted of two sections. The first section focussed on demographic data and services provided in the pharmacy. The second section was a slightly adapted version of the Behavioral Pharmaceutical Care Scale (BPCS) which consists of three main dimensions (direct patient care activities, referral and consultation activities and instrumental activities). Results Response rates ranged from 10–71% between countries. The mean total score achieved by community pharmacists, expressed as a percentage of the total score achievable, ranged from 31.6 (Denmark) to 52.2% (Ireland). Even though different aspects of pharmaceutical care were implemented to different extents across Europe, it was noted that the lowest scores were consistently achieved in the direct patient care dimension (particularly those related to documentation, patient assessment and implementation of therapeutic objectives and monitoring plans) followed by performance evaluation and evaluation of patient satisfaction. Pharmacists who dispensed higher daily numbers of prescriptions in Ireland, Germany and Switzerland had significantly higher total BPCS scores. In addition, pharmacists in England and Ireland who were supported in their place of work by other pharmacists scored significantly higher on referral and consultation and had a higher overall provision of pharmaceutical care. Conclusion The present findings suggest that the provision of pharmaceutical care in community pharmacy is still limited within Europe. Pharmacists were routinely engaged in general activities such as patient record screening but were infrequently involved in patient centred professional activities such as the implementation of therapeutic objectives and monitoring plans, or in self-evaluation of performance.
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| 8. |
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| 9. |
- Johansson, Melker S., et al.
(författare)
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Use of prescribed analgesics before and after exercise therapy and patient education in patients with knee or hip osteoarthritis
- 2023
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Ingår i: Rheumatology International. - 0172-8172.
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate utilisation patterns of prescribed analgesics before, during, and after an exercise therapy and patient education program among patients with knee or hip osteoarthritis. This cohort study is based on data from the nationwide Good Life with osteoarthritis in Denmark (GLA:D®) patient-register linked with national health registries including data on prescribed analgesics. GLA:D® consists of 8–12 weeks of exercise and patient education. We included 35,549 knee/hip osteoarthritis patients starting the intervention between January 2013 and November 2018. Utilisation patterns the year before, 3 months during, and the year after the intervention were investigated using total dispensed defined daily doses (DDDs) per month per 1000 population as outcome. During the year before the intervention, use of prescribed paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids increased with 85%, 79% and 22%, respectively. During the intervention, use of paracetamol decreased with 16% with a stable use the following year. Use of NSAIDs and opioids decreased with 38% and 8%, respectively, throughout the intervention and the year after. Sensitivity analyses indicated that the prescription of most analgesics changed over time. For paracetamol, NSAIDs, and opioids, 10% of analgesic users accounted for 45%, 50%, and 70%, respectively, of the total DDDs dispensed during the study period. In general, analgesic use increased the year before the intervention followed by a decrease during the intervention and the year after. A small proportion of analgesic users accounted for half or more of all paracetamol, NSAIDs, and opioids dispensed during the study period.
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| 10. |
- Kenny, Gavin G., et al.
(författare)
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A Late Paleocene age for Greenland’s Hiawatha impact structure
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- The ~31-km-wide Hiawatha structure, located beneath Hiawatha Glacier in northwestern Greenland, has been proposed as an impact structure that may have formed after the Pleistocene inception of the Greenland Ice Sheet. To date the structure, we conducted 40Ar/39Ar analyses on glaciofluvial sand and U-Pb analyses on zircon separated from glaciofluvial pebbles of impact melt rock, all sampled immediately downstream of Hiawatha Glacier. Unshocked zircon in the impact melt rocks dates to ~1915 million years (Ma), consistent with felsic intrusions found in local bedrock. The 40Ar/39Ar data indicate Late Paleocene resetting and shocked zircon dates to 57.99 ± 0.54 Ma, which we interpret as the impact age. Consequently, the Hiawatha impact structure far predates Pleistocene glaciation and is unrelated to either the Paleocene-Eocene Thermal Maximum or flood basalt volcanism in east Greenland. However, it was contemporaneous with the Paleocene Carbon Isotope Maximum, although the impact’s exact paleoenvironmental and climatic significance awaits further investigation.
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