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  • Adam, A, et al. (author)
  • Abstracts from Hydrocephalus 2016.
  • 2017
  • In: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
  • Journal article (peer-reviewed)
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  • Clark, Andrew G., et al. (author)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Journal article (peer-reviewed)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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  • Weinstein, John N., et al. (author)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
  • Research review (peer-reviewed)abstract
    • The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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  • Goodwin, G. M., et al. (author)
  • Evidence-based guidelines for treating bipolar disorder : Revised third edition recommendations from the British Association for Psychopharmacology
  • 2016
  • In: Journal of Psychopharmacology. - : SAGE PUBLICATIONS LTD. - 0269-8811 .- 1461-7285. ; 30:6, s. 495-553
  • Research review (peer-reviewed)abstract
    • The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
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  • Gallagher, P, et al. (author)
  • Neurocognitive intra-individual variability in mood disorders : effects on attentional response time distributions.
  • 2015
  • In: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 45:14, s. 2985-97
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Attentional impairment is a core cognitive feature of major depressive disorder (MDD) and bipolar disorder (BD). However, little is known of the characteristics of response time (RT) distributions from attentional tasks. This is crucial to furthering our understanding of the profile and extent of cognitive intra-individual variability (IIV) in mood disorders.METHOD: A computerized sustained attention task was administered to 138 healthy controls and 158 patients with a mood disorder: 86 euthymic BD, 33 depressed BD and 39 medication-free MDD patients. Measures of IIV, including individual standard deviation (iSD) and coefficient of variation (CoV), were derived for each participant. Ex-Gaussian (and Vincentile) analyses were used to characterize the RT distributions into three components: mu and sigma (mean and standard deviation of the Gaussian portion of the distribution) and tau (the 'slow tail' of the distribution).RESULTS: Compared with healthy controls, iSD was increased significantly in all patient samples. Due to minimal changes in average RT, CoV was only increased significantly in BD depressed patients. Ex-Gaussian modelling indicated a significant increase in tau in euthymic BD [Cohen's d = 0.39, 95% confidence interval (CI) 0.09-0.69, p = 0.011], and both sigma (d = 0.57, 95% CI 0.07-1.05, p = 0.025) and tau (d = 1.14, 95% CI 0.60-1.64, p < 0.0001) in depressed BD. The mu parameter did not differ from controls.CONCLUSIONS: Increased cognitive variability may be a core feature of mood disorders. This is the first demonstration of differences in attentional RT distribution parameters between MDD and BD, and BD depression and euthymia. These data highlight the utility of applying measures of IIV to characterize neurocognitive variability and the great potential for future application.
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  • Milner, A, et al. (author)
  • Gendered working environments as a determinant of mental health inequalities: a systematic review of 27 studies
  • 2021
  • In: Occupational and environmental medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 78:3, s. 147-152
  • Journal article (peer-reviewed)abstract
    • ‘Gendered working environments’ describes the ways in which (1) differential selection into work, (2) variations in employment arrangements and working hours, (3) differences in psychosocial exposures and (4) differential selection out of work may produce varied mental health outcomes for men and women. The aim of this study was to conduct a systematic review to understand gender differences in mental health outcomes in relation to the components of gendered working environments.MethodsThe review followed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search approach and focused on studies published in 2008–2018. The protocol for the review was prospectively registered with PROSPERO (CRD42019124066).FindingsAcross the 27 cohort studies included in the review, we found that (1) there was inconclusive evidence on the effect of occupational gender composition on the mental health of men and women, (2) women’s mental health was more likely to be affected by long working hours than men’s; however, precarious employment was more likely to be negatively associated with men’s mental health, (3) exposure to traditional constructs of psychosocial job stressors negatively affected the mental health of both women and men, and (4) unemployment and retirement are associated with poorer mental health in both genders.InterpretationThe findings from this review indicate that gendered working environments may affect the mental health of both men and women, but the association is dependent on the specific exposure examined. There is still much to be understood about gendered working environments, and future research into work and health should be considered with a gender lens.
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  • Abrahamsson, B., et al. (author)
  • Six years of progress in the oral biopharmaceutics area - A summary from the IMI OrBiTo project
  • 2020
  • In: European journal of pharmaceutics and biopharmaceutics. - : ELSEVIER. - 0939-6411 .- 1873-3441. ; 152, s. 236-247
  • Journal article (peer-reviewed)abstract
    • OrBiTo was a precompetitive collaboration focused on the development of the next generation of Oral Biopharmaceutics Tools. The consortium included world leading scientists from nine universities, one regulatory agency, one non-profit research organisation, three small/medium sized specialist technology companies together with thirteen pharmaceutical companies. The goal of the OrBiTo project was to deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This goal was achieved through novel prospective investigations to define new methodologies or refinement of existing tools. Extensive validation has been performed of novel and existing biopharmaceutics tools using historical datasets supplied by industry partners as well as laboratory ring studies. A combination of high quality in vitro and in vivo characterizations of active drugs and formulations have been integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of gastrointestinal drug absorption and some of the best practices has been highlighted. This approach has given an unparalleled opportunity to deliver transformational change in European industrial research and development towards model based pharmaceutical product development in accordance with the vision of model-informed drug development.
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  • Friedman, Rachel S., et al. (author)
  • Beyond the community in participatory forest management : A governance network perspective
  • 2020
  • In: Land use policy. - : Elsevier BV. - 0264-8377 .- 1873-5754. ; 97
  • Journal article (peer-reviewed)abstract
    • Governance of the environment and natural resources involves interests of multiple stakeholders at different scales. In community-based forest management, organisations outside of communities play important roles in achieving multiple social and ecological objectives. How and when these organisations play a role in the community-based forest management process remains a key question. We applied social network analysis to a case study in Indonesian Borneo to better understand the evolution of interactions between organisational actors, and with communities. NGOs featured most prominently in initiating the permit process, implementing management, and providing other support activities, while also being well-connected to donors and government actors. The network configurations indicated significant cooperation among organisations when initiating the community forest process, while bridging between village and organisational levels characterised all stages of the community forest process. While community-based forest management often evokes images of grassroots efforts and broad local capacity to manage forests, reality shows a more dynamic and heterogeneous picture and broader involvement of different actor types and motivations in Indonesia. These findings can be applied to other countries implementing and expanding their decentralised forest policies.
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  • Lennernäs, Hans, et al. (author)
  • In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation : Future Use of Modern Approaches and Methodologies in a Regulatory Context
  • 2017
  • In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:4, s. 1307-1314
  • Journal article (peer-reviewed)abstract
    • The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational Models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated: to the presentation of the most recent progress in the development of the regulatory use of PBPK in silk() modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include-definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the inter individual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.
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  • Lennernäs, Hans, et al. (author)
  • Oral biopharmaceutics tools - Time for a new initiative - An introduction to the IMI project OrBiTo
  • 2014
  • In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57:SI, s. 292-299
  • Research review (peer-reviewed)abstract
    • OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using active pharmaceutical ingredient (API), formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silica biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and modified-release formulations, as well as allowing optimization of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes.
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  • Malmenholt, A, et al. (author)
  • Orofacial Function, Articulation Proficiency, and Intelligibility in 5-Year-Old Children Born With Cleft Lip and Palate
  • 2019
  • In: The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. - : SAGE Publications. - 1545-1569. ; 56:3, s. 321-330
  • Journal article (peer-reviewed)abstract
    • To explore and describe orofacial function in 5-year-old children born with clefts affecting the palate and to investigate potential relationship with articulation proficiency and intelligibility. Design: A prospective cohort study of 88 consecutive patients born with cleft lip and palate (CLP) between July 2009 and June 2011. Participants: Excluding internationally adopted children and children with no speech production resulted in 52 children with different cleft types and additional malformations, examined at age 5. Data on orofacial function were available for 43 children. Outcome Measures: Screening of orofacial function resulted in a profile and a total score, narrow phonetic transcription of test consonants produced a percentage of consonants correct (PCC) score, and ratings of intelligibility by speech and language pathologists (SLPs) and by parents gave 2 estimates. Inter- and intra-transcriber agreement was calculated. Results: Orofacial dysfunction was found in 37% of children, with results not significantly different between cleft types but significantly more frequent than in children born without CLP. Age-appropriate articulation proficiency was found in 39%, 49% presented below −2 standard deviations. Just above 50% had good intelligibility and were always understood by different communication partners according to both SLP and parent ratings. No significant correlation was found between orofacial dysfunction and PCC or intelligibility. Conclusions: Orofacial dysfunction was not found to be an explanatory factor for speech outcome in children born with CLP.
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  • Milner, A, et al. (author)
  • Gendered Working Environments as a Determinant of Mental Health Inequalities: A Protocol for a Systematic Review
  • 2019
  • In: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 16:7
  • Journal article (peer-reviewed)abstract
    • Both gender and employment are critical and intersecting social determinants of mental and physical health. This paper describes the protocol used to conduct a systematic literature review of the relationship between “gendered working environments” and mental health. Gendered working environments (GWE) are conceptualised as involving: (1) differences in selection into work, and more specifically, occupations; (2) variation in employment arrangements and working hours; (3) disparities in psychosocial exposures at work, and; (4) differences in selection out of work. Methods/design: The review will adhere to a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search procedure. Key words will be identified that are specific to each of the four domains of GWE. The databases used for the search will be Scopus, Pubmed, Proquest, and Web of Science. Keywords will be adapted for the specific requirements of each electronic database. Inclusion criteria are: Using a validated scale to measure mental health (outcome); including exposures related to the four domains of GWE; reporting estimates for both men and women; and use of a cohort, case-control, or cross-sectional design. Studies will be excluded if they were published more than 10 years ago, are not in English or do not present extractable data on the relationship between GWE and mental health. Discussion: The proposed review will provide evidence about the numerous and complex ways in which employment and gender intersect (and are reinforced) to influence mental health over the life course.
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  • Mogren, A., et al. (author)
  • Children and adolescents with speech sound disorders are more likely to have orofacial dysfunction and malocclusion
  • 2022
  • In: Clinical and Experimental Dental Research. - : Wiley. - 2057-4347. ; 8:5, s. 1130-1141
  • Journal article (peer-reviewed)abstract
    • Background: Children with speech sound disorders (SSD) form a heterogeneous group that differs in terms of underlying cause and severity of speech difficulties. Orofacial dysfunction and malocclusions have been reported in children with SSD. However, the association is not fully explored. Objectives: Our aims were to describe differences in orofacial function and malocclusion between a group of children and adolescents with compared to without SSD and to explore associations between those parameters among the group with SSD. Methods: A total of 105 participants were included, 61 children with SSD (6.0-16.7 years, mean age 8.5 +/- 2.8, 14 girls and 47 boys) and 44 children with typical speech development (TSD) (6.0-12.2 years, mean age 8.8 +/- 1.6, 19 girls and 25 boys). Assessments of orofacial function included an orofacial screening test and assessment of bite force, jaw stability, chewing efficiency, and intraoral sensory-motor function. Possible malocclusions were also assessed. Result: Children with SSD had both poorer orofacial function and a greater prevalence of malocclusion than children with TSD. Furthermore, children with SSD and poorer orofacial function had a greater risk of malocclusion. Conclusion: Our result suggests that children with SSD are more prone to having poorer orofacial function and malocclusion than children with TSD. This illustrates the importance of assessing coexisting orofacial characteristics in children with SSD, especially since orofacial dysfunction may be linked to an increased risk of malocclusion. This result highlights the need for a multiprofessional approach.
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  • Plue, Jan, et al. (author)
  • European soil seed bank communities across a climate and land-cover gradient
  • 2020
  • Other publicationabstract
    • This is the data set used for the publication Buffering effects of soil seed banks on plant community composition in response to land use and climate, published in the journal Global Ecology and Biogeography.Aim.Climate and land use are key determinants of biodiversity, with past and ongoing changes posing serious threats to global ecosystems. Unlike most other organism groups, plant species can possess dormant life-history stages such as soil seed banks, which may help plant communities to resist or at least postpone the detrimental impact of global changes. This study investigates the potential for soil seed banks to achieve this.Location. EuropeTime period. 1978 – 2014Major taxa studied. Flowering plantsMethods.Using a space-for-time/warming approach, we study plant species richness and composition in the herb layer and the soil seed bank in 2796 community plots from 54 datasets in managed grasslands, forests and intermediate, successional habitats across a climate gradient.Results.Soil seed banks held more species than the herb layer, being compositionally similar across habitats. Species richness was lower in forests and successional habitats compared to grasslands, with annual temperature range more important than mean annual temperature for determining richness. Climate and land use effects were generally less pronounced when plant community richness included seed bank species richness, while there was no clear effect of land use and climate on compositional similarity between the seed bank and the herb layer.Main conclusions.High seed bank diversity and compositional similarity between the herb layer and seed bank plant communities may provide a potentially important functional buffer against the impact of ongoing environmental changes on plant communities. This capacity could, however, be threatened by climate warming. Dormant life-history stages can therefore be important sources of diversity in changing environments, potentially underpinning already observed time-lags in plant community responses to global change. However, as soil seed banks themselves appear, albeit less, vulnerable to the same changes, their potential to buffer change can only be temporary, and major community shifts may still be expected.MethodsThis dataset is a collection of 41 published and 5 unpublished data sets, consisting of 2796 plots with corresponding seed bank and herb layer community data. Sampling effort varied across data sets, but involved sampling of the soil and subsequent germination trials in a greenhouse to determine seed bank composition. Herb layer communities were determined by the identification of plants in relevés. Please consult the readme file and published paper for further details.Usage NotesPlease contact database or individual data set authors for further information and collaboration when using the data set or any of its component parts. Please also note that some of these data sets have already been published alongside their orginal papers. Finally, please cite data and datasets according to community standards.
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  • Borg, E, et al. (author)
  • Language development in hearing-impaired children - Establishment of a reference material for a 'Language test for hearing-impaired children', LATHIC
  • 2002
  • In: International Journal of Pediatric Otorhinolaryngology. - 1872-8464. ; 65:1, s. 15-26
  • Journal article (peer-reviewed)abstract
    • Objective: In Sweden, there has previously been no normalised test material for the evaluation of language development in individual hearing-impaired children, and for the assessment of various methods of auditory habilitation. The purpose of the present study was to compose, apply and evaluate a test for language development in hearing-impaired children, and to establish the first set of reference values related to age, sex, type and degree of hearing impairment. Methods: A test consisting of nine subtests was assembled and developed for, and subsequently applied to, hearing-impaired children in the age range 4-6 years. The inclusion criteria were a pure tone average of 80 dBHL or less and oral language (Swedish) as the first language. Two hundred and eleven hearing-impaired children and 87 normal hearing control children were tested. Results: The results show that: (1) children with hearing impairment-also unilateral-have a delayed language development; (2) the delay is greater in children with larger losses and tends to decrease with increasing age; (3) 6-year-olds with hearing loss greater than 60 dB have not reached the level of the control group; (4) no difference between right- or left sided deafness with respect to language development was observed; (5) a reference material, applicable during clinical assessment, was established for the most common types of hearing impairment. Conclusions: The test designed gave graded measures of important aspects of language development in hearing-impaired children. The results merit further application of the test material. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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  • Finkelmeyer, A., et al. (author)
  • Altered hippocampal function in major depression despite intact structure and resting perfusion
  • 2016
  • In: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 46:10, s. 2157-2168
  • Journal article (peer-reviewed)abstract
    • Background. Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation. Method. A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed. Results. The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow. Conclusions. Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression.
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  • Hemingway, H, et al. (author)
  • The effectiveness and cost-effectiveness of biomarkers for the prioritisation of patients awaiting coronary revascularisation: a systematic review and decision model.
  • 2010
  • In: Health Technology Assessment. - : National Coordinating Centre for Health Technology Assessment. - 1366-5278 .- 2046-4924. ; 14:9, s. 1-178
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To determine the effectiveness and cost-effectiveness of a range of strategies based on conventional clinical information and novel circulating biomarkers for prioritising patients with stable angina awaiting coronary artery bypass grafting (CABG).DATA SOURCES: MEDLINE and EMBASE were searched from 1966 until 30 November 2008.REVIEW METHODS: We carried out systematic reviews and meta-analyses of literature-based estimates of the prognostic effects of circulating biomarkers in stable coronary disease. We assessed five routinely measured biomarkers and the eight emerging (i.e. not currently routinely measured) biomarkers recommended by the European Society of Cardiology Angina guidelines. The cost-effectiveness of prioritising patients on the waiting list for CABG using circulating biomarkers was compared against a range of alternative formal approaches to prioritisation as well as no formal prioritisation. A decision-analytic model was developed to synthesise data on a range of effectiveness, resource use and value parameters necessary to determine cost-effectiveness. A total of seven strategies was evaluated in the final model.RESULTS: We included 390 reports of biomarker effects in our review. The quality of individual study reports was variable, with evidence of small study (publication) bias and incomplete adjustment for simple clinical information such as age, sex, smoking, diabetes and obesity. The risk of cardiovascular events while on the waiting list for CABG was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients with a mean of 59 days at risk). Risk factors associated with an increased risk, and included in the basic risk equation, were age, diabetes, heart failure, previous myocardial infarction and involvement of the left main coronary artery or three-vessel disease. The optimal strategy in terms of cost-effectiveness considerations was a prioritisation strategy employing biomarker information. Evaluating shorter maximum waiting times did not alter the conclusion that a prioritisation strategy with a risk score using estimated glomerular filtration rate (eGFR) was cost-effective. These results were robust to most alternative scenarios investigating other sources of uncertainty. However, the cost-effectiveness of the strategy using a risk score with both eGFR and C-reactive protein (CRP) was potentially sensitive to the cost of the CRP test itself (assumed to be 6 pounds in the base-case scenario).CONCLUSIONS: Formally employing more information in the prioritisation of patients awaiting CABG appears to be a cost-effective approach and may result in improved health outcomes. The most robust results relate to a strategy employing a risk score using conventional clinical information together with a single biomarker (eGFR). The additional prognostic information conferred by collecting the more costly novel circulating biomarker CRP, singly or in combination with other biomarkers, in terms of waiting list prioritisation is unlikely to be cost-effective.
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  • Lohmander, A., et al. (author)
  • Students take charge of Learning–Using e-learning in Perceptual Assessment in Speech–Language Pathology
  • 2020
  • In: Scandinavian Journal of Educational Research. - : Routledge. - 0031-3831 .- 1470-1170.
  • Journal article (peer-reviewed)abstract
    • Perceptual assessment is the basis for diagnosis and evaluation of treatment in speech–language pathology (SLP). Students need to practise assessment skills. A web-based platform with cases and expert feedback in cleft palate disorders was developed in national collaboration. The aim of the study was to evaluate the results of individual training on assessment skills in SLP students and their perception of e-learning. Forty-five students performed tests using a pre- and post-test set-up. Perceptual assessments were demonstrated and instructions provided during teacher-led activities in ongoing fully scheduled courses; students were then individually trained in their free time. Reference samples were available. A significant improvement was found in rating and phonetic transcriptions after training. Positive comments concerned accessibility and practice time.
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  • Mogren, A., et al. (author)
  • Malocclusion in children with speech sound disorders and motor speech involvement: a cross-sectional clinical study in Swedish children
  • 2022
  • In: European Archives of Paediatric Dentistry. - : Springer Science and Business Media LLC. - 1818-6300 .- 1996-9805. ; 23:4, s. 619-628
  • Journal article (peer-reviewed)abstract
    • Objectives The objectives of this study were to investigate the occurrence, types and severity of malocclusions in children with speech sound disorder (SSD) persisting after 6 years of age, and to compare these findings to a control group of children with typical speech development (TSD). Methods In total, 105 children were included: 61 with SSD and motor speech involvement (mean age 8:5 +/- 2:8 years; range 6:0-16:7 years, 14 girls and 47 boys) and 44 children with TSD (mean age 8:8 +/- 1:6; range 6:0-12:2 years, 19 girls and 25 boys). Extra-oral and intra-oral examinations were performed by an orthodontist. The severity of malocclusion was scored using the IOTN-DHC Index. Results There were differences between the SSD and TSD groups with regard to the prevalence, type, and severity of malocclusions; 61% of the children in the SSD group had a malocclusion, as compared to 29% in the TSD group. In addition, the malocclusions in the SSD group were rated as more severe. Functional posterior crossbite and habitual lateral and/or anterior shift appeared more frequently in the SSD group. Class III malocclusion, anterior open bite and scissors bite were found only in the SSD group. Conclusion Children with SSD and motor speech involvement are more likely to have a higher prevalence of and more severe malocclusions than children with TSD.
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36.
  • Sims, D. A., et al. (author)
  • The He(γ,n) reaction: a potential testing ground for the alpha-particle wavefunction
  • 1998
  • In: Physics Letters B. - 0370-2693. ; 442:1-4, s. 43-47
  • Journal article (peer-reviewed)abstract
    • Differential cross sections (σ(Eγ,θn)) for the He(γ,n) reaction have been measured at Eγ=50–71 MeV and θn=30–120°. These data are compared with theoretical predictions where a microscopic calculation of the He and He wavefunctions has been made within the Alt-Grassberger-Sandhas, integral-equation formalism.
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  • Tabor, J. B., et al. (author)
  • Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review
  • 2023
  • In: British Journal of Sports Medicine. - 0306-3674. ; 57:12
  • Research review (peer-reviewed)abstract
    • ObjectiveDetermine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC). DesignSystematic review. Data sourcesSearches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study. Eligibility criteria for selecting studiesStudies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants. ResultsA total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research. ConclusionsAdvanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice. PROSPERO registration numberCRD42020164558.
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40.
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41.
  • Bergström, Christel A. S., et al. (author)
  • Early pharmaceutical profiling to predict oral drug absorption : Current status and unmet needs
  • 2014
  • In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57, s. 173-199
  • Journal article (peer-reviewed)abstract
    • Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silica and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. (C) 2013 Elsevier B.V. All rights reserved.
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42.
  • Black, Richard, et al. (author)
  • Environment of Peace : Security in a New Era of Risk
  • 2022
  • Reports (other academic/artistic)abstract
    • The environmental crisis is increasing risks to security and peace worldwide, notably in countries that are already fragile. Indicators of insecurity such as the number of conflicts, the number of hungry people and military expenditure are rising; so are indicators of environmental decline, in climate change, biodiversity, pollution and other areas. In combination, the security and environmental crises are creating compound, cascading, emergent, systemic and existential risks. Without profound changes of approach by institutions of authority, risks will inevitably proliferate quickly. Environment of Peace surveys the evolving risk landscape and documents a number of developments that indicate a pathway to solutions––in international law and policy, in peacekeeping operations and among non-governmental organizations. It finds that two principal avenues need to be developed: (a) combining peace-building and environmental restoration, and (b) effectively addressing the underlying environmental issues. It also analyses the potential of existing and emerging pro-environment measures for exacerbating risks to peace and security. The findings demonstrate that only just and peaceful transitions to more sustainable practices can be effective––and show that these transitions also need to be rapid.
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45.
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46.
  • Cracknell, R. F., et al. (author)
  • Octane sensitivity in gasoline fuels containing nitro-alkanes : A possible means of controlling combustion phasing for HCCI
  • 2009
  • In: SAE technical paper series. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191.
  • Journal article (peer-reviewed)abstract
    • Addition of nitroalkanes to gasoline is shown to reduce the octane quality. The reduction in the Motor Octane Number (MON) is greater than the reduction in the Research Octane Number (RON). In other words addition of nitroalkanes causes an increase in octane sensitivity. The temperature of the compressed air/fuel mixture in the MON test is higher then in the RON test. Through chemical kinetic modelling, we are able to show how the temperature dependence of the reactions responsible for break-up of the nitroalkane molecule can lead to an increase in octane sensitivity. Results are presented from an Homogenous Charge Compression Ignition (HCCI) engine with a homogeneous charge in which the air intake temperature was varied. When the engine was operated on gasoline-like fuels containing nitroalkanes, it was observed that the combustion phasing was much more sensitive to the air intake temperature. This suggests a possible means of controlling combustion phasing for HCCI.
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47.
  • Elkabets, Moshe, et al. (author)
  • Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice
  • 2011
  • In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 121:2, s. 784-799
  • Journal article (peer-reviewed)abstract
    • Systemic instigation is a process by which endocrine signals sent from certain tumors (instigators) stimulate BM cells (BMCs), which are mobilized into the circulation and subsequently foster the growth of otherwise indolent carcinoma cells (responders) residing at distant anatomical sites. The identity of the BMCs and their specific contribution or contributions to responder tumor growth have been elusive. Here, we have demonstrated that Scal(+)cKit(-) hematopoietic BMCs of mouse hosts bearing instigating tumors promote the growth of responding tumors that form with a myofibroblast-rich, desmoplastic stroma. Such stroma is almost always observed in malignant human adenocarcinomas and is an indicator of poor prognosis. We then identified granulin (GRN) as the most upregulated gene in instigating Scal(+)cKit(-) BMCs relative to counterpart control cells. The GRN(+) BMCs that were recruited to the responding tumors induced resident tissue fibroblasts to express genes that promoted malignant tumor progression; indeed, treatment with recombinant GRN alone was sufficient to promote desmoplastic responding tumor growth. Further, analysis of tumor tissues from a cohort of breast cancer patients revealed that high GRN expression correlated with the most aggressive triple-negative, basal-like tumor subtype and reduced patient survival. Our data suggest that GRN and the unique hematopoietic BMCs that produce it might serve as novel therapeutic targets.
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49.
  • Guerrero, Angela M., et al. (author)
  • Achieving social-ecological fit through bottom-up collaborative governance : an empirical investigation
  • 2015
  • In: Ecology and Society. - 1708-3087. ; 20:4
  • Journal article (peer-reviewed)abstract
    • Significant benefits can arise from collaborative forms of governance that foster self-organization and flexibility. Likewise, governance systems that fit with the extent and complexity of the system under management are considered essential to our ability to solve environmental problems. However, from an empirical perspective the fundamental question of whether self-organized (bottom-up) collaborative forms of governance are able to accomplish adequate fit is unresolved. We used new theory and methodological approaches underpinned by interdisciplinary network analysis to address this gap by investigating three governance challenges that relate to the problem of fit: shared management of ecological resources, management of interconnected ecological resources, and cross-scale management. We first identified a set of social-ecological network configurations that represent the hypothesized ways in which collaborative arrangements can contribute to addressing these challenges. Using social and ecological data from a large-scale biodiversity conservation initiative in Australia, we empirically determined how well the observed patterns of stakeholder interactions reflect these network configurations. We found that stakeholders collaborate to manage individual parcels of native vegetation, but not for the management of interconnected parcels. In addition, our data show that the collaborative arrangements enable management across different scales (local, regional, supraregional). Our study provides empirical support for the ability of collaborative forms of governance to address the problem of fit, but also suggests that in some cases the establishment of bottom-up collaborative arrangements would likely benefit from specific guidance to facilitate the establishment of collaborations that better align with the ways ecological resources are interconnected across the landscape. In our case study region, this would improve the capacity of stakeholders to detect both the intended and unintended off-site impacts of management actions. Our approach offers an avenue for empirical evaluations of collaborative governance so that preconditions for effectiveness of environmental programs can be enhanced.
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