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Sökning: WFRF:(Milligan G)

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1.
  • Thomas, HS, et al. (författare)
  • 2019
  • swepub:Mat__t
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  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Prusti, T., et al. (författare)
  • The Gaia mission
  • 2016
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
  • Tidskriftsartikel (refereegranskat)abstract
    • Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
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  • Bonamy, AKE, et al. (författare)
  • Wide variation in severe neonatal morbidity among very preterm infants in European regions
  • 2019
  • Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 104:1, s. F36-F45
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates.DesignArea-based cohort study of all births before 32 weeks of gestational age.Setting16 regions in 11 European countries in 2011/2012.PatientsSurvivors to discharge from neonatal care (n=6422).Main outcome measuresSevere neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics.Results10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%–23.5%) and 13.8% including severe BPD (regional range 10.0%–23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%–18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P<0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P=0.50).ConclusionSevere neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.
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  • Cuttini, M, et al. (författare)
  • Breastfeeding outcomes in European NICUs: impact of parental visiting policies
  • 2019
  • Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 104:2, s. F151-
  • Tidskriftsartikel (refereegranskat)abstract
    • The documented benefits of maternal milk for very preterm infants have raised interest in hospital policies that promote breastfeeding. We investigated the hypothesis that more liberal parental policies are associated with increased breastfeeding at discharge from the neonatal unit.DesignProspective area-based cohort study.SettingNeonatal intensive care units (NICUs) in 19 regions of 11 European countries.PatientsAll very preterm infants discharged alive in participating regions in 2011–2012 after spending >70% of their hospital stay in the same NICU (n=4407).Main outcome measuresWe assessed four feeding outcomes at hospital discharge: any and exclusive maternal milk feeding, independent of feeding method; any and exclusive direct breastfeeding, defined as sucking at the breast. We computed a neonatal unit Parental Presence Score (PPS) based on policies regarding parental visiting in the intensive care area (range 1–10, with higher values indicating more liberal policies), and we used multivariable multilevel modified Poisson regression analysis to assess the relation between unit PPS and outcomes.ResultsPolicies regarding visiting hours, duration of visits and possibility for parents to stay during medical rounds and spend the night in unit differed within and across countries. After adjustment for potential confounders, infants cared for in units with liberal parental policies (PPS≥7) were about twofold significantly more likely to be discharged with exclusive maternal milk feeding and exclusive direct breastfeeding.ConclusionUnit policies promoting parental presence and involvement in care may increase the likelihood of successful breastfeeding at discharge for very preterm infants.
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  • Lenzini, P., et al. (författare)
  • Integration of genetic, clinical, and INR data to refine warfarin dosing
  • 2010
  • Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 87:5, s. 572-578
  • Tidskriftsartikel (refereegranskat)abstract
    • Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.
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  • Sánchez-Cano, Beatriz, et al. (författare)
  • Solar Energetic Particle Events Detected in the Housekeeping Data of the European Space Agency's Spacecraft Flotilla in the Solar System
  • 2023
  • Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 21:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite the growing importance of planetary Space Weather forecasting and radiation protection for science and robotic exploration and the need for accurate Space Weather monitoring and predictions, only a limited number of spacecraft have dedicated instrumentation for this purpose. However, every spacecraft (planetary or astronomical) has hundreds of housekeeping sensors distributed across the spacecraft, some of which can be useful to detect radiation hazards produced by solar particle events. In particular, energetic particles that impact detectors and subsystems on a spacecraft can be identified by certain housekeeping sensors, such as the Error Detection and Correction (EDAC) memory counters, and their effects can be assessed. These counters typically have a sudden large increase in a short time in their error counts that generally match the arrival of energetic particles to the spacecraft. We investigate these engineering datasets for scientific purposes and perform a feasibility study of solar energetic particle event detections using EDAC counters from seven European Space Agency Solar System missions: Venus Express, Mars Express, ExoMars-Trace Gas Orbiter, Rosetta, BepiColombo, Solar Orbiter, and Gaia. Six cases studies, in which the same event was observed by different missions at different locations in the inner Solar System are analyzed. The results of this study show how engineering sensors, for example, EDAC counters, can be used to infer information about the solar particle environment at each spacecraft location. Therefore, we demonstrate the potential of the various EDAC to provide a network of solar particle detections at locations where no scientific observations of this kind are available.
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  • Swat, M. J., et al. (författare)
  • Pharmacometrics Markup Language (PharmML) : Opening New Perspectives for Model Exchange in Drug Development
  • 2015
  • Ingår i: CPT. - : American Society for Clinical Pharmacology & Therapeutics. - 2163-8306. ; 4:6, s. 316-319
  • Tidskriftsartikel (refereegranskat)abstract
    • The lack of a common exchange format for mathematical models in pharmacometrics has been a long-standing problem. Such a format has the potential to increase productivity and analysis quality, simplify the handling of complex workflows, ensure reproducibility of research, and facilitate the reuse of existing model resources. Pharmacometrics Markup Language (PharmML), currently under development by the Drug Disease Model Resources (DDMoRe) consortium, is intended to become an exchange standard in pharmacometrics by providing means to encode models, trial designs, and modeling steps.
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  • van der Plas, F., et al. (författare)
  • Continental mapping of forest ecosystem functions reveals a high but unrealised potential for forest multifunctionality
  • 2018
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 21:1, s. 31-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Humans require multiple services from ecosystems, but it is largely unknown whether trade-offs between ecosystem functions prevent the realisation of high ecosystem multifunctionality across spatial scales. Here, we combined a comprehensive dataset (28 ecosystem functions measured on 209 forest plots) with a forest inventory dataset (105,316 plots) to extrapolate and map relationships between various ecosystem multifunctionality measures across Europe. These multifunctionality measures reflected different management objectives, related to timber production, climate regulation and biodiversity conservation/recreation. We found that trade-offs among them were rare across Europe, at both local and continental scales. This suggests a high potential for win-win' forest management strategies, where overall multifunctionality is maximised. However, across sites, multifunctionality was on average 45.8-49.8% below maximum levels and not necessarily highest in protected areas. Therefore, using one of the most comprehensive assessments so far, our study suggests a high but largely unrealised potential for management to promote multifunctional forests.
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  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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  • Appendino, G, et al. (författare)
  • Structure-activity relationships of the estrogenic sesquiterpene ester ferutinin. Modification of the terpenoid core
  • 2004
  • Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 67:9, s. 1557-1564
  • Tidskriftsartikel (refereegranskat)abstract
    • Esterification of p-hydroxybenzoic acid, a very weak estrogenic compound, with the daucane alcohol jaeschkeanadiol (1b) leads to a spectacular magnification of the estrogenic activity. To identify the structural elements responsible for this effect, the terpenoid core of jaeschkeanadiol p-hydroxybenzoate (ferutinin, 1a) was modified, capitalizing on the presence of two functionalities, the monoacylated, hydrogen-bonded 1,3-diol system and the double bond. The hydrogen bonding, while possibly useful, was not critical for activity, while hydrogenation and cyclopropanation of the double bond were tolerated. Conversely, oxidative modifications of the double bond that placed a hydroxyl on the a-face of the molecule proved detrimental. Taken together, these observations identified the substitution at C-8/C-9 as critical for activity.
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  • Fredholm, BB, et al. (författare)
  • G-protein-coupled receptors: an update
  • 2007
  • Ingår i: Acta physiologica (Oxford, England). - 1748-1708. ; 190:1, s. 3-7
  • Tidskriftsartikel (refereegranskat)
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  • Hansson, E K, et al. (författare)
  • PKPD Modeling of Predictors for Adverse Effects and Overall Survival in Sunitinib-Treated Patients With GIST
  • 2013
  • Ingår i: CPT. - : Wiley. - 2163-8306. ; 2, s. e85-
  • Tidskriftsartikel (refereegranskat)abstract
    • A modeling framework relating exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor (sVEGFR)-2, -3, soluble stem cell factor receptor (sKIT)), and tumor growth to overall survival (OS) was extended to include adverse effects (myelosuppression, hypertension, fatigue, and hand-foot syndrome (HFS)). Longitudinal pharmacokinetic-pharmacodynamic models of sunitinib were developed based on data from 303 patients with gastrointestinal stromal tumor. Myelosuppression was characterized by a semiphysiological model and hypertension with an indirect response model. Proportional odds models with a first-order Markov model described the incidence and severity of fatigue and HFS. Relative change in sVEGFR-3 was the most effective predictor of the occurrence and severity of myelosuppression, fatigue, and HFS. Hypertension was correlated best with sunitinib exposure. Baseline tumor size, time courses of neutropenia, and relative increase of diastolic blood pressure were identified as predictors of OS. The framework has potential to be used for early monitoring of adverse effects and clinical response, thereby facilitating dose individualization to maximize OS.
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26.
  • Holttinen, H., et al. (författare)
  • Design and operation of power systems with large amounts of wind power
  • 2009
  • Bok (refereegranskat)abstract
    • There are already several power systems coping with large amounts of wind power. Hi h penetration of wind power has impacts that have to be manage through proper plant interconnection, integration, transmission planning, and system and market operations. This report is a summary of case studies addressing concerns about the impact of wind power.s variability and uncertainty on power system reliability and costs. The case studies summarized in this report are not easy to compare due to different methodology and data used, as well as different assumptions on the interconnection capacity available. Integration costs of wind power need to be compared to something, like the production costs or market value of wind power, or integration cost of other production forms. There is also benefit when adding wind power to power systems: it reduces the total operating costs and emissions as wind fossil fuels. Severalissues that impact on the amount of wind power that can be integrated have been identified. Large balancing areas and aggregation benefits of large areas help in reducing the variability and forecast errors of wind power as well as help in pooling more cost effective balancing resources. System operation and working electricity markets at less than day-ahead time scales help reduce forecast errors of wind power. Transmission is the key to aggregation benefits, electricity markets and larger balancing areas. From the investigated studies it follows that at wind penetrations of up to 20 % of gross demand (energy), system operating cost increases arising from wind variability and uncertainty amounted to about 1.4 ./MWh. This is 10 % or less of the wholesale value of the wind energy.
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  • Huertas-Hernando, D., et al. (författare)
  • Hydro power flexibility for power systems with variable renewable energy sources : An IEA Task 25 collaboration
  • 2016
  • Ingår i: Wiley Interdisciplinary Reviews. - : John Wiley & Sons. - 2041-8396 .- 2041-840X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Hydro power is one of the most flexible sources of electricity production. Power systems with considerable amounts of flexible hydro power potentially offer easier integration of variable generation, e.g., wind and solar. However, there exist operational constraints to ensure mid-/long-term security of supply while keeping river flows and reservoirs levels within permitted limits. In order to properly assess the effective available hydro power flexibility and its value for storage, a detailed assessment of hydro power is essential. Due to the inherent uncertainty of the weather-dependent hydrological cycle, regulation constraints on the hydro system, and uncertainty of internal load as well as variable generation (wind and solar), this assessment is complex. Hence, it requires proper modeling of all the underlying interactions between hydro power and the power system, with a large share of other variable renewables. A summary of existing experience of wind integration in hydro-dominated power systems clearly points to strict simulation methodologies. Recommendations include requirements for techno-economic models to correctly assess strategies for hydro power and pumped storage dispatch. These models are based not only on seasonal water inflow variations but also on variable generation, and all these are in time horizons from very short term up to multiple years, depending on the studied system. Another important recommendation is to include a geographically detailed description of hydro power systems, rivers' flows, and reservoirs as well as grid topology and congestion.
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  • Sangeorzan, Irina, et al. (författare)
  • Toward Shared Decision-Making in Degenerative Cervical Myelopathy : Protocol for a Mixed Methods Study
  • 2023
  • Ingår i: JMIR Research Protocols. - : JMIR Publications. - 1929-0748. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this.Objective: The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes.Methods: Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders.Results: Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway.Conclusions: This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community.
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  • Smith, Katharine A., et al. (författare)
  • Digital Mental Health for Schizophrenia and Other Severe Mental Illnesses : An International Consensus on Current Challenges and Potential Solutions
  • 2024
  • Ingår i: JMIR Mental Health. - : JMIR Publications. - 2368-7959. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Digital approaches may be helpful in augmenting care to address unmet mental health needs, particularly for schizophrenia and severe mental illness (SMI).Objective: An international multidisciplinary group was convened to reach a consensus on the challenges and potential solutions regarding collecting data, delivering treatment, and the ethical challenges in digital mental health approaches for schizophrenia and SMI.Methods: The consensus development panel method was used, with an in -person meeting of 2 groups: the expert group and the panel. Membership was multidisciplinary including those with lived experience, with equal participation at all stages and coproduction of the consensus outputs and summary. Relevant literature was shared in advance of the meeting, and a systematic search of the recent literature on digital mental health interventions for schizophrenia and psychosis was completed to ensure that the panel was informed before the meeting with the expert group.Results: Four broad areas of challenge and proposed solutions were identified: (1) user involvement for real coproduction; (2) new approaches to methodology in digital mental health, including agreed standards, data sharing, measuring harms, prevention strategies, and mechanistic research; (3) regulation and funding issues; and (4) implementation in real -world settings (including multidisciplinary collaboration, training, augmenting existing service provision, and social and population -focused approaches). Examples are provided with more detail on human -centered research design, lived experience perspectives, and biomedical ethics in digital mental health approaches for SMI.Conclusions: The group agreed by consensus on a number of recommendations: (1) a new and improved approach to digital mental health research (with agreed reporting standards, data sharing, and shared protocols), (2) equal emphasis on social and population research as well as biological and psychological approaches, (3) meaningful collaborations across varied disciplines that have previously not worked closely together, (4) increased focus on the business model and product with planning and new funding structures across the whole development pathway, (5) increased focus and reporting on ethical issues and potential harms, and (6) organizational changes to allow for true communication and coproduction with those with lived experience of SMI. This study approach, combining an international expert meeting with patient and public involvement and engagement throughout the process, consensus methodology, discussion, and publication, is a helpful way to identify directions for future research and clinical implementation in rapidly evolving areas and can be combined with measurements of real -world clinical impact over time. Similar initiatives will be helpful in other areas of digital mental health and similarly fast -evolving fields to focus research and organizational change and effect improved real -world clinical implementation.
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