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- Díaz, S, et al.
(författare)
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Assessing nature's contributions to people
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 359:6373, s. 270-272
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge today and into the future is to maintain or enhance beneficial contributions of nature to a good quality of life for all people. This is among the key motivations of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES), a joint global effort by governments, academia, and civil society to assess and promote knowledge of Earth's biodiversity and ecosystems and their contribution to human societies in order to inform policy formulation. One of the more recent key elements of the IPBES conceptual framework is the notion of nature's contributions to people (NCP), which builds on the ecosystem service concept popularized by the Millennium Ecosystem Assessment. But as we detail below, NCP as defined and put into practice in IPBES differs from earlier work in several important ways. First, the NCP approach recognizes the central and pervasive role that culture plays in defining all links between people and nature. Second, use of NCP elevates, emphasizes, and operationalizes the role of indigenous and local knowledge in understanding nature's contribution to people. The broad remit of IPBES requires it to engage a wide range of stakeholders, spanning from natural, social, humanistic, and engineering sciences to indigenous peoples and local communities in whose territories lie much of the world's biodiversity. Being an intergovernmental body, such inclusiveness is essential not only for advancing knowledge but also for the political legitimacy of assessment findings.
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- Sandercock, P, et al.
(författare)
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EPITHET--where next?
- 2008
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Ingår i: The Lancet. Neurology. - 1474-4422. ; 7:7, s. 570-571
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Ahmad, Amais, et al.
(författare)
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IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 4 : Prediction accuracy and software comparisons with improved data and modelling strategies
- 2020
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 156, s. 50-63
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Tidskriftsartikel (refereegranskat)abstract
- Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro-in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico. Despite recent successes of PBPK in many areas of drug development, an improvement in their utility for evaluating oral absorption is much needed. Current status of predictive performance, within the confinement of commonly available in vitro data on drugs and formulations alongside systems information, were tested using 3 PBPK software packages (GI-Sim (ver.4.1), Simcyp® Simulator (ver.15.0.86.0), and GastroPlusTM (ver.9.0.00xx)). This was part of the Innovative Medicines Initiative (IMI) Oral Biopharmaceutics Tools (OrBiTo) project.Fifty eight active pharmaceutical ingredients (APIs) were qualified from the OrBiTo database to be part of the investigation based on a priori set criteria on availability of minimum necessary information to allow modelling exercise. The set entailed over 200 human clinical studies with over 700 study arms. These were simulated using input parameters which had been harmonised by a panel of experts across different software packages prior to conduct of any simulation. Overall prediction performance and software packages comparison were evaluated based on performance indicators (Fold error (FE), Average fold error (AFE) and absolute average fold error (AAFE)) of pharmacokinetic (PK) parameters.On average, PK parameters (Area Under the Concentration-time curve (AUC0-tlast), Maximal concentration (Cmax), half-life (t1/2)) were predicted with AFE values between 1.11 and 1.97. Variability in FEs of these PK parameters was relatively high with AAFE values ranging from 2.08 to 2.74. Around half of the simulations were within the 2-fold error for AUC0-tlast and around 90% of the simulations were within 10-fold error for AUC0-tlast. Oral bioavailability (Foral) predictions, which were limited to 19 APIs having intravenous (i.v.) human data, showed AFE and AAFE of values 1.37 and 1.75 respectively. Across different APIs, AFE of AUC0-tlast predictions were between 0.22 and 22.76 with 70% of the APIs showing an AFE > 1. When compared across different formulations and routes of administration, AUC0-tlast for oral controlled release and i.v. administration were better predicted than that for oral immediate release formulations. Average predictive performance did not clearly differ between software packages but some APIs showed a high level of variability in predictive performance across different software packages. This variability could be related to several factors such as compound specific properties, the quality and availability of information, and errors in scaling from in vitro and preclinical in vivo data to human in vivo behaviour which will be explored further. Results were compared with previous similar exercise when the input data selection was carried by the modeller rather than a panel of experts on each in vitro test. Overall, average predictive performance was increased as reflected in smaller AAFE value of 2.8 as compared to AAFE value of 3.8 in case of previous exercise.
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- Coyle, D., et al.
(författare)
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Emotional wellbeing
- 2014
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Ingår i: International journal of human-computer studies. - : Elsevier BV. - 1071-5819 .- 1095-9300. ; 72:8-9
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Tidskriftsartikel (refereegranskat)
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- Molter, A, et al.
(författare)
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A multicentre study of air pollution exposure and childhood asthma prevalence: the ESCAPE project
- 2015
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 45:3, s. 610-624
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine the effect of six traffic-related air pollution metrics (nitrogen dioxide, nitrogen oxides, particulate matter with an aerodynamic diameter <10 μm (PM10), PM2.5, coarse particulate matter and PM2.5 absorbance) on childhood asthma and wheeze prevalence in five European birth cohorts: MAAS (England, UK), BAMSE (Sweden), PIAMA (the Netherlands), GINI and LISA (both Germany, divided into north and south areas).Land-use regression models were developed for each study area and used to estimate outdoor air pollution exposure at the home address of each child. Information on asthma and current wheeze prevalence at the ages of 4–5 and 8–10 years was collected using validated questionnaires. Multiple logistic regression was used to analyse the association between pollutant exposure and asthma within each cohort. Random-effects meta-analyses were used to combine effect estimates from individual cohorts.The meta-analyses showed no significant association between asthma prevalence and air pollution exposure (e.g. adjusted OR (95%CI) for asthma at age 8–10 years and exposure at the birth address (n=10377): 1.10 (0.81–1.49) per 10 μg·m-3 nitrogen dioxide; 0.88 (0.63–1.24) per 10 μg·m-3 PM10; 1.23 (0.78–1.95) per 5 μg·m-3 PM2.5). This result was consistently found in initial crude models, adjusted models and further sensitivity analyses.This study found no significant association between air pollution exposure and childhood asthma prevalence in five European birth cohorts.
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- Rådholm, Karin, et al.
(författare)
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Older age is a strong predictor for poor outcome in intracerebral haemorrhage : the INTERACT2 study
- 2015
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 44:3, s. 422-427
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE:: Global ageing contributes greatly to the burden of stroke. We investigated the influence of age on the baseline profile and on outcomes in acute intracerebral haemorrhage (ICH) among participants of the INTERACT2 study.METHODS:: INTERACT2 was an international, randomised controlled trial in 2839 patients with spontaneous ICH within 6 h of onset and elevated systolic blood pressure (SBP; 150-220 mmHg) who were allocated to receive intensive (target SBP <140 mmHg within 1 h) or guideline-recommended (target SBP <180 mmHg) blood pressure lowering treatment. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Poor outcome was defined as death or major disability ('dependency', modified Rankin Scale scores 3-6) at 90 days. Health-related quality of life (HRQoL) was assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. Associations between age and outcomes were analysed in multivariable logistic regression models.RESULTS:: Stroke severity increased in categories of older age (P-trend 0.002). Stroke patients over 75 years old were four times more likely to die or be disabled at 90 days than those <52 years when other confounders were accounted for (odds ratio 4.36, 95% confidence interval 3.12-6.08). Older age was also associated with decreasing HRQoL, across mobility, self-care, usual activities and depression (all P-trend <0.001), and pain or discomfort (P-trend 0.022).CONCLUSION:: In the INTERACT2 cohort, older people had more severe ICH and worse outcomes (death, major disability and HRQoL). These data will help guide clinicians manage older people with haemorrhagic stroke. Clinical Trial Registration: http://www.clinicaltrials.gov (NCT00716079).
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- Sandercock, P, et al.
(författare)
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Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited
- 2011
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 12, s. 252-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and prediction of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit.DESIGN:International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics.RESULTS:The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials.CONCLUSION:The data from the trial will: improve the external validity and prediction of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. Trial registration ISRCTN25765518.
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- Wu, S, et al.
(författare)
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Hyperdense artery sign, symptomatic infarct swelling and effect of alteplase in acute ischaemic stroke
- 2021
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Ingår i: Stroke and vascular neurology. - : BMJ. - 2059-8696 .- 2059-8688. ; 6:2, s. 238-243
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Tidskriftsartikel (refereegranskat)abstract
- Alteplase improves functional outcomes of patients with acute ischaemic stroke, but its effects on symptomatic infarct swelling, an adverse complication of stroke and the influence of CT hyperdense artery sign (HAS) are unclear. This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association.MethodsWe included stroke patients whose prerandomisation scan was non-contrast CT. Raters, masked to clinical information, assessed baseline (prerandomisation) and follow-up (24–48 hours postrandomisation) CT scans for HAS, defined as an intracranial artery appearing denser than contralateral arteries. Symptomatic infarct swelling was defined as clinically significant neurological deterioration ≤7 days after stroke with radiological evidence of midline shift, effacement of basal cisterns or uncal herniation.ResultsAmong 2961 patients, HAS presence at baseline was associated with higher risk of symptomatic infarct swelling (OR 2.21; 95% CI 1.42 to 3.44). Alteplase increased the risk of swelling (OR 1.69; 95% CI 1.11 to 2.57), with no difference between patients with and those without baseline HAS (p=0.49). In patients with baseline HAS, alteplase reduced the proportion with HAS at follow-up (OR 0.67; 95% CI 0.50 to 0.91), where HAS disappearance was associated with reduced risk of swelling (OR 0.25, 95% CI 0.14 to 0.47).ConclusionAlthough alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS, it was also associated with accelerated clearance of HAS, which in return reduced swelling, providing further mechanistic insights to underpin the benefits of alteplase.
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