| 1. |
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| 2. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
- Falster, Daniel, et al.
(författare)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 4. |
- Witjes, J. Alfred, et al.
(författare)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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| 5. |
- Becker, Jeroen H, et al.
(författare)
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ST Analysis of the Fetal Electrocardiogram in Intrapartum Fetal Monitoring: A Meta-Analysis.
- 2012
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Ingår i: Obstetrics and Gynecology. - 1873-233X. ; 119:1, s. 145-154
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE:: To compare the effects of ST-waveform analysis in combination with cardiotocography with conventional cardiotocography for intrapartum fetal monitoring. DATA SOURCES:: We searched MEDLINE, Embase, and PubMed for randomized controlled trials (RCTs) evaluating ST-waveform analysis for intrapartum fetal monitoring. METHODS OF STUDY SELECTION:: We identified RCTs that compared ST-waveform analysis and conventional cardiotocography for intrapartum fetal monitoring of singleton pregnancies in cephalic presentation beyond 34 weeks of gestation and evaluating at least one of the following: metabolic acidosis, umbilical cord pH less than 7.15, umbilical cord pH less than 7.10, umbilical cord pH less than 7.05, umbilical cord pH less than 7.00, Apgar scores less than 7 at 5 minutes, admittance to the neonatal intensive care unit, need for intubation, presence of hypoxic ischemic encephalopathy, perinatal death, operative delivery, and number of fetal blood samplings. TABULATION, INTEGRATION, AND RESULTS:: Five RCTs, which included 15,352 patients, met the selection criteria. Random-effects models were used to estimate the combined relative risks (RRs) of ST analysis compared with conventional cardiotocography. Compared with conventional cardiotocography, ST analysis showed a nonsignificant reduction in metabolic acidosis (RR 0.72, 95% confidence interval 0.43-1.19, number needed to treat [NNT] 357). ST analysis significantly reduced the incidence of additional fetal blood sampling (RR 0.59, 95% confidence interval 0.44-0.79, NNT 11), operative vaginal deliveries (RR 0.88, 95% confidence interval 0.80-0.97, NNT 64), and total operative deliveries (RR 0.94, 95% confidence interval 0.89-0.99, NNT 64). For other outcomes, no differences in effect were seen between ST analysis and conventional cardiotocography, or data were not suitable for meta-analysis. CONCLUSION:: The additional use of ST analysis for intrapartum monitoring reduced the incidence of operative vaginal deliveries and the need for fetal blood sampling but did not reduce the incidence of metabolic acidosis at birth.
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| 6. |
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| 7. |
- Den Ruijter, Hester M., et al.
(författare)
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Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk Prediction A Meta-analysis
- 2012
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 308:8, s. 796-803
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Tidskriftsartikel (refereegranskat)abstract
- Context The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. Objective To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. Data Sources Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. Study Selection Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. Data Extraction Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. Results We included 14 population-based cohorts contributing data for 45 828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. Conclusion The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance. JAMA. 2012;308(8):796-803 www.jama.com
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| 8. |
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| 9. |
- Guida, Florence, et al.
(författare)
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Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins
- 2018
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Ingår i: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- Importance There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases.Objective To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria.Design, Setting, and Participants Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS).Main Outcomes and Measures Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity).Results In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P = .003 for difference in AUC). At an overall specificity of 0.83, based on the US Preventive Services Task Force screening criteria, the sensitivity of the integrated risk prediction (biomarker) model was 0.63 compared with 0.43 for the smoking model. Conversely, at an overall sensitivity of 0.42, based on the US Preventive Services Task Force screening criteria, the integrated risk prediction model yielded a specificity of 0.95 compared with 0.86 for the smoking model.Conclusions and Relevance This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.
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| 10. |
- Martens, Marvin, et al.
(författare)
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ELIXIR and Toxicology : a community in development
- 2021
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Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 10, s. 1129-1129
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Tidskriftsartikel (refereegranskat)abstract
- Toxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology, chemistry, pharmacology and medicine. With the rise of synthetic and new engineered materials, alongside ongoing prioritisation needs in chemical risk assessment for existing chemicals, early predictive evaluations are becoming of utmost importance to both scientific and regulatory purposes. ELIXIR is an intergovernmental organisation that brings together life science resources from across Europe. To coordinate the linkage of various life science efforts around modern predictive toxicology, the establishment of a new ELIXIR Community is seen as instrumental. In the past few years, joint efforts, building on incidental overlap, have been piloted in the context of ELIXIR. For example, the EU-ToxRisk, diXa, HeCaToS, transQST, and the nanotoxicology community have worked with the ELIXIR TeSS, Bioschemas, and Compute Platforms and activities. In 2018, a core group of interested parties wrote a proposal, outlining a sketch of what this new ELIXIR Toxicology Community would look like. A recent workshop (held September 30th to October 1st, 2020) extended this into an ELIXIR Toxicology roadmap and a shortlist of limited investment-high gain collaborations to give body to this new community. This Whitepaper outlines the results of these efforts and defines our vision of the ELIXIR Toxicology Community and how it complements other ELIXIR activities.
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| 11. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 12. |
- Schindler, Birgit Karin, et al.
(författare)
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The European COPHES/DEMOCOPHES project: Towards transnational comparability and reliability of human biomonitoring results.
- 2014
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Ingår i: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1618-131X .- 1438-4639. ; 217:6, s. 653-661
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Tidskriftsartikel (refereegranskat)abstract
- COPHES/DEMOCOPHES has its origins in the European Environment and Health Action Plan of 2004 to "develop a coherent approach on human biomonitoring (HBM) in Europe". Within this twin-project it was targeted to collect specimens from 120 mother-child-pairs in each of the 17 participating European countries. These specimens were investigated for six biomarkers (mercury in hair; creatinine, cotinine, cadmium, phthalate metabolites and bisphenol A in urine). The results for mercury in hair are described in a separate paper. Each participating member state was requested to contract laboratories, for capacity building reasons ideally within its borders, carrying out the chemical analyses. To ensure comparability of analytical data a Quality Assurance Unit (QAU) was established which provided the participating laboratories with standard operating procedures (SOP) and with control material. This material was specially prepared from native, non-spiked, pooled urine samples and was tested for homogeneity and stability. Four external quality assessment exercises were carried out. Highly esteemed laboratories from all over the world served as reference laboratories. Web conferences after each external quality assessment exercise functioned as a new and effective tool to improve analytical performance, to build capacity and to educate less experienced laboratories. Of the 38 laboratories participating in the quality assurance exercises 14 laboratories qualified for cadmium, 14 for creatinine, 9 for cotinine, 7 for phthalate metabolites and 5 for bisphenol A in urine. In the last of the four external quality assessment exercises the laboratories that qualified for DEMOCOPHES performed the determinations in urine with relative standard deviations (low/high concentration) of 18.0/2.1% for cotinine, 14.8/5.1% for cadmium, 4.7/3.4% for creatinine. Relative standard deviations for the newly emerging biomarkers were higher, with values between 13.5 and 20.5% for bisphenol A and between 18.9 and 45.3% for the phthalate metabolites. Plausibility control of the HBM results of all participating countries disclosed analytical shortcomings in the determination of Cd when using certain ICP/MS methods. Results were corrected by reanalyzes. The COPHES/DEMOCOPHES project for the first time succeeded in performing a harmonized pan-European HBM project. All data raised have to be regarded as utmost reliable according to the highest international state of the art, since highly renowned laboratories functioned as reference laboratories. The procedure described here, that has shown its success, can be used as a blueprint for future transnational, multicentre HBM projects.
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| 13. |
- Schuit, Ewoud, et al.
(författare)
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Effectiveness of electronic fetal monitoring with additional ST analysis in vertex singleton pregnancies at > 36 weeks of gestation: an individual participant data metaanalysis
- 2013
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 208:3, s. 1-187
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to assess the effectiveness of electronic fetal monitoring (EFM) alone and with additional ST analysis (EFM + ST) in laboring women with a singleton term pregnancy that is in cephalic presentation in the prevention of metabolic acidosis by the application of individual patient data metaanalysis. STUDY DESIGN: We conducted an individual patient data metaanalysis using data from 4 randomized trials, which enabled us to account for missing data and investigate relevant subgroups. The primary outcome was metabolic acidosis, which was defined as an umbilical cord-artery pH <7.05 and a base deficit that had been calculated in the extra cellular fluid compartment >12 mmol/L. We performed 8 explanatory subgroup analyses for 8 different endpoints. RESULTS: We analyzed data from 12,987 women and their newborn infants. Metabolic acidosis was present in 57 women (0.9%) in the EFM + ST group and 73 women (1.1%) in the EFM alone group (relative risk [RR], 0.76; 95% CI, 0.53-1.10). Compared with EFM alone, the use of EFM + ST resulted in a reduction in the frequency of instrumental vaginal deliveries (RR, 0.90; 95% CI, 0.83-0.99) and fetal blood samples (RR, 0.49; 95% CI, 0.44-0.55). Cesarean delivery rates were comparable between both groups (RR, 0.99; 95% CI, 0.91-1.09). Subgroup analyses showed that EFM + ST resulted in fewer admissions to a neonatal intensive care unit for women with a duration of pregnancy of >41 weeks (RR, 0.61; 95% CI, 0.39-0.95). CONCLUSION: EFM + ST does not reduce the risk of metabolic acidosis, but it does reduce the need for instrumental vaginal deliveries and fetal blood sampling.
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| 14. |
- Thielemann-Kühn, Nele, et al.
(författare)
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Optical control of 4f orbital state in rare-earth metals
- 2024
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:16
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Tidskriftsartikel (refereegranskat)abstract
- A change of orbital state alters the coupling between ions and their surroundings drastically. Orbital excitations are hence key to understand and control interaction of ions. Rare-earth elements with strong magneto-crystalline anisotropy (MCA) are important ingredients for magnetic devices. Thus, control of their localized 4f magnetic moments and anisotropy is one major challenge in ultrafast spin physics. With time-resolved x-ray absorption and resonant inelastic scattering experiments, we show for Tb metal that 4f-electronic excitations out of the ground-state multiplet occur after optical pumping. These excitations are driven by inelastic 5d-4f-electron scattering, altering the 4f-orbital state and consequently the MCA with important implications for magnetization dynamics in 4f-metals and more general for the excitation of localized electronic states in correlated materials.
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| 15. |
- Vinkler, Michal, et al.
(författare)
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Understanding the evolution of immune genes in jawed vertebrates
- 2023
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Ingår i: Journal of Evolutionary Biology. - : John Wiley & Sons. - 1010-061X .- 1420-9101. ; 36:6, s. 847-873
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Forskningsöversikt (refereegranskat)abstract
- Driven by co-evolution with pathogens, host immunity continuously adapts to optimize defence against pathogens within a given environment. Recent advances in genetics, genomics and transcriptomics have enabled a more detailed investigation into how immunogenetic variation shapes the diversity of immune responses seen across domestic and wild animal species. However, a deeper understanding of the diverse molecular mechanisms that shape immunity within and among species is still needed to gain insight into-and generate evolutionary hypotheses on-the ultimate drivers of immunological differences. Here, we discuss current advances in our understanding of molecular evolution underpinning jawed vertebrate immunity. First, we introduce the immunome concept, a framework for characterizing genes involved in immune defence from a comparative perspective, then we outline how immune genes of interest can be identified. Second, we focus on how different selection modes are observed acting across groups of immune genes and propose hypotheses to explain these differences. We then provide an overview of the approaches used so far to study the evolutionary heterogeneity of immune genes on macro and microevolutionary scales. Finally, we discuss some of the current evidence as to how specific pathogens affect the evolution of different groups of immune genes. This review results from the collective discussion on the current key challenges in evolutionary immunology conducted at the ESEB 2021 Online Satellite Symposium: Molecular evolution of the vertebrate immune system, from the lab to natural populations.
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| 16. |
- Abdellah, Mohamed, et al.
(författare)
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Drastic difference between hole and electron injection through the gradient shell of CdxSeyZn1−xS1−y quantum dots
- 2017
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 9:34, s. 12503-12508
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Tidskriftsartikel (refereegranskat)abstract
- Ultrafast fluorescence spectroscopy was used to investigate the hole injection in CdxSeyZn1-xS1-y gradient core-shell quantum dot (CSQD) sensitized p-type NiO photocathodes. A series of CSQDs with a wide range of shell thicknesses was studied. Complementary photoelectrochemical cell measurements were carried out to confirm that the hole injection from the active core through the gradient shell to NiO takes place. The hole injection from the valence band of the QDs to NiO depends much less on the shell thickness when compared to the corresponding electron injection to n-type semiconductor (ZnO). We simulate the charge carrier tunneling through the potential barrier due to the gradient shell by numerically solving the Schrodinger equation. The details of the band alignment determining the potential barrier are obtained from X-ray spectroscopy measurements. The observed drastic differences between the hole and electron injection are consistent with a model where the hole effective mass decreases, while the gradient shell thickness increases.
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| 17. |
- Ancel, P-A., et al.
(författare)
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History of induced abortion as a risk factor for preterm birth in European countries:results of the EUROPOP suvery
- 2004
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 19:3, s. 734-740
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objective of this study was to investigate the relationship between history of induced abortion and preterm delivery in various parts of Europe, and according to the main cause of preterm birth. METHODS: We used data from a case–control survey, the EUROPOP study; 2938 preterm births and 4781 controls at term from ten European countries were included. Based on national statistics, we distinguished three groups of countries with high, intermediate and low rates of induced abortion. RESULTS: Previous induced abortions were significantly associated with preterm delivery and the risk of preterm birth increased with the number of abortions. Odds ratios did not differ significantly between the three groups of countries. The extent of association with previous induced abortion varied according to the cause of preterm delivery. Previous induced abortions significantly increased the risk of preterm delivery after idiopathic preterm labour, preterm premature rupture of membranes and ante-partum haemorrhage, but not preterm delivery after maternal hypertension. The strength of the association increased with decreasing gestational age at birth. CONCLUSIONS: Identifying subgroups of preterm births on the basis of the complications involved in delivery increases our understanding of the mechanisms by which previous induced abortion affects subsequent pregnancy outcomes.
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| 18. |
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| 19. |
- Bieghs, Liesbeth, et al.
(författare)
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The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic
- 2014
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:22, s. 11193-11208
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Tidskriftsartikel (refereegranskat)abstract
- The ABT-analogous 737, 263 and 199 are BH3 mimetics showing potent anti-myeloma (MM) activity, but only on defined molecular subgroups of MM patients presenting a Bcl-2high/Mcl-1low profile. IGF-1 is a major survival factor in MM regulating the expression of Bcl-2 proteins and might therefore be a resistance factor to these ABT-analogous. We first show that IGF-1 protected human MM cell lines (HMCLs) against ABT-737. Concurrently, the IGF-1 receptor inhibitor picropodophyllin (PPP) synergistically sensitized HMCL, primary human MM and murine 5T33MM cells to ABT-737 and ABT-199 by further decreasing cell viability and enhancing apoptosis. Knockdown of Bcl-2 by shRNA protected MM cells to ABT-737, while Mcl-1 shRNA sensitized the cells. PPP overcame the Bcl-2 dependency of ABT-737, but failed to completely overcome the protective effect of Mcl-1. In vivo, co-treatment of 5T33MM bearing mice significantly decreased tumor burden and prolonged overall survival both in a prophylactic and therapeutic setting. Interestingly, proteasome inhibitor resistant CD138- 5T33MM cells were more sensitive to ABT-737, whereas PPP alone targeted the CD138+ cells more effectively. After co-treatment, both subpopulations were targeted equally. Together, the combination of an IGF-1R inhibitor and an ABT-analogue displays synergistic anti-myeloma activity providing the rational for further (pre)clinical testing.
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| 20. |
- Budnik, Lygia Therese, et al.
(författare)
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Diagnosis, monitoring and prevention of exposure-related non-communicable diseases in the living and working environment : DiMoPEx-project is designed to determine the impacts of environmental exposure on human health
- 2018
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Ingår i: Journal of Occupational Medicine and Toxicology. - : Springer Science and Business Media LLC. - 1745-6673. ; 13:1
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Forskningsöversikt (refereegranskat)abstract
- The WHO has ranked environmental hazardous exposures in the living and working environment among the top risk factors for chronic disease mortality. Worldwide, about 40 million people die each year from noncommunicable diseases (NCDs) including cancer, diabetes, and chronic cardiovascular, neurological and lung diseases. The exposure to ambient pollution in the living and working environment is exacerbated by individual susceptibilities and lifestyle-driven factors to produce complex and complicated NCD etiologies. Research addressing the links between environmental exposure and disease prevalence is key for prevention of the pandemic increase in NCD morbidity and mortality. However, the long latency, the chronic course of some diseases and the necessity to address cumulative exposures over very long periods does mean that it is often difficult to identify causal environmental exposures. EU-funded COST Action DiMoPEx is developing new concepts for a better understanding of health-environment (including gene-environment) interactions in the etiology of NCDs. The overarching idea is to teach and train scientists and physicians to learn how to include efficient and valid exposure assessments in their research and in their clinical practice in current and future cooperative projects. DiMoPEx partners have identified some of the emerging research needs, which include the lack of evidence-based exposure data and the need for human-equivalent animal models mirroring human lifespan and low-dose cumulative exposures. Utilizing an interdisciplinary approach incorporating seven working groups, DiMoPEx will focus on aspects of air pollution with particulate matter including dust and fibers and on exposure to low doses of solvents and sensitizing agents. Biomarkers of early exposure and their associated effects as indicators of disease-derived information will be tested and standardized within individual projects. Risks arising from some NCDs, like pneumoconioses, cancers and allergies, are predictable and preventable. Consequently, preventative action could lead to decreasing disease morbidity and mortality for many of the NCDs that are of major public concern. DiMoPEx plans to catalyze and stimulate interaction of scientists with policy-makers in attacking these exposure-related diseases.
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| 21. |
- Burger, Ronelle, et al.
(författare)
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Use of simulated patients to assess hypertension case management at public healthcare facilities in South Africa
- 2020
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Ingår i: Journal of Hypertension. - 1473-5598. ; 38:2, s. 362-367
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Our study aims to evaluate hypertensive case management in South Africa's public health sector using simulated patients.METHOD: Our study describes interactions between hypertensive simulated patients and primary healthcare workers at 39 public sector healthcare facilities in two metropolitan centres in the Eastern and Western Cape Provinces of South Africa. Our analysis focus on 97 interactions where our eight simulated patients tested within range for stage 1 hypertension, that is with SBP 140-159 mmHg and/or DBP 90-99 mmHg. For this subset, we describe how healthcare workers communicated the outcome of the blood pressure test, and whether they follow government guidelines on risk assessment and lifestyle advice.RESULTS: Healthcare workers highlighted the risks associated with hypertension in one out of three cases and stressed the importance of regular monitoring of blood pressure in less than half of cases. Hypertensive patients received advice on all six lifestyle risk factors in 8% of cases. 39% of patients received no lifestyle advice at all. In one out of four cases, hypertensive patients left the facility without a hypertension diagnosis and with no prospect of a follow-up visit.CONCLUSION: Simulated patients can assess the quality of hypertension case management, yielding granular and comprehensive information that can help mobilize resources to improve care. The management of hypertension patients in South African public healthcare facilities is critically insufficient. Given that hypertension is responsible for a rising share of deaths in South Africa and many of these deaths are preventable, urgent intervention is needed.
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| 22. |
- Chen, Junsheng, et al.
(författare)
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Size-And Wavelength-Dependent Two-Photon Absorption Cross-Section of CsPbBr3 Perovskite Quantum Dots
- 2017
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Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 8:10, s. 2316-2321
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Tidskriftsartikel (refereegranskat)abstract
- All-inorganic colloidal perovskite quantum dots (QDs) based on cesium, lead, and halide have recently emerged as promising light emitting materials. CsPbBr3 QDs have also been demonstrated as stable two-photon-pumped lasing medium. However, the reported two photon absorption (TPA) cross sections for these QDs differ by an order of magnitude. Here we present an in-depth study of the TPA properties of CsPbBr3 QDs with mean size ranging from 4.6 to 11.4 nm. By using femtosecond transient absorption (TA) spectroscopy we found that TPA cross section is proportional to the linear one photon absorption. The TPA cross section follows a power law dependence on QDs size with exponent 3.3 ± 0.2. The empirically obtained power-law dependence suggests that the TPA process through a virtual state populates exciton band states. The revealed power-law dependence and the understanding of TPA process are important for developing high performance nonlinear optical devices based on CsPbBr3 nanocrystals.
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| 23. |
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| 24. |
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| 25. |
- d'Alessandro, Elisa, et al.
(författare)
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Thrombo-Inflammation in Cardiovascular Disease : An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis
- 2020
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 538-564
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Tidskriftsartikel (refereegranskat)abstract
- Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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| 26. |
- Dam, Veerle, et al.
(författare)
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Association of menopausal characteristics and risk of coronary heart disease : A pan-European case-cohort analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:4, s. 1275-1285
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Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
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| 27. |
- Dong, Lan-Feng, et al.
(författare)
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Suppression of Tumor Growth In vivo by the Mitocan alpha-tocopheryl Succinate Requires Respiratory Complex II
- 2009
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Ingår i: CLINICAL CANCER RESEARCH. - 1078-0432. ; 15:5, s. 1593-1600
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Vitamin E analogues are potent novel anticancer drugs. The purpose of this study was to elucidate the cellular target by which these agents, represented by alpha-tocopoheryl succinate (alpha-TOS), suppress tumors in vivo, with the focus on the mitochondrial complex II (CII). Experimental Design: Chinese hamster lung fibroblasts with functional, dysfunctional, and reconstituted CII were transformed using H-Ras. The cells were then used to form xenografts in immunocompromized mice, and response of the cells and the tumors to alpha-TOS was studied. Results: The CII-functional and CII-reconstituted cells, unlike their CII-dysfunctional counterparts, responded to alpha-TOS by reactive oxygen species generation and apoptosis execution. Tumors derived from these cell lines reciprocated their responses to alpha-TOS. Thus, growth of CII-functional and CII-reconstituted tumors was strongly suppressed by the agent, and this was accompanied by high level of apoptosis induction in the tumor cells. On the other hand, alpha-TOS did not inhibit the CII-dysfuntional tumors. Conclusions: We document in this report a novel paradigm, according to which the mitochondrial CII, which rarely mutates in human neoplasias, is a plausible target for anticancer drugs from the group of vitamin E analogues, providing support for their testing in clinical trials.
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| 28. |
- Eechoute, Karel, et al.
(författare)
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A long-term prospective population pharmacokinetic study on imatinib plasma concentrations in GIST patients
- 2012
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 18:20, s. 5780-5787
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Imatinib minimal (trough) plasma concentrations after one month of treatment have shown a significant association with clinical benefit in patients with gastrointestinal stromal tumors (GIST). Considering that a retrospective pharmacokinetic analysis has also suggested that imatinib clearance increases over time in patients with soft tissue sarcoma and GIST, the primary aim of this study was to assess systemic exposure to imatinib at multiple time points in a long-term prospective population pharmacokinetic study. As imatinib is mainly metabolized in the liver, our secondary aim was to elucidate the potential effects of the volume of liver metastases on exposure to imatinib. Experimental Design: Full pharmacokinetic blood sampling was conducted in 50 patients with GIST on the first day of imatinib treatment, and after one, six, and 12 months. In addition, on day 14, and monthly during imatinib treatment, trough samples were taken. Pharmacokinetic analysis was conducted using a compartmental model. Volume of liver metastases was assessed by computed tomographic (CT) imaging. Results: After 90 days of treatment, a significant decrease in imatinib systemic exposure of 29.3% compared with baseline was observed (P < 0.01). For every 100 cm 3 increase of metastatic volume, a predicted decrease of 3.8% in imatinib clearance was observed. Conclusions: This is the first prospective pharmacokinetic study in patients with GIST, showing a significant decrease of approximately 30% in imatinib exposure after long-term treatment. This means that future "trough level - clinical benefit" analyses should be time point specific. GIST liver involvement, however, has a marginal effect on imatinib clearance.
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| 29. |
- Eide, Leslie S. P., et al.
(författare)
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Delirium as a predictor of physical and cognitive function in individuals aged 80 and older after transcatheter aortic valve implantation or surgical aortic valve replacement
- 2016
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 64:6, s. 1178-1186
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine how development of delirium after surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) could predict activity of daily living (ADL) and instrumental ADLs (IADL) disability, cognitive function, and self-reported health in individuals aged 80 and older.Design: Prospective cohort study. Setting: Tertiary university hospital.Participants: Individuals aged 80 and older undergoing elective SAVR or TAVI (N = 136).Measurements: Delirium was assessed for 5 days using the Confusion Assessment Method. The Barthel Index, Nottingham Extended ADL Scale, and SF-12 were used to determine ADL and IADL ability and self-reported health at baseline and 1- and 6-month follow-up. Cognition was assessed using the Mini-Mental State Examination at baseline and 6-month follow-up.Results: Participants had lower IADL scores 1 month after SAVR than at baseline (baseline 58, 1 month: delirium 42, no delirium 50, P ≤.02), but scores had returned to baseline levels at 6 months. The Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) Physical Component Summary (PCS) score was higher at 6-month follow-up (48) than at baseline (39), especially in participants who did not develop delirium (P <.001). No differences in other outcomes were found. Regression models suggest that delirium may help predict IADL disability 1 month after baseline (P ≤.07) but does not predict large differences in ADL disability, cognitive function, or SF-12-scores. Individuals who underwent TAVI and developed delirium had lower ADL (baseline 19, 1-month 16, P <.001) and IADL (baseline 49, 1-month 40, P =.003) scores at 1-month follow-up. SF-12 PCS score (baseline 30) increased from baseline to 1- (35, P =.04) and 6- (35, P =.02) month follow-up in individuals who underwent TAVI and did not develop delirium. Delirium after TAVI predicted greater ADL and IADL disability at 1-month but not at 6-month follow-up.Conclusion: Individuals who develop delirium after SAVR and TAVI have poorer short-term IADL function but do not seem to have long-term reductions in physical, mental, or self-reported health.
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| 30. |
- Fan, Tingting, et al.
(författare)
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Bright circularly polarized soft X-ray high harmonics for X-ray magnetic circular dichroism
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:46, s. 14206-14211
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate, to our knowledge, the first bright circularly polarized high-harmonic beams in the soft X-ray region of the electromagnetic spectrum, and use them to implement X-ray magnetic circular dichroism measurements in a tabletop-scale setup. Using counterrotating circularly polarized laser fields at 1.3 and 0.79 mu m, we generate circularly polarized harmonics with photon energies exceeding 160 eV. The harmonic spectra emerge as a sequence of closely spaced pairs of left and right circularly polarized peaks, with energies determined by conservation of energy and spin angular momentum. We explain the single-atom and macroscopic physics by identifying the dominant electron quantum trajectories and optimal phase-matching conditions. The first advanced phase-matched propagation simulations for circularly polarized harmonics reveal the influence of the finite phase-matching temporal window on the spectrum, as well as the unique polarization-shaped attosecond pulse train. Finally, we use, to our knowledge, the first tabletop X-ray magnetic circular dichroism measurements at the N-4,N-5 absorption edges of Gd to validate the high degree of circularity, brightness, and stability of this light source. These results demonstrate the feasibility of manipulating the polarization, spectrum, and temporal shape of high harmonics in the soft X-ray region by manipulating the driving laser waveform.
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| 31. |
- Frier, Emily M, et al.
(författare)
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Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.
- 2023
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure.The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records.The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.
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| 32. |
- Gossec, Laure, et al.
(författare)
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OARSI/OMERACT Initiative to Define States of Severity and Indication for Joint Replacement in Hip and Knee Osteoarthritis. An OMERACT 10 Special Interest Group
- 2011
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 38:8, s. 1765-1769
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of "need for joint replacement surgery," for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA). Methods. New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons' indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA. Results. In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%-12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0-100) + physical function (0-100) > 80]. Conclusion. These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define "nonresponders" to disease-modifying drugs in OA clinical trials. (J Rheumatol 2011;38:1765-9; doi:10.3899/jrheum.110403)
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| 33. |
- Gossec, Laure, et al.
(författare)
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OMERACT/OARSI initiative to define states of severity and indication for joint replacement in hip and knee osteoarthritis
- 2007
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 34:6, s. 1432-1435
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Time to theoretical indication of joint replacement surgery has been proposed as a primary outcome for potential structure-modifying interventions for osteoarthritis (OA). The objectives of this OMERACT/OARSI Working Group were to identify pain, physical function, and structure states that represent the progression from early to late disease for individuals with OA of the hip and knee, and to create a composite measure of these 3 domains to define states of OA severity and a surrogate measure of "need for joint replacement surgery." Methods. For pain, focus groups and one-on-one interviews were used. For function, Rasch analysis was performed on existing indices - the Hip Dysfunction and Osteoarthritis Outcome Score (HOOS) and the Knee injury and Osteoarthritis Outcome Score (KOOS), each of which subsumes the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) questions. For structure, a comparison of existing indices (Kellgren-Lawrence, OARSI stages, and joint space width) was performed for the hip and the knee. Results. For pain, key features of pain that are most distressing to people with OA from early to late disease were identified. For function, the reduction of the number of items based on the existing indices continues. For structure, the analysis is also ongoing. Conclusion. Preliminary results were presented at OMERACT 8; the final objective will be to combine the 3 domains (pain, function, and structure) and to create a composite index that could define states of severity and "need for total joint replacement," which could be used to evaluate treatment response to disease-modifying drugs in OA clinical trials.
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| 34. |
- Hobbins, John C., et al.
(författare)
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Antibiotic prophylaxis before amniocentesis
- 2011
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Ingår i: Prenatal Diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 31:12, s. 1213-1214
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 35. |
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| 36. |
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| 37. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 38. |
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| 39. |
- Knowles, Charles H., et al.
(författare)
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Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group
- 2009
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 118:2, s. 271-301
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Tidskriftsartikel (refereegranskat)abstract
- The term gastrointestinal neuromuscular disease describes a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular, including interstitial cell of Cajal, dysfunction. Such disorders commonly have impaired motor activity, i.e. slowed or obstructed transit with radiological evidence of transient or persistent visceral dilatation. Whilst sensorimotor abnormalities have been demonstrated by a variety of methods in these conditions, standards for histopathological reporting remain relatively neglected. Significant differences in methodologies and expertise continue to confound the reliable delineation of normality and specificity of particular pathological changes for disease. Such issues require urgent clarification to standardize acquisition and handling of tissue specimens, interpretation of findings and make informed decisions on risk-benefit of full-thickness tissue biopsy of bowel or other diagnostic procedures. Such information will also allow increased certainty of diagnosis, facilitating factual discussion between patients and caregivers, as well as giving prognostic and therapeutic information. The following report, produced by an international working group, using established consensus methodology, presents proposed guidelines on histological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology. The report addresses the main areas of histopathological practice as confronted by the pathologist, including suction rectal biopsy and full-thickness tissue obtained with diagnostic or therapeutic intent. For each, indications, safe acquisition of tissue, histological techniques, reporting and referral recommendations are presented.
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| 40. |
- Knowles, Charles H., et al.
(författare)
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The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group
- 2010
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 59:7, s. 882-887
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Tidskriftsartikel (refereegranskat)abstract
- Objective Guidelines on histopathological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology have been produced recently by an international working group (IWG). These addressed the important but relatively neglected areas of histopathological practice of the general pathologist, including suction rectal biopsy and full-thickness intestinal tissue. Recommendations were presented for the indications, safe acquisition of tissue, histological techniques, reporting and referral of such histological material. Design Consensual processes undertaken by the IWG and following established guideline decision group methodologies. Results and conclusion This report presents a contemporary and structured classification of gastrointestinal neuromuscular pathology based on defined histopathological criteria derived from the existing guidelines. In recognition of its origins and first presentation in London at the World Congress of Gastroenterology 2009, this has been named 'The London Classification'. The implementation of this classification should allow some diagnostic standardisation, but should necessarily be viewed as a starting point for future modification as new data become available.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Moseng, Tuva, et al.
(författare)
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EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis : 2023 update
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - 1468-2060.
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an update is needed.METHODS: The Standardised Operating Procedures for EULAR recommendations were followed. A multidisciplinary Task Force with 25 members representing 14 European countries was established. The Task Force agreed on an updated search strategy of 11 research questions. The systematic literature review encompassed dates from 1 January 2012 to 27 May 2022. Retrieved evidence was discussed, updated recommendations were formulated, and research and educational agendas were developed.RESULTS: The revised recommendations include two overarching principles and eight evidence-based recommendations including (1) an individualised, multicomponent management plan; (2) information, education and self-management; (3) exercise with adequate tailoring of dosage and progression; (4) mode of exercise delivery; (5) maintenance of healthy weight and weight loss; (6) footwear, walking aids and assistive devices; (7) work-related advice and (8) behaviour change techniques to improve lifestyle. The mean level of agreement on the recommendations ranged between 9.2 and 9.8 (0-10 scale, 10=total agreement). The research agenda highlighted areas related to these interventions including adherence, uptake and impact on work.CONCLUSIONS: The 2023 updated recommendations were formulated based on research evidence and expert opinion to guide the optimal management of hip and knee OA.
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| 46. |
- Nevens, Frederik, et al.
(författare)
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A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.
- 2016
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Ingår i: The New England journal of medicine. - 1533-4406. ; 375:7, s. 631-43
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Tidskriftsartikel (refereegranskat)abstract
- Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease.
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| 47. |
- Northcott, Paul A, et al.
(författare)
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Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
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| 48. |
- Olsen, Siv J. S., et al.
(författare)
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Changes in self-reported health and quality of life in octogenarian patients one month after transcatheter aortic valve implantation
- 2017
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Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 16:1, s. 79-87
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In addition to favourable results regarding mortality and morbidity it is important to identify the impact transcatheter aortic valve implantation (TAVI) has on patients' quality of life.AIMS: The aims were: (i) to describe clinical characteristics, self-reported health and quality of life in octogenarians before TAVI intervention; (ii) to determine changes in self-reported health and quality of life one month after TAVI; and (iii) to establish the clinical importance of the findings.METHODS: A prospective cohort study was conducted on consecutively enrolled octogenarians with severe aortic stenosis undergoing TAVI (N = 65). Self-reported health and quality of life were recorded at baseline and one month later using two global questions from the World Health Organization Quality of Life Instrument Abbreviated (WHOQOL-BREF), the generic Short Form Health 12 and the disease-specific Minnesota Living with Heart Failure Questionnaire.RESULTS: One month after TAVI, WHOQOL-BREF showed that self-reported health improved moderately (p < 0.001), while quality of life improved slightly, but not statistically significantly (p = 0.06). There were changes in all Short Form Health 12 domains, except social functioning and role emotional. The estimated changes were 3.6 to 5.8 with large confidence intervals. The Physical Component Summary increased statistically significantly from baseline to 30 days (30.6-34.7; p = 0.02), but the Mental Component Summary did not (46.9-50.0; p = 0.13).CONCLUSION: Despite being an advanced treatment performed in a high risk population, TAVI in octogenarians improves short-term self-reported global health and generic physical health and quality of life. These patient-reported outcomes have importance, particularly in this age group.
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| 49. |
- Pirhonen, J P, et al.
(författare)
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Frequency of anal sphincter rupture at delivery in Sweden and Finland--result of difference in manual help to the baby's head
- 1998
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 77:10, s. 974-977
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anal sphincter rupture is a serious complication of vaginal delivery and almost half the affected women have persistent defecatory symptoms despite adequate primary repair. During the past decade, the incidence of anal sphincter ruptures has been increasing in Sweden and is currently estimated to occur in 2.5% of vaginal deliveries. The aim of the study was to report the frequency of anal sphincter ruptures in two university hospitals in two Scandinavian countries, Malmo in Sweden and Turku in Finland, and analyze the potential determinants. METHODS: Retrospective analysis of a population of 30,933 deliveries (26,541 vaginal) during the years 1990 to 1994. RESULTS: The incidence of anal sphincter ruptures in Malmo, Sweden was 2.69%, and in Turku, Finland 0.36%. There were no significant population differences for the known risk factors (fetal weight, nulliparity or fetal head circumference). However, there is a difference in manual support given to the perineum and to the baby's head when crowning through the vaginal introitus between Malmo and Turku. The proportion of operative vaginal deliveries and abnormal presentations was significantly higher in Turku reflected in the lower Apgar score at 5 minutes and longer duration of second phase of labor. When high risk deliveries (operative vaginal delivery, abnormal presentation and newborns over 4,000 g) were excluded, the risk for anal sphincter ruptures was estimated to be 13 times higher in Malmo than in Turku. CONCLUSIONS: The difference in the incidence of anal sphincter rupture between Malmo, Sweden and Turku, Finland may be due to the difference in manual control of the baby's head when crowning.
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| 50. |
- Shephard, Mark, et al.
(författare)
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Independent clinic-based evaluation of point-of-care testing for the screening of Chlamydia trachomatis, Neisseria gonorrhoea and Trichomonas vaginalis in women-at-risk in Australia, Guatemala, Morocco, and South Africa
- 2024
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 24:Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa.METHODS: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs).RESULTS: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV.CONCLUSION: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV.TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries.
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